Utilization of Sugars in Organic Synthesis. Part XXXIV. Thio-Sugars. IV. Synthesis of Carbohydrate 1,3-Glycol (Six-Membered) Thionocarbonates and Their Attempted O-S Rearrangement.

Abstract

In previous papers, [1][2][3] we showed that when five-membered cyclic thionocarbonates formed from 1,2-glycols were treated with a catalytic amount of appropriate radical generators, they underwent O-S rearrangement to give thiolcarbonates in acceptable yields. Although the regioselectivity of the reaction is not always high, the sterereochemistry of the product is exclusively cis. The method was successfully applied to the synthesis of thio-sugars carrying a thiol group at the secondary positions in carbohydrate molecules, while ionic reaction 4) of the same substrate gave no reaction. The present study was undertaken to determine whether a similar rearrangement occurs in six-membered analogues formed from 1,3-glycols. During synthesis of these substrates, interesting acyl migration reactions were observed. Results and DiscussionSynthesis of Six-membered Cyclic Thionocarbonates For the 1,3-glycols, three derivatives of 1,2-O-isopropylidene-a-D-glucofuranose (6-O-benzoate 2, 5) 6-O-tosylate 6, 5) and 6-deoxy compound 9 6)) and two derivatives of pryanosides [methyl 2,3-di-O-methyl-a-and -b-D-glucopyranosides (12a, b)] 7) were chosen. Thiocarbonylation of these glycols was carried out by one of the following methods: (1) stannylation with Bu 2 SnO, then treatment with thiophosgene (CSCl 2 ); or (2) direct treatment with thiocarbonyldiimidazole (Im 2 CS).When the 6-O-benzoate 2 was thiocarbonylated using method (1), the product was not the expected 3,5-O-thionocabonate 5, but 3-O-benzoyl-5,6-O-thionocarbonate 3 3) (67%), indicating that an acyl migration took place during the reaction. To determine which process (activation by stannylation or the reaction with thiophosgene) is responsible for this migration, 2 was treated with Bu 2 SnO. The product was the 3-O-benzoate 4 (92%), revealing that the benzoyl migration from O-6 to O-3 occurred during the stannylation process through D→E→F. This compound 4 was previously reported as an intermediate in the alkaline hydrolysis of 3-Obenzoyl-5,6-O-thionocarbonate 3 to the triol 1.8) Detailed comparison of the spectral data of 2 and 4 revealed that the previously reported intermediate was not the 3-O-benzoate 4, but instead was the 6-O-benzoate 2, indicating that acyl migration from O-3 to O-6 had taken place during alkaline hydrolysis (as G→H). Thiocarbonylation of 2 with Im 2 CS (method 2) gave the expected 3,5-O-thionocarbonate 5 in 75% yield.Thiocarbonylation of the 6-O-tosylate 6 using method (1) gave the 3,6-ether 7, 3,8) indicating that the activated 3-OH attacked the 6-position in an SN2 manner. Treatment of 6 with Im 2 CS gave a solid in 75% yield, which contained one imidazole group and m/z of 312. The 1 H-NMR data were compatible with the structure 8 (the probable mechanism is indicated in brackets [J→K]).Thiocarbonylation of the 6-deoxy derivative 9 using method (1) gave two products, 10 (57%) and 11 (36%), while Im 2 CS gave only 10 in 83% yield, which was the expected 3,5-O-thionocarbonate. Compound 11 lacked a thiocarbonyl group and had the MS peak at m/z 40...

The Construction of Anhydro Monosaccharides

“…Another way to trigger the intramolecular cyclization of tosylates without using any alkali was reported by Tsuda and co‐workers. According to their protocol, a toluene solution of 6‐tosylated hexofuranoside ( 69 ) and Bu 2 SnO was heated at reflux for 4 h to provide 3,6‐anhydro compound 71 with the yield of 100 % (Scheme , part A) . The 3,6‐etherification was believed to occur through a 2,3‐ O ‐dibutylstannylene ( 70 ) as the intermediate.…”