CC BY ND NC 4.0 · SynOpen 2018; 02(02): 0122-0127
DOI: 10.1055/s-0036-1591999
paper
Copyright with the author

Diastereoselectivity in the Aza-Michael Reaction of Chiral α-Methylbenzylamines with α,β-Unsaturated Carbonyl Compounds

M. Kour
Department of chemistry, The IIS University, GurukulMarg, SFS, Mansarovar, Jaipur 302020, India   Email: bansal56@gmail.com
,
R. Gupta
Department of chemistry, The IIS University, GurukulMarg, SFS, Mansarovar, Jaipur 302020, India   Email: bansal56@gmail.com
,
R. Saini
Central Drug Research Institute, Sitapur Road, Lucknow 226031, India
,
R. K. Bansal*
Department of chemistry, The IIS University, GurukulMarg, SFS, Mansarovar, Jaipur 302020, India   Email: bansal56@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 15 March 2018

Accepted after revision: 05 April 2018

Publication Date:
07 May 2018 (online)

 

Abstract

The aza-Michael reaction of (S)-(–)- and (R)-(+)-α-methylbenzylamines with trans-cinnamaldehyde and other α,β-unsaturated carbonyl compounds occurs with 52–98% diastereoselectivity (de); however, in the reaction with crotonaldehyde, the de is lower (20–38%). In the products obtained from the reaction with α,β-unsaturated aldehydes, the de could be determined on the basis of the relative intensities of the aldehydic protons of the two diastereomers. Theoretical investigations of the reaction of (S)-(–)-α-methylbenzylamine with trans-cinnamaldehyde at the DFT (B3LYP/6-31+G*) level reveal that the diastereomer formed from the attack of the amine on the Re face is thermodynamically more stable. The calculations also show that the aldehydic proton of this diastereomer is expected to be more deshielded, which on the basis of the 1H NMR spectrum is the major product.


#

The aza-Michael reaction has emerged as one of the most powerful and reliable methods for the asymmetric synthesis of β-amino carbonyl compounds, which are important building blocks for the synthesis of a wide variety of nitrogen-containing compounds having pharmaceutical importance.[1] [2]

The reaction of a nucleophile with an activated alkene having prochiral faces is accompanied by the generation of one or more stereogenic centers in one step. Thus, by manipulating the reaction environment with appropriate chiral auxiliaries, asymmetry can be induced and the desired products may be obtained with high stereoselectivity. The use of chiral nitrogen nucleophiles is one such strategy. By following this approach, (S)-alanine benzyl ester was used as a Michael donor and reacted with 4-oxo-4-phenyl-2-butenoate to give a mixture of diastereomers, from which the major isomer could be separated.[3] Likewise, chiral N-(α-methylbenzyl)hydroxylamines react with methyl enoates to afford isoxazolidinone adducts in moderate to good diastereoselectivity,[4] which could be further enhanced by using chiral crotonate acceptors under double stereodifferentiation conditions.[5] Hawkins used an atropisomeric lithiated dinaphthoazepine derivative as a chiral nitrogen nucleo­phile and the reaction proceeded with very high diastereoselectivity to afford β-amino esters in excellent yields.[6] Davies­ and co-workers developed diastereoselective conjugate additions of enantiomerically pure lithium amides to a wide range of α,β-unsaturated esters and amides, making a wide range of β-amino acids and their derivatives available.[7] They proposed a mechanistic rationale that accounted for the high diastereoselection between prochiral faces.[8] Enders and co-workers, on the other hand, employed lithiated enantiopure hydrazines as nitrogen nucleophiles, which reacted with α,β-unsaturated esters and other acceptors with a high degree of diastereoselection.[9] Likewise, Michael addition of a d-mannitol derived hydrazine to alkylidenemalonates­ was accomplished with high diastereoselectivities.[10] A cyclic carbamate has also been employed as a nitrogen nucleophile for its conjugate addition to nitro­alkenes to afford products as single diastereomers.[11]

The Michael addition of homochiral α-methylbenzylamines to methyl crotonate[12] and some other activated alkenes[12e] has been reported earlier to occur with poor dia­stereoselectivity (2–19%). In all these investigations, alcohol was used as the solvent. As solvent has been found to affect diastereoselectivity in the Michael addition[13] and intramolecular Diels–Alder reactions,[14] we decided to investigate the reaction of (S)-(–)- and (R)-(+)-α-methylbenzylamines with a range of α,β-unsaturated carbonyl compounds in an aprotic solvent (dichloromethane) and found that the dia­stereoselectivity improved remarkably. As a result, an attempt was made to rationalize the observed diastereoselectivity theoretically by computing the model reaction at the DFT level involving the attack of (S)-(–)-α-methylbenzylamine on the Si and Re faces of trans-cinnamaldehyde. The results are presented herein.

