Catalytic Asymmetric Pictet-Spengler Reaction

A few intriguing developments in the area of tetrahydro-P-carboline synthetic methodology include the report of a catalytic asymmetric Pictet-Spengler reaction <06JACS1086> and an enantioselective Pd-catalyzed intramolecular allylic alkylation of indoles <06JACS1424>. A one-step synthesis of 1-substituted-P-carbolines from L-tryptophan has appeared that bypassed the tetrahydro intermediate <06T10900>. 

In 2007, Hiemstra et al. established a catalytic asymmetric Pictet-Spengler reaction that proceeds via (V-sulfenyliminium ions (Scheme 15) [27], Treatment of iV-sulfenylated tryptamines 42 with aldehydes 40 and BINOL phosphate (R)-3f (5 mol%, R = 3,5-(CF3)2-CgH3) afforded tetrahydro-P-carbohnes. After completion of the cyclization the sulfenyl group was cleaved by the use of HCl. This one-pot... 

Seayad J, Seayad AM, List B (2006) Catalytic asymmetric Pictet-Spengler reaction. J Am Chem Soc 128 1086-1087... 

Tian et al. have presented catalytic asymmetric Pictet-Spengler reactions of 4-(2-aminoaryl)indoles (263) with imines (264) in the presence of a commercially available chiral phosphoric acid (261) to give indolo[3,4-cd][l]benzazepines (265) in good to excellent yields and ee (Scheme 68). Enantioselective direct amination of enamides (266) with azodicarboxy-late (267) catalysed by chiral, non-racemic calcium bisphosphate complex (270), afforded optically active products (268-269) (Scheme 69). ... 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

Figure 6.17 Pyrrole thiourea derivatives evaluated for catalytic activity and selectivity in the asymmetric acetyl-Pictet-Spengler reaction.

The Pictet-Spengler reaction, the cyclization of an electron-rich aryl or heteroaryl group onto an imine electrophile, is the established method for the synthesis of tetrahydroisoquinoline and tetrahydro-/ -carboline ring systems. Catalytic asymmetric approaches to these synthetically important structures are mostly restricted to asymmetric hydrogenations of cyclic imines [77, 78]. In a noteworthy... 

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