Phosphorus compounds bearing chirality on the P-center are usually qualified as P-chirogenic or P-stereogenic. This chemical class concerns natural products, agrochemistry, molecular materials, biology and pharmacy, although it is certainly in coordination chemistry and in asymmetric catalysis using chiral transition metal complexes that P-chirogenic phosphorus compounds are the most used. The chiral phosphine ligands and their uses in asymmetric metal-catalyzed reactions have been widely reviewed in literature. However, an overview covering the applications as well as the stereoselective syntheses of all classes of phosphorus compounds has not yet been provided. This review reports the best stereoselective or asymmetric syntheses, the most efficient P*-building blocks and functionalisation of P-chirogenic compounds, in the light of chiral phosphorus compound applications. It is an extensive and useful documentation from pioneering work to recent advances in phosphorus stereochemistry.

Applications and stereoselective syntheses of P-chirogenic phosphorus compounds

Introducing Chirality at Phosphorus Atoms: An Update on the Recent Synthetic Strategies for the Preparation of Optically Pure P‐Stereogenic Molecules

Easily prepared menthyl phosphinates of high diastereoisomeric purity provide versatile intermediates for the synthesis of P-stereogenic compounds. Previous efforts starting about fifty years ago have been hampered by a lack of generality so the menthyl route has been nearly abandoned. Herein we provide a general solution to this long-standing problem and describe a general synthesis of menthyl H-phosphinate and disubstituted phosphinate esters. The method to prepare these versatile precursors relies on a simple and inexpensive process avoiding the use of phosphorus trichloride, Grignard reagents, and complicated cryogenic crystallizations. Established protocols can then be employed to synthesize P-stereogenic secondary and tertiary phosphine oxides and therefore P-stereogenic phosphine ligands.

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General synthesis of P-stereogenic compounds: the menthyl phosphinate approach

Functionalized P,C-stereogenic tertiary phosphine oxides were prepared by the addition of (RP)-menthyl phenylphosphine oxide to activated olefins, in high drP and drC, and were isolated in excellent yields. The reaction was readily catalyzed by Ca(OH)2 or occurred with gentle heating. A wide range of substrates, including vinyl ketones, esters, nitriles, and nitro alkenes, can be used in the reaction.

Preparation of Optically Pure Tertiary Phosphine Oxides via the Addition of P-Stereogenic Secondary Phosphine Oxide to Activated Alkenes.

Diastereoselective Hydrolysis of Asymmetric P–Cl Species and Synthesis of Optically Pure (RP)‐(–)‐Menthyl H‐Phenylphosphinate

Recent advances in acyl radical enabled reactions between aldehydes and alkenes

The direct difunctionalization of alkenes has emerged as a sustainable and versatile strategy for the efficient construction of complex molecules from simple chemical feedstocks. Specifically, the 1,3-difunctionalization of alkenes enables the simultaneous installation of functional groups at the non-classical 1,3-position of alkenes. Thus, these chemical transformations create new bond disconnection strategies in chemical synthesis. This emerging strategy has identified a novel pathway for the further development of alkene transformations, and has even been applied to the synthesis of various complex biologically active molecules and pharmaceutical candidates. This review summarizes the advances in the development of 1,3-difunctionalization of alkenes mediated by Pd-, Ni-, Fe-, and Cu-based catalysts, as well as under metal-free conditions, over the past few decades, with an emphasis on the reaction mechanisms and factors governing regioselectivity.

1,3-Difunctionalization of alkenes: state-of-the-art and future challenges

Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H–P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or α-carbon.

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Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism

Five-membered N-heterocycles play an important role in organic synthesis and material chemistry, as they are widespread through pharmaceutical molecules and natural products. Chemists have developed many synthetic strategies for constructing five-membered N-heterocycles from N-centered radicals, but the availability of mild and green methods for these transformations is still limited. The cyclization of visible-light-generated N-centered radicals with alkenes has emerged as a powerful tool to enable these chemical transformations in recent years. Through chosen representative examples, the significant developments in this promising field were outlined, including the selection of catalysts, substrate scope, mechanistic understanding (especially density functional theory calculations), and applications. The contents of this Minireview are categorized by intramolecular cyclization and intermolecular N-centered radical addition/cyclization reactions.

Hongxing Zheng

Papers

Recent advances in acyl radical enabled reactions between aldehydes and alkenes

1,3-Difunctionalization of alkenes: state-of-the-art and future challenges

Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism

Visible-Light-Catalyzed N-Radical-Enabled Cyclization of Alkenes for the Synthesis of Five-Membered N-Heterocycles.

Sulfonyl radical triggered selective iodosulfonylation and bicyclization of 1,6-dienes