An Approach to the Efficient Syntheses of Chiral Phosphino‐ Carboxylic Acid Esters

Abstract

Thec atalytic hydrophosphination reaction is one of the most sustainablec hemical transformations today.H ere,t he palladium-catalyzed asymmetric P À Ha ddition of diarylphosphines with N-enoylbenzotriazoles and analogues is described. Chiral phosphinep roductsa re obtained in 100%a tom economy and without cumbersome protection-deprotection manipulations.T he obtained productsc an be subsequently transformedt ob ear various functionalities,i ncluding phosphino-carboxylic esters which play critical roles in catalysisa nd as synthetic aids.A nti-tumour activities of the corresponding gold-phosphine complexes have been explored, contributing to existing chemotherapeuticr esearchi n cancer treatment.

Recent Advances in Metal-Catalyzed Asymmetric 1,4-Conjugate Addition (ACA) of Nonorganometallic Nucleophiles

“…Racemic secondary phosphines were also tolerated well, providing the corresponding tertiary phosphines with two chiral centers in high yields with reasonable enantiocontrol (up to 82% ee and 91:9 dr). Later, the application of this methodology was extended to the asymmetric hydrophosphination of dienones, yielding chiral bis-phosphines or tertiary P-heterocycles with excellent stereoselectivities (up to 99:1 dr and 99% ee; Scheme a). , Later studies showed that a range of α,β-unsaturated substituted alkenylisoxazoles, esters, and amides were suitable substrates for this reaction. − Most recently, the authors successfully developed a ( S )- 124a –Pd-promoted ACA of diphenylphosphine to ferrocenyl enones, which provided an efficient route to valuable chiral ferrocenyl phosphapalladacycle catalysts (Scheme b) . It is noteworthy that the substituent on the double bond of the ferrocenyl enones greatly affected the reactivity.…”

Copper(I)-Catalyzed Enantioselective 1,4-Conjugate Hydrophos­phination of α,β-Unsaturated Esters

“…The absolute configuration of 3ba was determined to be R by comparing its optical rotation value with reported data. 6g The stereochemistry in other products was tentatively assigned by structural analogy.…”

Recent Progress in Palladium-Catalyzed Asymmetric Hydrophos­phination

“…The prepared products could be further transformed into phosphine-carboxylic esters via a one-pot protocol with almost no loss in enantiomeric excess (Scheme 10). 24 One of the products prepared by this methodology was used to prepare a gold complex that showed tumor suppression potential.…”