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Synthesis of β-hydroxy carboxylic acids, esters and amides

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Catalytic Bu₄NOAc as silicon activator of ethyl 2-(trimethylsilyl)acetate enables the synthesis of β-hydroxy esters, whereas catalytic Bu₄NOTMS provides α,β-unsaturated esters. The established reaction conditions were applicable to a diverse range of aromatic, heteroaromatic, aliphatic aldehydes and ketones.
M. Das, A. Manvar, I. Fox, D. J. Roberts, D. F. O'Shea, Synlett, 2017, 28, 2401-2406.

Activation of the silicon-carbon bond of α-trimethylsilylethylacetate in the presence of P(i-PrNCH₂CH₂)₃N as catalyst allows an efficient synthesis of β-hydroxyesters and α,β-unsaturated esters. Selectivity for either of these two products can be achieved simply by altering the catalyst loading and reaction temperature.
K. Wadhwa, J. G. Verkade, J. Org. Chem., 2009, 74, 4368-4371.

An efficient and simple Cu-catalyzed Reformatsky reaction of carbonyl compounds with ethyl iodoacetate provides excellent yields of β-hydroxyl esters using inexpensive starting materials under mild reaction conditions.
L. Ouyang, J. H. Liao, Y. P. Xia, R. S. Luo, Synlett, 2020, 31, 1418-1422.

Boron compounds and a mild organic base (DBU) mediate a carboxylic acid selective aldol reaction. Electron-withdrawing groups in amino acid derivative ligands reacted with BH₃·SMe₂ forms a boron promoter with increased Lewis acidity at the boron atom, which facilitated the carboxylic acid selective enolate formation. The reaction tolerates other carbonyl groups such as amides, esters, ketones, or aliphatic aldehydes.
H. Nagai, Y. Morita, Y. Shimizu, M. Kanai, Org. Lett., 2016, 18, 2276-2279.

A proazaphosphatrane is a very efficient catalyst for Mukaiyama aldol reactions of aldehydes with trimethylsilyl enolates in THF solvent. The reaction conditions are mild and operationally simple, and a variety of aryl functional groups, such as nitro, amino, ester, chloro, trifluorometh yl, bromo, iodo, cyano, and fluoro groups, are tolerated.
V. R. Chintareddy, K. Wadhwa, J. G. Verkade, J. Org. Chem., 2009, 74, 8118-8132.

Rh-DuPhos catalyzes an in situ conjugate reduction of an unsaturated carbonyl compound with Cl₂MeSiH to provide an (E)-silylketene acetal. This enolate undergoes a noncatalyzed reaction with a variety of aldehydes to give the derived syn-aldol adducts in high yields and diastereoselection.
C.-X. Zhao, J. Bass, J. P. Morken, Org. Lett., 2001, 3, 2839-2842.

A direct enantioselective α-hydroxymethylation of aldehydes employing an α,α-diarylprolinol trimethylsilyl ether organocatalyst enables efficient access to β-hydroxycarboxylic acids and δ-hydroxy-α,β-unsaturated esters via an intermediate lactol in good yields, excellent enantioselectivity, and compatibility with a broad range of functional groups in the aldehyde.
R. K. Boeckman, K. F. Biegasiewicz, D. J. Tusch, J. R. Miller, J. Org. Chem., 2015, 80, 4030-4045.

Acetic Acid Aldol Reactions in the Presence of Trimethylsilyl Trifluoromethanesulfonate
C. W. Downey, M. W. Johnson, D. H. Lawrence, A. S. Fleisher, K. J. Tracy, J. Org. Chem., 2010, 75, 5351-5354.

The choice of either the solvent or temperature determines the diastereoselectivity during the enolboration-aldolization of methyl phenylacetate. In CH₂Cl₂, the reaction favors the anti-pathway at -78 °C and the syn-pathway at rt. Conversely, the reaction produces the anti-isomer up to rt and the syn-isomer at refluxing temperatures in nonpolar solvents.
P. V. Ramachandran, P. B. Chanda, Org. Lett., 2012, 14, 4346-4349.

