A new route to cyclopentenones via ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes

[RuCl2(CO)3]2/Et3N and (eta 3-C3H5)RuBr(CO)3/Et3N are highly effective catalyst systems for carbonylative cyclization of allylic carbonates with alkenes to give the corresponding cyclopentenones in high yields. For example, treatment of allyl methyl carbonate (1a) with 2-norbornene (2a) in the presence of a catalytic amount of [RuCl2(CO)3]2 (2.5 mol %) and Et3N (10 mol %) at 120 degrees C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltricyclo[5.2.1.0(2,6)]dec-4-en-3-one (3a), in 80% yield with high stereoselectivity (exo 100%).     

A mild and efficient method for the stereoselective formation of C-O bonds: palladium-catalyzed allylic etherification using zinc(II) alkoxides

[reaction: see text] A highly chemo- and stereoselective palladium-catalyzed allylic etherification reaction is described. The use of zinc(II) alkoxides proved effective in promoting the addition of the oxygen nucleophile derived from aliphatic alcohols to eta(3)-allylpalladium complexes. Using diethylzinc (0.5 equiv), 5 mol % of Pd(OAc)(2), and 7.5 mol % of 2-di(tert-butyl)phosphinobiphenyl in THF, the cross-coupling reaction between various aliphatic alcohols and allylic acetates proceeded at ambient temperature to furnish allylic ethers with high stereoselectivity.     

Enantioselective synthesis of 2,5-dihydrobenzo[b]azepine derivatives via iridium-catalyzed asymmetric allylic amination with 2-allylanilines and ring-closing-metathesis reaction

Iridium-catalyzed asymmetric allylic amination of allylic carbonates with 2-allylanilines was realized. With a catalyst generated from 2 mol% of [Ir(dbcot)Cl](2) (dbcot = dibenzo[a,e]cyclooctatetraene) and 4 mol% of phosphoramidite ligand (L3), the amination products were obtained in up to 99% yield and 99% ee. Subjecting amination products to trifluoroacetyl protection and ring-closing-metathesis reaction provided an efficient synthesis of enantioenriched 2,5-dihydrobenzo[b]azepine derivatives.     

Asymmetric allylic amination in water catalyzed by an amphiphilic resin-supported chiral palladium complex

[reaction: see text] Catalytic asymmetric allylic amination of cycloalkenyl carbonates (methyl cyclohexen-2-yl carbonate, methyl cyclohepten-2-yl carbonate, methyl 5-methoxycarbonylcyclohexen-2-yl carbonate, methyl cyclohexenyl carbonate, tert-butyl 5-methoxycarbonyloxy-1,2,5,6-tetrahydropyridinedicarboxylate) with dibenzylamines ((C6H5CH2)2NH, (C6H5CH2)(4-CH3OC6H4CH2)NH, (4-CH3OC6H4CH2)2NH) was achieved in water under heterogeneous conditions by use of a palladium complex of (3R,9aS)-3-[2-(diphenylphosphino)phenyl]-2-phenyltetrahydro-1H-imidazo[1,5-a]indole-1-one anchored on polystyrene-poly(ethylene glycol) copolymer resin to give the corresponding cycloalkenylamines with high enantiomeric selectivity (90-98% ee).     

Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: asymmetric synthesis of allylic sulfides,allylic sulfones,and allylic alcohols

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1 a-c and racemic acyclic allylic carbonates rac-3 aa and rac-3 ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate 1 a (>/=99 % ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2 aa, 2 b, 2 c, 2 d and 4 a-c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5 aa, 5 b, 5 ab, 6 aa-ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6 aa, 6 ab, 6 ac and 6 bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1 da and rac-1 db with 2-pyrimidinethiol gave the allylic sulfide 5 c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1 a and of the acyclic carbonates rac-3 aa and rac-3 ba with 2-pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1 a as well as of the highly enriched enantiomers 1 a (>/=99 % ee) and ent-1 a (>/=99 % ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1 a, ent-1 a (>/=99 % ee) and ent-1 c (>/=99 % ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1 a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1 a-c, ent-3 aa and ent-3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9 a-c (>/=99 % ee) and acyclic allylic alcohols 10 a (>/=99 % ee) and 10 b (99 % ee), respectively.     

