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Enantioselective Total Synthesis of Macfarlandin C, a Spongian Diterpenoid Harboring a Concave‐Substituted cis ‐Dioxabicyclo[3.3.0]octanone Fragment
Author(s) -
Allred Tyler K.,
Dieskau André P.,
Zhao Peng,
Lackner Gregory L.,
Overman Larry E.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201916753
Subject(s) - enantioselective synthesis , stereocenter , stereochemistry , chemistry , stereoselectivity , total synthesis , moiety , substituent , electrophile , butenolide , organic chemistry , catalysis
Abstract The enantioselective total synthesis of the rearranged spongian diterpenoid (−)‐macfarlandin C is reported. This is the first synthesis of a rearranged spongian diterpenoid in which the bulky hydrocarbon fragment is joined via a quaternary carbon to the highly hindered concave face of the cis ‐2,8‐dioxabicyclo[3.3.0]octan‐3‐one moiety. The strategy involves a late‐stage fragment coupling between a tertiary carbon radical and an electrophilic butenolide resulting in the stereoselective formation of vicinal quaternary and tertiary stereocenters. A stereoselective Mukaiyama hydration that orients a pendant carboxymethyl side chain cis to the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave‐substituted cis ‐dioxabicyclo[3.3.0]octanone fragment.