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Synthesis of chlorohydrins

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Highly regioselective ring opening of epoxides to halohydrins has been carried out in impressive yields with hydrogen and lithium halides in presence of β-cyclodextrin using water as solvent.
M. Arjun Reddy, K. Surendra, N. Bhanumathi, K. Rama Rao, Tetrahedron, 2002, 58, 6003-6008.

The use of trihaloisocyanuric acid/triphenylphosphine enables a regioselective conversion of epoxides to vicinal chloro-/bromohydrins and vicinal dihalides under mild and neutral conditions in acetonitrile. The reactions proceed smoothly in high yield at room temperature and at reflux, respectively, over a short time.
V. S. C. de Andrade, M. C. S. de Mattos, Synthesis, 2016, 48, 1381-1388.

The preparation of diverse β-chloroethers, β-chloroacetates, and chlorohydrins is efficiently achieved under mild conditions by reaction of alkenes with trichloroisocyanuric acid in alcohols, acetic acid or aqueous acetone, respectively.
G. Fonseca Mendonça, A. Manzolillo Sanseverino, M. C. S. de Mattos, Synthesis, 2003, 45-48.

G. Fonseca Mendonça, A. Manzolillo Sanseverino, M. C. S. de Mattos, Synthesis, 2003, 45-48.

A green, oxidant-free electrochemical method enables radical bromination, chlorination and trifluoromethylation-formyloxylation of various alkenes with readily available halogen radical (NaCl, NaBr), and trifluoromethyl radical (CF3SO2Na) sources in DMF as formyloxylation reagent in an undivided electrochemical cell.
X. Sun, H.-X. Ma, T.-S. Mei, P. Fang, Y. Hu, Org. Lett., 2019, 21, 3167-3171.

SnCl4 and TiCl4 as Lewis acids and chloride nucleophiles enable selective and regiodivergent openings of unsymmetrical phenonium ions at either the substituted internal position (SnCl4) or unsubstituted terminal position (TiCl4). These reactions are highly selective, stereospecific, operationally simple, and proceed in good to excellent yields.
S. Xu, H. M. Holst, S. B. McGuire, N. J. Race, J. Am. Chem. Soc., 2020, 142, 8090-8096.

The use of the commercially available trichloromethanesulfonyl chloride enables an efficient α-chlorination of aldehydes, including a catalytic asymmetric version, under very mild reaction conditions. This chlorinating reagent facilitates workup and purification of the product, and minimizes the formation of toxic, chlorinated organic waste.
C. Jimeno, L. Cao, P. Renaud, J. Org. Chem., 2016, 81, 1251-1255.

PhICl2 in wet DMF forms an efficient system for difunctionalization of various alkenes to provide either regioselective chloroformyloxylated products or α-chlorinated olefinic products, depending on the type of structure of the original unsaturated starting material. The mechanism of the reaction is proposed and discussed.
L. Liu, D. Zhang-Negrerie, Y. Du, K. Zhao, Org. Lett., 2014, 16, 436-439.

An optically active, C2-symmetric allene-containing bisphosphine oxide catalyzes the addition of SiCl4 to meso-epoxides with high enantioselectivity. The epoxide opening likely involves generation of a Lewis acidic, cationic (bisphosphine oxide)SiCl3 complex.
X. Pu, X. Qi, J. M. Ready, J. Am. Chem. Soc., 2009, 131, 10364-10365.


The reaction of (chloromethyl)magnesium chloride-lithium chloride (ClCH2MgCl·LiCl), a mixed lithium-magnesium carbenoid, with aromatic aldehydes bearing various functional groups enables a highly chemoselective synthesis of a range of aromatic chlorohydrins in high yields.
R. H. V. Nishimura, V. E. Murie, R. A. Soldi, G. C. Clososki, Synthesis, 2015, 47, 1455-1460.

The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and a subsequent reaction with aldehydes and ketones provides chlorohydrins and epoxides in good yields within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench.
T. von Keutz, D. Cantillo, C. O. Kappe, Org. Lett., 2020, 22, 7537-7541.