(S)-α-Methylbenzylamine (2a) and (R)-α-methylbenzylamine (2b) reacted with α,β-unsaturated carbonyl compounds (1ae) in dichloromethane at room temperature (ca. 25 °C) to afford mixtures of the diastereomers 3+4 and 5+6, respectively (Scheme [1]).

Zoom Image
Scheme 1 Reaction of (S)- and (R)-α-methylbenzylamines with α,β-unsaturated carbonyl compounds

All the products were obtained as colorless syrups, which could not be crystallized. The 1H NMR spectra indicated each to be a mixture of two diastereomers. In the case of a,b,c, and e, two characteristic signals for the aldehydic protons in the range of δ ca. 9 and 8 ppm confirmed the presence of two diastereomers in each case, the relative percentages of which could be calculated on the basis of the relative intensities of these signals. The presence of two diastereomers was further corroborated by two 13C NMR signals in the range of 195–160 ppm. These parts of the 1H and 13C NMR spectra of the product (3a+4a) obtained from the reaction of (S)-α-methylbenzylamine (2a) with trans-cinnamaldehyde (1a) are shown in Figure [1].

Zoom Image
Figure 1 Parts of the 1H NMR (A) and 13C NMR (B) spectra of the product 3a+4a

It may be noted that the aldehydic proton of the major diastereomer gives a double doublet (dd) at δ = 9.71 ppm (3 J H–H = 7.7 Hz, 3 J H–H = 1.0 Hz) due to its coupling with the vicinal diastereotopic protons HA and HB. However, the aldehydic proton of the minor diastereomer gives a simple doublet at δ = 8.12 ppm (3 J H–H = 8.1 Hz), possibly due to the orthogonal disposition of one of the two diastereotopic protons with respect to it. In the 13C NMR spectrum, signals at δ = 192.2 and 161.6 ppm are observed due to aldehydic carbon atoms of the two diastereomers.

The diastereomeric excess (de) in the reaction of (S)-α-methylbenzylamine (2a) with 1a was also determined by HPLC and the de obtained (52%) was very close to that calculated on the basis of the relative intensities of the signals of the aldehydic protons in the 1H NMR spectrum (56%). The chromatogram of the mixture of the diastereomers 3a+4a can be found in the Supporting Information.

Also in other cases, the de as determined on the basis of the 1H NMR spectra ranged from 52% to 98%, except in the reaction of (S)- and (R)-α-methylbenzylamines with trans-crotonaldehyde (1b) when it was found to be 20% and 38%, respectively. The low diastereoselectivity in these cases may be attributed to the smaller size of the β-methyl group.

We attempted to rationalize the experimentally observed diastereoselectivity in the reaction of (S)-α-methylbenzylamine with trans-cinnamaldehyde theoretically by computing two model reactions initiated by the attack of the amine on Si and Re faces of the aldehyde (Figure [2]).

Zoom Image
Figure 2 Attack of (S)-α-methylbenzylamine on Si and Re faces of trans-cinnamaldehyde

Geometries of the products 3a and 4a resulting from the attack of the amine on Si and Re faces, respectively, were optimized at the B3LYP/6-31+G* level and frequency calculations were carried out at the same level. Thus, total energies of the products were calculated by summing up the respective energies with the uncorrected zero-point correction energies and are given in Table [1].

Table 1 Total Energies of the Two Diastereomers Resulting from the Attack of (S)-α-Methylbenzylamine on Si and Re Faces of trans-Cinnamaldehyde

Product

E

(a.u.)

ZPE

(a.u.)

Total energies

(a.u.)

Energy difference

(kcal mol–1)

3a

–789.236435

0.321541

–788.914894

–2.84

4a

–789.240401

0.32097

–788.919424

We did not succeed in locating the transition structures involved in the amine attack on the Si and Re faces, and hence it has not been possible to determine which product (3a or 4a) is preferred kinetically. It can be seen, however, that product 4a, resulting from the attack on the Re face, is more stable than the product 3a, formed from Si attack, by 2.84 kcal mol–1. This corresponds to 100% de, which implies that the observed diastereoselectivity cannot be rationalized on the basis of the relative thermodynamic stabilities of the two products.

