Palladium-catalyzed Allylic Substitution Research Articles

Electronic differentiation competes with transition state sensitivity in palladium-catalyzed allylic substitutions

Electronic differentiations in Pd-catalyzed allylic substitutions are assessed computationally from transition structure models with electronically modified phospha-benzene-pyridine ligands. Although donor/acceptor substitutions at P and N ligand sites were expected to increase the site selectivity, i.e. the preference for "trans to P" attack at the allylic intermediate, acceptor/acceptor substitution yields the highest selectivity. Energetic and geometrical analyses of transition structures show that the sensitivity for electronic differentiation is crucial for this site selectivity. Early transition structures with acceptor substituted ligands give rise to more intensive Pd-allyl interactions, which transfer electronic P,N differentiation of the ligand more efficiently to the allyl termini and hence yield higher site selectivities.

Syntheses of C1-symmetric bidentate ligands having pyridyl and 1,3-Thiazolyl, 1-methylimidazolyl or pyrazinyl donor groups for enantioselective palladium-catalyzed allylic substitution and copper-catalyzed cyclopropanation

New chiral C 1-symmetric bidentate ligands, which possess two different nitrogen heterocycles, 1,3-thiazolyl, 1-methylimidazolyl or pyrazinyl and one pyridyl group, were prepared by Kröhnke condensation in 36–59% overall yield. Stable Pd(II)-allyl and Cu(II) chloride complexes formed by some of the ligands were obtained in 60–65% yields. X-ray crystal structure analysis of a copper(II) complex having 1-methylimidazolyl group indicated that it is a μ-chloro bridge dimer. The Pd(II)-allyl complexes were found to be active catalysts in the asymmetric allylic substitution of 1,3-diphenylprop-2-enyl acetate. The best result observed was 85% e.e. and 99% isolated yield. In addition, the in situ generated Cu(OTf) 2 complexes were found to be active catalysts in cyclopropanation of styrene with ethyl diazoacetate.

Palladium-catalyzed enantioselective allylic substitution by chiral p,n-heterodonor ligands

Chiral P,N-heterodonor ligands are effective in the enantioselective allylic substitution of 1,2-diphenyl-2-propenyl acetate with dimethylmalonate. The reactions are conveniently carried out at ambient temperature. The excellent levels of enantiomeric excess up to 98% were obtained in good conversion.

Synthesis of 4-diphenylphosphanylmethyl- and 4-phenylthiomethyl-1,4-methano-11,11-dimethyl-1,2,3,4-tetrahydroacridine: new N–P and N–S camphor-derived chiral ligands for asymmetric catalysis

A new procedure has been developed for the preparation of camphor-annulated quinoline with different substituents on the 1-methyl group of the (+)-camphor backbone. Amongst them, two new N–P and N–S ligands, namely the 4-(diphenylphosphanylmethyl)- and 4-(phenylthiomethyl)-1,4-methano-11,11-dimethyl-1,2,3,4-tetrahydroacridine, have been employed in asymmetric palladium-catalyzed allylic substitution.

Electronic differentiations in palladium-catalyzed allylic substitutions

The “ trans rule” in Pd-catalyzed allylic substitutions predicts trans to phosphorus additions of nucleophiles to Pd–allyl intermediates, e.g., with P,N-ligands. This computational study reveals that not only the intrinsic electronic differentiation between P- (i.e., PH 3) and N-ligands (i.e., para-X-substituted pyridines), but also the “late” or “early” nature of the transition structures is crucial for strong cis vs. trans discriminations and hence for selectivity. Although para-nitro pyridine exhibits less intrinsic electronic differentiation than para-dimethylamino pyridine, the higher reactivity of the Pd–allyl-intermediate and the earlier nature of the transition structure yield a higher sensitivity for electronic differentiation for X NO 2 than X NMe 2.

(–)-Sparteine-mediated stereoselective directed ortho metalation of ferrocene diamides

The utility of (–)-sparteine-mediated directed ortho metalation (DoM) has been investigated in stereoselective preparation of planar chiral ferrocenes derived from 1,1′-N,N,N′,N′-tetraisopropylferrocenedicarboxamide (5). In the synthesis of C2-symmetric analogs of 5, the protocol (base, solvent, and two-step DoM) was found to be crucial for obtaining high enantio- and diastereo-selectivities of the products. A variety of highly enantioenriched mono and doubly functionalized derivatives of 5 have been synthesized. The synthetic applications of these compounds as chiral ligands in asymmetric alkylation of aldehydes and asymmetric palladium-catalyzed allylic substitutions have been demonstrated.Key words: directed ortho metalation, stereoselective deprotonation, ferrocene ligands, asymmetric catalysis.

