Rearrangement of 2-Benzocycloammonium N-Methylides

Article abstract of DOI:10.1021/jo962226j

2-Methyl-2-[(trimethylsilyl)methyl]-2,3,4,5,6,7-hexahydro-1H-2- benzazoninium iodide (9), 2-methyl- 2-[(trimethylsilyl)methyl]-1,2,3,4,5,6-hexahydro-2-benzazocinium iodide (15), and 2-methyl-2-[(trimethylsilyl)methyl]-2,3,4,5-tetrahydro-1H-2-benzazepinium iodide (23) exist as mixtures of two stable conformational isomers (types A and B) in an aprotic solvent at room temperature. The corresponding conformational isomers of N-methylides 10A,B, 16A,B, and 24A,B were generated by fluoride ion-induced desilylation, and their rearrangement was investigated. Type A ylides gave [2,3] sigmatropic rearrangement products (isotoluenes) 11, 17, 18, and 27, while type B ylides gave Stevens rearrangement products 8, 20, and 29 via radical-cleavage and -recombination pathways.

Full text of DOI:10.1021/jo962226j

2544
J . Org. Chem. 1997, 62, 2544-2549
Rea r r a n gem en t of 2-Ben zocycloa m m on iu m N-Meth ylid es
Ken Narita, Naohiro Shirai, and Yoshiro Sato*
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku,
Nagoya 467, J apan
Received November 27, 1996X
2-Methyl-2-[(trimethylsilyl)methyl]-2,3,4,5,6,7-hexahydro-1H-2-benzazoninium iodide (9), 2-methyl-
2-[(trimethylsilyl)methyl]-1,2,3,4,5,6-hexahydro-2-benzazocinium iodide (15), and 2-methyl-2-[(tri-
methylsilyl)methyl]-2,3,4,5-tetrahydro-1H-2-benzazepinium iodide (23) exist as mixtures of two
stable conformational isomers (types A and B) in an aprotic solvent at room temperature. The
corresponding conformational isomers of N-methylides 10A,B, 16A,B, and 24A,B were generated
by fluoride ion-induced desilylation, and their rearrangement was investigated. Type A ylides gave
[2,3] sigmatropic rearrangement products (isotoluenes) 11, 17, 18, and 27, while type B ylides gave
Stevens rearrangement products 8, 20, and 29 via radical-cleavage and -recombination pathways.
Sch em e 1
In tr od u ction
Sommelet-Hauser rearrangement of R-phenylcycloam-
monium N-methylides is useful for three-carbon ring
enlargement of cyclic amines.1,2 For example, 2-methyl-
2,3,4,5,6,7-hexahydro-1H-2-benzazonine (2) was obtained
in high yield by the reaction of 1,1-dimethyl-2-phenylpi-
peridinium iodide (1) with sodium amide in liquid
ammonia.2a Hasiak and co-workers3 reported that simi-
lar treatment of 2,2-dimethyl-2,3,4,5,6,7-hexahydro-1H-
2-benzazoninium iodide (3) prepared from 2 gave a
mixture of five amines (4-8), as shown in Scheme 1. All
of these are isomerization products of three kinds of
ylides which were generated by R-deprotonation of 3.
Fluoride ion-induced desilylation of N-[1-(trimethyl-
silyl)alkyl]ammonium salts in an aprotic solvent is suit-
able for the selective formation of N-alkylides.4,5 Under
these reaction conditions, [2,3] sigmatropic rearrange-
ment products (isotoluenes) of the benzylammonium
ylides can be isolated at room temperature, especially in
the case of benzocycloammonium N-methylides.6 Treat-
ment of 2-methyl-2-[(trimethylsilyl)methyl]-2,3,4,5,6,7-
hexahydro-1H-2-benzazoninium iodide (9) with cesium
fluoride will selectively form ylide 10, which is a precur-
Sch em e 2
* Author to whom correspondence should be addressed. Fax: 81-
52-836-3459. E-mail: ysato@phar.nagoya-cu.ac.jp.
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) (a) Hesse, M. Ring Enlargement in Organic Chemistry; VCH:
Weinheim, 1991; p 83. (b) Marko´, I. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 3, p 913. (c) Bru¨ckner, R. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 6, p 873.
(2) (a) Lednicer, D.; Hauser, C. R. J . Am. Chem. Soc. 1957, 79, 4449.
(b) J ones, G. C.; Hauser, C. R. J . Org. Chem. 1962, 27, 3572.
(3) (a) Cotelle, P.; Hasiak, B.; Barbry, D.; Couturier, D. Chem. Lett.
