Urea and Thiourea as Chiral Catalysts

Abstract After an overview of chiral urea and thiourea synthetic methods, this review describes the main applications of urea and thiourea complexes in asymmetric catalysis. Some recent examples of thioureas as catalysts are also presented. Coordination chemistry of ureas and thioureas is briefly discussed. 

A variety of thiourea (or urea) compounds has been designed as chiral catalysts based on modification of substituent(s) (R and/or R ) with chiral functionality as shown in type C of Figure 9.1, which could recognize the substrate (and/or reagent) to construct an effective asymmetric environment in transition state. The additional functionality in monothiourea... 

In 2010, the Jacobsen group further advanced this chemistry to the combined use of strong achiral acid components with chiral urea and thiourea catalysts for Povarov reaction (Fig. 21) [77]. Different types of electron-rich alkenes, such as 2,3-dihydrofuran, various enamides and enecarbamates, can be used for the Povarov reaction with imine substrates. Detailed kinetic, as well as computational studies, led to the picture of inducing high enantioselectivity with protio-iminium... 

Jacobsen pioneered a number of chiral ureas and thioureas that function as chiral hydrogen-bond donors [40, 41], These were first showcased in enantioselective Strecker reactions in 1998 (see Chapter 10) [160]. The highly modular nature of these catalysts provided ready access to structural variants and facilitated the identification of thiourea 235 as an optimal catalyst in catalytic enantioselective Mannich reactions (Equation 20) [161]. Thus, a broad range of N-Boc-protected aromatic aldimines such as 233 afforded the corresponding products (cf 236) with excellent yield and enantioselectivity. 

In many examples of Brpnsted base catalysis, the combination of a chiral tertiary amine and a hydrogen-bonding donor, such as a urea or thiourea moiety, significantly enhances the selectivity of the formation of carbon-carbon bonds. Catalysts possessing this combination of functional groups have proven useful due to their ability to simultaneously stabilize and activate both electrophilic and nucleophilic components. 

The catalytic potential of base functionalities has been referred to in the previous chapter (see Sect. 7.4), wherein the interplay between an acidic (thio-)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such brfunctional thiourea-containing acid-base catalysts, chiral catalysts containing Lewis or Br0nsted-) base functionality as the sole catalyticaUy active group as weU as those having another H-bond donor like a hydroxy group e.g. Cinchona alkaloids) have found widespread applications in asymmetric catalysis (443-449). 

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