Whereas a dicyclohexylboron triflate/triethylamine (Cy₂BOTf/Et₃N)-mediated enolboration-aldolization reaction of methyl arylacetates provides anti-aldols at low temperatures, a combination of a less bulky boron reagent (dibutylboron triflate, Bu₂BOTf), a bulky amine (iPr₂NEt), and ambient temperature is required to obtain syn-aldols.
A. Y. Thomas, T. L. Walls III, B. N. Nelson, S. W. Primeaux, P. B. Chanda, J. Org. Chem., 2021, 86, 6184-6194.

The Mukayiama aldol reaction of aldehydes is efficiently catalyzed by a dimeric alumatrane complex at mild or subambient temperatures. The protocol tolerates a wide variety of electron-rich, neutral, and deficient aryl, alkyl, and heterocyclic aldehydes. A wide variety of enol silyl ethers are also tolerated.
S. M. Raders, J. G. Verkade, J. Org. Chem., 2009, 74, 5417-5428.

N-Heterocyclic Carbene-Catalyzed Mukaiyama Aldol Reactions
J. J. Song, Z. Tan, J. T. Reeves, N. K. Yee, C. H. Senanayake, Org. Lett., 2007, 9, 1013-1016.

Reusable polymer-bound lithium dialkylamides were employed in crossed aldol reaction of various carbonyl compounds with aldehydes to afford the corresponding β-hydroxycarbonyl compounds. The introduction of spacer chains between the base moiety and the polystyrene backbone increased the yields of the desired aldol adducts.
A. Seki, F. Ishiwata, Y. Takizawa, M. Asami, Tetrahedron, 2004, 60, 5001-5011.

One-Pot Enol Silane Formation-Mukaiyama Aldol-Type Addition to Dimethyl Acetals Mediated by TMSOTf
C. W. Downey, M. W. Johnson, K. J. Tracy, J. Org. Chem., 2008, 73, 3299-3302.

Simple thioesters undergo direct aldol addition to aldehydes in the presence of a Lewis acid and i-Pr₂NEt. The reactions proceed extremely rapidly and in excellent yield.
J. M. Yost, G. Zhou, D. M. Coltart, Org. Lett., 2006, 8, 1503-1506.

A novel method for Reformatsky-like reactions employs titanocene(III) chloride as a mild and homogeneous single-electron reductant. The reactions are simple, rapid and tolerate a wide range of functionalities. The addition is anti selective.
J. D. Parrish, D. R. Shelton, R. D. Little, Org. Lett., 2003, 5, 3615-3617.

An easy, direct, general, and efficient samarium diiodide-mediated preparation of 3-hydroxyacids in high yield by reaction of different aldehydes or ketones with commercially available iodoacetic acid is described.
J. M. Concellón, C. Concellón, J. Org. Chem., 2006, 71, 4428-4432.

A readily available chiral bisoxazolidine catalyzes the asymmetric Reformatsky reaction between ethyl iodoacetate and aromatic aldehydes to yield 3-hydroxy-3-(4-aryl)propanoates in high yields and good enantioselectivities in the presence of dimethylzinc and air at room temperature within 1 h. In contrast to aromatic substrates, relatively low ee’s are obtained with aliphatic aldehydes.
C. Wolf, M. Moskowitz, J. Org. Chem., 2011, 76, 6372-6376.

Efficient In- or In(I)-based diastereoselective Reformatsky-type reactions of simple ketones, α-alkoxy ketones, and β-keto esters were developed. High anti selectivity was established in the addition of the branched α-halo ester derivatives to simple ketones using indium metal under THF-refluxing conditions. Syn selective additions to α-alkoxy ketones and β-keto esters required either In(I)X or In-InCl₃ systems in toluene under ultrasonication.
S. A. Babu, M. Yasusa, I. Shibata, A. Baba, J. Org. Chem., 2005, 70, 10408-10419.

