Sumod A. Pullarkat

Direct Synthesis of Chiral Tertiary Diphosphines via Pd(II)-Catalyzed Asymmetric Hydrophosphination of Dienones

A highly diastereo- and enantioselective Pd(II)-catalyzed hydrophosphination of dienones with Ph(2)PH involving formation of double C*-P bonds has been developed, providing a series of chiral tertiary diphosphines (chiral PCP pincer ligands) in high yields. A catalytic cycle for the reaction was proposed.

Palladacycle-Catalyzed Asymmetric Hydrophosphination of Enones for Synthesis of C*- and P*-Chiral Tertiary Phosphines

A highly reactive and stereoselective hydrophosphination of enones catalyzed by palladacycles for the synthesis of C*- and P*-chiral tertiary phosphines has been developed. When Ph(2)PH was employed as the hydrophosphinating reagent, a series of C*-chiral tertiary phosphines were synthesized (C*-P bond formation) in high yields with excellent enantioselectivities, and a single recrystallization provides access to their enantiomerically pure forms. When racemic secondary phosphines rac-R(3)(R(4))PH were utilized, a series of tertiary phosphines containing both C*- and P*-chiral centers were generated (C*-P* bond formation) in high yields with good diastereo- and enantioselectivities. The stereoelectronic factors involved in the catalytic cycle have been revealed.

Asymmetric Synthesis of Enaminophosphines via Palladacycle-Catalyzed Addition of Ph2PH to α,β-Unsaturated Imines

A highly reactive, chemo- and enantioselective addition of diphenylphosphine to α,β-unsaturated imines catalyzed by a palladacycle has been developed, thus providing the access to a series of chiral tertiary enaminophosphines in high yields. A putative catalytic cycle has also been proposed.

Chiral Metal Complex-Promoted Asymmetric Hydrophosphinations

This chapter provides an account of the synthesis of a series of chiral tertiary phosphines via the metal complex-assisted asymmetric hydrophosphination methodology which involves secondary phosphines as the nucleophiles. Chiral aza- and phosphapalladacycles are found to function as highly efficient templates or catalysts for the asymmetric P–H addition reaction. The versatile protocol allows for the asymmetric hydrophosphination of olefinic C=C bonds of monophosphines thus yielding a family of tertiary C*-diphosphines as well as C*P*-diphosphines, depending on the nucleophile employed. The addition of two equivalents of HPPh2 to symmetrical bifunctionalized alkynes leading to generation of two new C* centers is also supported. The air-sensitive nucleophiles and the unsaturated substrates containing unprotected functionalities such as aldehyde, keto, ester, cyano, and alcohol can be utilized directly under this mild and facile reaction conditions. The methodology is equally efficient when applied to the generation of P–N ligand systems via hydrophosphination of unsaturated pyridyl-based substrates as well as systems with C=N moieties. The protocol has also the added advantage of allowing the selective formation of 1,1-, 1,2-, and 1,3-diphosphines simply by judicious control of reaction conditions. This reaction can also be extended to the synthesis of chiral triphosphine systems. This synthetic strategy therefore promises to be a versatile approach for the generation of a wide range of chiral tertiary phosphine ligands with potential applications in catalysis.

Asymmetric Synthesis of Diphosphine Ligands Containing Phosphorus and Carbon Stereogenic Centers by Means of a Chiral Palladium Complex Promoted Hydrophosphination Reaction

An organopalladium complex containing ortho-metalated (R)-(1-(dimethylamino) ethyl)naphthalene as the chiral auxiliary has been used to promote the asymmetric hydrophosphination reaction between diphenylphosphine and phenyldi[(Z)-prop-1-enyl]phosphine in high regio- and stereoselectivity under mild conditions. The hydrophosphination reaction generated only two diastereomers in a ratio of 1:1. The two hydrophosphination products contained both phosphorus and carbon stereogenic centers and were subsequently isolated by fractional crystallization. Their absolute stereochemistries were analyzed by X-ray crystallography. The naphthylamine auxiliary could be removed chemoselectively from the template products by treatment with concentrated hydrochloric acid to form the corresponding optically pure neutral dichloro complexes. Subsequently, the dichloro complexes underwent ligand displacement with aqueous cyanide to generate the optically pure diphosphine ligands in high yields.

A tandem Heck–aza-Michael addition protocol for the one-pot synthesis of isoindolines from unprotected amines

A palladacycle-catalyzed tandem Heck-intramolecular aza-Michael reaction protocol has been developed for the one-pot synthesis of 1-substituted isoindolines from N-unprotected 2-bromobenzylamines and acrylates with high yields.

Asymmetric Synthesis of Functionalized 1,3-Diphosphines via Chiral Palladium Complex Promoted Hydrophosphination of Activated Olefins

Aldehyde, ester- and keto-functionalized monophosphine palladium complexes containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary and reaction promoter were synthesized via hydrophosphination of acrolein and the subsequent Wittig reactions in a one-pot process. Under very mild conditions, the second-stage hydrophosphination of the monophosphine substrates gave the corresponding ester-, keto-, and hydroxyl-functionalized chiral 1,3-bis(diphenylphosphino)propane palladium complexes with good yields and stereoselectivities. The coordination properties and absolute configurations of the novel 1,3-diphosphine complexes were established by single crystal X-ray crystallography. The enantiomerically pure functionalized diphosphine ligands with ester and keto functionalities could be subsequently liberated stereospecifically by treatment of the corresponding dichloro palladium complexes with aqueous potassium cyanide in high yields.

Chiral cyclopalladated complex promoted asymmetric synthesis of diester-substituted P,N-ligands via stepwise hydrophosphination and hydroamination reactions

A series of enantiomerically pure 1,2-diester substituted P,N-ligands incorporating two chiral carbons in the backbone were generated in high yields and high stereoselectivity from acetylenedicarboxylate via initial hydrophosphination using diphenylphosphine followed by hydroamination with various primary and secondary amines. The reactions were activated and stereochemically controlled by the organopalladium complex containing ortho-palladated (S)-(1-(dimethylamino)ethyl)naphthalene under mild conditions. The absolute stereochemistry and the coordination chemistry of P,N-products were determined by the single crystal X-ray diffraction analysis. All the chiral P,N-ligands could be liberated from the palladium template without loss of optical purity. Subsequent recomplexation to selected chiral palladium centers confirmed the optical purity of the new functionalized chiral P,N-ligands.

Pd‐Catalyzed Enantiodivergent and Regiospecific phospha‐Michael Addition of Diphenylphosphine to 4‐oxo‐Enamides: Efficient Access to Chiral Phosphinocarboxamides and Their Analogues

The palladacycle-catalyzed asymmetric P-H addition of 4-oxo-enamides has been developed, which provides efficient access to phosphinocarboxamides and their analogues. Solvent-mediated reversal of stereoselectivity (ee from +96% to -92%) was observed, and the underlying mechanism that allows facile access to both enantiomers of the product by judicious choice of solvents is revealed.

Copper(II) Triflate Catalyzed Allylic Arylation of Allylic Alcohols: Direct and Selective Access to C‐Allylanilines

Copper(II) triflate was used as a simple and commercially available catalyst in the direct amination of allylic alcohols with anilines to provide C‐allylanilines. A wide range of functional groups were tolerated under the reaction conditions, and the products were obtained regioselectivity without the need of an activator. A detailed mechanistic investigation was undertaken. The efficacy of this protocol was demonstrated in the conversion of the 2‐allylanilines into substituted quinolines through an oxidative cycloaddition reaction.