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Synthesis of homoallylic alcohols


Name Reactions

Alder-Ene Reaction

Hosomi-Sakurai Reaction

Hosomi-Sakurai Reaction

Nozaki-Hiyama Coupling

[2,3]-Wittig Rearrangement

Recent Literature

The combination of Me3SiO- and Bu4N+ serves as a general activator of organotrimethylsilanes for addition reactions. A broad scope of bench-stable trimethylsilanes (including acetate, allyl, propargyl, benzyl, dithiane, heteroaryl, and aryl derivatives) can be used as carbanion equivalents for synthesis. Reactions are achieved at rt without the requirement of specialized precautions that are commonplace for other organometallics.
M. Das, D. F. O'Shea, J. Org. Chem., 2014, 79, 5595-5607.

AgF and (R)-DIFLUORPHOS predominantly formed a 1:1 complex that provided high enantioselectivity for the asymmetric Sakurai-Hosomi allylation of various simple ketones. Only 1,2-adducts were obtained from both acyclic and cyclic conjugate ketones. Highly diastereo- and enantioselective reactions with E- or Z-crotyltrimethoxysilane and racemic allylsilanes are described.
M. Wadamoto, H. Yamamoto, J. Am. Chem. Soc., 2005, 127, 14556-14557.

A general allylation of a diverse array of ketones with allyl boronates is effective with 2 mol % of a zinc alkoxide catalyst and with relatively short reaction times. Studies of the key exchange process are presented, which support a cyclic transition state for the boron to zinc exchange.
K. R. Fandrick, D. R. Fandrick, J. J. Gao, J. T. Reeves, Z. Tan, W. Li, J. J. Song, B. Lu, N. K. Yee, C. H. Senanayake, Org. Lett., 2010, 12, 3748-3751.

A general and mild CuCl-TBAT-catalyzed allylation of aldehydes, ketones, and imines was developed using allyltrimethoxysilane as the allylating reagent. Mechanism studies indicated that the copper alkoxide, allylfluorodimethoxysilane, and allyltrimethoxysilane are essential to promote the reaction efficiently.
S. Yamasaki, K. Fujii, R. Wada, M. Kanai, M. Shibasaki, J. Am. Chem. Soc., 2002, 124, 6536-6537.

A cationic iridium complex-catalyzed olefin transposition of (E)-1-alkenylboronates followed by a chiral phosphoric acid-catalyzed allylation reaction of aldehydes enables a highly diastereo- and enantioselective synthesis of anti homoallylic alcohols.
T. Miura, Y. Nishida, M. Morimoto, M. Murakami, J. Am. Chem. Soc., 2013, 135, 11497-11500.

A highly reactive nickel-catalyst system enables an in situ transposition of a homoallyl pinacol boronic ester to a Z-crotyl pinacol boronic ester, that reacts with various aldehydes to form syn-homoallylic alcohols in high diastereoselectivities. Also, the multiple transposition of pentenyl pinacol boronic ester was realized.
F. Weber, M. Ballmann, C. Kohlmeyer, G. Hilt, Org. Lett., 2016, 18, 548-551.

A highly diastereoselective Pd-catalyzed carbonyl allylation of aldehydes and isatins with simple acyclic olefins as allylating reagents consists of a Pd-catalyzed oxidative allylic C-H borylation and an allylboration of carbonyls accelerated by phosphoric acid. N-Fluorobenzenesulfonimide as oxidant plays a key role.
Z.-L. Tao, X.-H. Li, Z.-Y. Han, L.-Z. Gong, J. Am. Chem. Soc., 2015, 137, 4054-4057.

Chiral ruthenium(II) complexes catalyze a highly regio-, diastereo-, and enantioselective reaction of alkynes with primary alcohols to form homoallylic alcohols. In this enantioselective carbonyl allylation, alkynes serve as allylmetal equivalents.
T. Liang, K. D. Ngyuen, W. Zhang, M. J. Krische, J. Am. Chem. Soc., 2015, 137, 3161-3164.

