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Synthesis of allylic alcohols

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A highly enantioselective and catalytic vinylation of aldehydes leads to allylic alcohols that are then transformed to the allylic amines via Overman's [3,3]-sigmatropic rearrangement of imidates. Oxidative cleavage of the allylic amines furnishes amino acids in good yields and excellent ee's. The scope and utility of this method are demonstrated by the synthesis of challenging allylic amines and their subsequent transformation to valuable nonproteinogenic amino acids, including both D and L configured (1-adamantyl)glycine.
Y. K. Chen. A. E. Lurain, P. J. Walsh, J. Am. Chem. Soc., 2002, 124, 12225-12231.

The asymmetric addition of alkenylzincs to aromatic and α-branched aliphatic aldehydes catalyzed by (-)-2-exo-morpholinoisoborne-10-thiol generated the corresponding (E)-allylic alcohols with >95% ee and very good chemical yields.
H.-L. Wu, P.-Y. Wu, B.-J. Uang, J. Org. Chem., 2007, 72, 5935-5937.

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.

The use of a thioether-imidazolinium chloride as a heterobidentate carbene ligand precursor led to a high level of catalyst performance in the palladium-catalyzed 1,2-addition of aryl-, heteroaryl-, and alkenylboronic acids to aromatic, heteroaromatic, and aliphatic aldehydes.
M. Kuriyama, R. Shimazawa, R. Shirai, J. Org. Chem., 2008, 73, 1597-1600.

The use of DTBP as radical initiator and a copper salt as promoter enables the preparation of allylic alcohol, benzyl, and alkane derivatives via a radical mechanism. The C(sp³)-H bond in various alcohols, toluene derivatives, and alkanes were successfully alkenylated with β-nitrostyrenes to yield the desired products in good yields.
S.-r. Guo, Y.-q. Yuan, Synlett, 2015, 26, 1961-1968.

A highly efficient nickel-catalyzed asymmetric alkylative coupling of alkynes, aldehydes, and dimethylzinc in the presence of bulky spirobiindane phosphoramidite ligands affords allylic alcohols with tetrasubstituted olefin functionalities in high yields, high regioselectivities, and excellent enantioselectivities
Y. Yang, S.-F. Zhu, C.-Y. Zhou, Q.-L. Zhou, J. Am. Chem. Soc., 2008, 130, 14052-14053.

The combination of a chiral Co complex and a photocatalyst mediates a highly regio- and enantioselective reductive coupling of internal alkynes with aldehydes to provide enantioenriched allylic alcohols in excellent regio-, stereo-, and enantioselectivity. The method offers mild reaction conditions, broad substrate scope, and good functional group compatibility.
Y.-L. Li, S.-Q. Zhang, J. Chen, J.-B. Xia, J. Am. Chem. Soc., 2021, 143, 7306-7313.

An asymmetric addition of vinyl group to ketones using vinylaluminum reagents catalyzed by in situ prepared Ti(OiPr)₄ complexes of (S)-BINOL affords diversified tertiary allylic alochols. Various aromatic ketones can be converted to allylic alcohols in excellent enantioselectivities with high yields.
D. B. Biradar, H.-M. Gau, Org. Lett., 2009, 11, 499-502.

PtCl₂ plays a dual role as hydrosilylation and alkenylation catalysts in a one-pot hydrosilylation of terminal alkynes with triethylsilane and subsequent alkenylation of aldehydes with the resultant (E)-alkenylsilanes. The latter alkenylation step proceeds smoothly in the presence of p-benzoquinone and LiI to give allyl silyl ethers in good yields. This one-pot alkenylation tolerates a reasonable range of functional groups.
H. Kinoshita, R. Uemura, D. Fukuda, K. Miura, Org. Lett., 2013, 15, 5538-5541.

Use of a zirconocene catalyst based on the Brintzinger ligand and catalytic amounts of methyl aluminoxanes (MAO) effect a >99% regiocontrol of Negishi carboaluminations of 1-alkynes in toluene.
B. H. Lipshutz, T. Butler, A. Lower, J. Am. Chem. Soc., 2006, 128, 15396-15398.

Hydroboration of a variety of 1-bromo-1-acetylenes with dicyclohexyl borane, reaction with t-BuLi, and transmetalation to zinc generates a (Z)-disubstituted vinylzinc reagent. In situ reaction of this reagent with aldehydes generates (Z)-disubstituted allylic alcohols in high yields.
S.-J. Jeon, E. L. Fischer, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2006, 128, 9618-9619.

