Palladium mediated synthesis of N-heterocycles by iminoannulation of allenes. - Chapter 2 Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines[1]

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Palladium mediated synthesis of N-heterocycles by iminoannulation of allenes.

Diederen, J.J.H.

Publication date

2001

Link to publication

Citation for published version (APA):

Diederen, J. J. H. (2001). Palladium mediated synthesis of N-heterocycles by iminoannulation

of allenes.

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Chapter 2

Synthesis of N-Heterocycles by Iminoannulation of

Cyclopalladated Imines[i]

Abstract

Several imines 1 (R=Ph, p-Tol, p-An, p-Cl-C6H4, p-Br-C6H4, p-I-QH4/ p-N02-C6H4, CH2Ph, i-Pr)

were synthesized from a-tetralone by a condensation reaction with different amines. Cyclopalladation of imines 1 with Pd(OAc)2 and subsequent substitution of the acetate bridge

by chloride gave chloro-bridged palladium complexes 3. Reaction of 3 with 1,1-dimethylallene and vinylidenecyclohexane produced iminium salts 4 and 6, respectively, with high regioselectivities and in good yields. Iminium salts 4 were converted into enamines 8 by deprotonation with KOH or into amines 9 by reduction with NaBH4.

Synthesis of'N-Heterocycles by Iminoannulation of Cyclopalladated Imines

2.1 Introduction

Palladium complexes have found numerous applications in organic synthesis.[2] Most importantly, palladium offers many possibilities of carbon-carbon and carbon-heteroatom bond formation. One important property of palladium complexes is the ease of formation of a-Pd-C bonds either by oxidative addition, insertion or transmetallation.

Insertion of a Pd(II)-species into a C-H bond with a stabilizing intramolecularly coordinating heteroatom, has often led to the formation of aa-Pd-C bond (eq 1). This so-called cyclopalladation reaction (or orf/zo-palladation in the specific case of reactions involving the orf/ïo-position in the aromatic ring of the ligand), has been carried out with a large number of substrates and excellent reviews about this subject are available.[3-5]

PdX, A = Heteroatom X = CI, Br, OAc .PcT

V

In our laboratory it has been shown that aliènes insert into a a-Pd-C bond in such a way that migration of the nucleophilic a-bonded carbon substituent on palladium exclusively occurs to the central aliène carbon atom leading to a Pd-allyl species (eq 2).[6, 7] These Pd-allyl complexes are interesting intermediates for the formation of carbon-carbon and carbon-nitrogen bonds by reacting them with a wide range of nucleophiles (hard and soft carbanions, heteroatoms, organotins, etc).[2]

X

CI

" \

P d — ^ - C H3

_ci-

An interesting example of C-N bond formation was published by the group of Pfeffer, who synthesized various pyridinium salts via insertion of 1,1-dimethylallene into the a-Pd-C bond of cyclopalladated pyridines and subsequent intramolecular attack of the pyridine nitrogen. It was found that this latter nucleophilic attack of the sp2 nitrogen atom of the pyridine

occurred exclusively at the sterically less hindered carbon atom of the allylic unit. In the early stages of the reaction electronically favored products were produced (i.e. nucleophilic attack at

Chapter 2

the most substituted position). These products isomerized during the reaction towards the thermodynamically favored products (Scheme 1).[8]

PdCI/.

CH2C12 ; A

-Pd°

PdCI/2

Scheme 1

In the Vrieze research group the stoichiometric synthesis of 4H-isoquinolinium salts by reaction of cyclopalladated N,N-dimethylbenzylamine (dmba) with various aliènes has been investigated. It was shown that, in the case of 1,1-dimethylallene, nucleophilic displacement of Pd exclusively takes place at the least substituted position of the Pd-it-allyl intermediate, leading to products with an exocyclic double bond (eq 3).[9]

rPd-

R

I Ri

Recently it was reported that the carbonylation of o-iodophenol in the presence of an aliène, a base and a Pd(0)-catalyst affords 2,3-dihydro-4H-l-benzopyran-4-ones (eq 4). [10]

OH

V

These stoichiometric heteroannulation reactions of cyclopalladated complexes with aliènes prompted us to investigate the possibility of employing imines in this type of reactions.

Synthesis of N-Heterocycles by Iminoanmtlation of Cyclopalladated Imines

It is known that alcohols [10-20], carboxylic acids [16, 17, 19, 20], amines [8, 16-18, 21-32], (sulfon)amides [17, 33-37] and oximes [38, 39] are sufficiently nucleophilic to attack Pd-7i-allyl species leading to N-heterocycles. Cyclopalladated imines, bearing an sp^-nitrogen atom, are closely related to cyclopalladated pyridines and a large number of these complexes have been reported in the literature.[3-5] We have selected cyclopalladated a-tetralone ketimines[40] (Fig. 1) as substrates to investigate the nucleophilic character of imines and the regioselectivity of these iminoannulations.

Figure 1

2.2 Results and d i s c u s s i o n

2.2.1 Synthesis of cyclopalladated complexes

Starting from a-tetralone, the corresponding a-tetralone ketimine can be obtained via a condensation reaction with the appropriate amine in toluene at reflux temperature with a catalytic amount of p-TsOH (Scheme 2, step (i)). Nine different amines were used and the corresponding imines la-i are presented in Scheme 2, of which l h was already published in the literature.[41, 42] Most imines were recrystallized from pentane to give air-stable solids. Benzylimine l h could not be recrystallized and was used as an oil without further purification. These imines did not show any tautomerism towards the corresponding enamines as shown by 'H-NMR. It is known for imines that cis-trans isomerism can occur,[43] although generally imines exist only in the more stable trans configuration. Also, the imines of a-tetralone most likely exist as the trans isomers.

Chapter 2

(i)R-NH2 f Y (ii)Pd(OAc)2

p-TsOH cat. NaOAc; toluene, A ^ ^ CH2C12 - H20 l a. i a) R = Ph b)R = p-Tol

(iii)5equivLiCl I V , / X J) R = p-Q-C

H

The cyclopalladations of a-tetralone ketimines la-h by using Pd(OAc)2 (1 equiv) in the

presence of NaOAc (1 equiv) in dichloromethane at room temperature were straightforward, leading only to the desired ort/io-palladated products bearing an acetato-bridge between the Pd nuclei (Scheme 2, step (ii)).[40] Reaction of l i with Pd(OAc)2 did not lead to the desired

ortho-palladated product. Adding imine l i to a mixture of Pd(OAc)2 and NaOAc in CH2C12 at room

temperature or at 0 °C, gave rise to a rapid color change from yellow to dark green with extensive formation of palladium black. The only organic material that could be detected was imine l i . The presence of NaOAc is not necessary in these reactions but it facilitates the electrophilic aromatic substitution.

The products 2a-h may be purified by flash chromatography (MeOH / CH2CH2 2:98)

and recrystallized from a dichloromethane pentane mixture to give air-stable yellow solids. 'H-NMR of these complexes only showed the presence of one methyl group of the acetato unit indicating that in these complexes the two cyclopalladated a-tetralone ketimine moieties are in

trans position. Reaction of l h with Pd(OAc)2 led to the formation of 2h in which C-H activation

takes place exclusively at the tetralone ring. In principle this substrate offers two positions where C-H activation may occur, namely in the tetralone ring (position 1, Fig. 2) and in the N-benzyl group (position 2, Fig. 2). The 'H-NMR of 2h demonstrated that H„ and Hi r (see

experimental section) are not equivalent as in the free ligand. It is possible that the benzyl group is restricted in its rotation giving rise to two separate signals for Hn and Hn. Another possibility

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

is that the Pd-center is chiral because of two different coordination modes of the acetate ligands. They show a chemical shift difference of 0.6 ppm and a geminal coupling of 14 Hz.

Hu1'

y

^

. ,.

pd

x

n

/\ X

The cyclopalladation reaction of l h is similar to that of Albert et al., who studied cyclopalladation reactions of N-(benzylidene)-benzylamines with Pd(OAc)2 and PdCl2 (eq

5).[44] Our result may be explained in terms of the formation of a 5-membered aromatic ring involving the two conjugated double bonds of the (-C=C-C=N-) system and the filled palladium

d orbitals of appropriate symmetry. [45]

PdX, AcOH, A

R = H, CI, N 02

X = Cl,OAc

PdX/2 (5)

Cyclopalladated a-tetralone ketimines are the starting materials for intramolecular iminoannulations with aliènes leading to N-heterocycles. Because of the slightly nucleophilic character of the acetate anion which may compete with the imine nucleophile, the acetate bridges in complexes 2a-h were substituted by chloride. Reaction of complexes 2a-h with LiCl in acetone at room temperature led to the formation of chloro-bridged palladium complexes 3a-h (Sc3a-heme 2, step (iii)). In general t3a-he c3a-hloro-bridged palladium complexes were air-stable yellow solids which were insoluble in most common organic solvents (except DMSO). The

Cliapter 2

driving force for the formation of the chloro-bridged complexes is their insolubility. Characterization by NMR was performed on the bridge-opened monomeric deuterated pyridine complexes, produced after adding deuterated pyridine to the chloro-bridged dimers in CDCI3. In the case of 3h it was possible to determine a 'H-COSY of the chloro-bridged dimer without addition of pyridine to investigate whether the cyclopalladation indeed took place at the tetralone ring. In the aromatic region of the spectrum two sets of coupling protons could be seen, i.e. one set of three coupling protons and one set of five protons, respectively. In the case of cyclopalladation at the N-benzyl group (position 2, Fig. 2), two sets of four aromatic protons would be observed. This 'H-COSY spectrum also showed three sets of methylene protons of the a-tetralone moiety. The deuterated pyridine coordinates in a cis position relative to the palladated carbon, as indicated by the high-field shift of ca. 1 ppm of the aromatic proton in the

ortho position relative to the palladated carbon, owing to the shielding effect of the pyridine

ring. [46]

We were able to grow crystals of complex 3a', formed by chloride abstraction from 3a by AgO,SCF3 and subsequent coordination with 2,2'-bipyridine in acetonitrile (eq 6). The crystals

were suitable for an X-ray crystal structure determination. From the crystal structure (Fig. 3) it can be seen that the Pd-atom forms a square planar complex with the bipyridine ligand and the -V-phenyl-a-tetralone imine ligand. Carbon atom 17 showed disorder in the crystal structure. It appeared that the molecule packed into two distinct conformations of the saturated cyclohexane moiety (ratio 71.3 : 28.7). See Table 1 and Table 2 for information about bond distances and bond angles (experimental section).

