Synlett 2017; 28(16): 2093-2109
DOI: 10.1055/s-0036-1589084
account
© Georg Thieme Verlag Stuttgart · New York

Pursuit of Enantioselective Synthesis of Heterocycle-Bearing ­Stereocenters: The Development of a Stereocontrolled BINOL-­Catalyzed Conjugate Addition of Organoboron Nucleophiles

Department of Chemistry, University of Houston, 3585 Cullen Blvd, Fleming Building Room 112, Houston, TX 77204-5003, USA   Email: [email protected]
,
Thien S. Nguyen
,
Truong N. Nguyen
Department of Chemistry, University of Houston, 3585 Cullen Blvd, Fleming Building Room 112, Houston, TX 77204-5003, USA   Email: [email protected]
,
Phong Q. Le
,
Po-An Chen
Department of Chemistry, University of Houston, 3585 Cullen Blvd, Fleming Building Room 112, Houston, TX 77204-5003, USA   Email: [email protected]
,
Ravikrishna Vallakati
› Author Affiliations
This work was financially supported by the Welch Foundation (Grant E-1744)
Further Information

Publication History

Received: 05 June 2017

Accepted: 27 June 2017

Publication Date:
15 August 2017 (online)


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

 
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  • 2 Current affiliation: Biochemistry Department, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
  • 3 Current affiliation: Sciegen Pharmaceuticals, 89 Arkay Drive, Hauppauge, NY 11788, USA.
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