Catalysis thiourea

The conjugate addition of nitro olefins under chiral Cmc/mna-thiourea catalysis has shown promising results with a variety of Michael donors. Dixon conducted a screen of various chiral thioureas and identified catalyst 117 as a versatile catalyst that works well with p-substituted nitro-olefms (78) [74]. Aromatic, heteroaromatic... 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

The reader is encouraged to contemplate the mechanistic similarities and differences between each type of catalyst system as this will lead to a coherent and logical understanding of this seemingly disjointed field. Thiourea catalysis is not discussed as it is covered in the following chapter. 

For organizational reasons, several catalytic systems possessing multiple hydrogen bond donating functionalities have been included in this section which may not be classified as BBAs. For example, the bistrifylamide Mikami catalyst could perhaps be classified as a double-hydrogen bond donor catalyst akin to thiourea catalysis. 

Vermilion, B.R. and RJ.M. Hudson. 2007. Thiourea catalysis of MeHg hgand exchange between natural dissolved organic matter and a thiol-functionalized resin A novel method of matrix removal and MeHg preconcentration for ultratrace Hg speciation analysis in freshwaters. Anal. Bioanal. Chem. 388 341-352. 

Amongst the first intramolecular processes developed using thiourea catalysis was that of the acyl-Pictet-Spengler reaction, devised by Jacobsen in 2004 [36,37]. In the initial reaction, thiourea 112 was found to perform well in terms of both yield and enantio-selectivity and a range of substrates were shown to undergo reaction (Table 1.1). 

FIGURE 2.41. Takemoto s (A) and Papai s (B) alternative transition states for the bifunctional amine-thiourea catalysis of Michael addition to nitroolelins. 

Scheme 7.12 Domino aldol-q clisation reaction catalysed by thiourea catalysis and chiral cobalt catalysis.

Tandem Mannich-type-hydroamination-isomerisation catalysed by chiral thiourea catalysis and gold catalysis. 

For reviews on thiourea catalysis, see, Takemoto, Y. (2005) Organic and Biomolecidar Chemistry, 3, 4299-4306. Takemoto, Y. (2006) Yuki Gosei Kagaku Kyokaisfu, 64, 1139-47. Connon, S.J. (2006) Chemistry - A European Journal, 12, 5418-27. 

Table 30.2 Hydrocyanation of ketones supported by thiourea catalysis.

Chiral phosphoric acids 24e and ent-26f have been used recently to promote enantioselective F-C alkylations of indoles with 3-substituted 3-hydroxyisoindolin-1-ones 64 (Scheme 35.14) [32, 67]. Moreover, a,a-dicyanoolefins have also been used in association with 2-naphthols for the synthesis of naphthopyrans in high yields (up to 99%) and good selectivities (up to 90% ee) via hydrogen-bonding thiourea catalysis [68]. 

Subsequently, the same group showed that ji-indolyl hydroxylactams 283 could also be applied to a Pictet-Spengler reaction under chiral thiourea catalysis. In the presence of TMSCl, P-indolyl hydroxylactams were converted to chlorolactams... 

The anion-binding thiourea catalysis was applied further in asymmetric polycyclization of hydroxylactam derivatives 296 (Scheme 2.81). It was found that larger aromatic groups on the pyrrolidine ring of thiomea catalyst produced better results in terms of reactivity and enantioselectivity. The 4-pyrenyl-substituted thiourea 289c was found to be an optimal catalyst to promote polycyclization reactions which involved stabilizing cation-ji interactions to indnce the enantioselectivity [112]. 

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