Highly regioselective palladium-catalyzed annulation reactions of heteroatom-substituted allenes for synthesis of condensed heterocycles

Article abstract of DOI:10.1248/cpb.53.1502

We have developed a highly regioselective synthesis of heterocycles via palladium-catalyzed annulation reaction of heteroatom-substituted allenes. Various aryl halides were reacted and one regioisomer was observed exclusively in all reactions. In addition

Full text of DOI:10.1248/cpb.53.1502

1502
Notes
Chem. Pharm. Bull. 53(11) 1502—1507 (2005)
Vol. 53, No. 11
Highly Regioselective Palladium-Catalyzed Annulation Reactions of
Heteroatom-Substituted Allenes for Synthesis of Condensed Heterocycles
a,b
Kiyofumi INAMOTO,a Akio YAMAMOTO,a Kazutoshi OHSAWA,a Kou HIROYA,*,a and Takao SAKAMOTO
a Graduate School of Pharmaceutical Sciences, Tohoku University; Aoba-ku, Sendai 980–8578, Japan: and b Tohoku
University 21st Century COE Program “Comprehensive Research and Education Center for Planning of Drug
Development and Clinical Evaluation”; Sendai 980–8578, Japan.
Received July 11, 2005; accepted August 27, 2005; published online August 31, 2005
We have developed a highly regioselective synthesis of heterocycles via palladium-catalyzed annulation reac-
tion of heteroatom-substituted allenes. Various aryl halides were reacted and one regioisomer was observed ex-
clusively in all reactions. In addition, subsequent functionalizations of annulated products were carried out using
alkyl metal reagents, and the introduction of alkyl moieties was accomplished.
Key words palladium; annulation; allene; heterocycle; alkyl metal reagent
Palladium-catalyzed annulation processes have proved to
be extremely useful and powerful methods for the construc-
tion of diverse carbocycles and heterocycles.1—4) Among
them, reactions that involve carbopalladation of allenes,
which generate p-allylpalladium intermediates, followed by
internal nucleophilic attack by a heteroatom or carbanion, are
particularly valuable (Fig. 1).5—16) Larock et al. have exten-
sively investigated the palladium-catalyzed annulation reac-
tions of carbon-atom-substituted allenes using functionally
substituted aryl iodides or vinyl halides.13—16) Yields were
generally high and most of the reactions are both stereo- and
regioselective; however, the reactions sometimes afforded
Fig. 3. Synthesis of Allenes (1, 2)
mixtures of regioisomers, especially in six-membered-ring
formation.13,14) Meanwhile, only one example of an annula-
tion reaction of heteroatom-substituted allenes has been re- the palladium-catalyzed annulation reaction. Several metal
ported, and in that case the presence of the heteroatom on al- reagents were reactive and an alkyl moiety could be intro-
lenes and its electronic effect dominated the regioselectivity duced by this process.
(Fig. 2).17) With the aim of regioselectively synthesizing
Synthesis of Heteroatom-Substituted Allenes Hetero-
highly functionalized heterocycles, we employed heteroatom- atom-substituted allenes (1, 2) used for the palladium-cat-
substituted allenes for palladium-catalyzed annulation. We alyzed annulation reaction were prepared according to the
found that various aryl iodides and bromides reacted protocol as follows (Fig. 3).18—20)
smoothly and that one regioisomer was produced exclusively
O-Substituted allene 1 was obtained via O-benzylation of
both in five- and six-membered-ring formations. Further- propargyl alcohol followed by treatment with tBuOK in N,N-
more, in the course of our extensive studies on the synthetic dimethylformamide (DMF) at 70 °C.
application of annulated products, we also found that alkyl
N-Substituted allene 2 was synthesized using commer-
metal reagents reacted unexpectedly in SN2ꢀ fashion at the cially available N-Boc-N-tosylamide as a starting material.
exomethylene carbon of the annulated products obtained by Mitsunobu reaction of N-Boc-N-tosylamide with propargyl
alcohol, followed by removal of Boc using 3 N HCl in MeOH
under reflux, afforded N-propargyl-N-tosylamide 3 in 91%
yield. Benzylation of amide 3 and subsequent isomerization
produced the desired allene 2.
Palladium-Catalyzed Annulation Reactions of Allenes
Using Various Aryl Iodides/Bromides (Table 1) With
heteroatom-substituted allenes 1 and 2 in hand, we first ex-
amined the annulation reaction of them using various aryl io-
dides.
Fig. 1. Palladium-Catalyzed Annulation Reactions of Allenes
A variety of reaction conditions have been examined, and
the use of an inorganic base, K2CO3, and a polar solvent,
DMF, has proved to be effective for this process. All reac-
tions were highly regioselective and only one regioisomer
was observed.
In annulation of allene 1 using N-tosyl-2-iodoaniline as an
aryl halide, the reaction proceeded smoothly at 80 °C in the
Fig. 2. Effect of Heteroatoms for Regioselectivity
∗ To whom correspondence should be addressed. e-mail: hiroya@mail.pharm tohoku.ac.jp
© 2005 Pharmaceutical Society of Japan

November 2005
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Table 1. Pd-Catalyzed Annulation Reaction of Allenes (1, 2) Using Various Aryl Halides
Entry
1
Aryl halide
Allene
“Pd catalyst”a)
A
Conditions
80 °C, 19 h
Product
Yield (%)
99
1
2
1
A
80 °C, 1.5 h
71
3
4
1
1
1
2
2
2
2
2
1
1
1
1
1
A
A
B
A
A
B
A
B
A
B
A
B
A
120 °C, 1 h
120 °C, 2 h
120 °C, 2 h
50 °C, 72 h
80 °C, 16 h
100 °C, 1.5 h
50 °C, 40 h
80 °C, 2 h
75
52
86
81
65
99
42
62
0
5
6
7
8
9
10
11
12
13
14
15b)
80 °C, 19 h
120 °C, 2 h
120 °C, 4 h
120 °C, 2 h
120 °C, 5 h
75
54
52
76
Reaction conditions: Aryl halide (1.0 eq), allene 1 or 2 (1.5—4.0 eq), K2CO3 (1.5—3.0 eq), Pd(OAc)2 (10 mol%), P(2-Tol)3 (15 mol%) and DMF (5 ml). a) “Pd Catalyst”: A,
Pd(OAc)2; B, Pd(OAc)2/P(2-Tol)3. b) Bu4NBr was added as an additive.
