Diastereoselective reaction, chiral acetal

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... 

Reaction with chiral acetals. The chiral ketals derived from (2R,4R)-( - )-2,4-pentanediol (1) can be cleaved with high diastereoselectivity by aluminum hydride reagents, in particular DIB AH, C12A1H, and Br2AlH. Oxidative removal of the chiral auxiliary affords optically active alcohols. This process provides a useful method for highly asymmetric reduction of dialkyl ketones.3... 

Chiral acetals can be used as auxiliaries in the diastereoselective reactions of Grignard reagents with acyclic as well as cyclic a-keto acetals. Nucleophilic addition to the monoprotected diketone (69 equation 18) occurs with excellent stereoselectivity to generate the corresponding tertiary alcohol (70) as the major product, usually with greater than 95 5 selectivity. Removal of the ketal yields a-hydroxy ketones of high optical purity. In most examples, enantiomeric excesses of 95% and higher are observed in the resultant keto alcohols. Table 17 represents the results of additions to cyclic and acyclic substrates. 

Chiral acetate (204) shows excellent diastereofacial selectivity and has obvious utility as a reagent for asymmetric aldol reactions. As shown in equation (122), reaction of (204) with benzaldehyde provides diastereomers (205) and (206). As shown in Table 23, entry 1, the diastereoselectivity is 83% if the lithium enolate is formed in the conventional manner and the aldol reaction is carried out in THF at -78 C. A significant improvement is obtained by using the magnesium enolate (Table 23, entry 5), and diastereoselectivity of up to 98% is obtained by the use of very low reaction temperatures (Table 23, entries 10-13). 

Six-membered chiral acetals, derived from aliphatic aldehydes, undergo aldol-type coupling reactions with a-silyl ketones, silyl enol ethers," and with silyl ketene acetals " in the presence of titanium tetrachloride with high diastereoselectivities (equation 41) significant results are reported in Table 20. This procedure, in combination with oxidative destructive elimination of the chiral auxiliary, has been applied... 

Cyclic exo-methylene compounds bearing a chiral acetal function prove to be excellent dieno-philes in the noncatalyzed Diels-Alder reaction. Dioxolanones 8 react with cyclopentadiene (9) and acyclic dienes 12 and 15 to afford adducts with diastereoselectivities as high as 100% 28,29. The major adduct 16 from the addition of 8b to diene 15 has been applied to the synthesis of the top half of kijanolide30. 

A number of chiral acetal derivatives have also proved effective in asymmetric cyclopropanation reactions, with auxiliaries based on tartaric acid proving to be partieularly usefiil. In the case of cyclic a,P unsaturated compounds, di-O-benylthreitol derivatives (see 51) imdergo efficient and diastereoselective Simmons-Smith reactions to give the cyclopropanated products SS. ... 

A. Alexakis, J.-F. Normant - Chirals Acetals in Enantio- and Diastereoselective Substitution or Elimination Reactions, Pure Appl. Chem. 60,49,1988. 

Nucleophilic substitutions reactions with organocopper compounds or the more widely applied organocyanocuprates in the presence of Lewis acids have been reported on a./S-ethylenic acetals and allylic mesylates or acetates. Mangeney and co-workers have reported regio- and diastereoselective Sn2 or Sn2 reactions on chiral acetals of cyclic aldehydes promoted by PhCu and Furthermore, organocoppers react efficiently... 

Lewis acid, by enolsilane addition to chiral oxonium ions (cf. equation 40). Oxonium ions are also probably involved in the diastereoselective AlCb-mediated additions of enolsilanes to chiral 2-benzenesulfo-nyl cyclic ethers. In the diastereoselective additions to chiral acetals - (see Section 2.4.4.4), an extension of the methodology shown in Scheme 9 to the enantio differentiation of meso 1,2- and 1,4-diols was reported. An intramolecular Mukaiyama acetal-aldol reaction (see Section 2.4.4.S) was reported as the key step to construct the 11-memboed ring of hydroxyjatrophone A and B. "... 

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