Reserpine synthetic approaches

The hydrogen abstraction, in this instance, presumably occurs at the P-carbon of the enone (139). The resultant biradical ring closes to afford the observed products. The ic-ic excited triplet state is involved in the conversion of the enone (141) into the spiroketone (142). The reaction again involves hydrogen abstraction by the ft-carbon followed by cyclization within the biradical. Photocyclization of enamides such as (143) has led to a new synthetic approach to the yohimbine anreserpine type alkaloids. " The photocyclization of the enone (144) provides a route for the synthesis of 3.10-dimethoxyprotoberberines. ... 

In a previously described approach, a largely similar strategy was employed in order to generate enantio-selectively (—)-allo-yohimbane [84]. Yohimbane alkaloids such as reserpine and yohimbine were of long-standing interest from pharmacological and synthetic points of view, and the first enantio-selective (—)-alloyohimban synthesis was reported some time ago by Isobe et al. [88]. 

We will now look at several other syntheses of reserpine, some in more detail than others. Here we see an approach reported by Pearlman. The plan was related to the Woodward approach at a late stage, as 83 was projected to be an intermediate. The approach to 83, however, was very different. The plan was to prepare strained -hydroxyester 109 and then spring it loose to 83 by a retro-aldol reaction. The cyclobutane was to be prepared by a photocycloaddition between cyclohexene 110 and enol 111. The stereochemical and regiochemical issues associated with the cycloaddition were to be handled by making the photocycloaddition an intramolecular process. It is notable that this is an example of a synthesis that was designed to develop and illustrate new synthetic methodology, in this case a method for the directed addition of two functionalized carbons across a carbon-carbon r-bond. 

---