Allylic Cross-coupling Research Articles

Recent development of allyl–allyl cross-coupling and its application in natural product synthesis

This review summarises the significant advancements of allyl–allyl cross-coupling reaction that have provided access to a wide variety of 1,5 dienes and its application in natural product synthesis.

Regiocontrolled synthesis of enantioenriched 2-substituted dehydropiperidines by stereospecific allyl-allyl cross-coupling of a chiral allylic boronate.

The palladium-catalyzed cross-coupling of an optically enriched dehydropiperidinyl boronate with cinnamyl carbonates was optimized to minimize stereochemical erosion. Although the coupling of two unsymmetrical allyl fragments may generate four possible regioisomers, the optimal procedure using (p-CF3C6H4)3P as the ligand affords linear 2-allylated 3,4-dehydropiperidines exclusively (>98 : 2 rr) with enantiospecificity up to 99%.

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions.

The allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions is described. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes, allylic carbonates, and a silylboronate produces the corresponding homoallylic alcohol derivatives. This process involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(I) species and the subsequent palladium-catalyzed allylic substitution.

ChemInform Abstract: Copper‐Catalyzed γ‐Selective and Stereospecific Allylic Cross‐Coupling with Secondary Alkylboranes.

AbstractUtilisation of triphenylphosphine as a ligand allows for the coupling of alkyl‐9‐BBN derivatives with a variety of silicon‐ and non‐silicon‐containing cyclic and acyclic allylic (Z)‐phosphates.

Copper-catalyzed enantioselective allylic cross-coupling with alkylboranes

We have presented full details of our work on alkylboranes, which we have introduced as new reagents for copper-catalyzed SN2′-type enantioselective allylic substitutions. The copper catalysis delivered enantioenriched chiral products containing tertiary or quaternary carbon stereogenic centers branched with functionalized sp3-alkyl groups. The wide availability of alkylboranes via the established alkene hydroboration reaction is an attractive feature of these transformations. Various functional groups are tolerated in the substrates. A reaction pathway involving addition–elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.

ChemInform Abstract: Construction of Quaternary Stereogenic Carbon Centers Through Copper‐Catalyzed Enantioselective Allylic Cross‐Coupling with Alkylboranes.

A combination of an in situ generated chiral CuI/DTBM-MeO-BIPHEP catalyst system and EtOK enabled the enantioselective SN2′-type allylic cross-coupling between alkylborane reagents and γ,γ-disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp3-alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross-coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.

ChemInform Abstract: Catalytic Stereospecific Allyl—Allyl Cross‐Coupling of Internal Allyl Electrophiles with AllylB(pin).

Application of internal electrophiles in catalytic stereospecific allyl–allyl cross-coupling enable the rapid construction of multisubstituted 1,5-dienes, including those with all carbon quaternary centers. Compounds with minimal steric differentiation can be synthesized with high enantiomeric excess.

Cu-Catalyzed Enantioselective Allylic Cross-Coupling with Alkylboranes

Key words copper - alkylboranes - allylic substitution - all-carbon quaternary centers

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Cross‐Coupling with Alkylboranes

A combination of an in situ generated chiral Cu(I) /DTBM-MeO-BIPHEP catalyst system and EtOK enabled the enantioselective SN 2'-type allylic cross-coupling between alkylborane reagents and γ,γ-disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp(3) -alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross-coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.

Pd(Quinox)-Catalyzed Allylic Relay Suzuki Reactions of Secondary Homostyrenyl Tosylates via Alkene-Assisted Oxidative Addition.

Pd-catalyzed allylic relay Suzuki cross-coupling reactions of secondary alkyl tosylates, featuring a sterically-hindered oxidative addition and precise control of β-hydride elimination, are reported. The identification of a linear free energy relationship between the relative rates of substrate consumption and the electronic nature of the substrate alkene suggests that the oxidative addition requires direct alkene involvement. A study of the effect of chain length on the reaction outcome supports a chelation-controlled oxidative addition.

Catalytic Enantioselective Allyl–Allyl Cross-Coupling with a Borylated Allylboronate

Catalytic enantioselective allyl-allyl cross-coupling of a borylated allylboronate reagent gives versatile borylated chiral 1,5-hexadienes. These compounds may be manipulated in a number of useful ways to give functionalized chiral building blocks for asymmetric synthesis.

