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One‐Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α‐Aryl‐α‐Trifluoromethyl Alcohols
Author(s) -
Kani Ryunosuke,
Inuzuka Toshiyasu,
Kubota Yasuhiro,
Funabiki Kazumasa
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000550
Subject(s) - chemistry , trifluoromethyl , aryl , reagent , nucleophile , organic chemistry , functional group , combinatorial chemistry , medicinal chemistry , catalysis , polymer , alkyl
A novel straightforward one‐pot methodology for two successive turbo Grignard reagent ( i PrMgCl · LiCl) reactions, was developed for a facile synthesis of α‐aryl‐α‐trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of i PrMgCl · LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2‐trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one‐pot process: the i PrMgCl · LiCl‐mediated iodine/magnesium‐exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2‐trifluoroethyl trifluoroacetate; and the reduction of in‐situ generated aryl trifluoromethyl ketones with i PrMgCl · LiCl, to produce the corresponding α‐aryl or α‐heteroaryl‐α‐trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.