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Synthesis of 1,4-dienes


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Tributylmagnesate (nBu3MgLi) and the more reactive dibutylisopropylmagnesate (iPrnBu2MgLi) induce facile iodine/bromine-magnesium exchange to provide various polyfunctionalized arylmagnesium species. The exchange of alkenyl halides using this method proceeds with retention of configuration of the double bond.
A. Inoue, K. Kitagawa, H. Shinokubo, K. Oshima, J. Org. Chem., 2001, 66, 4333-4339.

In situ generated palladium(0) nanoparticles catalyze an efficient cross-coupling of allyl acetates with aryl and vinyl siloxanes. The reactions are stereoselective, and linear (E)-coupling products are obtained both from cis and trans allyl acetates. The coupling with vinyl siloxanes provides a novel protocol for the synthesis of 1,4-pentadienes.
R. Dey, K. Chattopadhyay, B. C. Ranu, J. Org. Chem., 2008, 73, 9461-9464.

Alkenyltrifluoroborates can be cross-coupled with allyl and benzyl chlorides using KOH as base in acetone-water (3:2) at 50 °C and low catalyst loadings of a 4-hydroxyacetophenone oxime derived palladacycle giving the corresponding 1,4-dienes and allylarenes, respectively. The use of overheated water as solvent and K2CO3 as base allows a coupling of alkenyltrifluoroborates with aryl and heteroaryl bromides.
E. Alacid, C. Nájera, J. Org. Chem., 2009, 74, 2321-2327.

A microwave synthesis of 1,4-pentadienes has been developed involving the palladium-catalyzed cross-coupling of potassium vinyltrifluoroborates with allyl acetates.
G. W. Kabalka, M. Al-Masum, Org. Lett., 2006, 8, 11-13.

A cross-coupling reaction of allylic and benzylic carbonates with organo[2-(hydroxymethyl)phenyl]dimethylsilanes proceeds in the presence of a palladium catalyst and in the absence of any activator. Various functional groups are tolerated to give a diverse range of 1,4-diene and diarylmethane products.
Y. Nakao, S. Ebata, J. Chen, H. Imanaka, T. Hiyama, Chem. Lett., 2007, 606-607.

The hydroallylation of terminal alkyl and aryl alkynes with simple allyl phosphates and 2-substituted allyl phosphates provides skipped dienes. The hydroallylation of functionalized internal alkynes enables the synthesis of complex trisubstituted alkenes.
M. Mailig, A. Hazra, M. K. Armstrong, G. Lalic, J. Am. Chem. Soc., 2017, 139, 6969-6977.

A CO2-promoted and Ni-catalyzed direct hydroallylation of terminal alkynes with allylic alcohols provides 1,4-dienes in good yield with excellent Markovnikov selectivity for alkyl- and aryl-substituted terminal alkynes under mild reaction conditions.
Z. Zhang, D. Li, C. Xi, Org. Lett., 2023, 25, 698-702.

An enhanced Lewis acid system of InCl3 and Me3SiBr can be used to promote a wide range of direct coupling reactions between alcohols and silyl nucleophiles in non-halogenated solvents. Highly chemoselective allylations toward a hydroxyl moiety over ketone and acetoxy ones have been demonstrated.
T. Saito, Y. Nishimoto, M. Yasuda, A. Baba, J. Org. Chem., 2006, 71, 8516-8522.

A Pd(0)-catalyzed allylic cross-coupling of homoallylic tosylate substrates with boronic acids and pinacol esters 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 and the tosylate, that includes secondary tosylates.
B. J. Stokes, S. M. Opra, M. S. Sigman, J. Am. Chem. Soc., 2012, 134, 11408-11411.

The reaction of an allyl titanium reagent prepared from 1-phenylthio-4-trimethylsilyl-2-butene with a ketone provides a tertiary alcohol, that undergoes a Brřnsted acid-mediated rearrangement reaction to generate a geminal divinyl compound.
R. Ogura, K. Satoh, W. Kiuchi, K. Kato, K. Ikeuchi, T. Suzuki, K. Tanino, Org. Lett., 2022, 24, 5041-5044.

A direct Ir-catalyzed asymmetric substitution reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity. This method allows rapid access to various 1,4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.
J. Y. Hamilton, D. Sarlah, E. M. Carreira, J. Am. Chem. Soc., 2013, 135, 994-997.

Enantioselective allylic additions of alkenyl units to readily accessible allylic electrophiles afford 1,4-dienes that contain a tertiary carbon stereogenic site in the presence of a copper complex of a chiral N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) compounds.
F. Gao, J. L. Carr, A. H. Hoveyda, J. Am. Chem. Soc., 2014, 136, 2149-2161.

