Bromo ketones, from alcohols

YVe saw in Section 17.4 that keLones react with NaBH4 to yield alcohols. We ll also see in Section 22.3 that ketones react writh Br2 to yield a-bromo ketones. Perhaps surprisingly, treatment with NaBH4 of the a-bromo ketone from acetophenone yields an epoxide rather than a bromo alcohol. Show the structure of the epoxide, and explain its formation. 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

Conjugation of the double bond to a ketone, with rearrangement, likewise gave a good yield of 6,6-diphenylbicyclo[3.1.0]hex-3-en-2-one (6) from the starting a-bromo ketone 5 and potassium fer/-butoxide in tert-butyl alcohol. 

Ye, L., and Zhang, L. (2009). Practical s3Tithesis of linear a-iodo/bromo-a, p-unsaturated aldehydes/ ketones from propargylic alcohols via Au/Mo bimetallic catalysis. Org. Lett., 11, 3646-3649. 

The chiral intermediate (S)-l-(2 -bromo-4 -fluorophenyl) ethanol was prepared by the enantioselective microbial reduction of 2-bromo-4-fiuoroacetophenone [lObj. Organisms from genus Candida, Hansmula, Pichia, Rhodotcnda, Saccharomyces, Sphingomonas, and baker s yeast reduced the ketone to the corresponding alcohol in... 

Preparation of 18,18,18-trifluororetinal required synthesis of trifluorocyclocitral as precursor. For this purpose, the 1,4-addition of a cuprate (prepared from an a>-bromo-trifluoromethylcarbinol) onto a vinylidene phosphonate was performed. The alcohol moiety is then deprotected and oxidized into ketone. A further intramolecular Wittig-Horner reaction, followed by reduction, led to trifluorocyclocitral. 18,18,18-Trifluororetinal is then easily obtained from this compound (Figure 4.25). ... 

In a new method of ring enlargement of oxiranes to oxetanes, the intramolecular Williamson reaction is the essential last step. Reaction of an oxirane with selenomethyl-lithium reagents, followed by bromination, gives y-bromo alcohols, which can be cyclized by base to oxetanes. Since the oxiranes can be prepared readily from ketones and the selenomethyllithium reagent, this is also a synthesis of oxetanes from ketones (80TL585). 

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