Palladium-Catalyzed Allylic Coupling of 1,2,3-Triazolo[4,5-d]pyrimidines (8-Azapurines)

The palladium-catalyzed coupling of the sodium salt of 7-amino-1,2,3-triazolo[4,5-d]pyrimidine (8-azaadenine, 1) with allylic phosphates or carbonates resulted in mixtures of 2- and 3-substituted 1,2,3-triazolopyrimidines, which were separated by chromatography. 1-Substituted triazolopyrimidines were not isolated from these reactions. Regioselectivity (and stereoselectivity) was also observed for substitution of the allylic moiety when more than one isomer is possible from the reaction. The use of 5-amino-1,2,3-triazolo[4,5-d]pyrimidin-7-ones (8-azaguanine, 2), instead of 8-azaadenine, also resulted in mixtures. Alternate syntheses of the 3-allyl-1,2,3-triazolo[4,5-d]pyrimidines confirmed the structures of these compounds.     

Palladium-catalyzed allylation of imines with allyl alcohols

A catalytic system, Pd(OAc)2 (10 mol %)-P(n-Bu)3 (20 mol %)-Et3B (360 mol %), promotes allylic alcohols to undergo the allylation of anisidine-imines of aromatic and aliphatic aldehydes and furnishes homoallylamines in good to moderate yields. The reaction shows unique stereoselectivity, giving anti-isomers selectively. [reaction: see text]     

Allylic etherification via Ir(I)/Zn(II) bimetallic catalysis

[reaction: see text] An efficient allylic etherification of aliphatic alcohols with allylic carbonates has been achieved by an iridium catalysis using stoichiometric zinc alkoxides or a two-component bimetallic catalytic system where the Ir(I) catalyst acts on allylic carbonates to generate electrophiles while aliphatic alcohols are separately activated by Zn(II) coordination to function as nucleophilies. This reaction occurs with complete regiospecificity and tolerates a wide range of functional groups.     

Palladium-catalyzed deracemization of allylic carbonates in water with formation of allylic alcohols: hydrogen carbonate ion as nucleophile in the palladium-catalyzed allylic substitution and kinetic resolution

The palladium-catalyzed deracemization of racemic cyclic and acyclic allylic methyl carbonates in water in the presence of N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphophino)benzamide] proceeds with high enantioselectivities to give the corresponding allylic alcohols in high yields. This deracemization involves a palladium-catalyzed allylic substitution with the in-situ-formed hydrogen carbonate ion and an irreversible decomposition of the intermediate allylic hydrogen carbonates, with formation of the corresponding allylic alcohols. The palladium-catalyzed reaction of racemic cyclic allylic acetates with potassium hydrogen carbonate in water in the presence of the chiral bisphosphane proceeds with a highly selective kinetic resolution to give the corresponding allylic alcohols and allylic acetates.     

Highly enantioselective syntheses of heterocycles via intramolecular Ir-catalyzed allylic amination and etherification

[reaction: see text] Enantioselective Ir-catalyzed intramolecular allylic aminations and etherifications are described. Up to 97% ee was achieved using catalysts prepared by in situ activation of mixtures of phosphorus amidites and [Ir(COD)Cl]2. Sequential aminations of bis-allylic carbonates, involving an inter- followed by an intramolecular reaction, gave trans-N-benzyl-2,5-divinylpyrrolidine and trans-N-benzyl-2,6-divinylpiperidine with > or = 99% ee. New phosphorus amidites as well as improved conditions for intermolecular aminations are reported.     

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.     

Palladium-catalyzed reactions of arylindium reagents prepared directly from aryl iodides and indium metal

Treatment of aryl iodides with indium metal in the presence of lithium chloride leads to the formation of an organoindium reagent capable of participating in cross-coupling reactions under transition-metal catalysis. Combination with aryl halides in the presence of 5 mol % Cl2Pd(dppf) furnishes biaryl compounds in good yields; similarly, reaction with acyl halides or allylic acetates/carbonates in the presence of 5-10 mol % palladium catalyst leads to arylketones and allylic substitution products, respectively, in moderate yields. The reactions are tolerant of the presence of protic solvents, and approximately 85% of the indium metal employed can be recovered by reduction of the residual indium salts with zinc(0).     