NMR spectroscopy has been used to determine absolute configuration.[15] In one such strategy, a secondary alcohol was derivatized with α-methoxy-α-trifluoromethylphenyl­acetic acid or a similar aryl group containing carboxylic acid. Two stereoisomers could be differentiated on the basis of the 1H NMR shielding or deshielding of the substituent group present on the chiral center caused by the phenyl ring.[16] The geometries of the two diastereomers formed from the attack of (S)-α-methylbenzylamine on Si and Re faces of trans-cinnamaldehyde optimized at the B3LYP/6-31+G* level are shown in Figure [3].

Zoom Image
Figure 3 Optimized geometries of the diastereomers formed from the attack of (S)-α-methylbenzylamine on Si (3a) and Re (4a) faces of trans-cinnamaldehyde

Notably, the aldehydic protons in 3a and 4a fall in the shielding and deshielding zones of the phenyl ring, respectively. If these observations are viewed in correlation with the 1H NMR spectrum of the mixture of 3a and 4a discussed earlier, the diastereomer 4a formed from the attack of the amine on the Re face of cinnamaldehyde can be concluded to be the major product, which is also thermodynamically more stable, as shown by DFT calculations.

In conclusion, the reaction of chiral α-methylbenzylamines with α,β-unsaturated carbonyl compounds in dichloromethane occurs with moderate to very high diastereo­selectivity, with de ranging from 52% to 98%, except in the reaction of (S)- and (R)-α-methylbenzylamines with trans-crotonaldehyde when the de were found to be 20% and 38%, respectively. The low diastereoselectivity in these cases may be attributed to the smaller size of the β-methyl group. It was possible to determine de in the reaction with cinnamaldehyde and other α,β-unsaturated aldehydes on the basis of the relative intensities of the aldehydic protons of the two diastereomers. Theoretical investigations at the DFT level along with the 1H NMR data indicate that the dia­stereomer resulting from the attack of the amine on the Re face of trans-cinnamaldehyde is the major diastereomer.

Commercially available amines, aldehydes and dichloromethane were purchased from Sigma–Aldrich. Dichloromethane was freshly dried and distilled.

IR spectra were recorded on NaCl plate with a Perkin–Elmer Precisely FT-IR spectrometer. NMR spectra were recorded with a Jeol Resonance-400 MHz spectrometer; 1H NMR at a frequency of 400 MHz and 13C NMR at a frequency of 100 MHz using TMS as the internal reference. High-resolution mass spectra (HRMS) were recorded with a Waters Xevo G2-S Q Tof instrument with UPLC. HPLC was carried out with a Waters-2998 instrument with photodiode array detector and pump-515 (hexane/2-propanol, 99:1).


#

Procedures

To a solution of 1 (1a, 1.03 g, 0.99 mL, 7.75 mmol; 1b, 0.54 g, 0.64 mL, 7.75 mmol; 1c, 0.91 g, 7.75 mmol; 1d, 1.26 g,7.75 mmol; 1e, 0.65 g, 0.75 mL, 7.75 mmol) in dichloromethane (10 mL) in a 100 mL RB flask was added dropwise, a solution of 1 equiv of amine (2a,b 0.94 g, 1 mL, 7.75 mmol) in dichloromethane (5 mL) at r.t. with continuous stirring. After addition was complete, the reaction mixture was stirred for another 3–4 h. The solvent was removed under reduced pressure to afford a syrupy residue.


#

Computational Methods

All calculations were carried out using Gaussian 03 software[17] within the density functional theory (DFT) framework.[18] Geometry optimizations were performed at the B3LYP/6-31+G* level.[19] Stationary points were analyzed by frequency calculations at the same level to confirm their character as local minima. To distinguish between different diastereomers, absolute configurations have been assigned on the basis of theoretical analysis.


#

(3R,1′S)- and (3S,1′S)-3-(α-Methylbenzyl)amino-3-phenylpropanals 3a+4a

Yield: 1.59 g (81%); de: 56%; colorless syrup.

