Cleavage acetals, -2,4-pentanediol

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... 

Cleavage of acetals. The acetals derived from (2R,4R)-2,4-pentanediol (this volume) are cleaved by organotitanium reagents of the type RTiCI, or R,TiCf. with high chemo- and stereoselectivity. Removal of the chiral auxiliary gives chiral secondary alcohols in high purity. Acetals complexed with TiCb arc also cleaved by treatment with an alkyllithium. 

Pentanediol is often superior to other diols such as 2,3-butanediol for these reactions because of higher distereoselectivities in reactions with nucleophiles and the more facile cleavage of the resulting hydroxy ether by oxidation-p-elimination. Removal of the chiral auxiliary is usually carried out with Pyri-dinium Chlorochromate oxidation followed by p-elimination using KOH, K2CO3, piperidinium acetate, dibenzylammonium trifluoroacetate, " or DBU. In some cases, 1,3-butanediol is preferred because the final 3-elimination may be effected under milder conditions. ... 

Reduction of Acetals. Reductions of acetals of 2,4-pentanediol can provide (after removal of the chiral auxiliary by oxidation and 3 elimination) secondary alcohols with good enan-tioselectivity. The choice of reagents dictates the configuration of the final product. Use of Dibromoalane gives products from selective syn cleavage of the acetal while Triethylsilane/Titanium(IV) Chloride gives the more usual anti cleavage products (eq 2). ... 

An enantioselective synthesis of (1-hydroxyaJkyl)phosphonic diesters commences with the cleavage, using (EtO)2P/TiCl, of the acetal (304) derived from (2X,45)-pentanediol, to give (305) and (306) in the ratio 91-94 9-6, relative yields... 

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