- Email: [email protected]
2-(chloromethyl)-3-tosylpropene as useful reagent for the general synthesis of functionalized 2-substituted 1,3-dienes. Application to the synthesis of (±)-ipsenol
00404039193 $6.00 + .OO k,8RCSSLtd
Tetddron Letters., Vol. 34. No. 23. pp.3781-3784.1993 PriitedinGreatBritain
2-(Chloromethyl)-34osylpropene General Synthesis
as Useful Reagent for the
of Functionalized
Application
2-Substituted
1,3=Dienes.
to the Synthesis of (A)-Ipsenol
Carmen
NSjerd
and Jost?
Miguel Sansano
Departirmcntode Qufmica Orghica, Univenidadde Aiicautc.Apdo. 99.03080 Alicante..Spain
Abrlracl: The reaction of the monolithium derivative of 2-(ckloromethyl)-3-tosylpropene (2) with bmwmethy1trim&y1r dfords the p-8ilyl sldfone 7. which aftex mwhphik lutbstitutiocl followed by fluoride induced @.hnbtion of to8yltrimethylsilrme gives 2-sulnltituted omjllgated dialed L whal cxnnpod 7 reacts first with zinc in the presence of iaovalemldehyde and that with ktrabutylamttonitmt fluoride’raccmic ipsend (10). an qpg&mphaomgsofIhebaskbc&Ipapt3nnxyiuusLaoia.L~
2-Substituted 13dienes of the type 1 are interesting compounds because their structure is present in natuml products such as terpenoids (e.g. myrcene derivatives) or pheromones (e.g. ipsenol) and are also useful in DielsAlder reaction&~.
m-i (e.g. synthesis of rings A and B of the taxane skeletons). However, there are not general
procedures for the syr@eais of these type of diene&? On the other hand, 2-(chloromethyl)-3-tosylpropene can act as a multicoupling reagent: (a) as a.l+dipole reaction+
of its phenylsulfonyl
methylenecyclop
(2)s
of the type 3 in palladium catalyzed cyclopenuumefation
homo1ogousSb. (b) as an allylic chlorinated dianion 4 in the synthesis of
and furans derivatives7. and as cationic or anionic synthon 5 in the preparation of
functionalized ally1 sulfoness. We apply here its reactivity first as monolithium derivative 6s and second as synthon 5 to the synthesis of Zsubstituted
l,%dienes through a straightforward three-step synthesis based on
Kocienski’s strategy9 for the synthesis of alkenes and dienes by means of fluoride induced g-elimination of f3silyl sulfonesl0.
WA..TyJg
Ts Li .....Cl 1
2
3 4
3781
Li
5,
l
. . . ..Cl
=+or6
3782
2-(Cbloromethyl)-3-tosylp1openc(2)5 was transformed directly into the g-silyl sulfone 7 (mp 57-SW. from hexane/ether) by reaction of its monolithium derivative 6 with bromomethylttimethylsihtne
11. This g-
silylated sulfone 7 reacted with heteronucleophiles or phenylmagnesium bromide, to give compounds 8, which were transformed into dienes 1 by treatment with tetrabutyhtmmonium fluoride (TBAFJe.12 in THF at 0°C (Scheme 1 and Table 1).
T&c,
i-iii )
Ts
x
iv
)
Ax
tVlt3&3 P 2 Scheme 1.
1
8 Reagents and corm
i. n-B&i. DMPU, -78oC; ii, Me$iCH$3r;
iii, Nu; iv, TBAF, THF, 0°C.