presence of 10 mol% of Pd(OAc)2, and indoline 5 was ob- nium salt as an additive resulted in an enhancement in yield
tained as the sole product in quantitative yield (entry 1). Sim- and tetrahydroisoquinoline 7 was obtained in 76% yield
ilarly, reactions between allene 1 and N-ethoxycarbonyl-2- (entry 15).22) Here again, the annulation reactions proceeded
iodoaniline (entry 2) or N-tosyl-2-iodobenzylamine (entry 3) in a highly regioselective manner and one regioisomer was
yielded the annulated products 6 and 7, respectively, in good formed exclusively in all cases.
yield. In the case of 2-iodobenzyl alcohol, the addition of
phosphine ligand, P(2-Tol)3, improved the yield (entry 4 vs. lation reactions most likely proceed as illustrated below, in a
5) and afforded isochroman 8 in high yield (entry 5).
manner similar to that postulated by Larock.13,15) Thus, the
Regioselectivity of Annulation Reactions These annu-
We also conducted an annulation reaction of N-substituted reaction begins with arylpalladium formation, followed by its
allene 2. Namely, N-tosyl-2-iodoaniline reacted at a tempera- addition to allene, producing a p-allylpalladium compound
ture as low as 50 °C, and indoline 9 was obtained in 81% which readily undergoes intramolecular nucleophilic attack
yield (entry 6). In the reactions of 2-iodobenzyl alcohol and by an oxygen or nitrogen atom to give the annulated product.
2-iodophenol, the best results were obtained using a catalyst Although the nucleophilic attack can occur at the a- or g-po-
system such as Pd(OAc)2/P(2-Tol)3 (entries 8, 10).
sition relative to the heteroatom (Fig. 4), the product via a-
Less reactive aryl bromides were also employed for annu- attack was obtained exclusively in our annulation process, re-
lation reactions of allene 1. The reaction of 2-bromobenzyl gardless of the bulkiness of the allene substituents. The cause
alcohol did not proceed at all in the absence of phosphine of the selectivity can be considered to be either of the follow-
ligand (entry 11). The addition of phosphine ligand, P(2- ing: (1) the electronegativity of an oxygen or nitrogen atom
Tol)3, increased the yield, and the annulated product 8 was on the allene makes the a-carbon more electron positive than
obtained in relatively high yield at higher temperature (entry the g-position, therefore the nucleophilic attack occurs at the
12). In contrast, in the reaction of N-tosyl-2-bromobenzyl- more substituted carbon or (2) the palladium complex has
amine, the addition of phosphine ligand did not increase the been reductively eliminated with the assistance of the het-
yield (entry 13 vs. 14). However, the use of tetrabutylammo- eroatom, and cyclization proceeds without participation of

1504
Vol. 53, No. 11
stitution products were obtained in high yield (entries 7, 12).
Interestingly, aryl metal reagents and alkynyl metal reagents
were completely ineffective in this reaction; however, the rea-
son for this as well as detailed reaction mechanism is obscure
at present.
In conclusion, highly regioselective annulation was ac-
complished using heteroatom-substituted allenes. In addition,
unprecedented SN2ꢀ reaction of alkyl metal reagents occurred
at the exomethylene position of annulated products, and sev-
eral alkyl moieties were introduced in good-to-high yields.
Continuing studies to extend the scope of the substrates and
to apply annulated products and products from the SN2ꢀ reac-
tion for natural product synthesis are underway.
Experimental
General Procedures Melting points were measured with a Yazawa
micro melting point apparatus and uncorrected. IR spectra were recorded on
a SHIMADZU FTIR-8400. 1H- and 13C-NMR spectra were recorded on a
JEOL JMN AL-400. Chemical shifts (d) are given from tetramethylsilane
(TMS) (0 ppm) as an internal standard for 1H-NMR and 13CDCl3 (77.0 ppm)
for 13C-NMR. Mass spectra and high resolution mass spectra were measured
on JEOL JMS-DX303 and MS-AX500 instruments, respectively.
Fig. 4. Plausible Reaction Mechanism for High Regioselectivity
the palladium complex.23) In such a case, the cyclization
mode for a-attack is 5-exo-trig (for nꢁ0) or 6-exo-trig (for
nꢁ1), and this may be an another reason for the selectivity.
Although we do not have any evidence for the above mecha-
nisms, it seems likely that the electronic effect, but not the
steric effect, is the major controlling factor for the observed
regioselectivity.24)
Benzyl 1,2-Propadienyl Ether (1) Benzyl bromide (25.7 g, 0.15 mol)
was added dropwise at 0 °C to a solution of propargyl alcohol (5.6 g,
0.10 mol) in DMSO (100 ml) and 3 N NaOH (50 ml) and the whole mixture
was stirred at room temperature for 24 h. The reaction mixture was extracted
with Et2O (30 mlꢂ3) and the combined ethereal layer was washed with brine
(30 mlꢂ3), and dried over MgSO4. The ethereal layer was removed under re-
duced pressure and the residue was purified by silica gel column chromatog-
raphy using hexane–AcOEt (19 : 1) as an eluent to give benzyl 2-propynyl
ether (20.6 g, 94%) as a colorless oil. To a solution of benzyl 2-propynyl
Synthesis of 4-Alkyl-Substitued Condensed Heterocy-
cles (Table 2) When annulated product 8 was treated with
t
alkyllithium reagents such as BuLi and BuLi, nucleophilic
attack occurred at the exomethylene carbon and the sub-
stitution products were obtained in 60% and 87% yield,
respectively (entries 1, 3). In the reaction of BuLi, the ad-
dition of N,N,Nꢀ,Nꢀ-tetramethylethylenediamine (TMEDA)
enhanced the yield (91%, entry 2). Also, reactions of 7 and
t
ether (6.1 g, 41.8 mmol) in DMF (30 ml), BuOK (0.94 g, 8.4 mmol) was
added at 0 °C and the whole mixture was stirred at 70 °C for 24 h. The reac-
tion mixture was extracted with Et2O (20 mlꢂ3) and the combined ethereal
layer was washed with brine (20 mlꢂ3), and dried over MgSO4. The ethereal
layer was removed under reduced pressure and the residue was purified by
5 with alkyllithium reagents proceeded in the same manner silica gel column chromatography using hexane–AcOEt (19 : 1) as an eluent
to give benzyl 1,2-propadienyl ether (1, 4.2 g, 69%) as a colorless oil. bp:
and substitution products were obtained in moderate to
good yield (entries 4, 5, 8—11). Organocuprate, BuCu(2-
thienyl)CNLi2, was also reactive in the reaction of tetrahy-
droisoquinoline 7, and the substitution product was obtained
in 83% yield (entry 6). Moreover, magnesium ate complex
such as EtMe2MgLi reacted smoothly with 7 and 5, and sub-
t
80 °C (22 mmHg, Kugelrohr). IR n (NaCl) cmꢃ1: 1960, 3050. 400 MHz 1H-
NMR (CDCl3) d (ppm): 4.61 (2H, s), 5.47 (2H, d, Jꢁ6.0 Hz), 6.83 (1H, t,
Jꢁ6.0 Hz), 7.29—7.35 (5H, m). 100 MHz 13C-NMR (CDCl3) d (ppm): 70.6,
91.1, 121.5, 127.7, 127.8, 128.3, 137.2, 201.1. EI-MS m/z (relative inten-
sity): 146 (Mꢄ, 11.3), 91 (Mꢄꢃ55, 100). HR-MS Calcd for C10H10O:
146.0732, Found: 146.0737.
