Michael addition-elimination mechanism for nucleophilic substitution reaction of cycloalkenyl iodonium salts and selectivity of 1,2-hydrogen shift in cycloalkylidene intermediate

Article abstract of DOI:10.1021/jo049218k

(Chemical Equation Presented) Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine β-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via λ³-iodane) and elimination-addition (via cyclohexyne) pathways.

Full text of DOI:10.1021/jo049218k

Michael Addition-Elimination Mechanism for Nucleophilic
Substitution Reaction of Cycloalkenyl Iodonium Salts and
Selectivity of 1,2-Hydrogen Shift in Cycloalkylidene Intermediate
Morifumi Fujita,* Wan Hyeok Kim, Koji Fujiwara, and Tadashi Okuyama*
Contribution from the Graduate School of Material Science, Himeji Institute of Technology,
University of Hyogo, Kohto, Kamigori, Hyogo 678-1297, Japan
fuji@sci.u-hyogo.ac.jp; okuyama@sci.u-hyogo.ac.jp
Received May 10, 2004
Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give
cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show
that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt,
followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene
intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine
â-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael
reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in
chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via λ3-iodane)
and elimination-addition (via cyclohexyne) pathways.
Introduction
reactivity at the R position. The cycloalkenyl structure
of the substrate excludes the possibility of R-elimination
and in-plane SN2 substitution (SNVσ)1m and may enable
observation of reactions at the â position. Thus, â-elim-
ination was observed with cyclohex-1-enyl iodonium salts
under mild basic conditions:8 the resulting cyclohexyne
readily undergoes nucleophilic attack, leading to overall
nucleophilic substitution via an elimination-addition
Alkenyl(phenyl)iodonium salts1 are highly electron-
deficient vinyl compounds with a positively charged
iodonio group, which is highly nucleofugal2 and respon-
sible for the high reactivity.1 Simple alk-1-enyl salts
undergo very facile R-elimination3,4 and SN2-type substi-
tution5-7 at the R position, but possible reactions at the
â position are not readily observed due to the higher
* To whom correspondence should be addressed. Phone: (81)791-
58-0169. Fax: (81)791-58-0115.
(3) (a) Ochiai, M.; Takaoka, Y.; Nagao, Y. J. Am. Chem. Soc. 1988,
110, 6565-6566. (b) Ochiai, M.; Uemura, K.; Masaki, Y. J. Am. Chem.
Soc. 1993, 115, 2528-2529. (c) Ochiai, M.; Sueda, T.; Uemura, K.;
Masaki, Y. J. Org. Chem. 1995, 60, 2624-2626. (d) Sueda, T.; Nagaoka,
T.; Goto, S.; Ochiai, M. J. Am. Chem. Soc. 1996, 118, 10141-10149.
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10.1021/jo049218k CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/14/2004
480
J. Org. Chem. 2005, 70, 480-488

Michael Reaction of Cycloalkenyl Iodonium Salts
SCHEME 1. Mechanisms for Reactions of
Cyclohexenyl Iodonium Salt with Nucleophiles
of the ground-state orbital concerned and the bonding
orbital of the migrating hydrogen14,15 and is also affected
by electronic16 and steric effects of adjacent groups. These
factors determine the migration origin if there are two
possibilities. In the Michael AE reaction of the iodonium
salts, the selectivity of the hydrogen migration of the
2-substituted cycloalkylidene intermediate determines
the product selectivity.
The Michael addition to vinylic compounds activated
with a positively charged onium group takes place to give
ylides.17,18 For vinyl iodonium salts, the Michael reaction
of 2-haloalk-1-enyliodonium salts with sulfinate is fol-
lowed by elimination of the halide to give the 2-sulfonyl-
alk-1-enyl iodonium salt.18 The Michael reactions are
more often observed for alkynyliodonium salts, which
lead to alkylidenecarbene intermediates by ensuing loss
of the iodonio group from incipient ylides.19 The intramo-
lecular insertion or migration of the carbene intermediate
results in cyclopentenylation or alkynylation.19 A similar
reaction was observed with alkynylbismuthonium salts,20
but the Michael reaction of alkynylselenonium salts
resulted in formation of ylides.21
Results
Reactions of cyclohex-1-enyl(phenyl)iodonium tetraflu-
oroborates (1a) and 4-tert-butyl derivative 1b with tet-
(EA) mechanism. Another possible reaction of nucleophile
at the â position is the Michael addition, but it has not
been observed probably due to the remaining competition
at the R position, out-of-plane substitution (SNVπ),1m or
the ligand coupling9-11 via a hypervalent iodine(III)
adduct (λ3-iodane).1 SN1-type solvolysis is also possible
for this secondary vinylic iodonium salt.2 In further
examinations we have now found and will present in this
paper that the Michael addition-elimination (AE) does
take place during the reaction of cyclohexenyl and
cyclopentenyl iodonium salts with cyanide ion in chloro-
form.12 Possible reaction pathways for the nucleophilic/
basic reactions of cyclohexenyliodonium salt are sum-
marized in Scheme 1 showing typical reaction conditions.
The Michael addition is followed by elimination of the
iodonio group to give a substituted cycloalkylidene in-
termediate in the last reaction. Small ring cycloalkylidene
is known to be a singlet carbene and undergoes 1,2-
hydrogen shift to give cycloalkene.13 Ease of the hydrogen
shift in a singlet carbene is controlled by the orientation
(14) (a) Press, L. S.; Shechter, H. J. Am. Chem. Soc. 1979, 101, 509-
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1985, 26, 1651-1654. (d) Tomioka, H.; Sugiura, T.; Masumoto, Y.;
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(a) Phosphonium salts: McIntosh, J. M.; Goodbrand, H. B.; Masse, G.
M. J. Org. Chem. 1974, 39, 202-206. Minami, T.; Sako, H.; Ikehira,
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G.; O’Connor, B. Tetrahedron Lett. 1985, 26, 1799-1802. Posner, G.
H.; Lu, S.-B. J. Am. Chem. Soc. 1985, 107, 1424-1426. Clerici, F.;
Gelmi, M. L.; Pocar, D.; Rondena, R. Tetrahedron 1995, 51, 9985-
9994. (b) Arsonium salts: Manske, R.; Gosselck, J. Tetrahedron 1975,
31, 2121-2124. Nesmeyanov, N. A.; Nikul’shina, V. V.; Kharitonov,
V. G.; Petrovskii, P. V.; Reutov, O. A. Izv. Akad. Nauk USSR 1988,
908-910. (c) Selenonium salts: Watanabe, Y.; Ueno, Y.; Toru, T. Bull.
