The diastereoselectively switchable enantioselective Mannich reaction of isatin imines with hydroxyacetone is reported. The chiral primary amino acid catalyzed this Mannich reaction to afford both anti- and syn-Mannich adducts in high yields, good diastereoselectivities, and enantioselectivities. The reason for the solvent control of the diastereoselectivity phenomenon was investigated.

The H8-BINOL-derived, phosphoric acid catalyzed, highly enatioselective alkylation reaction of enamides with indolyl alcohols has been described. A phosphoric acid derived from H8-BINOL enabled an asymmetric alpha-alkylation of enamides with indolyl alcohols to give beta-aryl 3-(3-indolyl)propanones in high yields (up to 96%) and with excellent enantioselectivity (up to 96% ee).

The development of asymmetric methodologies for the synthesis of chiral indoles has been a long-standing project in organic synthesis. Indole skeletons are heterocyclic systems and are present in numerous alkaloid products, pharmaceuticals, and agrochemicals.[1] Cyclopenta [b]indole skeletons can be found in a number of indole alkaloids, [2] but have not been extensively reported. Compounds that contain such a unit exhibit a wide range of biological activities.[3] For example, 2-aminocyclopenta[b]indoles, [4a] cyclopenta [b]indole-substituted acetic acids, [4b] and a series of yuehchukene analogues [5] have been successfully synthesized and used in medicinal chemistry. Although a number of methods have been developed for the synthesis of cyclopenta [b]indoles, [6] only few of them are asymmetric and especially catalytic asymmetric methods. [7] To the best of our knowledge, there is only one example of the synthesis of chiral cyclopenta [b]indoles by asymmetric catalysis with acceptable enantioselectivities.[8]The development of efficient methods for the construction of cyclopenta [b]indole units is therefore highly desirable. As a continuation of the work of our research group toward the catalytic asymmetric a-alkylation of carbonyl compounds, [9] we rationally designed a one-pot [10] three-step reaction, which consisted of the a-alkylation of an aldehyde, catalyzed by a primary-amine-substituted thiourea, [11] and two consecutive Brønsted acid catalyzed Friedel-Crafts reactions of an indole, [12] to construct chiral polysubstituted cyclopenta [b]indoles (Scheme 1). Herein, we report these consecutive organocatalyzed reactions, which gave structurally diverse cyclopenta [b]indoles in high yields (up to 85 %), and with excellent diastereoselectivities (up to > 99:1) and enantioselectivities (up to 99 % ee).The reactions shown in Scheme 1 were realized in three stages. In the first stage, we examined the a-alkylation of isobutylaldehyde 4 a with 3-indolylmethanol 3 a (step 1) under catalysis by chiral amines 1 and acids 2. Although several methods for the asymmetric amine-based catalysis have been used in similar a-alkylation reactions of aldehydes with diarylmethanol compounds, [11] to date a,a-disubstituted aldehydes have not been used as donors. For the method reported herein, a,a-disubstituted aldehydes were very important precursors because they could produce aldehydes 5 (Scheme 1), which could not be enolated during the following Friedel-Crafts alkylations; thus, there were fewer side reactions in this method. Several amine-based catalysts were investigated in the a-alkylation reaction of aldehyde 4 a.

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