An easy access to (Z)-trisubstituted allylic alcohols is based on E to Z isomerization of 1-bromo-1-dialkylvinylboranes upon reaction with dialkylzinc reagents. Subsequent transmetalation to give (Z)-trisubstituted vinylzinc species is followed by trapping with aldehydes to furnish a series of (Z)-trisubstituted allylic alcohols.
Y. K. Chen, P. J. Walsh, J. Am. Chem. Soc., 2004, 126, 3702-3703.

A stereoselective transformation of α-alkoxyacetoaldehydes gives the corresponding β-alkoxy vinyl triflates by treatment with phenyl triflimide and DBU. Subsequent transition metal-catalyzed cross-coupling reactions followed by [1,2]-Wittig rearrangements enable the stereoselective synthesis of structurally diverse (Z)-allylic alcohols.
F. Kurosawa, T. Nakano, T. Soeta, K. Endo, U. Ukaji, J. Org. Chem., 2015, 80, 5696-5703.

Various N-acylethylenediamine-based ligands were screened as catalysts for the asymmetric addition of vinylzinc reagents to aldehydes. The optimized ligand was found to catalyze the formation of (E)-allylic alcohols with high enantioselectivities for both aromatic and α-branched aldehydes, and vinylzinc reagents derived from both bulky and straight chain terminal alkynes.
C. M. Sprout, M. L. Richmond, C. T. Seto, J. Org. Chem., 2005, 70, 7408-7417.

Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc reagents generate (Z)-disubstituted vinylzinc intermediates. A subsequent reaction with aldehydes in the presence (-)-MIB generates (Z)-disubstituted allylic alcohols. Addition of tetraethylethylenediamine inhibits a fast, LiCl-promoted addition leading to racemic products.
L. Salvi, S.-J. Jeon, E. L. Fisher, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2007, 129, 16119-16125.

A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes afforded allylic alcohols with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process allows the enantioselective synthesis of α-hydroxy ketones.
K. M. Miller, W.-S. Huang, T. F. Jamison, J. Am. Chem. Soc., 2003, 125, 3442-3443.

The complementary use of small cyclopropenylidene carbene ligands or highly hindered N-heterocyclic carbene ligands allows the regiochemical reversal in aldehyde-alkyne reductive couplings with unbiased internal alkynes, aromatic internal alkynes, conjugated enynes, or terminal alkynes.
H. A. Malik, G. J. Sormunen, J. Montgomery, J. Am. Chem. Soc., 2010, 132, 6304-6305.

H. A. Malik, G. J. Sormunen, J. Montgomery, J. Am. Chem. Soc., 2010, 132, 6304-6305.

A new procedure for catalytic reductive coupling of aldehydes and alkynes uses Ni(COD)₂ with an imidazolium carbene ligand as the catalyst and triethylsilane as the reducing agent.
G. M. Mahandru, G. Liu, J. Montgomery, J. Am. Chem. Soc., 2004, 126, 3698-3699.

An indium-mediated coupling of 1,4-dibromo-2-butyne with carbonyl compounds in aqueous media provides 1,3-butadien-2-ylmethanols in good yields.
W. Lu, J. Ma, Y. Yang, T. H. Chan, Org. Lett., 2000, 2, 3469-3471.

An intermolecular reductive coupling of ynoates and aldehydes in the presence of a silane using catalytic amounts of Ni(COD)₂, an N-heterocyclic carbene ligand, and PPh₃ delivers invaluable silyl-protected γ-hydroxy-α,β-enoates. This methodology provides a quick entry to many other 1,4-difunctional compounds and oxygen-containing five-membered rings. The intermediacy of metallacycles in the catalytic process has been established.
S. K. Rodrigo, H. Guan, J. Org. Chem., 2012, 77, 8303-8309.

In the presence of catalytic amounts of PtCl₂ and metal iodides, β-substituted vinylsilanes reacted with aldehydes at the β-position to give allyl silyl ethers. Addition to aromatic aldehydes proceeded efficiently in the presence of LiI whereas MnI₂ was found to be effective in addition to aliphatic aldehydes.
K. Miura, G. Inoue, H. Sasagawa, H. Kinoshita, J. Ichikawa, A. Hosomi, Org. Lett., 2009, 11, 5066-5069.

