Applications diastereofacial selectivity

Enders et al. (96) recently described the application of the chiral azomethine precursor 61 (Scheme 12.21). The azomethine ylide was formed in situ by heating with different benzaldehydes. The reactions of four different azomethine ylides with A-phenyl maleimide led to the formation of endo-62 and exo-62 in ratios of 2 1 in very high yields. The diastereofacial selectivity was estimated to be >96% de for both products, since no other diastereomers were observed by proton nuclear magnetic resonance ( H NMR) spectroscopy. 

A and B are applicable to systems with R6 = H, whereas C has to be considered for cw-substi-tuted double bonds (R° 4= H)40. By far the most efficient and reliable alternative is depicted by model C40, which in many cases leads to high diastereofacial selectivities (>9 1). Therefore, it is necessary to introduce a dummy substituent, like trimethylsilyl or tributylstannyl, into the R6 position, which may be removed by protonolysis after the addition40. 

Mukai et al. (36,37) applied the chiral tricarbonyl(r 6-arene)chromium(0)-derived nitrone 24b in 1,3-dipolar cycloadditions with various alkenes, such as styrene 25 (Scheme 12.11). The analogous nonmetallic nitrone 24a was used in a reference reaction with 25, giving the isoxazolidine 26a with an endo/exo ratio of 82 18. By the application of nitrone 24b in the 1,3-dipolar cycloaddition with 25, the endo/exo-selectivity changed significantly to give exo-26b as the only observable product. The tricarbonylchromium moiety effectively shielded one face of the nitrone, leading to high diastereofacial selectivity. The product exo-26b was obtained with 96-98% de. 

The Danishefsky group has investigated the mechanism of this process in some detail. It has also been found that the cycloadditions show excellent diastereofacial selectivity with many chiral aldehydes. - Moreover, chiral catalysts have proven effective in controlling the enantioselectivity of the cycloaddition.These features of the reaction, along with applications to natural product total syntheses, are discussed in detail in Volume 2, Chapter 2.5. 

Boeckman, R. K., Jr., Liu, Y. Toward the Development of a General Chiral Auxiliary. 5. High Diastereofacial Selectivity in Cycloadditions with Trienol Silyl Ethers An Application to an Enantioselective Synthesis of (-)-Cassioside. J. Org. Chem. 1996, 61, 7984-7985. 

To achieve high stereoselectivity applicable to any aldehyde in the cyclocondensation reaction the use of double diastereofacial selectivity has been investigated. These studies revealed an interesting relationship between the chiral catalyst used in the reaction and the chiral auxiliary. Contrary to the notion that the selectivity of a chiral diene and chiral dienophile are enhanced only in a matched pair, the interactivity of a chiral catalyst with a chiral diene where the two individual components have an opposite facial preference seems to give a high degree of asymmetric induction in the cyclocondensation reaction. ... 

Reactions exhibiting diastereofacial selectivity, which occur when the imine or the enolate contains an endogenous stereocenter or a chiral auxiliary, have important applications for the synthesis of optically active 3-l ctams and 3-amino carboxylic acid derivatives. Early work by Furukawa et al. has demonstrated the viability of preparing optically active 3-amino acids from chiral imines. For example, the Schiff base derived from (5)-a-methylbenzylamine (110) reacts with Reformatsky reagent (111) to give, after hydrolysis and removal of the chiral auxiliary, 3-amino-2,2-dimethyl-3-phenylpropionic acid (112) in 33% ee (Scheme 21). Similar Reformatsky reactions have been performed using (-)-menthyl esters but the enantiomeric excess values are lower. ... 

In an application to asymmetric monobactam synthesis. Overman and Osawa observe a high level of 1,4-diastereofacial selectivity in the reaction of (5)-cyanoamine (235) with the enolate of STABASE-protected glycine ester (234), affording diastereomeric 3-amino-2-azetidinones (236) and (237) in a 10 1 ratio, respectively, and in 65% yield (Scheme 49). Based on the (E)-enolate geometry of glycine ester (234), determined in trapping experiments with TMSCl, the authors postulate a chelated, chair-like transition state (238) that is consistent with the observed stereoselectivity. 

This hydroxy-directed cyclopropanation method is also applicable to homoallylic alcohols27. Thus, f K-2-[(Z)-4-/err-butyldiphenylsilyloxy-1 -butenyl]-l-cyclopentanol and dichlorocarbcne combine to provide the adduct with perfect diastereofacial selectivity. On the other hand, the reaction of the diastereomeric /rau.s-substitutcd cvclopentanol proceeds with only moderate selectivity. 

However, with these isopropylidenated dienophiles, the diastereofacial selectivity was much higher than with the acetylated analogues, especially in the ribo and Ivxo isomers, a factor of importance in any proposed application in chiral synthesis. 

Most attempts to construct diastereoselective variants of the Passerini reaction have met with a certain degree of failure. Undoubtedly, the numerous uncertainties of the reaction mechanism have contributed to these difficulties. The usual low levels of control for the Passerini reaction have also impeded efforts to establish empirical trends in the diastereofacial selectivity. This is exemplified in the construction of peptidomimetics, a class of molecules which has stimulated numerous applications of the Passerini reaction, where the diastereoselectivity is typically in the range of 1 1 to 4 1, A survey of results of the diastereofacial selectivity of carbonyl addition does not consistently follow a clear trend of either the Felkin-Anh or chelation-controlled models of carbonyl addition. ... 

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