Halohydrins cyclization

Synthesis of Oxirans by Halohydrin Cyclizations and Related Reactions. One of the oldest commercial methods for the production of ethene oxide is the chlorohydrin route, involving chlorohydration of ethene followed by dehydrochlorination. An improved procedure for the second stage of this process has been reported in which a basic ion-exchange resin is used to... 

This is the second example of the direct observation of an arene oxide during animal liver metabolism of arenes and has provided further evidence that the corresponding epoxides are the key molecules involved in aromatic hydrocarbon carcinogenesis (see also the section on halohydrin cyclization on p. 20). Since the first isolation of a natural product containing an intact epoxide group (1939) a large number of molecules of this type have been isolated. Typical examples recently reported include the coumarins (71) and (72), where the isoprenoid side-chains have been enzymatically epoxidized. The previously isolated Cecrqpia juvenile hormones (73 R = H or Me) have... 

Base promoted cyclization of vicinal halohydrms (Section 16 10) This reaction is an intramolecu lar version of the Williamson ether synthesis The alcohol function of a vicinal halohydrin is con verted to its conjugate base which then displa ces halide from the adjacent carbon to give an epoxide... 

Bicyclic compounds possessing fused 1,3,2-oxathiaphospholan and tetrahydro-thiophen rings are obtainable by reaction between a suitable halohydrin (49) and the anhydride (50), followed by cyclization of the intermediate (51) to give (52).43... 

Alkenes are converted to halohydrins by the treatment of halides and water. When halohydrins are treated with a strong base (NaOH), an intramolecular cyclization occurs and epoxides are formed. For example, 1-butene can be converted to butylene oxide via butylene chlorohydrin. 

Cyclization of halohydrins 0-16 Cyclization of 1,2-diols 0-18 Payne rearrangement of 2,3-epoxy alcohols... 

Mildly basic to neutral conditions for the ring closure of 1,3-halohydrins include tetra-phenylantimony methoxide as an effective non-basic reagent for oxetane synthesis from 1,3-bromohydrins (90S106). The salts of (3-halo acids cyclize in ionizing media to oxetan-2-ones, as do (3-diazonium carboxylates (64HC(l9-2)787). Thietanes are obtained analogously. 

Chiral halohydrins epoxides.1 The esters (2) of the chiral alcohol 1 derived from camphor-10-sulfonic acid, are converted to a-chloro esters (3) by O-silylation and reaction with NCS with high diastereoselectivity. Reduction of 3 with Ca(BH4)2 results in the recovered auxiliary and the chlorohydrin 4 with clean retention. Cyclization of 4 to the terminal epoxide 5 proceeds with clean inversion. 

Syn- and anti -selective halo-Prins cyclizations of 8,s-unsaturated ketones to give 1,3-halohydrins have been catalysed by Lewis acids, with syn selectivity correlating (g) with acid strength.184... 

Three inosamines were obtained in the course of efforts to synthesize myo-inositol by the nitro-sugar cyclization (see p. 142). However, the methods which have been the most productive of new inosamines are those which are well known as means of preparing amino sugars and aminopolyhydric alcohols, namely, reduction of imine derivatives of carbonyl compounds (in this case, inososes) and ammonolysis of halohydrins and epoxides. 

Based on the (/ )-specific ADH from L. kefir, a recombinant E. coli strain was constructed as a whole-cell biocatalyst, and co-expressed GDH was used for regeneration of NADPH [157]. These designer cells were applied for the reduction of 4-fluoroacetophenone to the corresponding optically active (/ )-4-fluorophe-nylethan-l-ol at 0.5 M educt concentration [158]. After a reaction time of 23 h, a conversion of >95% has been achieved, and the purified isolated chiral alcohol showed an ee value of >99% (87% yield). (S)-p-Halohydrins were obtained with this whole-cell catalyst by means of an enantioselective reduction of the corresponding ketones with both high conversions of >95% and enantioselectivities of >99% (Fig. 40). Base-induced cyclization of the [S-halohydrin led to enantiomeri-cally pure (S)-epoxides in high yield and enantiomeric purity (>99% ee) [159]. 

Fig. 40 Concept for the two-step synthesis of enantiomerically pure (S)-epoxides out of aliphatic 1-halogenated 2-ketones. The ketone was reduced by a recombinant whole-cell catalyst bearing alcohol dehydrogenase from Lactobacillus kefir (LKADH) and glucose dehydrogenase (GDH) for regeneration of NADPH. Base-induced cyclization of the enantiomerically pure (5)-(3-halohydrin intermediate gave the desired (S)-epoxides in high yield and enantiomeric purity (>99% ee)...

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

The mechanistic outline of carbenoid/carbonyl reactivity follows the paradigm illustrated at the outset of this chapter (Scheme 1 X = halogen). The nucleophilic lithium species adds to the carbonyl compound and suffers elimination to provide the epoxide. Competition from molecular rearrangements emanating from the intermediate halohydrin or the product epoxides is sometimes a problem, particularly with cyclic ketones. Also, the initial adduct frequently fails to cyclize when the reaction is quenched at low temperature, but it is usually a simple matter to effect ring closure by treatment of the halohydrin with mild base in a separate step. 

As final examples of the versatility of the Ritter reaction, bridged hemiacetals react by means of their acyclic form in solution to afford amido ketones in good yield (equation 29), while halohydrins give a-amido halides, which are readily cyclized to oxazoline derivatives in an overall stereospecific process. ... 

Ring opening of oxiranes with iodotrimethylsilane provides silylated halohydrins <84CHEC-l(7)in). An exception to this reaction mode has been reported <9iJOC4598>. Silyl enol ether-terminated oxiranes, when treated with TMS-I in the presence of hexamethyldisilazide (HMDS) at low temperatures suffer C—C cleavage and cyclization to dihydrofurans. 

Agawa, T., Kubo, T., and Ohshiro, Y, Synthesis of dialkyl epoxyphosphonates. Synthesis, 27, 1971. Sturtz, G., and Pondaven-Raphalen, A., Cyclization of 1,2-halohydrins of diethyl ethylphosphonate for the synthesis of diethyl 1,2-epoxyethylphosphonate, Phosphorus Sulfur, 20, 35, 1984. 

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