Facile Synthesis of 7-Dimethylamino-endo-tricyclo[5.2.2.01,6]undec-10-en-9-ones

Abstract

Pentacarbonyl[(2E)-3-cyclohexenyl-3-dimethylamino-1-ethoxy-2-propen-1-ylidene]chromium (2) yields 7-dimethylamino-endo-tricyclo[5.2.2.0 1,6 ]undec-10-en-9-ones 5 (15−88%, 12 examples) upon treatment with alkynes 3 in pyridine, most probably by a 6π-electrocyclization followed by a subsequent reductive elimination/intermolecular Diels−Alder re-[ ‡] X-ray crystal structure analysis [a]

7‐(Dimethylamino)tricyclo[5.2.2.01,6]undecene Derivatives from β‐Cyclohexenyl β‐Dimethylamino‐Substituted α,β‐Unsaturated Fischer Carbenes

“…β‐(Dimethylamino)‐substituted α,β‐unsaturated Fischer carbene complexes 1 were prepared from lithiated 1‐ethynyl‐1‐cyclohexene, the respective hexacarbonylmetal, triethyloxonium tetrafluoroborate and dimethylamine according to the previously developed one‐pot procedure in excellent yields (94% for 1 ‐Cr1 and 87% for 1 ‐W). As mentioned previously,2 the cyclohexane‐annelated cyclopentadiene 6 is formed via a 6π‐electrocyclization, and the observed regional and facial selectivities in the Diels−Alder reactions of 7 with dienophiles 2 can be explained on the basis of a model proposed by Winterfeldt3 (Scheme 2). The applied alkynes add onto the more reactive 1,3‐diene 7 with syn ‐facial selectivity (with respect to the hydrogen in 7 ) and, as far as the larger groups R L are concerned, the ortho ‐selectivity rule (with respect to the dimethylamino group in 7 ) is obeyed 2…”

“…α,β‐Unsaturated Fischer carbenes have established their broad versatility in organic synthesis 1. Among a wide spectrum of easily accessible products from such metal complexes, 7‐(dimethylamino)tricyclo[5.2.2.0 1,6 ]undec‐10‐en‐9‐ones 4 were obtained from pentacarbonyl(3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene)chromium ( 1 ‐Cr) and alkynes 2 in one step with high regio‐ and stereoselectivity (Scheme ), as we communicated previously 2. The initial products were actually the cycloadducts 3 as assigned on the basis of 1 H and 13 C NMR spectra of the crude products.…”

“…Tetrahydrofuran was distilled from sodium benzophenone ketyl, and pyridine was distilled from calcium hydride. Pentacarbonyl[(2 E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene]chromium ( 1 ‐Cr),2 1‐ethynyl‐1‐cyclopentene ( 2a ),15 1‐ethynyl‐1‐cyclohexene ( 2b ),15 methyl p ‐ethynylbenzoate ( 2j ),16 2‐ethynylthiophene ( 2f ),17 2‐ethynylbenzotrifluoride ( 2l ),17 3‐ethynylbenzotrifluoride ( 2m ),17 4‐ethynylbenzotrifluoride ( 2n ),17 1‐ethynylnaphthalene ( 2o ),17 1‐phenyl‐4‐(trimethylsilyl)‐1,3‐butadiyne ( 2p ),17,18 1,4‐diethynylbenzene ( 2t ),19 1,3,5‐triethynylbenzene ( 2u ),19 2‐ethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2v ),9 2,7‐diethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2 ×) ,9 1,2‐bis(4‐ethynylphenyl)ethane ( 10c ),17,20 1,8‐diphenyl‐1,3,5,7‐octatetrayne ( 13 ),21 2bromo‐9,9‐di‐ n ‐hexyl‐7‐(3′‐hydroxy‐3′‐methylbut‐1′‐ynyl)fluorene17,22 were prepared according to published procedures.…”