Chem. Soc. Jpn. 1993, 66, 2042-2047. (d) Sulfonium salts: Knipe, A.
C. In The Chemistry of the Sulphonium Group, Part 1; Stirling, C. J.
M., Ed.; John Wiley & Sons: Chichester, 1981; Chapter 12.
(18) (a) Ochiai, M.; Kitagawa, Y.; Toyonari, M.; Uemura, K.; Oshima,
K.; Shiro, M. J. Org. Chem. 1997, 62, 8001-8008. (b) Ochiai, M.;
Kitagawa, Y.; Toyonari, M.; Uemura, K. Tetrahedron Lett. 1994, 35,
9407-9408. (c) Umemoto, T.; Gotoh, Y. Bull. Chem. Soc. Jpn. 1987,
60, 3307-3313.
(8) (a) Fujita, M.; Sakanishi, Y.; Kim, W. H.; Okuyama, T. Chem.
Lett. 2002, 908-909. (b) Fujita, M.; Kim, W. H.; Sakanishi, Y.;
Fujiwara, K.; Hirayama, S.; Okuyama, T.; Ohki, Y.; Tatsumi, K.;
Yoshioka, Y. J. Am. Chem. Soc. 2004, 126, 7548-7558.
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1997, 955-956. (b) Ochiai, M.; Shu, T.; Nagaoka, T.; Kitagawa, Y. J.
Org. Chem. 1997, 62, 2130-2138. (c) Okuyama, T.; Sato, K.; Ochiai,
M. Bull. Chem. Soc. Jpn. 2000, 73, 2341-2349. (d) Mart´ı-Santamar´ıa,
S.; Carroll, M. A.; Carroll, C. M.; Carter, C. D.; Pike, V. W.; Rzepa, H.
S.; Widdowson, D. A. Chem. Commun. 2000, 649-650.
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(11) For ligand exchange with metal complex, see: (a) Ochiai, M.;
Sumi, K.; Takaoka, Y.; Kunishima, M.; Nagao, Y.; Shiro, M.; Fujita,
E. Tetrahedron 1988, 44, 4095-4112. (b) Moriarty, R. M.; Epa, W. R.;
Awasthi, A. K. J. Am. Chem. Soc. 1991, 113, 6315-6317. (c) Moriarty,
R. M.; Epa, W. R. Tetrahedron Lett. 1992, 33, 4095-4098. (d) Hinkle,
R. J.; Poulter, G. T.; Stang, P. J. J. Am. Chem. Soc. 1993, 115, 11626-
11627. (e) Ryan, J. H.; Stang, P. J. J. Org. Chem. 1996, 61, 6162-
6165. (f) Kang, S.-K.; Lee, H.-W.; Jang, S.-B.; Ho, P.-S. J. Org. Chem.
1996, 61, 4720-4724. (g) Hinkle, R. J.; Leri, A. C.; David, G. A.; Erwin,
W. M. Org. Lett. 2000, 2, 1521-1523.
(19) (a) Ochiai, M.; Kunishima, M.; Nagao, Y.; Fuji, K.; Shiro, M.;
Fujita, E. J. Am. Chem. Soc. 1986, 108, 8281-8283. (b) Ochiai, M.;
Kunishima, M.; Tani, S.; Nagao, Y. J. Am. Chem. Soc. 1991, 113, 3135-
3142. (c) Kitamura, T.; Zheng, L.; Taniguchi, H.; Sakurai, M.; Tanaka,
R. Tetrahedron Lett. 1993, 34, 4055-4058. (d) Williamson, B. L.;
Tykwinski, R. R.; Stang, P. J. J. Am. Chem. Soc. 1994, 116, 93-98.
(e) Stang, P. J. In Modern Acetylene Chemistry; Stang, P. J., Diederich,
F., Eds.; VCH: Weinheim, 1995; pp 67-98.
(20) Matano, Y. Chem. Commun. 2000, 2233-2234.
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583-593.
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J. Org. Chem, Vol. 70, No. 2, 2005 481

Fujita et al.
ArCN
TABLE 1. Reaction of 1 with Bu4NCN in Chloroforma
yield (%)
subst.
[CN-] (M)
[MeOH] (M)
2
3
4
5
6
ArI
ArH
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b′
0.01
0.10
0.01d
0.01
0.01
0.01
0.01
0.01
0.10
0.01d
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0
12
15
17
9
18
16
25
54
65
64
73
5
b
25
33
17
4
c
c
64
62
75
80
90
85
89
64
49
70
75
70
75
68
91
83
81
f
c
c
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
c
0
b
b
0
c
c
0.08
0.16
0.25
0.82
0
b
c
c
5
b
3
c
c
3
b
2
c
c
<1
18
14
25
19
19
10
9
b
<1
25
36
19
6
c
c
12
7
6
19e
c
0
0
3
7
8
18
30
30
37
37
49
49
51
16
4
c
0.04
0.08
0.12
0.16
0.25
0.82
2.47
0
10
10
12
13
17
19
24
f
2
c
5
2
c
4
1
c
3
3
c
8
2
<1
17
3
1
c
2
<1
2
c
<1
20
c
10
14
a [1] ) 3 mM, at 60 °C for 1 h. b 4a is identical with 3a. c The yield was not determined by GC because of high volatility or for other
reasons. d A neutral salt Bu4NBF4 (0.09 M) was added. e Determined by 1H NMR in CDCl3. f GC peaks of 3 and ArI are overlapped.
TABLE 2. Reaction of 1 with Cyanide in Chloroform
Containing Crown Ethera
rabutylammonium cyanide were carried out in chloro-
form at 60 °C. The products include three cyanocyclo-
hexenes 2-4 (3a and 4a are identical where R ) H),
iodocyclohexene 5, iodobenzene, benzene, and a small
amount of cyclohexene 6 (eq 1). The reaction products
yield (%)
subst. cyanideb crown etherc
2
3
4
5
6
PhI
1a
1a
1a
1a
1b
1b
1b
1b
1b
Bu4NCN
NaCN
KCN
A(0.05)
A(0.08)
A(0.10)
B(0.08)
A(0.04)
A(0.09)
A(0.04)
A(0.08)
A(0.14)
13 19
22 32
24 30
22 32
d
13
11
18
11
e
62
81
82
81
69
72
79
73
72
d
d
d
e
e
e
6
6
3
6
6
NaCN
Bu4NCN
Bu4NCN
NaCN
KCN
26
26
25
32
29
5
7
6
6
6
14 27
18 22
13 15
15 24
16 24
KCN
a [1] ) 3 mM, at 60 °C for 1 h. Benzene was not detected by GC
because of the high volatility. Yield of benzonitrile is less than
1%. b Sodium and potassium salts were saturated in solution,
while the concentration of tetrabutylammonium salt was 0.01 M.
c A: 18-crown-6, B: 15-crown-5. The values in parentheses are
concentrations of the crown ether in M. d 4a is identical with 3a.
e Not determined.
are fully characterized by NMR and mass spectroscopy
and/or identified by comparison with authentic samples.
