Polyfunctionalized Cage Compounds by Pericyclic Domino Processes of 4,5-Dicyanopyridazine with Dienes: Applications and Limits

Article abstract of DOI:10.1021/jo991191v

The title compound 1 was found to behave as an attractive masked bis-diene to give 4-oxatricyclo-[4.3.1.0^3,7]dec-8-ene, 5-aza- and 5-silatricyclo[5.3.1.0^3,8]undec-9-ene, tricyclo[3.2.1.0^2,7]oct-3-ene, and tricyclo[5.3.1.0^3,8]undec-9-ene derivatives through purely pericyclic, three-step homodomino processes with diverse bis-dienophiles; whereas the reaction with myrcene (21) was characterized by a complete sitoselectivity affording compound 25, treatment of 1 with (R)-(-)-β-citronellene (26a) gave a 3:1 mixture of the homochiral diastereomers 30a and 31a. Some limits of this methodology, mainly arising from competitive side reactions upon the key cyclohexa-1,3-diene intermediates, are emphasized. The structures of the new compounds were established on the basis of spectral data.

Full text of DOI:10.1021/jo991191v

360
J . Org. Chem. 2000, 65, 360-364
P olyfu n ction a lized Ca ge Com p ou n d s by P er icyclic Dom in o
P r ocesses of 4,5-Dicya n op yr id a zin e w ith Dien es: Ap p lica tion s a n d
Lim its
Donatella Giomi,* Rodolfo Nesi,* Stefania Turchi, and Elena Mura
Dipartimento di Chimica Organica ‘Ugo Schiff’ - Centro di Studio del CNR sulla chimica e la
struttura dei composti eterociclici e loro applicazioni, Universita` di Firenze, Via Gino Capponi 9,
I-50121 Firenze, Italy
Received J uly 27, 1999
The title compound 1 was found to behave as an attractive masked bis-diene to give 4-oxatricyclo-
[4.3.1.03,7]dec-8-ene, 5-aza- and 5-silatricyclo[5.3.1.03,8]undec-9-ene, tricyclo[3.2.1.02,7]oct-3-ene, and
tricyclo[5.3.1.03,8]undec-9-ene derivatives through purely pericyclic, three-step homodomino processes
with diverse bis-dienophiles; whereas the reaction with myrcene (21) was characterized by a
complete sitoselectivity affording compound 25, treatment of 1 with (R)-(-)-â-citronellene (26a )
gave a 3:1 mixture of the homochiral diastereomers 30a and 31a . Some limits of this methodology,
mainly arising from competitive side reactions upon the key cyclohexa-1,3-diene intermediates,
are emphasized. The structures of the new compounds were established on the basis of spectral
data.
Sch em e 1
Although 1,2-diazines have been scarcely employed as
heterodienes in inverse-electron-demand [4 + 2] cycload-
ditions,1 probably due to some discouraging results,2 a
systematic investigation undertaken by our group clearly
demonstrated that 4,5-dicyanopyridazine (DCP) (1) ex-
hibits a remarkable reactivity toward several 2π electron
counterparts.3 Particularly, after DCP was shown to react
under relatively mild conditions with 2,3-dimethylbuta-
1,3-diene to give a tricyclo[3.2.1.02,7]oct-3-ene skeleton
through a pericyclic domino process,4 it has been more
recently exploited in similar reactions with diverse bis-
dienophiles for a direct access to carbo- and hetero-cage
derivatives.5 In this context, we wish now to report new
results on the possibility of expanding the scope of this
attractive strategy for the synthesis of title compounds.
Resu lts a n d Discu ssion
Treatment of 1 with an excess of allyl vinyl ether (2)
in chloroform at 110 °C for 24 h afforded nearly quanti-
tatively 8,9-dicyano-4-oxatricyclo[4.3.1.03,7]dec-8-ene (5)
by a three-step homodomino reaction: the labile primary
adduct, coming from an intermolecular [4 + 2] cycload-
dition of DCP upon the most activated double bond of 2,
evolved into the final product by loss of nitrogen followed
by an intramolecular Diels-Alder reaction of the result-
ing cyclohexadiene 4, strongly assisted by entropic ac-
celeration (Scheme 1). Noteworthy, no trapping was
observed for 4 by the large excess of the reagent.
The same substrate reacted more slowly with vinyl
methacrylate (6) to give the desired tricyclic lactone 8 in
56% yield; however, phathalonitrile (9) (39%) was also
obtained in this case through a competitive elimination
of methacrylic acid from the likely common intermediate
7 (Scheme 2). Even longer reaction times were required
with vinyl cinnamate (10) (Experimental Section), and
compound 11 was isolated as a pure product in 34% yield
by careful resolution of the complex reaction mixture.