The lithiation of 2+hlorcmethyl)-3-toaylptopene in the presence of A!Wdimethylpropyleneutea
(2) was carried out with n-hutyl-lithium in THF at -78°C
(DMPU. one equivalent) during 10 min to give intermediate 6,
which was allowed to react with bromomethyltrimethyisilane overnight allowing the mmpanmm toriIIeto2PC. to afford compoumi 7 in 62% yield (after column chtomatogmphy). The nucieophilic displacement of the chorine atom in compound 7 by representative heteronucleophiles such as morpholine. sodium axide, benxoic acidcesium
fluofi~3.
and sodium
phenylsulfide of phenyhnagnesium bromide under different reaction conditions
(see Table 1) yielded the corresponding compounds (k-e. The transformation
of compound 2 into pure
compaundslwascaniedoutwith~~~7inthecaseofdiemsl8_d,paificatianofthecareaponding intesmediates &-d being only necmmry (see Table 1). However, when phenylmagnmium bromide was used as nucleophile, pure compound 7 was used in order to avoid the presence of DMFU Dienes 1 were isolated as pure compuunds (> 95%. OlX) after acidic exttactive work-up and were distilled under reduced pmssure except the axide daivative lb due to its thermal potential instability. They ate in general very unstable compounds and decomposed on standing in hours or days. This synthetic methodology was then applied to the preparation of ipsenol (lo)?
sex pheromone of the
bark beetle Ips paruconJusus Lamer. by reacting the g-silyl sulfone 7 with isovalemfdehyde under Barbier conditions. The reaction of pure compound 7 with isovaieraldehyde in the presence of zinc, activated by 15 dibromcethane and trimethylchlorosilanes, alti
in anhydrous THF for 3d under reflux afforded the corresponding
9 (97% yield), which was treated with TBAF in THF at (PC during 30 min giving racemic ipsenol(10)
(869E1 yield after kugeltohr distillation, bp M”c117 Tot-r).
3783
Table 1. Preparation of 2-Substituted 1,3-Dienes 1.
@Silyl Sulfon* No.
8a
Nu
Solvent
(equiv.)
Cr. time)
Morpholine
CH3CN
(4) 8b
8C
8d
8e
DieJK9
(=K
Yield (%)b
66
StNcaUe
\ A-
No.
N
\Pla
Yield (96)~ Bp (“C/Torr)d
80
lW18
26)
NaN3
Etow)42oe
(10)
(9ooC. 2d)
PhCQHh
DMF
(I.9
(SCPC. lsd)
NaSPh
THF
(2)
(66°C. Id)
phwm
THFi
(2)
(u)oC. 26)
83i
Ph
le
97
115/181r
IAll pmdwtsarcpurc (TLCorGLC) and gave aatidadoryn~ data (JR,3OOh4Hz ~HNMTt,75ItJHz~3CNMRmdM3). ‘maahcmpound 2.aftacdunm duanatooy (ailicagd,hcxam9*). CM aa pure oxnpaau9 8. afta dintibtiot~ dbgdmhr. ~In4/1volmneratio.~Isdatedcndcprodud(>95%pmbyG~.cR~O~~(henandethcr: 5/l). b Inthepmaa~~of sodiumiodidc (3 apiv.) awlcesium flnmidc (1.5 apiv.)lf. iAnhydrous. Baaedon plrccxmpmd7. ~IA.W 71-75W5Tom
In conclusion, this methodology allows the general synthesis of functionalized 2-substituted conjugated dienes and also of mcemic ipsenol, which are generakd under mild reaction coalition@. References and Notes
1.
Fringuelli. F.; Tat&hi. A. In Dienes in fhe Diels-Alder Reaction; John Wiley & Sons: New York, 1990 pp.
3784
n-79.
2.
For syntheses of Zsubstituted dienes of the type 1 see, for instance: (a) Bailey, W. J.; Carpenter, W. G.; Hermes, M. E. .Z. Org. Chem. 1962.27,
19751978. (b) Borg-V&e. F.; Dawans. F. Synthesis 1979.
817-818. (c) Kajira, Y.; Ishikawa, K.; Yasuda, H.; Nakamura, A. Bull. Chem. Sot. Jp.
1980,53,3CBS-
3036. (d) Sakurai. H.; Hosomi. A.; Saito, M.; Sasaki. K.; Iguchi, H.; Sasaki. J.; An&i. Y. Tetrahedron 1983. 39.883894.
(e) Ueno. Y.; Sano, H.; Aoki. S.; Okawara, M. Tetruhedron L&t. 1981.22,
2675-
2678 (f) Kfusener. P. A. A.; Hommes, H. H.; Verkruijsse. H. D.; Brandsma, L. J. Chem. Sot., Chem.
