Synthesis of 3-substituted 3H-indol-3-ols by the reaction of 2-isocyanophenyl ketones with Grignard reagents

Article abstract of DOI:10.1016/j.tet.2010.08.023

A facile method for the synthesis of 3-substituted 3H-indol-3-ols has been developed. Thus, 2-isocyanophenyl ketones are allowed to react with various Grignard reagents to give the corresponding desired indolol derivatives in generally fair to good yields. The formation of 3-aryl-2,3-dimethylindolin-3-ols by the reaction of 2-isocyanobenzophenones with 2 M amounts of methylmagnesium bromide is also reported.

Full text of DOI:10.1016/j.tet.2010.08.023

Tetrahedron 66 (2010) 7961e7964
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Synthesis of 3-substituted 3H-indol-3-ols by the reaction of 2-isocyanophenyl
ketones with Grignard reagents
*
Kazuhiro Kobayashi , Yuta Okamura, Shuhei Fukamachi, Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 June 2010
Received in revised form 10 August 2010
Accepted 10 August 2010
Available online 14 August 2010
A facile method for the synthesis of 3-substituted 3H-indol-3-ols has been developed. Thus, 2-iso-
cyanophenyl ketones are allowed to react with various Grignard reagents to give the corresponding
desired indolol derivatives in generally fair to good yields. The formation of 3-aryl-2,3-dimethylindolin-
3-ols by the reaction of 2-isocyanobenzophenones with 2 M amounts of methylmagnesium bromide is
also reported.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
3H-Indol-3-ols
2-Isocyanophenyl ketones
Grignard reagents
Indolin-3-ols
Imidoyl anions
1. Introduction
knowledge, few other reports on the methods for the general prep-
aration of 3H-indol-3-ol derivatives have appeared so far.5
In the course of our studies on utilizations of 2-isocyanophenyl
ketones for the synthesis of benzene-fused heterocycles,1 we pre-
viously reported syntheses of 2,4-disubstituted quinolines,1a 2-func-
tionalized 4-alkylidene-4H-1,3-benzoxazines,1b,d and 4-substituted
quinoline-2(1H)-thiones.1c In this paper, we wish to report that the
reaction of 2-isocyanophenyl ketones with Grignard reagents pro-
vides an efficient route to 3-substituted 3H-indol-3-ols. 1H-Indoles
are undoubtedly very important heterocycles in organic synthesis.
3H-Indoles are also an important class of heterocycles, because
a number of molecules having this skeleton have been found in
nature2 and some 3H-indole derivatives have been utilized for the
construction of indoline alkaloids.2a Although a large number of
methods to prepare 1H-indoles have been reported, the methodolo-
gies for the synthesis of 3H-indole are very limited.3 Therefore,
development of new and convenient method for the synthesis of
3H-indoles is of considerable merit. 3H-Indol-3-ols are also of
potential importance in organic synthesis. Liu and McWhorter, have
reported a synthesis of 3-substituted 2-aryl-3H-indol-3-ols by the
reaction of 2-aryl-3H-indol-3-ones with Grignard reagents.3a They
have also reported an elaboration of the 3H-indol-3-ol derivatives to
more complex and important molecules.4 However, to the best of our
2. Results and discussion
The reactions for preparing 3-substituted 3H-indol-3-ols 2 from
2-isocyanophenyl ketones 1, which can be easily prepared from the
respective 2-aminophenyl ketones in two steps, were carried out as
shown in Scheme 1. Thus, isocyano ketones 1 were allowed to react
with an equimolar amount of Grignard reagents in THF at 0 ꢀC. The
reactions proceeded relative cleanly and completed within 10 min
to give 3H-indol-3-ols 2 after usual aqueous workup followed by
purification using column chromatography on silica gel using
Et2OeC6H6 (1:2, v/v) as an eluent.6 The results obtained from the
reactions of various isocyano ketones 1 with aliphatic and aromatic
Grignard reagents are summarized in Table 1, which indicates that
yields of the desired products 2 were generally good to excellent.