The trans configuration of 2b was confirmed by the
coupling constants and NOE observed in 1H NMR
(Experimental Section). The product yields were usually
determined by gas chromatographic analyses and are
summarized in Table 1. Formation of benzene was
confirmed by the 1H NMR spectrum of the reaction
mixture. 4-tert-Butylcyclohex-1-enyl(mesityl)iodonium tet-
rafluoroborate (1b′) was also examined, and the results
are similar to those obtained with 1b. Mesitylene was
determined by gas chromatography (Table 1).
Similar results were obtained using sodium and potas-
sium cyanide in the presence of crown ethers (Table 2).
In the absence of a crown ether, the sodium or potassium
salt is not very soluble in chloroform, and the reaction of
1 gave only a trace amount of cyanide-substitution
products.
TABLE 3. Reaction of 1-d3 with Bu4NCN in Chloroforma
yield (%)
subst. [MeOH] (M)
2
3
4
5
6
PhI PhCN
1a-d3
1a-d3
1a-d3
1a-d3
1a-d3
1b-d3
1b-d3
1b-d3
1b-d3
1b-d3
0
15
7
18
6
b
b
b
b
b
4
2
2
3
2
47
66
69
68
67
52
66
67
67
72
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
0.04
0.08
0.25
0.82
0
22 21
19 27
13 40
6
4
2
3
16
19
15
12
5
45
2
5
19
7
0.08
0.16
0.25
0.82
5
19
22
24
6
6
6
7
10 31
6
a [1] ) 3 mM, [CN-] ) 0.01 M, at 60 °C for 1 h. b Not
determined.
Table 3. Protium contents at the vinylic and allylic
1
positions of products 2-5 (eq 2) were determined by H
The cyanide reaction was also examined with 2,6,6-
trideuterated cyclohex-1-enyl iodonium salts 1-d3. The
deuterated substrates were prepared at ca. 90% D purity
from 2,2,6,6-tetradeuterated cyclohexanone, which was
obtained by H/D exchange. Product yields are given in
NMR spectroscopy and are summarized in Table 4. The
allylic products 2 contain deuterium atoms distributed
at positions 1, 2, and 3. The vinylic hydrogen of the
vinylic products 3 and 4 becomes mostly protium. Pro-
482 J. Org. Chem., Vol. 70, No. 2, 2005

Michael Reaction of Cycloalkenyl Iodonium Salts
a
TABLE 4. Protium Contents (%) of Products Obtained from 1-d3
2
3a
3b
4b
5
[MeOH] (M)
H-1
H-2
H-3
H-2
H-6
H-3
H-2
H-2
H-2
H-6
H-3
(a) products from 1a-d3
δ (ppm)b
0c
5.92
5.62
7
3.22
<5
<5
5
6.59
91
100
100
100
2.18
54
2.13
62
6.31
<5
e
<5
e
2.47
16
e
13
e
2.06
d
6
6
6
5
0.04
9
77
44
e
0.25c
0.82
16
12
72
42
100
e
8
62
48
(b) products from 1b-d3
δ (ppm)b
0
5.95
12
9
5.61
13
10
13
17
21
16
19
3.29
9
6.61
69
6.59
97
100
98
100
100
100
100
6.28
10
11
6
2.51
d
10
d
d
d
12
d
2.06
d
100
d
d
d
100
d
0c
9
85
0.08
0.16
0.25
0.25c
0.82
12
14
13
8
d
81
d
100
100
100
100
7
d
6
6
4
9
13
8
a The experimental errors for protium content are within (10%. Product yields are summarized in Table 3. b Chemical shifts of the
protons concerned. c Protium content was determined after purification by column chromatography. d The 1H NMR signal was overlapped
with other signals. e Cannot be determined due to a low yield of 5.
TABLE 5. Reaction of Cyclopentenyliodonium Salt 7 with Nucleophiles in Chloroforma
yield (%)
subst.
nucleophile (concentration, M)
time (h)
8
9
10
PhI
PhNu
C5H8
C6H6
7
CN- (0.10)
AcO- (0.01)
AcO- (0.10)
AcO- (0.10)
Br- (0.01)
22
84
27
22
24
15
18
18
19
<2
<2
27
25
24
58
64
26
29
10
17
30
70
60
82
64
<2
12
8
2
<2
<2
<2
<2
40
<2
<2
<2
<2
7
7
7-d3
7
9
20
a [7] ) 8 mM, at 60 °C.
tium is not incorporated at either the vinylic or allylic
position of iodocyclohexene 5.
bromide gave only the vinylic product 9c but no allylic
bromide 8c.
2,5,5-Trideuterated cyclopent-1-enyl iodonium salt 7-d3
(ca. 80% D) was employed for the acetate reaction.
Products 8b and 9b maintain most of the deuterium label
of the starting iodonium salt 7-d3 as shown in eq 4. The
allylic product 8b contains the deuterium labels at
positions 1, 2, and 3, as observed similarly for 3-cyano-
cyclohexene 2. The vinylic deuterium in the vinylic
product 9b was also retained, but it is noteworthy that
the deuterium label is distributed partially at position 3
of 9b (84% H content) at the expense of deuterium at
position 5.
Reactions of cyclopent-1-enyl(phenyl)iodonium tetraflu-
oroborate (7) with cyanide as well as acetate and bromide
were carried out in chloroform at 60 °C. The cyclopen-
tenyl derivative 7 is much less reactive than the cyclo-
hexenyl substrates 1. Products were determined in the
same way as cyclohexenyl derivatives. Observed products
are shown in eq 3, and yields are given in Table 5.
Rates for the reactions of cyclopentenyliodonium salt
7 and its deuterated analogue 7-d3 were determined at
60 °C and the ionic strength of 0.10 (Bu4NClO4) by
monitoring the decrease in absorbance at 280 nm due to
the iodonium salt. The reaction followed reasonably well
the pseudo-first-order kinetics, and the observed pseudo-
first-order rate constants are given in Table 6 as averages
of at least three runs within (5%. The reaction with
acetate is about 3-4 times faster than the bromide
reaction. The observed rate constants are not very
dependent on concentrations of the nucleophile. Kinetic
Although the main product of the cyanide reaction was
1-iodocyclopentene (10), the allylic cyano product 8a was
also obtained. The acetate reaction gave both allylic and
vinylic products 8b and 9b, while the reaction with
J. Org. Chem, Vol. 70, No. 2, 2005 483

Fujita et al.