IR (NaCl): 3420 (N-H st.), 1626 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 9.71 (dd, 3 J HH = 7.7 Hz, 3 J HH = 1.0 Hz, 1 H, CHO, major diastereomer), 8.12 (d, 3 J HH = 8.5 Hz, 1 H, CHO, minor diastereomer), 7.62–6.95 (unresolved m, 20 H, ArH), 4.50 (dq, 3 J HH = 9.8 Hz, 3 J HH = 6.6 Hz, 2 H, HD), 1.78 (dd, 2 J HH = 16.0 Hz, 3 J HH = 8.0 Hz, 2 H, HA), signals for HB and HC merged with that of HA, 1.63 (dd, 3 J HH = 6.6 Hz, 4 J HH = 1.8 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 192.2 (C=O, major), 161.6 (C=O, minor), 142.0–125.0 (aromatic carbon atoms), 67.2 (C3), 57.7 (C1′), 21.1 (CH3).

HRMS (ESI): m/z [M]+ calcd for C17H19NO: 253.1466; found: 253.1439.


#

(3R,1′R)- and (3S,1′R)-3-(α-Methylbenzyl)amino-3-phenylpropanals (5a+6a)

Yield: 1.57 g (80%); de: 96%; colorless syrup.

IR (NaCl): 3420 (N-H st.), 1633 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 9.74 (d, 3 J HH = 7.7 Hz, 1 H, CHO, major diastereomer), 9.35 (unresolved d, 1 H, CHO, minor diastereomer), 7.64–7.41 (unresolved m, 20 H, aromatic protons), 4.30 (dq, 3 J HH = 9.6 Hz, 3 J HH = 6.0 Hz, 2 H, HD), 2.36 (dd, 2 J HH = 16.0 Hz, 3 J HH = 8.0 Hz, 2 H, HA), signals for HB and HC merged, 1.42 (dd, 3 J HH = 6.0 Hz, 4 J HH = 1.2 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 193.59 (C=O, major), 161.6 (C=O, minor), 141–126 (aromatic carbon atoms), 67.2 (C3), 57.7 (C1′), 21.1 (CH3).

HRMS (ESI): m/z [M]+ calcd for C17H19NO: 253.1466; found: 253.1443.


#

(3S,1′S)- and (3R,1′S)-3-(α-Methylbenzyl)aminobutanals (3b+4b)

Yield: 1.53 g (78%); de: 38%; colorless syrup.

IR (NaCl): 3395 (N-H st.), 1657 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 9.52 (dd, 3 J HH = 8.0 Hz, 3 J HH = 1.0 Hz, 1 H, CHO, major diastereomer), 8.31 (unresolved d, 1 H, CHO, minor diastereomer), 7.99–7.29 (unresolved m, 10 H, aromatic protons), 4.49 (dq, 3 J HH =10.0 Hz, 3 J HH = 6.0 Hz, 2 H, HD), 2.39 (dd, 2 J HH =16.0 Hz, 3 J HH = 8.0 Hz, 2 H, HA), 1.92 (dd, 2 J HH = 16.0 Hz, 3 J HH = 8.0 Hz, 2 H, HB), signal for HC merged, 1.49 (dd, 3 J HH = 6.0 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 190.1 (C=O, major), 162.4 (C=O, minor), 129–124 (aromatic carbon atoms), 69.1 (C3), 59.8 (C1′), 22.7 (CH3).

HRMS (ESI): m/z [M + H]+ calcd for C12H18NO: 192.1388; found: 192.1310.


#

(3S,1′R)- and (3R,1′R)-3-(α-Methylbenzyl)aminobutanals (5b+6b)

Yield: 1.51 g (77%); de: 20%; colorless syrup.

IR (NaCl): 3400 (N-H st.), 1657 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 9.31 (dd, 3 J HH = 8.0 Hz, 3 J HH = 1.0 Hz, 1 H, CHO, major diastereomer), 8.42 (unresolved d, 1 H, CHO, minor diastereomer), 7.99–6.40 (unresolved m, 10 H, aromatic protons), 4.33 (dq, 3 J HH = 10.0 Hz, 3 J HH = 6.0 Hz, 2 H, HD), 2.63 (dd, 2 J HH = 16.0, 3 J HH = 8.0 Hz, 2 H, HA), 1.92 (dd, 2 J HH = 16.0, 3 J HH = 8.0 Hz, 2 H, HB), signal for HC merged, 1.49 (dd, 3 J HH = 6.0, 6 H, CH 3).

13C NMR (75.48 MHz, CDCl3): δ = 187.1 (C=O, major), 161.6 (C=O), 127–124 (aromatic carbon atoms), 76.1 (C2), 67.0 (C3), 57.7 (C1′), 22.5 (CH3).

