Diastereoselective nickel-catalyzed reductive coupling of alkynes and aldehydes and application towards the B-type amphidinolides

Abstract

The application of recently developed stereoselective nickel-catalyzed reductive coupling reactions of alkynes and aldehydes to the synthesis of complex natural product targets was explored. The "B-Type" amphidinolides were selected as ideal targets owing to their molecular complexity and the paucity of synthetically viable means for their total construction. The diastereoselective nickel-catalyzed reductive coupling of simple aryl-substituted alkynes and a-oxyaldehydes was developed and applied to the construction of the C15-C26 region of amphidinolide H3. ... Alternatively, the nickel-catalyzed reductive coupling reaction of 1,3-enynes and aldehydes was found to be a very effective way of installing the congested 1,3-diene moiety common to all members of this class of natural products. This methodology was further examined as a fragment coupling strategy for the syntheses of amphidinolides G3 and H4. This allowed for a highly convergent and functional group tolerant assembly of these ... molecules and, to date, stands as the most complicated setting for the application of the catalytic reductive coupling reaction.