Applications of the Fischer carbene polycyclic cyclopropanation reaction in natural product synthesis: (plus,minus)-carabrone, (plus,minus)-pentalenene, and (plus,minus)-thujopsene.

摘要

The Fischer carbene polycyclic cyclopropanation reaction was investigated as a route to sesquiterpenoid natural products. (1-Methoxy-2-(2-propenyl)pent-4-enylidene) pentacarbonylchromium(0) (80-Cr) was thermolyzed with various alkynes to produce bicyclo(4.1.0) derivatives in very good yields and excellent diastereoselectivities. {dollar}(pm){dollar}-{dollar}(1alpha,4alpha,6alpha {dollar})-1-Butyl-3-methoxy-4-(2-propenyl)bicyclo(4.1.0) hept-2-ene (95a) was elaborated into the tricyclic lactones ({dollar}pm{dollar})-(3a{dollar}alpha{dollar},4a{dollar}alpha{dollar},5a{dollar}alpha{dollar},6a{dollar}beta {dollar})-5a-butylhexahydrocyclopropa(f) benzofuran-2(3H)-one (100a) and ({dollar}pm{dollar})-(3a{dollar}alpha{dollar},4a{dollar}alpha{dollar},5a{dollar}alpha{dollar},6a{dollar}alpha{dollar})-5a -butylhexahydrocyclopropa (f) benzofuran-2(3H)-one (100b). (E-1-Methoxy-2-(E-6-methyl-2,6-heptadienyl)-8-methyl-4,8-nonadienylidene) pentacarbonylchromium(0) (75) was thermolyzed with propyne to provide ({dollar}pm{dollar})-(1{dollar}alpha,4alpha,6alpha,7 alpha{dollar})-7-(3-methyl-3-butenyl)-4-(E-6-methyl-2,6-heptadienyl)-1-methyl-3-methoxy-4-(2-propenyl)bicyclo (4.1d.0) heptan-3-one (107) which was elaborated into ({dollar}pm{dollar})-(3a{dollar}alpha{dollar},4a{dollar}alpha{dollar},5{dollar}alpha {dollar},5a{dollar}alpha{dollar},6a{dollar}alpha{dollar})-5a-methyl-5-(3-oxobutyl)hexahydrocyclopropa (f) benzofuran-2(3H)-one (73) constituting a formal synthesis of ({dollar}pm{dollar})-carabrone. ({dollar}pm{dollar})-3-(2,2-Dimethylpent-4-ynyl)-4-methylcyclopent-2-enone (125) was thermolyzed with (1-methoxymethoxyethylidene)pentacarbonylmolybdenum(0) (147-Mo) to provide ({dollar}pm{dollar})-(E-{dollar}1Rsp*{dollar},3a{dollar}Rsp*{dollar},6a{dollar}Ssp* {dollar})-3b-(2-methoxymethoxypropenyl)-1,5,{dollar}5 {dollar}-trimethylhexahydrocyclopropadicyclopenten-3-one (149) whose relative configuration was determined by X-ray diffraction. Compound 149 was converted to angular triquinane ({dollar}pm{dollar})-(1{dollar}Rsp*{dollar},8a{dollar}Ssp*{dollar})-1,4,7,7-tetramethyl-2,3a,7,8-tetrahydro-1H-cyclopenta (c) cyclopentalen-3-one (154) via ({dollar}pm){dollar}-{dollar}(E{dollar}-{dollar}4Rsp*,5Ssp*{dollar})-4,8,8-trimethyl-6-(2-oxopropylidene)spiro (4.4) nonan-2-one (143). Diene 154 has the skeleton of ({dollar}pm{dollar})-pentalenene. ({dollar}pm{dollar})-(1-Methoxy-3-methylbut-4-enylidene)pentacarbonylmolybdenum(0) (219) was thermolyzed with 7-methoxymethoxy-4,4-dimethylhept-2-yne (187) to produce ({dollar}pm{dollar})-1{dollar}alpha,2beta,5beta,6alpha{dollar})-1-(4-methoxymethoxy-1,{dollar}1 {dollar}-dimethylbutyl)-2,5-dimethylbicyclo (4.1.0) heptan-3-one (231). Compound 231 was elaborated into ({dollar}pm{dollar})-(1{dollar}alpha,2beta{dollar},4a{dollar}beta{dollar},8a{dollar}alpha{dollar})-2,4a,8,{dollar}8 {dollar}-tetramethyloctahydrocyclopropa (d) naphthalen-4-one (183) which has the thujopsane skeleton.