Synthesis and cycloaromatization of (Z)-1,2,4-heptatrien-6-ynes and (Z)-2,4,5-hexatrienenitriles

Full text of DOI:10.1021/jo9517149

1516
J . Org. Chem. 1996, 61, 1516-1518
Sch em e 1
Syn th esis a n d Cycloa r om a tiza tion of
(Z)-1,2,4-Hep ta tr ien -6-yn es a n d
(Z)-2,4,5-Hexa tr ien en itr iles
Kung K. Wang* and Zhongguo Wang
Department of Chemistry, West Virginia University,
Morgantown, West Virginia 26506
Prem D. Sattsangi
Department of Chemistry, The Pennsylvania
State University, Fayette Campus,
Uniontown, Pennsylvania 15401
Received September 19, 1995
Cycloaromatization of (Z)-1,2,4-heptatrien-6-yne (1) to
R,3-didehydrotoluene 2 is an attractive method for gen-
erating two radical centers simultaneously (eq 1).1 While
the process results in the loss of one chemical bond, the
reaction has been estimated to be exothermic by ca. 15
kcal/mol. Converting a π bond of 1 to a σ bond in 2 along
with gains from aromaticity and benzylic resonance are
mainly responsible for making the process energetically
favorable. Cyclization occurs at 37 °C with a half-life of
ca. 24 h. At 75 °C, the half-life of the reaction is reduced
to 30 min.
ylsilyl)-1-propyne (5)4 with n-butyllithium followed by
B-methoxy-9-borabicyclo[3.3.1]nonane (B-MeO-9-BBN)
4
and /3BF3‚OEt2 (Scheme 1).2 Subsequent condensation
with the conjugated allenic aldehydes 73,5 furnished, after
treatment with 2-aminoethanol, the condensation ad-
ducts 8 with high diastereoselectivity. The KH-induced
syn elimination of hydroxytrimethylsilane from 8a pro-
duced enyne-allene 9a (Z:E ) 96:4), which on exposure
to tetrabutylammonium fluoride (TBAF) furnished the
desilylated adduct 10a . Conversion of 8b to 10b (Z:E >
99:1) was achieved in one operation by treatment with
KH followed by desilylation with sodium ethoxide.
Compared to 3, enyne-allene 10a has an additional
methyl substituent at the terminus of the allenic moiety,
making it possible to produce a more stable tertiary
benzylic radical center in 11 after cycloaromatization and,
as a result, to increase the rate of reaction. Thermolysis
of 10a (0.122 g, 1.03 mmol, 0.2 M) in 5 mL of 1,4-
cyclohexadiene at 37 °C for 15 h produced cumene (12,
43%), 1,2-dimethyl-1,2-diphenylethane (13, 2%), and the
combination products 14a and 14b (1:1, 15%) (Scheme
2). The half-life of the reaction at 37 °C was determined
to be ca. 70 min by using the 1H NMR to monitor the
disappearance of 10a in C6D6 in the presence of an excess
of 1,4-cyclohexadiene.
Introduction of a methyl substituent at the terminus
of the allenic moiety accelerates the reaction rate by
approximately 6-fold, and 3 cyclizes with a half-life of
ca. 3.6 min at 78 °C (eq 2).1 The formation of a more
stable secondary benzylic radical in 4 is apparently
responsible for the rate enhancement.
We recently reported a simple synthetic method for the
preparation of (Z)-3-hexene-1,5-diynes by condensation
of (γ-(tert-butyldimethylsilyl)allenyl)borane 6 with the
conjugated acetylenic aldehydes followed by the elimina-
tion step of the Peterson olefination reaction.2 This
method was also successfully applied to the synthesis of
1,2,4-heptatrien-6-ynes (enyne-allenes) by utilizing con-
jugated allenic aldehydes for condensation.3 We now
have utilized 6 for the synthesis of enyne-allenes 10a
and 10b, and their rates of cycloaromatization to the
corresponding R,3-didehydrotoluene biradicals were stud-
ied. Similarly, the aza analogues, (Z)-2,4,5-hexatrieneni-
triles 18a and 18b in which a cyano group replaces the
acetylenic moiety of 10a and 10b were synthesized.
