Halohydrin formation from

Several examples of halohydrin formation from styrene derivatives and saccharides catalyzed by CPO are reviewed by Adam and coworkers [23], Formation of bromohydrin derivatives of some saccharides can be of interest for the preparation of bioactive compounds [72]. 

A MECHANISM FOR THE REACTION ] Halohydrin Formation from an Alkene 365... 

The more highly substituted carbon atom bears a greater positive charge because it resembles a more stable tertiary carbocation. [Notice how this reaction (and its explanation) resembles that given for halohydrin formation from unsymmetrical alkenes in Section 8.14 and attack on mercurinium ions.]... 

A silver-ion assisted halohydrin formation from a,p-unsaturated carboxylic acid derivatives was performed with chiral A-enoyl-2-oxazolidinones to form awri-o -halo- S-hydroxy carbonyls in good yields (90-94%, eq 2S). This alternate method of carboxyhalohydrin asymmetric-synthesis produced better diastereoselectivity (up to S,S RJi = 80 20) with AgOAc (or AgNOg) than with Ag2C03. The observed stereoselectivity required a nonnucleophilic (alkyl) substituent on the oxazolidi-none chiral auxiliary. 

Propylene oxide has found use in the preparation of polyether polyols from recycled poly(ethylene terephthalate) (264), haUde removal from amine salts via halohydrin formation (265), preparation of flame retardants (266), alkoxylation of amines (267,268), modification of catalysts (269), and preparation of cellulose ethers (270,271). 

Bartnicki EW, CE Castro (1969) Biodehalogenation. The pathway for transhalogenation and the stereochemistry of epoxide formation from halohydrins. Biochemistry 8 4677-4680. 

Numerous biocatalytic routes to this challenging intermediate have been reported. " For example. Fox et al. have recently developed an efficient regioselective cyanation starting from low-cost epichlorohydrin (Scheme 1.26). Initial experiments found that halohydrin dehydrogenase from Agrobacterium radiobacter expressed in E. coli produced the desired product, but inefficiently. To meet the projected cost requirements for economic viability, the product needed to be produced at 100 g L with complete conversion and a 4000-fold increase in volumetric productivity. The biocatalyst needed to function under neutral conditions to avoid by-product formation, which causes downstream processing issues. 

The diastereoselective halohydrin formation, resulting from the reaction of chiral /V -enoyI -2-oxazoI idinones with Br2/l2 and water, promoted in the presence of silver , in aqueous organic solvents, has been found to occur with high regioselectivity and moderate to good diastereoselectivities. The alkenoyl, cinnamoyl, and electron-deficient cinnamoyl substrates readily produced the bromohydrin in aqueous acetone, but no iodohydrin formation was observed under these conditions. On the other hand, ( ) electron-rich cinnamoyl substrates preferred to afford iodohydrins in aqueous acetone with moderate diastereoselectivity enhanced diastereoselectivity was observed for aqueous THF.31... 

Halohydrin formation with subsequent reductive dehalogcnation represents an interesting variation on the theme. For example, when the enone rac-1 was treated with A -bromosuccin-imide in aqueous dimethyl sulfoxide, the bromohydrin roc-2 was formed, predominantly as one diastereomer (the relative configuration at C-3 was not established)23. Reduction with tri-butyltin hydride gave the diastereomeric products exo-3 and endo-3 in 27% and 63% yield, respectively. Here, the product distribution can be explained by the preferred attack of the hydride reagent on the exo-face of the intermediate bicyclic carbon radical, i.e., by kinetic control. Thus, the predominant endo-orientation of the 2-(2-hydroxypropyl) substituent at C-3 was achieved, in contrast to what may be expected from a reversible, i.e., thermodynamically controlled, hydration of the enone rac-1. 

The mechanism for halohydrin formation is similar to the mechanism for halogenation addition of the electrophile X (from X2) to form a bridged halonium ion, followed by nucleophilic attack by H2O from the back side on the three-membered ring (Mechanism 10.4). Even though X is formed in Step [1] of the mechanism, its concentration is small compared to H2O (often the solvent), so H2O and not X" is the nucleophile. 

The mechanism for halohydrin formation involves the formation of a cyclic bromo-nium ion (or chloronium ion) in the first step of the reaction, because Br (or Cl ) is the only electrophile in the reaction mixture. In the second step, the bromonium ion rapidly reacts with whatever nucleophile it bumps into. In other words, the electrophile and nucleophile do not have to come from the same molecule. There are two nucleophiles present in solution H2O and Br . Because H2O is the solvent, its concentration far exceeds that of Br . Consequently, the bromonium ion is more likely to collide with a molecule of water than with Br . The protonated halohydrin that is formed is a strong acid (Section 1.19), so it loses a proton. 

From the following alkene precursors, show products of halohydrin formation. 

In a reaction resembling halohydrin formation (Section 6.17), vicinal haloethers are prepared from alkenes by reaction with an alcohol in the presence of halogens— usually bromine or iodine. This haleotherification proceeds through a cyclic halonium ion, which reacts with the alcohol. 1-Methylcyclohexene undergoes iodoetherification with ethanol in the presence of iodine to give ran -l-ethoxy-2-iodo-l-methylcyclohexane. 

Carbonyl Compounds by Oxidation of Alcohols and Aldehydes. Salts of palladium, in particular PdCl2 in the presence of a base, catalyze the CCI4 oxidation of alcohols to aldehydes and ketones. Allylic alcohols carrying a terminal double bond are transformed to 4,4,4-trichloro ketones at 110 °C, but yield halo-hydrins at 40 °C. These can be transformed to the corresponding trichloro ketones under catalysis of palladium acetate (eq 56). The latter transformation could be useful for the formation of ketones from internal alkenes provided the halohydrin formation is regioselective. 

The formation of vicinal halohydrins from alkenes was described in Section 6.17. Halohydrins are readily converted to epoxides on treatment with base ... 

---