Recent Advances in Stereoselective Ring Expansion of Spirocyclopropanes: Access to the Spirocyclic Compounds

Abstract

Spirocyclopropane represents a privileged structural scaffold for accessing synthetic libraries of densely functionalized spirocarbo- and heterocyclic compounds. Due to the ubiquity of spirocyclic motifs as a potent pharmacophore in natural products and pharmaceuticals, recent years have witnessed significant advances in developing synthetic strategies that exploits carbon–carbon bond scission in spirocyclopropanes. This paper summarizes the recent developments in stereoselective ring expansion of spirocyclopropanes in diversity-oriented synthesis and highlights the synthetic as well as mechanistic rationale of those methodologies. This review also encompasses the applicability of the protocols in bioactive natural product syntheses.

Additive‐Free Synthesis of Trifluoromethylated Spiro Cyclopropanes and Their Transformation into Trifluoromethylated Building Blocks

“…In addition to the inherent potential these spiro TFCps possess, the presence of donor and acceptor groups make them promising candidates for assembling valuable synthetic building blocks either through the ring expansion or ring opening reactions. [12] Drawing inspiration from the well-known annulations of spiro cyclopropanes, [13] we envisioned that an appropriate dipolarophile would take part in the ring expansive annulation reaction under Lewis acid conditions.…”

UV Light is no Longer Required for the Activation of 1,3,4-Oxadiazolines

“…The spirocyclopropane scaffold is found in numerous naturally occurring, bioactive compounds and constitutes a useful building block in the synthesis of carbocycles and heterocycles, etc. [52][53][54][55] For this reason, efficient methods for their preparation are highly valued. Therefore, we resolved to evaluate the utility of the developed methodology in the synthesis of structurally diverse spirocyclopropanes (Scheme 6).…”

Transition Metal/Lewis Acid Catalyzed Reactions of Zerumbone for Diverse Molecular Motifs

“…The structural diversity in NPs provided novel therapeutic leads in drug discovery endeavours, from medicinal plants, as anticancer and antimicrobial agents, [2] and the diversity can be achieved in an efficient manner by diversity‐oriented synthesis (DOS) [3] . Strategies in DOS for construction of small‐molecule libraries of biological relevance with skeletal and stereochemical diversity comprise build/couple/pair (B/C/P), ring‐distortion, complexity‐generation, cascade and multicomponent reactions [4–11] . DOS can be extended to even NP extracts by direct chemical derivatization to produce diversity‐enhanced extracts [12] …”

“…[3] Strategies in DOS for construction of small-molecule libraries of biological relevance with skeletal and stereochemical diversity comprise build/couple/pair (B/C/P), ringdistortion, complexity-generation, cascade and multicomponent reactions. [4][5][6][7][8][9][10][11] DOS can be extended to even NP extracts by direct chemical derivatization to produce diversity-enhanced extracts. [12] Abundant natural products provides an opportunity for derivatization using the versatile transition-metal catalyzed methodologies that enable carbon-carbon bond formations in a combinatorial chemistry approach to afford diverse molecular frameworks.…”