Categories: C-C Bond Formation > Alcohols, Arenes >
Synthesis of benzylic alcohols
Suzuki-Miyaura cross-coupling of aryl halides and triflates with potassium acetoxymethyltrifluoroborate afforded the corresponding benzylic alcohols in good yields.
N. Murai, M. Yonaga, K. Tanaka, Org. Lett., 2012, 14, 1278-1281.
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.
The use of tri(tert-butyl)phosphine as ligand has a significant effect in accelerating the Rh-catalyzed addition of aryl- and 1-alkenylboronic acids to aldehydes even at room temperature.
M. Ueda, N. Miyaura, J. Org. Chem., 2000, 65, 4450-4452.
A Ni complex with a 1,5-diaza-3,7-diphosphacyclooctane ligand catalyzes a reductive or redox-neutral coupling of aryl iodides with either aldehydes or alcohols, respectively. The P2N2 ligand was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs.
E. S. Isbrandt, A. Nasim K. Zhao, S. G. Newman, J. Am. Chem. Soc., 2021, 143, 14646-14656.
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.
Multicatalytic protocols convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition.
A. Casnati, D. Lichosyt, B. Lainer, L. Veth, P. Dydio, Org. Lett., 2021, 23, 3502-3506.
A visible-light-induced cobalt-catalyzed asymmetric reductive 1,2-addition of aryl iodides to aldehydes provides chiral benzyl alcohols in very good yield, and high ee. This methodology offers mild reaction conditions, good functionality tolerance, excellent enantiocontrol, the avoidance of mass metal wastes, and the use of precious metal catalysts.
X. Jiang, H. Jiang, Q. Yang, Y. Cheng, L.-Q. Lu, J. A. Tunge, W.-J. Xiao, J. Am. Chem. Soc., 2022, 144, 8347-8354.
Chiral amino thioacetate ligands were remarkably superior to the corresponding amino alcohols as catalysts for enantioselective aryl transfer reactions. Low catalyst loadings were sufficient to achieve excellent enantioselectivity as well as high conversion in short reaction time.
M.-J. Jin, S. M. Sarkar, D.-H. Lee, H. Qiu, Org. Lett., 2008, 10, 1235-1237.
Diastereomeric aziridine carbinols are applied as efficient chiral ligand in a catalyzed asymmetric arylation and sequential arylation-lactonization cascade. The two diastereomers, which are facilely synthesized from the same chiral source, function as pseudo enantiomers in arylation of aromatic aldehydes providing the different enantiomers of the diarylmethanols with almost the same excellent enantioselectivities.
X. Song, Y.-Z. Hua, J.-G. Shi, P.-P. Sun, M.-C. Wang, J. Chang, J. Org. Chem., 2014, 79, 6087-6093.
The value of stable and easily accessible triarylborane ammonia complexes as precursors for arylzinc reagents in asymmetric catalysis is demonstrated. Various chiral diarylmethanols were synthesized in high yield and enantioselectivity.
S. Dahmen, M. Lormann, Org. Lett., 2005, 7, 4597-4600.
A chiral N-heterocyclic carbene (NHC)-nickel complex catalyzes an enantioconvergent upgrading reaction of simple racemic secondary alcohols to enantioenriched tertiary alcohols. In this highly efficient formal asymmetric alcohol α-C-H arylation, a dehydrogenation with phenyl triflate as a mild oxidant is followed by asymmetric addition of arylboronic esters to the transient ketones.
Y. Cai, S.-L. Shi, J. Am. Chem. Soc., 2021, 143, 11963-11968.
A chiral zinc complex of salen is an efficient catalyst for the phenyl transfer from an organozinc reagent to aromatic aldehydes and acetophenones with high enantioselectivities.
K. Shimizu, H. Uetsu, T. Gotanda, K. Ito, Synlett, 2015, 26, 1238-1242.
Enantiomerically enriched diarylmethanols have been prepared by catalyzed asymmetric phenyl transfer reactions onto aromatic aldehydes with use of readily available β-hydroxysulfoximines as catalysts. Various functionalized aldehydes and heterocyclic substrates are tolerated, yielding synthetically relevant products.
