Total Synthesis Highlights

This concise synthesis of the dolabellane 3 showcases the power of the catalytic enantioselective
methods for the construction of both ternary and quaternary, including cyclic quaternary, centers
that Professor Hoveyda has developed. Clearly, asymmetric transformation of inexpensive
prochiral ring precursors such as 1 and 4 will make advanced, high ee intermediates such as 2 and
5 much more readily available than they have been in the past.
26. The Zakarian Synthesis of (+)-Pinnatoxin A
(+)-Pinnatoxin A (3), isolated from the shellfish Pinna muricata, is thought to be a calcium
channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc. 2008,
130, 3774.) by Armen Zakarian, now at the University of California, Santa Barbara, was the
diastereoselective Claisen rearrangement of 1 to 2.
The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The
absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol
catalyzed addition of diethyl zinc to the unsaturated aldehyde 5.
The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7.
Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation
provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case,
care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH 4