N-(2-Propynyl)-4-methylphenylsulfonamide (3) Under Ar atmo-
sphere, DEAD (1.4 g, 25.0 mmol, 40% in toluene) was added dropwise at
0 °C to a solution of N-Boc-4-methylphenylsulfonamide (4.1 g, 15.0 mmol),
propargyl alcohol (1.4 g, 25.0 mmol) and PPh3 (6.6 g, 25.0 mmol) in tetrahy-
drofuran (THF) (50 ml) and the whole mixture was stirred for 2 h at the
same temperature. After removal of THF under reduced pressure, the residue
was extracted with AcOEt (30 mlꢂ3) and dried over MgSO4. The organic
layer was removed under reduced pressure and the residue was purified by
silica gel column chromatography using hexane–AcOEt (9 : 1) as an eluent
to give N-Boc-N-(2-propynyl)-4-methylphenylsulfonamide as a yellow solid.
A solution of N-Boc-N-(2-propynyl)-4-methylphenylsulfonamide and 3 N
HCl (10 ml) in MeOH (30 ml) was heated under reflux for overnight. The re-
action mixture was extracted with AcOEt (20 mlꢂ3) and the combined or-
ganic layer was washed with brine (20 mlꢂ3), and dried over MgSO4. The
organic layer was removed under reduced pressure and the residue was puri-
fied by silica gel column chromatography using hexane–AcOEt (9 : 1) as an
eluent to give N-(2-propynyl)-4-methylphenylsulfonamide (3, 4.8 g, 91% for
2 steps) as a yellow solid. mp: 71—73 °C (recrystallized from hexane/ace-
Table 2. Reaction of Alkyl Metal Reagents with Annulated Products
Entry Substrate
Reagents
R
Product
Yield (%)
1
2
3
BuLi
BuLiꢄTMEDA
tBuLi
Bu
Bu
tBu
60
91
87
4
5
6
7
BuLiꢄHMPA
Bu
44
60
83
79
tBuLi
tBu
1
tone). IR n (NaCl) cmꢃ1: 3261. 400 MHz H-NMR (CDCl3) d (ppm): 2.11
tBuCu(2-thienyl)CNLi2 tBu
(1H, t, Jꢁ2.4 Hz), 2.44 (3H, s), 3.83 (2H, dd, Jꢁ2.4, 6.2 Hz), 4.63 (1H, br),
7.31 (2H, d, Jꢁ8.4 Hz), 7.77 (2H, d, Jꢁ8.4 Hz). 100 MHz 13C-NMR
(CDCl3) d (ppm): 21.6, 32.9, 73.0, 77.9, 127.3, 129.6, 136.4, 143.8. EI-MS
m/z (relative intensity): 209 (Mꢄ, 3.0), 91 (Mꢄꢃ118, 100). HR-MS Calcd
for C10H11NO2S: 209.0511, Found: 209.0490.
N-Benzyl-N-(2-propynyl)-4-methylphenylsulfonamide (4) Under Ar
atmosphere, a solution of N-(2-propynyl)-4-methylphenylsulfonamide (3,
0.31 g, 1.5 mmol) in DMF (5 ml) was added dropwise at 0 °C to a suspension
EtMe2MgLi
Et
8
9
10
11
12
BuLi
Bu
Bu
tBu
tBu
Et
40
83
68
76
93
BuLiꢄHMPA
tBuLi
tBuLiꢄHMPA
EtMe2MgLi

November 2005
1505
of NaH (0.090 g, 2.3 mmol, 60% in oil) in DMF (5 ml) and the mixture was
stirred for 1 h at the same temperature. Benzyl bromide (0.36 g, 2.3 mmol)
was added at 0 °C and the whole mixture was stirred at room temperature for
overnight. The reaction mixture was extracted with Et2O (15 mlꢂ3) and the
combined ethereal layer was washed with brine (15 mlꢂ3), and dried over
MgSO4. The ethereal layer was removed under reduced pressure and the
residue was purified by silica gel column chromatography using
hexane–AcOEt (9 : 1) as an eluent to give N-benzyl-N-(2-propynyl)-4-
methylphenylsulfonamide (4, 0.29 g, 65%) as a colorless oil. IR n (NaCl)
cmꢃ1: 1161, 1348. 400 MHz 1H-NMR (CDCl3) d (ppm): 2.01 (1H, t,
Jꢁ2.8 Hz), 2.45 (3H, s), 3.95 (2H, d, Jꢁ2.8 Hz), 4.36 (2H, s), 7.32—7.36
(7H, m), 7.80 (2H, d, Jꢁ8.4 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm):
21.6, 35.6, 49.8, 74.1, 76.2, 127.8, 128.0, 128.6, 128.7, 129.4, 134.8, 135.9,
143.5. EI-MS m/z (relative intensity): 299 (Mꢄ, 0.9), 144 (Mꢄꢃ155, 100).
HR-MS Calcd for C17H17NO2S: 299.0980, Found: 299.1017.
7.12 (2H, d, Jꢁ8.3 Hz), 7.17—7.28 (6H, m), 7.50 (2H, d, Jꢁ7.9 Hz), 7.61
(2H, d, Jꢁ8.3 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 21.5, 43.4, 68.9,
85.4, 112.7, 124.6, 125.8, 127.0, 127.3, 127.5, 127.7, 128.1, 128.2, 129.3,
129.7, 130.8, 136.0, 137.2, 137.6, 143.3. EI-MS m/z (relative intensity): 405
(Mꢄ, 3.8), 91 (Mꢄꢃ311, 100). HR-MS Calcd for C24H23NO3S: 405.1399,
Found: 405.1387.