A nickel-catalyzed cross-coupling of allyl alcohols with aryl- and alkenylzinc chlorides provides linear cross-coupling products.
B. Yang, Z.-X. Wang, J. Org. Chem., 2017, 82, 4542-4549.

The Suzuki-Miyaura cross-coupling with chiral γ,γ-disubstituted allylboronates provides nonracemic compounds with quaternary centers with high regioselectivity and enantiospecificity in the presence of RuPhos ligand. The reaction occurs by transmetalation with allyl migration, followed by rapid reductive elimination.
B. Potter, E. K. Edelstein, J. P. Morken, Org. Lett., 2016, 18, 3286-3289.

A nickel-catalyzed coupling of enones or enals with alkynes in the presence of silane and titanium alkoxide reductants provides direct access to skipped diene products via a net four-electron reductive coupling and deoxygenation. A new class of well-defined nickel(0) precatalysts bearing an unhindered N-heterocyclic carbene ligand is essential for the efficiency of the transformation.
D. P. Todd, B. B. Thompson, A. J. Nett, J. Montgomery, J. Am. Chem. Soc., 2015, 137, 12788-12791.

A mild, cobalt-catalyzed 1,4-hydrovinylation of acyclic 1,3-dienes with various functionalized terminal alkenes is described. Unsymmetrical 1,3-dienes yield products, where the new carbon-carbon bond is formed at the less substituted end of the 1,3-diene.
G. Hilt, S. Lüers, Synthesis, 2002, 609-618.

In cobalt-catalyzed 1,4-hydrovinylation, dppe/dppp ligands led to the formation of the branched product, whereas the SchmalzPhos ligand generates the corresponding linear product in both excellent yields and regioselectivities. The catalyst exhibits a high tolerance toward functional groups, and the very mild reaction conditions allow the synthesis of 1,4-dienes without isomerization into conjugated systems.
M. Arndt, M. Dindaroğlu, H.-G. Schmalz, G. Hilt, Org. Lett., 2011, 13, 6184-6187.

Monosubstituted acyclic (E)-1,3-dienes undergo efficient hydrovinylation giving (Z)-3-alkylhexa-1,4-dienes upon treatment with catalytic amounts of bidentate phosphine-CoCl2 complexes and Me3Al in an atmosphere of ethylene. Complexes derived from (RR)-DIOP and (SS)-BDDP at -45°C give very high enantioselectivities for several prototypical 1,3-dienes.
R. K. Sharma, T. V. RajanBabu, J. Am. Chem. Soc., 2010, 132, 3295-3297.

A nickel-catalyzed intermolecular process for direct allylation of nonconjugated, nonstrained simple alkenes affords the desired linear 1,4-dienes in high yield in both gram-scale and smaller scale coupling reactions.
R. Matsubara, T. F. Jamison, J. Am. Chem. Soc., 2010, 132, 6880-6881.

Sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes promote catalytic enantioselective allylic substitution reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site.
F. Gao. K. P. McGrath, Y. Lee, A. H. Hoveyda, J. Am. Chem. Soc., 2010, 132, 14315-14320.

Vinylaluminum reagents prepared from the reaction of commercially available DIBAL-H and a terminal alkyne can be used directly without purification in catalytic asymmetric allylic alkylation reactions with allylic phosphates in the presence of a readily available chiral N-heterocyclic carbene (NHC) complex and a commercially available and air stable Cu salt.
Y. Lee, K. Akiyama, D. G. Gillingham, M. Kevin Brown, A. H. Hoveyda, J. Am. Chem. Soc., 2008, 130, 446-447.

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium afforded skipped diene compounds bearing various functionals and heterocyclic groups. The products were readily transformed into structurally diverse polyenes.
C.-G. Wang, Y. Zhang, S. Wang, B. Chen, Y. Li, H.-L. Ni, Y. Gao, P. Hu, B.-Q. Wang, P. Cao, Org. Lett., 2021, 23, 535-541.

Treatment of (Z)-γ-trimethylsilyl allylic alcohols with a catalytic or stoichiometric amount of lithium tert-butoxide provides cyclic silyl ethers. A subsequent reaction with allylic halides followed by tetrabutylammmonium fluoride assisted hydrolysis produces 2,5-alkadien-1-ols with complete retention of configuration of the double bond.
H. Taguchi, K. Ghoroku, M. Tadaki, A. Tsubouchi, T. Takeda, Org. Lett., 2001, 3, 3811-3814.

