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Synthesis of allenes by 1,3-substitution with carbon nucleophiles


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Cross-coupling of propargylic bromide with Grignard reagent enables a convenient method for the synthesis of terminal allenes. The reaction of propargylic bromide with 1.2 equivalents of Grignard reagent catalyzed by a complex of Ni(acac)2 and Ph3P in THF produces terminal allenes in good yields and high regioselectivities at room temperature.
Q. Li, H. Gau, Synlett, 2012, 23, 747-750.

Boron "ate" complexes derived from pinacol boronic esters and tert-butyl lithium undergo stereospecific transmetalation to copper cyanide, followed by coupling with alkynyl bromides, allyl halides, propargylic halides, β-haloenones, hydroxylamine esters, and acyl chlorides. This simple transformation converts primary and secondary alkylboronic esters to a wide array of useful compounds.
N. Xu, H. Liang, J. P. Morken, J. Am. Chem. Soc., 2022, 144, 11546-11552.

The palladium-catalyzed of triorganoindium reagents to propargylic esters afforded via an SN2' rearrangement allenes in good yields and with high regioselectivity. The reaction of chiral, nonracemic propargylic esters takes place with high anti-stereoselectivity providing allenes with high enantiomeric excess.
R. Riveiros, D. Rodríguez, J. P. Sestelo, L. A. Sarandeses, Org. Lett., 2006, 8, 1403-1406.

Copper-catalyzed γ-selective coupling between propargylic phosphates and alkylboron compounds affords multisubstituted allenes with various functional groups. The reaction of enantioenriched propargylic phosphates to give axially chiral allenes proceeds with excellent chirality transfer with 1,3-anti stereochemistry.
H. Ohmiya, U. Yokobori, Y. Makida, M. Sawmura, Org. Lett., 2011, 13, 6312-6315.

Copper-catalyzed alkylation and arylation of chiral propargylic phosphates using alkyl boranes and arylboronic esters as organoboron nucleophiles enables the asymmetric synthesis of trisubstituted allenes with excellent chirality transfer and regioselectivity, together with good functional group compatibility.
M. R. Uehling, S. T. Marionni, G. Lalic, Org. Lett., 2012, 14, 362-365.

The SN2′ reaction of propragyl mesylates with organozinc reagents was dramatically improved in DMSO as solvent, and the conversion of a chiral substrate was successfully achieved without loss of optical purity using a LiCl-free diorganozinc reagent.
K. Kobayashi, H. Naka, A. E. H. Wheatley, Y. Kondo, Org. Lett., 2008, 10, 3375-3377.

The β-alkoxide elimination reaction of aryl- or alkyl-subsituted propargylic ethers with Negishi reagent leads to allenes after hydrolysis, whereas TMS-substituted substrates afford alkynes. Subsequent coupling reactions of the zirconium intermediates with aryl iodides in the presence of Pd(PPh3)4/CuCl provide a straightforward route for the synthesis of multisubstituted allenes.
H. Zhang, X. Fu, J. Chen, E. Wang, Y. Liu, X. Li, J. Org. Chem., 2009, 74, 9351-9358.

An enantiospecific approach to the synthesis of optically active, trisubstituted allenes from chiral propargylic benzoates and arylboronic acids is catalyzed by a complex formed in situ from [{Rh(cod)Cl}2] and a readily available phosphoramidite ligand. The method furnishes substituted allenes in high yields and excellent enantiospecificity under mild conditions.
J. Ruchti, E. M. Carreira, Org. Lett., 2016, 18, 2174-2176.

Pd(PPh3)2Cl2/Ph3P catalyzes a reaction of propargyl acetates with 1.2 equivalents of an organoaluminum reagent in the presence of K2CO3 in THF to produce tri- or tetrasubstituted allenes in good to excellent yields and high regioselectivities at 60°C.
Z. Zhang, S. Mo, G. Zhang, X. Shao, Q. Li, Y. Zong, Synlett, 2017, 28, 611-614.

A neighboring boronate group in vicinal bis(boronic esters) provides a dramatic rate acceleration in transmetalation to copper and thereby enables unprecedented site-selective cross-couplings  allyl, alkynyl, and propargyl electrophiles as well as a simple proton. This cross-coupling operates under practical experimental conditions.
N. Xu, Z. Kong, J. Z. Wang, G. J. Lovinger, J. P. Morken, J. Am. Chem. Soc., 2022, 144, 17815-17823.

A transition-metal-free intermolecular Claisen rearrangement process enables to introduce allyl and allenyl groups into the α position of tertiary amides in good yield under mild conditions. In this transformation, amides were activated by trifluoromethanesulfonic anhydride to produce keteniminium ion intermediates that exhibit strong electrophilic activity.
Z.-J. Niu, L.-H. Li, X.-S. Li, H.-C. Liu, W.-Y. Shi, Y.-M. Liang, Org. Lett., 2021, 23, 1315-1320.

