A mild and efficient method for the selective cleavage of primary p-methoxybenzyl protecting group of saccharides by Co 2 (CO) 8 –Me 2 PhSiH–CO system Peng-zhan Qian a , Wang Yao a , Lu-bai Huang a , Xiang-bao Meng a,b , Zhong-jun Li a,b,⇑ a The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, PR China article info Article history: Received 18 June 2015 Revised 12 July 2015 Accepted 16 July 2015 Available online 21 July 2015 Keywords: Co 2 (CO) 8 Cleavage p-Methoxybenzyl Regioselectivity abstract A mild and efficient method to selectively cleave p-methoxybenzyl (PMB) ether with a catalytic amount of Co 2 (CO) 8 , hydrosilane and CO (1 atm) is presented. The cleavage reaction shows regioselectivity to primary O-PMB of a variety of permethoxybenzylated saccharides and chemoselectivity to O-Bn, sulfur-containing group and common ester protecting groups. Ó 2015 Elsevier Ltd. All rights reserved. p-Methoxybenzyl (PMB) group is frequently used in organic synthesis for the protection of hydroxyl groups, especially in the synthesis of oligosaccharides. 1 Various methods have been devel- oped to cleave PMB ether. 2,3 Recent advances include selective cat- alytic hydrogenolysis, 4 oxidative cleavage, 5 and the use of new Lewis acids such as AgSbF 6 and POCl 3 . 3,6,7 Some other studies also focus on transforming PMB to other functional groups directly. 8 However, few protecting groups are stable under Lewis acid or oxidative conditions, especially in carbohydrate manipulations, and groups like thiol can greatly inhibit the reaction process during Pd catalyzed reaction. Therefore, it is necessary to explore milder conditions. Previous work in our laboratory has identified Co 2 (CO) 8 –hydrosilane–CO system as an effective method for the selective cleavage of benzyl ether. 9,10 Various substrates have been tested to show its broad applications and high functional groups tolerance. 10 Since PMB ether is similar to benzyl ether, we presume this mild method is also applicable for the selective cleavage of PMB ether. Based on these considerations, a model reaction was established using 1a as the substrate to investigate the reaction conditions (Table 1). Hydrosilane is proposed to react with Co 2 (CO) 8 first to form an active catalytic species Co(CO) 4 SiR 3 in situ. 9–12 The reactivity of hydrosilane determines the reaction rate of the cleavage process. Therefore, five hydrosilanes were firstly screened in the presence of 2.0 equiv of Co 2 (CO) 8 in benzene under balloon pressure of CO at 50 °C(Table 1, entries 1–6). As shown in Table 1, Me 2 PhSiH afforded the desired primary alcohol 1b in a higher yield than Et 3 SiH, EtMe 2 SiH, EtOMe 2 SiH, and (EtO) 2 MeSiH after the acid–labile silyl ether was hydrolyzed with a mixture of AcOH/H 2 O/THF 13 at RT (entries 1–6). 14,15 In order to probe the potential similarity of mechanism between the de-OPMB and de-OBn process which we reported previously, 9,10 triethylsilyl ether intermediate 1c (Table 1, entry 1) which is stable to silica gel chromatography (see SI). Solvents, temperature, and equivalents of Co 2 (CO) 8 were then screened. 16 Optimal result was achieved using 0.5 equiv of Co 2 (CO) 8 and 20 equiv of Me 2 PhSiH in refluxing CH 2 Cl 2 (entry 11), which yielded the de-6-O-PMB product (1b) in 86%. Lowering the temperature or reducing the equivalent of Me 2 PhSiH can decrease the yield of 1b, while a large amount of 1a was not consumed after stirring for 48 h (entries 12 and 14). It was reported that O-Bn group can be readily cleaved under the Co 2 (CO) 8 –HSiMe 2 Ph–CO system (Co 2 (CO) 8 : 0.1–0.2 equiv, HSiMe 2 Ph: 6–20 equiv), 10 which utilized less amount of Co 2 (CO) 8 compared with the optimized condition given in Table 1 (entry 11). Thus, the tolerance of secondary O-benzyl group in the pres- ence of primary O-PMB ether (compound 2a) under the optimized reaction condition was investigated. As shown in Table 2, when 2a http://dx.doi.org/10.1016/j.tetlet.2015.07.051 0040-4039/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: zjli@bjmu.edu.cn (Z.-j. Li). Tetrahedron Letters 56 (2015) 5238–5241 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet