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Synthesis of Bridged Benzazocines and Benzoxocines by a Titanium‐Catalyzed Double‐Reductive Umpolung Strategy
Author(s) -
Bichovski Plamen,
Haas Thomas M.,
Kratzert Daniel,
Streuff Jan
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201405852
Subject(s) - umpolung , chemistry , diastereomer , catalysis , titanium , combinatorial chemistry , selectivity , reductive elimination , stereochemistry , organic chemistry , medicinal chemistry , nucleophile
A sequence of two titanium(III)‐catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo‐ and benzoxozine building blocks. The first step is a reductive cross‐coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn ‐selectivity for the quinolone functionalization while the anti ‐diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn ‐chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X‐ray analyses and 2D NMR spectroscopic experiments.