Commun. 1985.1677-1678.
(g) Arenz. T.; Frauenrath. H. Angew. Gem., Znt. Ed. Engl. 1990.29. !?32-
933. (h) Yadav, J. S.; Ravishankar, R. Tetruhedron Lctt. 1991.32, Gradoz, N. Tetrahedron Lctt. 1992.33,6147-6150.
2629-2632. (i) Bioch. R.; Chaptai-
(j) Kozikowski. A. P.; Ognyanov. V. I.; Chen. C.;
Kurian. P.; Crews, F. T. Tetrahedron Lett. 1993.34. 219-222. 3.
(a) Brown, P. A.; Jenkins, P. R. J. Chem. Sot., Perkin Trans. 1 1986. 1303-1309. (b) Bonnert, R. V.; Jenkins, P. R. J. Chem. Sot., Perkin Trans.1 1989.
Tetruhedron L&t. 1988,29,
413418.
(c) Shea, K. J.; Haffner, C. D.
1367-1370. (d) Jackson, R. W.; Highby. R. G.; Gilman, J. W.; Shea, K. J.
Tetrahedron 1992,48,7013-7032. K. N. J. Org. Chem. 1991.56,
(e) Sakan, K.; Smith, D. A.; Babirad, S. A.; Fronczek, F. R.; Houk, 23112317.
4.
For syntheses of ipsenol see: Trost. B. M.; Rodriguez. M. S. Tetrahedron L&t. 1992, 33.4675-4678 and
5.
Najera, C.; Sansano, J. M. Tetrahedron 1992,48,5179-5190.
6.
(a) Breuilles,
references cited therein. P.; Uguen, D. TetrahedronLett. 1988, 29, 201-204. (b) Breuilles,
P.; Uguen, D.
Tetrahedron Z&t. 1987.28,6053-6056. 7.
NSrjera.C.; Sansano, J. M. Tetrahedron L&t. 1992,33,6543-6546.
8.
The conqonding
9.
(a) Kocienski. P. J. Tetrahedron Lett. 1979. 2649-2650. (b) Kocienski. P. J. J. Org. Gem.
monolithium intermediate of the phenylsulfonyl derivative has been described% 1980,45,
2037-2039. 10.
B-Stannyl suffones gave the same elimination reaction: (a) Ochiai. M.; Tada, S.; Sumi, K.; Fuji@ E Tetrahedron L&t. 1982, 23,2205-2208. (b) Pearlmann. B. A.; Putt, S. R.; Fleming, J. A. J. Org. Chem. 1985.50.
3622-3624.
11. The alkylation of a-litbiated suffones with iodomethyltrimethylsilane 9 or iodomethyhrimethylstannan~c the most simple way for @ilyl or @annyl
is
suffones, respectively.
12. For recent applications of this elimination reaction in synthesis of methylenecycloptopanes derivatives see: (a) Hsiao, C.; Hannick, S. M. Tetrahedron Lctt. 1990,3Z. 66096612. (b) Baldwin. J. E.; Adlington. R M.; Bebbington..
D.; Russell, A. T. J. Chem. Sot.,
Chem. Commun.
Ramaswamy. S.; Prasad, K; Repic, 0. J. Org. Chem. 1992.57,
1992,
1249-1251.
6344-6347. (d) Achmatowin.
(c) B.;
Kabat, M. M.; Kmjewski, J.; Wicha, J. Tetrahedron 1992.48, 10201-10210. 13. Sate. T.; Otera, J.; Nozaki. H. J. Org. Chem. 1992,57,2166-2169. Sodium iodide was also added to generate in situ the iodine derivative 8f (X=1). 14. Nunomoto, S.; Kawakami, Y.; Yamashita, Y. Bull. Chem. Sot. Jpn. 1981,54.2831-2832. 15. We are grateful to DGICYT of the Spanish Ministerio de Educaci6n y Ciencia (MEC) (Projects nos. PB880287 and PB91-0751) for financial support. J. M. S. thanks also to MEC for a ptedoctoral fellowship.