While the use of aryl Grignard reagents gave generally excellent
yields of the desired products (entries 2e7 and 11), alkyl Grignard
reagents, such as methyl- or ethyl-magnesium bromide, gave the
corresponding desired products in rather diminished yields com-
pared to those using aryl Grignard reagents (entries 1, 8e10, and
12). This is probably due to the formation of products arising from
the initial addition of Grignard reagents to the carbonyl moiety. The
reaction of 1a with methylmagnesium bromide was attempted in
a less polar solvent, such as toluene, resulted in the formation of
a rather complex mixture of products containing the starting 1a,
and a considerable decrease in the yield of the desired product 2a
* Corresponding author. Tel./fax: þ81 857 31 5263; e-mail address: kkoba@
chem.tottori-u.ac.jp (K. Kobayashi).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.023

7962
K. Kobayashi et al. / Tetrahedron 66 (2010) 7961e7964
(29%) was observed. It should be noted that the use of organo-
lithiums in place of Grignard reagents resulted in the formation of
complex mixtures of products.
BrMgO
R1
COR2
R2
R3
R3MgBr
R1
1
N
R3
N
HO
5
R1
COR2
NC
4
R2
R3
R1
R3MgBr
THF, 0
º
C
N
H3O+
1
2
2
Scheme 1.
Scheme 3.
3. Experimental
3.1. General
Table 1
Preparation of 3-substituted 3H-indol-3-ols 2
Entry
1
R
3 in R3MgBr
2 (Yield/%)a
1
2
3
4
5
6
7
8
1a (R1¼H, R2¼Ph)
Me
Ph
4-MeC6H4
3-ClC6H4
4-ClC6H4
3-MeOC6H4
3,4-(MeO)2C6H3
Me
Me
Me
Ph
2a (59)
2b (88)
2c (93)
2d (96)
2e (98)
2f (98)
2g (82)
2h (57)
2i (58)
2j (60)
2k (68)
2l (50)
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were
determined with a Shimadzu FTIR-8300 spectrophotometer. The 1H
NMR spectra were determined in CDCl3 using TMS as an internal
reference with a JEOL ECP500 FT NMR spectrometer operating at
500 MHz. The 13C NMR spectra were determined using TMS as an
internal reference with a JEOL ECP500 FT NMR spectrometer
operating at 125 MHz. Low-resolution MS spectra (EI, 70 eV) were
measured by a JEOL JMS AX505 HA spectrometer. TLC was carried
out on a Merck Kieselgel 60 PF254. Column chromatography was
performed using Merck Kieselgel 60 (0.063e0.200 mm). All of the
organic solvents used in this study were dried over appropriate
drying agents and distilled prior to use.
1a
1a
1a
1a
1a
1a
1b (R1¼H, R2¼4-ClC6H4)
1c (R1¼H, R2¼4-MeOC6H4)
1d (R1¼Cl, R2¼Ph)
1d
9
10
11
12
1e (R1¼Cl, R2¼Et)
Et
a
Isolated yields.
When 2 M amounts of methylmagnesium bromide were used,
3-substituted 2,2-dimethylindolin-3-ols 3 were obtained, as shown
in Scheme 2. Yields of the products are moderate as indicated in
Scheme 2 as well. 2-Ethyl- and 2-aryl-3H-indol-3-oxides in-
termediates (5; R3¼Et and Ar, respectively) were found to be ex-
tremely stable toward excess ethyl- or aryl-magnesium bromide,
and no formation of the corresponding 2,2-diethyl- or 2,2-diary-
lindolin-3-ols was observed even at elevating reaction tempera-
tures. Addition of methylmagnesium bromide to the solution from
the reaction of 1a with phenylmagnesium bromide did not allow us
to introduce a methyl group.
3.2. Starting materials
2-Isocyanophenyl ketones 1a, 1c, 1d, and 1e were prepared by
the previously reported our method.1a,b All other chemicals used in
this study were commercially available.
3.2.1. N-[2-(4-Chlorobenzoyl)phenyl]formamide. This compound was
prepared by treating 2-aminophenyl(4-chlorophenyl)methanone
with excess HCO2H in refluxing toluene under azeotropic con-
ditions1a in 93% yield; a yellow viscous oil; Rf10.25 (1:2 AcOEte
HO
R2
hexane); IR (neat) 3312, 1697, 1643, 1603 cmꢁ1; H NMR
d 7.15 (dd,
R1
2 equiv. MeMgBr
J¼7.8, 7.3 Hz, 1H), 7.48 (d, J¼8.2 Hz, 2H), 7.54 (d, J¼8.2 Hz, 1H), 7.60
1b, c
Me
Me
THF, 0 ºC
(dd, J¼8.2, 7.3 Hz, 1H), 7.67 (d, J¼8.2 Hz, 2H), 8.49 (s, 1H), 8.67 (d,
N
H
J¼7.8 Hz, 1H), 10.61 (s, 1H); 13C NMR
d 122.33, 122.83, 123.22, 128.73,
131.31, 133.19, 134.49, 136.67, 139.17, 139.25, 159.56, 198.06. Anal.
