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...

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...

A backbone amide linker strategy was chosen for the solidphase synthesis of triazole-containing cyclic tetra-and pentapeptides. An alkyne-substituted linker derived from 4-hydroxy-2-methoxybenzaldehyde was elongated by using standard "Fmoc-based" solid phase chemistry and terminated by coupling of an azido acid. In solution, the peptides were cyclized by a Cu I -catalyzed azide-alkyne cycloaddition reaction. The solid-supported synthesized linear peptides

Phenyl and 4-methylphenyl isocyanide dichlorides are models for byproduct that may be formed in the later stages of certain polyurethane production chains. Photochemical electron paramagnetic resonance (EPR) studies (λ > 310 nm), using the spin trap, N-tert-butyl-α-phenylnitrone, confirm a previously made suggestion that ArNCCl2 can behave as a chlorine radical source. EPR spectra recorded during and after irradiation and supported by simulations evolve over time and indicate formation of the short-lived spin trap–Cl• adduct and a longer lived benzoyl-N-tert-butylnitroxide radical. Photolysis of C6H5NCCl2, either alone or mixed with methylene diaryl isocyanate species, in o-C6H4Cl2, a polyurethane process solvent, led to the formation of mixtures containing dichloro- and trichlorobiphenyl isomers.

Fused pyridine derivatives R 0450Catalytic Asymmetric Pictet-Spengler Reactions via Sulfenyliminium Ions. -An efficient catalytic synthesis of tetrahydro-β-carbolines is accomplished on the basis of the Pictet-Spengler condensation of N-sulfenyltryptamines with a wide range of aldehydes in the presence of (R)-binaphthylphosphoric acid. Best enantioselectivities are obtained by reaction of the tritylsulfenylamine (III). To avoid the isolation of products of type (V), a one-pot, two-step cyclization/deprotection procedure is developed to give the free tetrahydrocarbolines. -(WANNER, M. J.; VAN DER HAAS, R. N. S.; DE CUBA, K. R.; VAN MAARSEVEEN, J. H.; HIEMSTRA*, H.; Angew.