Ketones, 2-halo acyclic

The rearrangement with ring contraction probably is the most important synthetic application of the Favorskii reaction it is for example used in the synthesis of steroids. Yields can vary from good to moderate. As solvents diethyl ether or alcohols are often used. With acyclic a-halo ketones bearing voluminous substituents in a -position, yields can be low a tcrt-butyl substituent will prevent the rearrangement. 

Trimethylsilyl iodide (TMS—I), as such or generated in situ, is especially effective as a mild dehalogenation agent for halo ketones. The reaction appears to generate the enol silyl ether initially, and this is converted to the carbonyl compound during work-up (equation 12). Both cyclic and acyclic a-bromo and a-chloro ketones are dehalogenated, generally in excellent yields. Methyltrichlorosilane, on the other... 

Deconjugation of acyclic P-halo enones. MejSiCl catalyzes the isomerization of j3-halo a,)3-un aturated ketones to the corresponding 8,7-unsaturated ketones. 

Scheme 5 illustrates Tilak thiannulation by means of an acyclic a-halo ketone. This variation leads to an alkyl-substituted, terminally condensed thiophene ring. The cyclization of 194 to 195 (m.p. 271.5°C UV similar to that of chrysene) was effected in only 14% yield.63 In the only other use of... 

The second general route to 1,3-dioxepanes (1) involves acid-catalyzed alcohol exchange of an acyclic acetal (6) with a 1,4-diol (transacetalization) <8iJOC298i>, as demonstrated by the synthesis of (12 X = C1, Br) by reaction of 2-halo-1,1-dialkoxyethane with 1,4-butanediol <79MI 911-01, 95JOC5729) or the preparation of (13) from benzil dimethyl acetal <90UKZlll6>. Transacetalization is preferred for the synthesis of 1,3-dioxepanes derived from ketones <61JOC4762> and the stereo-... 

In 1894, Alexie Favorskii published an early account of the rearrangement of simple acyclic a-halo ketones. This was followed in subsequent years with additional reports/ In 1914, he published the cyclic version featuring the ring contraction of 2-chlorocyclohexanone. This modification makes this transformation a reliable way to sjmthesize 1-substituted cycloalkane carboxylic acid derivatives. Later in the century, the rearrangement found application in the modification of steroids. Only in the last half of the 20 century has a clearer picture of the mechanism appeared. ... 

Michael-type additions to alkenylmetallics have serious defects because of the inapplicability due to readily-polymerizability of acyclic a,p-unsaturated ketones [17], Organoboranes, on the other hand, give good results, even for acyclic enones [18], but there is no direct and general method for the synthesis of p,p-disubstituted alkenylboranes. However, cross-coupling reaction [1-4] between 6-halo-y,6-unsaturated ketones and organometallics do afford the 6,6-disubstituted-Y,6-unsaturated ketones. 

Coates and coworkers recently reported that boron-based Lewis acids such as BCI3 (Equation 18) and BBrs (Equation 19) react with various acyclic and monocyclic 5,c-unsaturated ketones (25) to give the halide-terminated syn-selective halo-Prins cyclization products, thus providing the sterically congested chlorohydrin (26) and bromohydrins (28) [24]. Here, the use of SnCU as a Lewis acid afforded the opposite selectivity to give the trans-chlorohydrin product (27) (Equation 18), highlighting the complementarity often possible with boron halides. 

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