A bidentate chiral phosphoramide based on a 2,2'-bispyrrolidine skeleton afforded good yield, efficient turnover, and high enantioselectivity in allylation reactions of various unsaturated aldehydes with substituted allylic trichlorosilanes. The reaction of γ-disubstituted allylic trichlorosilanes allowed the construction of stereogenic, quaternary centers.
S. E. Denmark, J. Fu, M. J. Lawler, J. Org. Chem., 2006, 71, 1523-1536.

A mild and convenient defluorinative reductive cross coupling of gem-difluoroalkenes with aliphatic aldehydes provides diverse β-fluorinated allylic alcohols in good yields. The reaction is operationally simple and shows good functional group tolerance.
Y.-T. Liu, Y.-H. Fan, Y. Mei, D.-J. Li, Y. Jiang, W.-H. Yu, F. Pan, Org. Lett., 2023, 25, 549-554.

Highly diastereo- and enantioselective syntheses of 1,5-disubstituted (E)-1,5-anti-pent-2-endiols and (Z)-1,5-syn-pent-2-endiols have been achieved via the one-pot coupling of two different aldehydes with bifunctional γ-boryl-substituted allylborane reagents, which were generated in situ by the hydroboration of allenes with diisopinocampheylborane. The stereospecificity is discussed.
E. M. Flamme, W. R. Roush, J. Am. Chem. Soc., 2002, 124, 13644-13645.

Photoredox-catalyzed and nitrogen-centered radical-triggered cascade reactions of styrenes (or phenylacetylenes), enol derivatives, and O-acyl hydroxylamines in DMSO provide functionalized β-amino alcohols. Structurally diverse reaction components, including complex molecular scaffolds can be converted.
X.-D. An, Y.-Y. Jiao, H. Zhang, Y. Gao, S. Yu, Org. Lett., 2018, 20, 401-404.

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. Vadalà, G. Zanoni, G. Vidari, Org. Lett., 2006, 8, 2147-2150.

An effient cobalt-catalyzed enantioselective vinylation of α-ketoesters, isatins, and imines delivers a range of synthetically useful allylic alcohols and amines in high enantiopurity. This convenient method employs commercially available and easy to handle catalysts and reagents.
Y. Huang, R.-Z. Huang, Y. Zhao, J. Am. Chem. Soc., 2016, 138, 6571-6576.

An iridium-catalyzed, hydrogen-mediated reductive C-C bond formation of alkynes in the presence of α-ketoesters affords β,γ-unsaturated α-hydroxyesters in excellent yield, with complete control of olefin geometry and, in most cases, with excellent regiocontrol.
M.-Y. Ngai, A. Barchuk, M. J. Krische, J. Am. Chem. Soc., 2007, 129, 280-281.

A chiral dicationic palladium complex-catalyzed vinylation and dienylation of glyoxylate with vinylsilanes and dienylsilanes produces highly optical active allylic alcohols. The chiral palladium catalyst is readily employed and vinylsilanes as nucleophiles are easily synthesized, storable, and air- and moisture-stable.
K. Aikawa, Y. Hioki, K. Mikami, J. Am. Chem. Soc., 2009, 131, 13922-13923.

Highly enantioselective direct catalytic reductive couplings of 1,3-enynes to activated ketones such as ethyl pyruvate have been achieved by using chirally modified cationic rhodium catalysts in the presence of hydrogen to afford dienylated α-hydroxy esters with exceptional levels of regio- and enantiocontrol.
J.-R. Kong, M.-Y. Ngai, M. J. Krische, J. Am. Chem. Soc., 2006, 128, 718-719.

Catalytic hydrogenation of 1,3-enynes in the presence of ethyl glyoxalate at ambient pressure and temperature using a rhodium catalyst modified by (R)-(3,5-tBu-4-MeOPh)-MeO-BIPHEP results in highly regio- and enantioselective reductive coupling to furnish the corresponding α-hydroxy esters.
Y.-T. Hong, C.-W. Cho, E. Skucas, M. J. Krische, Org. Lett., 2007, 9, 3745-3748.

