Phosphine Organocatalysis Research Articles

Radical Coupling Initiated by Organophosphine Addition to Ynoates

AbstractDual nucleophilic phosphine photoredox catalysis is yet to be developed due to facile oxidation of the phosphine organocatalyst to the phosphoranyl radical cation. Herein, we report a reaction design that avoids this event and exploits traditional nucleophilic phosphine organocatalysis with photoredox catalysis to allow the Giese coupling with ynoates. The approach has good generality, while its mechanism is supported by cyclic voltametric, Stern–Volmer quenching, and interception studies.

Radical Coupling Initiated by Organophosphine Addition to Ynoates.

Dual nucleophilic phosphine photoredox catalysis is yet to be developed due to facile oxidation of the phosphine organocatalyst to the phosphoranyl radical cation. Herein, we report a reaction design that avoids this event and exploits traditional nucleophilic phosphine organocatalysis with photoredox catalysis to allow the Giese coupling with ynoates. The approach has good generality, while its mechanism is supported by cyclic voltametric, Stern-Volmer quenching, and interception studies.

Chiral Naphthyl-C2-Indole as Scaffold for Phosphine Organocatalysis: Application in Asymmetric Formal [4 + 2] Cycloaddition Reactions.

The applications of a newly designed chiral naphthyl-C2-indole bifunctional phosphine organocatalyst in stereoselective formal [4 + 2] cycloaddition reactions were reported. The chiral naphthyl-C2-indole skeleton was introduced to bifunctional phosphine organocatalysis for the first time, and excellent stereocontrol was achieved in two types of formal [4 + 2] cycloaddition reactions. With the optimal catalyst, a series of chiral spirooxindole and hydrodibenzofuran architectures were produced in moderate to good yields with excellent stereoselectivities (up to >99% ee, >20:1 dr).

Air-stable phosphine organocatalysts for the hydroarsination reaction

Readily-available triarylphosphines are explored as organocatalysts for the hydroarsination reaction. When compared to transition metal catalysis, phosphine organocatalysis greatly improved solvent compatibility of the hydroarsination of nitrostyrenes. Upon complete conversion, arsine products were isolated in up to 99% yield while up to 48% of the phosphine catalyst was still active. A mechanism was proposed and structure-activity analysis regarding catalyst activity concluded that sterically-bulkier catalysts were effective at minimizing catalyst deactivation.

Tuning the Structure of Phosphahelicenes for Targeted Applications in Enantioselective Phosphine Organocatalysis

The use of phosphahelicenes as nucleophilic organocatalysts for [3+2] cyclization reactions between allenoates and 2‐benzylidenemalononitriles has been extended by the systematic screening of phosphines with different helical scaffolds and substitution patterns. Among others, a new series of phosphahelicenes have been prepared by bromination/Suzuki coupling reactions of a pre‐formed phosphahelicene. This late bromination approach represents a suitable strategy for accessing a broad variety of substituted phosphahelicenes from a single intermediate. It represents a powerful tool for the catalysis‐oriented optimization of their structural features.

Asymmetric cyanation of imines via dipeptide-derived organophosphine dual-reagent catalysis.

Over the past few decades, enantioselective phosphine organocatalysis has evolved rapidly into a highly efficient catalytic strategy for a range of useful reactions. However, as restricted by the traditional catalytic modes, some important reactions, such as asymmetric Strecker-type reactions, have thus far been out of reach of this strategy. Reported herein is an application of enantioselective phosphine organocatalysis for asymmetric Strecker-type reactions, enabled by a dual-reagent catalyst system in which the key organophosphorus zwitterion intermediate, generated in situ by mixing a chiral dipeptide-derived multifunctional organophosphine with methyl acrylate, is used as a highly efficient chiral Lewis base catalyst. The high efficiency of this catalytic system is demonstrated in the asymmetric cyanation of isatin-derived ketimines and azomethine aldimines as well as in the kinetic resolution of racemic 3-substituted azomethines. Mechanistic studies provide experimental evidence for the intermediacy of the putative zwitterion and its role as a catalytically active Lewis base.

Phosphine-Catalyzed Vicinal Acylcyanation of Alkynoates.

Phosphine organocatalysis enabled vicinal acylcyanation of alkynoates with acyl cyanides to form acrylonitrile derivatives with a tetrasubstituted alkene moiety. The acyl and cyano groups were introduced at the α and β carbon atoms, respectively, of the C-C triple bond in the alkynoates with complete regioselectivity and high anti stereoselectivity. A variety of functional groups in the acyl cyanides and alkynoates were tolerated.

ChemInform Abstract: Applications of Chiral Phosphine‐Based Organocatalysts in Catalytic Asymmetric Reactions

AbstractReview: [advances in the field of enantioselective phosphine organocatalysis within the last couple of years; 58 refs.

ChemInform Abstract: anti‐Selective Vicinal Silaboration and Diboration of Alkynoates Through Phosphine Organocatalysis.

AbstractThe formed E‐borylsilyl olefines are further functionalized by palladium catalyzed coupling reactions.

ChemInform Abstract: Phosphine Organocatalysis for the Synthesis of Spirocyclic Compounds

AbstractReview: 60 refs.

