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Mutually Complementary Metal‐ and Organocatalysis with Collective Synthesis: Asymmetric Conjugate Addition of 1,3‐Carbonyl Compounds to Nitroenynes and Further Reactions of the Products
Author(s) -
Li Xiang,
Li Xiaojiao,
Peng Fangzhi,
Shao Zhihui
Publication year - 2012
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201200226
Subject(s) - stereocenter , chemistry , enantioselective synthesis , organocatalysis , combinatorial chemistry , catalysis , bifunctional , cascade reaction , conjugate , stereochemistry , organic chemistry , mathematical analysis , mathematics
The first metal‐catalyzed 1,4‐selective asymmetric addition of malonates to nitroenynes promoted by a simple chiral nickel(II)‐diamine catalyst, was developed, facilitating a mild synthesis of a novel type of multifunctional chiral β‐alkynyl acids bearing a nitro group. Based on this protocol, we have developed a practical and collective synthesis of a series of diverse functional molecules and building blocks including new types of chiral β‐alkynyl‐γ‐amino acids, β‐functionalized chiral δ‐keto‐γ‐lactones, chiral γ‐alkylidenelactones, alkynyl‐substituted pyrrole‐3‐carboxylic acid derivatives, tetrasubstituted furans and chiral β‐alkynyl‐γ‐lactams. Notably, we discovered two unusual tandem reactions leading to functionalized chiral 1,5‐dicarbonyl compounds. In addition, by employing simple bifunctional organocatalysts, we have developed the first regio‐, diastereo‐ and enantioselective conjugate addition of α‐substituted β‐keto esters to nitroenynes, which is poorly diastereoselective with chiral nickel(II)‐diamine catalysts, providing a new entry to adjacent quaternary and tertiary stereocenters in one step. Based on this protocol, we have developed a concise asymmetric synthesis of conformationally constrained bicyclic γ 2 ‐amino acids featuring an alkynyl side chain with an adjacent quaternary carbon stereocenter. The study described here demonstrates that the mutually complementary strategy of transition metal catalysis and organocatalysis is a powerful and promising tool in catalytic asymmetric synthesis.