1987, 1005. (b) Cotelle, P.; Barbry, D.; Hasiak, B.; Couturier, D. Chem.
Lett. 1989, 1113. (c) Barbry, D.; Spanneut, D.; Hasiak, B.; Couturier,
D. Tetrahedron 1991, 47, 47.
(4) Vedejs, E.; West, F. G. Chem. Rev. 1986, 86, 941.
(5) (a) Sato, Y. J . Synth. Org. Chem. J pn. 1992, 977. (b) Sato, Y.;
Shirai, N. Yakugaku Zasshi 1994, 114, 880.
(6) (a) Shirai, N.; Sumiya, F.; Sato, Y.; Hori, M. J . Org. Chem. 1989,
54, 836. (b) Okazaki, S.; Shirai, N.; Sato, Y. J . Org. Chem. 1990, 55,
334. (c) Sumiya, F.; Shirai, N.; Sato, Y. Chem. Pharm. Bull. 1991, 39,
36. (d) Kitano, T.; Shirai, N.; Sato, Y. Synthesis 1991, 996. (e) Kitano,
T.; Shirai, N.; Sato, Y. Chem. Pharm. Bull. 1992, 40, 768. (f) Kitano,
T.; Shirai, N.; Motoi, M.; Sato, Y. J . Chem. Soc., Perkin Trans. 1 1992,
2851. (g) Sato, Y.; Shirai, N.; Machida, Y.; Ito, E.; Yasui, T.; Kurono,
Y.; Hatano, K. J . Org. Chem. 1992, 57, 6711. (h) Sakuragi, A.; Shirai,
N.; Sato, Y.; Kurono, Y.; Hatano, K. J . Org. Chem. 1994, 59, 148. (i)
Maeda, Y.; Shirai, N.; Sato, Y. J . Chem. Soc., Perkin Trans. 1 1994,
393. (j) Koyama, S.; Shirai, N.; Sato, Y. Chem. Pharm. Bull. 1994, 42,
1331. (k) Kawanishi, N.; Shirai, N.; Sato, Y.; Hatano, K.; Kurono, Y.
J . Org. Chem. 1995, 60, 4272.
sor of 5 and 8 (Scheme 2). We report here the reaction
of 9 and the related eight- and seven-membered cycloam-
monium compounds 15 and 23 with cesium fluoride.
S0022-3263(96)02226-8 CCC: $14.00 © 1997 American Chemical Society

Rearrangement of Benzocycloammonium Methylides
J . Org. Chem., Vol. 62, No. 8, 1997 2545
F igu r e 1. 1H NMR spectra (400 MHz) of 23 at 170 °C in
(CD3)2SO (top), at room temperature in CDCl3 (middle), and
at -50 °C in CDCl3 (bottom).
Resu lts a n d Discu ssion
2-Methyl-2-[(trimethylsilyl)methyl]-2,3,4,5,6,7-hexahy-
dro-1H-2-benzazoninium iodide (9), 2-methyl-2-[(trimeth-
ylsilyl)methyl]-1,2,3,4,5,6-hexahydro-2-benzazocinium io-
dide (15), and 2-methyl-2-[(trimethylsilyl)methyl]-2,3,4,5-
tetrahydro-1H-2-benzazepinium iodide (23) were prepared
by quaternization of the corresponding cyclic amines 2,
14, and 22 with (trimethylsilyl)methyl triflate or iodo-
methane (Schemes 2-4). These all have sharp melting
points and gave good results in microcombustion analyses
(<(0.3%). Nevertheless, the signals in the 1H NMR
spectra (CDCl3, at 400 or 500 MHz) of 9 and 15 were
observed as doubled patterns of the expected proton
signals, except for the aromatic protons, from -50 to 170
°C. Although the signal of 23 was also doubled at -50
°C, similar to those of 9 and 15, it was much broader at
room temperature and became simpler at 170 °C, which
supports the structure of 23 (Figure 1).
These results suggest that 9 and 15 exist in solution
as mixtures of two stable conformational isomers, and
the isomers of 23 convert into each other slowly at room
temperature and quickly at 170 °C. We calculated the
optimized geometries of these compounds by MOPAC7
and found that two conformational isomers, type A and
type B, can exist as stable forms (Figure 2). The chemical
shifts of the (trimethylsilyl)methyl groups of type A will
be at a higher field than those of type B due to the dia-
magnetic anisotropy effect of the benzene rings, and the
relations of their N-methyl groups are reversed (Table 1).
