Impressive progress has been made in the construction of O-glycosides from 1-thioglycosides [1], and methods have been developed for the preparation of 1-thioglycosides (5-8) from acetylated glycosyl halides (1) (Scheme 1) [2-3], acetylated glycosides (2) [4][5][6][7], and methyl glycosides (3) [8]. However, because of neighboringgroup participation, the resultant thioglycosides (5-6) are usually of the 1,2-trans-configuration, whether derived from the reaction of an anomeric-stabilized a-bromide (1) with thiols [3] or from the Lewis acid-catalyzed coupling of peracylated sugars (2) with thiols [4]. These reactions occasionally provide both anomeric thioglycosides under conditions of strong acid-catalysis [5] 1 or high temperature [6], but yields are variable. For the conversion of methyl glycosides (3) into the corresponding thioglycosides (7-8), Hanessian's procedures or modifications are very suitable [8].
We envisioned that the use of protected sugar lactols 4 [9] would allow the conversion of either acetyl-or alkyl-protected glycopyranoses (4), into a variety of thioglycosides (5-8) under a single set of conditions. The reaction of such pyranose derivatives (4) with diaryl disulfides in the presence of trialkylphosphine yields the corresponding aryl thioglycosides [7b,10]. However, we found that alkyl thioglycosides could not be obtained by this method using either tributylphosphine or triphenylphosphine. Assuming that the likely mechanism of this reaction involves a rate-limiting attack of trialkylphosphine on disulfide, we reasoned that Lewis acids could provide effective catalysis for this attack. In fact, the addition of boron trifluoride etherate 2 to * Corresponding authors. 1 Reaction of glycosides and thiols in the presence of a strong acid is generally an unsatisfactory procedure for the synthesis of 1-thioglycosides due to facile formation of dithioacetals, see ref. [2].
2 The use of n-butylthiol to react directly with galactopyranose 4c by the boron trifluoride etherate-catalyzed procedure [4b] gives thioglycoside 8(I (57%) and the corresponding thioacetal (19%) as well.