Highly Stereoselective Nucleophilic Addition of Difluoromethyl‐2‐pyridyl Sulfone to Sugar Lactones and Efficient Synthesis of Fluorinated 2‐Ketoses

Abstract

Nucleophilic addition of difluoromethyl‐2‐pyridyl sulfone to sugar lactones proceeded with good yield and excellent stereoselectivity. The hitherto unknown direct addition intermediates are stable and capable of useful conversions: Formal elimination of the anomeric hydroxy and sulfonyl groups yielded a 1‐deoxy‐1‐difluoromethylene mannopyranose derivative. Directly from sugar lactones, by nucleophilic addition and subsequent one‐pot reduction with allylmagnesium chloride, unprecedented fluorinated 2‐ketose analogues were prepared efficiently.

Progress of Difluoromethyl Heteroaryl Sulfones as Difluoroalkylation Reagents

“…Gueyrard and Shen group [17,18] reported the gemdifluoroolefination of benzylated sugar-derived lactones by a modified Julia olefination with difluoromethyl-2-pyridyl sulfone separately (Schemes 9, 10). The reaction was shown to proceed efficiently in both pyranose (D-gluco, D-galacto, D-manno, 2-deoxy-D-gluco) and furanose (D-arabino) sugar series.…”

“…The reaction was shown to proceed efficiently in both pyranose (D-gluco, D-galacto, D-manno, 2-deoxy-D-gluco) and furanose (D-arabino) sugar series. Meanwhile, Shen group [18] carried out a one-pot reduction with Grignard reagent of sugar lactones for the preparation of fluorinated 2-ketoses (Scheme 11). Later in 2018, Silverman and his coworker [19] optimized the synthesis of (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-en-1-carboxylic acid (OV329), a potent inactivator of GABA aminotransferase (GABA-AT) via Julia-Kocienski reaction (Scheme 12).…”

Stereoselective and Regioselective Preparation of C‐Pentopyranosides and Formal Synthesis of Omarigliptin

“…Later, from non‐carbohydrate starting materials, a multistep synthesis including a key Ru‐catalyzed dynamic kinetic resolution reaction was developed for the manufacture of 7 ,. [8a] In the search for robust routes to C ‐pentopyranosides with lower costs, we considered lactone 8 as a promising starting point. According to Fleet et al, compound 8 was prepared efficiently (ca.…”

Difluoromethyl 2-pyridyl sulfone: a versatile carbonyl gem-difluoroolefination reagent

“…5,6 This reagent has also found broad applications in related synthetic methodologies. [7][8][9][10][11][12][13] In this tutorial account, we aim to provide a detailed introduction on the preparation and application of 2-PySO 2 CF 2 H as a gemdifluoroolefination reagent, which we hope could serve as a useful guideline for potential users. carbanion, and then the resulting adduct rearranges spontaneously to afford a sulfinate salt, which fragmentizes to give the alkene product.…”

“…Recently, the nucleophilic addition product of 2-PySO 2 CF 2 H and sugar lactone was also successfully converted to gem-difluoroolefin under reflux in the TBME solution of NaHCO 3 . 13 It should be noted that we also attempted the gem-difluoroolefination of the carbonyl groups in carboxylic esters and amides with 2-PySO 2 CF 2 H reagent, but were not successful.…”