TABLE 6. Pseudo-First-Order Rate Constants (kH and
kD) for the Reactions of Iodonium Salts 7 and 7-d3 with
Tetrabutylammonium Bromide or Acetate in Chloroform
at 60 °C
SCHEME 2. Possible Pathways of Formation of
Allylic Product
[Bu4NNu] (M)
105kH (s-1
Nu ) Br
1.45
)
105kD (s-1
)
kH/kD
0.001
0.005
0.025
0.075
1.10
1.07
1.04
1.08
1.3
1.4
1.5
1.5
1.46
1.52
1.57
Nu ) OAc
0.001
0.005
0.025
0.050
0.10
6.89
6.98
7.35
7.22
8.24
5.90
5.83
6.79
5.68
7.29
1.2
1.2
1.1
1.3
1.1
isotope effects are small for both the acetate (kH/kD ) 1.1-
1.3) and the bromide reactions (kH/kD ) 1.3-1.5).
the 1,2-diene, an external proton should have been
incorporated into position 2 of product 2 and should have
been detected when the reaction was started with deu-
terated substrate 1-d3. This mechanism is excluded since
position 2 was not protonated but the original three
deuterium atoms of 1-d3 were maintained at positions 1,
2, and 3 of 2. The results show that the original
deuterium atom should migrate to position 2 of 2.
The most reasonable route compatible with the isotope
incorporation experiments involves the initial Michael
addition of highly nucleophilic cyanide to give iodonium
ylide (I1), followed by elimination of the iodonio group to
yield a carbene intermediate (I2), which undergoes 1,2-
hydrogen (deuterium) migration to result in 2. The
iodonium ylide formation followed by elimination to give
carbene has been reported in the Michael reaction of
alkynyliodonium salts.19 Hydrogen has a high migratory
aptitude in the 1,2-rearrangement of singlet carbenes.13
There are two possible migration origins of hydrogen, but
the migration from >CHCN to give one of the vinylic
products 4 is less favorable, as shown by the isotope
incorporation experiments (Table 4, see the discussion
in the next section). Theoretical calculations support this
selectivity (see below).
Discussion
Reaction of Cyclohexenyliodonoium Salt 1 with
Cyanide. The cyanide reaction of 1 gave allylic cyanide
2 as well as ipso- and cine-substitution products, 3 and
4. This product pattern of substitution is completely
different from those observed previously for the reactions
of 1 (Scheme 1). Allylic products have never been
observed. When methanol was employed as a solvent, the
cyanide reaction of 1b gave rise to quite different re-
sults:8b the major reaction was the base-promoted â-elimi-
nation-addition (EA) to give ipso- and cine-substitution
products, and no allylic product was formed. Moreover,
the nucleophile was methoxide (or methanol), but cyanide
products were less than a few percent (eq 5).8b
Alternatively, an allylic cation intermediate I4 may not
be impossible to form via 1,2-hydrogen rearrangement
of the initial vinylic cation I3 if generated. This cationic
route can lead to 2 without loss of deuterium, but this is
less likely; the reaction medium is rather basic, and
furthermore, no allylic substitution product was obtained
during the solvolysis of 1, where the vinylic cation was
confirmed as a major intermediate.2
The allylic cyanide 2b is solely in the trans form. The
configuration indicates that the cyanide attack occurs
from the axial direction of cyclohexenyl ring of 1b. The
tendency of axial attack has been observed generally in
electrophilic additions to cyclohexanone enolates to avoid
an unstable twist-boat conformation during the bond-
formation step,22,23 and the stereochemical situation for
the present reaction is similar to the reaction of the
enolate. Formation of the allylic product 8 from cyclo-
pentenyliodonium salt 7 can also be explained by a
The effects of added methanol on the cyanide reaction
in chloroform are in fact large (Table 1). Yields of the
vinylic cyanides, 3 and 4, increase with increasing
methanol, whereas those of allylic cyanide 2 and iodocy-
clohexene 5 decrease. Concentrations of tetrabutyl-
ammonium cyanide and added tetrabutylammonium
tetrafluoroborate slightly affect the product yields, but
the effects are much weaker than those of methanol. The
vinylic ipso and cine cyanide products may be mainly
derived from the EA mechanism, but how is the allylic
product formed?
Mechanism for Formation of Allylic Product. A
characteristic product observed in the cyanide reaction
of 1 and 7 as well as in the acetate reaction of 7 is the
allylic substitution product, 2 or 8. The cyano group of
these products is located at the cine position next to the
original position of the leaving group. Possible mecha-
nisms for formation of the allylic product 2 are sum-
marized in Scheme 2 for the reaction of deuterated
substrate 1-d3. We first considered the elimination-
addition (EA) mechanism via cyclohexa-1,2-diene as an
extension of the EA mechanism via cyclohexyne to give
the ipso and cine products (3 and 4). If 2 was formed via
(22) Evans, D. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1984; Vol. 3, Chapter 1.
(23) Fraser, R. R.; Banville, J.; Dhawan, K. L. J. Am. Chem. Soc.
1978, 100, 7999-8001. Kuehne, M. E. J. Org. Chem. 1970, 35, 171-
175.
484 J. Org. Chem., Vol. 70, No. 2, 2005

Michael Reaction of Cycloalkenyl Iodonium Salts
similar mechanism involving the Michael addition-
elimination followed by 1,2-hydrogen shift.
hand, the possibility is excluded that 4 is formed via the
Michael AE and 1,2-hydrogen shift from the methylene
of the cyclohexylidene.
Mechanism for Formation of Vinylic Cyanides 3
and 4. As mentioned above, vinylic products 3 and 4 may
be derived from the EA mechanism via the intermediate
cyclohexyne. In this mechanism the vinylic hydrogen
should come from the external proton source, and it
should be completely protium if the reaction is carried
out with a deuterated substrate 1-d3 in a normal solvent.
This is the case for the products in the presence of
methanol (Table 4). Under these conditions, 3 and 4 are
major products, and about 3-fold preference of 4b over
3b was observed, in good agreement with the regiose-
lectivity of nucleophilic addition to 4-tert-butylcyclohex-
yne.8 Actually a similar product ratio (4b/3b ) 7/3) was
obtained during the reaction of 5-tert-butycyclohex-1-
enyliodonium salt 11 with cyanide (0.05 M) in the
presence of 1% (0.25 M) methanol (eq 6). The regioiso-
meric iodonium salt 11 can yield 4-tert-butylcyclohexyne
as a common intermediate to the reaction of 1b. Although
3 and 4 are identical (as 3a) in the reaction of 1a,
deuterium is distributed at both of the two allylic
positions (C-3 and C-6) of 3a in the reaction of deuterated
substrate 1a-d3. The observation is consistent with the
EA mechanism (eq 7).
