**1. Introduction**

The chemical synthesis of complex carbohydrates is an important research topic in carbohydrate chemistry due to their crucial roles in biological processes [1–5]. Thioglycoside donors are widely used in these syntheses due to their advantages, such as easy preparation, stable chemical properties, and various activation methods [6–12]. Generally, each glycosylation reaction between the donor and acceptor may produce a product in the α or β configuration, which will lead to adverse effects, such as reduced yield and difficult purification. Therefore, many studies have been devoted to solving the problem of stereoselectivity in glycosylation. Among them, the use of neighboring group participation (NGP) from 2-positions of glycoside donors to control stereoselectivity is a very effective method. The acyl group at 2-position is the most commonly used "NGP" group, which leads to the 1,2-*trans*-configuration of the products in glycosylation [13–17]. However, the "disarmed" effect of acyl groups often leads to low reactivity of glycosyl donors in glycosylation. Therefore, several methods using NGP from 2-ether groups of thioglycoside donors to control stereoselectivity have been developed recently, and phenyl-3,4,6-tri-*O*benzyl-1-thio-β-D-glucopyranoside **1** is often the precursor required for the synthesis of these donors (Figure 1) [18–22].

Although excellent stereoselectivity and high reactivity were shown in these methods, the synthesis of **1** is a challenge, which reduces the practicality of these methods. For example, the traditional "orthoester method" requires multiple-step protection and deprotection, leading to low synthesis efficiency (Figure 2a) [23–25]. More efficient methods involved the formation of 1,2-anhydro sugars by oxidation of glycals with oxone in acetone and the installation of the 1-thiophenyl group through ring-opening reactions of these 1,2-anhydro sugars. For example, the oxidation of glucal **2** by oxone yielded 1,2-anhydro glucose **3** (crude crystalline product): (a) the ring opening of **3** led to 43% (the use of TBASPh) [26] or 47% (the use of NaSPh) [27] yield of **1** in the presence of phenylthiolate at room temperature for overnight, and (b) the ring opening of **3** led to 37–55% yield [19,20] of **1** in the presence of PhSH and ZnCl2 at room temperature for overnight (Figure 2b). In this study, an improved method for the efficient synthesis of 2-OH, 1-thioaryl glycosides was developed, in which the ring opening reaction of 1,2-anhydro sugars occurred in the

**Citation:** Guo, Y.-F.; Luo, T.; Feng, G.-J.; Liu, C.-Y.; Dong, H. Efficient Synthesis of 2-OH Thioglycosides from Glycals Based on the Reduction of Aryl Disulfides by NaBH4. *Molecules* **2022**, *27*, 5980. https:// doi.org/10.3390/molecules27185980

Academic Editors: Mircea Darabantu, Alison Rinderspacher and Gloria Proni

Received: 28 August 2022 Accepted: 9 September 2022 Published: 14 September 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

presence of NaBH4 and alkyl disulfides at room temperature. As a result, 73% yield of **1** could be efficiently prepared from **2** (two-step reaction was completed within 90 min) under very mild conditions (Figure 2c). Furthermore, the glycosyl donors having both "armed" and "NGP" effects can be efficiently synthesized in a one-pot reaction based on this method.

**Figure 1.** Using NGP from 2-ether groups to control stereoselectivity.

**Figure 2.** Comparison of this method with previous methods.
