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Azaphilic versus Carbophilic Coupling at CN Bonds: Key Steps in Titanium‐Assisted Multicomponent Reactions
Author(s) -
Roth Torsten,
Wadepohl Hubert,
Clot Eric,
Gade Lutz H.
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.201503732
Subject(s) - chemistry , selectivity , reagent , aryl , titanium , combinatorial chemistry , metal , coupling reaction , carbon atom , nitrogen atom , group (periodic table) , organic chemistry , catalysis , alkyl
Consecutive C‐ and N ‐ arylation of N‐heterocyclic nitriles is mediated by titanium(IV) alkoxides. The carbo‐ and azaphilic arylation step may be separated by choosing the order in which the two equivalents of aryl transfer reagent are added. In the course of this transformation, the ancillary N‐heterocycle acts as both a directing anchor group and electron reservoir. In the selectivity‐determining step, the selectivity is governed by a choice between (direct) C‐ and Ti‐arylation; the latter opens up a reaction pathway that allows further migration to the nitrogen atom. The isolation of metal‐containing aggregates from the reaction mixture and computational studies gave insights into the reaction mechanism. Subsequently, a multicomponent one‐pot protocol was devised to rapidly access complex quaternary carbon centers.