C2‐(1 N/2 N‐Methyl‐tetrazole)methyl Ether (MeTetMe) as a Stereodirecting Group for 1,2‐trans‐β‐O‐Glycosylation

Abstract

Development of stereoselective synthetic methods for O‐glycosides is of paramount importance in the field of glycochemistry. Therefore, we report herein (1 N/2 N)‐methylated tetrazole methyl (MeTetMe) ethers as a C2‐directing group for the formation of 1,2‐trans‐β‐O‐glycosides. The synthesis of the tetrazole moiety was readily achieved by a 3+2 cycloaddition reaction on nitrile functionality. The tethered thioglycoside donors were found to deliver the β‐O‐glycosides when activated by PIFA‐TfOH reagent system. The reactions were performed with six newly synthesized phenyl and ethyl thioglycosides to obtain the glycosylated adducts in moderate to high yields and excellent to exclusive β‐selectivity. The glycosylation method was easily scalable up to grams without affecting the yield and stereoselectivity. The MeTetMe group was efficiently removed under Birch reduction conditions without affecting the benzyl ethers or isopropylidene acetal protection.

Amino-Acid-Derived Amides as Stereodirecting Leaving Groups for Ferrier Rearrangement via Pd(0)-Catalyzed Tsuji–Trost Reactions

“…Conventional Pd(0) co-ordinating groups, ethyl carbonate and picoloyl ester, have thus been reported by Liu’s group as suitable LGs for Ferrier rearrangements of glucal substrates 1 (Figure a). With our continued interest in design and development of efficient synthetic methods in glycochemistry, including stereoselective glycosylations, we have recently reported the β-directing ability of o -cyanobenzoate ( o -CNBz) ester 2 (Figure b). The presence of a nitrile moiety on the Bz ester enabled metal co-ordination for the stereoselective rearrangement, which is in stark contrast to the unreactive nature of the parent benzoate group in the same reaction.…”