New Approaches to the Use of Amino Acids as Chiral Building Blocks in Organic Synthesis [New Synthetic Methods (85)]

Abstract

a-Amino acids protected at nitrogen in quite different ways can be transformed without racemization into the corresponding a-amino aldehydes. Provided one chooses the right protecting groups (e.g., two benzyl residues on nitrogen) it is possible for the first time to carry out Grignard-like, aldol, and Me,SiCN additions, and hetero-Diels-Alder reactions with a high degree of nonchelation control. If the reactions of classical carbanions turn out to be nonselective, transmetalation, for example into organotitanium reagents, constitutes an important too1 in controlling stereoselectivity. Diastereoseiectivity can be reversed by specific variation of the protecting group and reagent. "Protecting-group tuning", "metal tuning", and "ligand tuning" are very useful in reactions of a-amino aldimines as well. The a-amino aldehydes can also be converted by Wittig reactions into electron-poor y-amino olefins, which in turn undergo stereoselective cuprate, Michael, and cycloadditions.

Resolution and absolute configuration of some α-aminoacetals: en route to enantiopure N-protected α-aminoaldehydes

“…The ee's of compounds 7a-b after ketalization showed no appreciable changes when compared with the ee's of compounds 7a-b before the acetal hydrolysis with formic acid. It is worth noting that the very mild procedure to obtain N-protected-a-aminoaldehydes through the corresponding acetal hydrolysis without detectable racemization constitutes a valuable route to these useful chiral building blocks (Jurczak and Golebiowski 1989;Reetz 1999Reetz , 1991Gryko et al 2003;Hili et al 2008;Baktharaman et al 2008;Izawa and Onishi 2006;Garner and Park 1987;Chowdari et al 2003;Tokuyama et al 2002;Dias et al 2003;Kwon and Myers 2005;Wen and Crews 1998;Hili and Yudin 2006;Myers et al 2000;Diness et al 2004). …”

Stereoselective synthesis of γ-amino acids

“…9). 290 Diastereoselective reduction of tetramic acids 756 and 757 is another methodology used in the stereoselective synthesis of statine derivatives. In this context, N-Boc tetramic acid On the other hand, the reduction of 755 with NaBH 3 CN in the presence of TMSCl in acetonitrile gave N-Cbz-Nmethyl-c-amino-b-hydroxy ethyl esters syn-698 and anti-699 in a ratio of 3:1 to 4:1 and excellent yield, via the ketoester derivative (Scheme 195).…”

1,3‐Dipolar Cycloaddition of Azomethine Ylides to Aldehydes: Synthesis of anti α‐Amino‐β‐Hydroxy Esters

“…These compounds are readily converted into the corresponding amino diols, which have been used as ligands for asymmetric catalysis, chiral auxiliaries, [18] and chiral building blocks. [19] It is then not surprising that large efforts have been directed toward stereocontrolled assembly of α-amino-β-hydroxy esters. [20,21] We have recently reported [22a] that the AMY obtained by reduction of 3-methyl-5-methoxy oxazolium triflate [22b] (6) adds to benzaldehyde to give the corresponding trans-4,5-disubstituted oxazolidine 2 (Scheme 1, route B; R 1 = Ph, R Scheme 1.…”