New catalytic reactions of (unsaturated) nitriles via metal-ligand cooperative activation of the
C≡N bond
Guo, Beibei
DOI:10.33612/diss.136481036
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Guo, B. (2020). New catalytic reactions of (unsaturated) nitriles via metal-ligand cooperative activation of the C≡N bond. University of Groningen. https://doi.org/10.33612/diss.136481036
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Chapter 5
Synthesis of Chiral Ruthenium and
Manganese PNP Pincer Complexes and
Their Application in Enantioselective
oxa-Michael Addition Reactions
ABSTRACT: In this chapter, we report the synthesis of chiral ruthenium and
manganese PNP pincer complexes, which contained a pyridine backbone with
a chiral phosphorus moiety. Treating the chiral PNP pincer ligands with the
corresponding metal precursors resulted in two chiral ruthenium PNP pincer
complexes in excellent yields. The manganese PNP pincer complexes were
obtained as a mixture of the neutral di-carbonyl complex and the cationic
tris-carbonyl complex with a bromide counter anion. These complexes were tested
in the enantioselective oxa-Michael addition reactions, which resulted in
moderate yields and low ee’s. The GC analysis suggested that the low ee’s are
probably due to rapid cis-trans isomerization of the substrates, a reaction that
is catalysed by the PNP pincer complexes.
5.1 Introduction
Compounds containing a chiral phosphorus moiety are widely used for asymmetric reactions, including (transfer)hydrogenation,1-6 C-C bond formation,3, 7 as
organocatalysts or as chiral ligands. The synthesis of these compounds in particular of
P-stereogenic ligands is often still challenging due to the lengthy synthetic pathways
and the need to work under strictly oxygen-free conditions.8 Transition metal pincer
complexes have received continuous attention, and recently many chiral P‑containing pincer ligands and the corresponding chiral complexes have been reported by Morris, 9-13 Mezzetti,2, 14-17 Kirchner,18 Clarke19 and Beller,20 among others. The most successful
application of these catalysts is in the (transfer) hydrogenation of ketones to produce the corresponding chiral secondary alcohols (Scheme 1A).1, 5-6 As to the application in
asymmetric conjugate addition reactions, only moderate enantioselectivity was obtained (Scheme 1B). The Imamoto group developed Pd/Ni catalysts containing a PCP or PNP chiral phosphine pincer ligand, which led to moderate to good ee’s in hydrophosphination21 and hydroamination.4, 22 The Togni group reported a new Ni
pincer complex based on the Pigiphos ligand and reached excellent enantioselectivity with methylacrylonitrile in the same reactions.23-27
Scheme 1. Selected chiral pincer ligands and its applications
Previously, our group and Milstein’s group respectively demonstrated conjugate addition of alcohols to α,β-unsaturated nitriles (oxa-Michael addition) catalysed by the Milstein-type Ru or Mn PNN pincer complexes via metal-ligand cooperative activation.28-30 Beyond the achiral catalysts, as we described in chapter 4, we recently
reported the synthesis of new chiral PNN pincer complexes (Scheme 2) and applied them to asymmetric hydrogenation and asymmetric hetero-Michael addition, which resulted into low ee’s.31 Based on these results, we decided to change our strategy and
Scheme 2. Asymmetric oxa-Michael addition catalysed by Ru chiral pincer complexes
5.2 Results and discussion
5.2.1 Synthesis and Characterization of P-chiral PNP pincer complexes
P-chiral PNP pincer metal complexes have been developed by the Mezzetti group at the ETH Zürich. A series of Fe and Mn PNP pincer complexes were synthesized and applied for the enantioselective transfer-hydrogenation of ketones.2, 14-16 In view of their
expertise in this area I have spent some weeks in the Mezzetti labs, where I have synthesized ligands 1a and 1b according to routes A and B (Scheme 3).32 Ligand 1c was
synthesized later.33
Treating the borane-protected dimethyl-tert-butylphosphine with sec-butyllithium and (-)-sparteine followed by oxidative quenching with O2/P(OEt)3 led to formation of
borane protected tert-butyl-hydroxymethyl-nethylphosphine in 75% ee.8, 15, 34, 35 The
enantiomeric purity was further increased via recrystallization of its benzoate ester.36
After deprotection via basic hydrolysis, Ru-catalyzed oxidation/decarboxylation produced the volatile borane protected chiral methyl-tert-butyl phosphine maintaining the high enantiopurity. After deprotonation by n-BuLi, reaction with bis(chloromethyl)pyridine led to the formation of the bis-borane protected l ligand 1a in moderate yield.
