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An approach to the skeleton of eriolanin
Terrahedron Letters. Vol. 36, No. 12, pp. 2067-2070. 1995 Elsevier Science Ltd Printed in Great Britain 004&4039/95 $9.50+0.00
0040-4039(95)0022 l-9
An Approach to the Skeleton of Eriolanin
Jsnine Cossy*, Jean-Luc Rannivosata, Vkonique Bellosta
Latxxatoire de Chimie Organique, As&C au CNRS. ESPCI, 10 rue Vauquelin, 7523 1 Paris Cedex 05 - France.
Abstract: The irradiation of 5-exo-bro/tro-6-endo-propargylo.ry-7-oxanorbornan-2-ones o/triethylamine leak directcv to the formation ojthe eriokmin skeleton.
in the presence
Whereas numerous methods exist for the synthesis of a-methylene-y-butyrolactones tised to cyclohexanes,l few direct methods are available for the preparation of a-methylene-y-butyrolactones of trans1,3-dihydroxycyclohexanes 2 which are present in the skeleton of eriolanin 1.3 Furthermore, the a-methylene-ybutyrolactone of a trans-1,3-diol structural unit is also present in the pseudoguaianolide helenalin 2.4
2
3
As a-methylene-y-butyrolactones are easily obtained by the oxidation of P-methylenehrans by the chromium trioxide-pyridine complex,5 syntheses of compounds of type 3 were envisaged from S-bromo-6-propargyloxyoxanorbornanones of type 7 vin intermediate 4
Oxanorbornenone 5, prepared according to Vogel’s procedure,6 was transformed into ketal 6 by treatment of 5 with propargylic silyl ether in the presence of trimethylsilyltriflate (TMSOTf) at 0°C in CH,Cl,. The transformation of 6 to ketal 8 was achieved with a yield of 77 % by treatment of 6 with 2.5 equivalents of n-butyllithium followed by the addition of 2.5 equivalents of methyliodide. Ketal 9 was synthesized with an 87 % yield by quenching the dianion of 6 by trimethylsilyl chloride. The treatment of these ketals 6, 8, 9 by bromine at -78’C in CH$& produced the corresponding bromocompounds 7, 10, 11 in yields higher than 90%. 2067
2068
o
o
o
.o laBeL, ~u%, /7CH3I O
o (cH3)asi(CH3)3Si~-'~O'~--'~
~ 0 , ~
o
o
The irradiation 7 of compounds 7, 10 and 11, at 254 nm, in acetonitrile, in the presence of 10 equivalents of triethylamine, for 75 rain, led to the formation of 12, 8 13 and 14 with yields of 65 %, 62 % and 72 %, respectively. Compounds 13 and 14 are l:l mixture of the corresponding (Z) and (E) isomers which could not be separated by chromatography. Startina material
Isolated prQduct
o
Yield
HO 65%
7
Ov,~
0
H 12
OBr 62%
v,-o 10
0 Br O ~ O E v ,,~Si(C H3)3 11
13 O ~
si(CH3)3 H
14
72%
2069
When compound 7 was irradiated for 60 rain, products 15 9 and 12 were formed with yields of 40 % and 37 %, respectively. No trace of compound 16 was observed. HO
o
07 ~ o B v , ~
hv o NEt3 10eq.