Unfortunately, repeated attempts to form in an analo-
gous fashion 5-oxatricyclo[5.3.1.03,8]undec-9-en-4-ones
were unsuccessful. Whereas reactions of 1 with allyl
methacrylate, allyl cinnamate, and allyl crotonate led to
untractable materials, treatment of DCP with 12 gave
the ester 14 in 40% yield as a result of a preferential
aromatization of the intermediate 13; according to a
previous result,5 this conversion probably involves a
hydrogen transfer from the latter to the starting dicy-
anopyridazine 1.
(1) (a) Boger, D. L.; Weinreb, S. N. Hetero Diels-Alder Methodology
in Organic Synthesis; Academic Press: New York, 1987; p 313. (b)
Coates, W. J . In Comprehensive Heterocyclic Chemistry II; Boulton,
A. J ., Ed.; Pergamon: Oxford, U.K., 1996; Vol. 6, p 30.
(2) (a) Maggiora, L.; Mertes, M. P. J . Org. Chem. 1986, 51, 950. (b)
Benson, S. C.; Gross, J . L.; Snyder, J . K. J . Org. Chem. 1990, 55, 3257.
(3) (a) Nesi, R.; Giomi, D.; Turchi, S.; Falai, A. J . Chem. Soc., Chem.
Commun. 1995, 2201. (b) Turchi, S.; Giomi, D.; Capaccioli, C.; Nesi,
R. Tetrahedron 1997, 53, 11711. (c) Turchi, S.; Nesi, R.; Giomi, D.
Tetrahedron 1998, 54, 1809. (d) Nesi, R.; Turchi, S.; Giomi, D.; Corsi,
C. Tetrahedron 1998, 54, 10851.
(4) Nesi, R.; Giomi, D.; Turchi, S.; Paoli, P. Tetrahedron 1994, 50,
9189.
(5) Giomi, D.; Nesi, R.; Turchi, S.; Coppini, R. J . Org. Chem. 1996,
61, 6028.
On the contrary, when 12 was replaced with the amide
15, the tricyclic δ-lactam 17 was obtained in 37% yield
through the open-chain compound 16 (Scheme 3).6
10.1021/jo991191v CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/05/2000

Pericyclic Domino Processes of 4,5-Dicyanopyridazine
J . Org. Chem., Vol. 65, No. 2, 2000 361
Sch em e 2
Sch em e 4
Sch em e 5
Sch em e 3
Sch em e 6
Efforts to carry out a direct domino conversion of DCP
and diallyldimethylsilane (18) into the cage system 20
at 110 °C caused both decomposition and isomerization
processes of the silylated reagent, and the complex
reaction mixtures contained only small amounts of the
desired product (1H NMR). On the other hand, although
the cyclohexadiene derivative 19 was easily isolated in
66% yield under milder conditions, its subsequent cy-
cloaddition into 20, strongly hampered by the encumber-
ing methyl groups, was achieved in only 32% yield by
prolonged heating at the original temperature (Scheme
4).
Similar steric effects also play a critical role in the
reaction of 1 with myrcene (21) characterized by a total
sitoselectivity. Thus, the intermediate 22, coming from
a primary interaction of DCP upon the terminal unsub-
stituted double bond of the terpene, afforded, together
with the corresponding aromatization product 24 (19%),
the more strained tricyclooctene 25 (24%) rather than the
cage derivative 23 by a preferential cycloaddition with
the less hindered vicinal dienophilic moiety (Scheme 5).
Replacement of 21 with the homochiral terpenes 26a ,b
caused a remarkable reduction of reactivity, and very
complex reactions were observed under forcing condi-
tions; nevertheless, whereas in the first case a 3:1
mixture of the diastereomeric tricycloundecenes 30a and
31a was obtained in 28% yield together with a minor
amount of the aromatic product 29a , in the second one
we succeeded in isolating, in addition to 29b (6%), the
cage compounds 30b and 31b in 12% and 19% yields,
respectively (Scheme 6).
Bearing in mind that the intramolecular cycloadditions
of the diastereomers 27a ,b and 28a ,b must compete
effectively both with aromatization processes and inter-
molecular Diels-Alder reactions of the same species with
the excess of the bis-dienophiles 26a ,b, the clear-cut
(6) For the greater reactivity of the bis-allyl amide moiety with
respect to the corresponding ester in intramolecular Diels-Alder
reactions, see: Swarbrick, T. M.; Marko´, I. E.; Kennard, L. Tetrahedron
Lett. 1991, 32, 2549.

362 J . Org. Chem., Vol. 65, No. 2, 2000
Giomi et al.
F igu r e 1.
Sch em e 7
predominance of 30a over 31a can be tentatively ac-
counted for by a different stabilization of the correspond-
ing chairlike transition structures I and II (Figure 1),
the latter being disfavored by a 1,3-diaxial methyl/
hydrogen interaction.7
F igu r e 2.
