Preparation of N-substituted sulfoximines by benzotriazole methodology

Alan R. Katritzky; Yuming Zhang; Sandeep K. Singh; Yves P. Le Gall

doi:10.3998/ark.5550190.0004.f13

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Preparation of N-substituted sulfoximines by benzotriazole methodology

Alan R. Katritzky; Yuming Zhang; Sandeep K. Singh; Yves P. Le Gall

Volume 2003, Issue 15, pp. 115-123

DOI: http://dx.doi.org/10.3998/ark.5550190.0004.f13

Paper ID: 03-980FP

Received on 2003-11-13; Accepted on 2004-01-09; Published on 2004-01-15

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Preparation of N-substituted sulfoximines by benzotriazole methodology Alan R. Katritzky,* Yuming Zhang, Sandeep K. Singh, and Yves P. Le Gall Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200 E-mail: Katritzky@chem.ufl.edu (received 13 Nov 03; accepted 09 Jan 04; published on the web 15 Jan 04) Abstract Diverse N-substituted sulfoximines 5a-n were prepared by nucleophilic replacement of the benzotriazole moiety in N-(benzotriazol-1-ylalkyl)sulfoximines 3a-e using organozinc reagents or allylsilanes. N-(Benzotriazol-1-ylalkyl)sulfoximines 3, in turn, were obtained by condensation of sulfoximines 1 with aldehydes 2 and benzotriazole. Keywords: N-Substituted sulfoximines, condensation, nucleophilic substitution, organozinc reagents, allylsilanes Introduction N-Functionalized sulfoximine derivatives are antimuscarinic, spasmolytic,1 antiarrhythmic,2 .-glutamylcysteine synthetase inhibitors,3 possess antitumor activity,4 and are important synthetic intermediates.5 Several methods have been developed for the preparation of N-substituted sulfoximines from NH-sulfoximines: (i) Eschweiler-Clark conditions for N-methylated sulfox- imines;6 (ii) palladium-catalyzed reactions for N-arylated sulfoximines;7 and (iii) base-catalyzed Michael-type additions8 or base-promoted alkylations9a or acylations9b (Scheme 1). Nucleophilic substitution of the benzotriazole moiety in benzotriazolylmethyl amines is an efficient method to prepare N-alkylated amines,10 amides,11 thioamides,12 or sulfonamides.13 Herein, we report the preparation of N-(benzotriazol-1-ylalkyl)sulfoximines 3 as intermediates and subsequent nucleophilic replacement of the benzotriazolyl anion to introduce a simple route to N-substituted sulfoximines 5. Results and Discussion Preparation of N-(benzotriazol-1-ylmethyl)sulfoximines 3a-e A variety of benzotriazolyl intermediates, which provide convenient routes to diverse hetero- cycles,14a are readily available by condensations of benzotriazole and aldehydes with amides, thio 0