1) CF3S03Ag 2) 2,2'-Bipy » MeCN -AgCl CF3SO3- (6) 3a 3a'

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

Figure 3

2.2.2.1 Reaction of the cyclopalladated complexes with 1,1-dimethylallene

Reactions of 1,1-dimethylallene (DMA) with cyclopalladated complexes 3a-h in dichloromethane at room temperature led to iminium salts in which the imine nucleophile predominantly attacked the disubstituted position of the aliène leading to 4a-d,f,h and 5a-d,f,h (Scheme 3 and Table 3). Because of a complex product mixture in the crude reaction mixture of the iminium salts with a chloride anion, the latter was exchanged with KPF6, leading to higher

yields of N-heterocyclic products. Reactions of 3d-f with DMA were generally more sluggish than 3a-c and 3g-h. It was also difficult to obtain pure iminium salts from substrates 3d,f. In the case of 3e no ring closed products could be observed. The reaction of 3g with DMA was very slow, requiring one week for complete conversion into a clear purple solution contaminated with some palladium black. The iminium salt was aromatized to product 4g by dehydrogenation of the tetrahydronaphthalene ring by the formed Pd(0) (Scheme 3). The iminium salts were successfully characterized by 'H and "C-NMR based on a detailed NMR investigation of 4b. All resonances of iminium salt 4b could be assigned by means of different 2D-NMR techniques (Fig. 4).

Cltapter 2

'.2.2.2 Characterization of iminium salts 4a-d, f,h

A 'H-COSY experiment provided information about the chemical shifts of the protons in the saturated ring and in the aromatic rings. It was, however, impossible to assign the two .inylic protons around 5 ppm without the help of 'H-NOESY NMR. H5. in 4b (Fig. 4) shows a

arger NOE effect with H, than H5. Furthermore, NOE effects were detected between H9 and H,7/

H7 and H3 and between the protons of the p-tolyl group and H18. It is interesting to note that

jrotons H9 resonate at a higher field than H7 (see experimental section). One would expect on

the basis of the inductive effect of N, that H„ is deshielded. However, H, is above the plane of the p-tolyl group which effectively shields these two protons, resulting in an overall high field shift of PL. 3a-h 1) A (IQ 2) 10 KPF6 MeOH (i) CH2C12 R PF6 a) R = Ph b) R = p-Tol c) R = p-An d) R = p-Cl-C6H4 f) R = p-I-C6H4 g) R = P-NO2-QH4 h) R = Bn N02 4a-f,h 5a-f,h Scheme 3 2.2.2.3 Regioselectivity

The regioselectivity found in these reactions was generally high. Nucleophilic attack of the imine predominantly took place at the sterically most hindered terminal allyl-carbon atom in reaction with DMA (Table 3).

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

Table 3: Regioselectivity in iminium salts 4 and 5' reaction with ratio yield (4 + 5)

DMA 4 / 5 (%) 3a 1 0 0 / 0 60 3b 9 3 / 7 81 3c 1 0 0 / 0 51 3d 7 5 / 2 5 79 3f 1 0 0 / 0 75 3g 8 2 / 1 8 65 3h 9 1 / 9 86

a: ratios of regioisomers were determined by NMR

NMR studies on (di)phosphine palladium-allyl complexes showed that alkylation with anions of dialkyl malonates predominantly takes place at the most stabilized position (i.e. the terminal allyl carbon atom with donating R groups, see eq 7). It was found ("C-NMR) that donating R-groups on an allyl terminus make this position more electrophilic and thus more prone towards nucleophilic attack, whereas the other terminus is made more nucleophilic.[47]

Ph2P PPh2 BF, X = electron donating Y = electron withdrawing Nu" (7)

From a steric point of view it is clear that nucleophilic attack would be more favored at the least hindered position. Recently, a similar annulation with cyclopalladated pyridines was published by Pfeffer and coworkers.[8] They showed that in the reaction of their complexes with DMA, ring closure took place at the sterically most favored position, in contrast to our results. Apparently electronic effects direct the regiochemistry in our reactions. The latter may be explained as follows: the net positive charge on the rc-allyl-palladium species is more located at the alkyl-substituted terminus. [17] Furthermore, electron-rich Pd(0)-ligand complexes favor coordination to the more electron deficient (less-substituted) double bond of the product. [48-50]

CImpter 2

Recently a carbonylative heteroannulation of o-iodophenol with 1,1-dimethylallene was :eported[10], in which nucleophilic attack of the phenolate anion also took place at the methyl

lisubstituted position of the allyl (eq 4).

It is interesting to note that our products 4, in which nucleophilic attack took place at the most hindered position of the allyl terminus, are kinetic products but can be isolated. They do not isomerize without the presence of a suitable Pd"-source. Refluxing solutions of regioisomers n MeOH with palladium metal did not lead to a substantial change in the ratio of regioisomers. The kinetic product 4b was converted into the thermodynamically more favored product 5b (with the iminium nitrogen adjacent to the methylene group) by refluxing 4b in methanol with 'd(PPh3)4 for 24 hours (eq 8). Due to separation problems, this regioisomer could not be isolated

n a pure state. 'H-NMR showed the presence of a syn and an anti methyl signal which are -trongly indicative for the regioisomer, with the methylene group adjacent to the iminium nitrogen atom.[9] cat. Pd(PPh3)4 MeOH (8) 4b 5b 2.2.2.4 Intermediates

It is difficult to observe Pd-n-allyl intermediates during this reaction with 'H-NMR. The activation barrier for the formation of the heterocycles is similar to the activation barrier for the insertion of DMA into the a-Pd-C bond leading to a Pd-it-allyl complex (Scheme 3, step (i)). Reaction of 3a with DMA in CDC13 showed the presence of broad signals around 3.98 ppm and

3.53 ppm, indicative for the syn- and anti protons of a Pd-7t-allyl complex.[6, 7] The reaction probably proceeds via a rc-allyl intermediate which is attacked intramolecularly by the nucleophilic imine nitrogen atom.

During the reaction of cyclopalladated complexes 3 with DMA, besides the iminium products, enamines could be observed in the crude reaction mixture, with 'H-NMR spectra identical to the ones described for enamines 8 (eq 9). This shows that the iminium salt, which possesses acidic protons (H9) next to the iminium group, is in equilibrium with the

corresponding enamine in CDC13 (eq 9). Probably owing to this equilibrium it was difficult to

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

enamine and iminium salt is shifted towards the iminium salt because of the higher pKa value

for HPF6 as compared with HCl.

-HCl + HC1

(9)

Reaction of 3g with 1,1-dimethylallene led to the dehydrogenated product 4g (Scheme 3). This is due to the fact that during the reaction predominantly the enamine was formed as indicated by 'H-NMR. This can be explained by the electron-withdrawing capacity of the p-N02

group attached to the imine nitrogen. The latter enamine was then easily dehydrogenated by the formed palladium black.

2.2.2.5 Kinetics

Reactions of complexes 3 (Scheme 3) with electron-releasing groups in the para position of the aniline with DMA were much faster than the corresponding reactions with electron-withdrawing groups. Very fast reactions were observed with the benzyl substituted imine 3h. Qualitatively, the reactions proceeded faster in the following order : R = p-N02-Ph < Ph < p-Tol

< p-An < Bn. The overall reaction rate is determined by the slowest of the following steps: the bridge breaking reaction by coordination of the aliène, insertion of the aliène into the a-Pd-C bond, and nucleophilic attack of the imine nitrogen on the formed Pd-n-allyl species. Precoordination of the aliène is faster if the palladium metal center is electron rich by electron donating substituents on the imine and therefore the bridge breaking reaction proceeds faster with these electron-rich imines. The rate of migration of the aryl group onto the aliène is enhanced by electron withdrawing groups on the imine, which makes the palladium more electrophilic. Nucleophilic attack of the imine on the allyl is enhanced by more electron releasing groups on the imine. Only in one case a Pd-ji-allyl species could be detected in the reaction mixture, which indicates that nucleophilic attack of the imine nitrogen cannot be the rate determining step in the formation of iminium salts. Therefore, taking into account that electron releasing groups on the imine accelerate the formation of iminium salts, it can be concluded that the bridge breaking reaction by the aliène probably is the rate determining step. Ryabov studied the mechanism of alkyne insertions in cyclopalladated complexes and showed, that there too the halide bridge breaking step by the alkyne was the rate determining step.[51]

Chapter 2

2.2.3 Reaction of cyclopalladated complexes with vinylidenecyclohexane

Reaction of complexes 3a-c with vinylidenecyclohexane (VCH) led to iminoannulation at the least substituted end of the allyl. Only low yields for iminium salts 6a-c were obtained. Electronically it would be favorable that nucleophilic attack takes place at the most substituted position (leading to 7a-c), but the bulky cyclohexane ring prevents this (Scheme 4 and Table 4).

Table 4: Regioselectivity in iminium salts 6 and 7' reaction with ratio yield (6 + 7)

VCH (%)

3a 9 7 / 3 < 5 3b 9 9 / 1 < 5 3c 9 6 / 4 < 5 a: Ratios of regioisomers were determined by 'H-NMR

MeCN 3a-c 1)A 2) 10 KPF6 MeCN 6a-c 7a-c a) R = Ph b) R = p-Tol c) R = p-An Scheme 4

Reactions of cyclopalladated complexes 3 with phenylallene did not lead to any N-heterocycle. We do not have a clear explanation for this result.

Synthesis ofN-Heteroq/cles by Iminoannulation of Cydopalkdated Imines

2.2.4 Synthesis of neutral IV-heterocycles from iminium salts

Conversion of the iminium salts into neutral N-heterocycles was carried out either by reaction with a suitable base (eq 10) or by hydrogenolysis of the iminium functional group by NaBH4 (eq 12). A strong base like KOH was needed as reactions with Na2C03 and NaOAc were

not successful to convert iminium salts 4 into enamines 8 (eq 10). Unfortunately these enamines could not be purified by flash chromatography because of the instability of these products under wet acidic conditions. Purification by extraction with pentane was suitable as demonstrated by NMR. However, yellow solutions of these enamines in CDCL, also showed decomposition to dark green products, probably due to the acidic character of CDC13 and the

presence of traces of water. Perhaps this is an acid catalyzed hydrolysis or air oxidation. The decomposition products could not be characterized.

4a-d,h

KOH MeOH

(10)

8a-d,h

Enamine 8g was prepared by reaction of 3g with DMA in the presence of pyridine as base (eq 11).

>

The reaction between 3g and DMA was followed by NMR in the absence of base. It turned out that the equilibrium (as shown in eq 9) lay towards the enamine as the p-N02QH4

Chapter 2

Hydrogénation of the iminium group in 4a-d,h with NaBHi in MeOH at room temperature easily gave amines 9a-d,h (eq 12). Purification of the amines proceeded without any decomposition. Reduction only took place at the iminium functional group. The exocyclic vinylic group was not attacked by NaBH4. Only in the case of 4h was the exocyclic double bond

hydrogenated, probably due to Pd impurities which may catalyze the hydrogénation of the exocyclic double bond. Besides the hydrogénation of the exocyclic double bond, a dehydrogenation of the tetrahydronaphthalene ring had occurred, similar to the formation of 4g from 3g by Pd(0) impurities (see Scheme 3).

