Chiral acetylenic acetals

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

The method is applicable to acetals of a. -acetylenic ketones such as 2.49 [IMl] (Figure 2.24). The other enantiomers can be obtained by using Et3SiH-TiCl4 on the same acetals [IMl, IM2, Mil]. This methodology provides a reduction of ketones to chiral alcohols that is complementary to the reduction effected by the chiral alumino- and borohydrides (Section 3.2.3). 

Midland and his co-workers have continued their work on the reduction of acetylenic keto-esters, e.g. (97), with chiral boranes to include a highly efficient synthesis of the insect pheromone (98). Catalytic hydrogenation of the lactone tetra-acetate (99) in the presence of triethylamine gives the triacetate (100) by... 

Numerous other nucleophiles participate in highly diastereoselective reactions with chiral acetals (Scheme 6.9). A few selected examples include the introduction of acetylene [30] and of cyanide [31] to give the chiral pro-pargylic alcohol 45 and the optically active cyanohydrins 46 and 47, respectively. Furthermore, Alexakis and Mangenay observed that diastereoselective acetal cleavages can be carried out with organocuprates to give 48 with 95 5 diastereoselectivity [32]. 

Chiral dioxanones have also been employed as acetal auxiliaries in nucleophilic additions [33, 34]. Because of the inherent differences between carbox-ylates and alcoholates as leaving groups, it is the carboxylate that exclusively undergoes displacement. This was shown for the chiral l,3-dioxan-4-one 49 in its reaction with trimethylsilyl acetylene to give 50 in 99 1 dr (Equation 3)... 

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