Glycal Cyclization InBr 3 -Catalyzed Cyclization of Glycals with Aryl Amines** JhilluS. Yadav,* BasiV.S. Reddy, KattaV. Rao, Kavuda Saritha Raj, Atlaluri R. Prasad, Singarapu KiranKumar, AjitC. Kunwar, Panjula Jayaprakash, and Bulusu Jagannath Dedicated to Professor Goverdhan Mehta on the occasion of his 60th birthday Glycals are ambident electrophiles capable of reacting with various nucleophiles such as alcohols, malonates, and silyl nucleophiles under the influence of acid catalysts or oxidants to produce 2,3-unsaturated glycosides. [1,2] In recent times, indium halides have emerged as versatile Lewis acid catalysts imparting high regio-, chemo-, and diastereoselectivity to a variety of organic transformations. [3] Compared to conven- tional Lewis acids, indium tribromide, in particular, has advantages of low catalyst loading, moisture stability, and catalyst recycling. [4] C-Glycosides bearing carbon-linked het- erocycles have attracted great attention owing to their potent antiviral and antitumor behavior. [5] Because of these proper- ties of aryl glycosides, we have attempted C-glycosidation with aryl amines to synthesize aryl C-glycosides with a free amino functionality for further derivatization. Interestingly, we observed for the first time an unusual formation of benzo- fused heterobicycles in the aminoglycosidation. In our continuing research on glycoside synthesis, [6] we have made unprecedented observations in the aminoglycosi- dation reactions of glycals with aryl amines, which we report here. Initially, we attempted the aminoglycosidation reaction of d-glucal with aniline using 10 mol % indium( iii ) bromide as a novel glycosyl activator. Interestingly, the unusual bicyclic adduct 3a (R = H) was isolated in 85% yield with high stereoselectivity (Scheme 1). The product 3a was characterized thoroughly by various NMR experiments including double-quantum-filtered corre- lation spectroscopy (DQFCOSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum cor- relation spectroscopy (HSQC), [7] and 3 J CH -optimized HMBC experiments. [8] The edited HSQC spectrum showed the presence of two methylene groups in addition to eight methine and two methyl groups. The location of the methylene group in the bridge of a bicyclononene-like structure was confirmed by the presence of small couplings between these protons and the bridgehead protons H1 and H3 (J H1-H2(pro-S) = 3.7 Hz, J H1-H2(pro-R) = 1.8 Hz, J H2(pro-S)-H3 = 2.4 Hz, and J H2(pro-R)-H3 = 4.6 Hz; Figure 1)). Fusion of the bicyclononene and the aromatic ring at C1 ÀC11 and NHÀC3 was confirmed by nOe interactions between H1 and H12. Further support for the structure came from HMBC peaks for H1/C12, H1/C11, H1/C16 and H12/C1. The two six-mem- bered rings of the bicyclononane moiety have two different conformations. The one containing oxygen takes a chair form, Scheme 1. Reaction of 3,4,6-tri-O-acetyl-d-glucal (2) with aryl amines. Figure 1. a) Characteristic nOe interactions, b) the chemical structure, and c) the energy-minimized structure of 3a. [*] Dr. J. S. Yadav, Dr. B. V. S. Reddy, K. V. Rao, K. Saritha Raj, Dr. A. R. Prasad Division of Organic Chemistry Indian Institute of Chemical Technology Hyderabad-500 007 (India) Fax: (+ 91) 40-2716-0512 E-mail: yadav@iict.ap.nic.in S. Kiran Kumar, Dr. A. C. Kunwar Centre for Nuclear Magnetic Resonance Indian Institute of Chemical Technology Hyderabad-500 007 (India) P. Jayaprakash, Dr. B. Jagannath Molecular Modelling and Drug Design Indian Institute of Chemical Technology Hyderabad-500 007 (India) [**] B.V.S.R., K.V.R., K.S.R., and S.K.K. thank the Council of Scientic and Industrial Research (CSIR), New Delhi, for the award of fellowships. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Communications 5198 # 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/anie.200351267 Angew. Chem. Int. Ed. 2003, 42, 5198 –5201