HRMS (ESI): m/z [M]+ calcd for C12H17NO: 191.1310; found: 191.1361.


#

(3R,1′S)- and (3S,1′S)-3-(α-Methylbenzyl)amino-3-(4-nitrophenyl)propanals (3c+4c)

Yield: 1.47 g (61%); de: 61%; colorless syrup.

IR (NaCl): 3398 (N-H st.), 1597 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.23 (d, 3 J HH = 8.0 Hz, 1 H, CHO, major diastereomer), 8.17 (d, 3 J HH = 8.1 Hz, 1 H, CHO, minor diastereomer), 7.61–6.59 (unresolved m, 18 H, aromatic protons), 4.49 (q, 3 J HH = 6.7 Hz, 2 H, HD), 2.24 (dd, 2 J HH = 16.0 Hz, 3 J HH = 8.0 Hz, 2 H, HA), 1.61 (unresolved dd, 2 H, HB), 1.42 (unresolved dd, 2 H, HC), 1.28 (d, 3 J HH = 6.7 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 186.2 (C=O, major), 172.6 (C=O, minor), 148–122 aromatic carbons, 62.5 (C3), 55.5 (C1′), 28.2 (CH3).

HRMS (ESI): m/z [M + H]+ calcd for C17H19N2O3: 299.1395; found: 299.1317.


#

(3R,1′R)- and (3S,1′R)-3-(α-Methylbenzyl)amino-3-(4-nitrophenyl)propanals (5c+6c)

Yield: 1.33 g (68%); de: 52%; colorless syrup.

IR (NaCl): 3401 (N-H st.), 1601 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.82 (d, 3 J HH = 8.0 Hz, CHO, 1 H, major diastereomer), 8.13 (unresolved d, 1 H, CHO, minor diastereomer), 7.52–6.49 (unresolved m, 18 H, aromatic protons), 4.55 (q, 3 J HH = 6.6 Hz, 2 H, HD), 2.62 (dd, 2 J HH = 16.0 Hz, 3 J HH = 8.5 Hz, 2 H, HA), signals for HB and HC merged, 1.45 (d, 3 J HH = 6.6 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 182.5 (C=O major), 162.1 (C=O, minor), 144–127 (aromatic carbon atoms), 66.1 (C3), 56.3 (C1′), 22.7 (CH3).

HRMS (ESI): m/z [M + H]+ calcd for C17H19N2O3: 299.1395; found: 299.1379.


#

(3R,1′S)- and (3S,1′S)-Methyl 3-(α-Methylbenzyl)amino-3-phenylpropanoate (3d+4d)

Yield: 1.43 g (73%); colorless syrup.

IR (NaCl): 3415 (N-H st.), 1637 (C=O st.), 1174 (C-O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.82–6.50 (unresolved m, 20 H, aromatic protons), 4.65 (q, 3 J HH = 7.6 Hz, 2 H, HD), 3.69 (s, 3 H, OCH 3, major), 3.68 (s, 3 H, OCH 3, minor), 1.89 (dd, 2 J HH = 16.0, 3 J HH = 7.7 Hz, 2 H, HA), 1.45 (dd, 2 J HH = 16.0, 3 J HH = 7.6 Hz, 2 H, HB), signal for HC merged.

13C NMR (100 MHz, CDCl3): δ = 171.8 (C=O), 148–129 aromatic carbons, 55.01 (O-CH3), 22.9 (CH3).

HRMS (ESI): m/z [M + H]+ calcd for C18H22NO2: 284.1650; found: 284.1673.


#

(3R,1′R)- and (3S,1′R)-Methyl 3-(α-Methylbenzyl)amino-3-phenylpropanoate (5d+6d)

Yield: 1.47 g (75%); colorless syrup.

IR (NaCl): 3413 (N-H st.), 1637 (C=O st.), 1174 (C-O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 7.81–6.50 (unresolved m, 20 H, aromatic protons), 4.25 (q, 3 J HH = 8.2 Hz, 2 H, HD), 3.79 (s, 3 H, OCH 3, major), 3.78 (s, 3 H, OCH 3, minor), 1.99 (unresolved dd, 2 H, HA), 1.49 (unresolved dd, 2 H, HB), HC merged, 1.37 (d, 3 J HH = 6.8 Hz, 6 H, CH 3).

