Subject diastereofacial selectivity

Quantitative Distribution of Adducts as a Function of Dienophile Stereochemistry. For accurate quantitation of the isomer distribution in the products of cycloaddition to each of the dienophiles 5—8, the entire mixtures of the four stereoisomeric products in each instance were first subjected to sequential Q-deacetylation and periodate oxidation to afford a mixture of two aldehydo esters 29 and 30, which upon reduction with LiAlH afforded trans-2-norbornene-5,6-dimethanol as an unequal mixture of the two enantiomers (only the 5S,6g enantiomer is shown). NMR analysis of the mixture of 29 and 30 showed distinctive resonances for the CH3O and CHO groups in exo and endo orientations, permitting accurate determination of the endo/exo ratio of the products in the mixture. The observed specific rotation of the diol, in comparison with that (+23 ) determined for the enantiomerically pure 5S,6S diol 26 (and its enantiomer), provided a quantitative measure of the si.re diastereofacial selectivity. 

The Brummond research group also illustrated that the stereoselectivity of these reactions can be controlled by tethering the first dienophile to the dendralene [22, 23]. In one such example, ester 84 underwent an e do-selective intramolecular DA reaction to provide the tricyclic diene 85 (Scheme 12.17). In this reaction, the dienophile is constrained to the bottom face of the molecule, thus controlling the it-diastereofacial selectivity of the cycloaddition. Piperidine 85 was then subjected to an ewdo-selective intermolecular DA reaction with NPhM to provide the pentacycle 86 in excellent yield. 

Cycloaddition precursor 167 was prepared through displacement of the chloride of chlorosilyldiene 166 with potassium nitroacetaldehyde. The nitroalkene 167 was then subjected to the MAPh-promoted [4-1-2]-cycloaddition with S,2R) isomer of 2-phenylcyclohexyl vinyl ether 168 affording trans nitronate 170 with excellent diastereofacial selectivity (SilRe = AAI ). The nitronate 170 resulted from an exclusively exo approach of s-fraws -configured vinyl ether 168 to the Si face of nitroalkene 167 establishing the S configuration at Cl of castanospermine 173 (Scheme 16.25). 

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