Carbocycles via enantioselective inter- and intramolecular iridium-catalysed allylic alkylations

Carbocycles with > 90% ee were prepared via Ir-catalysed asymmetric allylic alkylation/ring closing metathesis sequences or enantioselective Ir-catalysed intramolecular allylic alkylations.     

Gold(I)-catalyzed intramolecular amination of allylic alcohols with alkylamines

A 1:1 mixture of (1)AuCl [1 = P(t-Bu)(2)o-biphenyl] and AgSbF(6) catalyzes the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. Gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee, 95% de) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield with 96% ee, consistent with the net syn addition of the amine relative to the departing hydroxyl group.     

Palladium(0)-catalyzed amination of allylic natural terpenic functionalized olefins

The palladium(0) catalyzed amination of allylic acetates and carbonates derivatives from terpenic olefins was carried out under mild conditions. The reaction offers a very good method for the preparation of allylic amines and thus to provide a useful entry to new functionalized terpenic olefin products. The mechanism involving a formation of p-allyl-palladium intermediate complex is in good agreement with the results obtained with the optically active substrates, as well as via an analysis of the observed regio-and stereoselectivity.      

Direct palladium(0)-catalyzed amination of allylic alcohols with aminonaphthalenes

The direct activation of CO bonds in allylic alcohols by palladium complexes has been accelerated by carrying out the reactions in the presence of titanium reagents. The palladium-catalyzed amination of allylic alcohols using aminonaphthalenes gave N-allylic naphthylamines in good yields. The monoallylation products are formed in the main.     

Palladium(II)-catalyzed aerobic intramolecular allylic CH activation for the synthesis of indolines

A method for the preparation of indolines via palladium-catalyzed aerobic intramolecular allylic CH activation was developed. Oxygen was successfully used as oxidant with catalytic amount of 1,4-benzoquinone. 16 examples were reported, the majority of substrates gave moderate to good yields.     

Features and applications of [Rh(CO)(2)Cl](2)-catalyzed alkylations of unsymmetrical allylic substrates

A novel regio- and stereoselective [Rh(CO)2Cl]2-catalyzed allylic alkylation of unsymmetrical allylic carbonates was discovered. The regioselectivity of the reaction favors product ratios in which substitution occurs at the carbon bearing the leaving group. When an enantiomerically enriched carbonate (> or = 99% ee) was examined, the Rh(I)-catalyzed allylic alkylation proceeded stereoselectively to provide the alkylation product with retention of absolute stereochemistry (98% ee). To establish the scope of the [Rh(CO)2Cl]2-catalyzed allylic alkylation, a variety of carbon and heteroatom nucleophiles were examined and the results described. As an application of the Rh(I)-catalyzed allylic alkylation, a series of novel domino reactions have been developed that couple the unique regio- and stereoselective [Rh(CO)2Cl]2-catalyzed alkylation of allylic trifluoroacetates with an intramolecular Pauson-Khand annulation, a cycloisomerization, or a [5+2] cycloaddition. A unique aspect of the method described is the use of a single catalyst to effect sequential transformations in which the catalytic activity is moderated simply by controlling the reaction temperature. Implementation of such processes provides a rapid and efficient entry to a variety of bicyclic carbon skeletons from simple precursors.     

Direct, stereoselective substitution in [Rh(CO)(2)Cl](2)-catalyzed allylic alkylations of unsymmetrical substrates

[Rh(CO)(2)Cl](2) has been found to possess the unusual property of catalyzing allylic alkylations of unsymmetrical allylic carbonates with high levels of regioselectivity to provide products arising from substitution at the carbon atom bearing the leaving group, irrespective of the structure of the starting carbonate. The substitution reaction occurs with retention of stereochemistry at the reacting center, and the carbon-carbon double-bond stereochemistry of primary (Z)-allylic carbonates is maintained. [reaction: see text]     

Palladium(O)-catalyzed allylic alkylation and amination of allylic phosphates

Allyl diethyl phosphates (1) can be easily substituted with malonates and amines in the presence of palladium(O) catalyst. Synthetic utility of the reaction is demonstrated by the sequential amination-amination and alkylation-amination of (Z)-4-acetoxybut-2-enyl diethyl phosphate (1b) with high regio- and stereoselectivity.     

Cu(I)-catalyzed allylic amination of olefins

The copper(I) complex [Cu(CH₃CN)₄]PF₆ catalyzes the allylic amination of alkenes by aryl hydroxylamine in fair to moderate yields. Unsymmetrical alkenes react with high regioselectivity with N-functionalization occuring at the less substituted vinylic carbon. Trapping experiments indicate that free PhNO is not an intermediate in these reactions.     

Palladium(0)-catalyzed direct cross-coupling reaction of allylic alcohols with aryl- and alkenylboronic acids

Allylic alcohols can be used directly for the palladium(0)-catalyzed allylation of aryl- and alkenylboronic acids with a wide variety of functional groups. A triphenylphosphine-ligated palladium catalyst turns out to be most effective for the cross-coupling reaction and its low loading (less than 1 mol%) leads to formation of the coupling product in high yield. The Lewis acidity of the organoboron reagents and poor leaving ability (high basicity) of the hydroxyl group are essential for the cross-coupling reaction. The reaction process is atom-economical and environmentally benign, because it needs neither preparation of allyl halides and esters nor addition of stoichiometric amounts of a base. Furthermore, allylic alcohols containing another unsaturated carbon-carbon bond undergo arylative cyclization reactions leading to cyclopentane formation.     

