Rescheduling the regio- and stereo-chemistry of chemical reactions

6 Rescheduling the regio- and stereo-chemistry of parallel chemical reactions 

The control of kinetic vs thermodynamic product formation can often be achieved by suitable modification of reaction conditions. A far more difficult task is to switch from the formation of a favoured major product to a disfavoured minor product, especially when the transition states for the two processes share most features in common. This challenge has been met by antibodies with considerable success, both for reaction pathways differing in regioselectivity and also for ones differing in stereoselectivity. In both situations, control of entropy in the transition state must hold the key. 

In the Diels-Alder reaction between an unsymmetrical diene and dienophile, up to eight stereoisomers can be formed (March, 1992a). It is known that the regioselectivity of the Diels-Alder reaction can be biased so that only the four ori/io-adducts are produced (Fig. 21) through increasing the electron-withdrawing character of the substituent on the dienophile (Danishefsky and Hershenson, 1979). However, stereochemical control of the Diels-Alder reaction to yield the disfavoured exo-products in enantiomerically pure form has proved to be very difficult. 

Gouverneur et al. (1993) were interested in controlling the outcome of the reaction between diene [53] and MA-dimethylacrylamide [54] (Fig. 22). They had shown experimentally that the uncatalysed reaction gave only two 

Transition state geometry Calculated activation energy/kcal mol 1  

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