An efficient synthetic method provides tri- and tetra-substituted allenes by the reaction of allylindium reagents with 3°-propargyl alcohols. Allylindium reagents are generated in situ from indium and allyl bromides.
K. Lee, P. H. Lee, Org. Lett., 2008, 10, 2441-2444.

A Cu/Pd-catalyzed borylallenylation of alkynes with propargylic carbonates and bis(pinacolato)diboron enables the synthesis of boryl-substituted ene-allenes. Densely (tetra-, penta-, and hexa-) substituted ene-allenes were synthesized in acceptable yield with high regio- and stereoselectivity. More important molecule structures can be obtained by subsequent modifications.
S.-H. Yu, T.-J. Gong, Y. Fu, Org. Lett., 2020, 22, 2941-2945.

Conjugated allenynes can be accessed via a decarboxylative coupling of propargyl esters of propiolates. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to occur stereospecifically in an anti-SN2' fashion to provide a route to enantioenriched allenes.
M. K. Smith, J. A Tunge, Org. Lett., 2017, 19, 5497-5500.

A simple copper-catalyzed enantioselective synthesis of axially chiral chloroallenes from propargylic dichlorides leads to exclusive formation of the desired allenes with good enantioselectivities. Further transformations to trisubstituted allenes or terminal alkynes with a propargylic quaternary carbon center keep a high level of enantiopurity.
H. Li, D. Müller, L. Guénée, A. Alexakis, Org. Lett., 2012, 14, 5880-5883.

The combination of [(π-allyl)PdCl]2 with [(R)-ECNU-Phos], a new chiral bisphosphine ligand based on a biphenyl skeleton, demonstrates high enantioselectivity in a catalytic asymmetric carbonylation of readily available racemic propargylic carbonates to access optically active 2,3-allenoates.
Y. Wang, W. Zhang, S. Ma, J. Am. Chem. Soc., 2013, 135, 11517-11520.

An asymmetric AAC-SN2' ring opening sequence provides an efficient and operationally simple synthesis of di and trisubstituted enantiomeric allene derivatives. A highly efficient enantioselective synthesis of the naturally occurring antibiotic malyngolide highlights the utility of these allene derivatives in asymmetric organic synthesis.
Z. Wan, S. G. Nelson, J. Am. Chem. Soc., 2000, 122, 10470-10471.

Enantioenriched propargyl mesylates or perfluorobenzoates react with α-(N-carbamoyl)alkylcuprates to afford scalemic α-(N-carbamoyl) allenes. Subsequent N-Boc deprotection and AgNO3-promoted cyclization afford enantioenriched N-alkyl-3-pyrrolines.
R. K. Dieter, N. Chen, V. K. Gore, J. Org. Chem., 2006, 71, 8755-8760.

Palladium-catalyzed alkoxycarbonylation of 2,4-enyne carbonates proceeds in an alcohol and under balloon pressure of CO through 1,5-substitution. The olefin geometry controls the overall stereochemistry of this alkoxycarbonylation method.
E. Ş. Karagöz, M. Kuş, G. E. Akpınar, L. Artok, J. Org. Chem., 2014, 79, 9222-9230.

Pd(PPh3)4 catalyzes a cyanation of propargylic carbonates with trimethylsilyl cyanide in THF under reflux to afford cyanoallenes. The use of trimethylsilyl cyanide in excess (6 equiv) provides dicyanated products in high yields.
Y. Tsuji, M. Taniguchi, T. Yasuda, T. Kawamura, Y. Obora, Org. Lett., 2000, 2, 2635-2637.

Phenyl bromodifluoroacetate as bench-stable trifluoromethylation reagent converts readily available alcohols to trifluoromethanes in a Cu-catalyzed deoxytrifluoromethylation reaction. This reaction should be useful for a variety of medicinal, agricultural, and materials chemists.
F. de Azambuja, S. M. Lovrien, P. Ross, B. R. Amber, R. A. Altman, J. Org. Chem., 2019, 84, 2061-2071.

The ability of bipyridyl-derived ligands to control the regioselectivity of Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles provides various di-, tri-, and tetrasubstituted (trifluoromethyl)allenes, which can be further modified to generate complex fluorinated substructures.
B. R. Ambler, S. Peddi, R. A. Altman, Org. Lett., 2015, 17, 2506-2509.

Pd(0)-catalyzed carbonylation of (Z)-2-en-4-yn carbonates in the presence of CO and an alcohol gives vinylallenyl esters with an exclusively E-configuration in high yields. The unreactivity of E-configured enyne carbonates may indicate that the reaction is promoted via the cooperative coordination of palladium with both alkynyl and carbonate moieties.
G. E. Akpınar, M. Kuş, M. Uçncu, E. Karakuş, L. Artok, Org. Lett., 2011, , 748-751.