Based on Mislow’s and Han’s reports on synthesis of chiral phosphinates, the Mezzetti group optimized an alternative procedure for ligand 1b (Scheme 3B).15, 37-39 Starting
from (-)-menthol and PhPCl2, (-)-menthyl-H-phenylphosphinate was prepared and the
enantiopure isomer(RP) was isolated by crystallization below -30oC.38 Subsequently,
deprotonation, reaction with acetaldehyde and reduction with BH3 led to the desired
borane protected chiral (1-hydroxyethyl)-methyl-phenylphosphine on gram scale.40
This compound was treated with NaH and reacted with bis(chloromethyl)pyridine forming bis-borane protected ligand 1c with.
For the synthesis of ligand 1c with Ph and tBu substituents on phosphorus, the
carbanion formed by treating borane protected tert-butyl-phenylphosphine with n-BuLi and (-)-sparteine was reacted with 2,6-bis(iodomethyl)pyridine forming the
desired bis-borane protected P-chiral PNP ligand 1c on gram scale with >99% ee after crystallization from THF and hexane.
Scheme 3. Synthesis of chiral ligands. A) ligand 1a following Livinghouse’s route; B) ligand 1b via Evans’ and
Imamoto’s methods; C) ligand 1c reported by Mezzetti’s group
There are two general methods for the deprotection of borane protected phosphine ligands: a) mild heating with excess amine, such as Et2NH, pyrrolidine or morpholine;1, 21, 33 b) treating with a strong acid, for instance HBF4·Et2O in DCM.2, 22 Here, we used
Et2NH (20 ml/gram, related to ligand weight) for the deprotection of ligands 1a and 1c,
and 1,4-diazabicyclo[2.2.2]octane (DABCO, 10 eq.) for the deprotection of ligand 1c. However, following the reported procedures the products always contained amine-borane impurities. In order to improve the product purity, we extracted the reaction mixture after removal of the volatiles with a degassed toluene/water mixture under N2.
The resulting organic phase is essentially free from amine-borane impurties, and the deprotected ligands were obtained in good yields (85-99%, Scheme 4).
Scheme 4. Deprotection of ligands with amins
With the deprotected chiral ligands 2a-c in hand, the desired Ru pincer complexes were synthesized by heating the ligands in THF/toluene with Ru(PPh3)3(CO)HCl. The
reaction with ligand 2b resulted in a messy mixture. In the 1HNMR spectrum we
observed a Ru-hydride as a doublet of doublets at -13.85 ppm (dd, J = 21.9, 18.9 Hz, 1H) and in the 31P NMR two doublets at 40.60 ppm (d, J = 291.6 Hz) and 33.32 ppm (d, J =
291.5 Hz), which are close to the similar analogue reported by Castillón.1 Although this
suggests that the desired product is formed, we were unable to isolate it in pure form from this mixture. From the other two ligands the corresponding chiral ruthenium complexes 3a and 3c could be synthesized with excellent yields (86 and 94%, Scheme 5).
Scheme 5. synthesis of Ru chiral pincer complexes (PNP)Ru(H)(CO)Cl (3)
Since manganese pincer complexes also catalyze the hetero-Michael addition on unsaturated nitriles 29 we were interested in preparing the chiral manganese PNP
pincer complexes. These manganese complexes were synthesized by reacting Mn(CO)5Br with the chiral ligand by heating at 115 °C for 3 hours in toluene. From
previous reports, we know that different reaction temperatures may lead to the formation of different manganese complexes: the neutral di-carbonyl complex at rt or the cationic tris-carbonyl complex with a bromide counter anion at 115 °C.5, 20, 41
Unfortunately, we found that long reaction time at 115 °C led to the decomposition of the neutral di-carbonyl complex in the case of ligand 2c. As a result, the manganese pincer complexes 4c were isolated as a mixture in 84% yield (Scheme 6) containing
both forms (4cb is around 10%). Unfortunately, the other two ligands were not used due to the lockdown caused by the corona virus.
