Abstract:
The implementation of chiral centres within biologically active compounds has
been a perplexing yet motivational force in chemistry. This work presents the
attempted formation of a concurrent or sequential tandem catalyzed methodology of
enantioselective nucleophilic addition and electrophilic cyclization. The 2'-
arylalkynyl- aldehyde, ketone, and imine substrates used within were adeptly chosen
with a dually activated structure; 1) for nucleophilic addition to the electrophilic
substituents; and 2) for carbophilic activation of the alkyne substituent to undergo
cyclization. To accomplish the nucleophilic addition, two distinct allylation
methodologies were pursued: (/?)-BINOL catalyzed-allylboration and (5)-
BINAP-AgF catalyzed-allylsilylation. BINAP catalyzed enantioselective allylation of
2'-arylalkynyl-aldehydes, to form chiral homoallylic alcohols, was successful.
Homoallylic alcohols were isolated with high enantio-purity (>80%), which then
underwent sequential cyclization to form chiral allylic phthalans, in moderate yields.
An application of this methodology towards the construction of biologically active
compounds was included with the partial synthesis of the natural product and H.
pylori inhibitor, (+)-Spirolaxine methyl ether.