Entry 4 According to the general procedure, from 2-iodobenzyl alcohol
(0.23 g, 1.0 mmol), allene (1, 0.22 g, 1.5 mmol), K2CO3 (0.21 g, 1.5 mmol),
Pd(OAc)2 (0.022 g, 0.1 mmol) and DMF (5 ml) was obtained 8 (0.13 g, 52%)
as a colorless oil.
3-Benzyloxy-4-methyleneisochroman (8): IR n (neat) cmꢃ1: 1050, 1110,
1450, 2900, 3025. 400 MHz 1H-NMR (CDCl3) d (ppm): 4.61 (1H, d,
Jꢁ14.8 Hz), 4.71 (1H, d, Jꢁ12.2 Hz), 4.86 (1H, d, Jꢁ12.2 Hz), 5.01 (1H, d,
Jꢁ14.8 Hz), 5.17 (1H, s), 5.38 (1H, s), 5.71 (1H, s), 7.00—7.02 (1H, m),
7.18—7.38 (7H, m), 7.61—7.65 (1H, m). 100 MHz 13C-NMR (CDCl3) d
(ppm): 61.5, 69.0, 98.3, 110.8, 123.7, 124.1, 126.9, 127.6, 127.9, 128.3,
129.4, 133.3, 137.5, 138.0. EI-MS m/z (relative intensity): 252 (Mꢄ, 2.1),
146 (Mꢄꢃ106, 100). HR-MS Calcd for C17H16O2: 252.1150, Found:
252.176.
Entry 5 According to the general procedure, from 2-iodobenzyl alcohol
(0.12 g, 0.5 mmol), allene (1, 0.15 g, 1.0 mmol), K2CO3 (0.14 g, 1.0 mmol),
Pd(OAc)2 (0.011 g, 0.05 mmol), P(2-Tol)3 (0.023 g, 0.075 mmol) and DMF
(5 ml) was obtained 8 (0.11 g, 86%) as a colorless oil.
N-Benzyl-N-(1,2-propadienyl)-4-methylphenylsulfonamide (2) To a
solution of N-benzyl-N-(2-propynyl)-4-methylphenylsulfonamide (4, 0.11 g,
0.35 mmol) in DMF (10 ml), tBuOK (0.011 g, 0.10 mmol) was added at 0 °C
and the whole mixture was stirred at room temperature for 24 h. The reac-
tion mixture was extracted with Et2O (20 mlꢂ3) and the combined ethereal
layer was washed with brine (20 mlꢂ3), and dried over MgSO4. The ethereal
layer was removed under reduced pressure and the residue was purified by
silica gel column chromatography using hexane–AcOEt (4 : 1) as an eluent
to give N-benzyl-N-(1,2-propadienyl)-4-methylphenylsulfona-mide (2,
Entry 6 According to the general procedure, from N-(4-methylfenylsul-
fonyl)-2-iodoaniline (0.043 g, 0.12 mmol), allene (2, 0.051 g, 0.17 mmol),
K2CO3 (0.024 g, 0.17 mmol), Pd(OAc)2 (0.0026 g, 0.012 mmol) and DMF
(5 ml) was obtained 9 (0.051 g, 81%) as a white solid.
1
0.073 g, 70%) as a colorless oil. 400 MHz H-NMR (CDCl3) d (ppm): 2.43
(3H, s), 4.29 (2H, s), 5.12 (2H, d, Jꢁ6.2 Hz), 6.82 (1H, t, Jꢁ6.2 Hz), 7.22—
7.32 (7H, m), 7.70 (2H, d, Jꢁ8.4 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm):
21.6, 50.0, 88.0, 100.0, 127.1, 127.3, 127.7, 128.1, 129.6, 135.1, 136.1,
143.7, 201.9. EI-MS m/z (relative intensity): 299 (Mꢄ, 3.4), 144 (Mꢄꢃ155,
100). HR-MS Calcd for C17H17NO2S: 299.0980, Found: 299.0961.
General Procedure for Annulation Reaction of Allenes (1, 2) Using
Various Aryl Halides (Table 1) Under Ar atmosphere, a mixture of an
aryl halide (1 eq), an allene (1.5—4.0 eq), K2CO3 (1.5—3.0 eq), Pd(OAc)2
(10 mol%), P(2-Tol)3 (15 mol%) and DMF (5 ml) was allowed to react under
the conditions as listed in Table 1. The reaction mixture was extracted with
Et2O (10 mlꢂ3) and the combined ethereal layer was washed with brine
(10 mlꢂ3), and dried over MgSO4. The ethereal layer was removed under re-
duced pressure and the residue was purified by silica gel column chromatog-
raphy to give the annulated product.
2-[N-Benzyl-N-(4-methylphenylsulfonyl)amino]3-methylene-1-(4-
methylphenylsulfonyl)indoline (9): IR n (NaCl) cmꢃ1: 1173, 1364, 1599.
400 MHz 1H-NMR (CDCl3) d (ppm): 2.33 (3H, s), 2.40 (3H, s), 4.15 (1H, d,
Jꢁ15.2 Hz), 4.40 (1H, d, Jꢁ15.2 Hz), 5.38 (1H, s), 5.54 (1H, s), 6.57 (1H,
s), 6.97—7.05 (6H, m), 7.15—7.22 (6H, m), 7.55 (2H, d, Jꢁ10.4 Hz), 7.57
(1H, d, Jꢁ8.0 Hz), 7.84 (2H, d, Jꢁ8.4 Hz). 100 MHz 13C-NMR (CDCl3) d
(ppm): 21.5 (two carbons), 48.4, 76.3, 108.6, 116.6, 120.6, 124.7, 127.2,
127.4, 127.7, 128.4, 128.7, 129.1, 129.2, 129.8, 130.0, 133.7, 135.3, 137.2,
141.2, 142.7, 143.4, 144.5. EI-MS m/z (relative intensity): 544 (Mꢄ), 91
(Mꢄꢃ453, 100). HR-MS Calcd for C30H28N2O4S2: 544.1491, Found:
544.1492.
Entry 7 According to the general procedure, from 2-iodobenzyl alcohol
(0.059 g, 0.25 mmol), allene (2, 0.15 g, 0.50 mmol), K2CO3 (0.069 g,
0.50 mmol), Pd(OAc)2 (0.0056 g, 0.025 mmol) and DMF (5 ml) was obtained
10 (0.066 g, 65%) as a white solid.
