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.     

Ruthenium complex-catalyzed allylic alkylation of carbonucleophiles with allylic carbonates

Allylic carbonates except for allyl methyl carbonate reacted with carbonucleophiles such as ethyl acetoacetate in the presence of a catalytic amount of Ru(cod)(cot) [cod = cycloocta-1,5-diene, COT = cycloocta-1,3,5-triene] in N-methylpiperidine at 80°C to give the corresponding monoallylated carbonucleophiles in high yields with high regioselectivity. The regioselectivity was quite different from that in the palladium-catalyzed reactions. The allylation of carbonucleophiles using allyl methyl carbonate selectively gave the diallylated carbonucleophiles in high yields.     

Palladium-catalyzed allylic alkenylation of allylic alcohols with n-butyl acrylate

Various allylic alcohols reacted with n-butyl acrylate in the presence of p-toluenesulfonic anhydride and palladium catalysts to yield the corresponding n-butyl 2,5-dienoates with high regioselectivity.     

醋酸烯丙酯选择性地合成烯丙基硒醚

醋酸烯丙酯被Pd(PPh3)4-SmI2还原，并发生中间体π-烯丙基钯络合物的极性 反转，而后与芳基硒溴化物作用，生成烯丙基硒醚．     

Iridium-catalyzed allylic vinylation and asymmetric allylic amination reactions with o-aminostyrenes

An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.     

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.     

Asymmetric allylic alkylation of acyclic allylic ethers with organolithium reagents

A highly efficient, regio- and enantioselective Cu(I) /phosphoramidite-catalyzed asymmetric allylic alkylation of allyl ethers with organolithium reagents is reported. The use of organolithium reagents is essential for this catalytic C?C bond formation due to their compatibility with different Lewis acids. The versatility of allylic ethers under the copper-catalyzed reaction conditions with organolithium reagents is demonstrated in the shortest synthesis of (S)-Arundic acid.     

Direct, enantioselective iridium-catalyzed allylic amination of racemic allylic alcohols

The direct route: Iridium-catalyzed direct conversion of branched allylic alcohols into enantioenriched branched primary allylic amines is highly regio- and enantioselective (see scheme; coe=cyclooctene).     

Copper-free asymmetric allylic alkylation using grignard reagents on bifunctional allylic bromides

A series of substrates containing a vinylic bromide were employed in a copper-free methodology using bidendate NHC ligands. The desired compounds are generally obtained with good enantioselectivity and good regioselectivity. Importantly the copper-catalyzed system afforded a lower enantioselectivity value. The catalytic products could be transformed into a broad scope of new 1,1-disubstituted olefins in a single step transformation without erosion of the enantioselectivity.     

Gold-catalysed allylic alkylation of aromatic and heteroaromatic compounds with allylic alcohols

Friedel-Crafts allylic alkylation of a wide variety of aromatic and heteroaromatic compounds with allylic alcohols catalysed by AuCl(3) (5 mol%) under mild conditions at room temperature was accomplished in good to excellent yields (up to 99%) and regioselectivity.     

Some allylic substituent effects in ring-closing metathesis reactions: allylic alcohol activation

[formula: see text] Dienes 2a-e were used to study allylic substituent effects in the ring-closing metathesis reaction (RCM). Both the steric and electronic character of the allylic substituents were found to influence alkene reactivities. Free allylic hydroxyl groups exert a large activating effect on the RCM reaction rates.     

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.     

Gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols

A highly efficient gold- and silver-catalyzed allylic alkylation of 1,3-dicarbonyl compounds with allylic alcohols has been developed. The reaction was shown to proceed expediently for a wide variety of 1,3-dicarbonyl compounds and allylic alcohols, including 1° and terminal ones, under very mild conditions at room temperature in good to excellent yields (55-96%).     

Palladium-catalyzed enantioselective 1,3-rearrangement of racemic allylic sulfinates: asymmetric synthesis of allylic sulfones and kinetic resolution of an allylic sulfinate

Described is an asymmetric synthesis of cyclic and acyclic allylic S-aryl and S-alkyl sulfones through a highly selective palladium(0)-catalyzed 1,3-rearrangement of racemic allylic sulfinates. Treatment of racemic cyclic and acyclic allylic S-tolyl- and S-tert-butylsulfinates with Pd(2)(dba)(3).CHCl(3) as precatalyst and N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)benzamide] as ligand for the palladium atom afforded the corresponding isomeric allylic S-tolyl and S-tert-butyl sulfones of 93-99% ee in 82-96% yield. The rearrangement of the allylic sulfinates most likely proceeds in an intermolecular fashion via formation of a cationic pi-allylpalladium complex and the sulfinate ion. The racemic allylic sulfinates were obtained from the corresponding racemic alcohols and racemic tolylsulfinyl chloride and racemic tert-butylsulfinyl chloride, respectively, in high yields. Rearrangement of the racemic tert-butylsulfinic acid 2-cyclooct-1-enyl ester with Pd(2)(dba)(3).CHCl(3) and the bisphosphane was accompanied by a highly selective kinetic resolution of the substrate and gave at 50% conversion the (R)-configured sulfinate as mixture of the S(S) and R(S) diastereomers of 92% ee and 85% ee and the (S)-configured 3-tert-butylsulfonyl cyclooctene sulfone 15a with 98% ee in almost quantitative yields.     

Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines

[reaction: see text] A useful method for the conversion of prochiral allylic alcohols to chiral allylic amines of high enantiopurity is reported. N-(4-Methoxyphenyl)trifluoroacetimidates are excellent substrates for the palladium(II)-catalyzed allylic imidate rearrangement as the allylic trifluoroacetamide products can be deprotected in two steps to provide chiral nonracemic allylic amines. Di-mu-chlorobis[(eta(5)-(S)-(pR)-2-(2'-(4'-isopropyl))oxazolinylcyclopentadienyl,1-C,3'-N))(eta(4)-tetraphenylcyclobutadiene)cobalt]dipalladium (6a, COP-Cl) is a superior catalyst because it does not require activation with silver salts and provides rearranged allylic trifluoroacetamides in good yields and high enantiomeric purities.     

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.     

Regioselective synthesis of trifluoromethyl group substituted allylic amines via palladium-catalyzed allylic amination

The palladium-catalyzed regioselective allylic amination of α-trifluoromethylated allyl acetate occurred using Pd(OAc)₂/DPPE and [Pd(π-allyl)(cod)]BF₄/DPPF. The selective formation of the γ-product was attained by Pd(OAc)₂/DPPE, while the α-product was obtained using [Pd(π-allyl)(cod)]BF₄/DPPF.     

Enantioselective organocatalytic allylic amination

A new strategy for catalytic enantioselective allylic amination based on organocatalysis has been developed. Using a commercially available organocatalyst we demonstrate a direct highly enantioselective allylic electrophilic functionalization of alkylidene cyanoacetates and malononitriles with azodicarboxylates. The reaction is broad in scope and proceeds in high yields and with enantioselectivities up to 99%. Furthermore, we demonstrate the synthetic utility of the optically active products formed: highly diastereoselective Diels-Alder reaction, reduction, and formation of optically active building blocks, which are found in various important bioactive compounds such as quinacrine, chloroquine, and analogues thereof.     

Regioselective palladium-catalyzed allylic alkylations

Palladium-catalyzed allylic alkylations on asymmetrical allylic carbonates using a variety of chiral ligands gave good to excellent ee’s and poor to excellent regioselectivity depending on the nucleophile used.