6‐Methylenebicyclo[3.2.1]oct‐1‐en‐3‐one: A Twisted Olefin as Diels–Alder Dienophile for Expedited Syntheses of Four Kaurane Diterpenoids

Abstract

6-Methylenebicyclo[3.2.1]oct-1-en-3-one,atwisted and highly reactive enone,w as prepared for the first time by elimination of its bromide precursor.I ts reactions as ad ienophile with several dienes in Diels-Alder reactions proceeded smoothly to provide tricyclic and tetracyclic adducts,w hich allowed short syntheses (10-11 steps) of four kurane diterpenoids including 11b-hydroxy-16-kaurene,1 1 a-hydroxy-16kaurene,liangshanin G, and gesneroidin B. Figure 2. Formationa nd reaction of some bridgehead enones.

Enantioselective Total Syntheses of Grayanane Diterpenoids: (−)-Grayanotoxin III, (+)-Principinol E, and (−)-Rhodomollein XX

“…The gram-scale preparation of the grayanoid skeleton (19), together with the stereoisomers of natural products provided by this study, could serve future investigations on the biological activities of this intriguing family. Even though the solvolysis of bridgehead triflates was reported more than three decades ago, 35 the application of bridgehead carbocations in total synthesis has been limited compared to bridgehead enones; 15,36…”

Dearomative logic in natural product total synthesis

“…73 Although requiring preinstallation of the bicyclo[3.2.1]octane motif (via radical cyclization), Ma has demonstrated that Diels-Alder cycloaddition with transiently generated bridgehead enone 25 is a powerful tactic to rapidly construct the ent-kaurene skeleton in a convergent fashion (26 / 27). 74 This method was applied in the total syntheses of 11b-hydroxy-16-kaurene, 11a-hydroxy-16-kaurene, liangshanin G, and gesneroidin B. Biomimetic conversion of the beyerene skeleton to the kaurene skeleton through 1,2-alkyl shi (28 / 29) was recently achieved by Luo and coworkers, using Lewis acid-promoted epoxide opening to trigger the rearrangement. 75 This synthesis is also notable for its application of an interesting interrupted Nazarov cyclization.…”

Total Synthesis of Natural Products Containing a Bridgehead Double Bond

“…It could be easily prepared by elimination of the bromide A, 23 nevertheless, its isolation is not feasible even at low temperatures and enone B can only be detected by infrared (IR) and nuclear magnetic resonance (NMR) spectrums in solution at À78 C. 24 Bicyclic system with S = 6 could be considered as fleeting intermediates, e.g., the [3.2.1]bridgehead enone D (Figure 1C). It was prepared through intramolecular Wittig reaction in C, 25,26 or through elimination of the corresponding bromide E. 27 This enone D is too unstable to be detected, however, it can be trapped by the addition of nucleophiles such as MeOH, PhSeH, or H 2 O, and used for Diels-Alder reaction.…”