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.     

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]     

Highly enantioselective regiodivergent allylic alkylations of MBH carbonates with phthalides

Phthalides were used for the first time in the allylic alkylation reactions with MBH carbonates for the creation of chiral 3,3-disubstituted phthalides. Highly enantioselective regiodivergent synthesis of γ-selective or β-selective allylic alkylation products was achieved by employing bifunctional chiral phosphines or multifunctional tertiary amine-thioureas as the catalyst, respectively. It was demonstrated that proper selection of catalysts and reaction conditions would differentiate an S(N)2'-S(N)2' pathway and an addition-elimination process, yielding different regioisomers of the allylic alkylation products in a highly enantiomerically pure form.     

Pd-catalyzed regioselective and stereospecific Suzuki-Miyaura coupling of allylic carbonates with arylboronic acids

The Pd-catalyzed Suzuki-Miyaura coupling reaction of unsymmetric 1,3-disubstituted secondary allylic carbonates with arylboronic acids has been developed in a wet solvent under a base-free system to afford allyl-aryl coupling products in a high level of isolated yields with complete regio- and E/Z-selectivities with good to excellent chemoselectivities. The coupling reaction of optically active allyl carbonates gave allyl-aryl coupling products with excellent enantioselectivities with inversion of the stereochemistry. This coupling method was successfully applied to the synthesis of (S)-naproxen.     

Nickel‐Catalyzed Reductive Allylation of Tertiary Alkyl Halides with Allylic Carbonates

The construction of all C(sp³) quaternary centers has been successfully achieved under Ni‐catalyzed cross‐electrophile coupling of allylic carbonates with unactivated tertiary alkyl halides. For allylic carbonates bearing C1 or C3 substituents, the reaction affords excellent regioselectivity through the addition of alkyl groups to the unsubstituted allylic carbon terminus. The allylic alkylation method also exhibits excellent functional‐group compatibility, and delivers the products with high E selectivity.     

Palladium-catalyzed carbon dioxide elimination-fixation reaction of 4-methoxycarbonyloxy-2-buten-1-ols

A new type of palladium-catalyzed CO(2) recycling reaction using allylic carbonates is described. Reaction of trans-4-methoxycarbonyloxy-2-buten-1-ols in the presence of a palladium catalyst produces cyclic carbonates having a vinyl group via a CO(2) elimination-fixation process. A variety of allylic carbonates participate in the reaction giving cyclic carbonates with high efficiencies. Stereoselective construction of trans-cyclic carbonates is achieved by using nonsymmetric substrates. An enantiospecific reaction proceeds to give chiral cyclic carbonate when a chiral methyl-substituted substrate is subjected to the reaction conditions.     

Organocatalytic asymmetric allylic alkylation of sulfonylimidates with Morita-Baylis-Hillman carbonates

The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was accomplished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)2AQN.The corresponding allylic alkylation products were obtained in good yields with high stereoselectivities (up to 99% ee,89:11 dr).     

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.     

Synthesis of allyl aryl sulphides by palladium(0)-mediated alkylation of thiols

Various allylic aryl sulphides are readily prepared in high yields by the palladium(0)-catalyzed S-alkylation of allylic carbonates by various aromatic thiols.     

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.     

Enantioselective synthesis of acyclic allylic esters catalyzed by a palladium/BINAP(S) system

The synthesis of chiral nonracemic acyclic allylic pivalates via the Pd-catalyzed allylic substitution of racemic allylic carbonates is presented. Good to excellent enantioselectivities (up to 90%) were observed in several cases. An extraordinarily high preference for the production of the branched regioisomeric product is seen when starting from 3-buten-2-yl and crotyl substrates. A significant kinetic resolution (k_rel = 38) of the 1,3-dimethylallyl substrate was also observed, leading to the production of esters of both enantiomers of an allylic alcohol with a single enantiomer of catalyst.     

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh₃)Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh₃)Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product. Remarkably, this methodology is selective for the activation of tertiary allyl carbonates even in the presence of secondary allyl carbonates. This contrasts with the selectivity observed in cobalt-catalyzed allylic alkylations enabled by visible light photocatalysis. Mechanistic insights by means of experimental and computational investigations support a Co(I)/Co(III) catalytic cycle.     

