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Palladium‐Catalyzed Intramolecular C(sp 3 )H Functionalization: Catalyst Development and Synthetic Applications
Author(s) -
Hitce Julien,
Retailleau Pascal,
Baudoin Olivier
Publication year - 2007
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.200600811
Subject(s) - regioselectivity , palladium , chemistry , intramolecular force , catalysis , surface modification , olefin fiber , medicinal chemistry , ruthenium , combinatorial chemistry , stereochemistry , organic chemistry
A novel catalytic system, based on a mixture of palladium acetate and tris(5‐fluoro‐2‐methylphenyl)phosphane (F‐TOTP), has been designed for the intramolecular CH functionalization of alkane segments. Among other analogues of tris(2‐methylphenyl)phosphane (P( o‐ tol) 3 ), F‐TOTP was shown to have the optimal metal‐bonding properties for this reaction. This catalytic system operated under milder reaction conditions that allowed the regioselective production of various olefins adjacent to a quaternary benzylic carbon atom, as well as novel bi‐ and tricyclic molecules. A general mechanism was proposed, with the preferential formation of a six‐membered palladium( II ) palladacycle after oxidative addition and cyclopalladation. The regioselective CH functionalization of alkyl groups into olefins was illustrated in the synthesis of the antihypertensive drug verapamil ( 14 ) and an analogue ( 19 ). A particularly mild ruthenium‐catalyzed direct hydroamidation of the intermediate olefin in this synthesis is also reported.