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.