Doo‐Ha Yoon, H. Ha, B. Kim
Jul 27, 2010
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ChemInform
Abstract
Conjugate addition of benzylamine to chiral methyl cis-3-aziridin-2-yl-acrylates was successfully proceeded to yield 3-aziridin-2-yl-3-benzylaminopropionates in high yield with high stereoselectivity. The addition products were used for the asymmetric synthesis of vicinal diamine derivatives including 4amino-5-methylpyrrolidin-2-one, 3,4-diaminopentanoate, and 5-chloromethyl-4-alkoxycarbonylmethylimidazolidin-2-one. 2010 Elsevier Ltd. All rights reserved. Synthesis of stereochemically well-defined 1,2-diamines is still a great challenge to many organic chemists due to their vast utilities as catalysts, metal-ligands, and sub-unit of some natural products. Especially b,c-diamino acids and their cyclic forms like 4-aminopyrrolidin-2-one and imidazolidin-2-one have unique properties as peptidomimetics and as constituents of biologically active molecules including renin-inhibitory statin analogs, antifungal and cytotoxic microsclerodermins, and antipsychotic nemonapride. Furthermore, the reduced form of 4-aminopyrrolidin-2-one provides an entry into the 3-aminopyrrolidine family of alkaloids (Fig. 1). Considering the vast utilities of these compounds, limited methods are available and most of which is based on a-amino acids as starting material through homologations followed by introducing one more amine functionality. These known methods were suffered from the limited sources of starting substrates and the multi-reaction steps including low yield. In this Letter is described a general and facile synthetic method to access enantiomerically pure anti b,c-diamino acids and their cyclic forms using chiral aziridine. During last several years we have shown that enantiomerically pure aziridine-2-carboxylate is a configurationally stable surrogate of aor b-amino acids. Homologation and proper functionalization of carboxylate followed by aziridine ring opening provided many valuable compounds such as unnatural amino acids, sphinganine, phytosphingosine, ceramide analogs, and terminal 1,2-diamines. Homologation by two carbons and introduction of one more amino group adjacent to the aziridine-ring will be able to provide a good synthetic intermediate toward the targeted b,cdiamino acids and their cyclic forms. At first transand cis-3-[{(10R)-phenylethylaziridine}-(2R)and (2S)-yl]-acrylates were selectively prepared from aziridine-2-carboxaldehyde. The reaction of [(1R)-phenylethylaziridine]-(2R)carboxaldehyde with (EtO)2POCH2CO2R yielded trans-3-[{(10R)phenylethylaziridin}-(2S)-yl]-acrylate in more than 95% yield with the ratio of 98:2 regardless of R (methyl and ethyl). The same reaction with Ph3PCH2CO2R leading to alkyl cis-3-[{(10R)-phenylethylaziridin}-(2R)and (2S)-yl]-acrylates, 1 and 2, was also successfully provided in more than 93% yield with the ratio of 88:12 (R = Me) and 86:14 (R = Et). Interestingly, only the cis and trans isomers bearing methyl ester were chromatographically CO2H R NH2