Recent Advances in the Catalytic Synthesis of the Cyclopentene Core

Abstract

Five‐membered carbocycles are ubiquitously found in natural products, pharmaceuticals, and other classes of organic compounds. Within this category, cyclopentenes deserve special attention due to their prevalence as targets and as well as key intermediates for synthesizing more complex molecules. Herein, we offer an overview summarizing some significant recent advances in the catalytic assembly of this structural motif. A great variety of synthetic methodologies and strategies are covered, including transition metal‐catalyzed or organocatalyzed processes. Both inter‐ and intramolecular transformations are documented. On this ground, our expertise in the application of C−H functionalization reactions oriented towards the formation of this ring and its subsequent selective functionalization is embedded.

Electronic and Steric Effects in a Gold(I)‐Catalyzed Intramolecular C(sp3)−H Bond Activation Reaction of 1‐Bromoalkynes

“…[16] In spite of its apparent simplicity, the synthesis of substituted cyclopentene scaffolds is far from obvious. [17,18] As an example, the preparation of the key cyclopentene intermediate 3 in the synthesis of the tricyclic skeleton of Daphenylline was achieved in 11 steps, while our methodology allows its preparation in just 5 steps from commercially available non-8-yn-1-ol (Scheme 3). [19] Furthermore, the participation of a distant ester, amongst other functional groups, far from being a curiosity, allows anchoring the 1-bromoalkyne warhead to a variety of biologically relevant molecules as showcased by Estrone (see Scheme 2, 2 ak).…”

“…In spite of its apparent simplicity, the synthesis of substituted cyclopentene scaffolds is far from obvious [17,18] . As an example, the preparation of the key cyclopentene intermediate 3 in the synthesis of the tricyclic skeleton of Daphenylline was achieved in 11 steps, while our methodology allows its preparation in just 5 steps from commercially available non‐8‐yn‐1‐ol (Scheme 3).…”

Vinylcyclopropane-Cyclopentene (VCP-CP) Rearrangement Enabled by Pyridine-Assisted Boronyl Radical Catalysis

“…2 Among these, the vinylcyclopropane−cyclopentene (VCP-CP) rearrangement 3 represents a direct ring expansion of VCPs to obtain cyclopentenes (CPs), a core structure in numerous natural products and biologically active compounds (Scheme 1A). 4 Since its discovery, 5 its utility has been encumbered by inherent harsh conditions (typically at 300− 500 °C). In this regard, different strategies have been intensely explored to delve into milder alternative conditions.…”