Sigmatropic rearrangement of allenyl ethers furnishes α,β-unsaturated aldehydes in good yield.
P. J. Parsons, P. Thomson, A. Taylor, T. Sparks, Org. Lett., 2000, 2, 571-572.

Ketone-stabilized phosphonium ylides were allylated with high regioselectivity by primary allylic amines in the presence of 5 mol % Pd(PPh3)4 and 10 mol % B(OH)3. A subsequent one-pot Wittig olefination gave structurally diverse α,β-unsaturated ketones in good to excellent overall yields. Ester- and nitrile-stabilized phosphonium ylides can be converted if B(OH)3 is replaced with TsOH.
X.-T. Ma, Y. Wang, R.-H. Dai, C.-R. Liu, S.-K. Tian, J. Org. Chem., 2013, 78, 11071-11075.

A practical, highly enantioselective reaction of readily available 1,3-dienes and alkyl acrylates provides valuable, enantio-pure skipped 1,4-diene esters in the presence of commercially available cobalt salts and chiral ligands. This hetero-dimerization reaction tolerates various organic functional groups (e.g., aromatic substituents, halides, isolated mono- and di-substituted double bonds, esters, silyl ethers, and silyl enol ethers).
S. M. Jing, V. Balasanthiran, V. Pagar, J. C. Gallucci, T. V. Rajanbabu, J. Am. Chem. Soc., 2017, 139, 18034-18043.

An iridium-catalyzed allylic alkylation of phosphonates followed by a Horner-Wadsworth-Emmons olefination provides skipped dienes bearing a C3 stereogenic center, generally with outstanding enantioselectivities.
A. Seal, S. Mukherjee, Org. Lett., 2023, 25, 2253-2257.

A Ba/Pd cooperative catalysis system enables a dehydrative cross-coupling of allylic alcohols with P-ylides followed by a Wittig reaction in one pot. Various multisubstituted 1,4-dienes were isolated in very good yields with a broad range of P-ylides and aldehydes with excellent E selectivity.
P. Xie, W. Fu, X. Cai, Z. Sun, Y. Wu, S. Li, C. Gao, X. Yang, T.-P. Loh, Org. Lett., 2019, 21, 7055-7059.

An iridium-catalyzed directed olefinic C-H allylation and alkenylation of NH-Ts acrylamides in water provides various 1,4- and 1,3-diene skeletons. This practical and atom-economic reaction tolerated a wide scope of substrates under simple reaction conditions and enabled successful gram-scale preparation. Furthermore, an asymmetric synthesis of 1,4-dienes was achieved.
Y. Huang, L. Xu, F. Yu, W. Shen, X. Lu, L. Ding, L. Zhong, G. Zhong, J. Zhang, J. Org. Chem., 2020, 85, 7225-7237.

Use of copper(I) tert-butoxide and allylic halides enables the substitution of the silyl group in vinylsilanes by an allylic group. This synthetic application of a 1,3 Csp2-to-O silyl migration provides a useful method for the generation of vinyl anion equivalents.
A. Tsubouchi, M. Itoh, K. Onishi, T. Takeda, Synthesis, 2004, 1504-1508.

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.

Sulfonate-bearing chiral bidentate N-heterocyclic carbene (NHC) complexes of copper enable catalytic enantioselective allylic substitutions of allylic phosphonates with commercially available allenylboronic acid that result in addition of an allenyl group and formation of tertiary or quaternary C-C bonds in up to 95% yield, >98% SN2′ selectivity, and 98% ee.
B. Jung, A. H. Hoveyda, J. Am. Chem. Soc., 2012, 134, 1490-1493.

An asymmetric boronate addition to sulfonyl hydrazones catalyzed by chiral biphenols provides enantioenriched allenes in a traceless Petasis reaction. The resulting Mannich product from nucleophilic addition eliminates sulfinic acid, yielding a propargylic diazene that performs an alkyne walk to afford the allene. Two enantioselective approaches have been developed for the synthesis of allylic hydroxyl allenes and 1,3-alkenyl allenes.
Y. Jiang, A. B. Diagne, R. J. Thomson, S. E. Schaus, J. Am. Chem. Soc., 2017, 139, 1826-1829.

On exposure to BuLi, 3-bromo-2-iodocyclopent-2-enol O-TBS ether undergoes iodine-lithium permutation with complete regioselectivity. Reaction with different electrophiles affords the corresponding 2-substituted-3-bromocyclopentenol derivatives. Subsequent bromo-lithium exchange with t-BuLi, followed by reaction with an equal or different electrophile, affords 2,3-disubstituted cyclopentenols.
M. Luparia, A. Vadalŕ, G. Zanoni, G. Vidari, Org. Lett., 2006, 8, 2147-2150.