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. 2022 May 2;13(22):6567-6572.
doi: 10.1039/d2sc01563c. eCollection 2022 Jun 7.

Directed, nickel-catalyzed 1,2-alkylsulfenylation of alkenyl carbonyl compounds

Zi-Qi Li  1 , Wen-Ji He  1 , Hui-Qi Ni  1 , Keary M Engle  1
Affiliations

Directed, nickel-catalyzed 1,2-alkylsulfenylation of alkenyl carbonyl compounds

Zi-Qi Li et al. Chem Sci. .

Abstract

We report a regioselective, nickel-catalyzed syn-1,2-carbosulfenylation of non-conjugated alkenyl carbonyl compounds with alkyl/arylzinc nucleophiles and tailored N-S electrophiles. This method allows the simultaneous installation of a variety of C(sp3) and S(Ar) (or Se(Ar)) groups onto unactivated alkenes, which complements previously developed 1,2-carbosulfenylation methodology in which only C(sp2) nucleophiles are compatible. A bidentate directing auxiliary controls regioselectivity, promotes high syn-stereoselectivity with a variety of E- and Z-internal alkenes, and enables the use of an array of electrophilic sulfenyl (and seleno) electrophiles. Among compatible electrophiles, those with N-alkyl-benzamide leaving groups were found to be especially effective, as determined through comprehensive structure-reactivity mapping.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Background and synopsis of current work.
Scheme 2
Scheme 2. Optimization of sulfur electrophilea. aReaction conditions: Ni(COD)(DMFU)/1/Et2Zn/[N–S] = 0.01/0.1/0.15/0.18 (mmol). Batchwise addition: (1) [N–S]/Et2Zn = 0.12/0.1 (mmol), 30 min; (2) then [N–S]/Et2Zn = 0.12/0.1 (mmol), 20 h. Reaction was run in THF (0.1 M) at 60 °C. All percentages represent 1H NMR yields with CH2Br2 as internal standard. DMFU = dimethyl fumarate. bResult in parentheses obtained with Ni(COD)2 (10 mol%) as pre-catalyst and DMFU (20 mol%) as ligand.
Scheme 3
Scheme 3. Large-scale experiment and deprotection of directing auxiliarya. aLarge-scale reaction performed with: Ni(COD)2/DMFU/1/Et2Zn/[N–S] = 0.25/0.5/2.5/3.75/4.5 (mmol). Batchwise addition: (1) [N–S]/[Et2Zn] = 3.0/2.5 (mmol), 30 min; then (2) [N–S]/[Et2Zn] = 1.5/1.25 (mmol), 20 h. Deprotection of directing group experiment performed with 2a (0.1 mmol). Percentages represent isolated yields.
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