Anti-selective vicinal silaboration and diboration of alkynoates through phosphine organocatalysis.

Trialkylphosphine organocatalysts have enabled anti-selective vicinal silaboration and diboration of the C-C triple bond in alkynoates to produce β-boryl-α-silyl acrylates and α,β-diboryl acrylates, respectively. The anti stereoselectivity was complete and robust. A variety of functional groups were tolerated in the alkynoates. The two vicinally installed heteroatom substituents of the β-boryl-α-silyl acrylates and α,β-diboryl acrylates could be differentiated and transformed in a stepwise manner, allowing the synthesis of a diverse array of unsymmetrical tetrasubstituted alkenes.

Phosphine Organocatalysis for the Synthesis of Spirocyclic Compounds

This account describes the use of phosphines as simple organocatalysts that catalyze the synthesis of complex spirocyclic compounds. Besides our own results, coverage of relevant literature in this field is also provided, including asymmetric variants and synthetic applications. 1 Introduction 2 Cycloaddition Reactions Involving Allenoates or 2-Butynoates 2.1 [3+2] Cycloadditions 2.2 [4+2] Cycloadditions 2.3 [4+1] Cycloadditions 3 [3+2] Cycloadditions with Morita–Baylis–Hillman Adducts 4 Cycloaddition Reactions Using Ynone Derivatives 5 Cycloaddition Reactions Involving Methyl Vinyl Ketone ­ Derivatives 6 Miscellaneous Reactions 7 Conclusions

ChemInform Abstract: Phosphine Organocatalysis in the Synthesis of Natural Products and Bioactive Compounds

AbstractReview: 47 refs.

Nucleophilic Phosphine Organocatalysis: a Practical Synthetic Strategy for the Drug-Like Nitrogen Heterocyclic Framework Construction

Nucleophilic phosphine catalysis has proven to be a practical and powerful synthetic strategy in organic chemistry, which can provide easy access to five-, six-, seven-, and eight-membered nitrogen heterocyclic compounds. The reaction topologies can be controlled by a proper choice of the phosphine catalysts, as well as the functionalization of the reaction substrates. In many cases, the reactions take place smoothly at room temperature, with high efficiency and atom economy. This mini-review presents the recent advances in nucleophilic phosphine catalysis for the synthesis of drug-like nitrogen heterocylic compounds. The nitrogen heterocyclic compounds with significant biological activities derived from the library based on nucleophilic phosphine-catalyzed annulation reactions are also highlighted.

Progress in Enantioselective Phosphine Organocatalysis

Abstract Enantioselective phosphine organocatalysis has been a research frontier in the field of asymmetric catalysis. The comparable advantages, including short reaction time, mild reaction conditions, high catalytic activity, and environment benign, render the organocatalytic reaction to meet the development direction of green chemistry. This paper briefly reviews the recent advances in the development of chiral phosphine-catalyzed asymmetric reactions, such as Morita-Baylis-Hillman reaction, the asymmetric allylic substitution of Morita-Baylis-Hillman adducts, cycloaddition, esterification reaction, γ-addition reaction and other asymmetric reaction.

Phosphine Organocatalysis in the Synthesis of Natural Products and Bioactive Compounds

AbstractDuring the last few years, synthetic methods based on phosphine organocatalysis have experienced extremely fast developments. This short overview is intended to demonstrate that these methods can afford suitable tools for the constitution of either focused or diversity‐oriented‐synthesis (DOS) inspired libraries of small molecules for biological screening. It also reports selected examples where these organocatalytic methods have been used conveniently as key steps in the formal or total synthesis of complex natural products. Especially, synthetic applications of the inter‐ and intramolecular cyclizations of unsaturated substrates have been considered in this review.

Enantioselective Phosphine Organocatalysis

The broad potential synthetic usefulness of phosphine-promoted reactions has stimulated many recent investigations on enantioselective variants of known reactions of this family, as well as the search for new, specifically designed, chiral phosphorus catalysts. This short overview summarizes the state of the art in this field and highlights the most significant achievements, with special emphasis on our recent work.

Asymmetric total synthesis of the iridoid beta-glucoside (+)-geniposide via phosphine organocatalysis.

Phosphine-catalyzed [3 + 2] cycloaddition of ethyl-2,3-butadienoate with enone (S)-3b occurs with high levels of regio- and stereocontrol to deliver the cis-fused cyclopenta[c]pyran 4 characteristic of the iridoid family of natural products. Cycloadduct 4 was converted to the iridoid glycoside (+)-geniposide in 10 steps.

Nucleophilic Phosphine Organocatalysis

AbstractPhosphines have recently become popular choices as nucleophilic catalysts in organic synthesis. The unique reactivity of phosphines compared to amines has allowed the discovery of new nucleophilic addition reactions at the α‐ and γ‐positions of unsaturated carbonyl compounds, as well as novel [3+2] and [4+2] cycloaddition reactions of activated alkynes and alkenes. The accessibility of chiral phosphines has rendered several of these transformations enantioselective and has made possible the kinetic resolution of racemic secondary alcohols by phosphine‐catalyzed acylation. This mini‐review presents recent advances in nucleophilic phosphine organocatalysis for carbon‐carbon bond formation.