Tetracyclic cyclobutanes, synthesis,

An ingenious new method for the preparation of Woodward s intermediate (97) by Pearlman70 constitutes another formal synthesis of reserpine. The essence of this new approach is an adaptation of the de Mayo reaction which allows the introduction of vicinal aldehyde and acetic ester functions on to a double-bond (Scheme 13). An internal [2tt + 27r] photocyclization of the diene (98) gave the tetracyclic cyclobutane derivative (99), which was converted into the ester (100) by standard procedures. Methanolysis of the acetate function with concomitant retro-aldol fission completed the introduction of the vicinal aldehyde and acetic ester functions obvious manipulation then gave the desired intermediate (97). 

The sequence of intramolecular photocycloaddition-cyclobutane fragmentation has been used by Crimmins in an excellent manner for the synthesis of pentalenenes and the even more sophisticated lauren-l-ene (27). The latter synthesis was accomplished in 27 steps from cyclopentenone U66). One of the key steps is the reductive cleavage of the tetracyclic cyclobutane (167), followed by hydrogenation of the resulting P,7-unsaturated ester to give keto ester (168 Scheme 57). 

Irradiation of 231 gives, after the re ra-Mannich fragmentation of the photoadduct 232, a 91% yield of 233. The single stereogenic center in the photosubstrate leads to complete stereochemical control in the formation of the cyclobutane intermediate 232, which contains two new strereogenic centers. Treatment of 233 with lithium diisopropylamide, followed by an excess of ier butyldimethylsilyl triflate and reaction of the crude product with tetrabutylammonium fluoride, results in the formation of the desired tetracyclic product 234 in 51% yield. This compound is converted to tetracyclic ketone 235, which is an advanced intermediate in Buchi s synthesis of vindorosine. 

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