Highly ordered cyclic

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

The oxy-Cope and anionic-oxy-Cope rearrangements involve highly ordered cyclic transition states, so the asymmetry is almost completely transferred from the substrate to the product. Most commonly in acyclic systems as in other [3,3]-sigmatroplc rearrangements, the transition states are chairlike and the substituents adopt a quasiequatorial position to minimize unfavorable steric interactions. In unsubstituted substrates the diastereoselection is low, tout the introduction of an alkyl substituent at C4 improves the diastereoselectivity. In (Z)-1-substituted alkenes there is preference for the oxyanionic bond to be pseudo-equatorial, whereas in ( )-1-substituted alkenes it tends to... 

With respect to the stereochemical course of the reaction, the Cope substrates may have four elements of stereochemistry in the six-carbon framework (two double bonds and two stereocenters, e.g., 3), and these are transformed to four new elements of stereochemistry in the products. Due to the highly ordered cyclic transition state, the rearrangements are usually highly stereoselective with respect to both the formation of unsymmetrically substituted double bonds and the formation of stereogenic centers. 

The specific mechanism of reaction (Equation 5.105) includes formation and decomposition of the highly ordered cyclic hydrogen-bonded transition state ... 

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