4a-d,h

NaBH4

MeOH

(12)

2.3 C o n c l u s i o n s

Reactions of complexes 3a-h with aliènes show successful regioselective iminoannulations towards new N-heterocycles. In the case of 1,1-dimethylallene, nucleophilic attack predominantly takes place at the disubstituted end of the Pd-n-allyl terminus, leading to products 4a-h. Apparently the regiochemistry in these reactions is controlled by electronic effects, as two donating methyl groups on the most substituted terminus of the Pd-re-allyl moiety can stabilize a positive charge. Reactions of cyclopalladated complexes 2 with vinylidenecyclohexane lead to products in which nucleophilic attack takes place at the least substituted position. Electronically products 7a-c would be favored, but the bulky cyclohexyl group prevents this, resulting in the low yield of 6a-c.

Qualitatively, the reactions of complexes 2 with DMA proceed faster in the order p-N02

-Ph < -Ph < p-Tol < p-An < Bn. The rate determining step in these reactions is very likely the breaking of the chloride bridge upon coordination of the aliène to form a mononuclear species which then undergoes migration of the aryl unit to the central carbon atom of the aliène and subsequent intramolecular nucleophilic attack of the imine nitrogen to one of the terminal carbon atoms of the allyl unit.

Unfortunately these iminium salts cannot be fully purified by e.g. column chromatography. Iminium salts 4a-d,h were therefore successfully converted into neutral

N-Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

heterocycles either by reaction with KOH, leading to enamines 8a-d,h, or by reduction of the iminium group by NaBH4 to amines 9a-d,h. Pd impurities may be responsible for the

concomitant hydrogénation of an exocyclic double bond (9h) or the dehydrogenation of oc-tetralone ketiminium salts towards aromatized products (4g and 9h).

Cliapter 2

2.4 Experimental Section

General remarks

All manipulations were carried out in an atmosphere of purified, dry nitrogen by using standard Schlenk techniques. Solvents were dried according to literature procedures[52] and stored under nitrogen. a-Tetralone, p-toluidine, p-chloroaniline, p-bromoaniline, p-iodoaniline, p-nitroaniline, acetic acid, isopropylamine, KPF6 and KOH, were purchased from Acros

Chimica. Lithium chloride and sodium borohydride were obtained from Aldrich, p-anisidine and 1,1-dimethylallene from Fluka and p-toluene sulphonic acid monohydrate and sodium acetate from Merck. All of these compounds were used without further purification. Aniline and benzylamine were dried over calcium hydride and distilled. Propargyl alcohol was distilled from K2C03. Xylene (mixture of isomers) and toluene were distilled from sodium. Elemental

analyses were performed on a Vario EL in the Inorganic Laboratory of this university or by Kolbe Microanalytisches Laboratorium, Mülheim an der Ruhr, Germany. 'H and 13C{'H}-APT

NMR spectra were recorded on a Bruker AMX 300 spectrometer. 'H-COSY, HETCOR fH-13C)

and 'H-NOESY NMR were recorded on a Bruker DRX 300 spectrometer using standard COSY-45 (Gradient Selected), HETCOR [J(C-H) = 140 Hz] and 2D NOESY pulse sequences. C-H-HETCOR spectrum was used to calculate 'JC-H- AU NMR spectra were recorded in CDCL, (unless indicated otherwise). 'H-NMR spectra of complexes 3 were recorded in CDC13 with a drop of

pyridine-d5, except 3h which was measured in CDC13. Mass spectra and accurate mass

determinations were performed on a JEOL JMS SX/SX102A four-sector mass spectrometer, coupled to a JEOL MS-MP7000 data system.

Preparation of l a as general procedure A for the synthesis of a-tetralone ketimines (la-i)

3,4-Dihydro-2H-naphthalen-l-ylidene)-phenyl-amine (la) See step 1 in Scheme 2. In a 250 mL 3-necked flask containing 4Â molecular sieves, a-tetralone (10.96 g, 75 mmol) was dissolved in toluene (50 mL) together with freshly distilled aniline (6.98 g, 75 mmol) and p-toluenesulphonic acid monohydrate (0.30 g, 1.58 mmol). The mixture was heated to reflux for 1 day. After the mixture was cooled to room temperature the brown solution was filtered to remove the molsieves. The molsieves were washed with diethyl ether (2 x 25 mL). The volatile solvents in the combined extracts were removed in vacuo to give a brown oil. After recrystallization from pentane, l a (10.58 g, 48 mmol, 64%) was obtained as a yellow solid. 'H-NMR (300 MHz): 8.35 (d, 1 H, J = 7.7 Hz), 7.37 (m, 4 H),

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Intines

7.23 (d, 1 H, J = 7.2 Hz), 7.10 (t, 1 H, J = 7.4 Hz), 6.83 (d, 2 H, J = 7.2 Hz), 2.93 (t, 2 H, J = 6.1 Hz), 2.55 (t, 2 H, J = 6.4 Hz), 1.94 (p, 2 H, J = 6.3 Hz). "C-NMR (75 MHz): 165.4, 151. 5, 141.1, 133.7, 130.5, 128.8, 128.5, 126.3, 126.2, 122.8, 119.3, 117.4, 29.8, 29.7, 22.8. Anal. Found (calc. for C16H15N): C = 86.81 (86.84); H = 6.83 (6.84); N = 6.23 (6.33).

(3,4-Dihydro-2H-naphthalen-l-ylidene)-p-tolyl-amine (lb) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), p-toluidine (8.11 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, l b (10.72 g, 45.6 mmol, 61%) was obtained as a yellow solid. 'H-NMR (300 MHz): 8.33 (d, 1 H, J = 7.8 Hz), 7.28 (m, 3 H), 7.16 (d, 2 H, J = 8.1 Hz), 6.72 (d, 2 H, J = 8.1 Hz), 2.91 (t, 2 H, J = 6.1 Hz), 2.55 (t, 2 H, J = 6.4 Hz), 2.36 (s, 3 H, PhCH3), 1.92 (p, 2 H, J = 6.3 Hz).

"C-NMR (75 MHz): 165.4, 148.8, 141.0, 133.8, 132.2, 130.3, 129.3, 128.5, 126.2, 126.1, 119.3, 29.8, 29.6, 22.8, 20.7 (PhCH3). Anal. Found (calc. for C17H17N): C = 86.31 (86.76); H =

7.19 (7.29); N = 5.85 (5.95).

(3,4-Dihydro-2H-naphthalen-l-ylidene)-(4-methoxy-phenyl)-amine (lc) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), p-anisidine (9.24 g, 75 mmol) andp-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, l c (13.39 g, 53.3 mmol, 71%) was obtained as a yellow solid. !H-NMR (300 MHz): 8.36 (d, 1 H, J = 7.4 Hz), 7.30 (m, 2 H), 7.20 (d, 1 H, J = 7.4 Hz), 6.91 (d, 2 H, J = 8.8 Hz), 6.79 (d, 2 H, J = 8.8 Hz), 3.82 (s, 3 H, OCH3), 2.91 (t, 2 H, J = 6.1 Hz), 2.58 (t, 2 H, J = 6.4

Hz), 1.92 (p, 2 H, J = 6.2 Hz). ^C-NMR (75 MHz): 165.8,155.7,144.4,141.0,133.8, 130.4, 128.5, 126.2, 126.1, 120.7, 114.0, 55.3 (OCH3), 29.8, 29.7, 22.9. Anal. Found (calc. for C17H17NO): C = 79.78 (81.24); H = 6.61 (6.82); N = 5.37 (5.57).

(4-Chloro-phenyl)-(3,4-dihydro-2H-naphthalen-l-ylidene)-amine (Id) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), p-chloroaniline (8.59 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, Id (16.6 g, 54.8 mmol, 73%) was obtained as a yellow solid. XH-NMR (300 Mhz): 8.28 (d, 1

H, J = 7.4 Hz), 7.38 (t, 1 H, J = 7.4 Hz), 7.28 (m, 3 H), 7.20 (d, 1 H, J = 7.4 Hz), 6.73 (d, 2 H, J = 8.6 Hz), 2.90 (t, 2 H, J = 6.1 Hz), 2.50 (t, 2 H, J = 6.8 Hz), 1.92 (p, 2 H, J = 6.5 Hz). 13C-NMR (75 MHz): 166.1,150.0, 141.2,133.4,130.7,128.8,128.6,128.1,

Chapter 2

26.3, 126.2, 120.7, 29.7, 22.7. Anal, found (calc. for C16H14NCI): C = 74.69 (75.14); H = 5.45 5.52); N = 5.42 (5.48).

(4-Bromo-phenyl)-(3,4-dihydro-2H-naphthalen-l-ylidene)-amine ( l e ) According to general procedure A, starting from oc-tetralone (10.96 g, 75 mmol), p-bromoaniline (12.15 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, l e (14.6 g, 48.8 mmol, 65%) was obtained as a yellow solid. aH-NMR (300 MHz): 8.28 (d,

1 H, J = 7.4 Hz), 7.45 (d, 2 H, J = 8.6 Hz), 7.39 (t, 1 H, J = 7.4 Hz), 7.30 (t, 1 H, J = 7.4 Hz), 7.20 (d, 1 H, J = 7.4 Hz), 6.69 (d, 2 H, J = 8.6 Hz), 2.91 (t, 2 H, J = 6.1 Hz), 2.50 (t, 2 H, J = 6.8 Hz), 1.93 (p, 2 H, J = 6.4 Hz). 13C-NMR (75 MHz): 166.1, 150.5,

141.2, 133.4, 131.7, 130.7, 28.6, 126.3, 126.2, 121.2, 115.7, 29.72, 29.68, 22.7. Anal. Found (calc. for Ci6Hi4NBr): C = 63.81 (64.01); H = 4.67 (4.70); N = 4.64 (4.67).

(3,4-Dihydro-2H-naphthalen-l-ylidene)-(4-iodo-phenyl)-amine (If) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), p-iodoaniline (16.4 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, If (13.5 g, 39.0 mmol, 52%) was obtained as a yellow solid. JH-NMR (300 MHz): 8.27 (d, 1 H, J

= 7.7 Hz), 7.64 (d, 2 H, J = 8.4 Hz), 7.39 (t, 1 H, J = 7.7 Hz), 7.30 (t, 1 H, J = 7.7 Hz), 7.21 (d, 1 H, J = 7.7 Hz), 6.58 (d, 2 H, J = 8.4 Hz), 2.91 (t, 2 H, J = 6.1 Hz), 2.50 (t, 2 H, J = 6.5 Hz), 1.93 (p, 2 H, J = 6.2 Hz). 13C-NMR (75 MHz): 166.0, 151.2, 141.3,

'37.7, 133.4, 130.7, 128.6, 126.3, 126.2,121.6, 29.73, 29.69, 22.7. Anal. Found (calc. for Ci6Hi4NI):

= 51.56 (53.35); H = 4.06 (4.07); N = 3.77 (4.03).