Scheme 6. Synthesis of chiral manganese pincer complexes (4)
5.2.2 Preliminary study of enantioselective oxa-Michael addition to α,β-unsaturated nitriles with alcohols catalysed by chiral ruthenium and manganese PNP complexes
Table 1. Enantioselective oxa-Michael addition to cis-2-pentenenitrile with BnOH catalyzed by 3a
The chiral complexes described above were applied in the (asymmetric) addition of BnOH (2 eq.) to cis-2-pentenenitrile. At room temperature, the reaction catalysed by the chiral Ru PNP complex 3a (0.5 mol%) in toluene reached 82% conversion after 1 hour (table 1, entry 1), which is similar to the results obtained with our previously reported Ru PNN pincer complex.28 Repeating the reaction at -30 °C resulted in
significantly decreased activity, and gave only 6% conversion after 16 hours (table 1, entry 2). In both cases, the enantioselectivity was negligible (<4%). We also investigated the use of the mixture of complexes 4c in the same reaction. Under the same conditions, the reaction with benzyl alcohol proceeded with excellent conversion, however, the product was again racemic (table 2, entry 1) suggesting that a steric effect probably is not the main reason for the lack of enantioselectivity. Next, different nucleophiles were tested in the Michael addition on cis-pentenenitrile catalyzed by 4c
at room temperature in toluene. To our surprise, dodecylthiol, in spite of its excellent nuceophilicity, most likely deactives the manganese catalyst resulting in only traces of product. Using the secondary alcohol cyclohexanol, we finally observed an enantioselectivety that with 7% exceeded the error of measurement (Table 2, entry 3).
Table 2. Enantioselective oxa-Michael addition to cis-2-pentenenitrile catalyzed by 4c
Next, we repeated the reaction with cyclohexanol and analyzed conversion, selectivity and enantioselectivity by (chiral) GC. In the GC, besides starting material-cis-2-pentenenitrile at 4.6 min, a new peak was observed around 5.3 min, which most likely is the trans isomer of 3-pentenenitrile. The ratio of cis/trans isomers decreased from pure cis to 2 : 1, which can be explained by isomerization catalyzed by 4c via a metal-ligand cooperative mechanism28. In addition to the oxa-Michael addition product, new
species-dimers of pentenenitrile were also observed in the gas chromatogram at 14.4 min (major) and 14.8 min (minor) (ratio=3.4 : 1, Figure 3 in the Experimental Section). The 1H NMR resonances that can be assigned to the major isomer of the pentenenitrile
dimerization product include a peak for the vinyl proton that has a higher chemical shift and smaller coupling constant than that of the minor isomer. Thus, the major dimerization product could be assigned to the cis-isomer and the minor one to the
trans-isomer. With chiral GC analysis, the enantioselectivity toward the dimers was
determined to be 7% (major one, cis isomer) and 5% (minor one, trans isomer), respectively (Figure 4, middle).
Given our previous observation that also the non-conjugated substrate 3-pentenenitrile provides access to the same reactive intermediate and is thus a suitable substrate for oxa-Michael addition reactions,42 we also tested this as a substrate for enantioelective
addition using catalyst 4c. Under the same conditions, the reaction with cyclohexanol afforded a mixture of oxa-Michael addition product 5b and pentenenitrile dimer 6
(ratio = 57 : 43), in which the ratio of cis : trans decreased to 1 : 1 Surprisingly, the products were obtained with an significantly increased ee of 19% for the oxa-Michael addition product, and 22%/23% for the trans- and cis-dimer, respectively (Figure 4, bottom).Although the origin of this difference in ee is at present not clear, it may hint at the possibility that cis and trans isomers of the Michael acceptor substrate lead to distinct reactivity/enantioselectivity. More importantly, these preliminary results show that enantioselective conjugate additions can be achieved with this class of catalysts (albeit with very modest ee), and that both C-O and C-C bond formation is feasible.
Scheme 7. Enantioselective oxa-Michael addition of cyclohexanol to pentenenitrile catalyzed by 4c
5.3 Conclusions
In conclusion, chiral PNP pincer complexes were synthesized in excellent yields and preliminary studies on their application in enantioselective oxa-Michael additions with unsaturated nitriles were performed. Use of the primary alcohol BnOH resulted in good activity in the oxa-Michael addition, however, the product was racemic. Use of a thiol nucleophile deactivated the chiral PNP pincer complexes. We assume that the low enantioselectivities that we find is related to the rapid cis-trans isomerization of the substrates, a reaction that is catalyzed by these PNP pincer complexes. Due to the Covid-19 shutdown, we were not able to investigate this further. More research is required to evaluate the reactivity of Ru and Mn chiral PNP pincer complex in the enantioselective oxa-Michael addition.
