Gold catalysis-facilitated rapid synthesis of the daphnane/tigliane tricyclic core

Abstract

A concise approach to synthesize the 5-7-6 tricyclic carbon skeleton of the daphnane/tigliane diterpene natural products has been accomplished via a sequential gold-catalyzed furan formation and furan-allene [4+3] cycloaddition. This work provides new avenues for rapid and diverted synthesis of the medicinally important daphnane/tigliane diterpenes and their unnatural analogues.

Gold Catalysis and Furans: A Powerful Match for Synthetic Connections

“…The reaction was investigated in two papers directed towards the synthesis of natural products. In the first report, 56 the onepot tandem cycloisomerization/(4+3) cycloaddition of substrates 134 was envisaged to access the common tricyclic core of the daphnanes and the tiglianes, two classes of diterpene natural products isolated from Thymelaeaceae and Euphorbiaceae. The tandem process was attempted with different gold complexes, but without success, while running the two steps separately enabled the synthesis of the desired products 136 and 137 (Scheme 38).…”

Gold-Catalyzed Homogeneous (Cyclo)Isomerization Reactions

“…This last step is highly influenced by the nature of the R 1 substituent at the allene site. Terminal allenes (R 1 = H) are poor substrates for this (4+3) cycloaddition, producing a complex mixture of products whereas tricyclic systems 33b and 33c are obtained in good yields and with a moderate isomeric ratio for the target product 33 vs. the undesired ether (Li et al, 2017b).…”

Total Syntheses of the Reported Structures of Curcusones I and J through Tandem Gold Catalysis

“…We recently developed an approach featuring a sequential gold‐catalyzed furan formation and furan–allene [4+3] cycloaddition to rapidly assemble the [5‐7‐6] tricyclic carbon skeleton of the daphnane diterpenes (Scheme A, 9 → 10 → 11 ) . For the synthesis of the rhamnofolane diterpenes, we envisioned a different tandem gold‐catalyzed furan formation and furan–allene [4+3] cycloaddition to construct the 5,7‐fused ring system with an oxa‐bridge (Scheme B, 12 → 15 ).…”

“…[11] For the synthesis of the rhamnofolane diterpenes, we envisioned a different tandem gold-catalyzed furan formation [12] and furan-allene [4+3] cycloaddition [13] to construct the 5,7-fused ring system with an oxa-bridge (Scheme 1B, 12 → 15 ). The tandem process is expected to proceed through a gold-catalyzed 5- endo - dig cyclization of enyne alcohol 12 and the resulting dihydrofuran would then isomerize to furan 13 .…”