(3,4-Dihydro-2H-naphthalen-l-ylidene)-(4-nitro-phenyl)-amine (lg) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), p-nitroaniline (10.36 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, l g (6.38 g, 24 mmol, 35%) was obtained as a yellow solid. !H-NMR (300 MHz): 8.26 (d, 2 H, J = 9.8 Hz), 8.23 (d, 1 H, J = 8.9 Hz), 7.42 (t, 1 H, J = 7.6 Hz), 7.32 (t, 1 H, J = 7.6 Hz), 7.24 (d, 1 H, J = 7.6 Hz), 6.89 (d, 2 H, J = 8.9 Hz), 2.93 (t, 2 H, J = 6.0 Hz), 2.49 (t, 2 H, J = 6.4 Hz), 1.97 (p, 2 H, J = 6.2 Hz). 13C-NMR (75 MHz): 166.1, 157.9, 143.3,

141.6,132.7,131.3,128.7, 126.4,124.9,119.5, 30.2, 29.6, 22.6. Anal. Found (calc. for C16H14N2O2): C = 72.25 (72.16); H = 5.24 (5.30); N = 10.37 (10.52).

Synthesis ofN-Heterocycles by Iminoannulation of Cydopalladated Imines

Ph Benzyl-(3,4-dihydro-2H-naphthalen-l-ylidene)-amine (lh) According to general procedure A, starting from a-tetralone (2.28 g, 15.8 mmol), benzylamine (1.67 g, 15.6 mmol) and acetic acid (catalytic amount) in toluene (50 mL) with molecular sieves using a reaction time of 2 days at reflux, l h (2.69 g, 11.4 mmol, 73%) was obtained as a yellow solid. ÏH-NMR (300 MHz): 8.59 (d, 1 H, J = 6.9 Hz), 7.68 (d, 2 H, J = 7.4 Hz), 7.55 (m, 3 H), 7.45 (m, 2 H), 7.30 (d, 1 H, J = 8.5 Hz), 4.86 (s, 2 H, PhCH2), 2.95 (t, 1 H, J = 6.1 Hz), 2.74 (t, 1 H, J = 6.4 Hz), 2.08 (p, 1 H, J = 6.2

Hz). 13C-NMR (75 MHz): 165.1, 141.0, 140.4, 134.8, 129.7, 128.3, 127.7, 126.4, 126.3, 125.9, 54.5

(PhCH2), 29.8, 28.2, 22.6. HRMS calcd. for C17H17N 236.1439, found 236.1430.

S^-Dihydro-lH-naphthalen-l-ylideneHsopropylamine (li) According to general procedure A, starting from a-tetralone (10.96 g, 75 mmol), isopropylamine (9.24 g, 75 mmol) and p-TsOH (catalytic amount) in xylenes (200 mL) with molecular sieves using a reaction time of 2 days at reflux, l i (13.39 g, 53.3 mmol, 71%) was obtained as a yellow oil. ÏH-NMR (300 MHz): 8.22 (d, 1 H, J = 7.4 Hz), 7.27 (m, 2 H), 7.13 (d, 1 H, J = 7.5 Hz), 3.91 (sept, 1 H, J = 6.2 Hz, CH-(CH3)2), 2.83 (t,

2 H, J = 6.0 Hz), 2.63 (t, 2 H, J = 6.5 Hz), 1.95 (p, 2 H, J = 6.3 Hz), 1.21 (d, 6 H, J = 7.2 Hz, CH-(CH3)2). 13C-NMR (75 MHz): 140.0,129.2,128.0,126.1, 125.7,117.7,117.6,113.9,113.7, 49.6

(CH-(CH3)2), 29.7, 26.9, 23.4 (CH-(CH3)2), 22.7. HRMS calcd. for C i3H i7N 187.1361, found 187.1364.

Preparation of 2b as general procedure B for the synthesis of di-n-acetato-bis(N-substituted-tetraloneketimine-6,C,N)dipalladium(II) complexes (2a, b, c, d, e, f, g, h)

Di-|i-acetato-bis(N-p-tolyl-tetraloneketimine-6,C,N)dipalladium(II) (2b) See step 2 in Scheme 2. In a typical experiment a mixture of Pd(OAc)2

(1.02 g, 4.55 mmol), l b (1.07 g, 4.55 mmol) and NaOAc (410 mg, 4.55 mmol) in dichloromethane (25 mL) was stirred at room temperature for 1 day. The resulting solution was concentrated in vacuo and 2 b was precipitated by addition of pentane. The green powder was filtered and washed with water, diethyl ether and p e n t a n e . After flash chromatography over a short silica column ( M e O H / C H2C l2 1:99) 2b

(1.31 g, 1.64 mmol, 72%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.10 (d, 2 H, J = 8.8 Hz), 7.09 (t, 1 H, J = 7.3 Hz), 6.97 (d, 1 H, J = 7.3 Hz), 6.91 (d, 2 H, J = 8.8 Hz), 6.83 (d, 1 H, J = 7.3 Hz), 2.63 (m, 2 H), 2.34 (s, 3 H, PhCH3), 2.27 (m, 2 H), 1.73 (p, 2 H, J = 6.0 Hz), 1.45 (s, 3 H,

Chapter 2

24.0, 122.9, 30.7, 29.7, 28.8, 23.5 (C02CH3), 20.9 (PhCH3). HRMS calcd. for C38H38N2Pd204

'98.0901, found 798.0923.

Di-(i-acetato-bis(N-phenyl-tetraloneketimine-6,C,N)dipalladium(II) (2a) According to general procedure B, starting from Pd(OAc)2 (286 mg, 1.27 mmol), l a (310 mg, 1.40 mmol) in dichloromethane (25 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash chromatography and ecrystalization from dichloromethane and pentane, 2a (256 mg, 0.332 mmol, 52%) was obtained s a yellow solid. ÏH-NMR (300 MHz): 7.31 (t, 1 H, J = 7.9 Hz), 7.21 (d, 1 H, J = 7.5 Hz), 7.10 (d, 2 H, J = 7.5 Hz), 7.00 (d, 1 H, J = 7.9 Hz), 6.98 (m, 1 H), 6.86 (d, 1 H, J = 7.9 Hz), 2.64 (m, 2 H), 2.26

:n, 2 H), 1.73 (p, 2 H, J = 6.0 Hz), 1.45 (s, 3 H, CC^CH3). 13C-NMR (75 MHz): 182.2,180.3, 156.2,

44.9, 144.2, 141.7, 130.7, 129.7, 127.9, 126.1, 124.2, 123.0, 29.8, 28.3, 23.5, 23.0 (C02CH3). HRMS

ilcd. for C36H34N2Pd204 770.0588, found 770.0609.

Di-(x-acetato-bis(N-p-anisyl-tetraloneketimine-6,C,N)dipalladium(II) (2c) According to general procedure B, starting from Pd(OAc)2 (830 mg, 3.67 mmol), le (930 mg, 3.70 mmol) and NaOAc (301 mg, 3.67 mmol) in dichloromethane (25 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash chromatography and recrystalization from dichloromethane and pentane, 2c (966 mg, 1.16 mmol, 63%) was obtained as a brown solid. ^H-NMR (300 MHz): 7.06 (t, 1 H, J = 7.5 Hz), 6.94 (d, 1 H, J = 7.5 Hz), 6.94 (d, H, J = 7.6 Hz), 6.80 (d, 1 H, J = 7.5 Hz), 6.80 (d, 2 H, J = 7.6 Hz), 3.81 (s, 3 H, OCH3), 2.61 (m, 2

1), 2.24 (m, 2 H), 1.71 (p, 2 H, J = 5.7 Hz), 1.52 (s, 3 H, C02CH3). ^C-NMR (75 MHz): 182.4,

L70.7, 157.9, 156.8, 144.5, 141.8, 138.3, 131.1, 129.8, 125.8, 123.3, 113.2, 55.7 (OCH3), 30.1, 28.7,

23.9,23.5 (C02CH3). HRMS calcd. for C38H4oN206Pd2 832.0956, found 832.0957.

Di-|i-acetato-bis(N-p-chloro-phenyl-tetraloneketimine-6,C,N)-dipalladium (II) (2d) According to general procedure B, starting from Pd(OAc)2 (1.02 g, 4.55 mmol), l d (1.16 g, 4.55 mmol) and NaOAc (373 mg, 4.55 mmol) in dichloromethane (25 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash chromatography and recrystallization from dichloromethane and pentane, 2d (1.38 g, 1.66 mmol, 73%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.24 (d, 2 H, J = 8.8 Hz), 7.10 (t, 1

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

H, J = 7.6 Hz), 6.86 (d, 4 H, J = 7.7 Hz), 2.68 (m, 2 H), 2.26 (m, 2 H), 1.77 (p, 2 H, J = 6.1 Hz), 1.58 (s, 3 H, CO2CH3). 13C-NMR (75 MHz): 182.7, 180.2, 156.2, 143.9,143.2,141.9, 131.6, 130.7,130.1, 127.9, 125.7, 123.2, 29.8, 28.2, 23.5, 23.2 (CO2CH3). HRMS calcd. for C36H34N2Pd2Cl204

839.9965, found 839.9957.

Di-n-acetato-bis(N-p-bromo-phenyl-tetraloneketimine-6,C,N)-dipalladium(II) (2e) According to general procedure B, starting from Pd(OAc)2 (1.05 g, 4.68 mmol), l e (1.40 g, 4.68 mmol) and NaOAc (384 mg, 4.68 mmol) in dichloromethane (25 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash chromatography and recrystalization from dichloromethane and pentane, 2e (1.50 g, 1.61 mmol, 69%) was obtained as a yellow solid. ÏH-NMR (300 MHz): 7.39 (d, 2 H, J = 8.7 Hz), 7.10 (t, 1 H, J = 7.6 Hz), 6.87 (d, 2 H, J = 7.6 Hz), 6.81 (m, 2 H), 2.68 (m, 2 H, 2.26 (m, 2 H), 1.77 (p, 2 H, J = 6.1 Hz), 1.58 (s, 3 H, CO2CH3). 13C-NMR (75 MHz): 185.5,183.1,158.9,146.7, 146.5,144.8, 133.7, 133.5, 133.0, 128.9, 126.1, 122.4, 32.6, 31.1, 26.4, 26.1 (CO2CH3). HRMS calcd. for C36H32N2Pd2Br204 925.8798, found 925.!

