InBr₃‐Catalyzed Cyclization of Glycals with Aryl Amines

Abstract

Dedicated to Professor Goverdhan Mehta on the occasion of his 60th birthdayGlycals 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 conventional Lewis acids, indium tribromide, in particular, has advantages of low catalyst loading, moisture stability, and catalyst recycling.[4] C-Glycosides bearing carbon-linked heterocycles have attracted great attention owing to their potent antiviral and antitumor behavior.[5] Because of these properties 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 benzofused heterobicycles in the aminoglycosidation.In our continuing research on glycoside synthesis, [6] we have made unprecedented observations in the aminoglycosidation 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 3 a (R = H) was isolated in 85 % yield with high stereoselectivity (Scheme 1).The product 3 a was characterized thoroughly by various NMR experiments including double-quantum-filtered correlation spectroscopy (DQFCOSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum correlation 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 C1ÀC11 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-membered rings of the bicyclononane moiety have two different conformations. The one containing oxygen takes a chair form,

Application of Microwave Irradiation in the Synthesis of Carbohydrates

“…But instead of desired products we ended up with one interesting unusual adduct 47. While this work was in progress Jadav et al 52 reported results on InBr 3 catalyzed reactions at room temperature, which supports our observation. They used CH 2 Cl 2 and the same kind of aniline donors, and obtained the same type of cyclic compounds (Scheme 35).…”

Indium Tribromide: A Water-Tolerant Green Lewis Acid

“…10 Although the reaction also proceeded with InCl 3 , InBr 3 was found to be superior in terms of yield and reaction rate. This reaction can also be performed with stoichiometric amounts of TMSOTf.…”

A mild and efficient synthesis of chiral tetrahydroquinolino pyranose derivatives catalyzed by lanthanum(iii) nitrate hexahydrate

“…Most of the methods employed the hetero Diels-Alder method using different Lewis acids such as BF 3 ·OEt 2 [9], ZnCl 2 [10], BiCl 3 [11], and InCl 3 [12,13] and Brönsted acids such as HBF 4 , CF 3 COOH, TsOH [14], and also mineral acids [15] to produce 2,3-tetrahydroquinolinated pyranose derivatives. Recently, Yadav et al reported the synthesis of 2,4-tetrahydroquinolinated pyranose derivatives using InBr 3 , Bi(OTf) 3 , and CeCl 3 /NaI [16][17][18]. Many of these methods having one or more disadvantages such as high acidity, long-reaction times, high reaction temperatures, use of stoichiometric amounts of reagents, difficulty in preparation of the catalyst, and most of these methods were conducted under moisture-free conditions.…”