C(sp²)–C(sp³) Cross-Coupling Enabled by Alkyl Radical Capture at Isolable, Low-Spin (<i>S</i> = 1/2) Cobalt(II)–Monoaryl Catalysts

A cobalt(II) catalyst supported by the ligand 2-(diphenylphosphino)phenol (P,O) was developed for the C(sp2)–C(sp3) Negishi arylation of alkyl(pyridyl)sulfones, which are bench-stable, nonorganohalide C(sp3)–S electrophiles. Employing the catalyst generated in situ from 5 mol % P,O ligand and 5 mol % cobalt(II) bromide, a variety of (hetero)aryl C(sp2)–C(sp3) products were synthesized derived from primary and secondary alkyl sulfones, including difluoromethylation using 2-((difluoromethyl)sulfonyl)pyridine, and cross-coupling of sulfone derived from the thiol-containing ACE inhibitor captopril. Freeze-quench X-band EPR spectroscopy of a catalytic reaction established the catalyst resting state as low-spin (S = 1/2), square-pyramidal (P,O)cobalt(II)–aryl, a rare example of a cobalt(II)–aryl complex detected during a cross-coupling reaction. These data informed the cobalt(II/III/I/0) catalytic cycle involving alkyl radical capture at the (P,O)cobalt(II)–aryl catalyst resting state, enabling selective formation of the C(sp2)–C(sp3) product.本研究开发了一种由配体2-二苯基膦苯酚（2-(diphenylphosphino)phenol，P,O配体）负载的二价钴催化剂（cobalt(II) catalyst），用于烷基（吡啶基）砜的C(sp²)–C(sp³)根岸芳基化反应（Negishi arylation）。烷基（吡啶基）砜属于易于保存、稳定性良好的非有机卤化物类C(sp³)-S亲电试剂。采用由5摩尔百分比P,O配体与5摩尔百分比溴化二价钴原位生成的该催化剂，可由一级、二级烷基砜合成多种（杂）芳基C(sp²)–C(sp³)偶联产物，其中包括利用2-((二氟甲基)磺酰基)吡啶实现的二氟甲基化反应，以及含巯基的血管紧张素转换酶（ACE）抑制剂卡托普利衍生的砜的交叉偶联反应。通过对催化反应进行冷冻猝灭X波段电子顺磁共振波谱（Freeze-quench X-band EPR spectroscopy）表征，确定该催化剂的驻留态为低自旋（自旋量子数S=1/2）、四方锥构型的(P,O)二价钴-芳基配合物，这是交叉偶联反应中检测到的罕见二价钴-芳基配合物实例。上述实验数据佐证了涉及(P,O)二价钴-芳基催化剂驻留态处烷基自由基捕获的二价钴/三价钴/一价钴/零价钴催化循环，该循环可选择性生成C(sp²)–C(sp³)偶联产物。