The Pictet-Spengler condensation of tryptamine (or a substituted analogue) with an aldehyde, usually in the presence of an excess of a Brønsted acid, [1] is the reaction of choice for the preparation of tetrahydro-b-carbolines (for example, 1), a structural moiety present in many alkaloids and related biologically active molecules. [2] Several strategies have been applied to the synthesis of tetrahydro-b-carbolines in enantiomerically pure form. It is possible to start with an enantiomerically pure chiral tryptamine, such as a tryptophan derivative, or aldehyde; alternatively, the use of a chiral auxiliary attached to the nitrogen atom has been successful. Two remarkable examples are the cyclization of the N-acyliminium ion 2, in which an a-N,Nphthaloylamino acid is used as a chiral auxiliary, [3] and the cyclization of the N-sulfinyliminium ion 3, with the use of menthyl p-toluenesulfinate as a chiral reagent.[4] The former procedure proceeds with very high diastereoselectivity, but the chiral auxiliary can be removed only under relatively harsh reductive conditions. Lower selectivity is observed with the second method, but the diastereomers are readily separable, and the sulfinyl auxiliary can be cleaved easily by mild hydrolysis.The first example of a reagent-controlled enantioselective Pictet-Spengler-type cyclization was reported by Nakagawa and co-workers.[5] They described the ring closure of nitrone 4 with up to 90 % ee under the influence of a chiral borane (ca. 2 equiv) as a Lewis acid. Two examples of catalytic asymmetric Pictet-Spengler reactions have been reported recently: Taylor and Jacobsen described the cyclization of the N-acyliminium ion 5 with up to 95 % ee under the catalysis of an enantiomerically pure thiourea, [6a] and List and co-workers disclosed the cyclization of the iminium diester 6 with up to 96 % ee under the catalysis of an enantiomerically pure phosphoric acid derived from binaphthol.[6b] Although both methods are impressive examples of the power of asymmetric organocatalysis, the former has the disadvantage that the Nacetyl group is difficult to remove, and the latter is clearly limited in scope by the requirement of two ester functionalities.Within our research program on the development of asymmetric reactions of iminium ions catalyzed by chiral Brønsted acids, we considered the use of N-sulfenyliminium ions as intermediates in the Pictet-Spengler condensation. [7] The sulfenyl substituent was expected to stabilize the intermediate iminium ion and thus favor Pictet-Spengler cyclization over undesired enamine formation.[8] Another advantage of the sulfenyl group is that its ready removal after the cyclization is ensured. Herein, we demonstrate the powerful combination of chiral phosphoric acids and Nsulfenyl tryptamines as a useful method for catalytic asymmetric Pictet-Spengler reactions.The use of phosphoric acids derived from binaphthol as chiral catalysts in asymmetric synthesis was shown recently by two Japanese research groups to be highly successful for the addition of...