Enantioselective synthesis of N-heterocycles via intramolecular Pd(0)-catalysed allylic amination

An efficient and stereoselective synthesis of pyrrolidine-, piperidine-, and azepane-type N-heterocycles is described by the intramolecular Pd(0)-catalysed cyclisation of amino allylic carbonates. The use of chiral ligands gave the corresponding heterocyclic derivatives having er values that were from moderate to good.     

Mg(ClO4)2-catalyzed intramolecular allylic amination: application to the total synthesis of demethoxyfumitremorgin C

A Mg(ClO₄)₂-catalyzed intramolecular amination of allylic alcohols with carbamate or sulfonamide nucleophiles to form substituted piperidine and pyrrolidine derivatives has been developed. This method has been successfully applied to the total synthesis of demethoxyfumitremorgin C.     

Mechanistic studies of copper(I)-catalyzed allylic amination

The reactions of nitrosobenzene and N,N'-diethyl-4-nitrosoaniline with [Cu(CH3CN)4]PF6 provide novel Cu(I) complexes, [Cu(PhNO)3]PF6 (1) and [Cu(Et2NPhNO)3]PF6 (2); in 2 the copper atom is N-coordinated to the nitrosoarenes in a distorted trigonal planar geometry. Complex 1 is strongly implicated as a reactive intermediate in the Cu(I)-catalyzed allylic amination of olefins based on (i) its isolation from the catalytic reaction, (ii) its stoichiometric regioselective allylic amination of alpha-methyl styrene (AMS), (iii) the non-involvement of free PhNO in its amination of AMS, and (iv) its function as a catalyst for the amination of alkenes from phenylhydroxylamine. The reaction between AMS and 1 (80 degrees C, dioxane) is first order in both alkene and 1. Relative rate studies of the reaction of 1 with para substituted AMS derivatives gives a Hammett rho value of -0.035. Alkene adducts isolated from the reaction of 1 with styrene and alpha-methylstyrene are formulated as [(PhNO)3Cu(eta(2)-alkene)]PF6 (7,8) on the basis of spectroscopic characterization and thermolysis. PM3 and DFT MO calculations support the role of [(alkene)Cu(RNO)3]+ and (eta(1)- or eta(3)-allyl)Cu(RNO)2(RNHOH)+ complexes as probable catalytic intermediates and address the origin of the distinctive reaction regioselectivity. A mechanistic scheme is proposed which is consistent with the accumulated experimental and computational results.     

Palladium/BINAP(S)-catalyzed asymmetric allylic amination

The enantioselective allylic amination of acyclic allylic carbonates catalyzed by a palladium/(S)-BINAP(S) system was investigated. Amination of several substrates proceeded with high ee. Crotyl carbonates show an unusually high regioselectivity for the branched isomer. The use of (S)-TolBINAP(S) and (S)-3,5-xylyl-BINAP(S) as ligands was found to increase the enantioselectivity of the aminations. A P,S binding mode of the BINAP(S) ligand was found in an X-ray crystallographic study. [reaction: see text]     

Pd(O)-catalyzed electroreductive cleavage of allylic acetates

Pd(O)-catalyzed electroreductive cleavage of allylic acetates yielding alkenes and/or allyltrimethylsilanes is described. Deprotection of allyl esters can be performed in the same electrolysis system.     

(NHC)AuI]-catalyzed rearrangement of allylic acetates

[(NHC)AuCl] complexes (NHC = N-heterocyclic carbene), in conjunction with a silver salt, were found to efficiently catalyze the rearrangement of allylic acetates under both conventional and microwave-assisted heating. The optimization of several reaction parameters (solvent, silver salt, and ligand) as well as a study of the reaction scope are reported. The steric hindrance of the ligand bound to gold was found crucial for the outcome of the reaction as only extremely bulky ligands permitted the isomerization.     

Iridium(I)-catalyzed regio- and enantioselective allylic amidation

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely ‘salt-free’ conditions is described. A combination of [Ir(COD)Cl]₂, a chiral phosphoramidite ligand L^∗, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (−)-cytoxazone.     

Gold(I)-catalyzed intramolecular rearrangement of vinylidenecyclopropanes

Vinylidenecyclopropanes 1 can undergo intramolecular rearrangement to give the corresponding functionalized 1,2-dihydronaphthalenes in the presence of gold catalyst under mild conditions. A plausible rearrangement mechanism has been proposed on the basis of control experiments.     

Unusual regioselectivity in Pd(0)-catalyzed coupling of allylic monoacetates and nitroalkanes: one-pot isomerization-alkylation

A hitherto unknown palladium-catalyzed reaction of nitroalkanes with hydroxy allylic acetates is reported. The reaction led to the formation of γ-nitrocarbonyl compounds instead of the usual unsaturated nitroalcohol expected upon displacement of the allylic acetate group.