Di-n-acetato-bis(N-p-iodo-phenyl-tetraloneketimine-6,C,N)-dipalladium(II) (2f)According to general procedure B, starting from Pd(OAc)2 (1.02 g, 4.55 mmol), If (1.56 g, 4.55 mmol) and NaOAc (373 mg,

4.55 mmol) in dichloromethane (25 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash chromatography and recrystalization from dichloromethane and pentane, 2f (1.31 g, 1.41 mmol, 62%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.59 (d, 2 H, J = 8.6 Hz), 7.10 (t, 1 H, J = 7.6 Hz), 6.86 (d, 2 H, J = 8.6 Hz), 6.69 (d, 2 H, J = 7.7 Hz), 2.68 (m, 2 H), 2.26 (m, 2 H), 1.76 (p, 2 H, J = 6.0 Hz), 1.57 (s, 3 H, CO2CH3). 1 3C.N M R (75 M H z ) : 1 8 2.6 / i8 0. 3 , 156.1, 144.4, 143.9, 142.0, 136.9, 130.6,

130.1, 126.3, 123.2, 90.7, 29.8, 28.2, 23.5, 23.2 (CO2CH3). HRMS calcd. for C36H32N2Pd2Br204

925.8798, found 925.!

Di-n-acetato-bis(N-p-nitro-phenyl-tetraloneketimine-6,C,N)-dipalIadium(H) (2g) According to general procedure B, starting from Pd(OAc)2 (956 mg, 4.26 mmol), l g (1.13 g, 4.26 mmol) and NaOAc (349 mg, 4.26 mmol) in dichloromethane (25 mL) the crude product was obtained by concentration of the reaction mixture and precipitation by pentane. After flash chromatography and recrystalization from dichloromethane and pentane, 2g (1.30 g, 1.51 mmol, 71%) was

Chapter 2

obtained as a yellow solid. !H-NMR (300 MHz): 8.09 (d, 2 H, J = 9.0 Hz), 7.12 (t, 1 H, J = 7.6 Hz), 6.94 (d, 3 H, J = 9.0 Hz), 6.72 (d, 1 H, J = 7.6 Hz), 2.76 (t, 2 H), 2.31 (dd, 2 H), 1.86 (m, 2 H), 1.62 (s, 3 H, CO2CH3). 1 3

C-NMR (75 MHz): 183.5, 180.3, 156.0, 150.1, 145.5, 143.5, 142.8, 131.1, 130.5, 125.3, 123.6, 123.5, 30.0, 28.1, 23.6, 23.5 (CO2CH3). HRMS calcd. for C36H34N408Pd2 862.0446, found 862.0457.

Di-n-acetato-bis(N-benzyl-tetraloneketimine-6,C,N)dipalladium(II) (2h) According to general procedure B, starting from Pd(OAc)2 (500 mg, 2.23 mmol), l h (576 mg, 2.45 mmol) and NaOAc (201 mg, 2.45 mmol) in dichloromethane (25 mL) at a reaction temperature of 0 °C and a reaction time of 30 minutes the crude product was obtained after concentration of the reaction mixture and precipitation by pentane. After flash iiromatography and recrystalization from dichloromethane and pentane, 2h (739 mg, 0.925 imol, 83%) was obtained as a yellow solid. iH-NMR (300 MHz): 7.48 (d, 1 H, J = 7.1 Hz), 7.3 1, 3 H), 6.96 (m, 1 H, J = 7.1 Hz), 6.74 (d, 1 H, J = 7.3 Hz), 4.41 (d, 1 H, J = 3.9 Hz, NCHHTh), 3.85 (d, 1 H J = 3.9 Hz, NCHHTh), 2.57 (m, 2 H), 2.11 (m, 2 H), 2.11 (s, 3 H, CO2CH3), 1.61 (m, 2 ), . 13C-NMR (75 MHz): 182.2, 181.2, 156.8, 144.4, 140.8, 137.5, 130.2, 129.5, 128.7, 128.2, 127.4,

23.2, 54.5 (PhCH2N), 28.5, 28.1, 24.7 (CO2CH3), 23.3. HRMS calcd. for C38H4oN204Pd2

'.1058, found 800.1063.

reparation of 3b as general procedure C for the synthesis of di-n-chloro-bis(N-substituted-?traloneketimine-6,C,N)dipalladium(II) complexes (3a-h)

Di-n-chloro-bis(N-p-tolyl-tetraloneketimine-6,C,N)dipalladium(II) (3b) See step 3 in Scheme 2. A suspension of 2b (1.38 g, 1.73 mmol) and LiCl (0.73 g, 17 mmol) in acetone (25 mL) was stirred at room temperature for 15 minutes. The color changed gradually from yellow to pale yellow and some Pd(0) was formed. Addition of a few drops of water after 15 minutes is important because otherwise an extensive formation of palladium metal is observed. This decomposition seems to stem from a monomeric anionic complex which is formed after reaction of the chloro-ridged dimer with LiCl.[53] The resulting pale yellow complex was filtered and washed with water, acetone, diethylether and pentane. After drying in vacuo, 3b (1.19 g, 1.59 mmol, 92%.)

Synthesis ofN-Heterocycles by Iminoannulation of Cyclopalladated Imines

was obtained as a pale yellow solid. 1H-NMR (300 MHz): 7.87b (1 H), 7.17b (1 H), 7.05b (2 H),

6.86 (d, 2 H, J = 7.4 Hz), 5.98b (1 H), 2.76 (t, 2 H, J = 6.0 Hz), 2.47 (t, 2 H, J = 6.0 Hz), 2.17 (s, 3 H,

PhCH3), 1.87 (p, 2 H, J = 6.0 Hz); (b = broad). HRMS calcd. for C34H32N2Cl2Pd2 750.0012, found

750.0023.

Di-|i-chloro-bis(N-phenyl-tetraloneketimine-6,C,N)dipalladium(II) (3a) According to general procedure C, starting from 2a (103 mg, 0.133 mmol), LiCl (57 mg, 1.33 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3a (87 mg, 0.120 mmol, 90%) was obtained as a pale yellow solid. !H-NMR (300 MHz): 7.87b (1 H), 7.35b (1 H), 7.06b (3 H), 6.86 (d, 2 H, J = 7.4 Hz),

6.00b (1 H), 2.76 (t, 2 H, J = 5.9 Hz), 2.46 (t, 2 H, J = 5.9 Hz), 1.87 (p, 2 H, J = 5.9 Hz); (b = broad).

HRMS calcd. for C32H28N2Cl2Pd2 721.9699, found 721.9709.

+ 2,2'-Bipyridine)Pd(a-tetralone-phenyl ketimine)]+

(CF3S03)- (3a') According to a literature procedure,[40]

a mixture of 3a (48 mg, 0.066 mmol) and AgCF3SC>3 (34 CF3SO3" mg, 0.133 mmol, 2 equiv) in acetonitrile (5 mL) was stirred for 1 hour at room temperature. The resulting yellow solution was filtered through Celite to remove AgCl. To the filtrate was added 2,2'-bipyridine (22 mg, 0.15 mmol). After stirring for 1 hour the mixture was concentrated. Crystals of 3a' (38 mg, 0.060 mol, 91%) were obtained by slowly adding pentane on the acetonitrile solution. lH- and 13C-NMR data are similar as published by Selvakumar.[40]

Table 1. Selected bond distances (À) for 3a' (with ESD in parentheses)

Pd-N(l) 2.169(3) Pd-N(2) 2.048(2) Pd-N(3) 2.040(2) NQ)-C(l) 1.356(4) N(l)-C(5) 1.342(4) N(2)-C(6) 1.355(4) N(3)-C(19) 1.299(4) N(3)-C(21) 1.439(4) C(l)-C(2) 1.385(5) C(2)-C(3) 1.383(5) C(3)-C(4) 1.369(5) C(4)-C(5) 1.376(6) C(7)-C(8) 1.378(5) C(8)-C(9) 1.376(6) C(9)-C(10) 1.376(4) C(ll)-C(20) 1.405(4) C(12)-C(13) 1.389(4) C(13)-C(14) 1.378(4) C(15)-C(16) 1.502(5) C(15)-C(20) 1.402(4) C(16)-C(17) 1.429(9) C(17)-C(18) 1.545(9) C(18)-C(19) 1.494(4) C(18)-C(17A) 1.356(19) C(21)-C(22) 1.384(4) C(21)-C(26) 1.382(4) C(22)-C(23) 1.384(5) C(24)-C(25) 1.382(5) C(25)-C(26) 1.386(5) Pd-C(ll) 1.998(3) N(2)-C(10) 1.347(4) C(l)-C(6) 1.476(4) C(6)-C(7) 1.389(4) C(ll)-C(12) 1.385(4) C(14)-C(15) 1.389(4) C(16)-C(17A) 1.557(13) C(19)-C(20) 1.442(4) C(23)-C(24) 1.375(5)

Chapter 2

Table 2. Selected bond angles (°) for 3a' (with ESP in parentheses)

N(l)-Pd-N(2) 77.85(10) N(l)-Pd-N(3) 104.16(10) N(2)-Pd-N(3) 173.45(10) N(2)-Pd(Cll) 99.69(12) Pd-N(l)-C(l) 110.82(19) Pd-N(l)-C(5) 129.0(2) Pd-N(2)-C(6) 115.5(2) Pd-N(2)-C(10) 126.2(2) Pd-N(3)-C(19) 116.61(19) Pd-N(3)-C(21) 122.3(2) N(l)-C(l)-C(2) 121.7(3) N(l)-C(l)-C(6) 115.4(3) C(l)-C(2)-C(3) 119.3(3) C(2)-C(3)-C(4) 118.9(4) N(l)-C(5)-C(4) 123.0(3) N(2)-C(6)-C(l) 115.8(2) C(l)-C(6)-C(7) 122.8(3) C(6)-C(7)-C(8) 119.3(4) C(8)-C(9)-C(10) 118.9(3) N(2)-C(10)-C(9) 122.7(4) Pd-C(ll)-C(20) 112.9(2) C(12)-C(ll)-C(20) 117.5(3) C(12)-C(13)-C(14) 121.6(3) C(13)-C(14)-C(15) 120.1(3) C(14)-C(15)-C(20) 115.47(18) C(16)-C(15)-C(20) 119.7(3) C(15)-C(16)-C(17A) 112.6(6) C(16)-C(17)-C(18) 115.2(5) C(19)-C(18)-C(17A) 114.9(5) N(3)-C(19)-C(18) 125.3(5) C(18)-C(19)-C(20) 120.3(3) C(ll)-C(20)-C(15) 122.7(3) C(15)-C(20)-C(19) 121.2(3) N(3)-C(21)-C(22) 119.1(3) C(22)-C(21)-C(26) 121.0(3) C(21)-C(22)-C(23) 119.0(3) C(23)-C(24)-C(25) 119.7(3) C(24)-C(25)-C(26) 120.4(3) C(16)-C(17A)-C(18) 119.0(10) N(l)-Pd-C(ll) 164.23(10) N(3)-Pd-C(ll) 80.06(12) C(l)-N(l)-C(5) 117.7(3) C(6)-N(2)-C(10) 118.3(3) C(19)-N(3)-C(21) 121.1(2) C(2)-C(l)-C(6) 122.8(3) C(3)-C(4)-C(5) 119.3(3) N(2)-C(6)-C(7) 121.2(3) C(7)-C(8)-C(9) 119.3(3) Pd-C(ll)-C(12) 129.2(2) C(ll)-C(12)-C(13) 120.2(3) C(14)-C(15)-C(16) 122.6(3) C(15)-C(16)-C(17) 113.9(5) C(17)-C(18)-C(19) 111.2(3) N(3)-C(19)-C(20) 114.4(2) C(ll)-C(20)-C(19) 116.0(3) N(3)-C(21)-C(26) 119.8(2) C(22)-C(23)-C(24) 120.8(3) C(21)-C(26)-C(25) 119.1(3) Di-|i-chloro-bis(N-p-anisyl-tetraloneketimine-6,C,N)dipalladium(II) (3c) According to general procedure C, starting from 2c (966 mg, 1.16 mmol), LiCl (249 mg, 5.80 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction m i x t u r e and precipitation by water. After washing 3c (834 mg, 1.07 mmol, 92%) was obtained as a yellow solid. ÏH-NMR (300 MHz): 7.89b (1 H), 7.03b (3 H),

6.85 (d, 2 H , J = 7.3 Hz), 5.98b (1 H), 3.75 (s, 3 H, OCH3), 2.76 (t, 2 H, J =

5.9 Hz), 2.48 (t, 2 H, J = 5.9 Hz), 1.87 (p, 2 H, J = 5.9 Hz); (b = broad). 1RMS calcd. for C34H32N2C>2Cl2Pd2 781.9910, found 781.9922.

