From Oxygen to Sulfur and Back: Difluoro-H-phosphinothioates as a Turning Point in the Preparation of Difluorinated Phosphinates: Application to the Synthesis of Modified Dinucleotides

• Published in: Journal of organic chemistry Vol. 84; no. 9; pp. 5245 - 5260
• Main Authors: Zhang, Jun, Lambert, Emilie, Xu, Ze-Feng, Brioche, Julien, Remy, Pauline, Piettre, Serge R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.05.2019; Amer Chemical Soc
• Subjects: Chemical Sciences; Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; NUCLEOSIDE SYNTHESES; THIATION REAGENT; GENERAL-SYNTHESIS; ACID; PARA-METHOXYPHENYLTHIONOPHOSPHINE SULFIDE; N-GLYCOSIDES; PHOSPHONATE ANALOGS; EFFICIENT SYNTHESIS; ORGANOPHOSPHORUS COMPOUNDS; RADICAL-ADDITION REACTIONS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00232

A simple, two-step procedure to convert α,α-difluorinated H-phosphinic acids into the corresponding H-phosphinothioates is described. The usefulness of these species is demonstrated by their transformation into difluorinated phosphinothioyl radicals and their addition onto alkenes. Additionally, sequential treatment of H-phosphinothioates by a strong base and a primary alkyl iodide constitutes an alternate route to the formation of the C–P bond. Both methods efficiently deliver difluorinated phosphinothioates. Similar reactions carried out with the fully oxygenated counterparts clearly indicate the superiority of the sulfur-based species and emphasize the crucial role played by sulfur in the construction of the second C–P bond. Oxidation easily transforms the thereby obtained phosphinothioates into the corresponding phosphinates. The whole strategy is applied to the stereoselective preparation of dinucleotide analogues featuring either a difluorophosphinothioyl or a difluorophosphinyl unit linking the two furanosyl rings.