“…Pentacarbonyl[( 2E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2propen‐1‐ylidene]tungsten (1‐W): Following a previously published protocol,2,23 (2.50 mL, 21.3 mmol) of 1‐ethynyl‐1‐cyclohexene ( 2b ) in THF (100 mL) was treated with n ‐butyllithium (9.00 mL, 2.36 M in n ‐hexane, 21.2 mmol), hexacarbonyltungsten (8.01 g, 22.8 mmol), Et 3 OBF 4 (4.18 g, 22.0 mmol), and gaseous dimethylamine (1 equiv.). Flash chromatography on silica gel (120 g) eluting with pentane/Et 2 O (from 10:1 to 4:1) gave 9.77 g (87%) of 1 ‐W [ R f = 0.53 (pentane/Et 2 O, 1:1)] as a yellow solid, m.p.…”

7‐(Dimethylamino)tricyclo[5.2.2.01,6]undecene Derivatives from β‐Cyclohexenyl β‐Dimethylamino‐Substituted α,β‐Unsaturated Fischer Carbenes

“…β‐(Dimethylamino)‐substituted α,β‐unsaturated Fischer carbene complexes 1 were prepared from lithiated 1‐ethynyl‐1‐cyclohexene, the respective hexacarbonylmetal, triethyloxonium tetrafluoroborate and dimethylamine according to the previously developed one‐pot procedure in excellent yields (94% for 1 ‐Cr1 and 87% for 1 ‐W). As mentioned previously,2 the cyclohexane‐annelated cyclopentadiene 6 is formed via a 6π‐electrocyclization, and the observed regional and facial selectivities in the Diels−Alder reactions of 7 with dienophiles 2 can be explained on the basis of a model proposed by Winterfeldt3 (Scheme 2). The applied alkynes add onto the more reactive 1,3‐diene 7 with syn ‐facial selectivity (with respect to the hydrogen in 7 ) and, as far as the larger groups R L are concerned, the ortho ‐selectivity rule (with respect to the dimethylamino group in 7 ) is obeyed 2…”

“…α,β‐Unsaturated Fischer carbenes have established their broad versatility in organic synthesis 1. Among a wide spectrum of easily accessible products from such metal complexes, 7‐(dimethylamino)tricyclo[5.2.2.0 1,6 ]undec‐10‐en‐9‐ones 4 were obtained from pentacarbonyl(3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene)chromium ( 1 ‐Cr) and alkynes 2 in one step with high regio‐ and stereoselectivity (Scheme ), as we communicated previously 2. The initial products were actually the cycloadducts 3 as assigned on the basis of 1 H and 13 C NMR spectra of the crude products.…”

“…Tetrahydrofuran was distilled from sodium benzophenone ketyl, and pyridine was distilled from calcium hydride. Pentacarbonyl[(2 E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene]chromium ( 1 ‐Cr),2 1‐ethynyl‐1‐cyclopentene ( 2a ),15 1‐ethynyl‐1‐cyclohexene ( 2b ),15 methyl p ‐ethynylbenzoate ( 2j ),16 2‐ethynylthiophene ( 2f ),17 2‐ethynylbenzotrifluoride ( 2l ),17 3‐ethynylbenzotrifluoride ( 2m ),17 4‐ethynylbenzotrifluoride ( 2n ),17 1‐ethynylnaphthalene ( 2o ),17 1‐phenyl‐4‐(trimethylsilyl)‐1,3‐butadiyne ( 2p ),17,18 1,4‐diethynylbenzene ( 2t ),19 1,3,5‐triethynylbenzene ( 2u ),19 2‐ethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2v ),9 2,7‐diethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2 ×) ,9 1,2‐bis(4‐ethynylphenyl)ethane ( 10c ),17,20 1,8‐diphenyl‐1,3,5,7‐octatetrayne ( 13 ),21 2bromo‐9,9‐di‐ n ‐hexyl‐7‐(3′‐hydroxy‐3′‐methylbut‐1′‐ynyl)fluorene17,22 were prepared according to published procedures.…”