Allenylborane 6 was prepared in situ by treating the
readily available 3-(tert-butyldimethylsilyl)-1-(trimeth-
Enyne-allene 10b having two sterically demanding
tert-butyl groups exhibited a slower rate of cyclization
(t1/2 ) ca. 60 min at 76 °C) when compared to 10a
(Scheme 3). Cycloaromatization was conducted in C6D6
in the presence of an excess of 1,4-cyclohexadiene, and
1
the rate of the reaction was monitored by H NMR. On
thermolysis in refluxing benzene (80 °C) in the presence
of an excess of 1,4-cyclohexadiene, the reaction was
essentially complete within 5 h, and R,R-di-tert-butyl-
toluene (16) was isolated in 58% yield.
(1) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J . Am. Chem. Soc. 1989,
111, 8057-8059.
(4) (a) Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto,
H. Bull. Chem. Soc. J pn. 1984, 57, 2768-2776. (b) Yamakado, Y.;
Ishiguro, M.; Ikeda, N.; Yamamoto, H. J . Am. Chem. Soc. 1981, 103,
5568-5570.
(5) Clinet, J .-C.; Linstrumelle, G. Nouv. J . Chem. 1977, 1, 373-
374.
(2) Wang, K. K.; Wang, Z.; Gu, Y. G. Tetrahedron Lett. 1993, 34,
8391-8394.
(3) (a) Andemichael, Y. W.; Gu, Y. G.; Wang, K. K. J . Org. Chem.
1992, 57, 794-796. (b) Andemichael, Y. W.; Huang, Y.; Wang, K. K.
J . Org. Chem. 1993, 58, 1651-1652.
0022-3263/96/1961-1516$12.00/0 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 4, 1996 1517
Sch em e 2
180 °C, a large portion of 18a remained unreacted. A
mixture of unidentified products was produced on ther-
molysis of 18a in C6D6 in the presence of an excess of
1,4-cyclohexadiene at 200 °C for 30 min where the
anticipated 2-isopropylpyridine was not detected.8 The
thermal stability of 18b was even more remarkable,
remaining unchanged even on heating in toluene-d8 in
the presence of an excess of 1,4-cyclohexadiene at 260
°C for 15 h.
Exp er im en ta l Section
General procedures for manipulation of organoboranes and
other organometallic reagents were described previously.9 All
reactions were conducted in oven-dried glassware under
a
nitrogen atmosphere. Tetrahydrofuran (THF) was distilled from
sodium benzophenone ketyl prior to use. The following reagents
were purchased from Aldrich Chemical Co., Inc., and were used
without further purification: n-butyllithium (2.5 M in hexanes),
1-(trimethylsilyl)-1-propyne, tert-butyldimethylsilyl chloride,
3-methyl-1,2-butadiene, TBAF, 1,4-cyclohexadiene, trimethyl
borate, and triisopropyl borate. Potassium hydride (35 wt %
dispersion in mineral oil) was also purchased from Aldrich, and
mineral oil was removed by washing with pentane prior to use.
3-(tert-Butyldimethylsilyl)-1-(trimethylsilyl)-1-propyne (5),4 (tert-
butyldimethylsilyl)acetonitrile (17),4 B-MeO-9-BBN,10 and 4-meth-
yl-2,3-pentadienal (7a )3,5 were prepared according to the reported
procedures. 5,5-Dimethyl-4-(1,1-dimethylethyl)-2,3-hexadienal
(7b) was prepared in 80% isolated yield by treatment of 4,4-
dimethyl-3-(1,1-dimethylethyl)-1,2-pentadiene11 with n-butyl-
lithium followed by N,N-dimethylformamide and acidic hydrol-
ysis.3,5 1H (270 MHz) and 13C (67.9 MHz) NMR spectra were
recorded in CDCl3 or C6D6 using Me4Si, CHCl3 (1H δ 7.26), CDCl3
Sch em e 3
(
13C δ 77.02), C6D5H (1H δ 7.15), or C6D6 13C δ 128.00) as
(
When compared to 1, the rate of cycloaromatization of
10b is not significantly affected. Presumably, the small
size of the hydrogen atom at the terminal position of the
acetylenic moiety in 10b minimizes the steric interactions
even with the tert-butyl group, and the formation of a
more stable tertiary benzylic radical in 15 partially
compensates for the increased steric interactions.
