α-Tetrasubstituted aldehydes through electronic andstrain-controlled branch-selective stereoselectivehydroformylation

摘要

Hydroformylation utilizes dihydrogen, carbon monoxide, and a catalyst to transform alkenes into aldehydes. This work applies chiral bisdiazaphospholane (BDP) and bisphospholanoethane (BPE)-ligated rhodium complexes to the hydroformylation of a variety of alkenes to produce chiral tetrasubstituted aldehydes. 1,1’-Disubstituted acrylates bearing electron-withdrawing substituents undergo hydroformylation under mild conditions (1 mol% catalyst/BDP ligand, 150 psig gas, 60 °C) with high conversions and yields of tetrasubstituted aldehydes (e.g., 13:1 regioselectivity, 85% ee, and <1% hydrogenation for 1-fluoromethylacrylate). The scope also encompasses both acyclic 1,1’-disubstituted and trisubstituted, electron-poor alkenes, as well as di- and trisubstituted alkenes comprised of small rings with exocyclic and endocyclic unsaturation. For example, 1-methylene-β-lactam furnished the tetrasubstituted aldehyde with 98% selectivity and up to 83% ee. Notably, chiral trisubstituted bicyclic methyleneaziridines are transformed with >99% regioselectivity and >19:1 diastereoselectivity to tetrasubstituted aldehydes at rates >50 catalyst turnovers/hour. NMR studies of thenon-catalytic reaction of HRh(BDP)(CO)2 with methyl 1-fluoroacrylateenable interception of tertiary alkyl-rhodium intermediates, demonstratingmigratory insertion to acyl species is slower than formation of secondary andprimary alkyl-rhodium intermediates. Overall, these investigations reveal howthe interplay of sterics, electronics, and ring strain are harnessed to provideaccess to valuable α-tetrasubstituted aldehyde synthetic building blocksby promoting branched-selective hydroformylation.