Effects of catalyst activation and ligand steric properties on the enantioselective allylation of amines and phenoxides

[reaction: see text] The yields, enantioselectivities, and regioselectivities of the reactions of amines and phenoxides with allylic carbonates in the presence of a metallacyclic iridium catalyst were compared. These data show that both preactivation of the catalyst and the size of the ligand affect the yield, enantioselectivity, and regioselectivity. With the activated catalyst containing a bis-naphthethylamino group, the allylic amination and etherification of a broad range of allylic carbonates occurred in high yields and with high regioselectivities and enantioselectivities.     

Highly regioselective Pd-catalyzed allylic alkylation of fluorobis(phenylsulfonyl)methane

A highly regioselective palladium-catalyzed allylic alkylation of fluorobis(phenylsulfonyl)methane has been studied. Using different allylic carbonates, a variety of terminal mono-fluoromethylated compounds were achieved in 85-99% yields with high regioselectivities.     

Conclusive evidence for a retention-retention pathway for the molybdenum-catalyzed asymmetric alkylation

Enantiomerically enriched, deuterated branched carbonates (Z)-(S)-PhCH(O2COMe)-CH=CHD (1a), (Z)-(R)-PhCH(O2COMe)CH=CHD (2a), and linear carbonate (E)-(S)-PhCH=CHCHD(O2COMe) (12) were employed as probes in the Mo-catalyzed asymmetric allylic alkylation with sodium dimethyl malonate, catalyzed by ligand complex 10 derived from the mixed benzamide/picolinamide of (S,S)-trans-diaminocyclohexane and (norbornadiene)Mo(CO)4. X-ray crystallography, along with solution NMR structural analysis of the pi-allyl intermediate and competition experiments, conclusively established the reaction proceeded via a retention-retention pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic alkylations, which proceed via an inversion-inversion pathway.     

Regio- and enantioselective iridium-catalyzed intermolecular allylic etherification of achiral allylic carbonates with phenoxides

An enantioselective and regioselective iridium-catalyzed allylic etherification is described. The reaction of sodium and lithium aryloxides with achiral (E)-cinnamyl and terminal aliphatic allylic electrophiles in the presence of 2 mol % of an iridium-phosphoramidite complex provides chiral allylic aryl ethers in high yields and excellent levels of regio- and enantioselectivity. Lithium aryloxides containing a single substituent at an ortho, meta, or para position as well as sterically hindered phenoxides were tolerated. Reactions in THF displayed the most suitable balance of rate, regio-, and enantioselectivity. High ee's were also observed for the products from the reaction of alkyl (E)-allylic carbonates.     

Iridium-catalyzed selective N-allylation of hydrazines

A highly chemo- and regioselective iridium-catalyzed allylic amination is described. The reaction of various hydrazones and hydrazides with allylic carbonates proceeds at ambient temperature in the presence of an [Ir(COD)Cl]₂/pyridine catalyst, ammonium iodide, and diethylzinc to afford the corresponding N-allylation products in high yields with excellent chemo- and regioselectivities. Only the more nucleophilic nitrogen of a given hydrazine derivative undergoes the C-N bond formation to yield a branched allylic isomer as the exclusive product.     

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.     

Copper-catalyzed gamma-selective and stereospecific substitution reaction of allylic carbonates with diboron: efficient route to chiral allylboron compounds

A copper-catalyzed gamma-selective and stereospecific substitution reaction of allylic carbonates with a diboron reagent affording allylboron compounds is described. Boryl group was selectively introduced at the gamma-position of the leaving carbonate group. Functionalized allylboronates that have an acetal, ester, or isolated alkene were prepared. The reaction of optically active allylic carbonates underwent complete alpha-to-gamma chirality transfer with anti-stereochemistry to produce optically active allylboronates having a boron-substituted stereogenic center.     

Conversion of Allylic Alcohols into Allylic Nitromethyl Compounds via a Palladium-Catalyzed Solvolysis: An Enantioselective Synthesis of an Advanced Carbocyclic Nucleoside Precursor(1)

A two-step reaction sequence to homoallylic nitro compounds from allylic alcohols is presented. Ethoxy carbonylation of the alcohols with ethyl chloroformate provides the corresponding allylic ethyl carbonates in high yields. Exposure of these substrates to catalytic palladium(0) in CH(3)NO(2) initiates a reaction sequence, ionization-decarboxylation-nitromethylation, that culminates with the formation of nitroalkenes. The regio- and stereochemical outcomes of the nitromethyl allylation reaction can be explained by the behavior of the transient pi-allylpalladium complexes. This methodology serves as a centerpiece for the synthesis of an important carbocyclic nucleoside intermediate.