Catalytic allylic alkylation via the cross-dehydrogenative-coupling reaction between allylic sp3 C-H and methylenic sp3 C-H bonds

A catalytic allylic alkylation was developed via the cross-dehydrogenative-coupling reaction of allylic sp3 C-H and methylenic sp3 C-H catalyzed by copper bromide and cobalt chloride in the presence of an oxidizing reagent, t-BuOOH. This methodology provides a direct way to use allylic sp3 C-H bonds for forming C-C bonds.     

Retention of regiochemistry and chirality in the ruthenium catalyzed allylic alkylation of disubstituted allylic esters

The regiospecific nucleophilic substitution during the ruthenium catalyzed allylic alkylation of 1,3-unsymmetrical disubstituted allylic esters was demonstrated. The nucleophile was selectively introduced at the position originally substituted with leaving group in the 2-DPPBA or ip-pybox ligated [RuCl(2)(p-cymene)](2) catalyzed allylic alkylation of 1,3-unsymmetrical disubstituted allylic esters. The chirality of the optically active allylic esters was also transferred to the alkylated products.     

Pd.Et3B-catalyzed alkylation of amines with allylic alcohols

A combination of catalytic amounts of Pd (0.05 mmol) and Et3B (0.3 mmol) promotes allylic alkylation of primary and secondary aromatic and aliphatic amines (1.0 mmol) by the direct use of allylic alcohols, providing tertiary amines in excellent yields under mild conditions (room temperature approximately 50 degrees C).     

C-N bond cleavage of allylic amines via hydrogen bond activation with alcohol solvents in Pd-catalyzed allylic alkylation of carbonyl compounds

Hydrogen-bond-activated C-N bond cleavage of allylic amines was realized in Pd-catalyzed allylic alkylation to form the C-C bond product. The method could be expanded to a series of allylic amines and carbonyl compounds with excellent results. It provides a new and convenient access to C-C bond formation based on Pd-catalyzed allylic alkylation of allylic amines by using only inexpensive alcohol solvents.     

Deacylative allylation: allylic alkylation via retro-Claisen activation

A new method for allylic alkylation of a variety of relatively nonstabilized carbon nucleophiles is described herein. In this process of "deacylative allylation", the coupling partners, an allylic alcohol and a ketone pronucleophile, undergo in situ retro-Claisen activation to generate an allylic acetate and a carbanion. In the presence of palladium, these reactive intermediates undergo catalytic coupling to form a new C-C bond. In comparison to unimolecular decarboxylative allylation, a commonly utilized method for allylation of carbon anions, deacylative allylation is an intermolecular process. Moreover, deacylative allylation allows the direct coupling of readily available allylic alcohols. Lastly, the full utility of deacylative allylation is demonstrated by the rapid construction of a variety 1,6-heptadienes via 3-component couplings.     

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.     

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%).     

Iodine-catalyzed allylic alkylation of sulfonamides and carbamates with allylic alcohols at room temperature

A highly efficient iodine-catalyzed allylic alkylation of a wide variety of sulfonamides and carbamates with allylic alcohols is reported herein. The reaction is operationally straightforward and proceeds under very mild conditions at room temperature in good to excellent yields (up to 99%).     

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.     

Regio- and enantiospecific rhodium-catalyzed arylation of unsymmetrical fluorinated acyclic allylic carbonates: inversion of absolute configuration

The transition metal-catalyzed allylic substitution with unstabilized carbon nucleophiles represents an important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a new regio- and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical chiral nonracemic allylic alcohol derivatives with aryl zinc bromides. This study demonstrates that the hydrotris(pyrazolyl)borate rhodium catalyst and zinc(II) halide salt are crucial for efficiency, while the addition of lithium bromide to the catalyst is necessary for obtaining optimal regiospecificity. The stereochemical course of this reaction was established through the synthesis of (S)-ibuprofen, which demonstrated that the alkylation proceeds with net inversion of absolute configuration consistent with direct addition of the nucleophile to the metal center followed by reductive elimination.     