(Received in UK 14 April 1993)
Tetddron Letters., Vol. 34. No. 23. pp.3781-3784.1993 PriitedinGreatBritain
2-(Chloromethyl)-34osylpropene General Synthesis
as Useful Reagent for the
of Functionalized
Application
2-Substituted
1,3=Dienes.
to the Synthesis of (A)-Ipsenol
Carmen
NSjerd
and Jost?
Miguel Sansano
Departirmcntode Qufmica Orghica, Univenidadde Aiicautc.Apdo. 99.03080 Alicante..Spain
Abrlracl: The reaction of the monolithium derivative of 2-(ckloromethyl)-3-tosylpropene (2) with bmwmethy1trim&y1r dfords the p-8ilyl sldfone 7. which aftex mwhphik lutbstitutiocl followed by fluoride induced @.hnbtion of to8yltrimethylsilrme gives 2-sulnltituted omjllgated dialed L whal cxnnpod 7 reacts first with zinc in the presence of iaovalemldehyde and that with ktrabutylamttonitmt fluoride’raccmic ipsend (10). an qpg&mphaomgsofIhebaskbc&Ipapt3nnxyiuusLaoia.L~
2-Substituted 13dienes of the type 1 are interesting compounds because their structure is present in natuml products such as terpenoids (e.g. myrcene derivatives) or pheromones (e.g. ipsenol) and are also useful in DielsAlder reaction&~.
m-i (e.g. synthesis of rings A and B of the taxane skeletons). However, there are not general
procedures for the syr@eais of these type of diene&? On the other hand, 2-(chloromethyl)-3-tosylpropene can act as a multicoupling reagent: (a) as a.l+dipole reaction+
of its phenylsulfonyl
methylenecyclop
(2)s
of the type 3 in palladium catalyzed cyclopenuumefation
homo1ogousSb. (b) as an allylic chlorinated dianion 4 in the synthesis of
and furans derivatives7. and as cationic or anionic synthon 5 in the preparation of
functionalized ally1 sulfoness. We apply here its reactivity first as monolithium derivative 6s and second as synthon 5 to the synthesis of Zsubstituted
l,%dienes through a straightforward three-step synthesis based on
Kocienski’s strategy9 for the synthesis of alkenes and dienes by means of fluoride induced g-elimination of f3silyl sulfonesl0.
WA..TyJg
Ts Li .....Cl 1
2
3 4
3781
Li
5,
l
. . . ..Cl
=+or6
3782
2-(Cbloromethyl)-3-tosylp1openc(2)5 was transformed directly into the g-silyl sulfone 7 (mp 57-SW. from hexane/ether) by reaction of its monolithium derivative 6 with bromomethylttimethylsihtne
11. This g-
silylated sulfone 7 reacted with heteronucleophiles or phenylmagnesium bromide, to give compounds 8, which were transformed into dienes 1 by treatment with tetrabutyhtmmonium fluoride (TBAFJe.12 in THF at 0°C (Scheme 1 and Table 1).
T&c,
i-iii )
Ts
x
iv
)
Ax
tVlt3&3 P 2 Scheme 1.
1
8 Reagents and corm
i. n-B&i. DMPU, -78oC; ii, Me$iCH$3r;
iii, Nu; iv, TBAF, THF, 0°C.
The lithiation of 2+hlorcmethyl)-3-toaylptopene in the presence of A!Wdimethylpropyleneutea
(2) was carried out with n-hutyl-lithium in THF at -78°C
(DMPU. one equivalent) during 10 min to give intermediate 6,
which was allowed to react with bromomethyltrimethyisilane overnight allowing the mmpanmm toriIIeto2PC. to afford compoumi 7 in 62% yield (after column chtomatogmphy). The nucieophilic displacement of the chorine atom in compound 7 by representative heteronucleophiles such as morpholine. sodium axide, benxoic acidcesium
fluofi~3.