Reaction of 9 with cesium fluoride in DMF for 0.5 h at
room temperature gave a mixture of 8 and a new product,
11 (Table 2, entry 1). Although chromatographic isola-
tion of 11 failed, the structure was considered to be
3-methyl-13-methylene-3-azabicyclo[7.3.1]trideca-9,11-di-
F igu r e 2. Optimized structures of conformational isomers
9A,B, 14A,B, and 23A,B (selected hydrogens are shown).
Ta ble 1. 1H NMR Ch em ica l Sh ifts of 9A,B, 15A,B, a n d
23A,B a t Room Tem p er a tu r e
1H NMR (CDCl3) δ
salt
ratioa
Me3Si
N-Me
N-CH2-Si
9A
9B
15A
15B
23Ab
23Bb
31
69
40
60
55
45
0.27
0.33
0.27
0.34
0.23
0.37
3.34
3.09
3.75
3.26
3.79
2.96
2.64, 3.39
3.27, 3.40
not assigned
not assigned
2.48, 3.13
1
ene (isotoluene) based on a comparison of the H NMR,
3.97, 4.07
13C NMR, and UV spectra of the mixture with those of
an authentic sample of 8. The product ratio did not
change after 24 h (entry 2). However, when the reaction
was repeated in the presence of DBU (2.5 mol equiv),8 5
was formed with decreasing yield of 11 (entry 3).
a
Determined from the proton ratio in the 1H NMR spectrum.
b
Measured at -50 °C.
Isotoluene 11 is a [2,3] sigmatropic rearrangement
product of ylide 10 and a precursor of 5. It is unlikely
that 8 was formed from 11 by a [1,3] shift because 11 is
stable at room temperature and the amount of 8 was not
affected by the addition of DBU.8 The ratio of 8 to 11
(71-73:29-27) is close to the ratio of 9B to 9A (69:31).
Isotoluene 11 may be formed exclusively from ylide 10A,
(7) MOPAC 93, revision 2: Stewart, J . J . P. J CPE P081, J CPE
Newsletter 1995, 6, 76. AM1: Dewar, M. J . S.; Zoebish, E. G.; Healy,
E. F.; Stewart, J . J . P. J . Am. Chem. Soc. 1985, 107, 3902.
(8) Tanaka, T.; Shirai, N.; Sugimori, J .; Sato, Y. J . Org. Chem. 1992,
57, 5034.

2546 J . Org. Chem., Vol. 62, No. 8, 1997
Ta ble 2. Rea ction of 9, 15, a n d 23 w ith CsF in DMF a t Room Tem p er a tu r e
Narita et al.
amines (ratio)a
reaction
time, h
total amine
yield, %
ammonium salt
yield, %
entry salt
additive
Sommelet-Hauser Stevens isotoluene spiro compd other
1
2
3
4
5
6
9
9
9
15
15
23
0.5
24
24
24
24
86
82
79
46
40
23
8 (71)
8 (73)
8 (70)
20 (48)
20 (47)
29 (9)
11 (29)
11 (27)
11 (16)
17 (38)
17 (40)
26 (0)
12 (0)
12 (0)
12 (0)
18 (14)
18 (13)
27 (84)
DBU
DBU
5 (14)
21 (32)
21 (30)
30 (54)
24
25 (7)
a
Determined from the proton ratios in the 1H NMR spectra.
Sch em e 3
spectra. The strained structure of 17 was supported by
a hypsochromic shift of the UV spectrum compared with
the absorption maximum of the conjugated triene chro-
mophore6 (17, λmax(ether) 285 nm; 18, λmax(ether) 303 nm).
Compounds 17 and 18 may be formed competitively
from ylide 16A, which is generated from 15A, via either
of two sigmatropic rearrangement pathways a and b.
Compound 20 is a Stevens rearrangement product from
ylide 16B in which the ylide anion is located far from
the benzene ring. Some 18 and 20 would also be formed
from 17 via a [1,5] or [1,7] sigmatropic shift, respectively,
because the ratio of 17:18:20 (38:14:48) changed to 11:
1
29:60 when the H NMR spectrum was measured again
after 3 days. Ammonium salt 21 may be formed by
protonation of 16 during the reaction. Thus, the ratio of
both 17 and 18 (52) to 20 (48) does not agree with the
ratio of 15A to 15B (40:60). Aromatization of 17 to a
Sommelet-Hauser rearrangement product did not occur
when the reaction was carried out in the presence of DBU
(entry 5).
In the reaction of 23 with cesium fluoride, 3-methyl-
11-methylene-3-azaspiro[5.5]undeca-7,9-diene (27) was
obtained as the main product along with small amounts
of 2-methyl-2,3,4,5-tetrahydro-1H-2-benzazepine (25) and
3-methyl-1,2,3,4,5,6-hexahydro-1H-3-benzazocine (29) from
the ethereal extract of the reaction mixture (Scheme 4).
