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Practical Enantioselective Arylation and Heteroarylation of Aldehydes with In Situ Prepared Organotitanium Reagents Catalyzed by 3‐Aryl‐H 8 ‐BINOL‐Derived Titanium Complexes
Author(s) -
Uenishi Ami,
Nakagawa Yuya,
Osumi Hironobu,
Harada Toshiro
Publication year - 2013
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.201203946
Subject(s) - reagent , catalysis , aryl , enantioselective synthesis , chemistry , combinatorial chemistry , titanium , reaction conditions , in situ , organic chemistry , alkyl
A highly efficient and practical method for the catalytic enantioselective arylation and heteroarylation of aldehydes with organotitanium reagents, prepared in situ by the reaction of aryl‐ and heteroaryllithium reagents with ClTi(O i Pr) 3 , is described. Titanium complexes derived from DPP‐H 8 ‐BINOL ( 3 d ; DPP=3,5‐diphenylphenyl) and DTBP‐H 8 ‐BINOL ( 3 e ; DTBP=3,5‐di‐ tert ‐butylphenyl) exhibit excellent catalytic activity in terms of enantioselectivity and turnover efficiency for the transformation, providing diaryl‐, aryl heteroaryl‐, and diheteroarylmethanol derivatives in high enantioselectivity at low catalyst loading (0.2–2 mol %). The reaction begins with a variety of aryl and heteroaryl bromides through their conversion into organolithium intermediates by Br/Li exchange with n BuLi, thus providing straightforward access to a range of enantioenriched alcohols from commercially available starting materials. Various 2‐thienylmethanols can be synthesized enantioselectively by using commercially available 2‐thienyllithium in THF. The reaction can be carried out on a 10 mmol scale at 0.5 mol % catalyst loading, demonstrating its preparative utility.