It is worth noting that the benzylic radical center in
15 is an R,R-di-tert-butylbenzylic radical, which has been
reported to be persistent in dilute solution at room
temperature for several days.6 For steric reasons, the
R,R-di-tert-butylbenzylic radical prefers a conformation
with the p-orbital of the radical center perpendicular to
the π-bonds of the benzene ring, resulting in the loss of
13 kcal/mol of the resonance energy. This preference also
eliminates the possibility of twisting the terminal allenic
carbon of 10b during the course of cyclization to allow
at least a partial conjugation of the benzylic radical
center with the benzene ring at the transition state in
order to facilitate the rate of cyclization.1,7
internal standard. The isomer ratios were determined by
integration of the 1H NMR spectra.
(3S,4R)-3-(ter t-Bu tyld im eth ylsilyl)-7-m eth yl-1-(tr im eth -
ylsilyl)-5,6-octa d ien -1-yn -4-ol (8a ). To 1.36 g of 5 (6.0 mmol)
in 15 mL of THF was added 2.4 mL of a 2.5 M solution of
n-butyllithium (6.0 mmol) in hexanes at -10 °C. After 30 min
at -10 °C, 1.0 mL of B-MeO-9-BBN (0.92 g, 6.0 mmol) was
introduced by a syringe. After an additional 45 min at 0 °C,
1.0 mL of BF3‚OEt2 (1.14 g, 8.0 mmol) was added and the
reaction mixture was stirred at 0 °C for 20 min before 0.576 g
(6.0 mmol) of 7a was introduced. The reaction mixture was
allowed to warm to rt. After 2 h, THF and hexanes were
removed at reduced pressure under a slow stream of N2, and
the pressure was then restored with N2. Hexane (20 mL) was
added followed by 1.0 mL of 2-aminoethanol, and a white
precipitate was formed almost immediately. After 15 min, the
precipitate was removed by filtration, and the filtrate was
washed with water, dried over MgSO4, and concentrated. The
residue was purified by column chromatography (silica gel/5%
diethyl ether in hexanes) to furnish 1.481 g (4.6 mmol, 77%) of
8a as a light yellow liquid: IR (neat) 3357, 2158, 1969, 1250,
843 cm-1 1H (C6D6) δ 5.34 (1 H, d of septet, J ) 5.1 and 2.8
;
Hz), 4.30 (1 H, ddd, J ) 9.0, 5.1, and 2.6 Hz), 2.14 (1 H, d, J )
2.4 Hz), 2.03 (1 H, d, J ) 9.0 Hz), 1.66 (3 H, d, J ) 2.8 Hz), 1.60
(3 H, d, J ) 2.8 Hz), 0.96 (9 H, s), 0.34 (3 H, s), 0.18 (9 H, s),
0.11 (3 H, s); 13C (C6D6) δ 199.93, 106.74, 99.32, 94.81, 89.01,
68.88, 27.71, 27.20, 21.05, 20.46, 17.71, 0.36, -6.00, -6.50.
(Z)-2,4,5-Hexatrienenitriles 18a and 18b were synthe-
sized as the aza analogues of 10a and 10b, respectively.
Sequential treatment of (tert-butyldimethylsilyl)acetoni-
trile (17)4 with n-butyllithium, triisopropyl or trimethyl
borate, and the allenic aldehydes 7 furnished 18a (Z:E
) 9:1) and 18b (Z:E ) 98:2) with high geometric purity
(eq 3).
(6) Schreiner, K.; Berndt, A. Angew. Chem., Int. Ed. Engl. 1974,
13, 144-145.
(7) Koga, N.; Morokuma, K. J . Am. Chem. Soc. 1991, 113, 1907-
1911.
