The Cycloaddition Strategy for the Synthesis of Natural Products Containing Carbocyclic Seven‐Membered Rings

Abstract

Highly substituted carbocyclic seven-membered rings are frequently found in natural products and their synthesis represents a significant challenge to the synthetic chemist. Direct intramolecular cyclization of these systems often proves difficult and this fact has catalyzed the development of a variety of strategies based on a convergent intermolecular cycloaddition strategy. This concept article discusses the major cycloaddition approaches utilized to access these types of structures and primarily focuses on examples employed in the synthesis of natural products.

Synthesis of naturally occurring tropones and tropolones

“…Although seven-membered ring syntheses have been reviewed several times, these reviews often focus on one type of method, such as the [4+3] cycloaddition, 85–87 [5+2] cycloaddition, 88–89 or other reactions. 90–91 A recent review on synthetic strategies to access seven-membered carbocycles in natural products only discussed the total synthesis of a few tropone- and tropolone-containing natural products including pareitropone, imerubrine, isoimerubrine and grandirubrine. 92 …”

Gold‐Catalyzed Cyclopenta‐ and Cycloheptannulation Cascades: A Stereocontrolled Approach to the Scaffold of Frondosins A and B

“…[2] Both inter-and intramolecular rhodium-mediated [5+2] cycloadditions between vinylcyclopropanes and unsaturated moieties have been successfully developed. [3] Another widespread method uses rhodium-vinyl carbenoids and dienes in formal [4+3] cycloadditions.…”

Interception of a Rautenstrauch Intermediate by Alkynes for [5+2] Cycloaddition: Rhodium‐Catalyzed Cycloisomerization of 3‐Acyloxy‐4‐ene‐1,9‐diynes to Bicyclo[5.3.0]decatrienes

“…We envisioned that a conceptually new approach to seven-membered rings was possible if intermediate 6 in the Rautenstrauch rearrangement could be intercepted by a tethered alkyne in a [5+2] cycloaddition under rhodium catalysis. [12][13][14][15][16] We herein report a new atom-economical [17] synthesis of a bicyclo[5.3.0]decatriene 8 through a rhodium(I)-catalyzed cycloisomerization [18] of a 3-acyloxy-4-ene-1,9-diyne 7 [Eq. (1)].…”

“…For example, if a carbene intermediate similar to 5 is generated, it may undergo cyclopropanation or cyclopropenation with alkenes or alkynes in the system. However, when substrate 7 a, available in four steps from 2-butene-1,4-diol, [20] was treated with a catalytic amount of [{Rh(CO) 2 [11][12][13].…”