Direct use of allylic alcohols for platinum-catalyzed monoallylation of amines

A new direct catalytic amination of allylic alcohols promoted by the combination of platinum and a large bite-angle ligand DPEphos was developed in which the allylic alcohol was effectively converted to a pi-allylplatinum intermediate without the use of an activating reagent. The use of the DPEphos ligand was essential for obtaining high catalyst activity and high monoallylation selectivity of primary amines, allowing the formation of a variety of monoallylation products in good to excellent yield.     

Iridium complex-catalyzed allylic amination of allylic esters

Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.     

Pd-catalyzed allylic alkylation of thioamides

This work describes the first Pd-catalyzed allylic alkylation of thioamides. Various thioamides were efficiently α-allylated in high yields and with excellent selectivity for monoallylation under mild reaction conditions. The process not only provides a facile method for the synthesis of functionalized thioamides, but also presents a useful transformation for synthetically important thioamides.     

Pentacoordinated Carboxylate π‐Allyl Nickel Complexes as Key Intermediates for the Ni‐Catalyzed Direct Amination of Allylic Alcohols

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5‐cyclooctadiene)₂] and 1,1′‐bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu₄NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu₄NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η³‐allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.     

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.     

Influence of steric symmetry and electronic dissymmetry on the enantioselectivity in palladium-catalyzed allylic substitutions

Chiral P,N-ligands with pseudo-C2 and pseudo-Cs symmetry based on chiral pyrrolidine and phospholane rings or on dinaphthatodihydroazepino and dinaphthatodihydrophosphepino moieties were prepared and assessed in the palladium-catalyzed allylic substitutions of allylic acetates. Higher selectivity was achieved with pseudo-C2-symmetric ligands based on the binaphthyl skeleton than with the analogous C2-symmetric P,P- and N,N-analogues. Pseudo-C2-type ligands had properties superior to those of pseudo-meso-type ligands when 1,3-diphenyl-2-propenyl acetate was used as a substrate, whereas the reverse situation was found for 3-cyclohexenyl acetate. Chirally flexible ligands, prepared by substitution of one of the rigid binaphthyl skeletons for a flexible biphenyl system, were found to induce chirality to the same extent as a 1:1 mixture of the rigid ligands.     

Stereodivergent synthesis via iridium-catalyzed asymmetric double allylic alkylation of cyanoacetate

Methods that enable the rapid construction of multiple C–C bonds using a single catalyst with high diastereo- and enantio-control are particularly valuable in organic synthesis. Here, we report an Ir-catalyzed double allylic alkylation reaction in which bisnucleophilic cyanoacetate reacted successionally with electrophilic π-allyl-Ir species, producing various pseudo-C₂-symmetrical cyanoacetate derivatives in high yield with excellent stereocontrol. More challenging sequential allylic alkylation/allylic alkylation with two distinct allylic carbonates that can deliver the corresponding products bearing three contiguous tertiary–quaternary–tertiary stereocenters was also developed by using a modified catalytic system, which is revealed to be associated with the quasi-dynamic kinetic resolution of the initially formed diastereomeric monoallylation intermediates. Notably, stereodivergence for this sequential process depending on a single iridium catalyst was successfully realized, and up to six stereoisomers could be predictably prepared by combining the appropriate enantiomer of the chiral ligand for the iridium catalyst and adjusting the adding sequence of two distinct allylic precursors.

Ir-catalyzed asymmetric double AAA reaction of cyanoacetate was developed, affording cyanoacetate derivatives in high yield with excellent stereocontrol. Notably, quasi-DKR is involved in the sequential protocol with two distinct allylic carbonates.     

Metal-free synthesis of allylic amines by cross-dehydrogenative-coupling of 1,3-diarylpropenes with anilines and amides under mild conditions

Dehydrogenative cross-coupling reaction of primary anilines, secondary anilines, carboxamides, and sulfonamides with 1,3-diarylpropenes to form a series of allylic amines promoted by DDQ have been realized. Both monoallylation and diallylation products can be selectively synthesized when primary anilines are used as the starting materials. The method may provide a wide scope of allylamines in scientific research including biologically active compound library construction.     

Rhenium-catalyzed 1,3-isomerization of allylic alcohols: scope and chirality transfer

The scope of the triphenylsilyl perrhennate (O3ReOSiPh3, 1) catalyzed 1,3-isomerization of allylic alcohols has been thoroughly explored. It was found to be effective for a wide variety of secondary and tertiary allylic alcohol substrates bearing aryl, alkyl, and cyano substituents. Two general reaction types were found which gave high levels of product selectivity: those driven by formation of an extended conjugated system and those driven by selective silylation of a particular isomer. The efficiency of chirality transfer with various substrates was investigated, and conditions were found in which secondary and tertiary allylic alcohols could be formed with high levels of enantioselectivity. Consideration of selectivity trends with respect to the nature of the substituents around the allylic system revealed that this is a reliable and predictable method for allylic alcohol synthesis.     

Chiral phenylselenyl derivatives of pyrrolidine and Cinchona alkaloids: nitrogen–selenium donating ligands in palladium-catalyzed asymmetric allylic alkylation

Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu₃P in toluene at 0–25 °C to give the corresponding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethers obtained were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. When chiral selenium pyrrolidine derivatives were applied, the enantioselectivity observed was improved versus the respective sulfur pyrrolidine derivatives up to over 98% ee. The results suggest that the pyrrolidine selenoethers served as the effective N(sp³), Se-donating chiral ligands. The selenoethers obtained from Cinchona alkaloids also gave the allylic alkylation product with a higher ee over those for the corresponding thioethers. The results are in agreement with nucleophilic attack directed at the allylic carbon located trans to the chalcogen atom in the intermediate η³-allylpalladium complex.     

Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.     

The use of a new carboranylamidophosphite ligand in the asymmetric Pd-catalysed allylic alkylation in organic solvents and supercritical carbon dioxide

A novel P-monodentate ligand based on carboranyl alcohol and (S)-2-(anilinomethyl)pyrrolidine provides high enantioselectivities (ee’s up to 95%) in the Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate. The first example of the Pd-catalysed allylic alkylation in supercritical carbon dioxide is also described.     

Synthesis of tetrahydroxy perhydroaza-azulenes: tandem Johnson-Claisen rearrangement of D-glucose-derived allylic alcohols

The Johnson-Claisen rearrangement of D-glucose-derived allylic alcohols 5a,b, afforded sugar-substituted gamma,delta-unsaturated ester in high yield. Conversion of the ester group to an azidomethyl group, epoxidation of the double bond and hydrogenation gave pyrrolidine ring skeletons 13a and 13b, which were transformed to tetrahydroxy perhydroaza-azulenes 1a and 1b, respectively. Glycosidase inhibitory activity was also evaluated.     

Asymmetric synthesis of cis- and trans-2,5-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates: synthesis of (+)-preussin and analogs

Pyrrolidine enones, derived from 3-oxo pyrrolidine 2-phosphonates and a HWE reaction with aldehydes, on Luche reduction give pyrrolidine allylic alcohols. The alcohols on hydrogenation (Pd/H2) give cis-2,5-disubstituted pyrrolidines and on treatment with TFA-NaBH3CN undergo a hydroxy directed reduction to trans-2,5-disubstituted pyrrolidines.     

Enamines: efficient nucleophiles for the palladium-catalyzed asymmetric allylic alkylation

Enamines were tested to be efficient nucleophiles for palladium-catalyzed asymmetric allylic alkylation, avoiding the use of unstablilized ketone enolates formed by strong bases. The influence of the chiral metallocene-based ligands upon this reaction was studied in detail. It was shown that planar chirality played an important role in enantioselectivities. Meanwhile, different kinds of enamines and allylic acetate to the reactions were also investigated. High catalytic activity and excellent enantioselectivity (up to 99% ee) were obtained with pyrrolidine enamines of both aliphatic and aromatic ketone.     

Cu(I)-catalyzed, α-selective, allylic alkylation reactions between phosphorothioate esters and organomagnesium reagents

Regiocontrol of allylic alkylation reactions involving hard nucleophiles remains a significant challenge and continues to be an active area of research. The lack of general methods in which α-alkylation is favored underscores the need for the development of new processes for achieving this type of selectivity. We report that Cu(I) catalyzes the allylic substitution of phosphorothioate esters with excellent α-regioselectivity, regardless of the nature of the Grignard reagent that is used. To the best of our knowledge, the Cu-catalyzed allylic alkylation of phosphorothioate esters has never been described. We have also developed a simple protocol for inducing high α selectivity starting from secondary allylic halides. This is accomplished by using sodium phosphorothioates as an additive.     

(Pi-allyl)palladium complexes bearing diphosphinidenecyclobutene ligands (DPCB): highly active catalysts for direct conversion of allylic alcohols

The (pi-allyl)palladium complex bearing an sp2-hybridized phosphorus ligand (DPCB-OMe: 1,2-bis(4-methoxyphenyl)-3,4-bis[(2,4,6-tri-tert-butylphenyl)phosphinidene]cyclobutene) efficiently catalyzes direct conversion of allylic alcohols in the absence of activating agents of alcohols such as Lewis acids. N-Allylation of aniline proceeds at room temperature to afford monoallylated anilines in 90-97% yields. C-Allylation of active methylene compounds is also successful at 50 degrees C using a catalytic amount of pyridine as a base, giving monoallylation products in 85-95% yields. The catalytic mechanism involving hydrido- and (pi-allyl)palladium intermediates has been proposed on the basis of stoichiometric examinations using model compounds of presumed intermediates.     

Mechanistic Implications of the Observation of Kinetic Resolution in a Palladium-Catalyzed Enantioselective Allylic Alkylation

Preferential rotation in substrate—palladium intermediates in a catalyzed asymmetric allylic alkylation is proposed to be responsible for both the observed kinetic resolution of the racemic allylic acetate starting material as well as the high selectivity found in the enantiodiscriminating product-forming step [Eq. (a)].     

Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines

A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl‐hydrazide‐catalyzed asymmetric OH‐substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]₂, 4 mol % (S)‐SegPhos, and 10 mol % 2,5‐dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity.     

Direct substitution of primary allylic amines with sulfinate salts

The NH(2) group in primary allylic amines was substituted directly by sulfinate salts with excellent regio- and stereoselectivities. In the presence of 0.1 mol % [Pd(allyl)Cl](2), 0.4 mol % 1,4-bis(diphenylphosphino)butane (dppb), and excess boric acid, a range of α-unbranched primary allylic amines were smoothly substituted with sodium sulfinates in an α-selective fashion to give structurally diverse allylic sulfones in good to excellent yields with exclusive E selectivity. Replacing dppb with 1,1'-bi-2-naphthol (BINOL) allowed unsymmetric α-chiral primary allylic amines to be transformed into the corresponding allylic sulfones in good to excellent yields with excellent retention of ee. Importantly, the reaction complements known asymmetric methods in substrate scope via its unique ability to provide α-chiral allylic sulfones with high optical purity starting from unsymmetric allylic electrophiles.