S. A. Babu, M. Yasusa, I. Shibata, A. Baba, J. Org. Chem., 2005, 70, 10408-10419.

The addition of amide enolates to acylsilanes and a subsequent 1,2-Brook rearrangement generate β-silyloxy homoenolates nucleophiles that undergo smooth addition to alkyl halides, aldehydes, and ketones.
R. B. Lettan II, T. E. Reynolds, C. V. Galliford, K. A. Scheidt, J. Am. Chem. Soc., 2006, 128, 15566-15567.

A tandem Wittig Rearrangement/aldol reaction of O-benzyl or O-allyl glycolate esters generates two carbon-carbon bonds and two contiguous stereocenters with excellent diastereoselectivity in a single step from simple starting materials. The [1,2]-Wittig rearrangement proceeds under very mild reaction conditions.
M. B. Betrand, J. P. Wolfe, Org. Lett., 2006, 8, 4661-4663.

Chiral rhodium(bisoxazolinylphenyl) complexes efficiently catalyze the asymmetric reductive aldol reaction of aldehydes and α,β-unsaturated esters with hydrosilanes to give the corresponding β-hydroxypropionates with high anti-selectivity and enantioselectivity. The selectivity is discussed.
H. Nishiyama, T. Shiomi, Y. Tsuchiya, I. Matsuda, J. Am. Chem. Soc., 2005, 127, 6972-6973.

A new strategy for the catalytic asymmetric aldol reaction of ketones was developed that relies on a chiral copper(I) complex-catalyzed domino reduction/aldol reaction sequence in the presence of phenylsilane.
J. Deschamp, O. Chuzel, J. Hannedouche, O. Riant, Angew. Chem. Int. Ed., 2006, 45, 1292-1297.

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 conjugated and nonconjugated aldehydes with silyl ketene acetals and silyl dienol ethers (vinylogous aldol reactions). 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..

C-H functionalization of benzyl silyl ethers by means of rhodium-catalyzed insertions of aryldiazoacetates can be achieved in a highly diastereoselective and enantioselective manner by judicious choice of chiral catalyst or auxiliary. The use of (S)-lactate as a chiral auxiliary resulted in C-H functionalization with moderate diastereoselectivity and enantioselectivity. The best results were achieved using Hashimoto's Rh₂((S)-PTTL)₄ catalyst.
H. M. L. Davies, S. J. Hedley, B. R. Bohall, J. Org. Chem., 2005,70, 10737-10742.

Related

An efficient carbene-catalyzed formal [4 + 2] annulation of β-silyl enones with a HOBT ester followed by ring opening with nucleophiles provides γ-keto-β-silyl esters and amides, most with extremely high enantioselectivities. γ-Keto-β-silyl esters can be easily converted into enantioenriched β,σ-dihydroxyl esters.
Y. Zhang, X. Huang, J. Guo, C. Wei, M. Gong, Z. Fu, Org. Lett., 2020, 22, 9545-9550.

The catalytic generation of activated carboxylates from epoxyaldehydes enables a direct, anti-selective, convenient and mild synthesis of β-hydroxyesters.
K. Y.-K. Chow, J. W. Bode, J. Am. Chem. Soc., 2004, 126, 8126-8127.

A mild, Co₂(CO)₈-catalyzed carbonylative opening of terminal epoxides under 1 atm of carbon monoxide at room temperature in methanol provides β-hydroxy esters in good yields. This transformation tolerates various functional groups.
S. E. Denmark, M. Ahmad, J. Org. Chem., 2007, 72, 9630-9634.

A pH-independent asymmetric transfer hydrogenation of β-keto esters in water with formic acid/sodium formate can be conducted open to air and gives access to β-hydroxy esters in excellent yields and selectivities.
M. A. Ariger, E. M. Carreira, Org. Lett., 2012, 14, 4522-4524.

A mild, enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters using axially chiral BINAM N-heterocyclic carbene (NHC)-Rh(III) complexes as catalysts gave 3-hydroxy-3-arylpropionic acid methyl or ethyl esters in good yields with good to excellent enantioselectivities under mild conditions.
Q. Xu, X. Gu, S. Liu, Q. Duo, M. Shi, J. Org. Chem., 2007, 72, 2240-2242.