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Asymmetric Cyanation of Aldehydes, Ketones, Aldimines, and Ketimines Catalyzed by a Versatile Catalyst Generated from Cinchona Alkaloid, Achiral Substituted 2,2′‐Biphenol and Tetraisopropyl Titanate
Author(s) -
Wang Jun,
Wang Wentao,
Li Wei,
Hu Xiaolei,
Shen Ke,
Tan Cheng,
Liu Xiaohua,
Feng Xiaoming
Publication year - 2009
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.200900936
Subject(s) - cyanation , aldimine , trimethylsilyl cyanide , chemistry , cinchona , strecker amino acid synthesis , organic chemistry , catalysis , benzaldehyde , yield (engineering) , kinetic resolution , enantioselective synthesis , cyanide , cyanohydrin , combinatorial chemistry , medicinal chemistry , materials science , metallurgy
Full investigation of cyanation of aldehydes, ketones, aldimines and ketimines with trimethylsilyl cyanide (TMSCN) or ethyl cyanoformate (CNCOOEt) as the cyanide source has been accomplished by employing an in situ generated catalyst from cinchona alkaloid, tetraisopropyl titanate [Ti(O i Pr) 4 ] and an achiral modified biphenol. With TMSCN as the cyanide source, good to excellent results have been achieved for the Strecker reaction of N ‐Ts (Ts= p ‐toluenesulfonyl) aldimines and ketimines (up to >99 % yield and >99 % ee ) as well as for the cyanation of ketones (up to 99 % yield and 98 % ee ). By using CNCOOEt as the alternative cyanide source, cyanation of aldehyde was accomplished and various enantioenriched cyanohydrin carbonates were prepared in up to 99 % yield and 96 % ee . Noteworthy, CNCOOEt was successfully employed for the first time in the asymmetric Strecker reaction of aldimines and ketimines, affording various α‐amino nitriles with excellent yields and ee values (up to >99 % yield and >99 % ee ). The merits of current protocol involved facile availability of ligand components, operational simplicity and mild reaction conditions, which made it convenient to prepare synthetically important chiral cyanohydrins and α‐amino nitriles. Furthermore, control experiments and NMR analyses were performed to shed light on the catalyst structure. It is indicated that all the hydroxyl groups in cinchona alkaloid and biphenol complex with Ti IV , forming the catalyst with the structure of (biphenoxide)Ti(OR*)(O i Pr). The absolute configuration adopted by biphenol 4 m in the catalyst was identified as S configuration according to the evidence from control experiments and NMR analyses. Moreover, the roles of the protonic additive ( i PrOH) and the tertiary amine in the cinchona alkaloid were studied in detail, and the real cyanide reagent in the catalytic cycle was found to be hydrogen cyanide (HCN). Finally, two plausible catalytic cycles were proposed to elucidate the reaction mechanisms.