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Concise, Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes
Author(s) -
Nelson Ronald,
Gulías Moisés,
Mascareñas José L.,
López Fernando
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201607348
Subject(s) - enantioselective synthesis , cycloaddition , chemistry , stereoselectivity , catalysis , combinatorial chemistry , alkylation , ruthenium , transfer hydrogenation , platinum , yield (engineering) , diene , stereochemistry , organic chemistry , materials science , natural rubber , metallurgy
A practical synthesis of (−)‐englerin A was accomplished in 17 steps and 11 % global yield from commercially available achiral precursors. The key step consists of a platinum‐catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans ‐fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99 % ee ) stems from an asymmetric ruthenium‐catalyzed transfer hydrogenation of a readily assembled diene–ynone. The synthesis also features a highly stereoselective oxygenation, and a late‐stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.