J. Sedelmeier, C. Bolm, J. Org. Chem., 2007, 72, 8859-8862.
Simple nickel complexes of bipyridine and PyBox catalyze the addition of aryl halides to both aromatic and aliphatic aldehydes using zinc metal as the reducing agent. This convenient approach tolerates acidic functional groups that are not compatible with Grignard reactions, yet sterically hindered substrates still couple in high yield.
K. J. Garcia, M. M. Gilbert, D. J. Weix, J. Am. Chem. Soc., 2019, 141, 1823-1827.
The use of activated Magnesium (Rieke Magnesium) enables the preparation of functionalized Grignard reagents at low temperatures. The Grignard reagents were reacted with several electrophiles such as benzaldehyde, benzoyl chloride, or allyl iodide. The reaction of benzoyl chloride yielded ketones with little or no addition to the carbonyl functionality due to the low temperature.
J.-s. Lee, R. Valerde-Ortiz, A. Guijarro, R. D. Rieke, J. Org. Chem., 2000, 65, 5428-5430.
A variety of functionalized organozinc reagents undergo smooth addition reactions at ambient temperature to carbonyl compounds and carbon dioxide in the presence of stoichiometric amounts of MgCl2. Several reactions were performed on a large scale.
S. Bernhardt, A. Metzger, P. Knochel, Synthesis, 2010, 3802-3810.
An efficient new methodology for the arylation of aldehydes is disclosed which uses dirhodium(II) catalysts and N-heterocyclic carbene (NHC) ligands. An N-heterocyclic carbene monocomplex of dirhodium(II) acetate was shown to be the most active catalyst and was particularly efficient in the arylation of alkyl aldehydes.
A. F. Trindade, P. M. P. Gois, L. F. Veiros, V. André, M. T. Duarte, C. A. M. Afonso, S. Caddick, F. G. N. Cloke, J. Org. Chem., 2008, 73, 4076-4086.
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 1,2-addition of aryl- or heteroarylboronic acids to aldehydes in the presence of PdCl2 and P(1-Nap)3 affords carbinol derivatives in very good yields. The reaction tolerates nitro, cyano, acetamido, acetoxy, acetyl, carboxyl, trifluoromethyl, fluoro, and chloro groups and allows the conversion of aliphatic aldehydes and hindered substrates.
C. Qin, H. Wu, J. Cheng, X. Chen, M. Liu, W. Zhang, W. Su, J. Ding, J. Org. Chem., 2007, 72, 4102-4107.
Anionic four-electron donor-based palladacycles were highly efficient, practical catalysts for 1,4-additions of arylboronic acids with α,β-unsaturated ketones and 1,2-additions of arylboronic acids with aldehydes and α-ketoesters.
P. He, Y. Lu, C.-G. Dong, Q.-S. Hu, Org. Lett., 2007, 9, 343-346.
Cationic Pd(II) complex-catalyzed addition of arylboronic acids to aldehydes gave diarylmethanols in high yields with low catalyst loading. A one-pot synthesis of unsymmetrical triarylmethanes from arylboronic acids, aryl aldehydes, and electron-rich arenes was achieved in high yields.
S. Lin, X. Lu, J. Org. Chem., 2007, 72, 9757-9760.
The use of ZnCl2, Me3SiCH2MgCl, and LiCl effectively minimizes problematic side reactions in the 1,2-addition of strongly basic alkyl and aryl Grignard reagents to ketones. Aldimines give secondary amines in high yield. The simplicity of this reliable ZnCl2•Me3SiCH2MgCl•LiCl system might be attractive for industrial as well as academic applications.
M. Hatano, O. Ito, S. Suzuki, K. Ishihara, J. Org. Chem., 2010, 75, 5008-5016.
Aldehydes and siloxanes form methyl esters in a single step through mild oxidative esterification in the presence of a palladium catalyst or, alternatively, afford secondary alcohols via TBAF-promoted arylation in the absence of a catalyst at increased temperatures.
R. Lerebours, C. Wolf, J. Am. Chem. Soc., 2006, 128, 13052-13053.
A H8-binol derived catalyst allows high enantioselectivity in the reaction of diphenylzinc with both aliphatic and aromatic aldehydes. The use of this catalyst avoids the need for additives such as diethylzinc and the mild asymmetric reaction conditions make this chiral catalyst useful for general synthesis.