“…Pentacarbonyl[( 2E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2propen‐1‐ylidene]tungsten (1‐W): Following a previously published protocol,2,23 (2.50 mL, 21.3 mmol) of 1‐ethynyl‐1‐cyclohexene ( 2b ) in THF (100 mL) was treated with n ‐butyllithium (9.00 mL, 2.36 M in n ‐hexane, 21.2 mmol), hexacarbonyltungsten (8.01 g, 22.8 mmol), Et 3 OBF 4 (4.18 g, 22.0 mmol), and gaseous dimethylamine (1 equiv.). Flash chromatography on silica gel (120 g) eluting with pentane/Et 2 O (from 10:1 to 4:1) gave 9.77 g (87%) of 1 ‐W [ R f = 0.53 (pentane/Et 2 O, 1:1)] as a yellow solid, m.p.…”

Highly Selective Formation of [4+2] and [4+3] Cycloadducts of Tetrahydroindenes Generated in Situ from a (1-Alkynyl)carbene Tungsten Complex by the Metalla-1,3,5-hexatriene Route

“…It was anticipated that [4+2] cycloadducts might be derived both from compounds 7 and 8 ,16 depending on the reaction conditions and the nature of the dienophile. The reaction of the 1‐tungsta‐1,3,5‐hexatriene (3 E )‐ 5 a with pyridine in presence of PhC≡CCO 2 Et ( 3 a ) at 60 °C for 2 hours was shown to afford a 1:1 mixture of tricyclic compound 4 a and pentacarbonyl(pyridine)tungsten 17. Since compound 4 a is derived from tetrahydro‐7a H ‐indene 7 a , but not from its precursor tetrahydro‐3a H ‐indene 8 a , it can be stated that a [4+2] addition of 8 a to electron‐poor alkyne 3 to give adduct 10 would be slower than the isomerization of the 8 a to 7 a 6a, 10.…”

7‐(Dimethylamino)tricyclo[5.2.2.01,6]undecene Derivatives from β‐Cyclohexenyl β‐Dimethylamino‐Substituted α,β‐Unsaturated Fischer Carbenes

“…β‐(Dimethylamino)‐substituted α,β‐unsaturated Fischer carbene complexes 1 were prepared from lithiated 1‐ethynyl‐1‐cyclohexene, the respective hexacarbonylmetal, triethyloxonium tetrafluoroborate and dimethylamine according to the previously developed one‐pot procedure in excellent yields (94% for 1 ‐Cr1 and 87% for 1 ‐W). As mentioned previously,2 the cyclohexane‐annelated cyclopentadiene 6 is formed via a 6π‐electrocyclization, and the observed regional and facial selectivities in the Diels−Alder reactions of 7 with dienophiles 2 can be explained on the basis of a model proposed by Winterfeldt3 (Scheme 2). The applied alkynes add onto the more reactive 1,3‐diene 7 with syn ‐facial selectivity (with respect to the hydrogen in 7 ) and, as far as the larger groups R L are concerned, the ortho ‐selectivity rule (with respect to the dimethylamino group in 7 ) is obeyed 2…”

“…α,β‐Unsaturated Fischer carbenes have established their broad versatility in organic synthesis 1. Among a wide spectrum of easily accessible products from such metal complexes, 7‐(dimethylamino)tricyclo[5.2.2.0 1,6 ]undec‐10‐en‐9‐ones 4 were obtained from pentacarbonyl(3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene)chromium ( 1 ‐Cr) and alkynes 2 in one step with high regio‐ and stereoselectivity (Scheme ), as we communicated previously 2. The initial products were actually the cycloadducts 3 as assigned on the basis of 1 H and 13 C NMR spectra of the crude products.…”