Slow addition of a terminal alkyne and water to a mixture of an aldehyde, CrCl₂, NiCl₂ and a catalytic amount of triphenylphosphine in DMF at 25°C generates a 1,2-disubstituted allylic alcohol regioselectively.
K. Takai, S. Sakamoto, T. Isshiki, Org. Lett., 2003, 5, 653-655.

A cyclopentadienyliron dicarbonyl complex catalyzes a functionalization of the C(sp²)-H bonds of monosubstituted alkylallenes with aldehydes in the presence of triisopropylsilyl triflate to provide 1,1-disubstituted allenylic triisopropylsilyl ethers in good yields. Lithium bistriflimide was identified as a critical additive in this transformation.
R. Ding, Y. Wang, Y.-M. Wang, Synthesis, 2023, 55, 733-743.

Reactions of various carbonyl compounds with organoindium reagent in situ generated from indium and 1-bromopent-4-en-2-yne derivatives gives functionalized vinyl allenols in good yields. Treatment of vinyl allenols with gold catalyst, dienophile, or indium trihalide produced functionalized dihydrofuran, cyclohexene, or 2-halo-1,3-diene derivatives in very good yields.
J. Park, S. Hong, P. H. Lee, Org. Lett., 2008, 10, 5067-5070.

A highly regioselective chromium-catalyzed addition of 3-bromopropenyl acetate as a masked homoenolate nucleophile to aromatic, aliphatic, and α,β-unsaturated aldehydes allows the synthesis of homoaldol equivalent products in very good yields. The vinyl acetate adducts are easily hydrolyzed with mild base to provide formal homoaldol adducts, or transformed to other more functionalized products.
J. Y. Kang, B. T. Connell, J. Am. Chem. Soc., 2010, 132, 7826-7827.

A nickel(0) N-heterocyclic carbene complex-catalyzed coupling of α-silyloxy aldehydes and alkynylsilanes provides an effective entry to various anti-1,2-diols with excellent diastereoselectivity.
K. Sa-ei, J. Montgomery, Org. Lett., 2006, 8, 4441-4443.

Catalytic hydrogenation of acetylenic aldehydes using a chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols. Using an achiral hydrogenation catalyst, some chiral racemic acetylenic aldehydes engage in highly syn-diastereoselective reductive cyclizations.
J. U. Rhee, M. J. Krische, J. Am. Chem. Soc., 2006, 128, 10674-10675.

Related

β-Lithiooxyphosphonium ylides, generated in situ from aldehydes and Wittig reagents, react readily with halomethyl esters to form trisubstituted Z-allylic esters. The methodology was applied to a total synthesis of a geranylgeraniol-derived diterpene.
D. M. Hodgson, T. Arif, Org. Lett., 2010, 12, 4204-4207.

A short, efficient and mild synthesis of allylic TBS ethers and allylic alcohols is based upon a unique Kocienski-Julia olefination reaction. Various allylic alcohols and allylic ethers are obtained in good to excellent yields and with high (E)-selectivity.
J. Pospisil, I. E. Marko, Org. Lett., 2006, 8, 5983-5986.

A chemo- and regioselective, Cu-catalyzed asymmetric addition of Grignard reagents to 3-bromopropenyl esters provides allylic esters in high yields and enantioselectivities using Taniaphos as ligand. The method is a practical route to chiral, nonracemic allylic alcohols.
K. Geurts, S. P. Fletcher, B. L. Feringa, J. Am. Chem. Soc., 2006, 128, 15572-15573.

An in situ preparation of highly stereoretentive dithiolate ruthenium-based metathesis catalysts avoids the isolation of air-sensitive intermediates. The procedure can be use for performing cross-metathesis reactions without a glovebox, and on a small scale even Schlenk techniques are not required.
D. S. Müller, I. Curbet, Y. Raoul, J. Le Nôtre, O. Baslé, M. Mauduit, Org. Lett., 2018, 20, 6822-6826.

A transition metal-mediated/monophosphorus ligand system enables the selective synthesis of ketones or chiral allylic alcohols in high yields/enantiomeric excess from the 1,2-addition of arylboronic acids to α,β-unsaturated aldehydes. While a Ru/monophosphorus system provides chiral allylic alcohols, the rhodium-catalyzed reaction provides ketones.
R. Miao, J. Huang, Y. Xia, Y. Wei, R. Luo, L. Ouyang, J. Org. Chem., 2022, 87, 8576-8588.

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 C^sp2-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.