and sodium
phenylsulfide of phenyhnagnesium bromide under different reaction conditions
(see Table 1) yielded the corresponding compounds (k-e. The transformation
of compound 2 into pure
compaundslwascaniedoutwith~~~7inthecaseofdiemsl8_d,paificatianofthecareaponding intesmediates &-d being only necmmry (see Table 1). However, when phenylmagnmium bromide was used as nucleophile, pure compound 7 was used in order to avoid the presence of DMFU Dienes 1 were isolated as pure compuunds (> 95%. OlX) after acidic exttactive work-up and were distilled under reduced pmssure except the axide daivative lb due to its thermal potential instability. They ate in general very unstable compounds and decomposed on standing in hours or days. This synthetic methodology was then applied to the preparation of ipsenol (lo)?
sex pheromone of the
bark beetle Ips paruconJusus Lamer. by reacting the g-silyl sulfone 7 with isovalemfdehyde under Barbier conditions. The reaction of pure compound 7 with isovaieraldehyde in the presence of zinc, activated by 15 dibromcethane and trimethylchlorosilanes, alti
in anhydrous THF for 3d under reflux afforded the corresponding
9 (97% yield), which was treated with TBAF in THF at (PC during 30 min giving racemic ipsenol(10)
(869E1 yield after kugeltohr distillation, bp M”c117 Tot-r).
3783
Table 1. Preparation of 2-Substituted 1,3-Dienes 1.
@Silyl Sulfon* No.
8a
Nu
Solvent
(equiv.)
Cr. time)
Morpholine
CH3CN
(4) 8b
8C
8d
8e
DieJK9
(=K
Yield (%)b
66
StNcaUe
\ A-
No.
N
\Pla
Yield (96)~ Bp (“C/Torr)d
80
lW18
26)
NaN3
Etow)42oe
(10)
(9ooC. 2d)
PhCQHh
DMF
(I.9
(SCPC. lsd)
NaSPh
THF
(2)
(66°C. Id)
phwm
THFi
(2)
(u)oC. 26)
83i
Ph
le
97
115/181r
IAll pmdwtsarcpurc (TLCorGLC) and gave aatidadoryn~ data (JR,3OOh4Hz ~HNMTt,75ItJHz~3CNMRmdM3). ‘maahcmpound 2.aftacdunm duanatooy (ailicagd,hcxam9*). CM aa pure oxnpaau9 8. afta dintibtiot~ dbgdmhr. ~In4/1volmneratio.~Isdatedcndcprodud(>95%pmbyG~.cR~O~~(henandethcr: 5/l). b Inthepmaa~~of sodiumiodidc (3 apiv.) awlcesium flnmidc (1.5 apiv.)lf. iAnhydrous. Baaedon plrccxmpmd7. ~IA.W 71-75W5Tom
In conclusion, this methodology allows the general synthesis of functionalized 2-substituted conjugated dienes and also of mcemic ipsenol, which are generakd under mild reaction coalition@. References and Notes
1.
Fringuelli. F.; Tat&hi. A. In Dienes in fhe Diels-Alder Reaction; John Wiley & Sons: New York, 1990 pp.
3784
n-79.
2.
For syntheses of Zsubstituted dienes of the type 1 see, for instance: (a) Bailey, W. J.; Carpenter, W. G.; Hermes, M. E. .Z. Org. Chem. 1962.27,
19751978. (b) Borg-V&e. F.; Dawans. F. Synthesis 1979.
817-818. (c) Kajira, Y.; Ishikawa, K.; Yasuda, H.; Nakamura, A. Bull. Chem. Sot. Jp.
1980,53,3CBS-
3036. (d) Sakurai. H.; Hosomi. A.; Saito, M.; Sasaki. K.; Iguchi, H.; Sasaki. J.; An&i. Y. Tetrahedron 1983. 39.883894.
(e) Ueno. Y.; Sano, H.; Aoki. S.; Okawara, M. Tetruhedron L&t. 1981.22,
2675-
2678 (f) Kfusener. P. A. A.; Hommes, H. H.; Verkruijsse. H. D.; Brandsma, L. J. Chem. Sot., Chem.