5.4 Experimental Section
5.4.1 General considerations
The chemicals (Ph3P)3Ru(Cl)(CO)H (Strem Chemicals), Mn(CO)5Br (Sigma Aldrich,
98%), diazabicyclo[2.2.2]octane (DABCO, Sigma Aldrich, >99%) and KOtBu (Sigma Aldrich, >98%) were obtained commercially, and used without further purification. Diethylamine (Sigma Aldrich, 98%), crotonitrile (TCI, >98%), cis-2-pentenenitrile (Sigma Aldrich, 98%), trans-3-pentenenitrile (Sigma Aldrich, 98%) and 1-dodecanethiol (Sigma Aldrich, 98%) were obtained commercially, and degassed and passed over columns of Al2O3 prior to use. Toluene was passed over columns of Al2O3
(Fluka), BASF R3-11-supported Cu oxygen scavenger, and molecular sieves (Aldrich, 4 Å).THF (Aldrich, anhydrous, 99.8%) was dried by percolation over columns of Al2O3
(Fluka). Isopropanol (Boom, >99%), cyclohexanol (Sigma Aldrich, 99%) and benzyl alcohol (Fisher Scientific, >98%) were dried with calcium hydride (Sigma Aldrich) and distilled under N2 atmosphere prior to use. d8-THF and d6-benzene (Eurisotop) were
vacuum transferred from Na/K alloy and stored in the glovebox. The compounds
1a-b32 and 1c33 were prepared according to the literature procedure. The reactions for
which isolated yields are reported were carried out at least twice, which led to similar results (within 5 %); the values reported are the average. NMR spectra were recorded on Varian 400, Agilent 400 or Varian Inova 500 spectrometers and referenced using the residual solvent resonance. Gas chromatography measurements were performed on HP6890 series equipped with HP-5MS column for GC/MS and HP5890 series II equipped with Rtx-1701 column for GC-MS/FID. High resolution mass spectra (HRMS) were performed at the Microanalytical Department of the University of Groningen. Enantiomeric excess (ee) was determined by chiral HPLC analysis using a Shimadzu LC-20AD HPLC equipped with a Shimadzu SPD-M20A diode array detector and aChiracel OB-H column or GC analysis (Chirasil-Dex CB).
5.4.2 Synthesis of ligands and complexes
Synthesis of ligands 2
In the glovebox PNP•(BH
3)
2(1a) (561 mg, 1.65 mmol), DABCO (3.7 g, 33 mol,
20 eq.) and toluene (30 ml) was added to a Schlenk flask (100 mL). Then,
outside the glovebox, the
solution was stirred and heated at 60 °C overnight under N2. After cooling to room temperature, on the Schlenk line 15 mL dry toluene was addedinto the Schlenk flask, and the solution was washed with degassed water (3×10 ml) by syringe. After removal of toluene in vacuo, a light‑yellow oil remained (2a: 504 mg, 98% yield). 31P NMR (162 MHz, d8‑toluene) δ ‑7.1. 1H NMR (400 MHz, d8‑toluene) δ 7.24 –
7.02 (m, 1H), 6.84 (d, J = 7.5 Hz, 2H), 2.93 (dd, J = 12.5, 2.6 Hz, 2H), 2.70 (dd, J = 12.5, 2.9 Hz, 2H), 0.96 (d, J = 11.3 Hz, 18H), 0.90 (d, J = 3.8 Hz, 6H).
In the glovebox PNP•(BH3)2 (1b/c) (200 mg) was added to a pre-weighed Schlenk flask.
On the Schlenk line 4 mL distilled and degassed diethylamine (4 ml) was added and the solution was stirred and heated at 60 °C overnight. After cooling to room temperature, the volatiles were removed in vacuo. On the Schlenk line 15 mL dry toluene was added into the Schlenk flask, and the solution was washed with degassed water (3×5 ml) which was subsequently removed by syringe. After removal of toluene in vacuo, a light-yellow oil remained (2b: 157 mg, 85% yield; 2c: 187 mg, 99% yield).
2b:31P NMR (162 MHz, C6D6) δ -32.8. 1H NMR (400 MHz, C6D6) δ 7.12 (ddd, J = 8.3, 6.8,
1.7 Hz, 4H), 6.87 – 6.67 (m, 6H), 6.58 (t, J = 7.7 Hz, 1H), 6.19 (d, J = 7.7 Hz, 2H), 3.01 – 2.62 (m, 6H), 0.96 (t, J = 4.2 Hz, 6H).
