occurred. This explanation does fit the observed isotope effects. Our initial results, therefore, suggest that the great speed of many displacement reactions involving large atom nucleophiles in protic solvents may not be due so much to their polarizability as to their ease of desolvation, and that the leaving group isotope effects provide a probe for distinguishing between the two. These results are also consistent with the operation of a concerted transition state as opposed to an intermediate ion-pair mechanism such as proposed by Sneen and Larsen1 ^2 for other reactants and solvents.If these initial conclusions are substantiated by further experiments and are not found to be unduly complicated by the intervention of specific solvation of substituents,13 specific solvation of the leaving group, or mass effects upon changing the• nucleophile, the kinetic isotope effects of leaving groups may result in one of our more powerful yet subtle probes for transition-state geometry. We propose to explore these possible complications further.
Dammarenediols I (1a) and II (1b) were prepared by an efficient nonenzymatic biomimetic polyene
tetracyclization route. The cyclization substrate, pentaenol 3, contains a tetramethylallylic alcohol
initiator, an allyltrimethylsilane terminating group, and a fluorine atom at pro-C-13 to serve as a
cation-stabilizing (C-S) auxiliary controlling the regiochemistry of the C/D ring juncture. The
synthesis of 3 employed lithium−halogen exchange to create alcohols 10 and 19. The Z-fluoroalkene
in 3 was introduced stereoselectively via the Trost palladium-catalyzed alkylation of allylic acetate
11 (Z/E: 4.6/1). The cyclization of 3 was most efficient (62% isolated yield) when it was added as a
dilute solution in dichloromethane to trifluoroacetic acid at −45 °C to afford tetracyclic fluoro diene
24 possessing the trans−anti−trans−anti−trans ring stereochemistry of the dammaranes. Replacement of the fluorine atom of 24 with hydrogen with complete retention of configuration was
accomplished using the Ohsawa−Oishi reagent (Na/K alloy and crown ether). Wacker oxidation of
the resulting hydrocarbon provided ketone 28, which after ketalization was ozonolyzed with a
reductive workup to give the 3β-alcohol 30. Ketal hydrolysis followed by Grignard reaction with
isopentenylmagnesium bromide afforded the dammarenediols (1/3, 1a/1b).
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