Repeated attempts to build up larger carbo- or hetero-
cage skeletons with octa-1,7-diene (32), nona-1,8-diene
(33), and diallyl carbonate (36) were completely unsuc-
cessful, probably due to unfavorable entropic effects and
repulsive nonbonding interactions. Moreover, although
compounds 34, 35, and 37 were easily obtained in 50-
52% yields from 1 and the above dienes (1 equiv, 110 °C)
(Scheme 7), we did not succeed in isolating any phtha-
lonitrile as a pure product from the complex reaction
mixtures gained by heating the cyclohexadiene deriva-
tives at higher temperature.
attained, according to the spectral behavior of epimeric
6-methyltricyclo[5.3.1.03,8]undecanes,8 in the light of the
diagnostic downfield shift observed for the methyl group
at position 6 on going from the endo (δ 0.88) to the exo
configuration (δ 1.05), 30b was distinguished from 31b
on the basis of a positive NOE effect detected for the
former between the same substituent and H-8.
In conclusion, despite evident limits arising from a
scarce reactivity toward a few counterparts or concomi-
tant undesired evolution processes of the cyclohexadiene
key intermediates, compound 1 can be rightly regarded
as a versatile synthon in the realm of masked or latent
bis-dienes9 for elegant entries into diverse cage systems
through purely pericyclic domino reactions.
The structures of the new compounds 5, 8, 11, 14, 17,
19, 20, 24, 25, 29-31a ,b, 34, 35, and 37 were determined
on the basis of analytical and spectral evidence (Experi-
1
mental Section). Whereas the H NMR patterns of the
2,3-dicyanocyclohexa-1,3-dienes 19, 34, 35, and 37 are
characterized by a triplet and a doublet at δ 6.79-6.85
and 6.73-6.74 for the H-1 and H-4 protons, respectively,
their 13C coupled spectra exhibit two doublets at δ 143.5-
150.9 for the corresponding alkenyl carbons. As for the
benzoate 14, the CH2 resonance of the allyl moiety was
detected as a doublet of triplets at δ 4.88.
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points are uncorrected. IR
spectra of solid and oily products were measured as KBr pellets
and liquid films, respectively. Unless otherwise stated, 1H and
13C NMR spectra were recorded in CDCl3 solutions at 200 and
50 MHz, respectively. Silica gel plates (Merck F254) and silica
gel 60 (Merck, 230-400 mesh) were used for TLC and flash
chromatographies, respectively: petroleum ether employed for
chromatographic workup refers to the fractions of bp 40-70
°C. HPLC was performed with a RP18 5 µm column using CH3-
CN/H2O as eluent.
Th er m a l Rea ction s of 4,5-Dicya n op yr id a zin e (1) w ith
th e Dien es 2, 6, 10, 12, 15, 18, 21, 26a ,b, 32, 33, a n d 36:
Syn th esis of Com p ou n d s 5, 8, 11, 14, 17, 19, 24, 25, 29-
31a ,b, 34, 35, a n d 37. Gen er a l P r oced u r e. Unless otherwise
indicated, a mixture of 1 (1 mmol) and the reagent in CHCl3
(1 mL) was heated at 110 °C in a screw-capped tube (Pyrex
no. 13), and the residue left by evaporation to dryness under
reduced pressure was subjected to flash chromatography.
When the conversion of 1 was incomplete, the yields of the
isolated compounds were determined on the basis of the
recovered starting material. Analytical samples of oily products
were obtained by dissolution in dichloromethane, filtration,
The stereochemistry at C-10 for the γ-lactone 11,
determined by the E configuration of the cinnamate 10,
was confirmed by the lack of coupling between H-10 and
the vicinal H-6 proton (θ ) ca. 90°), which gives rise to a
doublet (J 6,7 ) 4.9 Hz) at δ 3.07 (Figure 2). The structure
1
of 25 was firmly established on the basis of the H and
13C NMR resonances at δ 5.05 and 123.1, respectively,
for the CH group of the terminal alkene moiety; further-
more, as previously reported for 3,4-dicyano-1,7-dimethyl-
tricyclo[3.2.1.02,7]oct-3-ene,4 a doublet (J ) 12.4 Hz) was
observed at δ 0.92 for the remarkably shielded endo
protons at positions 6 and 8, together with a triplet (J )
4.8 Hz) at δ 3.0 for the bridgehead H-5. Finally, whereas
the structures of the diastereomers 30a and 31a were
(7) Impressive diastereospecificity was observed for intramolecular
cycloadditions of cyclohexa-1,3-diene derivatives as a consequence of
a more pronounced methyl/methyl overcrowding: Na¨f, F.; Decorzant,
R.; Giersch, W.; Ohloff, G. Helv. Chim. Acta 1981, 64, 1387.
(8) Yamada, K.; Kyotani, Y.; Manabe, S.; Suanki, M. Tetrahedron
1979, 35, 293.
(9) Winkler, J . D. Chem. Rev. 1996, 96, 167.