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]     

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]     

Pd-catalyzed asymmetric allylic amination of Morita-Baylis-Hillman adduct derivatives using chiral diaminophosphine oxides: DIAPHOXs

[reaction: see text] Asymmetric allylic amination of allylic carbonates prepared from racemic Morita-Baylis-Hillman adducts proceeded in the presence of Pd catalyst, chiral diaminophosphine oxide (DIAPHOX), and BSA, affording the corresponding chiral aza-Morita-Baylis-Hillman adduct derivatives in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds such as chiral cyclic beta-amino acids.     

Very efficient phosphoramidite ligand for asymmetric iridium-catalyzed allylic alkylation

[reaction: see text] Linear or branched allylic carbonates or acetates undergo enantioselective iridium-catalyzed allylic substitution with sodium malonate. The reaction is wide in scope and affords the branched product in high yield and with high regio- (up to >99:1) and enantioselectivity (up to 98%). Ten aromatic or aliphatic substrates were successfully tested.     

1,2-Bis(diphenylphosphino)carborane as a dual mode ligand for both the Sonogashira coupling and hydride-transfer steps in palladium-catalyzed one-pot synthesis of allenes from aryl iodides

[reaction: see text] One-pot allene synthesis from aryl iodides 1 and propargyldicyclohexylamine 2 proceeded in the presence of Pd(2)(dba)(3).CHCl(3) catalyst (2.5 mol %), 1,2-bis(diphenylphosphino)carborane 5 (10 mol %), CuI (15 mol %), and Et(3)N (150 mol %) to give the corresponding allenes 4 in good to high yields. Electron-deficient bidentate phosphines, such as 1,2-bis(diphenylphosphino)carborane 5 and (C(6)F(5))(2)PC(2)H(4)P(C(6)F(5))(2), play the role of a dual mode ligand for both the Sonogashira coupling and hydride-transfer reactions.     

New versatile Pd-catalyzed alkylation of indoles via nucleophilic allylic substitution: controlling the regioselectivity

[reaction: see text] A systematic study addressed toward the optimization of the Pd-catalyzed alkylation of indoles by allylic carbonates is presented. The protocol uses a catalytic amount of [PdCl(pi-allyl)](2)/phosphine as a promoting agent, providing allylindoles in excellent yields. The regioselectivity of the reaction can be controlled by a proper choice of the base and the reaction media. The method proved to be effective also for intramolecular allylic alkylations of indolyl carbonates, providing a flexible route to fused indole alkaloids.     

A novel amphiphilic chiral ligand derived from D-glucosamine. Application to palladium-catalyzed asymmetric allylic substitution reaction in an aqueous or an organic medium, allowing for catalyst recycling

A novel amphiphilic phosphinite-oxazoline chiral compound, 2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[4-((diethylamino)methyl)phenyl]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline (1), has been prepared from natural D-glucosamine hydrochloride. The newly prepared complex, [Pd(2-methyl-4,5-[4,6-O-benzylidene-3-O-bis[(4-((diethylmethylammonium)methyl)phenyl)]phosphino-1,2-dideoxy-alpha-D-glucopyranosyl]-[2,1-d]-2-oxazoline)(eta3-C3H5)]3+ x 3BF4- (3), is soluble in water and an efficient catalyst for asymmetric allylic substitution reaction in water or an aqueous/organic biphasic medium (up to 85% ee). This catalytic system offers an easy separation of the aqueous catalyst phase from the product phase and allows recycling of the catalyst phase. In addition, compound 1 also works as an effective ligand for the palladium-catalyzed reaction under conventional homogeneous conditions in an organic medium, in which the catalyst (Pd-1 complex) can be recovered by simple acid/base extraction and reused in the second reaction.     

Allylic alcohol transposition by ortho ester-initiated carbonate extension. synthesis of the vasodilator 11(R),12(S),15(S)-trihydroxyeicosa- 5(Z),8(Z),13(E)-trienoic acid

[reaction: see text] The title compound 1 was obtained via methyl ester 2, which was synthesized in four steps from an isomeric 11,14,15-triol ester 5. In the key step, Boc orthoformate 9 was treated with TMS triflate to initiate intramolecular nucleophilic substitution with allylic transposition, forming cyclic carbonates 10 and 11.