Effective and highly stereoselective coupling with vinyldiazomethanes to form symmetrical trienes

Article abstract of DOI:10.1021/jo016135k

Diazo coupling reactions are capable of forming E,E,E-trienes from cinnamaldehydes in good yield. An efficient methodology is reported for the production of styryldiazomethanes that are subsequently used with catalysis for coupling and for cyclopropanatio

Full text of DOI:10.1021/jo016135k

602
J . Org. Chem. 2002, 67, 602-604
Sch em e 1
Effective a n d High ly Ster eoselective
Cou p lin g w ith Vin yld ia zom eth a n es To
F or m Sym m etr ica l Tr ien es
Michael P. Doyle* and Ming Yan
Department of Chemistry, University of Arizona,
Tucson, Arizona 85721
mdoyle@u.arizona.edu
Received September 21, 2001
Ta ble 1. Ca r ben e Cou p lin g Rea ction s of
Ar ylvin yld ia zom eth a n esa
yield of 2,b %
2t:2cc
Abstr a ct: Diazo coupling reactions are capable of forming
E,E,E-trienes from cinnamaldehydes in good yield. An
efficient methodology is reported for the production of styryl-
diazomethanes that are subsequently used with catalysis for
coupling and for cyclopropanation. A vast difference in
product selectivity is seen with styryldiazomethane gener-
ated from the corresponding hydrazone via manganese
dioxide oxidation and that formed in situ by treatment of
the tosylhydrazone sodium salt of cinnamaldehyde with
transition metal catalysts. This observation impacts under-
standing of the reaction mechanism for diazo decomposition.
Ar
C6H5
catalyst
Rh2(OAc)4
52
55
50
65
98:2
78:22
68:32
>98:2
Cu(MeCN)4PF6
Rh2(5S-MEPY)4
Rh2(OAc)4
p-NO2C6H4
a
Reactions performed at 0 °C in dry CH2Cl2 with 1.0 mol %
b
catalyst. Isolated yield of purified 2 following column chroma-
tography. c Determined by 1H NMR analysis.
trienes from cinnamaldehydes, the highly stereoselective
trapping of vinyl carbene intermediates with styrene, and
mechanistic considerations related to the method for
formation of vinyldiazo compounds.
The formation of alkenes from diazo compounds by
catalytic methods shows potential as a viable synthetic
transformation.1,2 However, the vast majority of examples
for what is commonly regarded as “carbene dimer forma-
tion” originate from diazocarbonyl compounds in inter-
molecular reactions.3,4 An early report by Shankar and
Shechter constitutes the only comprehensive examination
of catalyst and substrate substituent effects with aryl-
diazomethanes,5 and there has not been a report of
coupling from vinyldiazomethanes despite their obvious
synthetic potential for the synthesis of symmetrical
trienes (eq 1). Furthermore, vinyldiazoacetates exhibit
high diastereocontrol in cyclopropanation reactions,6 but
the stereoselectivity from vinyldiazomethanes is un-
known. Symmetrical trienes have been previously pre-
pared by Wittig reactions,7 palladium-catalyzed coupling
reactions,8 and by other methods.9 We now report a
highly efficient method for the synthesis of symmetrical
A general procedure was developed for the synthesis
of vinyldiazomethanes from the corresponding aldehydes
via hydrazone intermediates that are oxidized with
activated manganese dioxide (Scheme 1).
Treatment with representative catalysts in dichloro-
methane at 0 °C produced the results that are reported
in Table 1. There is an obvious catalyst dependence on
the product ratio, and use of Rh2(OAc)4 provides optimum
results with exceptionally high stereocontrol for the
E,E,E-isomer. Yields reported in the table are those from
the initial cinnamaldehyde reactant since intermediates
were not isolated before their use in subsequent steps.
Major byproducts were the cinnamaldehyde that was the
initial reactant, possibly re-formed during MnO2 oxida-
tion, and pyrazole 3, which was produced by rearrange-
ment of the initially formed vinyldiazo compound. At-
tempts to form branched trienes through the use of
R-methylcinnamaldehyde produced only pyrazole 4 after
treatment of the intermediate hydrazone with MnO2.
(1) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From Cyclopropanes
to Ylides; Wiley: New York, 1998.
(2) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911.
(3) Intermolecular coupling: (a) Grundman, C. J . Liebigs Ann.