2c:31P NMR (162 MHz, d8‑toluene) δ 8.7.1H NMR (400 MHz, d8‑toluene) δ 7.55 (ddd, J =
(dd, J = 13.8, 1.5 Hz, 2H), 0.94 (d, J = 11.6 Hz, 18H).
Synthesis of Ru complexes 3
In the glovebox, a Schlenk flask was loaded with ligand 2a (65 mg, 0.21 mmol, 1 eq.), (Ph3)3Ru(Cl)(CO)H ( 199 mg, 0.21 mmol, 1 eq.) and 10 mL of dry toluene. Then the
mixture was heated at 70˚C for 1 hour, during which time the Ru precursor dissolved and reacted with the pincer ligand. After removal of the solvent, the residue was washed with dry pentane (3x5 mL). The solid was dried under vacuum affording 3a as a grey solid product in 86% yield (86 mg, 0.180 mmol).31P NMR (162 MHz, d8-toluene) δ 76.61
(d, J = 277.4 Hz), 61.80 (d, J = 277.4 Hz).1H NMR (600 MHz, d8-toluene) δ 6.77 (t, J = 7.7
Hz, 1H), 6.50 – 6.38 (m, 2H), 3.93 (dd, J = 16.2, 9.4 Hz, 1H), 3.31 (dd, J = 16.2, 9.4 Hz, 1H), 2.91 (ddd, J = 16.2, 10.5, 2.5 Hz, 1H), 2.67 (dd, J = 16.2, 9.4 Hz, 1H), 1.69 (dd, J = 8.4, 2.4 Hz, 3H), 1.36 (dd, J = 7.6, 1.6 Hz, 3H), 1.23 (d, J = 14.3 Hz, 9H), 0.90 (d, J = 13.9 Hz, 9H), ‑ 14.34 (dd, J = 22.1, 16.2Hz, 1H).
In the glovebox, A Schlenk flask was loaded with ligand 2c (471 mg, 1.08 mmol, 1 eq.), (Ph3)3Ru(Cl)(CO)H ( 1.031 g, 1.08 mmol, 1 eq.) and 30 mL dry toluene. Then the mixture
was heated at 70˚C for 2 hours, during which time most of the Ru precursor dissolved. After removal of the solvent, the residue was washed with dry toluene (3x3 ml) and pentane (3x5 mL). The solid was dried under vacuum affording 3c as a light yellow solid product in 62% yield (401 mg, 0.67 mmol). The filtrate was concentated under vacuum, then was dissolved in a minimal amount of toluene for recrystallization in fridge affording another portion of 3c as a light yellow solid product in 32% yield (210 mg, 0.35 mmol). The NMR spectrum is in agreement with that reported in the literature:11H
NMR (400 MHz, CD2Cl2) δ 7.77 – 6.57 (m, 13H), 4.36 (dd, J = 16.0, 9.9 Hz, 1H), 3.90 (dd, J = 16.0, 9.9 Hz, 1H), 3.76 – 3.54 (m, 2H), 0.89 (d, J = 14.4 Hz, 9H), 0.67 (d, J = 14.4 Hz,
9H), ‑14.77 (dd, J = 23.7, 15.3 Hz, 1H).31P NMR (162 MHz, CD2Cl2) δ 80.4 (d, J = 268.4
Hz), 64.4 (d, J = 268.6 Hz).
Synthesis of mixture of Mn complexes 4c
In the glovebox, a Schlenk flask was loaded with ligand 2c (872 mg, 2.0 mmol, 1 eq.), Mn(CO)5Br ( 0.551 mg, 2.0 mmol, 1 eq.) and 30 mL dry toluene. Then the mixture was
heated at 115˚C for 2 hours. After removal of the solvent, the residue was washed with dry pentene (3x10 ml). After drying under vacuum, 4c was obtained as a light yellow solid in 84% yield (1.048 g, 1.67mmol).
4ca
31P NMR (162 MHz, d6-DMSO)) δ 91.54 (d, J = 95.9 Hz), 80.84 (d, J = 95.9 Hz). 1H NMR (400 MHz, d6-DMSO) δ 7.91 – 7.39 (m, 16H),4.53 – 4.34 (m, 2H), 4.34 – 4.18 (m, 1H), 4.02 – 3.80 (m, 1H), 1.01 (d, J = 13.6 Hz, 10H), 0.88 (d, J = 13.0 Hz, 9H). HRMS (ESI) calcd. for C29H34BrMnNO2P2 [M-HBr+H+]
546.15180, found 546.15079.
