Synthesis of N_β-Substituted α,β-Diamino Acids via Stereoselective N-Michael Additions to a Chiral Bicyclic Dehydroalanine

Abstract

The highly diastereoselective 1,4-conjugate additions of several nitrogen nucleophiles to chiral bicyclic dehydroalanines have been assessed effectively at room temperature in good to excellent yields without needing any catalyst or additional base. This methodology is general, simple, oxygen and moisture tolerant, high-yielding, totally chemo-and stereoselective. Significantly, most of the reaction adducts were obtained in nearly quantitative yield without column chromatography purification. This procedure offers an efficient and practical approach for the synthesis of Nβ-substituted α,βdiamino acids, such as 1-isohistidine, τ-histidinoalanine, β-benzylaminoalanine, β-(piperidin-1-yl)alanine, β-(azepan-1-yl)alanine and fluorescent and ciprofloxacincontaining amino acid derivatives.

Enzymatic and non-enzymatic crosslinks found in collagen and elastin and their chemical synthesis

“…157 Successful stereoselective syntheses of this crosslink have been reported by several groups. 158,159 Arginine. Recently, Eyre et al reported a new crosslink in cartilage formed by the spontaneous oxidation of a ketoamine with arginine to produce arginoline 57 (Fig.…”

Recent Progress in the Asymmetric Syntheses of α‐Heterofunctionalized (Masked) α‐ and β‐Amino Acid Derivatives

“…Besides carrying out asymmetric reductions of α,β-diamino alkenes as shown in Scheme 40, another synthetically usefully alkene-based strategy towards α,β-diamino acids are aza-Michael-initiated approaches (Scheme 41 and Scheme 42). [91][92][93][94] Several complementary, either catalyst-or chiral auxiliarycontrolled asymmetric protocols have been reported to achieve this transformation. One of the most commonly employed strategies is to carry out the addition of suited N-nucleophiles to chiral Ni complexes 180, as demonstrated by numerous research groups over the last years (Scheme 41A).…”

Recent advances in organocatalytic asymmetric oxa-Michael addition triggered cascade reactions

“…The Michael addition reaction is one of the most powerful and valuable tools for the formation of C-X (X = C, O, N, S) bonds, which plays a vital role in organic synthetic chemistry. [1][2][3] It is one of the most typical reactions between a nucleophile called a Michael donor and an activated Michael acceptor, and a huge number of optically functional structures and natural products have been prepared by this important transformation over the years. Meanwhile, the nucleophilicity and reactivity of alcoholic hydroxyl are relatively poor, but the oxa-Michael reaction, as an important part of the Michael reaction for the construction of the C-O bond, has also received considerably…”