The total amine yield was low, and the expected isotolu-
ene compound 26 was absent, whereas 2,2-dimethyl-
2,3,4,5-tetrahydro-1H-2-benzazepinium iodide (30) was
isolated in a yield of 54% from the aqueous layer after
ether extraction (Table 2, entry 6). Spiro compound 27
may be formed from ylide 24A, and Stevens product 29
and demethylene product 25 are generated from ylide
24B.
Sigmatropic rearrangement in the seven-membered
ring (from 24A to 27) requires a higher ring tension in
the transition state than that in the eight-membered ring
(from 16A to 17 or 18) or the nine-membered ring (from
10A to 11). Conversion between 24A and 24B may also
be possible, similar to the equilibrium between 23A and
23B. This would delay the rearrangement and result in
a lower yield of the amines and a higher yield of 30 by
protonation.
which is generated from 9A, and its ylide anion is located
near the benzene ring. Stevens product 8 may be formed
from ylide 10B, which is generated from 9B, via a
diradical intermediate (13) because the ylide anion is
located far from the benzene ring.
In the reaction of 15 with cesium fluoride, a mixture
of 3-methyl-12-methylene-3-azabicyclo[6.3.1]dodeca-8,10-
diene (17, isotoluene), 8-methyl-5-methylene-8-azaspiro-
[5.6]dodeca-1,3-diene (18, spiro compound), and 3-methyl-
2,3,4,5,6,7-hexahydro-1H-3-benzazonine (20, Stevens
rearrangement product) was obtained from the ethereal
extract of the reaction mixture, and 2,2-dimethyl-
1,2,3,4,5,6-hexahydro-2-benzazocinium iodide (21) was
isolated from the aqueous layer after ether extraction
(Scheme 3, Table 2, entry 4). Although isolation of pure
18 was difficult because of poor separation from 20 on
an HPLC column, structural assignment of the products
was achieved by comparison of the 1H NMR and UV
Thus, [2,3] sigmatropic rearrangement of benzocy-
cloammonium N-methylides 10, 16, and 24 occurs ex-
clusively on type A ylides, and their ring sizes affect the
reaction points on the benzene rings (paths a and b).
Thus, on nine-membered ylide 10A, rearrangement oc-
curs selectively at the 11-position (path a) to give iso-
toluene compound 11; on eight-membered ylide 16A,
paths a and b compete at the 6a- and 10-positions to
give isotoluene 17 and spiro compound 18; on seven-
membered ylide 24A, only one route (path b) is allowed
at the 5a-position to give spiro compound 27.

Rearrangement of Benzocycloammonium Methylides
J . Org. Chem., Vol. 62, No. 8, 1997 2547
Sch em e 4
spectra were recorded at 270, 400, or 500 MHz. Mass spectra
were obtained using EI ionization (70 eV). Aluminum oxide
(Merck; aluminum oxide F254 (type E), 0.25 mm, 20 × 20 cm)
was used for preparative TLC. All melting points and boiling
points are uncorrected.
2-Meth yl-2-[(tr im eth ylsilyl)m eth yl]-2,3,4,5,6,7-h exa h y-
d r o-1H-2-ben za zon in iu m Iod id e (9). A solution of 2-meth-
yl-2,3,4,5,6,7-hexahydro-1H-2-benzazonine2a (2) (7.1 g, 38 mmol)
and (trimethylsilyl)methyl triflate (15.0 g, 64 mmol) in CH2-
Cl2 (40 mL) was heated at reflux for 5 days. The solvent was
evaporated under reduced pressure, and the residue was added
to a mixture of CHCl3 (30 mL) and saturated aqueous KI (30
mL). The precipitated yellow solid was separated and recrys-
tallized from MeOH-Et2O to give 9 (14.0 g, 92%): mp 202-
204 °C; IR (Nujol) 1487, 1256, 1032, 850 cm-1; two conforma-
1
tional isomers (9A,B) were observed in the H NMR spectrum
1
(9A:9B, 31:69); H NMR (CDCl3) δ for 9A 0.27 (s, 9 H), 2.64
(d, 1 H, J ) 14.6 Hz), 3.34 (s, 3 H), 3.39 (d, 1 H, J ) 14.6 Hz),
4.47 (1 H, J ) 13.4 Hz), 5.02 (d, 1 H, J ) 13.4 Hz), 7.50 (d, 1
H, J ) 7.9 Hz), for 9B 0.33 (s, 9 H), 3.09 (s, 3 H), 3.27 (d, 1 H,
J ) 15.3 Hz), 3.40 (d, 1 H, J ) 15.3 Hz), 4.41 (1 H, J ) 14.0
Hz), 4.97 (d, 1 H, J ) 14.0 Hz), 7.45 (d, 1 H, J ) 7.9 Hz), other
signals overlapped 1.41-1.50 (1 H), 1.51-1.63 (1 H), 1.76-
1.94 (2 H), 2.13-2.34 (2 H), 2.60-2.78 (2 H), 2.84-2.92 (1 H),
3.19-3.23 (1 H), 7.22-7.25 (2 H), 7.32-7.41 (1 H). Anal.
