Chiral ketals bonds

Further examination of the chiral ketals reveals that the lone pairs available for reagent coordination are oriented either in a syw or an anti relationship to the neighboring methyl substituents. The influence of the chiral auxiliary over the reaction is now clear. If zinc coordination must occur proximal to the double bond. 

Addition of cinnamyl(mesityl)zinc to the C2 symmetrical cyclopropenone ketal 133 led to excellent diastereoselectivities with respect to the newly formed carbon—carbon bond (de = 97%) and induction from the chiral ketal (de = 91%). Deuteriolysis afforded the cyclopropanone ketal 134 in which three stereocenters have been generated99,10°. A product-like transition state model was proposed, in which the cyclopropene underwent considerable rehybridization and the zinc became preferentially attached to the less hindered equatorial olefinic carbon from the face opposite to the axial ketal methyl group (equation 65). 

With cyclic acetals and ketals, selective reductions allow the blocked hydroxy groups of the diol to be deprotected one at a time, a matter of some importance in carbohydrate chemistry. Although there have been a few studies of stereoselective reductions at the masked carbonium center of chiral ketals, more has been done with the formally related reactions in which C—C bonds are formed stereoselectively. ... 

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... 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

Treatment of polyolefinic ketal 230 with stannic chloride in pentane gave a mixture (30% yield) of about equal amounts of the two racemic D-homoster-oidal tetracyclic isomers 231 (88). In this cyclization, the first cationic intermediate is not chiral and the two faces of the 5,6-double-bond can react with equal facility with the carbonium ion as a consequence, the product obtained (231) is necessarily racemic. The conversion of the open-chain tetraenic acetal 230 having no chiral centers into a tetracyclic system having seven such centers and producing only two (231) out of a possible 64 racemates is a striking tribute to the power of stereoelectronic effects. 

An aldehyde or ketone can react with an alcohol in a 1 1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. Substitution of a second alcohol molecule produces an acetal or ketal. When the second alcohol is part of another sugar molecule, the bond produced is a glycosidic bond (p. 245). 

In this respect, the imine electrophile and the nucleophile are fixed in a spatial orientation, which is necessary for the stereoselective C-C bond formation, making the addition of a chiral catalyst unnecessary. As an example, here we wish to highlight only the most recent examples of the incorporation of an intramolecular Mannich reaction in the enantiose-lective total synthesis of L-Lys-derived alkaloids, namely, (-)-hippodamine (267) and (-)-lyconadine C (256). The latter was accessible from the bicyclic intermediate 252 in a tandem ketal removal/Mannich reaction to furnish the tricyclic core structure 254 (Scheme 11.53) [160],... 

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