Exocyclic stereocontrol via asymmetric hydrovinylation in the general synthesis of Pseudopterogorgia natural products. Stereoselective X -Y -mediated cyclization studies of an allene -ynamide and an allene -aldehyde

• Main Author: Mans, Daniel J
• Format: Dissertation
• Language: English
• Subjects: organic chemistry
• ISBN: 0549447970; 9780549447979

Asymmetric hydrovinylation, the heterodimerization of a prochiral olefin with ethylene gas, has been used to control the exocyclic stereochemistry in the construction of highly advanced intermediates for the synthesis of biologically relevant molecules such as helioporins and pseudopterosins. The exocyclic stereocenters were installed using asymmetric hydrovinylation of a vinylarene followed by that of a 1,3-diene, which in turn was prepared from the initial hydrovinylation adduct. One of these intermediates, tricyclic ketone 67, for which the relative configurations of all the newly created stereocenters were established by X-ray crystallography, can be further elaborated into aglycones of Pseudopterosins A-F and G-J. These molecules are noted for their anti-inflammatory properties. Other intermediates are useful for the synthesis of Helioporins B and D, which have antiviral/cytotoxic properties. A key side reaction of an intermediate also suggests a new approach to the elisabethane skeleton.
Several highly functionalized intermediates for the study of X-Y-mediated [X, Y = R3Si, R3Sn, -B(NR2)2] intramolecular cyclization of alleneyne and allene-aldehyde have also been synthesized. The allene-aldehyde cyclization mediated by silyl-stannanes, catalyzed by Pd, proceeded to form the cyclized product. The product of this reaction should serve as a key intermediate for the synthesis of trisubstituted pyrrolidines.