Calcd for C17H30NISi: C, 50.62; H, 7.49; N, 3.47. Found: C,
50.41; H, 7.44; N, 3.66.
Rea ction of 9 w ith CsF . A. Ammonium salt 9 (813 mg,
2 mmol) and 4A molecular sieves (2.0 g) were placed in a 30-
mL flask equipped with a magnetic stirrer and a septum, and
a test tube was connected to the flask by a short piece of bent
glass tubing. CsF (760 mg, 5 mmol) was placed in the test
tube. The apparatus was dried under reduced pressure and
flushed with N2. DMF (20 mL) was added to the flask with a
syringe. After stirring for 30 min, CsF was added to the
mixture from the test tube. The mixture was stirred for 0.5
or 24 h at room temperature, poured into 1% NaHCO3 (200
mL), and extracted with ether (3 × 100 mL). The ethereal
extract was washed with water (3 × 100 mL) and saturated
aqueous NaCl (100 mL), dried (MgSO4), and concentrated
under reduced pressure to give a mixture (348 or 331 mg) of
3-methyl-1,2,3,4,5,6,7,8-octahydro-3-benzazecine3c (8) and
3-methyl-13-methylene-3-azabicyclo[7.3.1]trideca-9,11-diene (11).
Isolation of pure samples by chromatography was difficult due
to insufficient separation. The ratio was determined on the
basis of the proton ratios in the 1H NMR spectra of the ethereal
extracts. The results are summarized in Table 2.
F igu r e 3. Reaction coordinate of the [2,3] sigmatropic rear-
rangement of ylides 10A, 16A, and 24A calculated by the AM1
method.
We calculated the reaction coordinate of the [2,3]
sigmatropic rearrangement of 10A, 16A, and 24A by the
AM1 method. The energies of the respective transition
structures TS1 and TS2 in paths a and b are shown in
Figure 3. While path a to 11 is more favorable than path
b to 12 in the reaction of 10A, paths a and b might be
comparable in the reaction of 16A to 17 and 18. Al-
though path b to 27 is more favorable than path a to 26
in the reaction of 24A, both activation energies are high,
compared with the reactions of 10A and 16A. This may
cause a low yield of 27.
Exp er im en ta l Section
Mixture of 8 and 11: UV λmax(ether) 320 nm; 1H NMR
(CDCl3) δ for 11 2.17 (s, 3 H), 4.92 (s, 1 H), 5.20 (s, 1 H), 5.66
(d, 1 H, J ) 5.1 Hz), 5.77 (dd, 1 H, J ) 5.5, 5.1 Hz), 5.94 (dd,
1 H, J ) 9.5, 5.5 Hz), for 8 2.04 (s, 3 H), other signals
Dichloromethane was distilled from CaH2. DMF was dried
by distillation under reduced pressure from BaO. CsF was
dried over P2O5 at 180 °C under reduced pressure. 1H NMR

2548 J . Org. Chem., Vol. 62, No. 8, 1997
Narita et al.
overlapped; 13C NMR (CDCl3) δ for 11 20.5 (CH2), 22.2 (CH2),
27.0 (CH2), 29.7 (CH2), 30.3 (CH), 33.3 (CH2), 45.8 (CH3), 56.6
(CH2), 113.3 (CH2), 123.6 (CH), 124.1 (CH), 130.5 (CH), 137.3
(C), 147.4 (C). Anal. Calcd for C14H21N: C, 82.70; H, 10.41;
N, 6.89. Found: C, 82.29; H, 10.56; N, 6.93.
B. In a manner similar to that described above, 9 (813 mg,
2 mmol), 4A molecular sieves (2.0 g), and CsF (760 mg, 5 mmol)
were placed in an apparatus and dried. DMF (20 mL) and
DBU (760 mg, 5 mmol) were added to the flask with syringes.
After the mixture stirred for 30 min, CsF was added to the
solution from the test tube. The mixture was stirred for 24 h
at room temperature and worked up to give a mixture (322
mg) of 3,13-dimethyl-3-azabicyclo[7.3.1]trideca-1,9,11-triene
(5,2-aza(7)metacyclophane3c) (5), 8, and 11. Compound 5 was
separated by preparative aluminum oxide TLC with hexane.
