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Atom‐Economical Dimerization Strategy by the Rhodium‐Catalyzed Addition of Carboxylic Acids to Allenes: Protecting‐Group‐Free Synthesis of Clavosolide A and Late‐Stage Modification
Author(s) -
Haydl Alexander M.,
Breit Bernhard
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201506618
Subject(s) - stereocenter , chemistry , rhodium , catalysis , combinatorial chemistry , polyketide , stereoselectivity , stereochemistry , protecting group , natural product , atom economy , enantioselective synthesis , organic chemistry , biosynthesis , enzyme , alkyl
Abstract Natural products of polyketide origin with a high level of symmetry, in particular C 2 ‐symmetric diolides as a special macrolactone‐based product class, often possess a broad spectrum of biological activity. An efficient route to this important structural motif was developed as part of a concise and highly convergent synthesis of clavosolide A. This strategy features an atom‐economic “head‐to‐tail” dimerization by the stereoselective rhodium‐catalyzed addition of carboxylic acids to terminal allenes with the simultaneous construction of two new stereocenters. The excellent efficiency and selectivity with which the C 2 ‐symmetric core structures were obtained are remarkable considering the outcome under classical dimerization conditions. Furthermore, this approach facilitates late‐stage modification and provides ready access to potential new lead structures.