General In(0)-catalyzed allylations of ketones proceeded smoothly in water under mild conditions, and water proved to be essential for these reactions. Both the substrate scope and the functional group tolerance were excellent. The In metal catalyst could be easily recovered and reused without loss of catalytic activity.
U. Schneider, M. Ueno, S. Kobayashi, J. Am. Chem. Soc., 2008, 130, 13824-13825.

The use of montmorillonite clay as catalyst provides a straightforward and scalable, highly diastereoselective method for the allylation and crotylation of a range of ketones and aldehydes with air- and water-stable potassium allyl and crotyltrifluoroborate salts.
F. Nowrouzi, A. N. Thadani, R. A. Batey, Org. Lett., 2009, 11, 2631-2634.

Insertion of 2-substituted dienes into the methanol C-H bond occurs in a regioselective manner to form all-carbon quaternary centers with excellent levels of enantioselectivity using an iridium-PhanePhos catalyst via methanol dehydrogenation, reversible diene hydrometalation, and regioisomeric formation of allyliridium-formaldehyde pairs.
K. D. Nguyen, D. Herkommer, M. J. Krische, J. Am. Chem. Soc., 2016, 138, 14210-14213.

A combined carbocupration of terminal alkynes followed by a zinc homologation and further reaction with ketones lead, in a single-pot operation, to homoallylic alcohols possessing two consecutive quaternary stereocenters with excellent diastereoselectivity.
B. Dutta, N. Gilboa, I. Marek, J. Am. Chem. Soc., 2010, 132, 5588-5589.

Asymmetric allylation of aldehydes with γ-disubstituted allyl halides in the presence of a sulfonamide/oxazoline chromium complex provides various synthetically useful α-homoallylic alcohols with two consecutive stereogenic centers, including one quaternary carbon, in a highly diastereoselective and enantioselective manner.
Y. Xiong, G. Zhang, Org. Lett., 2016, 18, 5094-5097.

In acetonitrile as solvent and in the presence of a simple cobalt halide as catalyst, the reduction by zinc dust of a mixture of aldehydes or ketones and allylic acetates affords the corresponding homoallylic alcohols in good yields.
P. Gomes, C. Gosmini, J. Périchon, Synthesis, 2003, 1909-1915.

Under catalysis by ruthenium trichloride in the presence of carbon monoxide, water, and triethylamine, a wide range of aromatic, olefinic, and aliphatic aldehydes are efficiently allylated with allyl acetate under mild conditions. The stoichiometric byproducts of this reaction are carbon dioxide and acetic acid.
S. E. Denmark, S. T. Nguyen, Org. Lett., 2009, 11, 781-784.

An iridium-catalyzed coupling of 1-aryl-1-propynes with primary alcohols gives secondary homoallylic alcohols as products. This reaction involves an iridium-catalyzed novel catalytic transformation of 2-alkynes and primary alcohols through the formation of hydrido(π-allyl)iridium as a possible key intermediate.
Y. Obora, S. Hatanaka, Y. Ishii, Org. Lett., 2009, 11, 3510-3513.

Titanocene dichloride catalyzes the formation of an organozinc species via catalytic activation of allyl halides. Nucleophilic addition to carbonyl derivatives provides the desired homoallylic alcohols in very good yields in short reaction times. This discovery will have wide ranging applicability in the generation of highly reactive organometallic reagents.
L. M. Fleury, B. L. Ashfeld, Org. Lett., 2009, 11, 5670-5673.

A rapid and efficient procedure for the solvent-free synthesis of homoallylic and homopropargyl alcohols has been achieved by zinc-mediated Barbier-type reaction of carbonyl compounds at room temperature.
J.-X. Wang, X. Jia, T. Meng, L. Xin, Synthesis, 2005, 2669-2672.