13C NMR (100 MHz, CDCl3): δ = 167.5 (C=O), 145–125 aromatic carbons, 51.72 (O-CH3).

HRMS (ESI): m/z [M + H]+ calcd for C18H22NO2: 284.1650; found: 284.1604.


#

(2S,3S,1′S)- and (2R,3R,1′S)-2-Methyl-3-(α-methylbenzyl)aminobutanals (3e+4e)

Yield: 1.37 g (70%); de: 66%: colorless syrup.

IR (NaCl): 3409 (N-H st.), 1629 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.91 (d, 3 J HH = 8.2 Hz, 1 H, CHO, major diastereomer), 8.61 (unresolved d, 1 H, CHO, minor diastereomer), 7.50–6.01 (unresolved m, 10 H, aromatic protons), 4.41 (q, 3 J HH = 8.0 Hz, 2 H, HD), 2.60 (unresolved q, 2 H, HA), 1.86 (d, 3 J HH = 8.0 Hz, 6 H, C(2)CH3), 1.52 (d, 3 J HH = 8.2 Hz, 6 H, C(3)CH3), 1.32 (d, 3 J HH = 7.8 Hz, 6 H, C(1′)CH 3), 0.91 (unresolved q, 2 H, HC).

13C NMR (100 MHz, CDCl3): δ = 177.5 (C=O, major), 169.4 (C=O, minor), 144–124 aromatic carbons, 57.0 (C3), 50.2 (C1′), 26.2 ((C2)CH3), 23.9 ((C1′)CH3).

HRMS (ESI): m/z [M-H]+ calcd for C13H18NO: 204.1388; found: 204.1353.


#

(2S,3S,1′R)- and (2R,3R,1′R)-2-Methyl-3-(α-methylbenzyl)aminobutanals (5e+6e)

Yield: 1.39 g (71%); de: 42%; colorless syrup.

IR (NaCl): 3377 (N-H st.), 1628 (C=O st.) cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.11 (d, 3 J HH = 8.2 Hz, 1 H, CHO, major diastereomer), 8.06 (d, 3 J HH = 8.2 Hz, 1 H, CHO, minor diastereomer),7.75–6.55 (unresolved m, 10 H, aromatic protons), 4.38 (unresolved, dq, 2 H, HD), 2.51 (unresolved q, 2 H, HA), 1.61 (unresolved d, 6 H, C(2)CH3), 1.50 (d, 3 J HH = 8.0 Hz, 6 H, C(3)CH3), 1.35 (d, 3 J HH = 8.0 Hz, 6 H, C(1′)CH 3), 1.31 (unresolved q, 2 H, HC).

HRMS (ESI): m/z [M]+ calcd for C13H19NO: 205.1466; found: 205.1481.


#
#

Acknowledgment

The authors thank the authorities of The IIS (deemed to be university) for providing necessary facilities.

