Abstract
This account chronicles the iterative development of an enantioselective conjugate
addition of organoboron nucleophiles to α,β-unsaturated enones and enals catalyzed
by BINOL derivatives. Beginning with a specific application of this transformation
to the total synthesis of the flinderole alkaloids, the transformation progressed
to encompass a much larger scope of heterocycle-substituted electrophiles. The next
phase saw progress toward the use of a broader scope of functional nucleophiles, with
application in a strategy to synthesize discoipyrrole D. At each stage of this chronologically
organized discussion, key problems, hypotheses, and solutions are presented to show
the sources of discovery and solutions to problems as the catalyst and other reaction
components were made more reactive. The interplay of target-directed reaction development,
efforts to increase the scope of compatible functional groups, mechanistic studies,
and empirical exploration is described to illustrate sources of chemical discovery.
1 Introduction
2 Synthesis of the Flinderole Natural Products
3 Indole-Bearing Stereocenters
4 Heteroaryl-Bearing Stereocenters
5 Bis-Heteroaryl Stereocenters
6 Synthetic Strategy for Discoipyrrole D
7 Bis-Aryl Stereocenters
8 Remaining Challenges
9 Conclusion
Key words heterocycles - organocatalysis - natural product total synthesis - conjugate addition
- BINOL catalysis - heteroaryl stereocenters
