29589-03-5Relevant academic research and scientific papers
SN2 displacement at the quaternary carbon center: A novel entry to the synthesis of α,α-disubstituted α-amino acids This Letter is dedicated to the late Professor Harry Wasserman, a great chemist as well as a splendid artist
Ishihara, Kotaro,Hamamoto, Hiromi,Matsugi, Masato,Shioiri, Takayuki
, p. 3169 - 3171 (2015/05/27)
A novel method for the SN2 reaction on quaternary carbon atoms using bis(p-nitrophenyl)phosphorazidate has been developed. Chiral tertiary alcohols were directly converted into the corresponding chiral tertiary azides with complete inversion of configuration. Several α,α-disubstituted α-amino esters or amino acids were prepared through the conversion of azides to the corresponding amines by catalytic hydrogenation.
An asymmetric synthesis of optically pure α,α-disubstituted amino aldehydes, α,α-disubstituted amino acids, and sterically demanding dipeptides
Wenglowsky, Steve
, p. 12468 - 12473 (2007/10/03)
Optically pure α-methyl-α-alkyl amino aldehydes were efficiently synthesized from the cyclohexylimine of propanal bearing an α-4(R),5(S)- diphenyl-2-oxazolidinone by asymmetric alkylation of the imine anion. α- Methylphenylalanine and α-methylleucine were
Enantiomerically Enriched α-Methyl Amino Acids. Use of an Acyclic, Chiral Alanine-Derived Dianion with a High Diastereofacial Bias
Berkowitz, David B.,Smith, Marianne K.
, p. 1233 - 1238 (2007/10/02)
Hindered esters derived from N-benzoylalanine and the following chiral alcohols have been synthesized: (1) (-)-isopinocampheol, (2) (-)-trans-2-phenylcyclohexanol, and (3) (-)-8-phenylmenthol.Sequential treatment of these esters with LDA (1.2 equiv) and n-butyllithium (2.4 equiv) at -78 deg C in THF generates the corresponding chiral dianions.Alkylation of each of these with benzyl bromide reveals that only the (-)-8-phenylmenthyl auxiliary confers a high diastereofacial bias upon its derivative dianion.In fact, that dianion (6) consistently displays diastereomeric ratios in the range of 89:11 to 94:6 for alkylations with a spectrum of nine alkyl halides.If one recrystallization step is included, a single diastereomeric product may be obtained, as is demonstrated for the benzylation of 6.Of particular note, the alkylation with 3,4-bis((tert-butyldimethylsilyl)oxy)benzyl bromide (18) (94:6 diastereomeric ratio, 72percent yield) constitutes a formal synthesis of the clinically important antihypertensive (S)-α-methyl-DOPA (Aldomet), in enantiomerically enriched form.In all cases studied, yields are markedly improved, yet diastereoselectivities unchanged, by the addition of 10percent HMPA to the reaction milieu.The (-)-8-phenylmenthol chiral auxiliary is conveniently recovered via ester cleavage with KO2/18-crown-6, following alkylation.Complete deprotection affords enantiomerically enriched (S)-α-methyl amino acids, in all cases examined, indicating that dianion 6 displays a substantial bias in favor of si face alkylation.This sense of diastereoselection is consistent with a chain-extended, internal chelate model for the reactive conformation of the dianion.
Synthesis of Optically Pure α-Alkylated α-Amino Acids and a Single-Step Method for Enatiomeric Excess Determination
Kruizinga, Wim H.,Bolster, John,Kellogg, Richard M.,Kamphuis, Johan,Boesten, Wilhelmus H. J.,et al.
, p. 1826 - 1827 (2007/10/02)
A method for the enzymatic resolution of the amides of some racemic α-alkylated amino acids is described as well as a method involving derivatization with (S)-2-chloropropionyl chloride followed by 1H NMR analysis to establish the enantiomeric excesses of the free amino acids.