Pericyclic Domino Processes of 4,5-Dicyanopyridazine
J . Org. Chem., Vol. 65, No. 2, 2000 363
evaporation to dryness, and prolonged evacuation at room
temperature (10-2 Torr).
dimethylsilane (19) (Rf ) 0.35, 0.160 g, 66%), as a pale yellow
1
oil: IR 2226 cm-1; H NMR δ 0.06 (s, 6H), 0.78 (m, 2H), 1.54
(d, J ) 8.5 Hz, 2H), 2.27 (m, 1H), 2.50-2.77 (m, 2H), 4.82-
4.90 (m, 2H), 5.73 (m, 1H), 6.73 (d, J ) 4.4 Hz, 1H), 6.79 (t,
J ) 4.6 Hz, 1H); 13C NMR δ -2.9 (q), 19.1 (t), 23.5 (t), 28.65
(d), 30.4 (t), 107.2 (s), 108.5 (s), 113.9 (t), 115.0 (s), 115.1 (s),
133.9 (d), 143.9 (d), 150.9 (d). Anal. Calcd for C14H18N2Si: C,
69.38; H, 7.48; N, 11.56. Found: C, 69.04; H, 7.59; N, 11.22.
G. Chromatographic resolution [petroleum ether/ethyl ac-
etate (7:1 v/v)] of the residue coming from 1 and myrcene (21)
(0.150 g, 0.19 mL, 1.1 mmol) (4 days) afforded, in order of
decreasing mobility, 1,2-dicyano-4-(6′-methylhepta-1′,5′-dien-
2′-yl)benzene (24) (Rf ) 0.61, 0.039 g, 19%) as a yellow oil: IR
A. Treatment of 1 with allyl vinyl ether (2) (0.421 g, 0.55
mL, 5 mmol) for 24 h afforded 8,9-dicyano-4-oxatricyclo-
[4.3.1.03,7]dec-8-ene (5) (0.184 g, 99%) that was crystallized
from ether as ivory-colored needles: mp 117-118 °C; IR 2215,
1105 cm-1; 1H NMR δ 1.45-1.84 (m, 4H), 2.34-2.45 (m, 1H),
3.01 (m, 1H), 3.31 (t, J ) 4.6 Hz, 1H), 3.78 (m, AB part of an
ABX system, J ) 8.1 and 3.7 Hz, 2H), 4.22 (t, J ) 6.0 Hz, 1H);
13C NMR δ 32.8 (d), 33.9 (t), 35.2 (d), 36.9 (t), 44.8 (d), 73.1
(d), 73.4 (t), 113.7 (s), 114.3 (s), 125.6 (s), 134.4 (s). Anal. Calcd
for C11H10N2O: C, 70.95; H, 5.41; N, 15.04. Found: C, 70.62;
H, 5.41; N, 15.37.
1
2234 cm-1; H NMR δ 1.52 (s, 3H), 1.66 (s, 3H), 2.12 (q, J )
B. The crude reaction product of 1 and vinyl methacrylate
(6) (1.121 g, 1.20 mL, 10 mmol) (4 days) was mixed with sand
and sublimed at 50 °C/18 Torr to give phthalonitrile (9) (0.050
g, 39%); the sand was then extracted with dichloromethane
(2 × 15 mL) to yield (1SR,3RS,6SR,7RS)-8,9-dicyano-6-methyl-
4-oxatricyclo[4.3.1.03,7]dec-8-en-5-one (8) (0.120 g, 56%) as an
ivory-colored solid: mp 212-213 °C (from chloroform); IR 2220,
7.5 Hz, 2H), 2.51 (t, J ) 7.5 Hz, 2H), 5.07 (m, 1H), 5.33 (sbr s,
1H), 5.44 (sbr s, 1H), 7.72-7.80 (m, 3H); 13C NMR δ 17.7 (q),
25.6 (q), 26.5 (t), 34.6 (t), 113.9 (s), 115.4 (s), 115.55 (s), 116.0
(s), 117.4 (t), 122.7 (d), 130.5 (d), 131.1 (d), 132.8 (s), 133.5 (d),
145.15 (s), 146.9 (s). Anal. Calcd for C16H16N2: C, 81.32; H,
6.82; N, 11.85. Found: C, 81.04; H, 6.53; N, 12.09.
1
1783 cm-1; H NMR (DMSO-d6) δ 1.03 (s, 3H), 1.24-1.38 (m,
The second band gave 3,4-dicyano-1-(2′-methylpent-2′-en-
5′-yl)tricyclo[3.2.1.02,7]oct-3-ene (25) (Rf ) 0.49, 0.050 g, 24%)
1H), 1.56-1.83 (m, 2H), 2.06 (m, 1H), 3.26 (br s, 1H), 3.91 (d,
J ) 5.6 Hz, 1H), 4.72 (t, J ) 5.6 Hz, 1H); 13C NMR (DMSO-d6)
δ 19.6 (q), 31.0 (t), 35.2 (d), 35.6 (t), 41.7 (s), 47.85 (d), 73.7
(d), 114.4 (s), 115.05 (s), 124.0 (s), 135.5 (s), 179.3 (s). Anal.
