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A Highly Stereoselective Synthesis of Tetrahydrofurans
Author(s) -
Appun Johannes,
Boomhoff Michael,
Hoffmeyer Patrick,
Kallweit Isa,
Pahl Maik,
Belder Detlev,
Schneider Christoph
Publication year - 2017
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.201700774
Subject(s) - stereoselectivity , stereocenter , chemistry , aldol reaction , lewis acids and bases , silylation , combinatorial chemistry , catalysis , organic chemistry , stereochemistry , enantioselective synthesis
The development of a direct and highly stereoselective synthesis of 2,3,5‐substituted tetrahydrofurans has been accomplished through a combination of batch‐ and microchip‐MS‐experiments. This sequential transformation comprises a Lewis acid‐mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ‐bonds and three stereogenic centers in a one‐pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip‐MS‐experiments include a vinylogous aldol reaction and a Prins‐type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi‐ and tricylic products by carbonyl–ene reactions, proceeding with excellent yields and diastereoselectivity.