+o H H 15 1;' (40%) (37%) I hv NEt~
HO
o~--"~,.Ii ~ o
H 16 (0%)
(66%)
Furthermore, tile irradiation of 7 in an acetonitrile solution (5 x 10-2 M), in the presence of 10 equivalents of triethylamine, for 30 min, led exclusively to the formation of 15 with a 98 % yield for a rate of 63 % conversion. We should also point out that the irradiation of 15 in the presence of triethylamine for 60 min generated 12 with a 68 % yield. The photochemical transformation of substituted bromo-oxanorbornanones to the precursor of amethylene-'t-butyrolactone of
trans-l,3-dihydroxycyclohexanes involves an
electron-transfer to the bromide in
the first step, which produces the cleavage of the C-Br bond.l° A radical cyclization takes place to form the corresponding methylene-furan. The second step is the photoreduction of the carbonyl moiety of the oxanorbornanone which involves the formation of a ketyl anion-radical that provokes the cleavage of the C-O bond of the oxa bridge. This cleavage appears to be easier in compound 15 than in compound 7 as the former is probably more strained. It is likely that the radical-anion X is responsible for this ring opening as radicals a to an oxa bridge are not able to induce cleavage of the ethereal link. 11
O
O
O
NEt3 hv
-OnO "~ l HO
H
The use of this methodology to the syntheses of natural products is presently under investigation in our laboratory. Since both (-)- and (+)-7-oxanorbornanone 5 can be obtained in optically pure forms, 12 the synthesis of enantiomerically pure natural products could be envisaged.
2070
Acknowledgments
: One of us (J.-L. R.) thanks the Ministere de la Recherche et de la Technologic for a grant.
References and notes
1.
2. 3.
4. 5. 6. 7. 8.
9.
10. 11.
12.
a) Grieco, P. A. Synthesis 1975, 67-82. b) Hoffmann, H. M R.; Rabe, J. Angew. Chem. btt. Ed. Engl. 1985, 24, 94-110. c) Sarma, J. C.; Sharma, R. P. Heterocycles 1986, 24, 441-457. d) Dulcrre, J. P; Rodriguez, J.; Santelli, M.; Zahra, J. P. Tetrahedron Lett. 1987, 28, 2009-2012. a) Marino, J. P.; Farina, J. S. J. Org. Chem. 1976, 41, 3213-3215. b) Krafft, M. E. Tetrahedron Lett. 1986, 27, 771-774. Isolation of eriolanin : Kupchan, S. M.; Baxter, R. L.; Chiang, C K.; Gilmore, C. J.; Bryan, R.F.J. Chem. Soc. Chem. Comm. 1973, 842-843. Syntheses of 1 : a) Grieco, P. A.; Oguri, T.; Gilman, S. d. Ant. Chem. Soc. 1980, 102, 5886-5891. b) Roberts, M. R.; Schlessinger, R. H. J. Ant. Chem. Soc. 1981, 103, 724-725. Heathcock, C. H. " The Total Synthesis o f Natural Products ", Apsimon, J. Ed.; John Wiley and Sons, Inc., New York, Vol. 5, 1983, 369-373. a) Dauben, W. G.; Lorber, M.; Fullerton, D. S. J. Org. Chem. 1969, 34, 3587-3592. b) Ratcliffe, R.; Rodehorst, R. J. Org. Chem. 1970, 35, 