Calcd for C12H10N2O2: C, 67.28; H, 4.71; N, 13.08. Found: C,
67.00; H, 4.63; N, 13.40.
as a pale yellow oil: IR 2214 cm-1 1H NMR δ 0.92 (d, J )
;
12.4 Hz, 2H), 1.50-1.77 (m, 10H), 1.89-2.11 (m, 4H), 3.0 (t,
J ) 4.8 Hz, 1H), 5.05 (m, 1H); 13C NMR δ 17.7 (q), 24.1 (d),
25.7 (q), 26.2 (t), 27.3 (t), 27.6 (d), 30.6 (t), 31.5 (t), 31.6 (s),
36.6 (d), 114.8 (s), 115.1 (s), 122.5 (s), 123.1 (d), 123.7 (s), 132.5
(s). Anal. Calcd for C16H18N2: C, 80.63; H, 7.61; N, 11.75.
Found: C, 80.42; H, 7.38; N, 12.03.
C. Chromatographic workup [toluene/ethyl acetate (20:3
v/v)] of the crude product from 1 and (E)-vinyl cinnamate (10)
(0.871 g, 0.81 mL, 5 mmol) (9 days) afforded (1RS,3RS,6SR,-
7SR,10RS)-8,9-dicyano-10-phenyl-4-oxatricyclo[4.3.1.03,7]dec-
8-en-5-one (11) (Rf ) 0.34, 0.095 g, 34%), as colorless crystals:
Some unreacted DCP was recovered from the slowest
moving fractions (Rf ) 0.11, 0.017 g).
H. Operating as above with petroleum ether/ethyl acetate
(12:1 v/v) as eluent, the crude product of 1 with (R)-(-)-â-
citronellene (26a ) (0.691 g, 0.91 mL, 5 mmol) (5 days) yielded
a 3:1 mixture of (1S,3S,6R,7R,8R)-9,10-dicyano-2,2,6-trimeth-
yltricyclo[5.3.1.03,8]undec-9-ene (30a ) and (1R,3R,6R,7S,8S)-
9,10-dicyano-2,2,6-trimethyltricyclo[5.3.1.03,8]undec-9-ene (31a )
(Rf ) 0.50, 0.058 g, 28%) as a white solid: 1H NMR δ 0.85 (s),
0.88 (d, J ) 6.6 Hz, 3H), [1.05 (d, J ) 7.3 Hz)], 1.14 (s), [1.19
(s)], 1.20-2.0 (m), 2.47 (m), 2.58 (t, J ) 2.5 Hz), [2.85 (m)];
13C NMR δ [18.2 (q)], 20.4 (q), 20.5 (t), [20.85 (t)], 21.4 (q),
[21.8 (q)], [22.4 (t)], 25.5 (t), 25.6 (t), [26.1 (t)], [30.4 (d)], 33.0
(q), [33.2 (q)], 33.5 (d), [36.1 (d)], 36.2 (d), 37.1 (d), [37.7 (d)],
38.15 (s), [38.4 (s)], [39.3 (d)], 46.4 (d), 47.7 (d), [48.15 (d)],
[113.7 (s)], 114.5 (s), [114.6 (s)], 114.9 (s), 131.05 (s), [131.1
(s)], 132.3 (s), [132.9 (s)].11
1
mp 166.5-167 °C (from ether); IR 2227, 1778 cm-1; H NMR
δ 1.80 (m, 1H), 2.20 (m, 1H), 3.07 (sbr d, J ) 4.9 Hz, 1H), 3.50
(m, 1H), 3.59 (m, 1H), 4.07 (t, J ) 4.9 Hz, 1H), 4.78 (dd, J )
7.5 and 4.9 Hz, 1H), 6.96-7.03 (m, 2H), 7.30-7.42 (m, 3H);
13C NMR δ 33.25 (t), 43.15 (d), 43.3 (d), 43.8 (d), 45.6 (d), 74.3
(d), 113.0 (s), 113.5 (s), 123.9 (s), 126.9 (d), 128.15 (d), 129.3
(d), 133.9 (s), 138.7 (s), 175.65 (s). Anal. Calcd for C17H12N2-
O2: C, 73.90; H, 4.38; N, 10.14. Found: C, 73.79; H, 4.48; N,
9.87.
