Synthesis of Sulfoximine Carbamates by Rhodium-Catalyzed Nitrene Transfer of Carbamates to Sulfoxides

Abstract

Sulfoximines are of considerable interest for incorporation into medicinal compounds. A convenient synthesis of N-protected sulfoximines is achieved, under mild conditions, by rhodium-catalyzed transfer of carbamates to sulfoxides. The first examples of 4-membered thietane-oximines are prepared. Sulfoximines bearing Boc and Cbz groups are stable to further cross coupling reactions, and readily deprotected. This method may facilitate the preparation of NH-sulfoximines providing improved (global) deprotection strategies, which is illustrated in the synthesis of methionine sulfoxide (MSO).

Novel Pieces for the Emerging Picture of Sulfoximines in Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues of Marketed Drugs and Advanced Clinical Candidates

“…Sulfide oxidation to the corresponding sulfoxide 17 was carried out in good yield with aqueous H 2 O 2 , without sulfone formation. Direct rhodium‐catalyzed imination of 17 with tert ‐butyl carbamate following the procedure described by Luisi, Bull, and co‐workers gave the Boc‐protected sulfoximine 18 in 83 % yield. Reduction of the nitro group by hydrogenolysis proceeded cleanly to provide the aminopyridine 19 in 68 % yield.…”

Transfer of Electrophilic NH Using Convenient Sources of Ammonia: Direct Synthesis of NH Sulfoximines from Sulfoxides

“…Sulfoximines are most often prepared by the transfer of a protected nitrogen group to sulfoxides,16 including the transfer of sulfonamide,17, 18, 19 trifluoroacetamide,17 carbamate,20 and amide groups21 using transition‐metal catalysis (Scheme 1 a). These sulfoximines have been deprotected to yield the free NH derivatives, and further functionalized to generate N‐aryl, N‐acyl, and N‐alkyl, as well as cyclic derivatives, offering varying properties 22.…”

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ6‐sulfanenitrile Intermediate

“…To further confirm this, 18 OH 2 was added to the reaction (with acetic acid), and mass spectrometry of the obtained sulfonimidamide product indicated incorporation of 18 Oi nt he product in aroughly 1:2ratio to the 16 Oisotope (Scheme 5b). Using iPrOH as the reaction solvent gave a74:26 ratio of 5b/2a on evaporation of the reaction mixture as determined by 1 HNMR analysis.The same result was obtained with an aqueous work-up indicating the stability of 5b to water.…”

“…[14] The NH transfer occurred with sources of ammonia, with ammonium carbamate preferred, in the presence of bis-(acetoxy)iodobenzene as the oxidant. [16][17][18] Herein, we report the development of an ew strategy for the direct synthesis of NH-sulfonimidamides from sulfenamides as simple,r eadily available,a nd previously unexplored substrates.Ahighly selective one-pot NH and O transfer is achieved using operationally simple conditions. [15] We,a nd others, recently reported related conditions for the conversion of sulfides into sulfoximines in ao ne-pot process through ahighly chemoselective NH and Ot ransfer.…”