4000-4002. a) Vieira, E.; Vogel, P. Hell,. Chim. Acta 1982, 65, 1700-1720. b) Black, K. A.; Vogel, P. Heh,. Chim. Acta 1984, 67, 1612-1615. c) Vogel, P.; Fattori, D.; Gasparini, F.; Le Drian, C. Synlett 1990, 173-185. Irradiations were performed in a quartz vessel, at 254 nm ("merry-go-round" irradiator with 8 Philips TUV 15 lamps), in CH3CN ( 10-2 M solutions ), in the presence of 10 equivalents of triethylamine. Spectral data of12 : IR (film) : 3440, 1700, 1660 cm-1. 1H NMR (CDCI3, 300 MHz) 5 (ppm) : 2.00-2.30 (m, OH); 2.45 (ddd, 1H, J = 16.5 Hz, J = 5.2 Hz, J = 1.5 Hz); 2.61 (dd, IH, J = 16.5 Hz, J = 2.9 Hz); 2.70 (dd, 1H, J = 17.3 Hz, J = 2.9 Hz); 2.85 (dd, 1H, J = 17.3 Hz, J = 3.3 Hz); 2.97 (m, 1H); 4.15 (ddd, 1H, d = 5.2 Hz, J = 2.9 Hz, J = 2.9 Hz); 4.27 (dddd, 1H, J = 13.6 Hz, J = 2.6 Hz, J = 2.6 Hz, J = 1.5 Hz); 4.44 (dddd, 1H, J = 13.6 Hz, J = 1.8 Hz, J = 1.8 Hz, J = 1.8 Hz); 4.48 (ddd, 1H, J = 6.6 Hz, J = 3.3 Hz, J = 2.9 Hz); 5.16 (m, 2H). 13C NMR (CDC13, 75 MHz) 5 (ppm) : 41.7 (t); 44.3 (t); 49.0 (d); 70.8 (t); 70.9 (d); 77.0 (d); 107.1 (t); 149.1 (s); 208.0 (s). MS (70 eV) : 168 (M +, 2); 150 (1); 111 (1); 95 (3); 82 (100). Spectral data of 15 : IR (film) : 1760, 1660 cm-1. 1H NMR (CDC13, 300 MHz) 6 (ppm) : 2.35 (ddd, 1H, d = 17.9 Hz, J = 0.9 Hz, J = 0.5 Hz); 2.46 (ddddd, 1H, J = 17.9 Hz, J = 5.9 Hz, J = 0.9 Hz, J = 0.9 Hz, J = 0.6 Hz); 3.64 (m, 1H); 4.37 (dddd, 1H, J = 5.4 Hz, J = 1.2 Hz, d = 1.2 Hz, J = 0.6 Hz); 4.50 (m, 2H); 4.89 (ddddd, 1H, J = 5.9 Hz, J = 5.9 Hz, J = 1.1 Hz, d = 1.1 Hz, J = 1.1 Hz); 4.92 (dddd, 1H, J = 8.5 Hz, J = 5.4 Hz, d = 1.1Hz, J = 1.1 Hz); 5.04 (ddd, 1H, J = 2.4 Hz, J = 2.4 Hz, J = 1.9 Hz); 5.08 (ddd, 1H, J = 2.1 Hz, d = 2.1 Hz, d = 2.1 Hz). 13C NMR (CDCI3, 75 Mz) 5 (ppm) : 39.6 (t); 51.8 (d); 76.9 (t); 78.7 (d); 82.6 (d); 84.5 (d); 107.9(t); 145.0 (s); 207.4 (s). MS ( 70 eV) : 166 (M +, 6); 148 (2); 137 (11); 124 (12); 109 (36); 95 (100). Cossy, J.; Ranaivosata, J.-L.; Bellosta, V. Tetrahedron Lett. 1994, 35, 8161-8162. Cossy, J.; Ranaivosata, J.-L.; Bellosta, V. unpublished results; see also : Renaud, P.; Vionnet, J.-P.; Vogel, P. Tetrahedron Lett. 1991, 32, 3491-3494; Bimwala, R. M.; Vogel, P. J. Org. Chem. 1992, 57, 2076-2083; Renaud, P.; Vionnet, J.-P. J. Org. Chem. 1993, 58, 5895-5896; Ferritto, R.; Vogel, P. Tetrahedron Asymmetry 1994, 5, 2077-2092. a) Vieira, E.; Vogel, P. Heh,. Chim. Acta 1983, 66, 1865-1871. b) Warm, A.; Vogel, P. Heh,. Chim. Acta 1987, 70, 690-700. c) Reymond, J. L.; Vogel, P. Tetrahedron Asymmetry 1990, 1, 729-736. d) Saf, R.; Faber, K.; Penn, G.; Griengl, H. Tetrahedron 1988, 44, 389-392. e) Ronan, B.; Kagan, H.B. Tetrahedron AsymmeO'y 1991, 2, 75-90. f) Corey, E. J.; Loh, J.-P. Tetrahedron Lett. 1993, 34, 3979-3982.
