Superbase-Mediated gem-Difluoroalkenylations of Sulfoximines

Abstract

At ambient temperature, deprotonated sulfoximines react with 1-trifluoromethylalkenes to provide either N-or C-gemdifluoroalkenylated products. The reaction site depends upon the N substituent of the starting material. The optimal conditions involve the use of a superbasic system NaOH in dimethyl sulfoxide. The reactions are characterized by a broad substrate scope and medium to high yields. Scale-up experiments of both the N-and C-gem-difluoroalkenylations proceeded well. Treatment of a Ndifluoroallyl sulfoximine with an aryl thiol under dioxygen afforded the corresponding oxygenated addition product.

A One-Pot Domino Reaction Providing Fluorinated 5,6-Dihydro-1,2-thiazine 1-Oxides from Sulfoximines and 1-Trifluoromethylstyrenes

“…In THF, 95% of hydrolysis product 3 was detected (Table , entry 6). As assumed from our previous results, sulfoximines with N groups other than TFA behaved very differently, and with the combination of 2 equiv of NaH in DMSO, only the corresponding C - gem -difluoroalkenylated products 5 were detected (Table , entries 7–10). In each case, the N–X fragment remained intact, and the yields varied between 38% for 5ba with an N -acetyl group and 65% for N -tosyl 5da .…”

“…For the initial investigation of the process, N- TFA S -isopropyl S -phenyl sulfoximine ( 1a ) was selected a sulfur component. Reacting it with 1-trifluoromethylstyrene ( 2a ) under the previously optimized conditions with NaOH as the base in DMSO gave 5,6-dihydro-1,2-thiazine 1-oxide 7aa in 38% yield [as determined by 1 H NMR spectroscopy with mesitylene as the internal standard (Table , entry 1)]. In addition, N - gem -difluoroalkenylated product 4 was formed, suggesting that a hydrolytic cleavage of the TFA group had occurred and that in a subsequent step the free NH (or its anionic form) had reacted with 2a following an S N 2′ pathway.…”

“…In previous work, we observed site-selective couplings of sulfoximines with 1-trifluoromethylstyrenes to yield either N-or C-gem-difluoroalkenylated products depending on the N substituent of the starting material. 9 With simple NH derivatives, N-difluoroalkenylations occurred, whereas Nprotected compounds gave (double) C-functionalized products (Scheme 1, top). While screening more substrate combinations, we observed an unusual behavior of sulfoximines with Ntrifluoroacetyl (N-TFA) substituents.…”

Visible-light-mediated C–F bond cleavage for the synthesis of polyfluorinated compounds

“…3 In recent years, a new strategy for the synthesis of different gem -difluoroolefins has been successfully established by using the β-F elimination of α-trifluoromethyl alkenes (Scheme 1a). 4–9 Under the conditions of transition-metal catalysis ( e.g. Ni, Fe, Cu, etc .…”

Synthesis of o-Sulfinylanilines from N-Alkyl Sulfoximines and Arynes

“…N -Alkyl sulfoximines can be prepared by various routes. , Due to their relevance in drug development, we decided to focus our initial attention on the use of N -methyl derivatives . In general, such compounds are stable, and only a few degradation pathways by S–C and SN cleavage reactions are known. , …”