Mechanism for Vinylic Substitution of Cyclopen-
tenyl Iodonium Salt 7. Reaction of 7 with bromide ion
gave the vinylic bromide 9c and bromobenzene ac-
companied by the formation of the counterpart iodoben-
zene and 1-iodocyclopentene (10) (Table 5). The nucleo-
philic substitutions both at the vinylic and phenyl groups
of vinyl(phenyl)iodonium salt are observed during the
ligand-coupling mechanism in λ3- iodane9 (Scheme 3). The
observed rate constants are not very dependent on the
concentration of bromide, and this will be explained by
a mechanism involving the initial equilibrium formation
of λ3-iodane, which is an equilibrium of the two confor-
mational isomers due to pseudorotation and leads to two
pairs of ligand-coupling products.9 Small kinetic isotope
effects observed (kH/kD ) 1.3-1.5) are not incompatible
with this mechanism. Some unidentified side reactions
may be partially responsible for the observed isotope
effects. The ligand-coupling mechanism has been pro-
posed for reactions of some vinylic iodonium salts with
halide ions and other nucleophiles.9
SCHEME 3. Ligand Coupling Mechanism
Data in Table 3 show that deuterium-labeled iodonium
salts 1-d3 generally give lower yields of 3 and 4 than
normal 1 (Table 1) in the reaction with cyanide. These
results conform to the EA mechanism via cyclohexyne,
where deprotonation is rate determining and the primary
isotope effects are operative. The cyclohexyne intermedi-
ate could be trapped by tetraphenylcyclopentadienone
under the reaction conditions to give tetrahydronaph-
thalene in 37% yield (eq 8).
Acetate substitution reaction of 7 also gave both vinylic
acetate 9b and phenyl acetate in addition to allylic
acetate 8b. The deuterium label essentially remains at
the vinylic position of the product 9b in the reaction of
7-d3 (eq 4). These results are consistent with the ligand-
coupling mechanism for the formation of 9b and phenyl
acetate. Allylic acetate 8b must be formed via the
Michael AE mechanism as discussed above. Thus, the
acetate reaction of 7 proceeds through both the Michael
AE and ligand-coupling pathways. Small kinetic isotope
effects (kH/kD ) 1.1-1.3) were observed for the acetate
reaction (Table 6), and the deuterium labeling in 7-d3 did
not affect the product ratio of 8b/9b. These results are
compatible with the competing ligand-coupling and
Michael AE pathways, both of which exert no primary
deuterium isotope effects in the rate-determining or
product-determining step.
In the absence of methanol, yields of the vinylic
cyanides decrease and the relative amount of the ipso
product 3b increases (4b/3b ) ca. 2/1). Under these
conditions some deuterium is retained at the vinylic
position of the ipso substitution product 3 but not in the
other vinylic product 4. Thus, some additional reaction
pathway other than the EA mechanism must be at work
to give the ipso vinylic cyanide 3 without loss of the
vinylic deuterium in the absence of effects of methanol.
Ligand coupling within the cyanide-coordinated hyper-
valent iodine complex (λ3-iodane) is the most probable
pathway to give the additional 3 (eq 9). On the other
The concentration of acetate ion does not affect product
distribution or yields in the range of [AcO-] ) 0.01-0.1
M (Table 5) nor affect the observed rate constant (Table
6). These results suggest that both the ligand-coupling
and the Michael reaction pathways proceed via λ3-iodane.
J. Org. Chem, Vol. 70, No. 2, 2005 485

Fujita et al.
SCHEME 4. Mechanism for Nucleohilic
Substitution Reactions of 7
SCHEME 5. 1,2-Hydrogen Shift in 2-Substituted
Cycloalkylidene
CHART 1
The Michael reaction yields a cyclopentylidene interme-
diate, which leads to allylic product 8 and possibly to
vinylic product 9. The vinylic deuterium label of 9b is
essentially retained, but the allylic labels are distributed
at the two allylic positions of 9b. The distribution of
allylic labels of 9b can be rationalized if 9b is formed
both via ligand-coupling and Michael AE mechanisms
(Scheme 4). In the latter mechanism, the hydrogen at
>CHOAc of 2-acetoxycyclpentylidene may migrate pref-
erentially (see the theoretical discussion below).
On the other hand, the cyanide reaction of 7 gave only
8a but no 9a, the former of which may be derived via
the Michael AE followed by 1,2-hydrogen shift from
>CH2 of the carbene intermediate. That is, the hydrogen
shift occurs from >CH2 rather than >CH(CN) of 2-cy-
anocyclpentylidene in a manner similar to 2-cyanocyclo-
hexylidene. The migration ability of hydrogen of substi-
tuted cycloalkylidenes will be theoretically discussed
below.
TABLE 7. Activation Energies for 1,2-Hydrogen Shift in
Substituted Cycloalkylidenes Calculated by
B3LYP/6-31G(d)
∆G‡ (∆E‡)a/kcal mol-1
carbene
Ha
Hb
Hc
I5
I6
I7
I8
4.6(7.3)
4.1(6.4)
6.1(7.3)
4.6(5.6)
3.8(6.2)
3.0(5.4)
5.7(6.7)
7.8(9.2)
3.0(5.4)
2.4(4.7)
4.2(5.3)
5.1(6.2)
a Gibbs free energies ∆G‡ are calculated at 298.15 K and 1.00
atm.
respectively. Theoretical calculations were carried out on
the transition states for 1,2-hydrogen shift in these
carbenes at the level of B3LYP/6-31G(d). 2-Substituted
cycloalkylidene contains three different hydrogens, Ha,
Hb, and Hc, which can participate in the 1,2-hydrogen
shift (Scheme 5), and the intramolecular competition of
hydrogen shift determines the destination of intermediate
carbene to vinylic or allylic product.
Any sign of the EA mechanism was not found for the
cyclopentenyliodonium salt 7. This is not unexpected
because of a high ring strain of cyclopentyne. The Michael
reaction of acetate with 7 (but not with 1) may take place
for this reason.