A range of polysubstituted allylic zinc chlorides were obtained in good yield using a LiCl-mediated zinc dust insertion in polysubstituted allylic chlorides. A highly diastereoselective synthesis of homoallylic alcohols bearing up to two adjacent quaternary centers by the addition of polysubstituted allylic zinc reagents to carbonyl compounds.
H. Ren, G. Dunet, P. Mayer, P. Knochel, J. Am. Chem. Soc., 2007, 129, 5376-5377.

A solvent- and metal-free process for the direct methallylboration of ketones with a stable B-methallylborinane is accelerated by tertiary alcohols. In the presence of 2.0 equiv of tert-amyl alcohol, the methallylation products were prepared at room temperature in excellent yields. The process offers simple operation, high efficiency, and mild reaction conditions.
Y. Zhang, N. Li, N. Goyal, G. Li, H. Lee, B. Z. Lu, C. H. Senanayake, J. Org. Chem., 2013, 78, 5775-5781.

An In(III)-catalyzed intermolecular glyoxylate-ene reaction enables an efficient synthesis of homoallylic alcohols with high enantioselectivities and anti-diastereoselectivities. Only alkene isomers having a proton β-cis to the substituent reacted in this catalytic system.
X. Zhang, M. Wang, R. Ding, Y.-H. Xu, T.-P. Loh, Org. Lett., 2015, 17, 2736-2739.

In situ generation of allylic boronates by iridium-catalyzed borylation of cyclic alkenes in the presence of additives, such as methylimidazole and DBU, followed a reaction with aldehydes allows the synthesis of stereodefined homoallylic alcohols. Cycloalkenes without additives as well as acyclic substrates gave vinylic boronates, which were coupled with organohalides in a Suzuki-Miyaura sequence.
V. J. Olsson, K. J. Szabó, J. Org. Chem., 2009, 74, 7715-7723.

A regio- and diastereoselective nickel-catalyzed reductive coupling of carbonyls with dienes in the presence of a stoichiometric amount of bis(pinacolato)diboron furnishes allyl boronic esters as the reaction product, which was readily converted to the derived allylic alcohol by oxidative workup.
H. Y. Cho, J. P. Morken, J. Am. Chem. Soc., 2008, 130, 16140-16141.

Trapping of β,γ-alkynyl aldehydes, generated in situ by treatment of alkynyloxiranes with a catalytic amount of Sc(OTf)3 or BF3ˇOEt2, by a variety of allyl nucleophiles affords homopropargylic homoallylic alcohols in good yield and selectivity. Subsequent enyne metathesis gives functionalized vinylcyclopentenols.
L. Wang, M. L. Maddess, M. Lautens, J. Org. Chem., 2007, 72, 1822-1825.

The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl 1,2-enediol carbonates gives exclusively α-hydroxyketones in very good yields and high enantiomeric excesses using Lnaph as ligand in DME. The reaction proceeds under extremely mild conditions and tolerates a broad range of esters.
B. M. Trost, J. Xu, T. Schmidt, J. Am. Chem. Soc., 2008, 130, 11852-11853.

In a new, efficient, catalytic asymmetric protocol for the synthesis of α-tertiary hydroxyaldehydes from readily available α-halo or α-hydroxy ketones or enol silyl ethers, the chiral ligand controls the regioselectivity as well as the enantioselectivity.
B. M. Trost, J. Xu, M. Reichle, J. Am. Chem. Soc., 2007, 129, 282-283.

Chiral α-(carbamoyloxy)alkylcopper reagents, prepared using Hoppe's sBuLi/(-)-sparteine methodology and subsequent transmetalations with ZnCl2 and CuCN, reacted with various electrophiles to give enantiomerically pure alcohols after deprotection.
J. P. N. Papillon, R. J. K. Taylor, Org. Lett., 2002, 4, 119-122.