New Developments in Stereoselective Palladium-Catalyzed Allylic Alkylations of Preformed Enolates

Whereas the enantioselective palladium-catalyzed allylic substitution with ‘soft’, stabilized carbanions can be considered as established and versatile method today, nonstabilized, preformed enolates were used for this purpose only very reluctantly. This ­report focuses on progress made recently in combining π-allyl ­palladium complexes with different metal enolates derived from carboxylic esters and ketones. The elaboration of protocols that ­permit enantioselective and - at the same time - diastereoselective allylic alkylations are emphasized in this report. The stereochemistry in the approach of the enolate to the π-allyl palladium complex is also discussed.

New Carbohydrate‐Based Phosphite‐Oxazoline Ligands as Highly Versatile Ligands for Palladium‐Catalyzed Allylic Substitution Reactions

AbstractWe have designed and synthesized a new family of readily available phosphite‐oxazoline ligands for Pd‐catalyzed asymmetric allylic substitution reactions. These ligands can be tuned in two regions to explore their effect on catalytic performance. By carefully selecting the ligand components, we obtained high enantioselectivities in the Pd‐catalyzed allylic substitution in substrates with different steric properties

Hydrogen-bond directed palladium-catalyzed allylic substitution of cyclic substrates

The regioselectivity of the Pd-catalyzed allylic substitution of cyclic substrates possessing an adjacent amide functional group was investigated. With imide-like nucleophiles, six-membered ring substrates were found to proceed with a high level of regiodirection whereas hydrogen-bond directed addition was not a significant factor in the five-membered ring substrates.

The preparation and resolution of 2-(2-pyridyl)- and 2-(2-pyrazinyl)-Quinazolinap and their application in palladium-catalysed allylic substitution

The preparation and resolution of two new axially chiral quinazoline-containing phosphinamine ligands, 2-(2-pyridyl)-Quinazolinap and 2-(2-pyrazinyl)-Quinazolinap, is described. The ligands were synthesised in good yield over eight steps and included two Pd-catalysed reactions, a Suzuki coupling to form the biaryl linkage and the introduction of the diphenylphosphino group, as the key transformations. The racemic ligands were resolved via the fractional crystallisation of diastereomeric palladacycles derived from (+)-di-μ-chlorobis{( R)-dimethyl[1-(1-naphthyl)ethyl]aminato-C 2,N}dipalladium (II) X-ray crystal structures of the ( S, R)-2-pyridyl- and ( S, R)-2-pyrazinyl-palladacycles are included. Displacement of the resolving agent by reaction with 1,2-bis(diphenylphosphino)ethane gave enantiopure 2-(2-pyridyl)-Quinazolinap and 2-(2-pyrazinyl)-Quinazolinap, new atropisomeric phosphinamine ligands for asymmetric catalysis. These ligands were applied in the palladium-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate resulting in moderate conversions and enantioselectivities of up to 81%.

Selective Synthesis of Allylated Oxime Ethers and Nitrones Based on Palladium-Catalyzed Allylic Substitution of Oximes

[reaction: see text] The viability of oximes as nucleophiles in transition-metal-catalyzed allylic substitution was examined. The oxygen atom of oxime acted as a reactive nucleophile in the reaction of a pi-allyl palladium complex. In the presence of Pd(PPh3)4, the allylic substitution of oximes with allylic carbonate afforded the linear O-allylated oxime ethers selectively without a base. In contrast, the palladium-catalyzed reaction with allylic acetate proceeded smoothly in the presence of K2CO3 or Et2Zn as a base. Selective formation of nitrones was achieved by using palladium(II) catalyst. In the presence of Pd(cod)Cl2, the allylic substitution of oximes with allylic acetate afforded the N-allylated nitrones under solvent-free conditions, as a result of the reaction with the nitrogen atom of oximes.

Asymmetric synthesis of an aminomethyl morpholine via double allylic substitution

The development of an asymmetric route to an aminomethyl morpholine intermediate via palladium-catalysed allylic substitution is described.

Chiral 5-(diphenylphosphanyl)-1,2,3,4-tetrahydroacridines: new N,P-ligands for asymmetric catalysis

Three chiral 5-(diphenylphosphanyl)-1,2,3,4-tetrahydroacridines, as first representative examples of a new class of chiral N,P-ligands were prepared from (+)-nopinone, (+)-camphor and 5α-androst-2-en-17-one. These ligands have been assessed in the enantioselective palladium-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate. Enantioselectivity up to 74% has been obtained.

Aziridine-Derived Iminophosphine Ligands in Palladium-Catalyzed Allylic Substitution.

For Abstract see ChemInform Abstract in Full Text.

Palladium-Catalyzed Asymmetric Allylic Substitutions by Axially Chiral P,S-, S,S-, and S,O-Heterodonor Ligands with a Binaphthalene Framework.