Reaction of iodonium salt 1 or 7 with cyanide ion
involves an appreciable side reaction, giving iodocycloalk-
ene 5 or 10 with accompanying benzene (mesitylene from
1b′). The ligand-coupling pathway can yield iodocycloalk-
ene, but the counterpart product, benzonitrile, was not
observed. The observed counterpart product was benzene,
and the pair of iodocycloalkene and benzene must be
produced by one-electron reduction of iodonium ion,
followed by homolysis to iodocycloalkene and phenyl
radical.9b,24,25 This reaction is particularly obvious for the
cyclopentenyl derivative 7 (Table 5), reflecting the slower
nucleophilic reaction in competition.
Hydrogen Shift in Substituted Cycloalkylidenes.
The Michael reaction pathway takes place during the
reaction of 1 with cyanide and the reaction of 7 with
acetate and cyanide ions to give 2-cyanocyclohexylidene,
2-acetoxycyclopentylidene, and 2-cyanocyclopentylidene,
Calculations were carried out on cycloalkylidenes I5-
I8 (Chart 1). Activation energies calculated for the
hydrogen shift are summarized in Table 7.26 For 2-cy-
anocyclohexylidene, the axial conformer I5 is slightly
more stable than the equatorial conformer (by 0.27 kcal
mol-1). Both conformers give similar results regarding
energy barriers for the hydrogen shift, and the results
for the latter conformation are not recorded here. For the
4-tert-butyl derivative, the trans isomer I6 was employed
for calculations, since the allylic product 2b is in the trans
configuration. For cyanocycloalkylidenes I5-I7, the shift
of Hc from the methylene has a lower barrier and is more
favorable than that of Ha from the methine, thus pref-
erentially leading to the allylic cyanide. This is compat-
ible with the product distribution in cyanide reactions
of 1 and 7. In contrast, acetoxycyclopentylidene I8 has a
lower barrier for the shift of Ha than that of Hb or Hc.27
The migration origin of hydrogen shift in carbene is
controlled by substitution at the â-position of carbene.
Methoxy, phenyl, and alkyl substituents facilitate the
(24) (a) Tanner, D. D.; Reed, D. W.; Setiloane, B. P. J. Am. Chem.
Soc. 1982, 104, 3917-3923. (b) Grushin, V. V.; Demkina, I. I.; Tolstaya,
T. P. J. Chem. Soc., Perkin Trans. 2 1992, 505-511. (c) Chen, D.-W.;
Ochiai, M. J. Org. Chem. 1999, 64, 6804-6814.
(25) The possibility of the reduction product formation via benzyne
intermediate can be eliminated: similar reduction was observed in both
cases of 1b and 1b′, although 1b′ cannot give the benzyne-type
intermediate.
(26) A small difference between ∆G‡ for the shift of the axial Hc
and equatorial Hb agrees well with the previous calculations of
cycloalkylidenes.15
486 J. Org. Chem., Vol. 70, No. 2, 2005

Michael Reaction of Cycloalkenyl Iodonium Salts
(relative intensity, %) 107 (36, M+), 92 (58), 79 (100). The data
agree well with the reported values: 1H NMR (CCl4) δ 5.9 (m,
1H), 5.6 (m, 1H), 3.15 (m, 1H), 2.2-1.6 (m, 6H).29 Selected data
for 3b: 1H NMR (600 MHz, CDCl3) δ 6.61 (m, 1H), 2.32-2.28
(m, 1H), 2.25-2.16 (m, 2H), 1.92-1.86 (m, 2H), 1.29-1.23 (m,
1H), 1.21-1.11 (m, 1H), 0.85 (s, 9H); 13C NMR (150 MHz,
CDCl3) δ 145.67, 119.75, 112.10, 42.55, 32.14, 28.02, 27.57,
26.95, 22.97; MS (EI) m/z (relative intensity, %) 163 (10, M+),
148 (10), 107 (50), 57 (100). The data agree well with the
reported values: 1H NMR (CCl4) δ 6.7-6.4 (m, 1H), 2.5-1.0
(m, 7H), 0.89 (s, 9H); MS (EI) m/z (relative intensity, %) 163
(69, M+), 148 (63), 107 (100), 57 (84).30
migration of the hydrogen on the same carbon (Ha).13 The
effect of the acetoxy group in I8 is similar to these groups,
but the cyano group exerts adverse effects. The electron-
withdrawing ability of the cyano group may be respon-
sible for this tendency. When the C-H bond is partially
cleaved in the transition state for 1,2-hydrogen shift in
carbene, a positive charge develops at the carbon,16 which
is stabilized by electron-donating groups including the
acetoxy group but destabilized by the cyano group.
In summary, reactions of cycloalkenyl iodonium salts
1 and 7 with cyanide ion involve a new type of reaction
pathway of vinyliodonium salts, Michael addition-
elimination. The Michael reaction leads to a cycloalky-
lidene intermediate, and the reactivity of the carbene
affects the product distribution. 2-Cyanocycloalkylidenes
undergo a shift of the methine hydrogen preferentially
to give the allylic cyanide product, in contrast to phenyl-,
alkyl-, methoxy-, and acetoxy-substituted cycloalkyli-
denes.
Authentic samples of 3a and 4b were also prepared from
reaction of KCu(CN)2 with 1a and 5-tert-butylcyclohex-1-enyl-
(phenyl)iodonium tetrafluoroborate (11), respectively. Selected
data for 3a: 1H NMR (600 MHz, CDCl3) δ 6.59 (m, 1H), 2.20-
2.16 (m, 2H), 2.15-2.10 (m, 2H), 1.67-1.62 (m, 2H), 1.61-
1.58 (m, 2H); MS (EI) 107 (59, M+), 92 (96), 79 (100), 67 (33),
52 (45). The data agree well with the reported values: 1H NMR
(CDCl3) δ 6.72-6.44 (m, 1H), 2.36 (br, 4H), 1.86-1.46 (m,
4H).31 Selected data for 4b: 1H NMR (600 MHz, CDCl3) δ 6.59
(m, 1H), 2.30 (dq, J ) 19.9, 2.4 Hz, 1H), 2.22 (m, 1H), 2.13 (m,
1H), 1.98 (m, 1H), 1.83 (m, 1H), 1.29 (tdd, J ) 12.4, 5.5, 2.7
Hz, 1H), 1.12 (qd, J ) 12.4, 5.5 Hz, 1H), 0.87 (s, 9H); 13C NMR
(CDCl3, 150 MHz) δ 144.84, 119.90, 112.68, 42.20, 32.23, 28.41,
27.18, 26.97, 22.27; MS (EI) 163 (6, M+), 148 (5), 107 (57), 57
(100); HRMS (ESI) calcd for C11H17NNa (M + Na) 186.1259,
found 186.1269.