The ratio of 5, 8, and 11 was determined based on the proton
ratios in the 1H NMR spectrum of the mixture.
B. In a manner similar to that described above, 15 (390
mg, 1 mmol), 4A molecular sieves (1.0 g), and CsF (380 mg,
2.5 mmol) were placed in a flask. DMF (10 mL), DBU (380
mg, 2.5 mmol), and CsF (380 mg, 2.5 mmol) were successively
added, and the mixture was treated as described above. The
results are shown in Table 2 (entry 5).
2-Meth yl-2-[(tr im eth ylsilyl)m eth yl]-2,3,4,5-tetr a h yd r o-
1H-2-ben za zep in iu m Iod id e (23). A mixture of 2,3,4,5-
tetrahydro-1H-2-benzazepine10 (4.0 g, 27 mmol), (chloromethyl)-
trimethylsilane (8.0 g, 66 mmol), and K2CO3 (4.0 g, 29 mmol)
in acetonitrile (100 mL) was heated at reflux for 24 h. The
mixture was poured into water (300 mL) and extracted with
ether (3 × 100 mL). The extract was washed with water, dried
(MgSO4), and concentrated under reduced pressure. The
residue was chromatographed on aluminum oxide (hexane-
Et2O) to give 2-[(trimethylsilyl)methyl]-2,3,4,5-tetrahydro-1H-
2-benzazepine (22) (5.5 g, 87%): IR (film) 2928, 1453, 1248,
855, 754 cm-1; 1H NMR (CDCl3) δ 0.06 (s, 9 H), 1.69-1.74 (m,
2 H), 1.91 (s, 2 H), 2.87-2.90 (br t, 2 H, J ) 5.6 Hz), 3.10-
3.13 (br t, 2 H, J ) 5.2 Hz), 3.90 (s, 2 H), 7.09-7.18 (m, 4 H).
Anal. Calcd for C14H23NSi: C, 72.04; H, 9.93; N, 6.00.
Found: C, 71.89; H, 10.03; N, 5.84.
2-Meth yl-2-[(tr im eth ylsilyl)m eth yl]-1,2,3,4,5,6-h exa h y-
d r o-2-ben za zocin iu m Iod id e (15). A solution of 2-methyl-
1,2,3,4,5,6-hexahydro-2-benzazocine2 (14) (2.6 g, 15 mmol) and
(trimethylsilyl)methyl triflate (5.1 g, 20 mmol) in CH2Cl2 (25
mL) was heated at reflux for 4 days. The solvent was
evaporated under reduced pressure, and the residue was added
to a mixture of CHCl3 (15 mL) and saturated aqueous KI (15
mL). The mixture was stirred at room temperature for 1 h.
The organic layer was separated, and the aqueous layer was
extracted with CHCl3 (3 × 5 mL). The combined extract was
dried (MgSO4) and concentrated. The residue was recrystal-
lized from MeOH-Et2O to give 15 (4.7 g, 81%): mp 224-225
°C; IR (Nujol) 1425, 1256, 1032, 858, 770, 708 cm-1; two
conformational isomers were observed in the 1H NMR spec-
A solution of 22 (1.9 g, 8.2 mmol) and iodomethane (10.1 g,
71 mmol) in acetonitrile (30 mL) was stirred at room temper-
ature for 2 h. The solvent was evaporated under reduced
pressure, and the residue was recrystallized from acetone to
give 23 (2.8 g, 92%): mp 180-182 °C; IR (Nujol) 1256, 984,
914, 764 cm-1; two conformational isomers were observed in
1
the 1H NMR spectrum at -50 °C (23A:23B, 55:45); H NMR
(CDCl3, at -50 °C) δ for 23A 0.23 (s, 9 H), 2.48 (d, 1 H, J )
15.4 Hz), 3.13 (d, 1 H, J ) 15.4 Hz), 3.79 (s, 3 H), 4.54-4.60
(m, 1 H), 5.03 (d, 1 H, J ) 12.8 Hz), 5.36 (d, 1 H, J ) 12.8 Hz),
7.76 (d, 1 H, J ) 7.3 Hz), for 23B 0.37 (s, 9 H), 2.96 (s, 3 H),
3.97 and 4.07 (AB-q, 2 H, J ) 14.5 Hz), 4.20-4.26 (m, 1 H),
4.88 (d, 1 H, J ) 13.7 Hz), 5.36 (d, 1 H, J ) 13.7 Hz), 7.69 (d,
1 H, J ) 7.0 Hz), other signals overlapped 1.83-2.01 (1 H),
2.19-2.24 (1 H), 2.85-2.96 (1 H), 3.34-3.54 (1 H, 2 H), 3.79-
3.85 (1 H), 7.20-7.38 (m, 3 H); 1H NMR (DMSO-d6, at 170 °C)
δ 0.25 (s, 9 H), 2.03 (br s, 2 H), 2.92-3.03 (m, 2 H), 2.95
(s, 3 H), 3.06 and 3.11 (AB-q, 2 H, J ) 15.0 Hz), 3.60 (t, 2 H,
J ) 5.7 Hz), 4.58 and 4.71 (AB-q, 2 H, J ) 13.6 Hz), 7.26 (t, 2
H, J ) 7.7 Hz), 7.35 (m, 2 H). Anal. Calcd for C15H26NISi:
C, 47.80; H, 6.98; N, 3.73. Found: C, 47.58; H, 6.85; N,
3.90.