D. Chromatographic resolution [petroleum ether/ethyl ac-
etate (4:1 v/v)] of the residue coming from 1 and allyl acrylate
(12) (0.561 g, 0.56 mL, 5 mmol) (48 h) gave allyl 3,4-
dicyanobenzoate (14) (Rf ) 0.43, 0.085 g, 40%) as ivory-colored
crystals: mp 62-62.5 °C (from n-pentane/ether); IR 2235, 1726
cm-1; 1H NMR δ 4.88 (dt, J ) 6.0 and 1.2 Hz, 2H), 5.33-5.49
(m, 2H), 5.93-6.13 (m, 1H), 7.93 (d, J ) 8.1 Hz, 1H), 8.37-
8.47 (m, 2H); 13C NMR δ 67.1 (t), 114.6 (s), 114.7 (s), 116.5 (s),
119.4 (s), 120.0 (t), 131.0 (d), 133.8 (d), 133.9 (d), 134.3 (d),
134.8 (s), 162.8 (s). Anal. Calcd for C12H8N2O2: C, 67.92; H,
3.80; N, 13.20. Found: C, 67.68; H, 3.80; N, 12.96.
E. Operating as above with ethyl acetate/petroleum ether
(2:1 v/v) as eluent, the crude reaction product from 1 and N,N-
diallyl acrylamide (15)10 (0.166 g, 1.1 mmol) (6 days) yielded
5-allyl-9,10-dicyano-5-azatricyclo[5.3.1.03,8]undec-9-en-4-one (17)
(Rf ) 0.32, 0.094 g, 37%) that was crystallized from ethyl
acetate as colorless needles: mp 180.5-181 °C; IR 2216, 1634
cm-1; 1H NMR δ 1.44 (ddd, J ) 13.0, 5.1 and 2.6 Hz, 1H), 1.66-
2.20 (m, 4H), 2.52-2.65 (m, 1H), 3.08 (quintet, J ) 2.6 Hz,
1H), 3.14 (dd, J ) 4.0 and 2.6 Hz, 1H), 3.35 (m, AB part of an
ABX system, J ) 12.7, 4.0, and 1.6 Hz, 2H), 3.80 (m, 1H), 4.18
(m, 1H), 5.14-5.29 (m, 2H), 5.63-5.83 (m, 1H); 13C NMR δ
29.0 (t), 29.2 (d), 33.5 (t), 34.4 (d), 35.4 (d), 38.0 (d), 49.0 (t),
50.1 (t), 113.6 (s), 113.7 (s), 118.8 (t), 129.3 (s), 131.9 (d), 133.1
(s), 170.3 (s). Anal. Calcd for C15H15N3O: C, 71.13; H, 5.97; N,
16.59. Found: C, 71.07; H, 5.99; N, 16.33.
HPLC resolution of the above mixture yielded 30a (0.015
g) as a white solid; an analytical sample, obtained by washing
with the minimun amount of anhydrous ether, gradually
wrinkled above 80 °C and melted at 93-94 °C: [R]22 ) (+)-
D
72.6° (c 0.5, CHCl3); IR 2214 cm-1
;
1H NMR δ 0.85 (s, 3H),
0.88 (d, J ) 6.6 Hz, 3H), 1.14 (s, 3H), 1.20-1.82 (m, 9H), 2.47
(t, J ) 2.8 Hz, 1H), 2,58 (t, J ) 2.5 Hz, 1H). Anal. Calcd for
C
16H20N2: C, 79.96; H, 8.39; N, 11.66. Found: C, 79.68; H,
8.33; N, 11.85.
The second band gave 1,2-dicyano-4-[(6′R)-2′-methylhept-
2′-en-6′-yl)]benzene (29a ) (Rf ) 0.37, 0.012 g, 6%) as a pale
yellow oil: [R]24 ) (-)100.0° (c 0.2, CHCl3); IR 2234 cm-1; 1H
D
NMR δ 1.26 (d, J ) 7.0 Hz, 3H), 1.50 (s, 3H), 1.58-1.64 (m,
2H), 1.67 (s, 3H), 1.80-1.88 (m, 2H), 2.83 (sextet, J ) 7.0 Hz,
1H), 5.02 (m, 1H), 7.51-7.75 (m, 3H); 13C NMR δ 17.65 (q),
21.5 (q), 25.6 (q), 25.7 (t), 37.7 (t), 39.4 (d), 113.1 (s), 115.5 (s),
115.6 (s), 115.9 (s), 123.2 (d), 132.0 (d), 132.4 (d), 132.5 (s),
133.5 (d), 154.4 (s). Anal. Calcd for C16H18N2: C, 80.63; H, 7.61;
N, 11.75. Found: C, 80.30; H, 7.35; N, 12.06.
A small amount of 1 (0.020 g) was recovered by washing
the column with ethyl acetate.
I. The reaction mixture of 1 with (R)-(-)-linalool (26b) (0.771
g, 0.89 mL, 5 mmol) (8 days) was resolved into three compo-
nents with petroleum ether/ethyl acetate (2:1 v/v) as eluent.