Entry 1 According to the general procedure, from N-(4-methylfenyl-
sulfonyl)-2-iodoaniline (0.19 g, 0.50 mmol), allene (1, 0.29 g, 2.0 mmol),
K2CO3 (0.21 g, 1.5 mmol), Pd(OAc)2 (0.011 g, 0.050 mmol) and DMF (5 ml)
was obtained 5 (0.026 g, 99%) as a white solid.
3-[N-Benzyl-N-(4-methylphenylsulfonyl)amino]-3-methyleneisochroman
1
(10): IR n (NaCl) cmꢃ1: 1163, 1342. 400 MHz H-NMR (CDCl3) d (ppm):
2-Benzyloxy-3-methylene-1-(4-methylphenylsulfonyl)indoline (5): IR n
1
(neat) cmꢃ1: 1117, 1358, 1601. 400 MHz H-NMR (CDCl3) d (ppm): 2.32
2.40 (3H, s), 4.25 (1H, d, Jꢁ15.6 Hz), 4.37 (1H, d, Jꢁ15.6 Hz), 4.58 (1H, d,
Jꢁ14.6 Hz), 4.68 (1H, d, Jꢁ14.6 Hz), 5.26 (1H, s), 5.64 (1H, s), 6.28 (1H,
s), 6.97 (1H, dd, Jꢁ3.6, 5.6 Hz), 7.12—7.24 (9H, m), 7.42 (1H, dd, Jꢁ3.6,
5.6 Hz), 7.62 (2H, d, Jꢁ8.4 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 21.6,
48.6, 66.2, 86.5, 112.5, 123.8, 124.3, 126.9, 127.4, 127.5, 127.7, 127.9,
128.8, 129.1, 131.4, 133.5, 136.6, 136.9, 137.3, 143.0. EI-MS m/z (relative
intensity): 405 (Mꢄ, 36.6), 145 (Mꢄꢃ260, 100). HR-MS Calcd for
C24H23NO3S: 405.1399, Found: 405.1396.
(3H, s), 4.63 (1H, d, Jꢁ11.3 Hz), 4.69 (1H, d, Jꢁ11.3 Hz), 5.33 (1H, s), 5.67
(1H, s), 6.02 (1H, s), 7.05 (1H, t, Jꢁ7.6 Hz), 7.13 (2H, d, Jꢁ8.2 Hz), 7.27—
7.36 (7H, m), 7.61 (2H, d, Jꢁ8.2 Hz), 7.64 (1H, d, Jꢁ8.0 Hz). 100 MHz 13C-
NMR (CDCl3) d (ppm): 21.6, 67.4, 91.9, 109.4, 116.1, 121.0, 124.3, 127.1,
127.6, 128.4, 128.1, 128.2, 129.6, 130.1, 135.1, 137.1, 141.5, 142.5, 144.0.
EI-MS m/z (relative intensity): 391 (Mꢄ, 24.8), 91 (Mꢄꢃ300, 100). HR-MS
Calcd for C23H21NO3S: 391.1242, Found: 391.1239.
Entry 2 According to the general procedure, from N-ethoxycarbonyl-2-
iodoaniline (0.15 g, 0.5 mmol), allene (1, 0.11 g, 0.75 mmol), K2CO3 (0.10 g,
0.75 mmol), Pd(OAc)2 (0.011 g, 0.05 mmol) and DMF (5 ml) was obtained 6
(0.11 g, 71%) as a colorless oil.
Entry 8 According to the general procedure, from 2-iodobenzyl alcohol
(0.015 g, 0.066 mmol), allene (2, 0.079 g, 0.26 mmol), K2CO3 (0.027 g,
0.20 mmol), Pd(OAc)2 (0.0015 g, 0.0066 mmol), P(2-Tol)3 (0.0030 g,
0.0099 mmol) and DMF (5 ml) was obtained 10 (0.026 g, 99%) as a white
solid.
Ethyl 2-Benzyloxy-3-methyleneindoline-1-carboxylate (6): IR n (KBr)
1
cmꢃ1: 1060, 1270, 1380, 1410, 1470, 1600, 1720, 2925. 400 MHz H-NMR
Entry
9
According to the general procedure, from 2-iodophenol
(CDCl3) d (ppm): 1.36 (3H, t, Jꢁ7.2 Hz), 4.32 (2H, q, Jꢁ7.2 Hz), 4.54 (1H,
d, Jꢁ11.4 Hz), 4.60 (1H, d, Jꢁ11.4 Hz), 5.37 (1H, s), 5.75 (1H, s), 6.15 (1H,
s), 7.00 (1H, t, Jꢁ7.6 Hz), 7.21—7.34 (6H, m), 7.43 (1H, d, Jꢁ7.6 Hz), 7.78
(1H, d, Jꢁ8.0 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 14.6, 62.0, 67.4,
89.6, 108.2, 115.7, 120.3, 123.0, 127.0, 127.5, 127.8, 128.2, 130.1, 138.2,
142.3, 143.4, 153.0. EI-MS m/z (relative intensity): 309 (Mꢄ, 29.4), 91
(Mꢄꢃ218, 100). HR-MS Calcd for C19H19NO3: 309.1365, Found: 309.1354.
Entry 3 According to the general procedure, from N-(4-methylfenylsul-
fonyl)-2-iodobenzylamine (0.39 g, 1.0 mmol), allene (1, 0.22 g, 1.5 mmol),
K2CO3 (0.21 g, 1.5 mmol), Pd(OAc)2 (0.022 g, 0.1 mmol) and DMF (5 ml)
was obtained 7 (0.30 g, 75%) as a white solid.
3-Benzyloxy-4-methylene-2-(4-methylphenylsulfonyl)-1,2,3,4-tetrahy-
droisoquinoline (7): IR n (neat) cmꢃ1: 1160, 1360, 1460, 1500, 2875, 2925,
3050. 400 MHz 1H-NMR (CDCl3) d (ppm): 2.34 (3H, s), 4.46 (1H, d,
Jꢁ16.0 Hz), 4.58 (1H, d, Jꢁ11.8 Hz), 4.61 (1H, d, Jꢁ16.0 Hz), 4.63 (1H, d,
Jꢁ11.8 Hz), 5.20 (1H, s), 5,64 (1H, s), 5.83 (1H, s), 7.02 (1H, d, Jꢁ6.9 Hz),
(0.052 g, 0.24 mmol), allene (2, 0.14 g, 0.47 mmol), K2CO3 (0.066 g,
0.47 mmol), Pd(OAc)2 (0.0053 g, 0.024 mmol) and DMF (5 ml) was obtained
11 (0.039 g, 42%) as a white solid.
