Categories: C-O Bond Formation > Synthesis of alcohols (hydroxylation) >
Synthesis of β-hydroxy ketones, esters, nitriles and related compounds
The direct addition of water and a variety of alcohols to activated olefins was observed in the presence of nucleophilic phosphine catalysts. Unlike existing methods, the reactions proceed at room temperature and in the absence of transition metals, or strong acids or bases.
I. C. Stewart, R. G. Bergman, F. D. Toste, J. Am. Chem. Soc., 2003, 125, 8696-8697.
A combined amino- and N-heterocyclic carbene (NHC)-catalyzed one-pot reaction sequence using commercially available catalysts at low catalyst loadings gives β-hydroxy and β-amino esters in high yield and excellent enantiopurity. The generation of quaternary stereocenters and application in gram-scale synthesis were also realized, with no requirements of inert or anhydrous reaction conditions.
H. Jiang, B. Gschwend, Ł. Albrecht, K. A. Jørgensen, Org. Lett., 2010, 12, 5052-5055.
Bidentate Oxazoline-substituted imidazolium salts based on [2.2]paracyclophane with planar and central chirality can be used as ligand in Cu(I)-catalyzed asymmetric β-boration of α,β-unsaturated esters, giving the desired products in high enantioselectivities and yields.
Z. Niu, J. Chen, Z. Chen, M. Ma, C. Song, Y. Ma, J. Org. Chem., 2015, 80, 602-608.
A Rh-catalyzed hydroboration of α, β-unsaturated carbonyl compounds with pinacolborane proceeds with high levels of regio-, diastereo-, and enantioselectivities to provide products with two vicinal stereocenters. Through the appropriate choice of substrate geometry (E or Z) and ligand enantiomer, all possible diastereoisomers are readily accessible.
T.-T. Gao, W.-W. Zhang, X. Sun, H.-X. Lu, B.-J. Li, J. Am. Chem. Soc., 2019, 141, 4670-4677.
An N-heterocyclic carbene-catalyzed oxidative single-electron-transfer reaction enables the β-hydroxylation of enals through a pathway involving multiple radical intermediates, as supported by experimental observations. The reaction allows a highly enantioselective access to β-hydroxyl esters that are widely found in natural products and bioactive molecules.
Y. Zhang, Y. Du, Z. Huang, J. Xu, X. Wu, Y. Wang, M. Wang, S. Yang, R. D. Webster, Y. R. Chi, J. Am. Chem. Soc., 2015, 137, 2416-2419.
An efficient intermolecular conjugate addition of various primary and secondary alcohols to unsaturated ketones and esters is catalyzed by the free carbene derived from IMes·HCl. No oligomerization is observed under these mild conditions. In addition to reactions with activated alkenes, IMes catalyzes the formation of vinyl ethers through the 1,4-addition of alcohols to ynones.
E. M. Phillips, M. Riedrich, K. A. Scheidt, J. Am. Chem. Soc., 2010, 132, 13179-13181.
A variety of α,β-unsaturated ketones effectively reacted in an efficient chromium(III) chloride-catalyzed Michael-type addition with either water or alcohols to give the corresponding β-hydroxyl ketones or β-alkoxyl ketones in good yields with excellent functional group compatibility. The approach was further utilized for the preparation of synthetically useful tetrahydrofuran derivatives.
J.-J. Yun, X.-Y. Liu, W. Deng, X.-Q. Chu, Z.-L. Shen, T.-P. Loh, J. Org. Chem., 2018, 83, 10898-10907.
A new palladium-catalyzed method allows the oxygenation of unactivated sp3 C-H bonds of a wide variety of alkane substrates containing readily available oxime and/or pyridine directing groups with extremely high levels of chemo-, regio-, and in some cases diastereoselectivity.
L. V. Desai, K. L . Hull, M. S. Sanford, J. Am. Chem. Soc., 2004, 126, 9542-9543.
R. Shintani, K. Okamoto, T. Hayashi, Org. Lett., 2005, 7, 4757-4759.
Low-valent Cp2TiCl selectively reduces selected α,β-epoxy ketones to the corresponding aldol products under mild conditions. A chiral epoxide was converted without any loss of optical purity. The addition of collidine hydrochloride enables a system catalytic in titanocene.
C. Hardouin, F. Chevallier, B. Rousseau, E. Doris, J. Org. Chem., 2001, 66, 1046-1048.