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Review
. 2020 Apr 21;53(4):988-1000.
doi: 10.1021/acs.accounts.0c00076. Epub 2020 Apr 9.

Evolution of Anion Relay Chemistry: Construction of Architecturally Complex Natural Products

Yifan Deng  1 , Amos B Smith 3rd  1
Affiliations
Review

Evolution of Anion Relay Chemistry: Construction of Architecturally Complex Natural Products

Yifan Deng et al. Acc Chem Res. .

Abstract

Multicomponent union tactics in which three or more fragments are rapidly connected are highly prized in the construction of architecturally complex natural products. Anion Relay Chemistry (ARC), a multicomponent union tactic, has just such potential to elaborate structurally diverse scaffolds in a single operation with excellent stereochemical control. Conceptually, the ARC tactic can be divided into two main classes: "Through-Bond," by the relay of negative charge through the bonding system of a molecule; and "Through-Space," by the migration of negative charge across space by a transfer agent. "Through-Space" Anion Relay Chemistry, the focus of this Account, can be further subdivided into two types: Type I ARC, originated from the Tietze-Schaumann-Smith coupling reaction, which for the first time permits controllable Brook rearrangements to construct unsymmetrical adducts, and as such has been successfully employed in the total syntheses of diverse natural products, including the mycoticins, bryostatin 1, spongistatins, rimocidin, indolizidine alkaloids, and enigmazole A; and Type II ARC, central to which is the design of novel bifunctional linchpins that enable rapid assembly of linear and cyclic fragments with diverse architectural features, ranging from polyols, spiroketals, and polyenes to polypropionate scaffolds. Recently, the Type II ARC tactic has been exploited as the key construction tactic in the total syntheses of the spirastrellolides, the cryptocarya acetates, secu'amamine A, mandelalide A, and nahuoic acid Ci (Bii). This Account will present the evolution of both the Type I and Type II Anion Relay tactics, in conjunction with some prominent applications.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
The Hierarchy of Anion Relay Chemistry.
Scheme 2.
Scheme 2.
Example of [1,2]-Brook Rearrangement.
Scheme 3.
Scheme 3.
Type I and Type II ARC.
Scheme 4.
Scheme 4.
Initial Work on Type I ARC.
Scheme 5.
Scheme 5.
Smith’s Modified Type I ARC.
Scheme 6.
Scheme 6.
Five-Component Type I ARC in the Synthesis of Mycoticins.
Scheme 7.
Scheme 7.
Type I ARC in Hale’s Synthesis of Bryostatin B-Ring.
Scheme 8.
Scheme 8.
Construction of the AB- and CD-Spiroketal Fragment
Scheme 9.
Scheme 9.
Construction of the C(1–19) Fragment of Rimocidin.
Scheme 10.
Scheme 10.
Synthesis of the Indolizidine Natural Products.
Scheme 11.
Scheme 11.
Construction of Eastern Hemisphere of Enigmazole A.
Scheme 12.
Scheme 12.
Early studies on Type II ARC.
Scheme 13.
Scheme 13.
Selected Examples of Type II ARC Linchpins.
Scheme 14.
Scheme 14.
Examples of Cross-coupling and Cyclization Reaction Employing Type II Linchpins.
Scheme 15.
Scheme 15.
Multi-component Union Tactics Employing Type II Linchpins.
Scheme 16.
Scheme 16.
Type II Linchpins for Various Synthetic Targets.
Scheme 17.
Scheme 17.
“Through-Bond/Through-Space” Type II ARC Tactic.
Scheme 18.
Scheme 18.
Type II ARC Cyclization Tactic.
Scheme 19.
Scheme 19.
Type II ARC involving [1,5]-Brook Rearrangement.
Scheme 20.
Scheme 20.
Unification of Type II ARC with Cross-Coupling Reaction.
Scheme 21.
Scheme 21.
Construction of BC Spiroketal Fragment of Spirastrellolides.
Scheme 22.
Scheme 22.
Total Synthesis of Cryptocarya Family.
Scheme 23.
Scheme 23.
Synthesis of the Weinreb Intermediate of (−)-Secu’amamine A.
Scheme 24.
Scheme 24.
Total Synthesis of Mandelalide A by ARC.
Scheme 25.
Scheme 25.
Construction of Polyol Sidechain of Nahuoic Ci (Bii).
Scheme 26.
Scheme 26.
Final Elaboration to Nahuoic Ci (Bii).
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References

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    1. Smith AB III; Wuest WM Evolution of Multi-Component Anion Relay Chemistry (ARC): Construction of Architecturally Complex Natural and Unnatural Products. Chem. Commun 2008, 5883–5895 and references therein. - PMC - PubMed
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