Chem. 1938, 536, 2936. (b) Ernest, I.; Stanek, J . Collect. Czech. Chem.
Commun. 1959, 24, 530. (c) Oshima, T.; Hagar, T. Tetrahedron Lett.
1980, 21, 1251. (d) Palmisano, G.; Danieli, B.; Lesma, G.; Riva, R. J .
Org. Chem. 1985, 50, 3322.
(4) Intramolecular coupling: (a) Font, J .; Serratosa, F.; Vallis, J . J .
Chem. Soc., Chem. Commun. 1970, 721. (b) Kulkowit, S.; McKervey,
M. A. J . Chem. Soc., Chem. Commun. 1983, 1069. (c) Doyle, M. P.;
Hu, W.; Phillips, I.; Wee, A. G. H. Org. Lett. 2000, 2, 1777.
(5) Shankar, B. K. R.; Shechter, H. Tetrahedron Lett. 1982, 23, 2277.
(6) (a) Davies, H. M. L.; Church, L. A.; Clark, J . Tetrahedron Lett.
1989, 30, 5057. (b) Davies, H. M. L.; Bruzinski, P. R.; Fall, M. J .
Tetrahedron Lett. 1996, 37, 4133.
(7) (a) J ousselme, B.; Blanchard, P.; Fre`re, P.; Roncali, J . Tetra-
hedron Lett. 2000, 41, 5057. (b) Sonoda, Y.; Nakao, Y. J . Chem. Soc.,
Perkin Trans 1 1993, 1147. (c) Tsukahara, Y.; Kinoshita, H.; Inomata,
K.; Kotake, H. Bull. Chem. Soc. J pn. 1984, 57, 3013. (d) Misumi, S.;
Nakagawa, M. Bull. Chem. Soc. J pn. 1963, 36, 399.
(8) (a) Villiers, P.; Vicart, N.; Ramondene, Y.; Ple´, G. Eur. J . Org.
Chem. 2001, 561. (b) Kasahara, A.; Izumi, T.; Kirdou, N. Synthesis
1988, 704. (c) Mitsudo, T.; Fischetti, W.; Heck, R. F. J . Org. Chem.
1984, 49, 1640.
The use of 1 for catalytic cyclopropanation reactions
was also explored. Here styrene in 5-fold molar excess
(9) (a) Rao, Ch. S.; Singh, O. M.; Ila, H.; J unjappa, H. Synthesis
1992, 1075. (b) Santini, C. C.; Mathey, F. Can. J . Chem. 1983, 61, 21.
(c) Hashimoto, I.; Ryang, M.; Tsutsumi, S. J . Org. Chem. 1968, 33,
3955.
10.1021/jo016135k CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/22/2001

Notes
J . Org. Chem., Vol. 67, No. 2, 2002 603
Sch em e 2
Sch em e 3
Ta ble 3. Com p etitive Ca ta lytic Cyclop r op a n a tion of
Styr en e w ith 8a
Ta ble 2. Com p etitive Ca ta lytic Cyclop r op a n a tion of
yield of
Styr en e w ith (E)-Styr yld ia zom eth a n ea
temp, 5 + 2,b
% ee
catalyst
solvent
°C
%
5:2c 5c/5tc of 5cd
yield of
catalyst
5 + 2,b %
5:2c
5c/5tc
% ee of 5cd
Rh2(OAc)4
dioxane 35
Cu(MeCN)4PF6 dioxane 35
Rh2(OAc)4 CH2Cl2 reflux
Cu(MeCN)4PF6 CH2Cl2 reflux
Rh2(4S-IBAZ)4 CH2Cl2 reflux
Rh2(S-DOSP)4 CH2Cl2 reflux
14e
4f
38
0
2
4
96:4
90:10
98:2
4.0
0.8
6.0
Rh2(OAc)4
Cu(MeCN)4PF6
CuPF6/6
50
57
17
15
8:92
92:8
88:12
80:20
7
22
14
9
25
16
87:13
93:7
1.4
1.7
34
12
Rh2(S-DOSP)4
a
Reactions performed at 0 °C in dry CH2Cl2 with 1.0 mol %
catalyst and 5.0 molar equiv of styrene based on reactant cinnam-
a
Reactions were carried out with a ratio of styrene:8:BnEt3NCl:
b
catalyst ) 5:1:0.1:0.01. Isolated yield following column chroma-
b
aldehyde. Isolated yield following column chromatography. c De-
tography. c Determined by 1H NMR analysis. Obtained by GC
d
d
termined by 1H NMR analysis. Obtained by GC on a Chiraldex
on a Chiraldex B-PM column. e Pyrazole 3 was isolated in 32%
yield. f Pyrazole 3 was isolated in 83% yield.
