Copper(I)‐Catalyzed Asymmetric Hydrophosphination of 3,3‐Disubstituted Cyclopropenes

Abstract

Herein, a copper(I)‐catalyzed asymmetric hydrophosphination of 3,3‐disubstituted cyclopropenes is uncovered, which provides a series of phosphine derivatives in high to excellent diastereo‐ and enantioselectivities. The methodology enjoys broad substrate scopes on both 3,3‐disubstituted cyclopropenes and diarylphosphines. The high stereoselectivity is attributed to both the high stability of Cu(I)‐(R,R)‐QUINOXP* complex in the presence of stoichiometric HPPh2 and the produced phosphines and the high‐performance asymmetric induction of the Cu(I)‐(R,R)‐QUINOXP* complex. Finally, the method is used for the synthesis of new chiral phosphine‐olefin compounds built on a cyclopropane skeleton, one of which serves as a wonderful ligand in Rh‐catalyzed asymmetric conjugate addition of phenylboronic acid to various α,β‐unsaturated compounds.

Highly Diastereo- and Enantioselective Synthesis of Chiral Cyclohexylphosphines by Cu-Catalyzed Phosphination-Aldol Cyclization of Ketone-Enamides

“…Various chiral alkyldiaryl phosphines can be prepared efficiently (Scheme a). Ring-strained alkenes also showed high reactivity and selectivity toward diaryl phosphines to give the corresponding chiral phosphines bearing a 3-membered or a fused-ring driven by strain release (Scheme b) . Distinct from the above-reported methods for construction of cycloalkyl-substituted phosphines, herein, we disclose a diastereo- and enantioselective phosphination-aldol cyclization of ketone-enamides with secondary diarylphosphines enabled by copper catalysis, providing access to a range of chiral cyclohexylphosphines at ambient temperature (Scheme c).…”

“…We have made continuous efforts in hydrophosphination for the synthesis of phosphine products. ,, During the previous studies, we found that preparation of chiral cycloalkylphosphines by catalytic addition of HPAr 2 to cyclic electron-deficient alkenes is not effective in most cases, presumably due to the lack of efficient control of reactivity and enantioselectivity. However, this can be overcome by the introduction of ring strain to the cyclic alkene substrates . In the present study, we disclose a tandem conjugate phosphination-enolate trapping strategy as a complementary approach for the synthesis of chiral cycloalkylphosphines.…”

P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

“…Yin and co-workers have investigated the Cu(I)-catalyzed asymmetric hydrophosphination of 3,3-disubstituted cyclopropenes with diarylphosphines, revealing that QuinoxP* is the most effective among several commercially available chiral bisphosphine ligands, while Ph-BPE serves as a slightly inferior ligand to QuinoxP*. 659 Notable is that a variety of the addition products 207 could be synthesized by this protocol in high diastereo-and enantioselectivities (Scheme 223). The synthetic potential of this protocol has been demonstrated by the transformation of a product (R 1 = Ph, R 2 = HOCH 2 ; Ar = Ph) to new and useful chiral phosphine−alkene hybrid ligands with a cyclopropane backbone.…”

“…Yin and co-workers have investigated the Cu­(I)-catalyzed asymmetric hydrophosphination of 3,3-disubstituted cyclopropenes with diarylphosphines, revealing that QuinoxP* is the most effective among several commercially available chiral bisphosphine ligands, while Ph-BPE serves as a slightly inferior ligand to QuinoxP* . Notable is that a variety of the addition products 207 could be synthesized by this protocol in high diastereo- and enantioselectivities (Scheme ).…”

Cobalt- or rhodium-catalyzed synthesis of 1,2-dihydrophosphete oxides via C–H activation and formal phosphoryl migration

“… 1 The development of efficient methods for the synthesis of functionalized organophosphorus compounds has attracted continuous attention. 2 In particular, four-membered phosphorus compounds have found vast applications in the studies of catalysis, medicinal chemistry, and materials science ( Fig. 1 ).…”