Synthesis of Sulfoximine Propargyl Carbamates under Improved Conditions for Rhodium Catalyzed Carbamate Transfer to Sulfoxides

Abstract

Sulfoximines provide aza-analogues of sulfones, with potentially improved properties for medicinal chemistry. The sulfoximine nitrogen also provides an additional vector for the inclusion of other functionality. Here, we report improved conditions for rhodium catalyzed synthesis of sulfoximine (and sulfilimine) carbamates, especially for previously low-yielding carbamates containing π-functionality. Notably we report the preparation of propargyl sulfoximine carbamates to provide an alkyne as a potential click handle. Using Rh 2 (esp) 2 as catalyst and a DOE optimization approach provided considerably increased yields.

Overlooked aza-S(iv) motifs: synthesis and transformations of sulfinamidines and sulfinimidate esters

“…as the base, with a catalyst loading of 2.0 mol%, furnishing the product in 38% yield. 27 In a recent work, Lu and colleagues reported the efficient imination of N-acylsulfenamides 10 using PhI(OAc) 2 to obtain N-acyl sulfinamidines 11 (Scheme 8). 28 The optimized protocol employed an excess of oxidant (PhI(OAc) 2 , 1.5 equiv.…”

Synthesis of Sulfoximines and Sulfonimidamides Using Hypervalent Iodine Mediated NH Transfer

“…Notably, Bolm developed numerous methods for the preparation of sulfoximines using transition metal catalysis with iminoiodinane reagents, using Rh catalysis for the transfer of trifluoroacetamide [ 40 ], and silver- [ 41 ] and iron-catalysed processes to prepare different N-protected derivatives [ 42 , 43 ]. We contributed to this area through the development of the Rh-catalysed synthesis of sulfoximine carbamates [ 44 , 45 ]. Bolm also demonstrated metal free processes for sulfoximine synthesis from sulfoximines using hypervalent iodine reagents [ 46 , 47 ].…”

Synthesis of Pyrazolesulfoximines Using α-Diazosulfoximines with Alkynes

“…With the emergence of sulfoximines in drug discovery, their synthesis has seen notable advances. 3 Developed strategies include N-transfer to sulfoxides, 10 N,O transfer to sulfides, 11 and several approaches to C–S bond formation, involving nucleophilic 12 and electrophilic sulfur reagents. 13 Despite this, there remain relatively few sulfoximine containing reagents whereby a preformed sulfoximine motif can be installed in a strategic step.…”