An efficient, convergent synthesis of the core bicyclo[4.3.1]decane ring system of welwitindolinones is described. Key steps in the synthesis include an intramolecular palladium-catalyzed enolate arylation reaction to create the desired bicyclic skeleton and a Curtius rearrangement to install the bridgehead isocyanate unit. [reaction: see text]

A combination of proton-resonance-spectroscopic and dipole-moment measurements confirms that tropanes exist with the piperidine ring in a chair conformation and with the N-methyl substituent predominantly equatorial. A 3a-substituent causes considerable ring deformation.Two aspects of the stereochemistry of tropane derivatives have received attention : (a) whether the piperidine ring exists in a chair (I, 111) or a boat (11, IV) conformation; (b) whether the ii-methyl group is equatorial (I, 11) or axial (111, IV). by one of us has shown that tropane derivatives yield on quat ernisation principally or exclusively the derivative in which the entering group takes up the equatorial position, The not unreasonable conclusion was drawn I. that unquaternised tropanes existed with the N-substituent axial, and this was rationalised in terms of Pitzer strain in the N-equatorial conformation. However, as was pointed out by Closs,2 the quaternisation For reviews see G. Fodor, Tetrahedron, 1957, 1, 86; Ex-A series of Publications p e v h t i a , 1955, 11, 129.could be kinetically controlled if the conformer with the N-substituent axial was present in small proportion, but reacted much faster than the equatorial conformer. Kinetic control of quaternisation occurs in the quinolizidine series.3 Closs argued,2 from the nuclear magnetic resonance (n.m.r.) spectra of some tropane deuterohalides, that the N-substituent in tropanes is predominantly equatorial. Although evidence presented in the present Paper confirms his main conclusions, it should be pointed out that his argument depended on the following assumptions. (i) The steric requirement of a lone pair is not greater

[reaction: see text] Generation of the lithium salt of the norbornenol shown (M = H) followed by quenching with aqueous NH(4)Cl solution gives predominantly the beta-epimeric ketone 6. Similar production of the potassium alkoxide leads instead to the alpha-epimer (99:1). These results reveal the potential importance of alkali metal counterions as stereocontrol elements.

Alkaloids U 0600Rapid Synthesis of the N-Methylwelwitindolinone Skeleton. -The title synthetic method is developed with the key steps being an intramolecular palladium-catalyzed enolate arylation reaction to create the bicyclic skeleton and a Curtius rearrangement to install the bridgehead isocyanate unit. -(MACKAY, J. A.; BISHOP, R. L.; RAWAL*, V. H.; Org. Lett. 7 (2005) 16, 3421-3424; Dep. Chem., Univ. Chicago, Chicago, IL 60637, USA; Eng.) -Y. Steudel 49-179

No abstract