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

Di-n-chloro-bis(N-p-chloro-phenyl-tetraloneketimine-6,C,N)dipalladium(II) (3d) According to general procedure C, starting from 2d (949 mg, 1.13 mmol), LiCl (240 mg, 5.65 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3d (813 mg, 1.03 mmol, 91%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.87b (1

H), 7.04b (3 H), 6.86 (d, 2 H, J = 7.3 Hz), 5.99b (1 H), 2.76 (t, 2 H, J = 5.8

Hz), 2.47 (t, 2 H, J = 5.8 Hz), 1.87 (p, 2 H, J = 5.8 Hz); (b = broad). HRMS calcd. for C32H27N2Cl2Pd2 790.8998, found 790.9003.

Di-n-chloro-bis(N-/>bromo-phenyl-tetraloneketimine-6,C,N)dipalladium(II) (3e) According to general procedure C, starting from 2e (1.03 g, 1.11 mmol), LiCl (236 mg, 5.56 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3e (867 mg, 0.988 mmol, 89%) was obtained as a yellow solid. 2H-NMR (300 MHz): 7.67b (1

H), 7.06b (1 H), 7.06 (d, 2 H, J = 7.8 Hz), 6.87 (d, 2 H, J = 7.8 Hz), 6.00b (1

H), 2.78 (t, 2 H, J = 5.6 Hz), 2.47 (t, 2 H, J = 5.6 Hz), 1.88 (p, 2 H, J = 5.6 Hz); (b = broad). HRMS calcd. for C32H27N2Cl2Br2Pd2 (M+H) 878.7988, found 878.7992.

Di-fj-chloro-bis(N-substituted-tetraloneketimine-6,C,N)dipalladium(II) (3f) According to general procedure C, starting from 2f (1.07 g, 1.16 mmol), LiCl (245 mg, 5.78 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3f (1.05 mg, 1.08 mmol, 93%) was obtained as a yellow solid. aH-NMR (300 MHz): 7.69b (1 H), 7.05b (3 H),

6.86 (d, 2 H, ) = 7.4 Hz), 6.00b (1 H), 2.76 (t, 2 H, J = 6.0 Hz), 2.45 (t, 2 H, J

= 6.5 Hz), 1.89 (p, 2 H, J = 6.5 Hz); (b = broad). HRMS calcd. for C32H26N2Cll2Pd2 (M+H; -HCl) 938.7944, found 938.7958.

Cliapter 2

Di-(j-chloro-bis(N-p-nitro-phenyl-tetraloneketimine-6,C,N)dipalladium(II) (3g) According to general procedure C, starting from 2g (1.05 g, 1.22 mmol), LiCl (259 mg, 6.10 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3g (1.03 g, 1.06 mmol, 87%) was obtained as a yellow solid. XH-NMR (300 MHz): 8.27 (d, 2 H, J

= 8.4 Hz), 7.40 (d, 1 H, J = 7.3 Hz), 6.96 (t, 1 H, J = 7.3 Hz), 6.87 (d, 2 H, J = 8.4 Hz), 6.14 (d, 1 H, J = 7.3 Hz), 2.80 (t, 2 H, J = 5.7 Hz), 2.47 (t, 2 H, J = 7 Hz), 1.93 (p, 2 H, J = 5.7 Hz).

Di-(i.-chloro-bis(N-benzyl-tetraloneketimine-6,C,N)dipalladium(II) (3h) According to general procedure C, starting from 2h (739 mg, 0.925 mmol), LiCl (284 mg, 6.69 mmol) in acetone (10 mL) the crude product was obtained after concentration of the reaction mixture and precipitation by water. After washing 3h (626 mg, 0.832 mmol, 90%) was obtained as a yellow solid. iH-COSY NMR (300 MHz): 7.59 (d, 2 H, J = 7.4 Hz), 7.33 (t, 1 H, J = 7.4 Hz), 7.20 (d, 1 H, J = 7.4 Hz), 6.87 (t, 1 H, J = 7.3 Hz), 6.81 (d, 1 H, J = 3 Hz), 6.00 (d, 1 H, J = 7.3 Hz), 5.29 (s, 2 H, NCH2Ph), 2.69 (t, 2 H, J = 6.0 Hz), 2.63 (t, 2 H, J =

6.0 Hz,), 1.98 (p, 2 H, J = 6.0 Hz). HRMS calcd. for C36H38Cl2N2Pd2 782.4458, found 782.4457.

eparation of 4b as general procedure D for the synthesis of iminium salts (4a-h)

2,2-Dimethyl-3-methylene-l-p-tolyl-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (4b) See Scheme 3. To a suspension of 3b (323 mg, 0.43 mmol) in dichloromethane (10 mL) was added 1,1-dimethylallene (DMA, 107 \xL, 108 mmol, 2.5 equiv) and the mixture was stirred for one day. During the reaction the pale yellow suspension turned into a red purple clear solution. After removing the solvent, the residue was dissolved in methanol and the mixture was heated to reflux for 15 minutes. During this time the color of the solution changed from purple to yellow green with formation of Pd(0). The resulting mixture vas filtered over Celite to remove Pd(0) and to the resulting solution was added KPF^ (790 mg, 1.3 mmol, 10 equiv). After anion exchange for one day the solvent was removed and the

roducts were extracted in CH2CI2 and filtered over Celite to remove inorganic salts. After :oncentration of the solution, 4b was precipitated by adding diethylether. After filtration and -frying in vacuo 4b (156 mg, 0.348 mmol, 81%.) was obtained as a pale yellow solid.

iH-COSY-Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Imines

NMR (300 MHz): 7.73 (dd, 1 H, Ji_2 = 7.5 Hz, J2_3 = 7.7 Hz, H2), 7.56 (d, 1 H, Ji_2 = 7.5 Hz, Hi),

7.43 (d, 1 H, Ji7_i8 = 8.2 Hz, Hi8), 7.40 (d, 1 H, J2.3 = 7.7 Hz, H3), 7.24 (d, 1 H, Ji7_i8 = 8.2 Hz, H i / ) , 5.79 (s, 1 H, H5' ), 5.64 (s, 1 H, H5), 3.01 (t, 2 H, J7-8 = 6.2 Hz, H7), 2.71 (t, 2 H, J8.9 = 6.4 Hz, H9), 2.44 (s, 3 H, PhCH3), 1.92 (m, 2 H, J7.8 = 6.2 Hz, ]8-9 = 6.4 Hz, Hg), 1.51 (s, 6 H, H2i). 1 3 C-NMR (75 MHz): 178.4 (C=N), 146.9, 142.2, 141.3, 138.3, 135.8, 134.3, 131.3 (Jc-H= 160 Hz, Cig), 130.1 (JC-H = 163 Hz, C3), 125.3 (JC-H = 161 Hz, C17), 123.5 (JC-H = 164 Hz, Ci), 120.7, 117.4 (JC -H(5) = 162 Hz, Jc-H(5') = 160 Hz, C5), 67.4 (Ci3), 33.3 (JC-H = 132 Hz, C9), 28.2 (JC.H = 131 Hz, C7), 25.4 (Jc-H = 130 Hz, C21), 21.3 (Jc-H = 125 Hz, Q ) , 21.1 (JC-H = 114 Hz, C20). 31P-NMR (121

MHz): - 143.9 (JP.F = 719 Hz). Anal. Found (calc. for C2 2H2 4NF6P): C = 57.97 (59.06); H = 5.35

(5.41); N = 3.17 (3.13). HRMS calcd. f0rC22H25N 303.1987, found 303.1956.

2,2-Dimethyl-3-methylene-l-phenyl-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (4a) According to general procedure D, starting from 3a (287 mg, 0.395 mmol), DMA (98 LXL, 0.988 mmol) in dichloromethane (50 mL), 4a (197 mg, 0.454 mmol, 60%) was obtained as a yellow solid. ÏH-NMR (300 MHz): 7.82 (t, 1 H, J = 7.4 Hz), 7.63 (d, 1 H, J = 7.4 Hz), 7.62 (d, 1 H, J = 7.6 Hz), 7.40 (d, 1 H, J = 7.5 Hz), 7.40 (d, 2 H, J = 7.5 Hz), 7.39 (d, 2 H, J = 7.5 Hz), 5.82 (s, 1 H, H5'), 5.67 (s, 1 H, H5), 3.03 (t, 2 H, J7.8 = 6.1 Hz, H7), 2.74 (t, 2 H, fe.9 = 6.4 Hz, H9), 1.94 (m, J7.8 = 6.1 Hz, J8_9 = 6.4 Hz, H8), 1.52 (s, 6 H, H2i). 13C-NMR (75 MHz): 178.3 (C=N), 146.9,141.9,138.4 (C2), 136.9, 135.9, 130.9 (C19), 130.8 (Ci8), 130.1 (C3), 125.7 ( Q7) , 123.6 (Ci), 120.6, 117.6 (C5), 67.4 (C13), 33.4 (Cg), 28.2 (C7), 25.4 (C2i), 21.3 (Cg). 31P-NMR (121 MHz): -143.9 (Jp.F = 715 Hz).

