Thiophenol-Catalyzed Radical Hydroformylation of Unactivated Sterically Hindered Alkenes

Sterically congested alkenes─ubiquitous in pharmaceuticals and industrial intermediates─remain inaccessible to classical hydroformylation due to prohibitive steric strain in transition-metal catalysis. Here, we report a thiophenol-catalyzed radical hydroformylation that overcomes dual steric and electronic constraints through a synergistic system: bench-stable α-chloro <i>N</i>-methoxyphthalimides (formyl precursors) and a tailored thiophenol HAT catalyst. This metal-free strategy achieves unprecedented hydroformylation of unactivated, tri-, and tetrasubstituted alkenes─including electron-rich styrenes and aliphatic alkene systems─with high chemo- and regioselectivity. Key advances include: 1) the first hydroformylation of tetrasubstituted styrenes, delivering β-aryl aldehydes with quaternary centers (up to 74% yield); 2) thiophenol lowers the HAT barrier by 8.3 kcal/mol to enable catalytic turnover under steric congestion. Mechanistic studies confirm a formyl radical pathway, while syngas (CO/H₂) elimination establishes a safe, sustainable platform for synthesizing medicinally relevant motifs (e.g., oxime ethers) and industrial targets like Lilial derivatives.