“…Tetrahydrofuran was distilled from sodium benzophenone ketyl, and pyridine was distilled from calcium hydride. Pentacarbonyl[(2 E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene]chromium ( 1 ‐Cr),2 1‐ethynyl‐1‐cyclopentene ( 2a ),15 1‐ethynyl‐1‐cyclohexene ( 2b ),15 methyl p ‐ethynylbenzoate ( 2j ),16 2‐ethynylthiophene ( 2f ),17 2‐ethynylbenzotrifluoride ( 2l ),17 3‐ethynylbenzotrifluoride ( 2m ),17 4‐ethynylbenzotrifluoride ( 2n ),17 1‐ethynylnaphthalene ( 2o ),17 1‐phenyl‐4‐(trimethylsilyl)‐1,3‐butadiyne ( 2p ),17,18 1,4‐diethynylbenzene ( 2t ),19 1,3,5‐triethynylbenzene ( 2u ),19 2‐ethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2v ),9 2,7‐diethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2 ×) ,9 1,2‐bis(4‐ethynylphenyl)ethane ( 10c ),17,20 1,8‐diphenyl‐1,3,5,7‐octatetrayne ( 13 ),21 2bromo‐9,9‐di‐ n ‐hexyl‐7‐(3′‐hydroxy‐3′‐methylbut‐1′‐ynyl)fluorene17,22 were prepared according to published procedures.…”

“…Pentacarbonyl[( 2E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2propen‐1‐ylidene]tungsten (1‐W): Following a previously published protocol,2,23 (2.50 mL, 21.3 mmol) of 1‐ethynyl‐1‐cyclohexene ( 2b ) in THF (100 mL) was treated with n ‐butyllithium (9.00 mL, 2.36 M in n ‐hexane, 21.2 mmol), hexacarbonyltungsten (8.01 g, 22.8 mmol), Et 3 OBF 4 (4.18 g, 22.0 mmol), and gaseous dimethylamine (1 equiv.). Flash chromatography on silica gel (120 g) eluting with pentane/Et 2 O (from 10:1 to 4:1) gave 9.77 g (87%) of 1 ‐W [ R f = 0.53 (pentane/Et 2 O, 1:1)] as a yellow solid, m.p.…”

Highly Selective Formation of [4+2] and [4+3] Cycloadducts of Tetrahydroindenes Generated in Situ from a (1-Alkynyl)carbene Tungsten Complex by the Metalla-1,3,5-hexatriene Route

“…It was anticipated that [4+2] cycloadducts might be derived both from compounds 7 and 8 ,16 depending on the reaction conditions and the nature of the dienophile. The reaction of the 1‐tungsta‐1,3,5‐hexatriene (3 E )‐ 5 a with pyridine in presence of PhC≡CCO 2 Et ( 3 a ) at 60 °C for 2 hours was shown to afford a 1:1 mixture of tricyclic compound 4 a and pentacarbonyl(pyridine)tungsten 17. Since compound 4 a is derived from tetrahydro‐7a H ‐indene 7 a , but not from its precursor tetrahydro‐3a H ‐indene 8 a , it can be stated that a [4+2] addition of 8 a to electron‐poor alkyne 3 to give adduct 10 would be slower than the isomerization of the 8 a to 7 a 6a, 10.…”

7‐(Dimethylamino)tricyclo[5.2.2.01,6]undecene Derivatives from β‐Cyclohexenyl β‐Dimethylamino‐Substituted α,β‐Unsaturated Fischer Carbenes

“…β‐(Dimethylamino)‐substituted α,β‐unsaturated Fischer carbene complexes 1 were prepared from lithiated 1‐ethynyl‐1‐cyclohexene, the respective hexacarbonylmetal, triethyloxonium tetrafluoroborate and dimethylamine according to the previously developed one‐pot procedure in excellent yields (94% for 1 ‐Cr1 and 87% for 1 ‐W). As mentioned previously,2 the cyclohexane‐annelated cyclopentadiene 6 is formed via a 6π‐electrocyclization, and the observed regional and facial selectivities in the Diels−Alder reactions of 7 with dienophiles 2 can be explained on the basis of a model proposed by Winterfeldt3 (Scheme 2). The applied alkynes add onto the more reactive 1,3‐diene 7 with syn ‐facial selectivity (with respect to the hydrogen in 7 ) and, as far as the larger groups R L are concerned, the ortho ‐selectivity rule (with respect to the dimethylamino group in 7 ) is obeyed 2…”

