Synlett 2023; 34(08): 889-911
DOI: 10.1055/a-1977-1006
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Stereo- and Regioselective Synthesis of (E,E)-Dienes: Evolution from the Transition-Metal-Catalyzed Cross-Coupling to Titanium Alkoxide-Based Alkyne–Alkyne Reductive Coupling

Bin Cai
a   Department of Chemistry, Metcalf Center for Science and Engineering, Boston University, Boston, MA 02215, USA
,
Ren Wei Toh
b   Department of Chemistry, National University of Singapore, Singapore, R. of Singapore
,
Hwee Ting Ang
b   Department of Chemistry, National University of Singapore, Singapore, R. of Singapore
,
Jie Wu
b   Department of Chemistry, National University of Singapore, Singapore, R. of Singapore
,
a   Department of Chemistry, Metcalf Center for Science and Engineering, Boston University, Boston, MA 02215, USA
› Author Affiliations
We are grateful for the financial support provided by the Department of Chemistry at Boston University and support was obtained from the National Institute of General Medical Sciences (NIGMS) CMLD initiative (P50 GM067041) and RO1 (GM55740).


Abstract

The pursuit of step- and atom-economy in natural product and complex molecule syntheses continuously inspires the development of synthetic methodologies. In this context, to enable efficient synthesis of (E,E)-dienes as common structural subunits in natural products, our lab has established robust protocols based on modified Negishi cross-couplings and evolved them to more concise titanium-mediated alkyne–alkyne reductive coupling. In this review, we summarize the natural product synthesis driven methodology development and their applications in the total synthesis of complex molecules, focusing on the studies from our laboratory.

1 Introduction

2 Transition-Metal-Catalyzed Cross-Coupling in Natural Product Synthesis

2.1 Synthesis of Branched Trisubstituted Conjugated Dienes by Negishi Coupling

2.2 Stereo- and Regiocontrolled Synthesis of Branched Trisubstituted Conjugated Dienes by Modified Negishi Coupling

2.3 Enantioselective Total Synthesis of Reveromycin B by Drouet & Theodorakis

2.4 Enantioselective Synthesis of the Protein Phosphatase Inhibitor (–)-Motuporin by Hu & Panek

2.5 Total Synthesis of (–)-Callystatin A by Langille & Panek

2.6 Total Synthesis of Brevisamide by Lee & Panek

3 Titanium Alkoxide-Mediated Reductive Coupling in Natural Product Synthesis

3.1 Titanium Alkoxide-Mediated Alkyne–Alkyne Reductive Coupling

3.2 Total Synthesis of Callystatin A by Reichard & Micalizio

3.3 Total Synthesis of (–)-Virginiamycin M2 by Wu & Panek

3.4 Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68) by Cai & Panek

3.5 Titanium Alkoxide-Based Regioselective Alkyne–Alkyne Reductive Coupling Mediated by in situ Generated Arylamidate

4 Summary



Publication History

Received: 05 October 2022

Accepted after revision: 11 November 2022

Accepted Manuscript online:
11 November 2022

Article published online:
30 December 2022

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