2-[N-Benzyl-N-(4-methylphenylsulfonyl)amino]3-methylene-2,3-dihy-
drobenzofuran (11): 400 MHz 1H-NMR (CDCl3) d (ppm): 2.44 (3H, s), 4.09
(1H, d, Jꢁ16.0 Hz), 4.27 (1H, d, Jꢁ16.0 Hz), 5.11 (1H, d, Jꢁ2.5 Hz), 5.45
(1H, d, Jꢁ2.5 Hz), 6.69 (1H, d, Jꢁ8.4 Hz), 6.87 (1H, t, Jꢁ7.6 Hz), 6.94 (1H,
t, Jꢁ2.5 Hz), 7.08—7.17 (5H, m), 7.23—7.31 (4H, m), 7.72 (2H, d,
Jꢁ8.4 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 21.5, 47.4, 92.3, 107.0,
110.2, 120.9, 121.2, 124.3, 127.1, 127.71, 127.74, 128.6, 129.5, 130.8,
136.5, 136.9, 141.0, 143.6, 160.9. EI-MS m/z (relative intensity): 391 (Mꢄ,
17.8), 91 (Mꢄꢃ300, 100). HR-MS Calcd for C23H21NO3S: 391.1242,
Found: 391.1250.
Entry 10 According to the general procedure, from 2-iodophenol
(0.029 g, 0.13 mmol), allene (2, 0.078 g, 0.26 mmol), K2CO3 (0.036 g,
0.26 mmol), Pd(OAc)2 (0.0029 g, 0.013 mmol), P(2-Tol)3 (0.0061 g,

1506
Vol. 53, No. 11
(2H, d, Jꢁ8.2 Hz), 7.63 (2H, d, Jꢁ8.2 Hz). 100 MHz 13C-NMR (CDCl3) d
(ppm): 21.5, 29.98, 31.8, 48.2, 120.6, 122.4, 125.5, 125.6, 128.6, 126.9,
127.9, 127.3, 128.1, 129.4, 132.6, 134.6, 143.7. EI-MS m/z (relative inten-
sity): 355 (Mꢄ, 30.6), 142 (Mꢄꢃ213, 100). HR-MS Calcd for C21H25NO2S:
355.1601, Found: 355.1582.
0.020 mmol) and DMF (5 ml) was obtained 11 (0.032 g, 62%) as a white
solid.
Entry 12 According to the general procedure, from 2-bromobenzyl al-
cohol (0.094 g, 0.50 mmol), allene (1, 0.29 g, 2.0 mmol), K2CO3 (0.14 g,
1.0 mmol), Pd(OAc)2 (0.011 g, 0.050 mmol), P(2-Tol)3 (0.023 g, 0.075
mmol) and DMF (5 ml) was obtained 8 (0.063 g, 75%) as a white solid.
Entry 13 According to the general procedure, from N-(4-methylpenyl-
sulfonyl)-2-bromobenzylamine (0.17 g, 0.50 mmol), allene (1, 0.29 g,
2.0 mmol), K2CO3 (0.21 g, 1.5 mmol), Pd(OAc)2 (0.011 g, 0.050 mmol) and
DMF (5 ml) was obtained 7 (0.11 g, 54%) as a white solid.
Entry
6
According to the general procedure, from 7 (0.070 g,
t
0.17 mmol) and BuCu(2-thienyl)CNLi2, prepared from lithium 2-thienylcy-
canocuprate (1.2 ml, 0.30 mmol, 0.25 M in THF solution) and tBuLi (0.25 ml,
0.34 mmol, 1.46 M in pentane solution), was obtained 14b (0.050 g, 83%) as
a colorless oil.
Entry 14 According to the general procedure, from N-(4-methylpenyl-
sulfonyl)-2-bromobenzylamine (0.17 g, 0.50 mmol), allene (1, 0.29 g,
2.0 mmol), K2CO3 (0.21 g, 1.5 mmol), Pd(OAc)2 (0.011 g, 0.50 mmol), P(2-
Tol)3 (0.023 g, 0.075 mmol) and DMF (5 ml) was obtained 7 (0.11 g, 52%)
as a white solid.
Entry 15 According to the general procedure, from N-(4-methylpenyl-
sulfonyl)-2-bromobenzylamine (0.17 g, 0.50 mmol), allene (1, 0.29 g,
2.0 mmol), K2CO3 (0.21 g, 1.5 mmol), Pd(OAc)2 (0.011 g, 0.050 mmol),
Bu4NBr (0.16 g, 0.50 mmol) and DMF (5 ml) was obtained 7 (0.15 g, 76%)
as a white solid.
General Procedure for Reaction of Alkyl Metal Reagents with Annu-
lated Products (Table 2) Under Ar atmosphere, an alkyl metal reagent
was added dropwise at ꢃ78 °C to the THF solution of an annulated product,
and the whole mixture was stirred at the same temperature. The reaction
mixture was extracted with AcOEt (10 mlꢂ3) and the combined organic
layer was washed with brine (10 mlꢂ3), and dried over MgSO4. The organic
layer was removed under reduced pressure and the residue was purified by
silica gel column chromatography to give the substituted product.
Entry
7
According to the general procedure, from 7 (0.070 g,
0.17 mmol) and EtMe2MgLi, prepared from methyl lithium (1.3 ml,
1.50 mmol, 1.14 M in Et2O solution) and EtMgBr (0.74 ml, 0.74 mmol, 1.0 M
in THF solution), was obtained 14c (0.064 g, 79%) as a colorless oil.
4-Propyl-2-(4-methylphenylsulfonyl)-1,2-dihydroisoquinoline (14c): IR n
(film) cmꢃ1: 1169, 1350, 1636. 400 MHz H-NMR (CDCl3) d (ppm): 0.93
1
(3H, t, Jꢁ7.3 Hz), 1.53 (2H, sext, Jꢁ7.3 Hz), 2.36 (3H, s), 2.36 (2H, t,
Jꢁ7.3 Hz), 4.51 (2H, s), 6.59 (1H, s), 6.98 (1H, d, Jꢁ7.3 Hz), 7.08 (1H, d,
Jꢁ7.3 Hz), 7.11 (1H, t, Jꢁ7.3 Hz), 7.17 (1H, t, Jꢁ7.3 Hz), 7.21 (2H, d,
Jꢁ7.9 Hz), 7.64 (2H, d, Jꢁ7.9 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm):
13.9, 21.7, 29.7, 31.9, 47.7, 121.6, 122.2, 122.9, 125.5, 127.0, 127.1, 127.6,
128.6, 129.5, 131.3, 134.7, 143.6. EI-MS m/z (relative intensity): 327 (Mꢄ,
38.8), 172 (Mꢄꢃ155, 100). HR-MS Calcd for C19H21NO2S: 327.1293,
Found: 327.1290.