(8) Recently, a conference abstract concerning cycloaromatization
of a (Z)-2,4,5-hexatrienenitrile to the corresponding aniline derivative
appeared. Gillmann, T.; Heckhoff, S.; Weeber, T. Abstracts of Papers,
209th National Meeting of the American Chemical Society, Anaheim,
CA, April 2-6, 1995; American Chemical Society: Washington, DC,
1995; ORGN 93.
(9) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Syntheses via Boranes; Wiley-Interscience: New York, 1975.
(10) Kramer, G. W.; Brown, H. C. J . Organomet. Chem. 1974, 73,
1-15.
(11) Crandall, J . K.; Conover, W. W.; Komin, J . B.; Machleder, W.
H. J . Org. Chem. 1974, 39, 1723-1729.
The conjugated nitrile 18a exhibited much higher
thermal stability than that of 10a and showed no sign of
change on prolonged storage at rt. Even after 10 min at

1518 J . Org. Chem., Vol. 61, No. 4, 1996
Notes
(3S,4R)-3-(ter t-Bu t yld im et h ylsilyl)-8,8-d im et h yl-7-(1,1-
dim eth yleth yl)-1-(tr im eth ylsilyl)-5,6-n on adien -1-yn -4-ol (8b).
The same reaction procedure was repeated as described for 8a
except that 1.08 g (6.0 mmol) of 7b was used to furnish 1.58 g
(3.89 mmol, 65%) of 8b as a light yellow liquid: IR (neat) 3561,
Cycloa r om a tiza tion of 10b. A mixture of 0.202 g (1.00
mmol) of 10b and 0.8 g (10 mmol) of 1,4-cyclohexadiene in 20
mL of benzene under an N2 atmosphere was heated to reflux
for 5 h. The reaction mixture was concentrated, and the residue
was purified by column chromatography (silica gel/hexanes) to
furnish 0.119 g (0.58 mmol, 58%) of 16 as a colorless liquid: IR
(neat) 1393, 1367, 740, 706 cm-1; 1H (CDCl3) δ 7.48-7.07 (5 H,
m), 2.42 (1 H, s), 1.11 (18 H, s); 13C (CDCl3) δ 144.66, 133.36,
128.25, 127.25, 126.70, 125.39, 65.97, 35.97, 32.07; MS m/ e 148
(M+ - 56), 131, 117, 105, 91, 57.
1
2158, 1941, 1249, 841 cm-1; H (CDCl3) δ 5.30 (1 H, d, J ) 5.0
Hz), 4.20 (1 H, ddd, J ) 10.1, 5.1, and 1.8 Hz), 2.16 (1 H, d, J )
1.8 Hz), 2.02 (1 H, d, J ) 10.1 Hz), 1.21 (9 H, s), 1.19 (9 H, s),
0.95 (9 H, s), 0.16 (3 H, s), 0.13 (9 H, s), 0.10 (3 H, s); 13C (CDCl3)
δ 199.94, 125.12, 105.80, 97.41, 89.77, 68.90, 35.14, 34.76, 32.46,
32.18, 27.26, 26.98, 17.57, 0.17, -6.55, -6.70.
The rate of cycloaromatization of 10b was also measured by
conducting the reaction in C6D6 in the presence of an excess of
1,4-cyclohexadiene. The rate of disappearance of 10b and the
appearance of 16 were monitored by 1H NMR at 76 °C. The
half-life of the reaction was determined to be ca. 60 min.
(Z)-6-Meth yl-2,4,5-h ep ta tr ien en itr ile (18a ). To a solution
of 0.446 g (2.9 mmol) of 17 in 6 mL of THF was added dropwise
1.15 mL of a 2.5 M solution of n-butyllithium (2.9 mmol) in
hexanes at -78 °C. After 10 min, a solution of 0.553 g (0.67
mL, 2.9 mmol) of triisopropyl borate in 1.5 mL of THF was
added. After an additional 10 min, 0.28 g (2.9 mmol) of the
conjugated allenic aldehyde 7a was introduced, and the reaction
mixture was allowed to stir at rt for 12 h. Hexanes (10 mL)
was added, and the reaction mixture was washed with water,
dried over Na2SO4, and concentrated. The residue was purified
by column chromatography (silica gel/2.5% ethyl acetate in
hexanes) to furnish 0.235 g (1.97 mmol, 68%) of 18a (Z:E ) 9:1)
as a light yellow liquid: IR (neat) 2214, 1949, 1592, 1232, 743
(Z)-7-Meth yl-1-(tr im eth ylsilyl)-3,5,6-octa tr ien -1-yn e (9a ).