(Received in France 30 November 1994; accepted 27 January 1995)
0040-4039(95)0022 l-9
An Approach to the Skeleton of Eriolanin
Jsnine Cossy*, Jean-Luc Rannivosata, Vkonique Bellosta
Latxxatoire de Chimie Organique, As&C au CNRS. ESPCI, 10 rue Vauquelin, 7523 1 Paris Cedex 05 - France.
Abstract: The irradiation of 5-exo-bro/tro-6-endo-propargylo.ry-7-oxanorbornan-2-ones o/triethylamine leak directcv to the formation ojthe eriokmin skeleton.
in the presence
Whereas numerous methods exist for the synthesis of a-methylene-y-butyrolactones tised to cyclohexanes,l few direct methods are available for the preparation of a-methylene-y-butyrolactones of trans1,3-dihydroxycyclohexanes 2 which are present in the skeleton of eriolanin 1.3 Furthermore, the a-methylene-ybutyrolactone of a trans-1,3-diol structural unit is also present in the pseudoguaianolide helenalin 2.4
2
3
As a-methylene-y-butyrolactones are easily obtained by the oxidation of P-methylenehrans by the chromium trioxide-pyridine complex,5 syntheses of compounds of type 3 were envisaged from S-bromo-6-propargyloxyoxanorbornanones of type 7 vin intermediate 4
Oxanorbornenone 5, prepared according to Vogel’s procedure,6 was transformed into ketal 6 by treatment of 5 with propargylic silyl ether in the presence of trimethylsilyltriflate (TMSOTf) at 0°C in CH,Cl,. The transformation of 6 to ketal 8 was achieved with a yield of 77 % by treatment of 6 with 2.5 equivalents of n-butyllithium followed by the addition of 2.5 equivalents of methyliodide. Ketal 9 was synthesized with an 87 % yield by quenching the dianion of 6 by trimethylsilyl chloride. The treatment of these ketals 6, 8, 9 by bromine at -78’C in CH$& produced the corresponding bromocompounds 7, 10, 11 in yields higher than 90%. 2067
2068
o
o
o
.o laBeL, ~u%, /7CH3I O
o (cH3)asi(CH3)3Si~-'~O'~--'~
~ 0 , ~
o
o
The irradiation 7 of compounds 7, 10 and 11, at 254 nm, in acetonitrile, in the presence of 10 equivalents of triethylamine, for 75 rain, led to the formation of 12, 8 13 and 14 with yields of 65 %, 62 % and 72 %, respectively. Compounds 13 and 14 are l:l mixture of the corresponding (Z) and (E) isomers which could not be separated by chromatography. Startina material
Isolated prQduct
o
Yield
HO 65%
7
Ov,~
0
H 12
OBr 62%
v,-o 10
0 Br O ~ O E v ,,~Si(C H3)3 11
13 O ~
si(CH3)3 H
14
72%
2069
When compound 7 was irradiated for 60 rain, products 15 9 and 12 were formed with yields of 40 % and 37 %, respectively. No trace of compound 16 was observed. HO
o
07 ~ o B v , ~
hv o NEt3 10eq.