Commun. 1985.1677-1678.
(g) Arenz. T.; Frauenrath. H. Angew. Gem., Znt. Ed. Engl. 1990.29. !?32-
933. (h) Yadav, J. S.; Ravishankar, R. Tetruhedron Lctt. 1991.32, Gradoz, N. Tetrahedron Lctt. 1992.33,6147-6150.
2629-2632. (i) Bioch. R.; Chaptai-
(j) Kozikowski. A. P.; Ognyanov. V. I.; Chen. C.;
Kurian. P.; Crews, F. T. Tetrahedron Lett. 1993.34. 219-222. 3.
(a) Brown, P. A.; Jenkins, P. R. J. Chem. Sot., Perkin Trans. 1 1986. 1303-1309. (b) Bonnert, R. V.; Jenkins, P. R. J. Chem. Sot., Perkin Trans.1 1989.
Tetruhedron L&t. 1988,29,
413418.
(c) Shea, K. J.; Haffner, C. D.
1367-1370. (d) Jackson, R. W.; Highby. R. G.; Gilman, J. W.; Shea, K. J.
Tetrahedron 1992,48,7013-7032. K. N. J. Org. Chem. 1991.56,
(e) Sakan, K.; Smith, D. A.; Babirad, S. A.; Fronczek, F. R.; Houk, 23112317.
4.
For syntheses of ipsenol see: Trost. B. M.; Rodriguez. M. S. Tetrahedron L&t. 1992, 33.4675-4678 and
5.
Najera, C.; Sansano, J. M. Tetrahedron 1992,48,5179-5190.
6.
(a) Breuilles,
references cited therein. P.; Uguen, D. TetrahedronLett. 1988, 29, 201-204. (b) Breuilles,
P.; Uguen, D.
Tetrahedron Z&t. 1987.28,6053-6056. 7.
NSrjera.C.; Sansano, J. M. Tetrahedron L&t. 1992,33,6543-6546.
8.
The conqonding
9.
(a) Kocienski. P. J. Tetrahedron Lett. 1979. 2649-2650. (b) Kocienski. P. J. J. Org. Gem.
monolithium intermediate of the phenylsulfonyl derivative has been described% 1980,45,
2037-2039. 10.
B-Stannyl suffones gave the same elimination reaction: (a) Ochiai. M.; Tada, S.; Sumi, K.; Fuji@ E Tetrahedron L&t. 1982, 23,2205-2208. (b) Pearlmann. B. A.; Putt, S. R.; Fleming, J. A. J. Org. Chem. 1985.50.
3622-3624.
11. The alkylation of a-litbiated suffones with iodomethyltrimethylsilane 9 or iodomethyhrimethylstannan~c the most simple way for @ilyl or @annyl
is
suffones, respectively.
12. For recent applications of this elimination reaction in synthesis of methylenecycloptopanes derivatives see: (a) Hsiao, C.; Hannick, S. M. Tetrahedron Lctt. 1990,3Z. 66096612. (b) Baldwin. J. E.; Adlington. R M.; Bebbington..
D.; Russell, A. T. J. Chem. Sot.,
Chem. Commun.
Ramaswamy. S.; Prasad, K; Repic, 0. J. Org. Chem. 1992.57,
1992,
1249-1251.
6344-6347. (d) Achmatowin.
(c) B.;
Kabat, M. M.; Kmjewski, J.; Wicha, J. Tetrahedron 1992.48, 10201-10210. 13. Sate. T.; Otera, J.; Nozaki. H. J. Org. Chem. 1992,57,2166-2169. Sodium iodide was also added to generate in situ the iodine derivative 8f (X=1). 14. Nunomoto, S.; Kawakami, Y.; Yamashita, Y. Bull. Chem. Sot. Jpn. 1981,54.2831-2832. 15. We are grateful to DGICYT of the Spanish Ministerio de Educaci6n y Ciencia (MEC) (Projects nos. PB880287 and PB91-0751) for financial support. J. M. S. thanks also to MEC for a ptedoctoral fellowship.
(Received in UK 14 April 1993)