Thiourea indolyl thioureas

Scheme 6.53 Proposed mechanism for the 53-catalyzed asymmetric Pictet-Spengler-type cyclization of P-indolyl ethyl hydroxylactams Hydroxylactam (1) forms chlorolactam (2) followed by chiral N-acyliminium chloride-thiourea complex (3) and the observed product generated by intramolecular cyclization catalysis and enantioinduction result from chloride abstraction and anion binding.

The simply obtainable thiourea compounds 142-145 were the first organo-catalysts for the catalytic conjugate addition of indoles with nitroalkenes to yield optically active 2-indolyl-l-nitro derivative as 2.R-50 in fairly good yields and enantioselectivity. The simple thiourea-based organo catalyst 145 could be easily accessed in both enantiomeric forms from the commercially available materials. At the same time, the extremely simple methodology has proved the new approach useful for the synthesis of optically active target... 

The AFC reaction of indoles with less reaetive aryl aldimines catalyzed by organocatalystwas reported by the group of Deng in 2006. Bifunctional cinchona alkaloid-derived thioureas were utilized to promote the AFC reaetion of indoles with N-Ts- or AT-Bs-protected imines. With 10 mol% of eatalyst 29, 3-indolyl methanamine derivatives 30 were obtained in high yields with up to 97% ee for both aryl and alkyl imines (Scheme 6.12). 

Jprgensen s group has very recaitly d onstrated the usefulness of o,P-unsaturated acyl phosphonates as hydrogen-bond acceptors in the enantioselective Hiedel-Crafts reaction with indoles [341]. Since the acyl phosphonate moiety is a powerful ester and amide surrogate, this reaction is an interesting approach towards the synthesis of optically active p-(3-indolyl)esters and amides as represented in Scheme 2.119 for selected examples. The reaction is catalyzed by chiral thiourea-based catalyst ent-191 that activates the nucleophile and the electrophile through hydrogen-bond interactions. 

In 2007, the Jacobsen group reported a thiourea-catalyzed Pictet-Spengler reaction in a four-step total synthesis of (+)-harmicine (202), in which the key Pictet-Spengler cyclization of tryptamine derivative indole 199 using thiourea 200 as a catalyst gave the jS-indolyl ethyl hydroxylactams 201 in 97% ee (Scheme 17.34) [81]. The reduction of lactam 201 completed the synthesis of (+)-harmicine (202). 

The formation of N-acyUminium ions by a thiourea-mediated catalytic reaction was investigated with P-indolyl ethyl hydroxylactams. The generation of the N-acyltmrriinium in the presence of an indole can be successfully used in a Pictet-Spengler-type cycUzation of such compounds, affording highly enantioenriched indoUzidinones and quinoUzidinones (Scheme 26.14) [88]. 

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... 

SCHEME 2.77 Chiral thiourea-catalyzed Pictet-Spengler reaction of 3-indolyl hydroxy-lactams. 

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