B-PM column.
was used, and reactions were carried out in the same
manner as those for the coupling process (Scheme 2),
except that the diazo compound was added over 1 h
rather than all at once. Rhodium(II) acetate gave mainly
coupling product 2, but use of Cu(MeCN)4PF6 resulted
in the formation of mainly 5 whose cis/trans ratio was
an exceptionally high 22 (Table 2). Attempted use of
chiral catalysts, including CuPF6/bis(oxazoline) 6,10 led
to significant decreases in product yield (5 + 2) due to
competitive formation of 3, and the % ee of cis-5 was low.
The chiral dirhodium(II) carboxylate catalyst first re-
ported by Davies,11 Rh2(S-DOSP)4, was employed because
its reactivity is reported to be at least as great as
Rh2(OAc)4 and much greater than those for chiral di-
rhodium(II) carboxamidates.
is applied to reactions with cinnamaldehyde (Scheme 3),
the results obtained were quite different from those
obtained directly from styryldiazomethane generated by
MnO2 oxidation (Table 3). The reported advantages of
this methodology included minimization of carbene dimer
formation, and this is evident in the comparison of results
reported in Tables 2 and 3. Indeed, with Rh2(OAc)4 as
the catalyst, 2 is virtually the exclusive product from 1
(5:2 ) 8:92) but not from 8 (5:2 ) 98:2). However, the
production of 3 is much more dominant in reactions with
8, and this could be due to the expected coordination of
rhodium(II) with the amide nitrogen of 8 that becomes
the terminal nitrogen of styryldiazomethane (Scheme 4).
In this way rhodium(II) can be understood to activate
the diazo compound to form 3 at a much faster rate than
would occur if the diazo compound was generated prior
to interaction with Rh2(OAc)4. The question of which site
of diazomethane and its derivatives represents the more
likely site of attack by Lewis acids is longstanding,1 and
the comparison of results from this study provides one
measure of its operational characteristics.
Exp er im en ta l Section
High cis diastereoselectivity for the formation of cyclo-
propane products using phenyldiazomethane has been
reported, but with styrene and Rh2(OAc)4 the Z/E ratio
was only 3.3.12 Higher Z-selectivities were reported for
the cyclopropane product from stoichiometric reactions
with (CO)5WdCHPh and related organometallic re-
agents13 but none as high as that found with (E)-
styryldiazomethane catalyzed by Cu(MeCN)4PF6.
Aggarwal has recently reported an alternative meth-
odology for catalytic reactions with aryldiazomethanes
via direct treatment of the sodium salt of the tosyl-
hydrazone with rhodium(II) acetate.14 When the method
Gen er a l Meth od s. 1H and 13C NMR spectra were obtained
as solutions in CDCl3, and chemical shifts are reported in parts
per million (ppm, δ) downfield from the internal standard, Me4Si
(TMS). Dichloromethane was distilled from calcium hydride prior
to use. Manganese dioxide was commercially available and was
oven dried before use. Dirhodium(II) acetate and copper(I)
hexafluorophosphate15 were crystallized prior to use. Bis(oxazo-
18
line) ligand 6,16 Rh2(5S-MEPY)4,17 and Rh2(4S-IBAZ)4 were
prepared by standard methods.
Syn th esis of (E,E,E)-1,6-Dia r yl-1,3,5-h exa tr ien es. The
general procedure began with the addition of anhydrous hydra-
(14) Aggarwal, V.; de Vicente, J .; Bonnert, R. V. Org. Lett. 2001, 3,
2785.
(10) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J .
Am. Chem. Soc. 1991, 113, 726.
(11) Davies, H. M. L.; Bruzinski, P.; Hutcheson, D. K.; Fall, M. J .
J . Am. Chem. Soc. 1996, 118, 6897.
(12) Doyle, M. P.; Griffin, J . H.; Bagheri, V.; Durow, R. L. Organo-
metetallics 1984, 3, 53.
(13) Doyle, M. P. Chem. Rev. 1986, 86, 919.
(15) Kubas, G. J . Inorg. Synth. 1979, 19, 90.