Y.-C. Qin, L. Pu, Angew. Chem. Int. Ed., 2006, 45, 273-277.
In a highly efficient enantioselective organozinc addition to ketones, chiral phosphoramide-Zn(II) complexes serve as conjugate Lewis acid-Lewis base catalysts. From a variety of nonactivated aromatic and aliphatic ketones, the corresponding optically active tertiary alcohols were obtained in high yields with high enantioselectivities under mild reaction conditions.
M. Hatano, T. Miyamoto, K. Ishihara, Org. Lett., 2007, 9, 4535-4538.
The asymmetric addition of phenyl groups from diphenylzinc to ketones gives good to excellent enantioselectivity with a range of substrates, using a catalyst generated from a dihydroxy bis(sulfonamide) ligand and titanium tetraisopropoxide.
C. Garcia, P. J. Walsh, Org. Lett., 2003, 5, 3641-3644.
An efficient palladium-catalyzed Suzuki-Miyaura reaction of oxygen atom-substituted allylboronates with aryl/vinyl bromides, iodides, and triflates provides various allylic siloxanes with high efficiency and excellent regioselectivity. This alternative approach for the synthesis of allylic alcohols offers broad substrate scope, excellent functional group tolerance, and gram-scale preparation.
J. Li, X. Zhang, Y. Yao, Y. Gao, W. Yang, W. Zhao, J. Org. Chem., 2022, 87, 6951-6959.
A palladium(0) complex with chloroform is able to catalyze the addition of arylboronic acids to aldehydes in the presence of a base, affording the corresponding secondary alcohols in good yields. A catalytic amount of chloroform seems to be essential for this reaction.
T. Yamamoto, T. Ohta, Y. Ito, Org. Lett., 2005, 7, 4151-4155.
The addition of diverse organometallic reagents to 1-phenylsulfonylcyclopropanols enables a simple and high-yielding synthesis of 1-substituted cyclopropanols. The transformation is amenable to sp-, sp2-, or sp3-hybridized organometallic C-nucleophiles under mild conditions, and the use of enantioenriched substrates led to highly diastereoselective additions.
R. M. Rivera, Y. Jang, C. M. Poteat, V. N. G. Lindsay, Org. Lett., 2020, 22, 6510-6515.
Kinetic vs thermodynamic deprotonation studies on secondary and tertiary sulfonamides using n-BuLi have been carried out. Application of the developed conditions allows the synthesis of diverse sulfonamide products (E=CH(OH)Ph).
S. L. MacNeil, O. B. Familoni, V. Snieckus, J. Org. Chem, 2001, 66, 3662-3670.
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.
A combination of weak Lewis acid (LiCl) and weak Brønsted acid (hexafluoroisopropanol, HFIP) promotes efficiently the Friedel-Crafts reaction of electron-rich aromatic compounds with ethyl glyoxylate.
M. Willot, J. Chen, J. Zhu, Synlett, 2009, 577-580.
The asymmetric Friedel-Crafts reaction of N,N-dialkylanilines with ethyl glyoxylate has been achieved by the catalysis of titanium complexes of BINOL derivatives to give the corresponding mandelic acid ethyl esters in high yields (85-99%) and good to excellent enantioselectivity (80-96.6% ee).
Y. Yuan, X. Wang, X. Li, K. Ding, J. Org. Chem., 2004, 69, 146-149.
Enantioconvergent arylation reactions of boronic acids and racemic β-stereogenic α-keto esters are catalyzed by a chiral (diene)Rh(I) complex and provide a wide array of β-stereogenic tertiary aryl glycolate derivatives with high levels of diastereo- and enantioselectivity.
S. L. Bartlett, K. M. Keiter, J. S. Johnson, J. Am. Chem. Soc., 2017, 139, 3911-3916.
Chiral allenes appended with basic functionality can serve as ligands for transition metals. An allene-containing bisphosphine coordinated to Rh(I) promotes the asymmetric addition of arylboronic acids to α-keto esters with high enantioselectivity. Solution and solid-state structural analysis reveals that one olefin of the allene can coordinate to transition metals, generating bi- and tridentate ligands.
F. Cai, X. Pu, X. Qi, V. Lynch, A. Radha, J. M. Ready, J. Am. Chem. Soc., 2011, 133, 18066-18069.