Total Synthesis and Structural Revision of the 6,11-Epoxyisodaucane Natural Sesquiterpene Using an Anionic 8π Electrocyclic Reaction

Abstract

A new synthetic strategy that forms a seven-membered carbocycle using an anionic 8π electrocyclic reaction facilitated the first total synthesis of the 6,11-epoxyisodaucane natural sesquiterpene in 9.0% yield over 10 steps in the longest linear sequence. The misassigned proposed stereochemistry was corrected by the synthesis of both the proposed structure and its C6 epimer. In addition, the 5-7-fused ring system was concisely constructed by tandem decyanation/five-membered-ring formation from an epoxynitrile.

Diastereoselective Synthesis oftrans‐anti‐Hydrophenanthrenes via Ti‐mediated Radical Cyclization and Total Synthesis of Kamebanin

“…According to the total synthesis of Glaucocalyxin A reported by Jia et al., [5g,21] Birch reduction without a proton source afforded the desired alcohol 24 as a major isomer in 58 % yield. The best result of the one‐electron reduction was obtained when an excess of Ca metal in MeOH [22] was used, where the desired 14β‐alcohol 24 was obtained in 66 % yield (dr=2.6 : 1). Finally, allylic oxidation with SeO 2 , Dess–Martin oxidation, and removal of MOM groups completed the total synthesis of (±)‐kamebanin (17 steps from 7 with an overall yield of 6.5 %).…”

The Electrocyclization of Heptatrienyl Anions

“…The above electrocyclization-Horner-Wadsworth-Emmons sequence was elegantly extended to silyloxy-substituted skipped trienes (Scheme 23). 46 Treatment of the keto-phosphonate system 153 with base results in deprotonation at the most activated position to generate the corresponding stabilized enolate, which is protected as its silyl enol ether 154. Subsequent treatment with additional base in situ causes a second deprotonation, this time at the bis allylic site, resulting in formation of the heptatrienyl anion and electrocyclization.…”

Cascade Vinylation/8π-Electrocyclization and Cu(II)-Catalyzed Dehydrogenation toward Highly Stable Formally Antiaromatic Cycloheptatrienyl Anions

“…This disconnection is convenient for the synthesis of electron-deficient seven-membered systems since the nature of both nucleophilic and electrophilic reagents imply the presence of electron-withdrawing groups. The synthetic path based on such a disconnection includes three vinylation steps of the CH-acid followed by 8π-electrocyclizationa powerful transformation to assemble a seven-membered ring from an acyclic substrate; yet it is highly restricted by the availability of conjugated heptatrienyl anions and therefore rarely utilized. ,− Previously, 1,2-(dimethoxycarbonyl)­vinylpyridinium (VP) was established as an easily generated and highly electrophilic vinylative reagent (Scheme B) . A number of CH-acids have been tested in the given reaction; however, only dimethylmalonate and methoxycarbonylmethylpyridinium gave seven-membered products.…”