Calcd C14H10ClNO2: C, 64.75; H, 3.88; N, 5.39. Found: C, 64.63; H,
4.00; N, 5.32.
3a R1 = H, R2 = 4-ClC6H4 43%
3b R1 = H, R2 = 4-MeOC6H4 41%
3c R1 = Cl, R2 = Ph 48%
Scheme 2.
3.2.2. 4-Chlorophenyl(2-isocyanophenyl)methanone (1b). This com-
pound was prepared by dehydration of the above formamide with
POCl3eEt3N in THF at 0 ꢀC7 in 77% yield; yellow crystals; mp
The pathway leading to 3-substituted 3H-indol-3-ols 2 from
2-isocyanophenyl ketones 1 and Grignard reagents is illustrated in
Scheme 3. The first step of the present transformation is the
addition of a Grignard reagent to the isocyano carbon of 1, gener-
ating an imidoyl anion intermediate 4. This intermediate cyclizes
rapidly by the intramolecular attack of the imidoyl anion on the
carbonyl carbon to give the 3H-indol-3-oxide intermediate 5,
which is protonated by aqueous workup to provide 2.
85e88 ꢀC (hexaneeEt2O); IR (KBr) 2130, 1661 cmꢁ1; 1H NMR
d 7.48
(d, J¼8.7 Hz, 2H), 7.51e7.55 (m, 3H), 7.59 (ddd, J¼7.8, 7.3, 1.8 Hz, 1H),
7.76 (d, J¼8.7 Hz, 2H); 13C NMR
d 127.93, 129.17 (two overlapped
C’s), 129.29, 129.35, 131.37, 131.67, 134.50, 135.73, 140.67, 169.34,
192.44. Anal. Calcd C14H8ClNO: C, 69.58; H, 3.34; N, 5.80. Found: C,
69.42; H, 3.32; N, 5.50.
As mentioned above, the reaction of 2-isocyanophenyl ketones
with Grignard reagents under milder conditions has allowed pre-
paring a range of 3-substituted 3H-indol-3-ols. The use of an excess
amount of methylmagnesium bromide has also allowed preparing
3-substituted 2,2-dimethylindolin-3-ols. The present synthetic
method may be of value in organic synthesis because it has
advantages over the previous method;3a the readily availability of
the starting materials and the simplicity of the operations.
3.3. General procedure for the reaction of 2-isocyanophenyl
ketones 1 with Grignard reagents
To a stirred solution of one of 2-isocyanophenyl ketones
(2.0 mmol) in THF (5 mL) at 0 ꢀC was added one of Grignard
reagents (Et2O solution, 1.0 mmol for the preparation of 2 or
2.0 mmol for 3) dropwise; the mixture was stirred for 10 min at the
same temperature. Saturated aqueous NH4Cl (10 mL) was added

K. Kobayashi et al. / Tetrahedron 66 (2010) 7961e7964
7963
and organic materials were extracted with Et2O three times (10 mL
1603 cmꢁ1; 1H NMR
d
3.56 (s, 1H), 3.83 (s, 3H), 3.84 (s, 3H), 6.66 (d,
each). The combined extracts were washed with brine, dried over
anhydrous Na2SO4, and concentrated by evaporation of the solvent.
The residue was subjected to column chromatography on silica gel
(1:2 Et2OeC6H6) to give the desired products.
J¼8.2 Hz, 1H), 7.05 (dd, J¼7.8, 7.3 Hz, 1H), 7.11 (d, J¼7.8 Hz, 1H),
7.19e7.22 (m, 2H), 7.26 (dd, J¼7.8, 7.3 Hz, 2H), 7.34e7.37 (m, 3H), 7.45
(dd, J¼8.2, 1.4 Hz, 1H), 7.59 (d, J¼1.4 Hz, 1H); 13C NMR
d 55.73, 55.76,
87.09, 110.21, 111.20, 121.61, 122.76, 123.73, 123.84, 124.15, 126.24,
127.48, 128.68, 129.74, 140.27, 143.75, 148.52, 151.69, 152.72, 179.93;