A novel nickel(II)-N,N′-dioxide complex facilitated the asymmetric synthesis of biologically interesting α-hydroxy carbonyl compounds under mild conditions by a highly enantioselective carbonyl-ene reactions of glyoxal derivatives with various alkenes. Various aromatic, aliphatic, and heteroaromatic glyoxal derivatives, as well as glyoxylate, were tolerated.
K. Zheng, J. Shi, X. Liu, X. Feng, J. Am. Chem. Soc., 2008, 130, 15770-15771.

Highly enantioselective carbonyl-ene reactions of various 1,1-disubstituted and trisubstituted alkenes with ethyl glyoxylate are catalyzed by a new Co-salen complex under nearly ideal conditions at room temperature using low catalyst loadings. The reaction provides chiral, homoallylic alcohol products in excellent yields, enantioselectivities, and diastereoselectivities.
G. E. Hutson, A. H. Dave, V. H. Rawal, Org. Lett., 2007, 9, 3869-3872.

3-Substituted-2-alkoxycarbonyl allylboronates are readily produced by the cross-coupling of Baylis-Hillman acetate adducts and bis(pinacolato)diboron in the presence of a palladium catalyst. Subsequent addition of excess aqueous KHF2 gives stable allyl trifluoroborate salts. Allylboronate and allyltrifluoroborate derivatives react stereoselectively with aldehydes to afford functionalized homoallylic alcohols.
G. W. Kabalka B. Venkataiah, G. Dong, J. Org. Chem., 2004, 69, 5807-5809.

A highly regioselective vinylogous aldol reaction catalyzed by SiCl4 and a chiral phosphoramide, provides δ-hydroxy enones for a variety of aldehyde and dienol ether structures in good yields, excellent enantioselectivities, and in some cases excellent anti diastereoselectivities.
S. E. Denmark, G. L. Beutner, J. Am. Chem. Soc., 2003, 125, 7800-7801.

The weakly acidic species, silicon tetrachloride (SiCl4), can be activated by binding of a strongly Lewis basic chiral phosphoramide, leading to in situ formation of a chiral Lewis acid for catalysis of the aldol reaction of silyl ketene acetals and silyl dienol ethers (vinylogous aldol reactions) to conjugated and nonconjugated aldehydes. The high levels of regio-, anti diastereo-, and enantioselectivity observed are discussed.
S. E. Denmark, G. L. Beutner, T. Wynn, M. D. Eastgate, J. Am. Chem. Soc., 2005, 127, 3774-3789.

N,O-Silyl dienyl ketene acetals are useful reagents for highly enantioselective vinylogous aldol additions to various aldehydes in the presence of SiCl4 and the catalytic action of a chiral phosphoramide.
S. E. Denmark, J. R. Heemstra, Jr., J. Am. Chem. Soc., 2006, 128, 1038-1039.

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.

Addition of α-alkenylzirconacyclopentenes to aldehyde enables a highly stereoselective synthesis of β-hydroxyallenes with multiple stereogenic centers including allenic axial chirality, as well as center chirality. Remarkably, the reaction occurs with completely different chemoselectivity in comparison with the usual alkyl- or aryl-substituted zirconacyclopentenes.
Y. Zhou, J. Chen, C. Zhao, E. Wang, Y. Liu, Y. Li, J. Org. Chem., 2009, 74, 5326-5330.

A highly regio- and stereoselective palladium-catalyzed synthesis of various 2-silylallylboronates from allenes and 2-(dimethylphenylsilanyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane afforded the corresponding silaboration products in moderate to excellent yields. In the absence of an organic iodide, the silaboration gives products having completely different regiochemistry. In the presence of an aldehyde, the silaboration reaction afforded homoallylic alcohols in one pot in good to excellent yields, with exceedingly high syn selectivity.
K.-J. Chang, D. K. Rayabarapu, F.-Y. Yang, C.-H. Cheng, J. Am. Chem. Soc., 2005, 127, 126-131.

Enantioselective Allylic Carbon-Carbon Bond Construction