Experimental Section
Preparation of Deuterium-Labeled Iodonium Salts.
Cyclic ketones were treated with D2O in THF containing
K2CO3 to yield the deuterium-incorporated ketones. The
deuterium-labeled iodonium salt 1-d3 was prepared from the
labeled ketone according to the literature procedures.8b,11a The
isotopic purity was determined by comparison of 1H NMR peak
areas due to the vinylic and allylic protons with that for the
aromatic protons. Selected data for 1a-d3: Deuterium contents
at C-2 (δ ) 7.0 ppm) and C-6 (δ ) 2.56 ppm) are 96 and 91
atom %, respectively. HRMS (ESI) calcd for C12H11D3I (M -
BF4) 288.0329, found 288.0291. Selected data for 1b-d3:
Deuterium contents at C-2 (δ ) 7.0 ppm) and C-6 (δ ) 2.66
ppm) are 91 and 93 atom %, respectively. HRMS (ESI) calcd
for C16H19D3I (M - BF4) 344.0955, found 344.0935. Selected
data for 7-d3: Deuterium contents at C-2 (δ ) 6.93 ppm) and
C-5 (δ ) 2.7 ppm) are 81 and 80 atom %, respectively. HRMS
(ESI) calcd for C11H9D3I (M - BF4) 274.0172, found 274.0128.
Reaction of 1 with Nucleophile. The tetrafluoroborate
salt of 1 (4 mg) was dissolved in 3 mL of chloroform containing
tetrabutylammonium cyanide and kept at 60 °C. After addition
of an ether solution containing tetradecane (5 µmol), the
products were extracted with ether and washed with water.
The yields of the products were determined by gas chroma-
tography with tetradecane as an internal standard. The
retention times of 2a, 3a, and 5a were 8.5, 10.6, and 13.3 min,
respectively, at a column temperature of 50 °C (DB-1). In the
GC analysis of the reaction mixture from 1b, products 6b, 2b,
4b, 3b, and 5b were detected at retention times of 2.1, 8.3,
10.8, 11.2, and 12.5 min, respectively, when the temperature
of the column (DB-1) was maintained at 100 °C during the
trans-5-tert-Butyl-3-cyanocyclohexene (2b).32 Reaction
of 1b (109 mg, 0.25 mmol) with Bu4NCN (101 mg, 0.38 mmol)
was carried out in chloroform (20 mL) at room temperature
for 1 h to give 2b, which was purified (3.2 mg, 8% yield) by
1
preparative GC. The NMR peaks are assigned using H-1H
and 13C-1H COSY. 1H NMR (600 MHz, CDCl3) δ 5.95 (ddt,
J1,2 ) 9.6 Hz, J1,6eq ) 5.5 Hz, J1,6ax ) 2 Hz, J ) 2 Hz, 1H, H-1),
5.61 (ddt, J1,2 ) 9.6 Hz, J2,3 ) 5 Hz, J ) 2 Hz, 1H, H-2), 3.29
(tq, J3,4ax ) J2,3 ) 5 Hz, J3,4eq ) 2 Hz, J ) 2 Hz, 1H, H-3), 2.14
(dddt, J6eq,6ax ) 17.9 Hz, J1,6eq ) 5.5 Hz, J5,6eq ) 4.8 Hz, J ) 2
Hz, 1H, H-6eq), 2.08 (d quint, J4eq,4ax ) 13.1 Hz, J4eq,5 ) J3,4eq
) 2 Hz, J ) 2 Hz, 1H, H-4eq), 1.81 (ddq, J6eq,6ax ) 17.9 Hz,
J5,6ax ) 11.7 Hz, J1,6ax ) 2 Hz, J ) 2 Hz, 1H, H-6ax), 1.62 (dddd,
J4ax,5 ) 12 Hz, J5,6ax ) 11.7 Hz, J5,6eq ) 4.8 Hz, J4eq,5 ) 2 Hz,
1H, H-5), 1.40 (ddd, J4eq,4ax ) 13.1 Hz, J4ax,5 ) 12 Hz, J3,4ax
)
5 Hz, 1H, H-4ax), 0.88 (s, 9H, t-Bu); 13C NMR (150 MHz, CDCl3)
δ 132.94 (C-1), 121.12 (CN), 120.05 (C-2), 40.35 (C-5), 32.03
(t-Bu), 27.49 (C-3), 27.32 (C-4), 26.95 (t-Bu), 26.44 (C-6); MS
(EI) m/z (relative intensity, %) 163 (2, M+), 148 (5), 121 (6),
107 (22), 79 (20), 57 (100); HRMS (ESI) calcd for C11H17NNa
(M + Na) 186.1259, found 186.1267; NOE between H-5 (δ )
1.62 ppm) and H-3 (δ ) 3.29 ppm) was not observed, and NOE
between H-4ax (δ ) 1.40 ppm) and H-6ax (δ ) 1.81 ppm) and
that between H-4ax (δ ) 1.40 ppm) and H-3 (δ ) 3.29 ppm)
were detected with 2% and 4%, respectively.
Reaction of 7 with Nucleophile. Iodonium salt 7 (1.5 mg)
was dissolved in chloroform-d (0.5 mL) containing tetrabutyl-
ammonium salt of nucleophile. The NMR tube containing the
solution was sealed and kept at 60 °C. Product yields were
determined by 1H NMR using the residual CHCl3 as an
internal standard. Authentic samples of 8b33 and 9b34 were
prepared according to the reported methods. 1-Iodocyclopen-
tene (10) was prepared by the reaction of 7 with tetrabutyl-
initial 10 min and then raised at the rate of 10 °C min-1
.
Authentic samples of 2a,28 3b,11a and 5a,b11a were prepared
according to the literature methods. Selected data for 2a: 1H
NMR (600 MHz, CDCl3) δ 5.92 (m, 1H), 5.62 (m, 1H), 3.22 (m,
1H), 1.94-1.91 (m, 2H), 1.85-1.54 (m, 4H); MS (EI) m/z
(27) The barrier in Table 7 is for the most stable conformer of I8
among some torsional conformers due to the rotation of acetoxy group.
An acetoxy-bridged structure is by 2.4 kcal mol-1 more stable than
the most stable conformation of I8 and gives the acetoxy migration
product with a low energy barrier (∆G‡ ) 0.5 kcal mol-1). However,
the free-energy barrier from I8 to the bridged form is 12.1 kcal mol-1
and much higher than ∆G‡ for the 1,2-hydrogen shift shown in Table
7. The energy diagram for the acetoxy shift in I8 is shown in Scheme
S1 (Supporting Information). That is, the possibility of acetoxy
migration in I8 is excluded from the reaction pathway to 9b.