Allyl–Allyl Cross-Coupling Reactions Catalyzed by Triflimide

Allyl–Allyl Cross-Coupling Reactions Catalyzed by Triflimide

Palladium-Catalyzed Allylic Cross-Coupling Reactions of Primary and Secondary Homoallylic Electrophiles

The Pd(0)-catalyzed allylic cross-coupling of homoallylic tosylate substrates using boronic acids and pinacol esters is reported. The reaction uses 2-(4,5-dihydro-2-oxazolyl)quinoline (quinox) as a ligand and is performed at ambient temperature. The scope of the reaction is broad in terms of both the boronate transmetalating reagent and the substrate and includes secondary tosylates. Mechanistic studies support an alkene-mediated S(N)2-type stereoinvertive oxidative addition of unactivated primary and secondary alkyl tosylates.

Triflimide-catalyzed allyl–allyl cross-coupling: a metal-free allylic alkylation

A highly efficient metal-free intermolecular C(sp3)-C(sp3) allyl-allyl cross-coupling protocol between allyl acetates and allyltrimethylsilanes, which proceeded smoothly in the presence of catalytic triflimide to form 1,5-dienes with good to excellent regioselectivity, has been developed.

Palladium-Catalyzed Asymmetric Allyl–Allyl Cross-Coupling

Key words palladium - enantioselective allyl–allyl cross-coupling - allyl chlorides - allyl boronates

Palladium‐Catalyzed Allyl Cross‐Coupling Reactions with In Situ Generated Organoindium Reagents

Inter- and intramolecular palladium-catalyzed allyl cross-coupling reactions, using allylindium generated in situ from allyl halides and indium, is demonstrated. Allylindium compounds may be effective nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions. A variety of allyl halides, such as allyl iodide, allyl bromide, crotyl bromide, prenyl bromide, geranyl bromide, and 3-bromocyclohexene afforded the allylic cross-coupling products in good to excellent yields. Stereochemistry of the double bond is retained in the allylic cross-coupling reactions. Electrophilic cross-coupling partners, such as aryl and vinyl halides, dibromoolefin, alkynyl iodide, and aryl and vinyl triflates participate in these reactions. The presence of various substituents, such as n-butyl, ketal, acetyl, ethoxycarbonyl, nitrile, N-phenylamido, nitro, and chloride groups on the aromatic ring of electrophilic coupling partners showed little effect on the efficiency of the reactions. The present conditions work equally well for not only intermolecular but also intramolecular palladium-catalyzed cross-coupling reactions. These methods provide an efficient synthetic method for the introduction of an allyl group, which can be easily further functionalized to afford an sp(2)- and sp-hybridized carbon. The present method complements existing synthetic methods as a result of advantageous features such as easy preparation and handling, thermal stability, high reactivity and selectivity, operational simplicity, and low toxicity of allylindium reagents.

Cooperative Catalysis by Indium and Palladium for the Allyl Cross-Coupling Reactions

Cooperative Catalysis by Indium and Palladium for the Allyl Cross-Coupling Reactions

A general, regioselective synthesis of substituted benzocyclobutenedione monoacetals

A general, regioselective synthesis of substituted benzocyclobutenedione monoacetals is reported. Palladium-catalyzed coupling of a variety of 4-chlorocyclobutenones with 3-(tri-n-butylstannyl)-3-cyclobutene-1,2-dione 2-(ethylene acetal) and heating up to 70-100 o C produces substituted benzocyclobutenedione monoacetals in good to excellent yields. This chemistry is presumed to proceed through palladium-catalyzed formation of a 3-(1-oxo-2-cyclobuten-4-yl)-3-cyclobutene-1,2-dione-2-(ethylene acetal) followed by a thermally induced ring opening to a dienyl ketene and subsequent six-electron electrocyclic ring closure and tautomerization. 2,3-Disubstitued 4-chlorocyclobutenones afford palladium intermediates which couple exclusively at the least-substituted allylic terminus. 2,3,4-Trisubstituted 4-chlorocyclobutenones have not been studied in detail; however, preliminary results suggest that regioselective allylic cross-coupling can be achieved. The methodology described provides an expedient and efficient route to previously difficult-to-prepare benzocyclobutenedione derivatives. These function as important synthetic intermediates in a variety of reactions developed in these and other laboratories

ChemInform Abstract: Improved Procedures for the Palladium‐Catalyzed Intermolecular Arylation of Cyclic Alkenes.

Abstract Improved procedures for the palladium-catalyzed, intermolecular, allylic cross-coupling of aryl halides and cyclic alkenes inhibit double-bond isomerization and accommodate many important functional groups.

Improved procedures for the palladium-catalyzed intermolecular arylation of cyclic alkenes

Improved procedures for the palladium-catalyzed, intermolecular, allylic cross-coupling of aryl halides and cyclic alkenes inhibit double-bond isomerization and accommodate many important functional groups.