Axially chiral P,S-heterodonor ligand L1 is effective in the asymmetric allylic substitution of 1,3-diphenylpropenyl acetate with dimethyl malonate. its bidentate coordination pattern to a I'd metal center with both P and S atoms has been unambiguously established by X-ray diffraction and NMR spectroscopic analyses. Herein, we further disclose that axially chiral S,S-heterodonor ligands L2-L4 are also effective in the same reaction to give the allylic alkylation product in moderate to good ee. However, the corresponding S,O-heterodonor ligands are not as effective as the corresponding P,S- or S,S-heterodonor ligands in the same asymmetric reaction. (C) 2004 Elsevier Ltd. All rights reserved.

Palladium-Catalyzed Allylic Substitution Reaction in Polymer Synthesis

Polymer synthesis via the palladium-catalyzed allylic substitution reaction between allylic esters and malonic esters, namely the Tsuji-Trost reaction, is summarized in this review. Due to the versatility and potential of the Tsuji-Trost reaction, four polymerization patterns for various functionalized polymers have been reported.

Synthesis of a New Chiral Source, (1R,2S)‐1‐Phenylphospholane‐2‐carboxylic Acid, via a Key Intermediate α‐Phenylphospholanyllithium Borane Complex: Configurational Stability and X‐ray Crystal Structure of an α‐Monophosphinoalkyllithium Borane Complex

A synthetic route to enantiomerically pure (1R,2S)-1-phenylphospholane-2-carboxylic acid (1), which is a phosphorus analogue of proline, has been established. A key step is the deprotonation-carboxylation of the 1-phenylphospholane borane complex 3 by using sBuLi/1,2-dipiperidinoethane (DPE). Configurational stability of the key intermediate, the amine-coordinated alpha-phosphinoalkyllithium borane complex 4, was investigated by employing lithiodestannylation-carboxylation of both diastereomers of the 1-phenyl-2-trimethylstannylphospholane borane complex 7 in the presence of several kinds of amines, and as a result, 4 was found to be configurationally labile even at -100 degrees C. The key intermediate, the DPE-coordinated trans-1-phenyl-2-phospholanyllithium borane complex 9, was isolated, and the structure was identified by X-ray crystal structure analysis. This is the first X-ray crystal structure determined for an alpha-monophosphinoalkyllithium borane complex. Remarkably, the alkyllithium complex is monomeric and tricoordinate at the lithium center with a slightly pyramidalized environment, and the existence of a Li--C bond (2.170 A) has been confirmed. Moreover, (1)H-(7)Li HOESY and (6)Li NMR analyses suggested the structure of 9 in solution as well as the existence of an equilibrium between 9, its cis isomer, and the ion pair 8 at room temperature, which was extremely biased towards 9 at -100 degrees C. Finally, 1 was used as a chiral ligand in a palladium-catalyzed allylic substitution, and the desired product was obtained in high yield with good enantioselectivity.

Aziridine-derived iminophosphine ligands in palladium-catalyzed allylic substitution

New iminophosphines have been synthesized from ( R, R)-1-amino-2-diphenylphosphino cyclohexane ( R. R)- 1 in good to excellent yields. The catalysts obtained from iminophosphines 3a– g and [Pd(C 3H 5)Cl] 2 promote the enantioselective allylic substitution of 1,3-diphenyl-2-propenyl acetate ( 6) with diethyl malonate with good enantioselectivity. The air-stable complex PdCl 2[κ 2- P, N-( R, R)-2-Ph 2PC 6H 10N CHPh] ( 4) has been prepared and structurally characterized by X-ray crystallography.

Homogeneous Two‐Component Polycondensation Without Strict Stoichiometric Balance via the Tsuji—Trost Reaction: Remote Control of Two Reaction Sites by Catalysis.

Carothers and Flory established the fundamental principles of homogeneous two-component polycondensation reactions by which a variety of commonly used polymers such as polyesters and polyamides (nylons) are synthesized even now. One of the most critical factors to achieve a high degree of polymerization is a strict adherence of stoichiometric balance of the two components. An imbalanced ratio of the two starting materials leads to lower degree of polymerization and, consequently, polymers of poor quality. Here we report the details of a strategy, validated by appropriate experiments, which enables an efficient homogeneous two-component polycondensation via palladium-catalyzed allylic substitution (the Tsuji−Trost) reaction without strict stoichiometric balance.

A new class of chiral P,N-ligands and their application in palladium-catalyzed asymmetric allylic substitution reactions.

An efficient and modular synthesis of a series of chiral nonracemic P,N-ligands is reported. The P,N-ligands were prepared from 2-chloro-4-methyl-6,7-dihydro-5H-[1]pyrindine-7-one and a series of substituted chiral C(2)-symmetric 1,2-ethanediols (R = Me, i-Pr, and Ph). The ligands were evaluated for use in catalytic asymmetric synthesis in the palladium-catalyzed allylic substitution reactions of a racemic allylic acetate and dimethyl malonate. In the case of the P,N-ligand (R = Ph), the reaction was found to be highly stereoselective (90% ee).