(S)-2-[(N-arylamino)methyl]pyrrolidines-Based PhosphoramiditeP,N-Ligand Library for Asymmetric Metal-Catalyzed Allylic Substitution and Conjugate 1,4-Addition

Abstract

A library of easy‐to‐prepare and modular chiral P,N‐phosphoramidites based on [1,1′‐biaryl]‐2,2′‐diols and C1‐symmetric 1,2‐diamines has been designed and developed. The structures of the novel ligands have been elucidated by means of 2D‐NMR and confirmed in the solid state by X‐ray diffraction analysis. Stereoselectors of this type exhibited high enantioselectivities in Pd‐catalyzed allylic substitution reactions of (E)‐1,3‐diphenylallyl acetate with NaSO2pTol (up to 91 % ee), CH2(CO2Me)2 (up to 89 % ee), (C3H7)2NH (up to 94 % ee) and (EtO)2P(O)CH2NH2 as a novel nucleophile (up to 98 % ee). Ee values of up to 88 % and 72 % have been obtained in the Pd‐catalyzed desymmetrization of N,N′‐ditosyl‐meso‐cyclopent‐4‐ene‐1,3‐diol biscarbamate and in the Cu‐catalyzed 1,4‐conjugate addition of diethylzinc to chalcone, respectively. The reactions of P,N‐bidentate ligands with [Pd(Cod)Cl2] at molar ratios of L/M=1 and 2 have been studied using 1H, 13C, 13C‐1H HSQC, 13C‐1H HMBC, 1H‐1H COSY, 1H‐1H ROESY, DOSY and 31P NMR spectroscopy as well as HR ESI mass spectrometry.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…Ligand L88 provided high enantiocontrol in the allylic substitution of rac -1,3-diphenylallyl acetate with para -toluenesulfinate, pyrrolidine and diethyl aminomethylphosphonate ( ee values up to 98%; Scheme 79 b). 274 …”

“…Ligand L88 provided high enantiocontrol in the allylic substitution of rac-1,3-diphenylallyl acetate with para-toluenesulfinate, pyrrolidine and diethyl aminomethylphosphonate (ee values up to 98%; Scheme 79b). 274 Other examples include several phosphite/phosphoramiditeamine ligands 271−275 of which ligand L89 provided high ee values for linear and cyclic disubstituted substrates with several α-substituted malonates (Scheme 80), as well as 1,3-diketones, benzylamines, and electron-poor benzylic alcohols. 273 Another interesting example is found in the work of Hamada's group who developed the amine-diaminophosphine oxide (S,R P )-Ph-Diaphox, which is transformed in situ into the diamidophosphite-amine ligand L90 with the N,O-bis-(trimethylsilyl)acetamide (BSA) under the reaction conditions employed.…”

“…The quest for more stable and inexpensive ligands spurred the interest for bidentate heterodonor P,N­(sp 3 )-ligands. In most examples either amines − or amides − were used as N-donor groups and most studies focused on reactions of the benchmark linear substrate with dimethyl malonate as nucleophile (see Scheme ). The low selectivity of this class of ligand has been attributed to the low stereoselective coordination of the N-sp 3 group, which leads to the formation of diastereoisomeric mixtures of catalytic species.…”

First Tetradentate Diamidophosphite Based on [5,10,15,20-Tetrakis(4-hydroxyphenyl)porphyrinato]zinc: Synthesis, Spectral Features, Coordination, and Application in Asymmetric Pd-Catalyzed Reactions

“…To examine the complexing capacity of tetradiamidophosphite 2, two coordination reactions were investigated. In particular, reaction of 2 with Pd(COD)Cl 2 (our standard precursor, [39,56,57,62] COD -cycloocta-1,5-diene) proceeded in CD 2 Cl 2 and surprisingly resulted in insoluble polymeric residue. In order to shed light on the coordination properties of 2, we carried out the investigation of the ruthenium(II) complex obtained from the ligand.…”

2‐(Het)aryl‐N‐phosphorylpyrrolidines via Cyclization of Phosphorus Acid Amides: A Regioselective Approach

“…Pyrrolidine core is widespread in natural products and synthetic drugs . Phosphorus‐containing pyrrolidine derivatives are of a special interest due to their various biological and catalytic properties. Among them, (pyrrolidin‐1‐yl)phosphoramidates are proposed for hepatitis C, malaria and tuberculosis treatment, possess anti‐HIV and anti‐tumor activity.…”