Effective synthesis of bicyclodienes via palladium-catalyzed asymmetric allylic alkylation and ruthenium-catalyzed cycloisomerization

[n.3.0]Bicycles (n = 3–6) can be synthesized using palladium-catalyzed asymmetric allylic alkylation followed by ruthenium-catalyzed cycloisomerization. New types of triarylphosphino-1,2-diaminooxazoline ligands show the same high levels of enantioselectivity observed with Trost ligand when employed in Pd-catalyzed allylic alkylation reactions. The enyne products of these allylic alkylation reactions were further elaborated using a Ru-catalyzed redox isomerization process, for which a mechanism is proposed.     

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.     

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).     

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.     

Palladium-catalyzed regio- and enantioselective allylic alkylation of bis allylic carbonates derived from Morita-Baylis-Hillman adducts

Morita-Baylis-Hillman diene adducts are used as substrates in the palladium-catalyzed asymmetric allylic alkylation reaction with oxygen and carbon nucleophiles in good regio- and enantioselectivity.     

Enantiospecific and regioselective rhodium-catalyzed allylic alkylation: diastereoselective approach to quaternary carbon stereogenic centers

The enantiospecific and regioselective rhodium-catalyzed allylic alkylation of a series of chiral nonracemic allylic carbonates, followed by ozonolysis and reductive lactonization, provides a convenient route to optically active gamma-lactones. Sequential alkylation and reductive alkylation furnished the alpha-quaternary-beta-ternary substituted gamma-lactone derivative as a >/=10:1 mixture of diastereoisomers.     

Solid-phase synthesis of 4-methylene pyrrolidines and allylic amines using palladium-activated allylic linkers

The solid-phase synthesis of 4-methylene pyrrolidines and allylic amines has been achieved using palladium-catalysed nucleophilic cleavage of allylic linkages. Six pyrrolidines were synthesised in five steps from a carboxyethyl resin 20, where the key transformations included a Lewis-acid promoted imino-Sakurai type reaction and reductive alkylation prior to the final palladium-catalysed cyclisation cleavage of the allylic carboxylate linkage. Allylic carboxylate resin 22 was also shown to undergo "traceless" cleavage using various hydride sources in the presence of catalytic palladium. A more robust allylic ether linkage was also investigated. Starting from a phenol resin 36, a number of 3-aryl-allylamines were prepared using a palladium-catalysed nucleophilic cleavage reaction.     

Efficient metal-catalyzed direct benzylation and allylic alkylation of 2,4-pentanediones

[reaction: see text] A highly effective metal-catalyzed benzylation and allylic alkylation of 2,4-pentanediones has been developed. This new bismuth-catalyzed direct carbon-carbon bond forming reaction provides the corresponding monoalkylated dicarbonyl compounds in high yields after short reaction times using the lowest amounts of catalyst (1 mol %) and the free alcohol. In addition, a new route to substituted indenes is presented.     

Role of planar chirality of S,N- and P,N-ferrocene ligands in palladium-catalyzed allylic substitutions

Palladium-catalyzed asymmetric allylic substitutions using thioether and phosphino derivatives of ferrocenyloxazoline as ligands have been investigated with a focus on studying the role of planar chirality. In allylic alkylation, up to 98% ee and 95% ee were achieved with S,N- and P,N-ligands, respectively. In allylic amination, 97% ee was realized with P,N-ligands in the presence of TBAF. Several palladium allylic complexes were characterized by X-ray diffraction and/or solution NMR. Thioether derivatives of ferrocenyloxazolines with only planar chirality showed lower enantioselectivity in the allylic alkylation except 5c because of the formation of a new chirality on sulfur atom during the coordination of sulfur with palladium. On the other hand, in the planar chiral P,N-ligands without central chirality, (Sp)-11a-c there was no such disturbance and comparatively higher enantioselectivity in both palladium-catalyzed allylic alkylation and amination was provided.     

Asymmetric allylic alkylation of cycloalkenediol diacetates using a chiral phosphine ligand bearing a carboxyl group

Asymmetric induction in the allylic alkylation of cycloalkenediol diacetates was performed using a chiral alkylphosphine ligand bearing a carboxyl group, 3-(diphenylphosphino)butanoic acid. An increase in enantiomeric excess of the monoalkylated products of cis-cycloalkenediol diacetates was observed through a sequential asymmetric allylic alkylation–kinetic resolution process.