1
trum (15A:15B, 40:60); H NMR (CDCl3) δ for 15A 0.27 (s, 9
H), 3.75 (s, 3 H), 7.65 (d, 1 H, J ) 7.3 Hz), for 15B 0.34 (s, 9
H), 3.26 (s, 3 H), 7.61 (d, 1 H, J ) 7.3 Hz), other signals could
not be assigned because the peaks were broad. Anal. Calcd
for C16H28NISi: C, 49.35; H, 7.25; N, 3.60. Found: C, 49.16;
H, 7.32; N, 3.33.
Rea ction of 15 w ith CsF . A. In a manner similar to that
described for 9, 15 (390 mg, 1 mmol), 4A molecular sieves (1.0
g), and CsF (380 mg, 2.5 mmol) in DMF (10 mL) were treated
to give a mixture (87 mg) of 3-methyl-12-methylene-3-azabicyclo-
[6.3.1]dodeca-8,10-diene (17), 8-methyl-5-methylene-8-azaspiro-
[5.6]dodeca-1,3-diene (18), and 3-methyl-2,3,4,5,6,7-hexahydro-
1H-3-benzazonine (20). The mixture was chromatographed on
an HPLC column (Nakarai Cosmosil 5NH2, 10 × 250 mm).
The mobile phase was initially a mixture of 0.5% Et2O in
hexane at a flow rate of 5 mL/min and was increased linearly
to 3% in 9 min and then to 10% in 2 min. Fractions of 17
(6-7 min), a mixture of 18 and 20 (9-10 min), and 20 (10-11
min) were collected. The product ratio was determined based
Rea ction of 23 w ith CsF . In a manner similar to that
described for 9, a mixture of 23 (375 mg, 1 mmol), 4A molecular
sieves (1.0 g), and CsF (380 mg, 2.5 mmol) in DMF (10 mL)
was treated to give a mixture (40 mg) of 3-methyl-11-meth-
ylene-3-azaspiro[5.5]undeca-7,9-diene (27), 3-methyl-1,2,3,4,5,6-
hexahydro-1H-3-benzazocine (29), and 2-methyl-2,3,4,5-tet-
rahydro-1H-2-benzazepine (25). Samples were isolated by
preparative TLC (aluminum oxide, Et2O-hexane, 1:3). The
ratio was determined based on the proton ratios in the 1H
NMR spectrum of the mixture.
27: 1H NMR (CDCl3) δ 1.25-1.33 (m, 1 H), 1.55-1.60 (m,
1 H), 1.75-1.78 (m, 1 H), 1.85 (d, 1 H, J ) 11.0 Hz), 1.90-
2.00 (m, 2 H), 2.20 (s, 3 H), 2.75 (d, 1 H, J ) 11.0 Hz), 2.84-
2.85 (m, 1 H), 5.07 (s, 1 H), 5.13 (s, 1 H), 5.80 (ddt, 1 H, J )
9.2, 5.5, 1.2 Hz), 5.96 (ddd, 1 H, J ) 9.8, 5.5, 1.2 Hz), 6.11 (d,
1 H, J ) 9.2 Hz), 6.36 (d, 1 H, J ) 9.8 Hz); MS m/ z 175 (78,
M+), 132 (42), 117 (99), 70 (100), 57 (23); exact mass calcd for
C12H17N 175.1362, found 175.1396.
1
on the proton ratios in the H NMR spectrum of the mixture.