+o H H 15 1;' (40%) (37%) I hv NEt~
HO
o~--"~,.Ii ~ o
H 16 (0%)
(66%)
Furthermore, tile irradiation of 7 in an acetonitrile solution (5 x 10-2 M), in the presence of 10 equivalents of triethylamine, for 30 min, led exclusively to the formation of 15 with a 98 % yield for a rate of 63 % conversion. We should also point out that the irradiation of 15 in the presence of triethylamine for 60 min generated 12 with a 68 % yield. The photochemical transformation of substituted bromo-oxanorbornanones to the precursor of amethylene-'t-butyrolactone of
trans-l,3-dihydroxycyclohexanes involves an
electron-transfer to the bromide in
the first step, which produces the cleavage of the C-Br bond.l° A radical cyclization takes place to form the corresponding methylene-furan. The second step is the photoreduction of the carbonyl moiety of the oxanorbornanone which involves the formation of a ketyl anion-radical that provokes the cleavage of the C-O bond of the oxa bridge. This cleavage appears to be easier in compound 15 than in compound 7 as the former is probably more strained. It is likely that the radical-anion X is responsible for this ring opening as radicals a to an oxa bridge are not able to induce cleavage of the ethereal link. 11
O
O
O
NEt3 hv
-OnO "~ l HO
H
The use of this methodology to the syntheses of natural products is presently under investigation in our laboratory. Since both (-)- and (+)-7-oxanorbornanone 5 can be obtained in optically pure forms, 12 the synthesis of enantiomerically pure natural products could be envisaged.
2070
Acknowledgments
: One of us (J.-L. R.) thanks the Ministere de la Recherche et de la Technologic for a grant.
References and notes
1.
2. 3.
4. 5. 6. 7. 8.
9.
10. 11.
12.
a) Grieco, P. A. Synthesis 1975, 67-82. b) Hoffmann, H. M R.; Rabe, J. Angew. Chem. btt. Ed. Engl. 1985, 24, 94-110. c) Sarma, J. C.; Sharma, R. P. Heterocycles 1986, 24, 441-457. d) Dulcrre, J. P; Rodriguez, J.; Santelli, M.; Zahra, J. P. Tetrahedron Lett. 1987, 28, 2009-2012. a) Marino, J. P.; Farina, J. S. J. Org. Chem. 1976, 41, 3213-3215. b) Krafft, M. E. Tetrahedron Lett. 1986, 27, 771-774. Isolation of eriolanin : Kupchan, S. M.; Baxter, R. L.; Chiang, C K.; Gilmore, C. J.; Bryan, R.F.J. Chem. Soc. Chem. Comm. 1973, 842-843. Syntheses of 1 : a) Grieco, P. A.; Oguri, T.; Gilman, S. d. Ant. Chem. Soc. 1980, 102, 5886-5891. b) Roberts, M. R.; Schlessinger, R. H. J. Ant. Chem. Soc. 1981, 103, 724-725. Heathcock, C. H. " The Total Synthesis o f Natural Products ", Apsimon, J. Ed.; John Wiley and Sons, Inc., New York, Vol. 5, 1983, 369-373. a) Dauben, W. G.; Lorber, M.; Fullerton, D. S. J. Org. Chem. 1969, 34, 3587-3592. b) Ratcliffe, R.; Rodehorst, R. J. Org. Chem. 1970, 35, 4000-4002. a) Vieira, E.; Vogel, P. Hell,. Chim. Acta 