N,N′-Bis[3,5-bis(trifluoromethyl)phenyl]thiourea: a privileged motif for catalyst development

Abstract

Over the last decade, the use of (thio)urea derivatives as organocatalysts in organic chemistry has increased rapidly. One of the key features is their ability to activate substrates and subsequently stabilize partially developing negative charges (e.g., oxyanions) in the transition states employing explicit double hydrogen bonding. Among (thio)urea-based catalysts, N,N'-bis[3,5-bis(trifluoromethyl)phenyl]thiourea developed by Schreiner's group (abbreviated here as Schreiner's thiourea) has played a very important role in the development of H-bond organocatalysts. Nowadays it is used extensively in promoting organic transformations, and the 3,5-bis(trifluoromethyl)phenyl motif thereof is used ubiquitously in H-bond catalysts. This review summarizes the key developments of Schreiner's thiourea-mediated reactions with the aim to further expand the applications of (thio)urea-based catalysts.

Recent Developments in Stereoselective Chemical Glycosylation

“…In 2013, Schmidt's group reported the glycosylation of glucosyl and galactosyl trichloroacetimidates could be catalyzed by both phosphoric acid 17 and thiourea 18 (Schreiner's thiourea, Scheme ) . The reaction is β‐selective, which the authors suggested arises through the cooperative action of both catalysts in the transition state.…”

Enantioselective Syntheses of Heteroyohimbine Natural Products: A Unified Approach through Cooperative Catalysis

“…In our initial additive screen, we found that Brønsted acids (entries 6-8) had no effect on conversion;h owever,t he addition of astoichiometric amount of Schrieners thiourea [21] (I,e ntry 9) promoted the full consumption of 16 within our desired timeframe.U nfortunately,t his reaction was plagued by the formation of several undesired side products,t hough the product could be isolated in modest yield and good enantioselectivity.T his result suggested that the ideal approach would need to involve an H-bond donor [22] to activate the previously unreactive ester.B ys witching to the more sterically demanding primary amine F (entry 10), we could increase the enantioselectivity.T hen, switching the Hbond donor to catechol (II,e ntry 12) and increasing the temperature to 40 8 8C, complete consumption of 16 was observed in only 96 h, but yield and selectivity were diminished slightly.W eultimately desired to achieve catalysis with the amine and found that increasing the concentration facilitated this goal (entries [13][14][15]. Finally,w eo bserved that changing the solvent had drastic effects on conversion and selectivity,w ith cyclopentyl methyl ether [23] (CPME) being the optimal solvent (entry 18), providing 15 in good yield and excellent enantioselectivity in just 48 h. Gratify-ingly,the optimized catalysis conditions could be scaled up to provide multigram quantities of enantioenriched piperidine 15 (absolute stereochemistry determined by X-ray crystallographic analysis).…”

A novel thiourea type organocatalyst possessing a single NH functionality

“…[31][32][33][34] In this way, H-bonding secures the chiral environment of the reacting molecules and may also increase the reactivity of the bonded component(s). [38][39][40][41][42] Interestingly, recently an additional role of this moiety has been proposed, namely, its involvement in the formation of the H-bond in which the aromatic ortho C-H bond participates. 35 Current tendencies in designing novel organocatalysts of this type are generally focused on polyfunctionalised derivatives, which possess additional H-bonding fragments within the proximity of the thiourea moiety.…”