Asymmetric alkene substitution patterns

Asymmetric Dihydroxylation Reactions. A substantial amount of work has been reported on the development of the asymmetric dihydroxylation (AD) reaction as originally described by Sharpless. A greater understanding has emerged of the functional group tolerance of the AD reaction and also its applicability towards differing alkene substitution patterns. The mechanism of the AD reaction has been the subject of intense debate especially with respect to the question of whether a [2 + 2] or [3 + 2] pathway is followed, and some insightful mechanistic studies have followed from this discussion. ... 

In contrast to the intermolecular cyclopropanation, the dirhodium tetraprolinates give modest enantioselectivities for the corresponding intramolecular reactions with the do-nor/acceptor carbenoids [68]. For example, the Rh2(S-DOSP)4-catalyzed reaction with al-lyl vinyldiazoacetate 32 gives the fused cyclopropane 33 in 72% yield with 72% enantiomeric excess (Eq. 4) [68]. The level of asymmetric induction is dependent upon the substitution pattern of the alkene cis-alkenes and internally substituted alkenes afford the highest asymmetric induction. Other rhodium and copper catalysts have been evaluated for reactions with vinyldiazoacetates, but very few have found broad utility [42]. 

Not unexpectedly, the enantioselectivity of the catalytic asymmetric dihydroxylation of alkenes is rather dependent on the substitution pattern of the starting alkene. (E)-, 2-Disubstituted, including a,/(-unsaturated esters, and trisubstituted alkenes are the most well behaved substrates and are dihydroxylated with ligands 1 f/2f in enantioselectivities usually exceeding 90% ee6a. 

High to total 1,2-asymmetric induction was observed in the iodocyclization of IV-alkoxy-3-sub-stituted 4-alkenylamines, the cyclic products 1 have predominantly the 2,3-trans relationship. When the C-3 substituent is a methyl group, the induced diastereoselectivity also depends on the substitution pattern of the alkene, e.g., changing the toaZ double bond, dramatically increases the trans/cis ratio from 67 33 to 100 0. Diastereomeric ratios were determined by H NMR and chromatographic purification of individual diastereomers77. 

The formation of chiral products from hydrosilylation depends on the substitution pattern of the olefin and the regioselectivity of the hydrosilylation process. The products of the hydrosilylation of 1,1-disubstituted olefins are cliiral if the two substituents on the alk-ene are different. Hydrosilylation of terminal olefins can generate chiral products if the regioselectivity of the hydrosilylation is reversed from that typically observed, and the hydrosilylation process forms branched products. Asymmetric hydrosilylation of gemi-nally disubstituted alkenes has not generated products with high enantiomeric excess, but asymmetric hydrosilylation by additions to terminal olefins to form branched alkylsilanes has occurred with high ee. 

The important point of difference between the behavior of 3 and other known asymmetric hydroborating agents is its greater sensitivity to differences in the substitution pattern at the beta rather than alpha carbon of the double bond undergoing hydroboration. Thus, the orientation of the a-CHMe (i. e. C-2 ) is reversed in cis vs, trans alkenes and the qpposite relative configuration is obtained for these isomers after the boron adds to this center. Consistent with this hypothesis, the hydroboration of a-methylstyrene was found to be very slow (ca 96 h, 25 C), but produces the P-boryl adduct in 62% de, a remarkable result The reaction intermediates were characterized by NMR a technique which provides a direct analysis of the boranes (58-60), However, quite clearly the selectivity of optically pure 3 was required to ultimately provide enantiomerically enriched products in asymmetric organoborane conversions. 

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