17: 1H NMR (CDCl3) δ 1.35 (m, 1 H), 1.44-1.60 (m, 2 H),
1.86-2.00 (m, 2 H), 2.20 (m, 2 H), 2.26 (s, 3 H), 2.42 (dt, 1 H,
J ) 12.5, 4.0 Hz), 2.58 (dd, 1 H, J ) 13.4, 8.1 Hz), 2.73 (m, 2
H), 4.94 (s, 1 H), 5.06 (s, 1 H), 5.66 (d, 1 H, J ) 2.6 Hz), 5.93
(m, 2 H); MS m/ z 189 (98, M+), 149 (68), 105 (92), 84 (100);
UV λmax(ether) 285 nm; exact mass calcd for C13H19N 189.1519,
found 189.1514.
18: 1H NMR (CDCl3) δ 1.66 (m, 4 H), 1.77 (m, 2 H), 2.31 (s,
3 H), 2.46 and 2.50 (AB-q, 2 H, J ) 14.1 Hz), 2.50-2.62 (m, 2
H), 5.02 (s, 1 H), 5.21 (s, 1 H), 5.77 (dd, 1 H, J ) 9.0, 5.8 Hz),
5.90 (dd, 1 H, J ) 9.6, 5.8 Hz), 6.05 (d, 1 H, J ) 9.6 Hz), 6.07
(d, 1 H, J ) 9.6 Hz); UV λmax(ether) 303 nm.
29: 1H NMR (CDCl3) δ 1.67-1.72 (m, 2 H), 2.29 (t, 2 H, J
) 5.5 Hz), 2.38 (s, 3 H), 2.73 (dd, 2 H, J ) 6.1, 4.9 Hz), 2.80
(dd, 2 H, J ) 6.7, 6.1 Hz), 2.84 (dd, 2 H, J ) 6.1, 4.9 Hz), 7.09-
7.16 (m, 4 H); MS m/ z 175 (100, M+), 132 (39), 117 (80), 70
(99), 57 (21); exact mass calcd for C12H17N 175.1362, found
175.1388.
20: 1H NMR (CDCl3) δ 1.14 (m, 2 H), 1.77 (m, 2 H), 2.35 (s,
3 H), 2.44 (t, 2 H, J ) 5.8 Hz), 2.54 (m, 2 H), 2.78 (m, 2 H),
3.06 (t, 2 H, J ) 6.2 Hz), 7.00-7.10 (m, 4 H); MS m/ z 189 (95,
M+), 174 (15), 146 (30), 105 (41), 84 (100), 71 (43); exact mass
calcd for C13H19N 189.1519, found 189.1522.
25: 1H NMR (CDCl3) δ 1.74-1.78 (m, 2 H), 2.31 (s, 3 H),
2.88 (t, 2 H, J ) 5.5 Hz), 3.01 (dd, 2 H, J ) 5.5, 4.9 Hz), 3.79
(s, 2 H) 7.10-7.15 (m, 4 H). MS m/ z 161 (100, M+), 160 (96),
The aqueous layer after ether extraction was evaporated
under reduced pressure, and the residue was extracted with
CHCl3. Evaporation of the solvent gave 2,2-dimethyl-1,2,3,4,5,6-
hexahydro-2-benzazocinium iodide9 (21) (100 mg, 32%).
146 (36), 132 (35), 117 (72); exact mass calcd for C11H15
161.1206, found 161.1200.
N
(9) Elmasmodi, A.; Barbry, D.; Hasiak, B.; Couturier, D. Synthesis
1987, 727.
(10) Meyers, A. I.; Hutchings, R. H. Tetrahedron 1993, 49, 1807.

Rearrangement of Benzocycloammonium Methylides
J . Org. Chem., Vol. 62, No. 8, 1997 2549
The aqueous layer after ether extraction was concentrated
under reduced pressure and extracted with CHCl3. Evapora-
tion of the solvent gave 2,2-dimethyl-2,3,4,5-tetrahydro-1H-
2-benzazepinium iodide (30; 175 mg, 58%): 1H NMR (CDCl3)
δ 7.19 (d, 1 H, J ) 7.3 Hz), 7.25 (ddd, 1 H, J ) 7.9, 6.7, 1.2
Hz), 7.33 (ddd, 1 H, J ) 7.9, 6.7, 1.2 Hz), 7.72 (d, 1 H, J ) 6.7
Hz), other signals were broad. Anal. Calcd for C12H18NI: C,
47.54; H, 5.98; N, 4.62. Found: C, 47.33; H, 6.18; N, 4.54.
No. 08672438) from the Ministry of Education, Science
and Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Coordinates and
energies for structures in Figures 2 and 3 optimized at the
AM1 level (42 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.
Ack n ow led gm en t. This work was supported by
Grants-in-Aid for Scientific Research (No. 08672437 and
J O962226J