HRMS calcd. for C2i H2 3N (M+H) 289.1830, found 289.1833.

l-(4-Methoxy-phenyl)-2,2-dimethyl-3-methylene-2,7,8,9-tetrahydro-3H-1-azonia-phenalene, hexafluoro phosphate (4c) According to general procedure D, starting from 3c (332 mg, 0.423 mmol), DMA (105 \>L, 1.06 mmol) in dichloromethane (10 mL) 4c (200 mg, 0.216 mmol, 51%) was obtained as a yellow solid. ÎH-NMR (300 MHz): 7.74 (t, 1 H, J = 7.4 Hz), 7.58 (d, 1 H, J = 7.4 Hz), 7.42 (m, 2 H, J = 7.4 Hz), 7.30 (d, 2 H, J = 8.9 Hz), 7.12 (d, 2 H, J = 8.9 Hz), 5.80 (s, 1 H, H5'), 5.66 (s, 1 H, H5), 3.89 (s, 3 H,

OCH3), 3.03 (t, 2 H, J7.8 = 6.1 Hz, H7), 2.74 (t, 2 H, J8.9 = 6.4 Hz, H9), 1.94

(m, 2 H, J7.8 = 6.1 Hz, J8.9 = 6.4 Hz, H8), 1.52 (s, 6 H, I ^ i ) . 13C-NMR (75

MHz): 178.9 (C=N), 160.9, 147.0, 142.3 ( Q9) , 138.2 (C2), 135.8, 130.1 (C3), 129.3,126.9 (Ci8), 123.4

(Ci), 120.8, 117.2 (C5), 115.7 (CJ 7), 67.6 (C13), 55.6 (OMe), 33.4 (C9), 28.2 (C7), 25.4 (C2i), 21.3

72 (57.02); H = 5.20 (5.22); N = 3.07 (3.02).

Chapter 2

l-(4-Chloro-phenyl)-2,2-dimethyl-3- methylene-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (4d) According to general procedure D, starting from 3d (274 mg, 0.347 mmol), DMA (85 nL,

13' 0.868 mmol) in dichloromethane (10 mL) a

mixture of 4d and 5d' (89 mg, 0.274 mmol, 79%, ratio 3:1) was obtained as a yellow solid. !H-NMR (300 MHz): 7.76-7.54 (m, 8 [), 7.40 (d, 4 H, 8.7 Hz), 7.30 (d, 2 H, 7.5 Hz), 5.82 (s, 1 H, H5>; 4d), 5.67 (s, 1 H, H5, 4d), 4.86 (s, 2 ';, H14; 5d), 2.99 (dt, 4 H, J7_8 = 6.5 Hz, H7; 4d+5d), 2.79 (t, 2 H, J8-9 = 6.3 Hz, H9; 5d), 2.73 (t, 2 , Js-9 = 6.3 Hz, H9; 4d), 2.08 (s, 3 H, H13; 5d), 2.01 (s, 3 H, H13'; 5d), 2.01 (m, 4 H, H8; 4d+5d), 53 (s, 6 H, H21). 13C-NMR (75 MHz): 180.6 (C=N), 148.9, 148.3,143.5, 142.6, 140.2,138.6,137.5, 36.7,132.8, 132.7,131.8, 130.0,128.9, 128.3,127.2,125.2, 122.3,119.3, 119.2, 117.7, 69.2, 67.2(Ci3; d), 58.9, 35.1, 32.9, 30.1, 29.7, 27.0, 24.2, 23.3, 22.8, 22.6. 31p-NMR (121 MHz): -144.0 (Jp.F = 720

Hz). HRMS calcd. for C21H21NCI 322.1363, found 322.1378.

l-(4-Iodo-phenyl)-2,2-dimethyl-3-methylene-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, chloride (4f) According to general procedure D, starting from 3f (354 mg, 0.363 mmol), DMA (89 nL, 0.908 mmol) in dichloromethane (10 mL) 4f (113 mg, 0.274 mmol, 75%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.81 (d, 1 H, J = 7.7 Hz), 7.69 (m, 5 H), 7.40 (d, 1 H, J = 7.7 Hz), 5.80 (s, 1 H, H5'), 5.67 (s, 1 H, H5), 3.20 (m, 2

H, H7), 3.05 (m, 2 H, H9), 2.02 (m, 2 H, H8), 1.58 (s, 6 H, H2i). 13C-NMR

could not be interpreted safely because of too many side-signals. 3 1P

-NMR (121 MHz): -143.8 (Jp_F = 715 Hz). HRMS calcd. for C21H21NI M+H) 415.0797, found 415.0831.

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalkdated Imines

2,2-Dimethyl-3-methylene-l-p-nitro-phenyl-2,3-dihydro-lH-l-aza-phenalene (4g) According to general procedure D, starting from 3g (468 mg, 0.575 mmol), DMA (143 nL, 1.45 mmol) in dichloromethane (10 mL) with a reaction time of one week, 4g (275 mg, 0.75 mmol, 65%) was obtained as a yellow solid. ÎH-NMR (300 MHz): 8.32 (d, 2 H, J i7.1 8 = 8.8

Hz, Hi8), 7.78 (d, 1 H, J = 7.6 Hz), 7.66 (d, 1 H, J = 7.6 Hz), 7.50 (t, 1 H, J = 7.8 Hz), 7.49 (t, 1 H, J = 7.6 Hz), 7.42 (d, 2 H, J1 7.1 8 = 8.8 Hz), 7.27 (t, 1 H, J = 7.8 Hz), 7.16 (t, 1 H, J = 7.8 Hz), 5.60 (s, 1 H, H5-), 5.23 (s, 1 H, H5), 1.39 (s, 6 H, CH3). 31p-NMR (121 MHz): -143.8 (JP_F = 719 Hz). HRMS calcd. for C2i H i8N20 2 (M-HC1) 330.1368, found 330.1384. l-Benzyl-2,2-dimethyl-3-methylene-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (4h) According to general procedure D, starting from 3h (205.5 mg, 0.273 mmol), DMA (68 \iL, 0.683 mmol) in dichloromethane (10 mL) 4h (211 mg, 0.472 mmol, 86%) was obtained as a yellow solid. !H-NMR (300 MHz): 7.74 (t, 1 H, J = 7.7 Hz), 7.57 (d, 1 H, J = 7.6 Hz), 7.40 (d, 1 H, J = 7.7 Hz), 7.40 (m, 4 H), 7.13 (d, 2 H, J = 7.0 Hz), 5.78 (s, 1 H, H5'), 5.66 (s, 1 H, H5), 5.39 (s, 1 H, Hi6), 3.19 (t, 2 H, Jn. 12 = 6.2 Hz, H n ) , 3.02 (t, 2 H, Ji2-13 = 6.1 Hz, H13), 2.01 (m, 2 H, Jn_1 2 = 6.2 Hz, J1 2-i3 = 6.1 Hz, Hi 2) , 1.65 (s, 6 H, H3). !3C-NMR (75 MHz): 177.7 (C=N), 146.1, 142.1, 137.8 (C8), 135.8, 131.9, 130.1, (C9), 129.5 (Ci9), 128.3 (C20), 124.7 ( d8) , 123.6 (C7), 120.9,117.5 (C5), 67.0 (C2), 53.0 (Ci6), 31.6 (C13), 28.3 (Cu), 24.0 (C3), 21.7 (Ci2). 31P-NMR (121 MHz): -143.8 (JP.F = 711 Hz). HRMS

calcd. for C22H25N 303.1987, found 303.1975.

4/4' 5/5' 6/6 23.2. CI 2 5/5' 4/4'

1-Chloro-l-ethynyl cyclohexane This synthesis was carried out according to a procedure published by Brandsma.[54] ÏH-NMR (300 MHz): 2.66 (s, 1 H, Hi), 2.13 (m, 2 H, H2), 1.98 (m, 2 H, H2'), 1.65 (m, 4 H, H5+H5'), 1.49 (m,

1 H, H6), 1.38 (m, 1 H, H6')- 13C-NMR (75 MHz): 85.98, 73.3, 62.2, 42.1, 24.5,

5 4 _{Vinylidenecyclohexane This synthesis was carried out according to a} ^ - procedure published by Brandsma.[54] ÏH-NMR (300 MHz): 4.54 (p, 2 H, Hi),

2.14 (m, 4 H, H4), 1.47 (m, 6 H, H5+H6). 13C-NMR (75 MHz): 203.2 (C2), 100.9

Clmpter 2

reparation of 6a as general procedure E for the synthesis of iminium salts (6a, b, c)

3-Cyclohexylidene-l-phenyl-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluorophosphate (6a) See Scheme 4. In a 50 mL Schlenk flask was added vinylidenecyclohexane (93 mg, 0.857 mmol, 3 equiv) to a suspension of 3a (188 mg, 0.269 mmol) in MeCN (25 mL). The mixture was heated to reflux for 10 minutes after which a clear green solution formed together with some Pd black. The mixture was iltered over Celite to remove Pd(0). After anion exchange with KPF6 (494 mg, 2.69 mmol, 10 :quiv) for 1 night the solvent was removed in vacuo and the iminium salt was extracted in 'H2C12- 6a was precipitated by addition of pentane. The resulting brown / black sluggish oil vas dissolved in MeCN and washed with pentane. The latter procedure was repeated several times. The resulting black solid was isolated. The yield was so low that it was not determined. H-NMR (300 MHz): 7.70-7.50 (m, 5 H), 7.26 (m, 3 H), 4.80 (s, 2 H, H l l ) , 3.00 (t, 2 H, J = 5.9 Hz), .78 (t, 2 H, J = 6.3 Hz), 2.54 (m, 2 H), 2.36 (m, 2 H), 1.99 (p, 2 H, J = 6.1 Hz, H8), 1.70 (m, 6 H). 3C-NMR (75 MHz): 177.2 (C=N), 149.0,146.5,140.9,137.1,136.7,131.0,130.7,128.5,126.6,123.9, 23.4, 113.3, 56.8 (NCH2), 31.6, 31.4, 31.1, 28.5, 28.3, 28.0, 26.1, 21.0. HRMS calcd. for C24H26F6NP 473.1707, found 473.1707. 3-Cyclohexylidene-l-p-tolyl-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (6b) According to general procedure E, starting from vinylidenecyclohexane (114 |iL, 0.738 mmol), 3b (181 mg, 0.246 mmol) and K P F ö (830 mg, 4.49 mmol), 6b was obtained. !H-NMR (300 MHz): 7.66 (t, 1 H, J = 7.7 Hz), 7.45-7.30 (m, 6 H), 4.88 (s, 2 H, H l l ) , 3.02 (t, 2 H, J = 5.9 Hz), 2.83 (t, 2 H, J = 6.2 Hz), 2.54 (m, 2 H), 2.45 (s, 3 H, PhCH3), 2.37 (m, 2 H), 2.00 (p, 2 H, J =

6.1 Hz, H8), 1.70 (m, 6 H). 13C-NMR (75 MHz): 177.2 (C=N), 149.0,

146.4, 141.2, 138.4, 137.1, 136.5, 131.4, 128.4, 126.5, 123.6, 123.4, 113.3, 56.9 (Cn), 31.6, 31.4, 31.1, 28.5, 28.3, 28.0, 26.0, 21.04 (Me), 21.00. HRMS calcd. for C25H28N 342.2222, found 342.2223.

