Metal‐to‐Ligand Ratio‐Dependent Chemodivergent Asymmetric Synthesis

Abstract

Chemodivergent asymmetric synthesis was achieved by tuning the metal-to-ligand ratio in an organometallic catalytic system. Using N-(aroyloxy)phthalimide as the precursor of either an oxygen-centered aroyloxy radical or an itrogen-centered phthalimidyl radical, enantioselective oxocyanation or aminocyanation of alkenes was achieved separately through ad ual photoredoxa nd copper catalysis. The metal-to-ligand ratio can exert chemoselective control while retaining the high enantiopurity of divergent products. Both reactions proceed efficiently with catalyst loading as low as 0.2 mol %a nd can be performed on ag ram scale without loss of chemoselectivity or enantioselectivity.C hemodivergent asymmetric 1,5-aminocyanation or 1,5-oxocyanation of vinylcyclopropane can also be realized by this protocol. Mechanistic investigations involving electron paramagnetic resonance (EPR) experiments were performed to shed light on the stereochemical and chemodivergent results.Scheme 1. Metal-to-ligand ratio-dependent chemodivergent asymmetric synthesis (this work).

Switchable Divergent Synthesis Using Photocatalysis

“…Lu reported the chemodivergent asymmetric difunctionalization of alkenes using photoredox and copper catalysts (Scheme ). Their reaction was switched depending on the ratio of the copper catalyst and chiral bisoxazoline ligand. In this case, 1,2-aminocyanation selectively occurs during the reaction performed with a copper-to-ligand ratio of 1:7.5 to give product 21 - 4 from NHP ester 21 - 1 , styrene ( 21 - 2 ), and trimethylsilyl cyanide ( 21 - 3 ).…”

Metal‐to‐Ligand Ratio‐Dependent Chemodivergent Asymmetric Synthesis

“…Thea bsolute configurations of typical products were confirmed by X-ray crystallographic analysis. [28] Several experiments were performed in an effort to further understand the reaction mechanism (Scheme 4a nd Figures S1,S2 in the SI). Quenching experiments were performed and are shown in Figure S1.…”

Hydroesterification and Difunctionalization of Olefins with N-Hydroxyphthalimide Esters

“…22−24 Finally, the modest regioselectivity observed with terminal olefins contrasts with the high selectivity observed in reported additions of Ocentered radicals to olefins. 13,25 Alternatively, olefin could react directly with triplet 1a* to yield the phthalimide radical and the alkyl radical 30. In this scenario, relaxation of 1a* in the presence of less-reactive substrates could explain why we recover 1a.…”

“…Third, we have observed no evidence of allylic C–H abstraction or oxidation other than a single example (product 17 ). By contrast, Li and co-workers showed allylic C–H oxidation of cyclohexene with benzoyloxy radicals. , Fourth, we observed no evidence of decarboxylation, which has also been reported for benzoyloxy radicals. − Finally, the modest regioselectivity observed with terminal olefins contrasts with the high selectivity observed in reported additions of O-centered radicals to olefins. , Alternatively, olefin could react directly with triplet 1a* to yield the phthalimide radical and the alkyl radical 30 . In this scenario, relaxation of 1a* in the presence of less-reactive substrates could explain why we recover 1a .…”