TETRAHEDRON LETTERS Tetrahedron Letters 43 (2002) 7009–7012 Pergamon CeCl 3 ·7H 2 O: a novel reagent for the synthesis of 2-deoxysugars from D-glycals J. S. Yadav,* B. V. S. Reddy, K. Bhaskar Reddy and M. Satyanarayana Organic Chemistry Division -I, Indian Institute of Chemical Technology, Hyderabad 500 007, India Received 23 April 2002; revised 17 July 2002; accepted 29 July 2002 Abstract—D-Glycals react smoothly with a variety of alcohols in a highly stereoselective manner in the presence of the CeCl 3 ·7H 2 O–NaI reagent system in refluxing acetonitrile under neutral conditions to afford the corresponding 2-deoxy--glycopy- ranosides in high yields. In the absence of NaI, the glycals undergo Ferrier rearrangement under the influence of CeCl 3 ·7H 2 O in refluxing acetonitrile to afford the corresponding 2,3-unsaturated hexopyranosides in good yields. © 2002 Elsevier Science Ltd. All rights reserved. Deoxyglycosides are well-known structural components of several biologically active compounds, especially antitumor antibiotics such as anthracyclines, aureolic acids, orthosamycins, angucyclins, and enediynes. 1 In particular, 2-deoxy--glycosides are present in many bioactive natural products including compactin, olivomycin, mithramycin, daunomycin, calicheamicin and many others. 2 In this context, several methods have been developed for the preparation of 2-deoxy sugars in a multi-step sequence. 3,4 Of these, the acid-catalyzed addition of an alcohol to acetylated glycals appears to be the most direct method for the synthesis of 2-deoxy pyranosides. 5 However, only a few methods have been reported so far for the direct synthesis of 2-deoxy--gly- cosides from glycals. 5,6 To date, the generality of this process to prepare 2-deoxy sugars has remained unattractive as the protected glycals often give rear- ranged products under acidic conditions. 7 Thus the development of a neutral alternative such as the CeCl 3 – NaI reagent system would extend the scope of this transformation. Lanthanide salts are unique Lewis acids 8 that are currently of great research interest. In particular, cerium reagents are relatively non-toxic, readily available at low cost and are fairly stable in water. 9 We wish to report a mild and efficient method for the synthesis of 2-deoxyglycosides from glycals and alco- hols using the CeCl 3 ·7H 2 O–NaI reagent system. Thus, treatment of 3,4,6-tri-O -acetyl-D-glucal with allyl alco- hol in the presence of cerium(III) chloride heptahy- drate–sodium iodide in acetonitrile afforded the corresponding 2-deoxyglycopyranoside in 87% yield with high -selectivity (Scheme 1). The -anomer was obtained exclusively, the structure of which was characterized by spectroscopic data. The predominant formation of the -anomer may arise from a thermodynamic anomeric effect. The reaction proceeded smoothly using CeCl 3 ·7H 2 O–NaI in refluxing acetonitrile under neutral conditions. The combination of cerium(III) chloride with NaI works efficiently to afford the corresponding 2-deoxyglycopyranosides in high yields (entries a-1, Table 1). However, in the absence of NaI, the glycals underwent Ferrier rear- rangement under the influence of CeCl 3 ·7H 2 O in reflux- ing acetonitrile to afford the corresponding 2,3-unsaturated hexopyranosides in good yields (Scheme 2). In the absence of sodium iodide, the products were obtained as a mixture of - and -anomers, favoring the -anomer. The ratios of products were determined by the examination of the 1 H NMR spectra of the crude products (entries a-l, Table 2). This clearly indi- cates that the addition of 1 equiv. of NaI is crucial to Scheme 1. Keywords : cerium reagents; D-glycals; 2-deoxysugars; carbohydrates. * Corresponding author. Fax: +91-40-7160512; e-mail: yadav@ iict.ap.nic.in 0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(02)01584-8