Supporting Information

  • References

    • 1a Enders D. Wang C. Liebich JX. Chem. Eur. J. 2009; 15: 11058
    • 1b Weiner B. Szymanski W. Janssen DB. Minnaard AJ. Feringa BL. Chem. Soc. Rev. 2010; 39: 1656
    • 1c Phua PH. White AP. J. de Vries JG. Hii KK. Adv. Synth. Catal. 2006; 348: 587
    • 1d Phua PH. Mathew SP. White AP. J. de Varies JG. Blackmond DG. Hii KK. Chem. Eur. J. 2007; 13: 4602
    • 1e Hamashima Y. Somei H. Shimura Y. Tamura T. Sodeoka M. Org. Lett. 2004; 6: 1861
    • 2a Reboule I. Gil R. Collin J. Eur. J. Org. Chem. 2008; 532
    • 2b Scettri A. Massa A. Polombi L. Villano R. Acocella MR. Tetrahedron: Asymmetry 2008; 19: 2149
    • 2c Uraguchi D. Nakashima D. Ooi T. J. Am. Chem. Soc. 2009; 131: 7242
    • 2d Vicario JL. Badia D. Carrillo L. Synthesis 2007; 2065
  • 3 Urbach H. Henning R. Tetrahedron Lett. 1984; 25: 1143
    • 4a Baldwin SW. Aube J. Tetrahedron Lett. 1987; 28: 179
    • 4b Baldwin JE. Harwood LM. Lombard MJ. Tetrahedron 1984; 40: 4363
  • 5 Ishikawa T. Nagai K. Kudoh T. Saito S. Synlett 1995; 1171
    • 6a Howkin JM. Lewis TA. J. Org. Chem. 1992; 57: 2114
    • 6b Howkin JM. Fu GC. J. Org. Chem. 1986; 51: 2820
    • 7a Davies SG. Smith AD. Price PD. Tetrahedron: Asymmetry 2005; 16: 2833
    • 7b Davies SG. Fletcher AM. Roberts PM. Thomson JE. Tetrahedron: Asymmetry 2012; 23: 1111
  • 8 Costello JF. Davies SG. Ichihara O. Tetrahedron: Asymmetry 1994; 5: 1999
    • 9a Enders D. Bettray W. Raabe G. Runsink J. Synthesis 1994; 1322
    • 9b Enders D. Muller SF. Raabe G. Angew. Chem. Int. Ed. 1999; 38: 195
    • 9c Enders D. Wallert S. Synlett 2002; 304
  • 10 Prieto A. Fernandez R. Lassaletta JM. Vazquez J. Alvarez E. Tetrahedron 2005; 61: 4609
  • 11 Lucet D. Sabelle S. Kostelitz O. Gall TL. Mioskowski C. Eur. J. Org. Chem. 1999; 2586
    • 12a Estermann H. Seebach D. Helv. Chim. Acta 1988; 71: 1824
    • 12b Seebach D. Estermann H. Tetrahedron Lett. 1987; 28: 3103
    • 12c Davies SG. Ichihara O. Tetrahedron: Asymmetry 1991; 2: 183
    • 12d Juaristi E. Escalante J. Lamatsch B. Seebach D. J. Org. Chem. 1992; 57: 2396
    • 12e Furukawa M. Okawara T. Terawaki Y. Chem. Pharm. Bull. 1977; 25: 1319
  • 13 Torneg J. Prunet J. Org. Lett. 2008; 10: 45
  • 14 Tomberg A. Cesco SD. Huot M. Moitessier N. Tetrahedron Lett. 2015; 56: 6852
  • 15 Wenzel TJ. Tetrahedron: Asymmetry 2017; 28: 1212
  • 16 Dale JA. Mosher HS. J. Am. Chem. Soc. 1973; 95: 512
  • 17 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Jr. Montgomery JA. Vreven T. Kudin KN. Burant JC. Millam JM. lyengar SS. Tomasi J. Barone V. Mennucci B. Cossi M. Scalmani G. Rega N. Petersson GA. Nakatsuji H. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Klene M. Li X. Knox JE. Hratchian HP. Cross JB. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Auatin AJ. Cammi R. Pomelli C. Ochterski JW. Ayala PY. Morokuma K. Voth GA. Salvador P. Dannenberg JJ. Zakrzewski VG. Dapprich S. Daniels AD. Strain MC. Farkas O. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Ortiz JV. Cui Q. Baboul AG. Clifford S. Cioslowski J. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Challacombe M. Gill PM. W. Johnson B. Chen W. Wong MW. Gonzalez C. Pople JA. Gaussian 03 (revision B.05); Gaussian, Inc., Wallingford, CT, USA, 2003
  • 18 Becke AD. J. Chem. Phys. 1993; 98: 5648
  • 19 Lee C. Yang W. Parr RG. Phys. Rev. B: Condens. Matter Mater. Phys. 1998; 37: 785

