Highly Chemoselective NH- and O-Transfer to Thiols Using Hypervalent Iodine Reagents: Synthesis of Sulfonimidates and Sulfonamides.

Arianna Tota,Renzo Luisi,Gala Ogalla Estévez,Leonardo Degennaro,Edward L. Briggs,Michelle Afonso,James A. Bull,Sahra St John-Campbell

doi:10.1021/acs.orglett.8b00788

Arianna Tota, Renzo Luisi + Show 6 more

Open Access

https://doi.org/10.1021/acs.orglett.8b00788

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Abstract

Aryl thiols can be selectively converted to sulfonimidates or sulfonamides with three new S-X connections being made selectively in one pot. Using hypervalent iodine reagents in the presence of ammonium carbamate, NH- and O-groups are transferred under mild and practical conditions. Reducing the loading of ammonium carbamate changed the product distribution, converting the sulfonimidate to the sulfonamide. Studies into the possible intermediate species are presented, suggesting that multiple pathways may be possible via sulfinate esters, or related intermediates, with each species forming the same products.

Highlights

F unctional groups that contain S−O and S−N linkages comprise some of the most useful motifs used in medicinal chemistry.[1]
Sulfoximines have emerged as valuable groups for medicinal chemistry as chiral alternatives to sulfones[2] and have progressed into clinical trials in several compounds.[3]
We report the selective formation of sulfonimidates through a highly chemoselective NH, O, and OR transfer to aryl thiols using hypervalent iodine reagents

Summary

Introduction

F unctional groups that contain S−O and S−N linkages comprise some of the most useful motifs used in medicinal chemistry.[1]. We report the selective formation of sulfonimidates through a highly chemoselective NH, O, and OR transfer to aryl thiols using hypervalent iodine reagents. Reboul reported related mechanistic and synthetic work at a similar time, which indicated that the O atom derived from methanol or acetate.[13] Adopting these ammonium carbamate and bisacetoxyiodobenzene conditions, Stockman and Lücking reported NH transfer to sulfinamides to form sulfonimidamides with chemoselective NH transfer.[16] Previously, the oxidation of sulfinamides to methyl sulfonimidates was demonstrated by Malacria using iodosobenzene in methanol to promote oxidation.[17]

Results

Conclusion