Acetal diastereoselective cleavage

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

Diastereoselective cleavage of propynyl acetals of enantiomeric pure diols with organocopper(I) reagents leads to alkoxyallenes with high diastereomeric purity, in which the chiral auxiliary is included... 

While the diastereoselective cleavage of cyclic chiral acetals is quite well established [108-110], enantioselective variants, e.g., desymmetrizations of me o-acetals [Eq. (7)], are much less reported. The group of Harada used chiral aryl-boron Lewis acids for the enantioselective ring cleavage of 1,3-dioxolanes by si-lyl enol ethers as carbon nucleophiles [111, 112]. 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

The new heterocyclic derivative 130 has been shown to be an efficient chiral auxilliary for asymmetric desymmetrization of cyclic meso-l,2-diols via diastereoselective acetal cleavage . 

Conagenin (39) is a promising anticancer natural product isolated in 1991 from the culture broths of Streptomyces roseosporus20 (Scheme 4.1n). The chelation-controlled Zn(B 114)2 reduction of the p-hydroxy ketone 40 produced the 1,3-syn-diol 41 in 30 1 diastereoselectivity. Protection of the hydroxyl groups gave the bis-acetate 42, which was then subjected to oxidative cleavage to afford the acid 43. 

Lead acetate azides, Pb(OAc)4 (N3)n, prepared in situ from lead tetraacetate and azidotrimethylsilane, react with alkenes to yield a variety of products, depending on the structure of the alkene 1,2-diazides. 1,2-acetoxy azides, a-azido ketones, allylic azides, and <5-oxo nitriles (by the oxidative cleavage of cyclohexene rings)97. The diazides and acetoxy azides are formed by preferential syn addition, but the diastereoselectivity (up to 3 1) is far from satisfactory with both acyclic and cyclic alkenes98,99. 

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