4cb
31P NMR (162 MHz, d6-DMSO)) δ 85.98. HRMS (ESI) calcd. for C30H34BrMnNO3P25.4.3 Enantioselective oxa-Michael addition of cyclohexanol to pentenenitrile
Fresh catalyst solution: In the glovebox in a 5ml vial was added 4c (12.5 mg, 0.02 mmol, 1eq.) and toluene 1 ml. After adding tBuOK (2.2 mg, 0.02 mmol, 1eq.) and stirring at
room temperature for 0.5 hour, the solution was passed through a 1 mL syringe with a plastic filter and then the filtrate was used for next step directly.
1) In the glovebox, vials were prepared containing cis-2-pentenenitrile (2 mmol, 1 eq.), 1 ml cyclohexanol and 1 mL of solvent. To these vials were added 1 mL (1 mol%) of fresh catalyst stock solution at room temperature. The reaction mixtures were taken out of the glovebox after 22 hoursand exposed to air to quench the reaction. After the volatiles were removed under vacuum, two different workup procedures allow isolation of either the oxa-Michael addition product 5b or the dimerization products 6 as described below.
Isolation of 5b: Kugelrohr distillation of the residue at 95℃ under 0.5 mmHg vacuum afforded the desired product 5b (202 mg, 1.12 mmol, 56% yield). 1H NMR (300 MHz,
CDCl3) δ 3.60 (p, J = 6.0 Hz, 1H, CHCH2CN), 3.41 – 3.25 (m, 1H, Cyhex-CH), 2.47 (d, J =
5.8 Hz, 2H, CHCH2CN), 1.94 –1.16 (m, 12H, CH2CH3 andCyhex-CH2), 0.95 (t, J = 7.4 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 118.1 (CN), 77.0 (Cyhex-CH), 73.9 (CHCH2CN),
33.1 (Cyhex-CH2), 32.7 (Cyhex-CH2), 28.1 (CH2CH3), 25.8 (Cyhex-CH2), 24.3 (Cyhex-CH2),
24.3 (Cyhex-CH2), 23.7 (CH2CN), 9.7 (CH3). HRMS (ESI) calcd. for C11H19NO [M+H+]
182.15394, found 182.15176.
Isolation of 6: Column chromatography of the residue on silica using hexane/ethyl acetate as the eluent (gradient from 20:1 to 8:1) gave the dimer 6 as a cis/trans mixture (25.9 mg, 0.16 mmol, 8% yield).
1H NMR (300 MHz, CDCl3) δ 6.58 (t, J = 7.7 Hz, 0.16H), 6.36 (t, J = 7.6 Hz, 0.66 H), 2.63 –
2.31 (m, 4H), 1.70 – 1.57 (m, 2H), 1.19 – 1.01 (m, 3H), 1.01 – 0.83 (m, 3H).
2) In the glovebox, vials were prepared containing trans-3-pentenenitrile (2 mmol, 1 eq.), 1 ml cyclohexanol and 1 mL of solvent. To these vials were added 1 mL (1 mol%) of fresh catalyst stock solution at room temperature. The reaction mixtures were taken out of the glovebox after 22 hours and exposed to air to quench the reaction. After the volatiles were removed under vacuum, the residues were filtered through a plug of silica with hexane/EtOAc (5:1). After drying under vacuum, the mixture was dissolved in heptane for GC analysis.
Figure 1 1H NMR spectrum of 3‑(cyclohexyloxy)pentanenitrile 5b
Figure 3 Chiral GCspectrum of 3‑(cyclohexyloxy)pentanenitrile and dimer; racemic mixture (top), chiral products from cis‑2‑pentenenitrile (middle), chiral products from trans‑3‑pentenenitrile (bottom);[peak 1‑ 2:cis‑dimer 6; peak 3‑4: trans‑dimer 6; peak 5‑6: product 5b].
Figure 4 GCspectrum of enantioselective oxa‑Michael addition of cyclohexanol to cis‑2‑pentenenitrile catalysed by 4c; [peak 1‑2: pentenenitrile; peak 3‑4: dimer 6 ; peak 5: product 5b; peak 6: internal standard].
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