The faster running band afforded 1,2-dicyano-4-[(6′R)-6′-
hydroxy-2′-methylhept-2′-en-6′-yl)]benzene (29b) (Rf ) 0.60,
F . Chromatographic workup [petroleum ether/ethyl acetate
(8:1 v/v)] of the reaction product obtained from 1 and diallyl-
dimethylsilane (18) (0.702 g, 0.91 mL, 5 mmol) at 70 °C for 6
days gave allyl[(2,3-dicyanocyclohexa-1,3-dien-5-yl)methyl]-
(10) Naito, T.; Honda, Y.; Miyata, O.; Ninomiya, I. J . Chem. Soc.,
Perkin Trans. 1 1995, 19.
(11) The values in square brackets refer to the minor diastereomer.

364 J . Org. Chem., Vol. 65, No. 2, 2000
Giomi et al.
1
0.016 g, 6%) as a yellow oil: [R]24D ) (-)2.6° (c 0.2, CHCl3); IR
3497, 2237 cm-1; 1H NMR δ 1.48 (sbr s, 3H), 1.55 (s, 3H), 1.64
(sbr s, 3H), 1.84-1.90 (m, 4H), 2.16 (sbr s, 1H), 5.04 (m, 1H),
7.78 (m, 2H), 7.93 (m, 1H); 13C NMR δ 17.7 (q), 22.6 (q), 25.6
(q), 30.5 (t), 43.3 (t), 74.7 (s), 113.7 (s), 115.45 (s), 115.6 (s),
115.8 (s), 123.0 (d), 129.8 (d), 130.5 (d), 133.3 (d), 133.4 (s),
154.6 (s). Anal. Calcd for C16H18N2O: C, 75.56; H, 7.13; N,
11.01. Found: C, 75.28; H, 6.99; N, 11.35.
0.113 g, 50%) as a colorless liquid: IR 2227 cm-1; H NMR δ
1.20-1.50 (m, 8H), 2.04 (q, J ) 6.8 Hz, 2H), 2.25-2.32 (m,
1H), 2.49-2.60 (m, 2H), 4.91-5.03 (m, 2H), 5.78 (m, 1H), 6.74
(d, J ) 4.1 Hz, 1H), 6.81 (t, J ) 4.6 Hz, 1H); 13C NMR δ 26.25
(t), 27.6 (t), 28.6 (t), 28.8 (t), 32.3 (d), 33.05 (t), 33.5 (t), 108.1
(s), 108.6 (s), 114.5 (t), 114.95 (s), 115.0 (s), 138.6 (d), 144.2
(d), 149.05 (d). Anal. Calcd for C15H18N2: C, 79.61; H, 8.02; N,
12.38. Found: C, 79.91; H, 7.85; N, 12.13.
The following band gave (1R,3R,6R,7R,8R)-9,10-dicyano-6-
hydroxy-2,2,6-trimethyltricyclo[5.3.1.03,8]undec-9-ene (31b )
(Rf ) 0.40, 0.048 g, 19%) that, after crystallization from ether,
gradually wrinkled above 165 °C and melted at 181-182 °C:
N. Chromatographic purification [petroleum ether/ethyl
acetate (2:1 v/v)] of the brown residue coming from 1 and
diallyl carbonate (36) (0.156 g, 0.16 mL, 1.1 mmol) (5 days)
gave allyl (2,3-dicyanocyclohexa-1,3-dien-5-yl)methyl carbonate
(37) (Rf ) 0.30, 0.127 g, 52%) as a yellow oil; IR 2229, 1746
[R]19 ) (-)66.0° (c 0.45, CHCl3); IR 2221 cm-1 1H NMR δ
;
D
1
0.87 (s, 3H), 1.16 (s, 3H), 1.24 (s, 3H), 1.30-1.80 (m, 9H), 2.50
(m, 1H), 3.33 (m, 1H); 13C NMR δ 21.6 (t), 21.9 (q), 24.2 (t),
30.1 (q), 30.9 (t), 33.05 (q), 36.9 (d), 38.2 (s), 40.2 (d), 41.85
(d), 48.1 (d), 71.45 (s), 114.5 (s), 114.8 (s), 131.2 (s), 132.8 (s).
Anal. Calcd for C16H20N2O: C, 74.97; H, 7.86; N, 10.93.
Found: C, 74.68; H, 7.62; N, 11.18.
cm-1; H NMR δ 2.34-2.70 (m, 2H), 2.90-3.09 (m, 1H), 4.17
(m, 2H), 4.64 (d, J ) 5.9 Hz, 2H), 5.30 (sbr d, J ) 10.3 Hz,
1H), 5.38 (sbr d, J ) 16.5 Hz, 1H), 5.84-6.03 (m, 1H), 6.74 (d,
J ) 4.0 Hz, 1H), 6.85 (t, J ) 4.6 Hz, 1H); 13C NMR δ 24.5 (t),
32.5 (d), 67.2 (t), 68.95 (t), 108.75 (s), 110.1 (s), 114.5 (s), 114.6
(s), 119.5 (t), 131.0 (d), 143.5 (d), 143.8 (d), 154.5 (s). Anal.