“…α,β‐Unsaturated Fischer carbenes have established their broad versatility in organic synthesis 1. Among a wide spectrum of easily accessible products from such metal complexes, 7‐(dimethylamino)tricyclo[5.2.2.0 1,6 ]undec‐10‐en‐9‐ones 4 were obtained from pentacarbonyl(3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene)chromium ( 1 ‐Cr) and alkynes 2 in one step with high regio‐ and stereoselectivity (Scheme ), as we communicated previously 2. The initial products were actually the cycloadducts 3 as assigned on the basis of 1 H and 13 C NMR spectra of the crude products.…”

“…Tetrahydrofuran was distilled from sodium benzophenone ketyl, and pyridine was distilled from calcium hydride. Pentacarbonyl[(2 E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2‐propen‐1‐ylidene]chromium ( 1 ‐Cr),2 1‐ethynyl‐1‐cyclopentene ( 2a ),15 1‐ethynyl‐1‐cyclohexene ( 2b ),15 methyl p ‐ethynylbenzoate ( 2j ),16 2‐ethynylthiophene ( 2f ),17 2‐ethynylbenzotrifluoride ( 2l ),17 3‐ethynylbenzotrifluoride ( 2m ),17 4‐ethynylbenzotrifluoride ( 2n ),17 1‐ethynylnaphthalene ( 2o ),17 1‐phenyl‐4‐(trimethylsilyl)‐1,3‐butadiyne ( 2p ),17,18 1,4‐diethynylbenzene ( 2t ),19 1,3,5‐triethynylbenzene ( 2u ),19 2‐ethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2v ),9 2,7‐diethynyl‐9,9‐di‐ n ‐hexylfluorene ( 2 ×) ,9 1,2‐bis(4‐ethynylphenyl)ethane ( 10c ),17,20 1,8‐diphenyl‐1,3,5,7‐octatetrayne ( 13 ),21 2bromo‐9,9‐di‐ n ‐hexyl‐7‐(3′‐hydroxy‐3′‐methylbut‐1′‐ynyl)fluorene17,22 were prepared according to published procedures.…”

“…Pentacarbonyl[( 2E )‐3‐cyclohexenyl‐3‐(dimethylamino)‐1‐ethoxy‐2propen‐1‐ylidene]tungsten (1‐W): Following a previously published protocol,2,23 (2.50 mL, 21.3 mmol) of 1‐ethynyl‐1‐cyclohexene ( 2b ) in THF (100 mL) was treated with n ‐butyllithium (9.00 mL, 2.36 M in n ‐hexane, 21.2 mmol), hexacarbonyltungsten (8.01 g, 22.8 mmol), Et 3 OBF 4 (4.18 g, 22.0 mmol), and gaseous dimethylamine (1 equiv.). Flash chromatography on silica gel (120 g) eluting with pentane/Et 2 O (from 10:1 to 4:1) gave 9.77 g (87%) of 1 ‐W [ R f = 0.53 (pentane/Et 2 O, 1:1)] as a yellow solid, m.p.…”

Highly Selective Formation of [4+2] and [4+3] Cycloadducts of Tetrahydroindenes Generated in Situ from a (1-Alkynyl)carbene Tungsten Complex by the Metalla-1,3,5-hexatriene Route

“…It was anticipated that [4+2] cycloadducts might be derived both from compounds 7 and 8 ,16 depending on the reaction conditions and the nature of the dienophile. The reaction of the 1‐tungsta‐1,3,5‐hexatriene (3 E )‐ 5 a with pyridine in presence of PhC≡CCO 2 Et ( 3 a ) at 60 °C for 2 hours was shown to afford a 1:1 mixture of tricyclic compound 4 a and pentacarbonyl(pyridine)tungsten 17. Since compound 4 a is derived from tetrahydro‐7a H ‐indene 7 a , but not from its precursor tetrahydro‐3a H ‐indene 8 a , it can be stated that a [4+2] addition of 8 a to electron‐poor alkyne 3 to give adduct 10 would be slower than the isomerization of the 8 a to 7 a 6a, 10.…”