Ring Contraction Reactions in the Total Synthesis of Biologically Active Natural Products

Abstract

Strategic reactions in synthetic organic chemistry are those that increase the molecular complexity of the starting material. Particularly important are the transformations where new carbon–carbon bonds are formed. Although during a ring contraction the number of carbon–carbon bonds is conserved, the reorganization of the skeleton may occur with a high level of selectivity leading to a product not easily accessed by other methods. Even highly strained systems can be obtained using the Favorskii and Wolff rearrangements. Additionally, a ring contraction approach opens new applications for the chiral pool and for readily available starting materials. This chapter presents ring contraction reactions as an efficient tool in the stereoselective synthesis of biologically active natural products. The reactions discussed are Favorskii rearrangement, oxidative rearrangements, Wolff rearrangement, thermolysis of aryliodonium ylides, and rearrangements through cationic and radical intermediates.

Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines

“… 11 − 14 Such reactions are known for a limited subset of molecules, including venerable carbonyl rearrangements such as the Bayer–Villiger, Beckmann, and Wolff rearrangements. 15 − 18 However, the practical attractiveness of these classic reactions varies greatly from case to case by virtue of their conditions and limitations. The Ciamician–Dennstedt rearrangement ( Figure 1 B) represents a stark example of such a transformation; the attractive underlying retrosynthetic logic is hindered by practical limitations that have largely precluded its widespread adoption.…”

“…In this vein, “single-atom” manipulations of ring systems (i.e., targeted insertions or deletions) are of particular interest, in part due to their retrosynthetic simplicity. − Such reactions are known for a limited subset of molecules, including venerable carbonyl rearrangements such as the Bayer–Villiger, Beckmann, and Wolff rearrangements. − However, the practical attractiveness of these classic reactions varies greatly from case to case by virtue of their conditions and limitations. The Ciamician–Dennstedt rearrangement (Figure B) represents a stark example of such a transformation; the attractive underlying retrosynthetic logic is hindered by practical limitations that have largely precluded its widespread adoption. , The reaction is principally limited to the production of 3-halopyridines through haloform-derived carbenes, and typical yields and functional group tolerances are low, due in part to competitive Reimer–Tiemann formylation .…”

Unlocking mild-condition benzene ring contraction using nonheme diiron N-oxygenase

“…Carbon-ring contractions provide elegant and efficient synthetic routes to many drugs, natural products, and industrial materials. [1][2][3][4][5] Among all carbon-ring structures, benzene is notably the most widely distributed one in nature, rendering it a promising reservoir for RCTs. Representative benzene ring contracted structures, such as cyclopentene and saturated cyclic hydrocarbons, carry substantial signicance within the pharmaceutical and industrial domains (Fig.…”