To a dispersion of 0.72 g (18 mmol) of KH in 20 mL of a 1:1
mixture of pentane and diethyl ether at 0 °C under N2 was added
1.45 g (4.5 mmol) of 8a . After 30 min of stirring, KH was
removed by filtration, and the reaction mixture was washed with
water, dried over MgSO4, and concentrated. The residue was
purified by column chromatography (silica gel/hexanes) to
furnish 0.695 g (3.66 mmol, 81%) of 9a (Z:E ) 96:4) as a colorless
liquid: IR (neat) 2144, 1947, 1250, 846 cm-1; 1H NMR (C6D6) δ
6.70 (1 H, dm, J ) 11.2 and 1 Hz), 6.24 (1 H, t, J ) 10.9 Hz),
5.32 (1 H, dd J ) 10.6 and 0.9 Hz), 1.49 (6 H, d J ) 2.7 Hz),
0.17 (9 H, s); 13C NMR (C6D6) δ 207.70, 139.03, 107.93, 102.75,
101.32, 96.87, 91.25, 20.02, 0.03; MS m/ e 190 (M+), 175, 159,
131, 115, 84, 73.
(Z)-7-Meth yl-3,5,6-octa tr ien -1-yn e (10a ). To a solution of
0.342 g (1.80 mmol) of 9a in 10 mL of THF at 0 °C under N2
was added 10 mL of a 1.0 M solution of TBAF in THF. The
reaction mixture turned dark immediately. After 1 h of stirring
at 0 °C, the reaction mixture was poured over a mixture of 15
mL of ice water and 25 mL of pentane contained in a separatory
funnel. The organic layer was separated and washed with
water, a 0.05 M solution of HCl, a saturated aqueous NaHCO3
solution, and a saturated aqueous NaCl solution. The organic
layer was then dried over MgSO4 and concentrated. The residue
was purified by column chromatography (silica gel/pentane) to
furnish 0.122 g (1.03 mmol, 57%) of 10a (Z:E ) 96:4) as a
colorless liquid: 1H (C6D6) δ 6.54 (1 H, dd of septet, J ) 11.0,
1.1 and 2.8 Hz), 6.21 (1 H, td, J ) 11.0 and 1 Hz), 5.18 (1 H,
ddd, J ) 10.5, 2.4, and 1 Hz), 2.91 (1 H, dd, J ) 2.4 and 1 Hz),
1.48 (6 H, d, J ) 2.8 Hz); 13C (C6D6) δ 207.68, 139.60, 106.75,
96.85, 90.86, 84.09, 80.66, 20.01; MS m/ e 118 (M+), 103, 91, 77.
Cycloa r om a tiza tion of 10a . A mixture of 0.122 g (1.03
mmol) of 10a in 5 mL of 1,4-cyclohexadiene was kept under an
N2 atmosphere at 37 °C for 15 h. The reaction products were
analyzed by GC and were found to contain 43% of cumene (12),
2% of 1,2-dimethyl-1,2-diphenylethane (13), and 15% of the
combination products 14a and 14b (1:1).
1
cm-1; H NMR (CDCl3) δ 6.69 (1 H, t, J ) 10.9 Hz), 6.14 (1 H,
dd of septet, J ) 11.2, 0.9, and 2.8 Hz), 5.08 (1 H, dd, J ) 10.6
and 0.9 Hz), 1.75 (6 H, d, J ) 2.8 Hz); 13C NMR (CDCl3) δ 209.82,
148.29, 116.32, 98.17, 94.75, 90.07, 19.68; MS m/ e 119 (M+),
118, 104, 91, 77. A minor set of the 1H NMR signals at 6.86 (l
H, dd, J ) 15.9 and 10.8 Hz), 5.75 (1 H, dd of septet, J ) 10.8,
0.7 and 2.8 Hz), and 5.26 (1 H, dd, J ) 16.0 and 10.6 Hz)
attributable to the presence of the E isomer were also observed.