Synthesis of N-Heterocycles by Iminoannulation ofCyclopalladated lmines

3-Cyclohexylidene-l-(4-methoxy-phenyl)-2,7,8,9-tetrahydro-3H-l-azonia-phenalene, hexafluoro phosphate (6c) According to general procedure E, starting from vinylidenecyclohexane (121 mg, 1.12 mmol), 3c (352 mg, 0.449 mmol) and KPF6 (830 mg, 4.49 mmol), 6c was

obtained. Due to inseparable side-products interpretation of NMR-spectra is difficult. ÏH-NMR (300 MHz): 7.74 (t, 1 H, J = 7.7 Hz), 7.65 (t, 1 H, J = 7.7 Hz), 7.43 (d, 2 H, J = 9.1 Hz), 7.32 (d, 1 H, J = 7.7 Hz), 7.27 (d, 1 H, J = 7.7 Hz), 7.09 (d, 2 H, J = 9.1 Hz), 4.85 (s, 2 H, Hn) , 3.87 (s, 3

H, OMe), 3.00 (t, 2 H, J = 6.1 Hz), 2.83 (t, 2 H, J = 7.0 Hz), 2.52 (m, 2 H), 2.37 (m, 2 H), 2.00 (m, 2 H), 1.69 (m, 6 H). 13C-NMR (75 MHz): 159.0, 143.1, 140.9, 133.7, 129.2, 128.8, 126.6, 121.4, 117.2,

117.1, 115.5, 98.1, 55.7 ( Cn) , 55.34 (OMe), 33.1, 31.7, 30.5, 29.4, 28.4, 26.5, 21.8. HRMS could not

be determined.

= . Propargyl tosylate This synthesis was carried out by a procedure of Westmijze et OTs a/-[55] !H-NMR (300 MHz): 7.82 (d, 2 H, J = 8.3 Hz), 7.36 (d, 2 H, J = 8.3 Hz), 4.70 (d, 2 H, J = 2.4 Hz, CH2); 2.48 (d, 1 H, J = 2.4 Hz, O C H ) , 2.46 (s, 3H, Me). ^C-NMR (75 MHz):

145.0,132.7, 129.6,127.9, 60.2, 57.1, 21.5 (PhCH3), 14.0 (C=CH).

/ = , = Phenylallene To a well stirred suspension of CuBr (21.52 g, 0.15 mol) in THF (250

Ph

mL) at 0 °C was added a solution of freshly prepared PhMgBr (0.15 mol in 150 mL THF). After addition the mixture was stirred for 30 min at 0 °C. The mixture was cooled to - 30 °C and propargyl tosylate (21.0 g, 0.10 mol) in THF (50 mL) was added dropwise. After addition the mixture was allowed to warm to room temperature and was stirred for 1 h. The solution was poured into a mixture of KCN (3 g) dissolved in saturated aqueous NH4CI solution (500 mL). The water layer was washed with Et20 (2 x 200 mL). The combined extracts were dried (MgSC>4). After removing the solvent the product was extracted in pentane and filtered over Celite. After distillation under reduced pressure, phenylallene (5.52 g, 47.6 mmol, 48%) was obtained as a colorless liquid. !H-NMR (300 MHz): 7.4 - 7.3 (m, 5 H), 6.17 (t, 1 H, J = 6.8 Hz, PhCH=C), 5.15 (d, 2 H, J = 6.8 Hz, C=CH2). 13C-NMR (75 MHz): 209.6 (C=C=C), 133.7, 128.4,

126.7,126.5, 93.7, 78.5.

Attempted syntheses of iminium salts with phenylallene Conditions similar to the synthesis of iminium salts 4 and 5 were both unsuccessful to obtain clean reaction products starting from cyclopalladated chloro dimers of a-tetralone ketimines (3a-c) and phenylallene. Attempts to perform the reaction in MeOH were also unsuccessful.

Chapter 2

eparation of 8a as general procedure F for the synthesis of enamines (8a, b, c, d, g, h)

2,2-Dimethyl-3-methylene-l-phenyl-2,3,7,8-tetrahydro-LH-l-aza-phenalene (8a) See step (i) in Scheme 5. To a solution of 4a (53.8 mg, 0.124 mmol) in methanol (2 mL) with 4Â molecular sieves was added KOH (55.7 mg, 0.992 mmol, 8 equiv) and the resulting mixture was allowed to stand at room temperature for 1 day. The mixture was separated from the molecular sieves. The molecular sieves were . a s h e d with methanol ( 3 x 2 mL) and the washings were collected. After removal of the lethanol, 8a (30.8 mg, 0.107 mmol, 87%) was obtained after extraction in pentane as a yellow il. It was impossible to purify this oil by flash chromatography because of hydrolysis of the enamine on the column. *H-NMR (300 MHz): 7.41 (m, 3 H), 7.32 (d, 1 H, J = 7.2 Hz), 7.23 (m, 3

)), 7.18 (d, 1 H, J = 7.6 Hz), 7.11 (d, 1 H, J = 7.1 Hz), 5.42 (s, 1 H, Hi2), 5.13 (s, 1 H, Hi2'), 4.21 (t, H, Js-9 = 4.7 Hz, H9), 2.76 (t, 2 H, J7_8 = 7.9 Hz, H7), 2.20 (td, J7-8 = 7.9 Hz, J8-9 = 4.7 Hz, Hg), .25 (s, 6 H, His). 13C-NMR (75 MHz): 149.3, 144.5, 140.4, 136.7, 131.5, 130.6, 128.7, 126.9, 126.8, 26.7,126.4,123.1,105.5 (Cr2), 101.3 (C9), 56.2 (Ci 3), 28.3 (C7), 26.7 (C15), 22.6 (C8). HRMS calcd. ir C21H22N (M+H) 288.1752, found 288.1740. 2,2-Dimethyl-3-methylene-l-p-tolyl-2,3,7,8-tetrahydro-lH-l-aza-phenalene (8b) According to general procedure F, starting from 4b (20.4 mg, 0.0456 mmol) and KOH (10 mg, 0.178 mmol) in methanol (2 mL), 8b (11.2 mg, 0.037 mmol, 81%) was obtained as a yellow oil after extraction in pentane. !H-COSY-NMR (300 MHz): 7.38 (d, 1 H, J = 7.7 Hz), 7.20-7.10 (m, 6 H), 5.41 (s, 1 H, Hi2), 5.13 (s, 1 H, Hx 2'), 4.22 (t, 1 H,

J8.9 = 4.7 Hz, H9), 2.76 (t, 2 H, J7.8 = 8.0 Hz, H7), 2.39 (s, 3 H, PhCH3),

2.21 (td, 2 H, J7.8 = 8.0 Hz, J8.9 = 4.7 Hz, H8), 1.24 (s, 6 H, H15). 1 3C

-NMR (75 MHz): 149.3, 141.7, 140.5, 136.0, 135.7, 131.1, 130.6, 129.4, 127.2, 126.8, 126.7, 123.1, 105.4 (Ci2), 101.0 (C9), 56.2 (C13), 28.3 (C7), 26.6 (C15), 22.6 (C8), 20.9 (C2 0). HRMS calcd. for

Synthesis of N-Heterocycles by Iminoannulation of Cyclopalladated Mines

l-(4-Methoxy-phenyl)-2,2-dimethyl-3-methylene-2,3,7,8-tetrahydro-1-H-l-aza-phenalene (8c) According to general procedure F, starting from 4c (32.7 mg, 0.0706 mmol) and KOH (32 mg, 0.717 mmol) in methanol (2 mL), 8c (20.6 mg, 0.0650 mmol, 92%) was obtained as a yellow oil after extraction in dichloromethane. XH-NMR (300 MHz):

7.40 (d, 1 H, Ji_2 = 7.5 Hz, Hi), 7.17 (m, 4 H, H17, H8-H9), 6.91 (d, 2 H,

J17-18 = 8.9 Hz, His), 5.40 (s, 1 H, H1 2), 5.13 (s, 1 H, H12'), 4.21 (t, 1 H,

J8-9 = 4.7 Hz, H9), 3.84 (s, 3 H, O Π3 ) , 2.75 (t, 2 H, J7_8 = 7.9 Hz, H7),

2.20 (td, 2 H, J7_8 = 7.9 Hz, J8_9 = 4.7 Hz, Hg), 1.23 (s, 6 H, H15). 1 3C

-NMR (75 MHz): 157.8, 149.4, 140.6, 137.0, 135.8, 132.2, 130.6, 127.1, 126.73, 126.68, 123.1, 113.9, 105.4 (C12), 100.7 (C9), 56.3 (C13), 55.1 (C2o), 28.4 (C7), 26.6 (C15), 22.6 (C8). HRMS calcd. for

C22H24NO (M+H) 318.1858, found 318.1837.

l-(4-Chloro-phenyl)-2,2-dimethyl-3- methylene-2,3,7,8-tetrahydro-lH-l-aza-p h e n a l e n e (8d) According to general procedure F, starting from a mixture of 4d and 4d' (44.9 mg, 0.0960 mmol, ratio 3:1) and KOH (43 mg, 0.535 mmol) in methanol (2 mL) a mixture of 8d and 8d' (20.8 mg, 0.0647 mmol, 67%, ratio 3:1) was obtained as a yellow oil after extraction in dichloromethane. 1H-NMR

(300 MHz): 7.45 (m, 3 H), 7.28 (d, 1 H), 7.15 (m, 11 H), 5.43 (s, 1 H, H12; 8d), 5.13 (s, 1 H, H: 2' ; 8d), 5.03 (t, 1 H, J8.9 = 4.8 Hz, H9; 8d'), 4.25 (t, 1 H, J8.9 = 4.5 Hz, H9; 8d), 4.08 (s, 2 H, H14; 8d'), 2.76 (t, 4 H, J7_8 = 7.8 Hz, H7; 8d+8d'), 2.22 (m, 4 H, H8; 8d'+8d), 2.04 (s, 3 H, H13; 8d'), 1.81 (s, 3 H, H13- 8d'), 1.24 (s, 6 H, H15, 8d). 8d : " C - N M R (75 MHz): 149.0, 143.1, 140.4, 136.5, 135.7, 132.8, 132.0, 130.5, 129.0, 127.0, 126.8, 123.2, 105.7 (C12), 102.2 (C9), 56.3 (C13), 28.2 (C7), 26.7 (C15), 22.5 (C8). 8d' : 13C-NMR (75 MHz): 101.4 (C9), 52.1 (C15), 39.2 (C13), 28.4 (C7), 26.3 (C13O,

22.1 (C8) (aromatic signals have too little signal to noise ratio to be interpreted safely). HRMS