Categories: C-C Bond Formation > Oxygen-containing molecules > Alcohols >
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.
A reductive coupling of terminal alkynes with α-chloro boronic esters affords
allylic alcohols with excellent regioselectivity (anti-Markovnikov) and an E/Z
ratio greater than 200:1. The reaction can be performed in the presence of a
wide range of functional groups, is stereospecific, and allows for the robust
and highly selective synthesis of chiral allylic alcohols.
A. B. Shaff, L. Yang, M. T. Lee, G. Lalic, J. Am. Chem. Soc.,
2023, 145, 24615-24624.
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.
TMSCF2Br can serve as two different precursors, namely, a TMSCF2
radical precursor and a difluorocarbene precursor. Efficient trifluorovinylation
and pentafluorocyclopropylation of aldehydes provide a broad range of alcohols
containing trifluorovinyl or pentafluorocyclopropyl moieties from abundantly
available aldehydes.
A. Liu, X. Zhang, F. Zhao, C. Ni, J. Hu, J. Am. Chem. Soc.,
2024, 146, 1806-1812.
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 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.