1982, 65, 1700-1720. b) Black, K. A.; Vogel, P. Heh,. Chim. Acta 1984, 67, 1612-1615. c) Vogel, P.; Fattori, D.; Gasparini, F.; Le Drian, C. Synlett 1990, 173-185. Irradiations were performed in a quartz vessel, at 254 nm ("merry-go-round" irradiator with 8 Philips TUV 15 lamps), in CH3CN ( 10-2 M solutions ), in the presence of 10 equivalents of triethylamine. Spectral data of12 : IR (film) : 3440, 1700, 1660 cm-1. 1H NMR (CDCI3, 300 MHz) 5 (ppm) : 2.00-2.30 (m, OH); 2.45 (ddd, 1H, J = 16.5 Hz, J = 5.2 Hz, J = 1.5 Hz); 2.61 (dd, IH, J = 16.5 Hz, J = 2.9 Hz); 2.70 (dd, 1H, J = 17.3 Hz, J = 2.9 Hz); 2.85 (dd, 1H, J = 17.3 Hz, J = 3.3 Hz); 2.97 (m, 1H); 4.15 (ddd, 1H, d = 5.2 Hz, J = 2.9 Hz, J = 2.9 Hz); 4.27 (dddd, 1H, J = 13.6 Hz, J = 2.6 Hz, J = 2.6 Hz, J = 1.5 Hz); 4.44 (dddd, 1H, J = 13.6 Hz, J = 1.8 Hz, J = 1.8 Hz, J = 1.8 Hz); 4.48 (ddd, 1H, J = 6.6 Hz, J = 3.3 Hz, J = 2.9 Hz); 5.16 (m, 2H). 13C NMR (CDC13, 75 MHz) 5 (ppm) : 41.7 (t); 44.3 (t); 49.0 (d); 70.8 (t); 70.9 (d); 77.0 (d); 107.1 (t); 149.1 (s); 208.0 (s). MS (70 eV) : 168 (M +, 2); 150 (1); 111 (1); 95 (3); 82 (100). Spectral data of 15 : IR (film) : 1760, 1660 cm-1. 1H NMR (CDC13, 300 MHz) 6 (ppm) : 2.35 (ddd, 1H, d = 17.9 Hz, J = 0.9 Hz, J = 0.5 Hz); 2.46 (ddddd, 1H, J = 17.9 Hz, J = 5.9 Hz, J = 0.9 Hz, J = 0.9 Hz, J = 0.6 Hz); 3.64 (m, 1H); 4.37 (dddd, 1H, J = 5.4 Hz, J = 1.2 Hz, d = 1.2 Hz, J = 0.6 Hz); 4.50 (m, 2H); 4.89 (ddddd, 1H, J = 5.9 Hz, J = 5.9 Hz, J = 1.1 Hz, d = 1.1 Hz, J = 1.1 Hz); 4.92 (dddd, 1H, J = 8.5 Hz, J = 5.4 Hz, d = 1.1Hz, J = 1.1 Hz); 5.04 (ddd, 1H, J = 2.4 Hz, J = 2.4 Hz, J = 1.9 Hz); 5.08 (ddd, 1H, J = 2.1 Hz, d = 2.1 Hz, d = 2.1 Hz). 13C NMR (CDCI3, 75 Mz) 5 (ppm) : 39.6 (t); 51.8 (d); 76.9 (t); 78.7 (d); 82.6 (d); 84.5 (d); 107.9(t); 145.0 (s); 207.4 (s). MS ( 70 eV) : 166 (M +, 6); 148 (2); 137 (11); 124 (12); 109 (36); 95 (100). Cossy, J.; Ranaivosata, J.-L.; Bellosta, V. Tetrahedron Lett. 1994, 35, 8161-8162. Cossy, J.; Ranaivosata, J.-L.; Bellosta, V. unpublished results; see also : Renaud, P.; Vionnet, J.-P.; Vogel, P. Tetrahedron Lett. 1991, 32, 3491-3494; Bimwala, R. M.; Vogel, P. J. Org. Chem. 1992, 57, 2076-2083; Renaud, P.; Vionnet, J.-P. J. Org. Chem. 1993, 58, 5895-5896; Ferritto, R.; Vogel, P. Tetrahedron Asymmetry 1994, 5, 2077-2092. a) Vieira, E.; Vogel, P. Heh,. Chim. Acta 1983, 66, 1865-1871. b) Warm, A.; Vogel, P. Heh,. Chim. Acta 1987, 70, 690-700. c) Reymond, J. L.; Vogel, P. Tetrahedron Asymmetry 1990, 1, 729-736. d) Saf, R.; Faber, K.; Penn, G.; Griengl, H. Tetrahedron 1988, 44, 389-392. e) Ronan, B.; Kagan, H.B. Tetrahedron AsymmeO'y 1991, 2, 75-90. f) Corey, E. J.; Loh, J.-P. Tetrahedron Lett. 1993, 34, 3979-3982.
(Received in France 30 November 1994; accepted 27 January 1995)