Calcd for C13H12N2O3: C, 63.93; H, 4.95; N, 11.47. Found: C,
63.61; H, 4.75; N, 11.70.
The slowest moving fractions yielded (1S,3S,6R,7S,8S)-9,-
10-dicyano-6-hydroxy-2,2,6-trimethyltricyclo[5.3.1.03,8]undec-
9-ene (30b ) (Rf ) 0.20, 0.031 g, 12%), as a pale yellow oil:
[R]22D ) (+)67.0° (c 0.95, CHCl3); IR 3473, 2223 cm-1; 1H NMR
δ 0.87 (s, 3H), 1.0-2.10 (m, 8H), 1.19 (s, 3H), 1.24 (s, 1H), 1.35
(s, 3H), 2.51 (t, J ) 2.7 Hz, 1H), 2.75 (t, J ) 2.8 Hz, 1H); 13C
NMR δ 21.55 (q), 22.8 (t), 23.7 (t), 27.4 (q), 31.7 (t), 33.1 (q),
37.1 (d), 38.1 (s), 42.7 (d), 43.1 (d), 47.6 (d), 71.6 (s), 114.4 (s),
114.7 (s), 129.8 (s), 133.55 (s). Anal. Calcd for C16H20N2O: C,
74.97; H, 7.86; N, 10.93. Found: C, 75.21; H, 7.98; N, 10.70.
L. Chromatographic workup [petroleum ether/ethyl acetate
(4:1 v/v)] of the reaction product of 1 and octa-1,7-diene (32)
(0.121 g, 0.17 mL, 1.1 mmol) (4 days) afforded 2,3-dicyano-5-
(hexen-6′-yl)cyclohexa-1,3-diene (34) (Rf ) 0.41, 0.110 g, 52%)
9,10-Dicyan o-5,5-dim eth yl-5-silatr icyclo[5.3.1.03,8]u n dec-
9-en e (20). A solution of compound 19 (0.071 g, 0.29 mmol)
in CHCl3 (0.5 mL) was heated at 110 °C in a sealed tube for 9
days, and the residue left by evaporation to dryness was
subjected to flash chromatography with petroleum ether/ethyl
acetate (15:1 v/v) as eluent to yield 20 (Rf ) 0.48, 0.018 g, 32%)
that was crystallized from ether as colorless needles: mp 146-
147 °C; IR 2218 cm-1 1H NMR δ 0.02 (s, 3H), 0.28 (s, 3H),
;
0.76-1.08 (m, 4H), 1.42 (ddd, J ) 12.8, 5.5, and 2.2 Hz, 2H),
1.77 (m, 2H), 2.09-2.23 (m, 2H), 2.54 (t, J ) 2.6 Hz, 1H), 2.95
(m, 1H); 13C NMR δ 0.1 (q), 2.6 (q), 17.7 (t), 30.1 (d), 32.3 (t),
35.8 (d), 45.1 (d), 114.3 (s), 114.6 (s), 130.2 (s), 134.7 (s). Anal.
Calcd for C14H18N2Si: C, 69.38; H, 7.48; N, 11.56. Found: C,
69.05; H, 7.46; N, 11.25.
1
as a pale yellow oil: IR 2226 cm-1; H NMR δ 1.29-1.50 (m,
6H), 2.04 (q, J ) 6.8 Hz, 2H), 2.21-2.34 (m, 1H), 2.46-2.64
(m, 2H), 4.92-5.04 (m, 2H), 5.66-5.87 (m, 1H), 6.74 (d, J )
3.7 Hz, 1H), 6.81 (t, J ) 4.6 Hz, 1H); 13C NMR δ 25.7 (t), 27.4
(t), 28.4 (t), 32.2 (d), 32.8 (t), 33.3 (t), 107.8 (s), 108.3 (s), 114.7
(t), 115.0 (s), 115.05 (s), 138.2 (d), 144.45 (d), 149.1 (d). Anal.
Calcd for C14H16N2: C, 79.21; H, 7.60; N, 13.20. Found: C,
78.87; H, 7.49; N, 13.53.
Some unreacted starting material (Rf ) 0.12, 0.015 g) was
recovered from the slower moving band.12
Ack n ow led gm en t. We wish to thank Mrs. Brunella
Innocenti for the analytical data.
J O991191V
M. Operating as above with petroleum ether/ethyl acetate
(7:1 v/v) as eluent, the residue from the reaction of 1 with nona-
1,8-diene (33) (0.137 g, 0.18 mL, 1.1 mmol) (5 days) yielded
2,3-dicyano-5-(hepten-7′-yl)cyclohexa-1,3-diene (35) (Rf ) 0.20,
(12) When a total conversion of 19 was attained under more forcing
conditions, the desired compound 20 was isolated in much lower yield
from the more complex reaction mixture.