Hydroxy sulfones, from keto sulfone

As discussed in Section 3.1.11.1, which covers the reductive cleavage of the 3-hydroxy sulfone derivatives to alkenes, the Julia reaction proceeds by the formation of an anion that is able to equilibrate to the thermodynamic mixture prior to elimination. Therefore, there is no inherent advantage in producing the erthyro- or threo-fi-hydroxy sulfone selectively fix>m the keto sulfone. The ( )/(Z)-mixture of alkenes should be the same. This method is used to produce alkenes in cases where the acid derivative is more readily available or more reactive. The reaction of the sulfone anion with esters to form the keto sulfone, followed by reduction with metal hydrides has been studied. The steric effects in the reduction do become important for the reaction to produce vinyl sulfones, which are formed from the anti elimination of the 3-hydroxy sulfone adduct, as mentioned in Section 3.1.11.6.2. Some examples of the use of esters are presented below. 

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

Reactions of 1,3-Diketones - Irradiation of the 1,3-diketone (238) in ethanol or benzene results in the formation of l-hydroxy-2-naphthaldehyde. The site of photochemical hydrogen abstraction reactions within the keto esters (239, X = S) is controlled by SET transfer reactions from the thio substituent to the excited carbonyl group. The usual reaction train following this event yields the biradical (240) which undergoes cyclization to yield (241) in modest to good yields. The involvement of an SET process is proven by the failure of the sulfone derivative (239, X = SO2) to undergo the same reaction. 

Selective reduction. A soln. of borane in tetrahydrofuran added dropwise at -18 during 19 min. to a mixture of adipic acid monoethyl ester and tetrahydrofuran, stirred and allowed to warm to room temp, during 16 hrs. -> ethyl 6-hydroxy-hexanoate. Y 75-88%. - Other functional groups such as cyano, halogeno, keto, or nitro, are likewise retained during this highly convenient reduction. F. e., also reduction of sterically hindered acids, s. N. M. Yoon, H. C. Brown et al., J. Org. Chem. 38, 2786 (1973) 2-aminoalcohols from a-aminocarboxylic acids s. M. L. Anhoury et al., Soc. Perkin 11974,191 via reduction with aq. NaBH of enolesters obtained from the acids and N-ethyl-5-phenylisoxazolium 3 -sulfonate (s. Synth. Meth. 16, 448) s. P. L. Hall and R. B. Perfetti, J. Org. Chem. 39, 111 (1974). 

The reduction of P-keto sulfones [86,136,145,148-152] offers a synthetic approach to p-hydroxy esters of opposite configuration than those obtained from the yeast-mediated reduction of the corresponding p-keto esters. Thus, from 110 (Fig. 29) 111 was obtained (in 98% e.e.) that gave upon desulfuration (i )-112 (S)-112 was obtained by BY reduction of 113 [86] (Fig. 30). The BY reduction of 7- and 8-keto sulfones has been used as a key step in the synthesis of several natural products [153]. 

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