Experimental and Theoretical Studies in Hydrogen-Bonding Organocatalysis

Abstract

Chiral thioureas and squaramides are among the most prominent hydrogen-bond bifunctional organocatalysts now extensively used for various transformations, including aldol, Michael, Mannich and Diels-Alder reactions. More importantly, the experimental and computational study of the mode of activation has begun to attract considerable attention. Various experimental, spectroscopic and calculation methods are now frequently used, often as an integrated approach, to establish the reaction mechanism, the mode of activation or explain the stereochemical outcome of the reaction. This article comprises several case studies, sorted according to the method used in their study. The aim of this review is to give the investigators an overview of the methods currently utilized for mechanistic investigations in hydrogen-bonding organocatalysis.

CF3-groups critically enhance the binding of thiourea catalysts to ketones – a NMR and FT-IR study

“…Hydrogen-bonding donors like thioureas have been established as efficient organocatalysts. [1][2][3][4][5][6][7][8][9][10] In particular, the wide range of catalyzed reactions, including addition, allylation, Strecker, Michael-and Nitro-Mannich reactions, 11 renders thioureas promising catalysts, which are available at relatively low costs. In particular, substituted diphenylthioureas, pioneered by Schreiner and co-workers, have been shown to provide fast reaction rates and high stereoselectivity for e.g.…”

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

“…1) [1]. Many privileged hydrogen bond donor scaffolds capable of forming single or double hydrogen bonds with the substrate have been developed and explored as catalysts of numerous organic transformations [2–15]. Such catalysts (i.e., I–IX ) [16] may contain one or several highly polarized A–H···A bonds, where A is oxygen or nitrogen and are often designed to mimic enzymatic reactions through the electrostatic substrate activation or stabilization of charged transition states or reaction intermediates.…”

A novel thiourea type organocatalyst possessing a single NH functionality

“…[3][4][5][6][7][8][9][10] As a result of the enormous activity in this area, organocatalysis has emerged as an efficient strategy in the production of enantiomerically enriched compounds with wide application in the synthesis of natural products and biologically active compounds. [18][19][20][21][22][23][24][25] The first reports discussing the propensities of ureas/thioureas to promote chemical transformations appeared more than fifteen years ago. [18][19][20][21][22][23][24][25] The first reports discussing the propensities of ureas/thioureas to promote chemical transformations appeared more than fifteen years ago.…”