Physical Organic Study of Structure–Activity–EnantioselectivityRelationships in Asymmetric Bifunctional Thiourea Catalysis: Hints for the Design of New Organocatalysts

摘要

Hydrogen-bonding catalysis, which is ubiquitous in nature,has become a prominent organocatalytic motif that enables a broad range of transformations.[1] Among a variety of hydrogen- bonding organocatalysts explored so far, chiral thioureas have received special attention owing to their bidentate NH hydrogen-bonding ability for versatile bi- or multifunctional catalysis as in the cases such as the Jacobsen catalyst,[ 2] Takemoto catalyst,[3] the cinchona-type catalysts,[4] and so on.[5] Although intensive research efforts have been devoted to studying the mechanism of bifunctional thiourea catalysis by using either experimental or computational approaches,[ 1, 6] the in-depth knowledge is still substantially lacking and the use, therefore, for new catalyst designs remains elusive and warrants further exploration. In this regard, few studies have been performed on systematic examination of the structure–activity–stereoselectivity relationship, particularly from the point view of electronic effects on this type of catalysis.[7]