CBr 4 -photoirradiation protocol for chemoselective deprotection of acid labile primary hydroxyl protecting groups Ming-Yi Chen, a, * Laxmikant N. Patkar, b Mi-Dan Jan, b Adam Shih-Yuan Lee c and Chun-Cheng Lin b, * a Department of General Education, Taipei Nursing College, Taipei 112, Taiwan b Institute of Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan c Department of Chemistry, Tamkang University, Tamsui 251, Taiwan Received 6 August 2003; revised 5 September 2003; accepted 15 October 2003 Abstract—CBr 4 -photoirradiation protocol was found to be a mild, highly efficient and selective method for deprotection of iso- propylidene, benzylidene, triphenylmethyl and tert-butyldimethylsilyl protecting groups on sugar molecules. The conditions of this reaction can also be used to cleave peptides off from acid-labile resin linkers in solid-phase peptide synthesis. Ó 2003 Elsevier Ltd. All rights reserved. The success of the multi-step synthesis of complex nat- ural products depends on efficient protection–deprotec- tion of the several functional groups involved. 1 Although many methods have been reported for the selective deprotection of protected hydroxyl groups, a great need remains to explore simple, effective and selective ones for carbohydrate chemistry. Of the vari- ous protecting groups used for hydroxyl groups in car- bohydrate chemistry, isopropylidene, benzylidene, triphenylmethyl (trityl) and tert-butyldimethylsilyl groups are those most frequently used for protecting primary hydroxyl due to their availability for selective protection and orthogonal deprotection. 1 A catalytic amount of carbon tetrabromide (CBr 4 ) in methanol, at a reflux temperature, was demonstrated to successfully deprotect trityl, 2 p-methoxybenzyl (PMB), 3 b-(trimethylsilyl)ethoxymethyl, 4 methoxyethoxymethyl, 5 tetrahydropyranyl 6 and trialkylsilyl 7 ethers and gem- diacetates, 8 ketals 9 and acetals. 9 However, this method did not exhibit any chemoselectivity for deprotection of the most acid-labile protecting groups from other acid- sensitive groups. Recently, we reported a mild, highly efficient and selective deprotection of primary tert- butyldimethylsilyl (TBDMS) ethers in the presence of secondary silyl ethers using a catalytic amount of CBr 4 in methanol under photochemical reaction conditions. 10 Our longstanding interest in carbohydrate chemistry prompted us to investigate further the application of this methodology to the deprotection of other acid-labile protecting groups. Here we report the extension of this methodology to the deprotection of isopropylidene, benzelidene, trityl and TBDMS groups on sugar mole- cules. Moreover, this method is applicable to cleaving some types of acid-labile linkers in solid-phase peptide synthesis. 11 Although many reagents have been reported to be effective in the cleavage of isopropylidene groups, 1;8;9 lack of selectivity was encountered with most of the methods. Recently, a few of selective isopropylidene deprotection methods were reported. 12 Here, we first examined the selective deprotection of isopropylidene of furanose derivatives with various hydroxyl protecting groups at position C-3 using CBr 4 -photoirradiation method 10 (Table 1, entries 1–4). The selective removal of the isopropylidene group attached to the primary hydroxyl group was observed in the presence of acetyl, PMB, p-toluenesulfonyl and TBDMS, all of which remained intact during the reactions. Although the time required varied widely (24–48 h), uniformly high yields (81–89%) were obtained, indicating the efficiency of the method. Remarkably, the acetyl group migration reported under CBr 4 /MeOH reflux conditions 2 was not observed when the present protocol was applied (entry 1). Also, the PMB group, reported to be cleaved easily * Corresponding author. E-mail: cclin@chem.sinica.edu.tw 0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2003.10.205 Tetrahedron Letters 45 (2004) 635–639 Tetrahedron Letters