Stereoselective total syntheses of (±)-sinularene and of (±)-5-epi-sinularene via intramolecular type-I-“magnesium-ene” reaction

A general intramolecular Diels–Alder approach to tricyclic sesquiterpenes: stereoselective total syntheses of (±)-sinularene and (±)-5-epi-sinularene

“…Proton magnetic resonance spectra were measured at 80 MHz with a Bruker WP8O spectrometer employing a chloroform lock, at 60 MHz with a Varian EM 360 spectrometer, or at 400 MHz (at the University of Alberta) with a Bruker WH 400 spectrometer. Signal positions are reported in ppm downfield from tetramethylsilane (6 scale) as an internal standard; multiplicity, the number of protons, coupling constants, and proton assignments are indicated in parentheses. Mass spectra were determined on a V.G.…”

“…The esters 18 were reduced quantitatively with lithium aluminum hydride to the primary alcohols 1 9 but, unfortunately, direct introduction of the exocyclic methylene using either selenoxide elimination or dehydrobromination proved impractical. Therefore, the acetate 20c was prepared (Ac20, pyridine, 99%) and (*)-sinularene was obtained in 77% yield via pyrolysis of this acetate in a flow apparatus at 550°C (5,6). The sesquiterpene possessed spectral features ('H nmr, ir, ms) identical to those published for the natural product (3) and completed a direct stereoselective synthesis of (+)-sinularene in 22% overall yield from the major aldol diastereomer 8 (9% from 7).…”

“…The first by Collins and Wege utilized a Wagner-Meerwein rearrangement, followed by intramolecular alkylative ring closure (5). Subsequently Oppolzer et al employed an intramolecular "magnesium-ene" reaction as the key step (6) and, more recently, have also prepared 12-acetoxysinularene by this procedure (7). Coincident with the completion of our own work (8), Piers and Jung described an efficient Cope rearrangement sequence to the bicyclo[3.2.l]octane nucleus, followed by intramolecular alkylation to generate sinularene (9).…”

Preparation and thermal rearrangement of 2-(tert-butyldimethylsiloxy)-5-methyl-6-exo-[(Z)-3-methyl-1-butenyl]- 4 - exo - vinylbicyclo[3.1.0]hex-2-ene. A total synthesis of (±)-sinularene

“…Subsequently, two oxygenated sinularane-type sesquiterpenoids, (-)-12-acetoxysinularene (2) and (+)-12-acetoxycyclosinularene (3), were obtained from a dichloromethane extract of 1 R = H 2 R = OAc Clavularia injata, collected near Laing Island, Papua -New Guinea (2). To our knowledge, three total syntheses of (t)-sinularene (1) have been reported (3)(4)(5) in addition to that described herein. A preparation of (2)-12-acetoxysinularene (2) has also been accomplished (6).…”

Stereoselective total syntheses of (±)-sinularene and (±)-5-epi-sinularene: a general intramolecular Diels–Alder approach to tricyclic sesquiterpenes

“…Among the diverse structures produced in nature, the bridged sesquiterpenes sinularene (5, 6), longifolene (7,8), and sativene (9, 10) occupy a prominent position. All have been the object of a variety of synthetic approaches and served as a challenge for new synthetic methodology (sinularene syntheses (1 1, 12),' longifolene syntheses (1 [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18], sativene syntheses (17 -25)). …”