(Z)-7,7-Dim eth yl-6-(1,1-d im eth yleth yl)-2,4,5-octa tr ien en -
itr ile (18b). To a solution of 0.31 g (2.0 mmol) of 17 in 20 mL
of THF was added 0.80 mL of a 2.5 M solution of n-butyllithium
(2.0 mmol) in hexanes at -78 °C. After 20 min, 0.30 mL (0.27
g, 2.6 mmol) of trimethyl borate was added. After an additional
20 min at -78 °C, 0.36 g (2.0 mmol) of 7b in 5 mL of THF was
introduced, and the reaction mixture was stirred at -78 °C for
1 h before 6 mL of water was added. The organic layer was
separated, and the aqueous layer was extracted with diethyl
ether (3 × 20 mL). The combined organic layers were dried over
MgSO4 and concentrated. The residue was purified by column
chromatography (silica gel/hexanes) to furnish 0.35 g (1.74 mmol,
87%) of 18b (Z:E ) 98:2) as a light yellow liquid: IR (neat) 2214,
1916, 1585, 1471, 1083, 736, 700, 679 cm-1; 1H NMR (CDCl3) δ
6.67 (1 H, dd, J ) 11.2 and 10.6 Hz), 6.29 (1 H, dd, J ) 11.3 and
1.0 Hz), 5.03 (1 H, dd, J ) 10.6 and 0.9 Hz), 1.20 (18 H, s); 13C
NMR (CDCl3) δ 211.11, 148.70, 124.37, 116.51, 93.65, 93.51,
35.17, 31.81; MS m/ e 203 (M+), 188, 147, 146, 132, 91, 77, 57.
The rate of the reaction was measured by conducting cy-
cloaromatization of 10a (ca. 0.2 M) in C6D6 in the presence of
an excess of 1,4-cyclohexadiene (1.2 M) under an N2 atmosphere
at 37 °C. The rate of disappearance of 10a was monitored by
the 1H NMR using 1,4-dibromobenzene as an internal standard.
The half-life of the reaction at 37 °C was determined to be ca.
70 min.
(Z)-8,8-Dim eth yl-7-(1,1-d im eth yleth yl)-3,5,6-n on a tr ien -
1-yn e (10b). To a dispersion of 0.72 g (18 mmol) of KH in 30
mL of a 1:1 mixture of pentane and diethyl ether at 0 °C was
added 1.71 g (4.21 mmol) of 8b. After 4 h of stirring, KH was
removed by filtration, and the filtrate was treated with 2 g of
NaOEt in 20 mL of EtOH. After 12 h of stirring, the reaction
mixture was extracted with pentane, washed with water, and
concentrated. The residue was purified by column chromatog-
raphy (silica gel/hexanes) to furnish 0.713 g (3.53 mmol, 84%)
of 10b (Z:E > 99:1) as a colorless liquid: IR (neat) 3312, 1919,
Ack n ow led gm en t. The financial support of the
National Science Foundation (CHE-9307994) to K.K.W.
and sabbatical leave and a Research Development Grant
of the Pennsylvania State University to P.D.S. are
gratefully acknowledged.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of 7b, 8a , 8b, 9a , 10a , 10b, 16, 18a , and 18b (18
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
1
1683 cm-1; H (CDCl3) δ 6.34 (1 H, d, J ) 10.8 Hz), 6.28 (1 H,
td, J ) 11.0 and 0.9 Hz), 5.26 (1 H, dd, J ) 9.3 and 2.7 Hz), 3.24
(1 H, dd, J ) 2.4 and 0.7 Hz), 1.19 (18 H, s); 13C (CDCl3) δ 208.72,
140.62, 123.15, 104.61, 93.63, 83.01, 80.86, 35.22, 32.12; MS m/ e
202 (M+), 187, 159, 145, 117, 91, 77.
J O9517149