| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1346887 | Tetrahedron: Asymmetry | 2011 | 16 Pages |
The conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to a range of aryl substituted tert-butyl cinnamate esters followed by reaction of the resultant lithium β-amino enolates with D2O provides access to anti configured α-deuterio-β-aminocinnamate esters in high dr. The corresponding syn configured diastereoisomers were also obtained with high diastereoselectivity via the conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to a range of tert-butyl α-deuteriocinnamate esters followed by reaction of the resultant lithium β-amino enolates with 2-pyridone. After deprotection both the syn- and anti-diastereoisomers of the corresponding α-deuterio-β3-amino acids can be isolated in high dr.
Graphical abstractBoth the syn- and anti-diastereoisomers of α-deuterio-β3-phenylalanine derivatives can be prepared via diastereoselective protonation or deuteration of the intermediate lithium β-amino enolates obtained from the conjugate addition of an enantiopure lithium amide to α-deuteriocinnamates or α-protiocinnamates, respectively, followed by deprotection.Figure optionsDownload full-size imageDownload as PowerPoint slide
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-phenylpropanoateC28H32DNO2[α]D22 −8.8 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-(α-methylbenzyl)amino]-3-phenylpropanoateC21H26DNO2[α]D21 −18.3 (c 0.3 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (3R,αS)-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-bromophenyl)propanoateC28H32BrNO2[α]D25 −6.6 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,αS)
tert-Butyl (3R,αS)-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-fluorophenyl)propanoateC28H32FNO2[α]D21 −0.5 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,αS)
tert-Butyl (3R,αS)-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(2′-bromophenyl)propanoateC28H32BrNO2[α]D25 −26.6 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(4′-methoxyphenyl)propanoateC29H34DNO3[α]D25 −2.3 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl]amino)-3-(4′-bromophenyl)propanoateC28H31BrDNO2[α]D24 +2.5 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-bromophenyl)propanoateC28H31DBrNO2[α]D25 −5.9 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-fluorophenyl)propanoateC28H31DFNO2[α]D25 −2.3 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(2′-bromophenyl)propanoateC28H31DBrNO2[α]D25 −34.7 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (2S,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(2′-iodophenyl)propanoateC28H31DINO2[α]D25 −24.8 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R,αS)
tert-Butyl (3R,αS)-2,2-dideuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-phenylpropanoateC28H31D2NO2[α]D25 −9.1 (c 0.6 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-phenylpropanoateC28H32DNO2[α]D21 −7.0 (c 0.7 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(4′-bromophenyl)propanoateC28H31DBrNO2[α]D25 +1.8 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-bromophenyl)propanoateC28H31DBrNO2[α]D25 −5.1 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(3′-fluorophenyl)propanoateC28H31DFNO2[α]D25 −1.9 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(2′-bromophenyl)propanoateC28H31DBrNO2[α]D25 −30.1 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2R,3R,αS)-2-deuterio-3-[N-benzyl-N-(α-methylbenzyl)amino]-3-(2′-iodophenyl)propanoateC28H31DINO2[α]D25 −17.7 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,αS)
tert-Butyl (2S,3R)-2-deuterio-3-amino-3-phenylpropanoateC13H20DNO2[α]D21 +24.5 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)
(2S,2R)-2-Deuterio-3-amino-3-phenylpropionic acidC9H10DNO2[α]D22 +0.7 (c 0.2 in H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,2R)
tert-Butyl (R,R)-2-deuterio-3-amino-3-phenylpropanoateC13H18DNO2[α]D25 +3.5 (c 1.0 in CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)
(R,R)-2-Deuterio-3-amino-3-phenylpropanoic acidC9H10DNO2[α]D25 +6.0 (c 1.0 in H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (R,R)
