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Synthesis of Benzodihydrofurans by Asymmetric C−H Insertion Reactions of Donor/Donor Rhodium Carbenes
Author(s) -
Lamb Kellan N.,
Squitieri Richard A.,
Chintala Srinivasa R.,
Kwong Ada J.,
Balmond Edward I.,
Soldi Cristian,
Dmitrenko Olga,
Castiñeira Reis Marta,
Chung Ryan,
Addison J. Bennett,
Fettinger James C.,
Hein Jason E.,
Tantillo Dean J.,
Fox Joseph M.,
Shaw Jared T.
Publication year - 2017
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.201701630
Subject(s) - chemistry , rhodium , cycloaddition , electrophile , diazo , enantioselective synthesis , allylic rearrangement , catalysis , stereoselectivity , combinatorial chemistry , lewis acids and bases , steric effects , insertion reaction , medicinal chemistry , stereochemistry , organic chemistry
Abstract Metal carbenes appended with two electron‐donating groups, known as “donor/donor” carbenes, undergo diastereo‐ and enantioselective rhodium‐catalyzed C−H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron‐withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO 2 ). Although this sequence often can be performed in one‐pot, control experiments have elucidated why a “two‐pot” process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C−H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.