(16) Evans, D. A.; Peterson, G. S.; J ohnson, J . S.; Barnes, D. M.;
Campos, K. R.; Woerpel, K. A. J . Org. Chem. 1998, 63, 4541.
(17) Doyle, M. P.; Winchester, W. R.; Hoorn, J . A. A.; Lynch, V.;
Simonsen, S. H.; Ghosh, R. J . Am. Chem. Soc. 1993, 115, 9968.
(18) Doyle, M. P.; Zhou, Q.-L.; Simonsen, S. H.; Lynch, V. Synlett
1996, 697.

604 J . Org. Chem., Vol. 67, No. 2, 2002
Notes
Sch em e 4
zine (0.3 mL, 10 mmol, 5 equiv) to a solution of cinnamaldehyde
(0.264 g, 2.00 mmol) and triethylamine (1.4 mL, 10 mmol, 5
equiv) in 10 mL of anhydrous ethanol at room temperature. After
stirring of the mixture for for 1 h, solvent and excess reagents
were removed at 0 °C under reduced pressure. The resulting
colorless oil was dissolved in 10 mL of cold anhydrous CH2Cl2
that was then added to an ice-bath-cooled mixture of MnO2 (1.68
g, 20 mmol, 10 equiv) and Na2CO3 (2.12 g, 20 mmol, 10 equiv)
in 25 mL of CH2Cl2. The resulting mixture was stirred for 2 h
at 0 °C. Excess MnO2 was filtered through a layer of Celite to
provide a red solution of the styryldiazomethane that was used
immediately to minize formation of pyrazole 3. The red solution
was added in one portion to a solution of catalyst (0.020 mmol,
0.010 equiv) in 5 mL of ice-bath-cooled CH2Cl2, and stirring was
continued at that temperature for an additional 30 min. After
removal of the solvent under reduced pressure, the residue was
purified by column chromatography (hexanes:ethyl acetate )
100:1) to give the product triene. Products were identified by
comparison to the spectral properties of the known compounds.7-9
The (E,Z,E)-isomer has also been reported.7b Pyrazoles were
identified by their characteristic NMR, IR, and mass spectral
data.
Cyclop r op a n a tion of Styr en e. The same procedure that
was used for coupling was employed to prepare styryldiazo-
methane for cyclopropanation reactions. To a solution of catalyst
(0.020 mmol, 1.0 mol %) and styrene (10 mmol, 5.0 equiv) in 5
mL of anhydrous dichloromethane at 0 °C was added the cooled
solution of styryldiazomethane in dichloromethane by syringe
pump over 1 h. The solution was then stirred at 0 °C for an
additional 1 h, and the solvent was removed under vacuum. The
residue was purified by column chromatography (hexane:EtOAc
) 100:1) to give 1-styryl-2-phenylcyclopropane as a colorless oil.
This compound (both cis and trans isomers) was compared
spectrally with the authentic compound.19
Tosylh yd r a zon e Sod iu m Sa lt P r oced u r e.14 The tosyl-
hydrazone of cinnamaldehyde was converted to its sodium salt
using sodium in methanol which was removed under vacuum
to reveal a yellow solid. This solid (323 mg, 1.00 mmol),
benzyltriethylammonium chloride (23 mg, 0.10 mmol), Rh2(OAc)4
(4.42 mg, 0.010 mmol), and styrene (0.57 mL, 5.0 mmol) were
mixed with 5.0 mL of CH2Cl2, and the resulting mixture was
refluxed for 6 h. After addition of water (7 mL), the resulting
mixture was twice extracted with 10-mL portions of CH2Cl2. The
combined organic layer was dried over anhydrous MgSO4, and
the solvent was removed under reduced pressure. Elution in
column chromatography with hexane:EtOAc ) 100:1 provided
the cyclopropane product as a colorless oil, and continued elution
with hexanes:EtOAc ) 2:1 gave 3-phenylpyrazole20 as a brown
oil.
Ack n ow led gm en t. We are grateful to the National
Science Foundation and to the National Institutes of
Health (Grant GM 46503) for their support of this
research. We thank Huw H. M. L. Davies for a sample
of Rh2(S-DOSP)4.
J O016135K
(19) Horikawa, Y.; Nomura, T.; Watanabe, M.; Fujiwara, T.; Takeda,
T. J . Org. Chem. 1997, 62, 3678.
(20) Brewbaker, J . L.; Hart, H. J . Am. Chem. Soc. 1969, 91, 711.