Premium
A Combined Vinylogous Mannich/Diels–Alder Approach for the Stereoselective Synthesis of Highly Functionalized Hexahydroindoles
Author(s) -
Ruff Bettina M.,
Zhong Sabilla,
Nieger Martin,
Sickert Marcel,
Schneider Christoph,
Bräse Stefan
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100996
Subject(s) - stereocenter , chemistry , stereoselectivity , cycloaddition , bicyclic molecule , mannich reaction , organic chemistry , organocatalysis , diels–alder reaction , combinatorial chemistry , stereochemistry , catalysis , enantioselective synthesis
A versatile strategy for the formation of hydroindole derivatives is reported. The molecules synthesized are highly functionalized and bear up to six stereogenic centers. We were able to develop a stereoselective route starting from nonchiral commercially available materials. Key steps in the formation of the bicyclic products are an organocatalytic vinylogous Mukaiyama–Mannich and a Diels–Alder reaction. The former uses a 1,1′‐bi‐2‐napthol (BINOL)‐based chiral Brønsted acid catalyst to build the first stereogenic center. The [4+2] cycloaddition proceeds highly diastereoselectively and furnishes one main stereoisomer, which represents the scaffold of the mycotoxins Rostratin B–D. Other transformations include iodolactonization, a Curtius rearrangement, additions, oxidations, and reductions.