Transition-Metal-Catalyzed Cycloadditions for the Synthesis of Eight-Membered Carbocycles: an Update from 2010 to 2020

Abstract

Eight-membered carbocycles are widely found in natural products with significant biological activities and other molecules ranging from perfumes to potential materials. Therefore, accessing these eight-membered carbocycle embedded molecules is important for drug discovery, biological investigation, fragrance industry, material development and many other fields. However, the synthesis of eight-membered carbocycles is still posing challenges to synthetic chemists. Hence, tremendous efforts have been endeavored by many leading chemists to discover and develop new reactions in order to synthesize eight-membered carbocycles. Among these reactions, transition-metal-catalyzed cycloadditions of [m＋n], [m＋n＋o], [m＋ n＋o＋p] have evolved as powerful tools to achieve this aim. This topic has been reviewed in 2010. Summarized here are many new developments in this field and applications of the previously developed reactions in natural product synthesis since then.

Mechanism and Stereochemistry of Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Ene–Vinylcyclopropanes and Carbon Monoxide Revealed by Visual Kinetic Analysis and Quantum Chemical Calculations

“…Eight-membered carbocycles are widely found in natural products, pharmaceuticals, and fragrances. − Yet due to the unfavorable enthalpic and entropic effects associated with the ring-closure processes, , only a limited number of strategies and tactics have been applied to the construction of eight-membered carbocycles. − Among them, transition-metal-catalyzed cycloadditions have been proven to be an efficient and atom-economical way to synthesize eight-membered carbocycles with different substitution patterns and stereostructures. − …”

Regioselective activation of benzocyclobutenones and dienamides lead to anti-Bredt bridged-ring systems by a [4+4] cycloaddition

“…With the highly diastereomerically pure benzo-fused bridged cyclic compounds 2 in hand, we hypothesized that if a Schmidt rearrangement reaction can be performed (Fig. 4), which would further extended the structural diversity [49][50][51][52][53] based on this [4 + 4] annulation strategy. In addition, it may be considered as a reaction surrogate for using the oxindole 3 as the annulation substrate, which has been an elusive substrate in C-C bond activation due to the more reactive amide bonds.…”

Syntheses of (+)-Antrodiellin B, (−)-Hypnophilin and (−)-Coriolin and Strained 5/5/5 and 5/6/4 Skeletons via [5+2+1]/Epoxidation/Transannular Radical Cyclization

“…[48][49][50][51][52][53] This can be understood because preparation of eight-membered carbocycles was usually more challenging than direct synthesis of five-membered rings. [54][55] But today, more methods and strategies of accessing eight-membered carbocycles have been discovered and developed, [56][57][58] Implying that more transannular strategies now and in the future to reach 5/5/5 or other multicycles by using easily accessed 5/8 precursors would become viable. Actually, we previously developed three transannular strategies, all of which used 5/8 precursors synthesized by Rh-catalyzed [5+2+1] reaction, [59][60] followed by either an aldol reaction 50 or an ene reaction, [52][53] to access 5/5/5 tricyclic skeletons (Fig.…”