  • References

    • 1a Enders D. Wang C. Liebich JX. Chem. Eur. J. 2009; 15: 11058
    • 1b Weiner B. Szymanski W. Janssen DB. Minnaard AJ. Feringa BL. Chem. Soc. Rev. 2010; 39: 1656
    • 1c Phua PH. White AP. J. de Vries JG. Hii KK. Adv. Synth. Catal. 2006; 348: 587
    • 1d Phua PH. Mathew SP. White AP. J. de Varies JG. Blackmond DG. Hii KK. Chem. Eur. J. 2007; 13: 4602
    • 1e Hamashima Y. Somei H. Shimura Y. Tamura T. Sodeoka M. Org. Lett. 2004; 6: 1861
    • 2a Reboule I. Gil R. Collin J. Eur. J. Org. Chem. 2008; 532
    • 2b Scettri A. Massa A. Polombi L. Villano R. Acocella MR. Tetrahedron: Asymmetry 2008; 19: 2149
    • 2c Uraguchi D. Nakashima D. Ooi T. J. Am. Chem. Soc. 2009; 131: 7242
    • 2d Vicario JL. Badia D. Carrillo L. Synthesis 2007; 2065
  • 3 Urbach H. Henning R. Tetrahedron Lett. 1984; 25: 1143
    • 4a Baldwin SW. Aube J. Tetrahedron Lett. 1987; 28: 179
    • 4b Baldwin JE. Harwood LM. Lombard MJ. Tetrahedron 1984; 40: 4363
  • 5 Ishikawa T. Nagai K. Kudoh T. Saito S. Synlett 1995; 1171
    • 6a Howkin JM. Lewis TA. J. Org. Chem. 1992; 57: 2114
    • 6b Howkin JM. Fu GC. J. Org. Chem. 1986; 51: 2820
    • 7a Davies SG. Smith AD. Price PD. Tetrahedron: Asymmetry 2005; 16: 2833
    • 7b Davies SG. Fletcher AM. Roberts PM. Thomson JE. Tetrahedron: Asymmetry 2012; 23: 1111
  • 8 Costello JF. Davies SG. Ichihara O. Tetrahedron: Asymmetry 1994; 5: 1999
    • 9a Enders D. Bettray W. Raabe G. Runsink J. Synthesis 1994; 1322
    • 9b Enders D. Muller SF. Raabe G. Angew. Chem. Int. Ed. 1999; 38: 195
    • 9c Enders D. Wallert S. Synlett 2002; 304
  • 10 Prieto A. Fernandez R. Lassaletta JM. Vazquez J. Alvarez E. Tetrahedron 2005; 61: 4609
  • 11 Lucet D. Sabelle S. Kostelitz O. Gall TL. Mioskowski C. Eur. J. Org. Chem. 1999; 2586
    • 12a Estermann H. Seebach D. Helv. Chim. Acta 1988; 71: 1824
    • 12b Seebach D. Estermann H. Tetrahedron Lett. 1987; 28: 3103
    • 12c Davies SG. Ichihara O. Tetrahedron: Asymmetry 1991; 2: 183
    • 12d Juaristi E. Escalante J. Lamatsch B. Seebach D. J. Org. Chem. 1992; 57: 2396
    • 12e Furukawa M. Okawara T. Terawaki Y. Chem. Pharm. Bull. 1977; 25: 1319
  • 13 Torneg J. Prunet J. Org. Lett. 2008; 10: 45
  • 14 Tomberg A. Cesco SD. Huot M. Moitessier N. Tetrahedron Lett. 2015; 56: 6852
  • 15 Wenzel TJ. Tetrahedron: Asymmetry 2017; 28: 1212
  • 16 Dale JA. Mosher HS. J. Am. Chem. Soc. 1973; 95: 512
  • 17 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Jr. Montgomery JA. Vreven T. Kudin KN. Burant JC. Millam JM. lyengar SS. Tomasi J. Barone V. Mennucci B. Cossi M. Scalmani G. Rega N. Petersson GA. Nakatsuji H. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Klene M. Li X. Knox JE. Hratchian HP. Cross JB. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Auatin AJ. Cammi R. Pomelli C. Ochterski JW. Ayala PY. Morokuma K. Voth GA. Salvador P. Dannenberg JJ. Zakrzewski VG. Dapprich S. Daniels AD. Strain MC. Farkas O. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Ortiz JV. Cui Q. Baboul AG. Clifford S. Cioslowski J. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Challacombe M. Gill PM. W. Johnson B. Chen W. Wong MW. Gonzalez C. Pople JA. Gaussian 03 (revision B.05); Gaussian, Inc., Wallingford, CT, USA, 2003
  • 18 Becke AD. J. Chem. Phys. 1993; 98: 5648
  • 19 Lee C. Yang W. Parr RG. Phys. Rev. B: Condens. Matter Mater. Phys. 1998; 37: 785

Zoom Image
Scheme 1 Reaction of (S)- and (R)-α-methylbenzylamines with α,β-unsaturated carbonyl compounds
Zoom Image
Figure 1 Parts of the 1H NMR (A) and 13C NMR (B) spectra of the product 3a+4a
Zoom Image
Figure 2 Attack of (S)-α-methylbenzylamine on Si and Re faces of trans-cinnamaldehyde
Zoom Image
Figure 3 Optimized geometries of the diastereomers formed from the attack of (S)-α-methylbenzylamine on Si (3a) and Re (4a) faces of trans-cinnamaldehyde