Entry
8
According to the general procedure, from 5 (0.030 g,
0.077 mmol) and BuLi (0.26 ml, 0.38 mmol, 1.45 M in hexane solution) was
obtained 15a (0.011 g, 40%) as a colorless oil.
1-(4-Methylphenylsulfonyl)-3-pentylindole (15a): IR n (film) cmꢃ1: 1173,
1
Entry
1
According to the general procedure, from 8 (0.074 g,
1367. 400 MHz H-NMR (CDCl3) d (ppm): 0.89 (3H, t, Jꢁ7.1 Hz), 1.32—
0.30 mmol) and BuLi (0.46 ml, 0.59 mmol, 1.29 M in hexane solution) was
obtained 13a (0.036 g, 60%) as a colorless oil.
1.34 (4H, m), 1.67 (2H, quint, Jꢁ7.1 Hz), 2.32 (3H, s), 2.63 (2H, t,
Jꢁ7.1 Hz), 7.19—7.31 (5H, m), 7.46 (1H, d, Jꢁ7.6 Hz), 7.72 (2H, d,
Jꢁ8.5 Hz), 7.97 (1H, d, Jꢁ8.3 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm):
14.1, 21.6, 22.5, 24.9, 28.6, 32.6, 113.7, 119.4, 122.5, 122.8, 123.6, 124.4,
126.6, 129.6, 131.1, 135.26, 135.29, 144.5. EI-MS m/z (relative intensity):
341 (Mꢄ, 56.6), 130 (Mꢄꢃ211, 100). HR-MS Calcd for C20H23NO2S:
341.1450, Found: 341.1440.
4-Pentyl-1H-isochromene (13a): IR n (NaCl) cmꢃ1: 756, 1144, 1632,
1
2928. 400 MHz H-NMR (CDCl3) d (ppm): 0.90 (3H, m), 1.33—1.37 (4H,
m), 1.51—1.54 (2H, m), 2.32, (2H, t, Jꢁ8.0 Hz), 5.00 (2H, s), 6.46 (1H, s),
7.02 (1H, d, Jꢁ7.6 Hz), 7.12 (1H, d, Jꢁ7.6 Hz), 7.16 (1H, t, Jꢁ7.6 Hz), 7.26
(1H, t, Jꢁ7.6 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 14.2, 22.6, 27.7,
28.5, 31.7, 68.3, 116.1, 120.2, 123.9, 126.4, 127.9, 129.0, 131.5, 142.2. EI-
MS m/z (relative intensity): 202 (Mꢄ, 100). HR-MS Calcd for C14H18O:
202.1358, Found: 202.1359.
Entry
9
According to the general procedure, from 5 (0.030 g,
0.077 mmol), BuLi (0.12 ml, 0.15 mmol, 1.26 M in hexane solution) and
HMPA (0.033 g, 0.18 mmol) was obtained 15a (0.022 g, 83%) as a colorless
Entry
2
According to the general procedure, from 8 (0.076 g,
oil.
0.30 mmol), BuLi (0.93 ml, 1.20 mmol, 1.29 M in hexane solution) and
TMEDA (0.17 g, 1.44 mmol) was obtained 13a (0.055 g, 91%) as a colorless
Entry 10 According to the general procedure, from
5 (0.030 g,
0.077 mmol) and tBuLi (0.26 ml, 0.38 mmol, 1.46 M in pentane solution) was
oil.
obtained 15b (0.018 g, 68%) as a colorless oil.
Entry
3
According to the general procedure, from 8 (0.076 g,
3-(2,2-Dimethylpropyl)-1-(4-methylphenylsulfonyl)indole (15b): IR
n
t
(film) cmꢃ1: 1173, 1362. 400 MHz 1H-NMR (CDCl3) d (ppm): 0.91 (9H, s),
2.32 (3H, s), 2.54 (2H, s), 7.17—7.19 (5H, m), 7.46 (1H, d, Jꢁ7.8 Hz), 7.72
(2H, d, Jꢁ7.8 Hz), 7.97 (1H, d, Jꢁ8.1Hz). 100 MHz 13C-NMR (CDCl3) d
(ppm): 21.6, 29.7, 32.0, 38.6, 100.5, 113.6, 120.1, 120.8, 122.8, 124.1,
124.4, 126.6, 129.6, 132.3, 135.2, 144.6. EI-MS m/z (relative intensity): 341
(Mꢄ, 34.6), 284 (Mꢄꢃ57, 100). HR-MS Calcd for C20H23NO2S: 341.1450,
Found: 341.1440.
0.30 mmol) and BuLi (0.55 ml, 0.60 mmol, 1.10 M in pentane solution) was
obtained 13b (0.053 g, 87%) as a colorless oil.
4-(2,2-Dimethylpropyl)-1H-isochromene (13b): IR n (NaCl) cmꢃ1: 758,
1
1123, 1624, 2953. 400 MHz H-NMR (CDCl3) d (ppm): 0.93 (9H, s), 2.27
(2H, s), 4.94 (2H, s), 6.40 (1H, s), 7.01 (1H, d, Jꢁ7.6 Hz), 7.14 (1H, t,
Jꢁ7.0 Hz), 7.19—7.23 (2H, m). 100 MHz 13C-NMR (CDCl3) d (ppm): 30.0,
31.7, 40.2, 68.8, 114.0, 121.0, 124.0, 126.1, 127.6, 128.4, 132.7, 144.7. EI-
MS m/z (relative intensity): 202 (Mꢄ, 75.2), 145 (Mꢄꢃ57, 100). HR-MS
Calcd for C14H18O: 202.1358, Found: 202.1344.
Entry 11 According to the general procedure, from
5 (0.030 g,
0.077 mmol), BuLi (0.26 ml, 0.38 mmol, 1.46 M in pentane solution) and
Entry
4
According to the general procedure, from 7 (0.089 g,
HMPA (0.066 g, 0.37 mmol) was obtained 15b (0.011 g, 40%) as a colorless
0.22 mmol), BuLi (0.26 ml, 0.33 mmol, 1.26 M in hexane solution) and
HMPA (0.070 g, 0.39 mmol) was obtained 14a (0.034 g, 44%) as a colorless
oil.
oil.
