title: Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions.
abstract: The carboxyl group (COOH) is an omnipresent functional group in organic molecules, and its direct catalytic activation represents an attractive synthetic method. Herein, we describe the first example of a direct catalytic nucleophilic activation of carboxylic acids with BH3·SMe2, after which the acids are able to act as carbon nucleophiles, i.e. enolates, in Mannich-type reactions. This reaction proceeds with a mild organic base (DBU) and exhibits high levels of functional group tolerance. The boron catalyst is highly chemoselective toward the COOH group, even in the presence of other carbonyl moieties, such as amides, esters, or ketones. Furthermore, this catalytic method can be extended to highly enantioselective Mannich-type reactions by using a (R)-3,3'-I2-BINOL-substituted boron catalyst.
authors.affiliation: †Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Morita
authors.affiliation: †Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: †Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Nagai
authors.affiliation: †Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: †Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|‡ERATO, Japan Science Technology Agency, Kanai Life Science Catalysis Project, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D001895:Boron / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis
chemical_list: D002264:Carboxylic Acids; D001895:Boron