Premium
One‐Pot and Reducible‐Functional‐Group‐Tolerant Synthesis of α‐Aryl‐ and α‐Heteroaryl‐α‐Trifluoromethyl Alcohols via Tandem Trifluoroacetylation and MPV Type Reduction
Author(s) -
Funabiki Kazumasa,
Hayakawa Ayaka,
Kani Ryunosuke,
Inuzuka Toshiyasu,
Kubota Yashuhiro
Publication year - 2019
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.201901049
Subject(s) - chemistry , trifluoromethyl , aryl , moiety , reagent , isopropyl , functional group , combinatorial chemistry , tandem , medicinal chemistry , organic chemistry , alkyl , polymer , materials science , composite material
We have developed a new one‐pot synthesis of α‐aryl‐ and α‐heteroaryl‐α‐trifluoromethyl alcohols carrying not only arenes with electron‐withdrawing groups but also electron‐deficient nitrogen‐containing heteroarenes, which are of increasing interest because these compounds are some of the most important units in current fluorine‐containing inhibitors or antagonists. This new method includes three tandem reactions in a one‐pot synthesis: (1) the in situ generation of functionalized aromatic and electron‐deficient heteroaromatic Grignard reagents, (2) trifluoroacetylation of the generated Grignard reagents with diphenylmethyl trifluoroacetate, and (3) successive Meerwein–Ponndorf–Verley type reduction. It offers several advantages, including no need for expensive transition metals and gaseous trifluoromethylating reagents, toleration of not only reducible functional groups on the aryl groups but also electron‐deficient nitrogen‐containing heterocycles, easy scalability, and the ability to suppress the formation of the bis‐aldol product as a by‐product by changing the ester moiety of the trifluoroacetate from an isopropyl to a diphenylmethyl group.