Entry 12 According to the general procedure, from
5 (0.042 g,
0.11 mmol) and EtMe2MgLi, prepared from methyl lithium (0.53 ml,
0.60 mmol, 1.14 M in Et2O solution) and EtMgBr (0.33 ml, 0.32 mmol, 1.0 M
in THF solution), was obtained 15c (0.032 g, 93%) as a colorless oil.
1-(4-Methylphenylsulfonyl)-3-propylindole (15c): IR n (film) cmꢃ1: 1173,
1369. 400 MHz 1H-NMR (CDCl3) d (ppm): 0.96 (3H, t, Jꢁ7.3 Hz), 1.70
(2H, sext, Jꢁ7.3 Hz), 2.32 (3H, s), 2.62 (2H, t, Jꢁ7.3 Hz), 7.18—7.30 (5H,
m), 7.46 (1H, d, Jꢁ7.6 Hz), 7.73 (2H, d, Jꢁ8.3 Hz), 7.96 (1H, d, Jꢁ8.3 Hz).
100 MHz 13C-NMR (CDCl3) d (ppm): 14.0, 21.6, 22.1, 27.0, 113.6, 119.3,
119.5, 122.6, 122.8, 122.9, 123.3, 124.4, 126.4, 126.6, 135.2, 144.5. EI-MS
m/z (relative intensity): 313 (Mꢄ, 100), 284 (Mꢄꢃ29, 96). HR-MS Calcd for
C18H19NO2S: 313.1137, Found: 313.1153.
2-(4-Methylphenylsulfonyl)-4-pentyl-1,2-dihydroisoquinoline (14a): IR n
1
(film) cmꢃ1: 1169, 1350, 1639. 400 MHz H-NMR (CDCl3) d (ppm): 0.87
(3H, t, Jꢁ7.4 Hz), 1.31—1.50 (6H, m), 2.36 (3H, s), 2.37 (2H, t, Jꢁ7.4 Hz),
4.51 (2H, s), 6.58 (1H, s), 6.98 (1H, d, Jꢁ7.4 Hz), 7.09 (1H, t, Jꢁ7.4 Hz),
7.11 (1H, t, Jꢁ7.4 Hz), 7.16 (1H, d, Jꢁ7.4 Hz), 7.21 (2H, d, Jꢁ8.2 Hz), 7.64
(2H, d, Jꢁ8.2 Hz). 100 MHz 13C-NMR (CDCl3) d (ppm): 14.2, 21.6, 22.5,
28.3, 29.8, 31.6, 47.7, 121.6, 122.4, 122.8, 125.5, 127.0, 127.1, 127.7, 128.6,
130.0, 131.3, 134.6, 143.6. EI-MS m/z (relative intensity): 355 (Mꢄ, 16.5),
142 (Mꢄꢃ213, 100). HR-MS Calcd for C21H25NO2S: 355.1601, Found:
355.1607.
Entry
5
According to the general procedure, from 7 (0.071 g,
t
0.18 mmol) and BuLi (0.15 ml, 0.21 mmol, 1.40 M in pentane solution) was
obtained 14b (0.037 g, 60%) as a colorless oil.
References and Notes
1) Nakamura I., Yamamoto Y., Chem. Rev., 104, 2127—2198 (2004).
2) Yamamoto Y., Radhakrishnan U., Chem. Soc. Rev., 28, 199—207
(1999).
3) Zeni G., Larock R. C., Chem. Rev., 104, 2285—2309 (2004).
4) Larock R. C., Pure Appl. Chem., 71, 1435—1442 (1999).
4-(2,2-Dimethylpropyl)-2-(4-methylphenylsulfonyl)-1,2-dihydroisoquino-
line (14b): IR n (film) cmꢃ1: 1169, 1348, 1628. 400 MHz 1H-NMR (CDCl3)
d (ppm): 0.84 (9H, s), 2.35 (3H, s), 2.35 (2H, s), 4.47 (2H, s), 6.56 (1H, s),
6.98 (1H, d, Jꢁ7.4 Hz), 7.08 (1H, t, Jꢁ7.4 Hz), 7.14—7.16 (2H, m), 7.20

November 2005
1507
5) Ma S., “Handbook of Organo-palladium Chemistry for Organic Syn-
thesis,” Vol. I, Chap. IV.7, ed. by Negishi E.-I., John Wiley & Sons,
New York, 2002.
17) Desarbre E., Merour J.-Y., Tetrahedron Lett., 37, 43—46 (1995).
18) Hoff S., Brandsma L., Arens J. F., Recl. Trav. Chim. Pays-Bas, 87,
1179—1184 (1968).
6) Ma S., Acc. Chem. Res., 36, 701—712 (2003).
19) Russell C. E., Hegedus L. S., J. Am. Chem. Soc., 105, 943—949
7) Ma S., Negishi E.-I., J. Am. Chem. Soc., 117, 6345—6357 (1995).
8) Bates R. W., Satcharoen V., Chem. Soc. Rev., 31, 12—21 (2002).
9) Zimmer R., Dinesh C. U., Nandanan E., Khan F. A., Chem. Rev., 100, 21) All the structures of annulated products were confirmed by H-NMR,
(1983).
20) Zimmer R., Synthesis, 1993, 165—178 (1993).
1
3067—3125 (2000).
13C-NMR, 1H-COSY, HMQC and NOESY.
10) Watanabe K., Hiroi K., Heterocycles, 59, 453—457 (2003).
11) Grigg R., Koppen I., Rasparini M., Sridharan V., Chem. Commun.,
2001, 964—965 (2001).
22) Larock carried out his annulation reactions in the presence of tetra-
butylammonium chloride13—16); however, the role of such an ammo-
nium salt is obscure at present.
12) Grigg R., Sridharan V., J. Organomet. Chem., 576, 65—87 (1999).
13) Larock R. C., Berrios-Pena N. G., Fried C. A., J. Org. Chem., 56,
2615—2617 (1991).
23) The asymmetric induction for this reaction with BINAP as a chiral lig-
and according to Larocks’ report16) did not show any chiral induction.
This observation may support the latter mechanism.
14) Larock R. C., He Y., Leong W. W., Han X., Refvic M. D., Zenner J. 24) For Related intermolecular processes employing methoxyallene and
M., J. Org. Chem., 63, 2154—2160 (1998).
vinyl halides, see: Chaptal N., Colovray-Gotterland V., Grandjean C.,
15) Larock R. C., Tu C., Pace, P., J. Org. Chem., 63, 6859—6866 (1998).
16) Zenner J. M., Larock R. C., J. Org. Chem., 64, 7312—7322 (1999).
Cazes B., Gore J., Tetrahedron Lett., 32, 1795—1798 (1991).