Aromatics to Triquinanes:  p-Cresol to (±)-Δ⁹⁽¹²⁾-Capnellene

Abstract

A novel, efficient and stereospecific synthesis of the marine natural product capnellene from p-cresol is described. Generation of 4-methyl-6,6-spiroepoxycyclohexa-2,4-dienone (9) from 5-methylsalicyl alcohol (8), its in situ cycloaddition with cyclopentadiene (in situ), and the photochemical oxa-di-π-methane reaction of an endo tricyclo[5.2.2.02,6]undecenone are the key features of our strategy. An efficient synthetic route to appropriately designed endo tricyclo[5.2.2.02,6]undecenones (compounds 6, 11−13) endowed with most of the structural and stereochemical features of capnellene, from the keto epoxide 7, are described. The photochemical reaction of 6, and 11b,d upon sensitized irradiation readily gave the oxa-di-π-methane products 5, 14, and 15 respectively. The tetracyclic compound 5 was elaborated to capnellene after cleavage of the peripheral cyclopropane bond, Barton's deoxygenation, deprotection of the carbonyl group, and Wittig reaction.

Benzofuran as a dienophile in π4s+π2s cycloaddition with cyclohexa-2,4-dienones. Studies on synthesis and photoreaction of dihydrobenzofuran annulated bicyclo[2.2.2]octenones

“…13 It was indeed gratifying to note the efficiency of 1,3-acyl shift in 15a as in a majority of cases, direct irradiation of b,g-enones induces other competing reactions such as decarbonylation, ketene elimination, etc. The substrates 15c and 15d also underwent a smooth 1,3-acyl shift upon direct irradiation in benzene to give the corresponding tetracyclic products 17c and 17d, respectively (Scheme 7).…”

“…1 H NMR (400 MHz, CDCl 3 ): d 7.23 (d, J¼7.5 Hz, 1H), 7.14 (merged dd, J 1 ¼J 2 ¼7.9 Hz, 1H), 6.85 (merged dd, J 1 ¼J 2 ¼7.5 Hz, 1H), 6.71 (d, J¼8.0 Hz, 1H), 4.57 (dd, J 1 ¼8.8 Hz, J 2 ¼3.9 Hz, 1H), 5.30 (br s, 1H), 3.60 (d, J¼8.8 Hz, 1H), 3.18 (part of an AB system, J AB ¼6.2 Hz, 1H), 2.97e2.92 (multiplet merged with part of an AB system, J AB ¼6.2 Hz, total 2H), 1.88 (d, J¼1.6 Hz, 3H), 1.46 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): d 205.2, 161.4, 141.0, 129.3, 126.2, 125.5, 125.1, 120.3, 109.2, 83.0, 55.3, 53.0, 51.4, 49.8, 48.4, 22.2, 15.3. HRMS (ESI) (m/z): found 291.0992 (MþNa) þ ; calcd for C 17 H 16 NaO 3 : 291.0992.…”

“…13-Chloromethyl-13-hydroxy-3-oxa-tetracyclo [9.2.2.0 2,10 .0 4,9 ]pentadeca-4,6,8,14-tetraen-12-one (8a) A mixture of chlorohydroxy dimer 6a (1.0 g, 3.15 mmol), benzofuran 2 (1.0 mL, 9.46 mmol) and BHT (Butylated Hydroxy Toluene) (0.003 g) in toluene (4 mL 15e7.10 (m, 2H), 6.84 (merged dd, J 1 ¼J 2 ¼7.6 Hz, 1H), 6.70 (d, J¼8.1 Hz, 1H), 6.34 (merged dd, J 1 ¼J 2 ¼7.3 Hz, 1H), 6.02 (merged dd, J 1 ¼J 2 ¼7.3 Hz, 1H), 5.57 (dd, J 1 ¼8.6 Hz, J 2 ¼3.6 Hz, 1H), 4.05 (dd, J 1 ¼8.6 Hz, J 2 ¼2.5 Hz, 1H), 3.93e3.90 (m, 1H), 3.66 (part of an AB system, J AB ¼8.0 Hz, 1H), 3.59e3.55 (multiplet merged with part of an AB system, J AB ¼8.0 Hz, total 2H), 2.85(s, 1H). 13 C NMR (100 MHz, CDCl 3 ): d 207. 0, 161.0, 132.4, 129.4, 128.4, 126.4, 124.5, 120.8, 109.4, 80.9, 73.5, 52.5, 50.5, 45.8, 44.9 4.3.…”

“…1 H NMR (400 MHz, CDCl 3 ): d 7.15e7.07 (m, 2H), 6.84 (merged dd, J 1 ¼J 2 ¼7.5 Hz, 1H), 6.68 (d, J¼8.3 Hz, 1H), 6.40 & 6.30 (merged dd, J 1 ¼J 2 ¼7.0 Hz, total 1H), 5.94 (merged dd, J 1 ¼J 2 ¼7.0 Hz, 1H), 5.33 and 5.20 (dd, J 1 ¼9.0 Hz, J 2 ¼3.5 Hz, total 1H), 3.86 & 3.80 (d, J¼9.0 Hz, 1H), 3.48e3.35 (m, total 2H), 2.25e2.05 (m, 1H), 1.25 and 1.16 (d, J¼7.2 Hz, total 3H). 13 C NMR (100 MHz, CDCl 3 ): d 212. 6, 160.9, 134.8, 133.0, 129.1, 127.6, 127.0, 126.9, 124.59, 124.54, 120.7, 120.6, 109.2, 109.0, 84.3, 81.5, 53.3, 53.1, 45.2, 44.3, 44.2, 43.3, 40.9, 40.0, 16.9, 14.4 (merged dd, J 1 ¼J 2 ¼7.5 Hz, 1H), 6.68 (d, J¼8.2 Hz, 1H), 6.43 (merged dd, J 1 ¼J 2 ¼7.4 Hz, 1H), 5.96 (merged dd, J 1 ¼J 2 ¼7.4 Hz, 1H), 5.40 (dd, J 1 ¼8.9 Hz, J 2 ¼3.6 Hz, 1H), 3.93e3.80 (merged m, 3H), 3.67e3.60 (m, 1H), 3.50e3.47 (m, 1H), 2.51e2.30 (multiplet merged with broad signal, 2H).…”

“…6, 160.9, 134.8, 133.0, 129.1, 127.6, 127.0, 126.9, 124.59, 124.54, 120.7, 120.6, 109.2, 109.0, 84.3, 81.5, 53.3, 53.1, 45.2, 44.3, 44.2, 43.3, 40.9, 40.0, 16.9, 14.4 (merged dd, J 1 ¼J 2 ¼7.5 Hz, 1H), 6.68 (d, J¼8.2 Hz, 1H), 6.43 (merged dd, J 1 ¼J 2 ¼7.4 Hz, 1H), 5.96 (merged dd, J 1 ¼J 2 ¼7.4 Hz, 1H), 5.40 (dd, J 1 ¼8.9 Hz, J 2 ¼3.6 Hz, 1H), 3.93e3.80 (merged m, 3H), 3.67e3.60 (m, 1H), 3.50e3.47 (m, 1H), 2.51e2.30 (multiplet merged with broad signal, 2H). 13 C NMR (100 MHz, CDCl 3 ): d 212. 1, 160.9, 134.6, 129.2, 127.6, 126.8, 124.5, 120.6, 109.2, 81.8, 61.9, 53.9, 48.5, 45.6, 41. 4.11.…”