(29) (a) Davies, S. G.; Whotham, G. H. J. Chem. Soc., Perkin Trans.
1 1976, 2279-2280. (b) Andell, O. S.; Ba¨ckwall, J.-E.; Moberg, C. Acta
Chem. Scand. B 1986, 40, 184-189.
(30) House, H. O.; Umen, M. J. J. Org. Chem. 1973, 38, 3893-3901.
(31) Minami, I.; Nisar M.; Yuhara, M.; Shimizu, I.; Tsuji, J.
Synthesis 1987, 992-998.
(32) Preparation of 5-tert-butyl-3-cyanocyclohexene has been re-
ported in ref 29a.
(33) Hirano, M.; Nakamura, K.; Morimoto, T. J. Chem. Soc., Perkin
Trans. 2 1981, 817-820.
(28) Yoshida, K.; Kanbe, T.; Fueno, T. J. Org. Chem. 1977, 42, 2313-
2317. Mousseron, M.; Winternitz, F.; Jullien, J.; Jacquier, R. Bull. Soc.
Chim. Fr. 1948, 79-84; Chem. Abstr. 1948, 42, 4951d.
(34) Jones, R. A.; Stokes, M. J. Tetrahedron 1984, 40, 1051-1060.
Tirpak, R. E.; Rathke, M. W. J. Org. Chem. 1982, 47, 5099-5102.
J. Org. Chem, Vol. 70, No. 2, 2005 487

Fujita et al.
ammonium iodide, and the 1H NMR and MS spectra agree well
respectively. Chemical shifts for H-1, H-2, and H-3 of 3-ac-
etoxycyclopentene (8b) were assigned to be 6.08, 5.81, and 5.68
ppm, respectively.38 1H NMR peaks due to 1-acetoxycyclopen-
tene (9b) were assigned by comparison with the normal
product from 7 and the selectively deuterated sample prepared
by reaction of 7-d3 with cupric acetate in acetic acid. Chemical
shifts for H-2, H-3, and H-5 of 1-acetoxycyclopentene (9b) are
5.38, 2.35, and 2.42 ppm, respectively. Protium contents at
these positions are calculated from the peak areas in reference
to that for the acetoxy group, which is independently observed
at 2.11 and 2.01 ppm for 8b and 9b, respectively. The protium
contents are shown in eq 4. The peak at 6.08 ppm for H-1 of
8b overlaps with that for the vinylic proton of 10. The ratio of
the peak area at 6.08 ppm and that for the acetyl group at
2.11 ppm is 0.36:3, indicating that the protium content at C-1
of 8b is less than 36%, probably about 20%.
Trapping of Cyclohexyne with Tetraphenylcyclopen-
tadienone. A solution containing 1a (36.3 mg, 0.098 mmol),
tetrabutylammonium cyanide (70 mg, 0.26 mmol), tetraphe-
nylcyclopentadienone (85.5 mg, 0.22 mmol), and methanol (0.6
mL) in chloroform (20 mL) was stirred at 60 °C for 1 h. The
mixture was purified by chromatography (SiO2, eluent: 40%
CHCl3 in hexane) to give 5,6,7,8-tetraphenyl-1,2,3,4-tetra-
hydronaphthalene8b (15.6 mg, 0.036 mmol, 37% yield).
with those reported.35 The products 8a,36 9a,37 and 9c35 were
1
assigned by H NMR in comparison with the reported data.
Determination of Protium Contents of Products from
Labeled Iodonium Salts. The reaction mixture obtained
from 1-d3 was analyzed by both GC and 1H NMR. GC analysis
reveals the ratio of products, 2a, 3a, 5a, and iodobenzene. The
1H NMR measurements provide the relative peak areas due
to respective protons. Protium contents were calculated from
the GC and 1H NMR analysis by using iodobenzene as an
internal standard. Assignments of the vinylic and allylic
protons for 3a and 5 were undertaken by comparison with
authentic samples of deuterated 3a and 5. The selectively
deuterated samples of 3a and 5 were prepared by the reaction
of 1-d3 with KCu(CN)2 and iodide salt, respectively. Signals
due to 2 were assigned using the 1H-1H COSY NMR mea-
surements described above. The chemical shifts of the protons
concerned are given in Table 4.
Direct 1H NMR determination of protium contents without
GC analysis was also carried out for 2b isolated from the
reaction mixture of 1b-d3 by preparative GC. The protium
content of 2b was determined using the peak area due to t-Bu
(0.88 ppm) as a reference: Protium contents at H-1, H-2, and
H-3 of 2b are 12%, 16%, and 7%, respectively (Supporting
Information). The results agree well with those in Table 4,
which are determined by combination of 1H NMR and GC peak
areas.
Acknowledgment. This work was partially sup-
ported by a Grant-in-Aid for Scientific Research on
Priority Areas (Reaction Control of Dynamic Complexes,
No. 15036260) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
The reaction of 7-d3 (16 mM, 19 mg) with Bu4NOAc (0.1 M)
was carried out in CHCl3 (3 mL), and the reaction mixture
1
extracted with pentane was analyzed by GC and H NMR in
CDCl3. The molar ratio of 8b:9b:10b:PhI determined by GC
is 0.3:0.3:0.15:1.0. The ratio agrees well with the product yields
determined in an independent run of reaction of 7-d3, which
gave 8b, 9b, 10b, and PhI in 19%, 24%, 10%, and 82% yield,
Supporting Information Available: General experimen-
tal procedures, computational details, and additional data for
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(35) Erickson, K. L.; Markstein, J.; Kim, K. J. Org. Chem. 1971,
36, 1024-1030.
(36) Colombini, M.; Crotti, P.; Bussolo, V. D.; Favero, L.; Gardelli,
C.; Macchia, F.; Pineschi, M. Tetrahedron 1995, 51, 8089-8112.
(37) Curran, D. P.; Lin, C.-H.; DeMello, N.; Junggebauer, J. J. Am.
Chem. Soc. 1998, 120, 342-351. Ros, F.; de la Rosa, J.; Enfedaque, J.
J. Org. Chem. 1995, 60, 5419-5424. Funabiki, T.; Kishi, H.; Sato, Y.;
Yoshida, S. Bull. Chem. Soc. Jpn. 1983, 56, 649-650.
JO049218K
(38) (a) Hansson, S.; Heumann, A.; Rein, T.; Akermark, B. J. Org.
Chem. 1990, 55, 975-984. (b) Araki, M.; Nagase, T. Ger. Offen.
2625030.
488 J. Org. Chem., Vol. 70, No. 2, 2005