MS m/z 345 (Mþ, 100). Anal. Calcd C22H19NO3: C, 76.50; H, 5.54; N,
4.06. Found: C, 76.13; H, 5.54; N, 4.10.
3.3.1. 2-Methyl-3-phenyl-3H-indol-3-ol (2a). Colorless needles; mp
179e184 ꢀC (C6H6eTHF); IR (KBr) 3208 cmꢁ1; 1H NMR
d
1.93 (s, 3H),
4.25 (br s, 1H), 7.14 (t, J¼7.3 Hz, 1H), 7.21 (d, J¼7.3 Hz, 1H), 7.24e7.32
(m, 7H); 13C NMR
14.09, 87.09, 119.73, 123.68, 124.84, 126.44,
d
3.3.8. 3-(4-Chlorophenyl)-2-methyl-3H-indol-3-ol (2h). A yellow
solid; mp 189e191 ꢀC (hexaneeEt2O); IR (KBr) 3130 cmꢁ1; 1H NMR
127.75, 128.55, 129.46, 138.60, 143.43, 153.07, 187.06; MS m/z 223
(Mþ, 100). Anal. Calcd C15H13NO: C, 80.69; H, 5.87; N, 6.27. Found: C,
80.54; H, 5.94; N, 6.24.
d
1.97 (s, 3H), 3.70 (br s, 1H), 7.14e7.19 (m, 3H), 7.27 (d, J¼8.7 Hz,
2H), 7.31e7.34 (m, 3H); 13C NMR
d
14.12, 86.78, 119.94, 123.60,
126.39, 126.65, 128.79, 129.84, 133.74, 137.09, 142.80, 153.14, 186.42;
MS m/z 257 (Mþ, 100). Anal. Calcd C15H12ClNO: C, 69.91; H, 4.69; N,
5.43. Found: C, 69.89; H, 4.71; N, 5.47.
3.3.2. 2,3-Diphenyl-3H-indol-3-ol (2b)8. A white solid; mp
195e197 ꢀC (hexaneeEt2O) (lit.,8 mp 197e199 ꢀC). The spectral (IR
and 1H NMR) data for this product were identical to those reported
previously.9 13C NMR
d
87.32, 121.12, 122.82, 124.17, 126.79, 127.58,
3.3.9. 3-(4-Methoxylphenyl)-2-methyl-3H-indol-3-ol (2i). An or-
ange solid; mp 176e179 ꢀC (hexaneeTHF); IR (KBr) 3131,
128.32, 128.76, 129.23, 129.72, 130.89, 131.16, 139.65, 143.87, 152.51,
180.27.
1609 cmꢁ1; 1H NMR
d 2.06 (s, 3H), 3.00 (s, 1H), 3.79 (s, 3H), 6.84 (d,
J¼8.7 Hz, 2H), 7.14e7.21 (m, 4H), 7.34 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H),
3.3.3. 2-(4-Methylphenyl)-3-phenyl-3H-indol-3-ol (2c). A white
solid; mp 170e174 ꢀC (hexaneeEt2O); IR (KBr) 3152, 1614 cmꢁ1; 1H
7.41 (d, J¼7.8 Hz, 1H); 13C NMR
d 14.37, 55.23, 86.98, 114.00, 119.96,
123.50, 126.20, 126.38, 129.62, 130.42, 143.01, 153.45, 159.30,
186.60; MS m/z 253 (Mþ, 100). Anal. Calcd C16H15NO2: C, 75.87; H,
5.97; N, 5.53. Found: C, 75.71; H, 6.09; N, 5.31.
NMR
d
2.33 (s, 3H), 2.87 (s, 1H), 7.10e7.13 (m, 3H), 7.16 (dd, J¼7.3,
0.9 Hz, 1H), 7.21 (tt, J¼7.3, 1.4 Hz, 1H), 7.27 (dd, J¼7.8, 7.3 Hz, 2H),
7.32 (td, J¼7.3, 1.4 Hz, 1H), 7.38 (dd, J¼7.8, 1.4 Hz, 2H), 7.56 (d,
J¼7.8 Hz, 1H), 7.92 (d, J¼8.2 Hz, 2H); 13C NMR
d
21.58, 87.28, 120.95,
3.3.10. 5-Chloro-2-methyl-3-phenyl-3H-indol-3-ol (2j). A yellow
solid; mp 131e134 ꢀC (hexaneeEt2O); IR (KBr) 3128 cmꢁ1; 1H NMR
122.77, 124.17, 126.53, 127.52, 128.21, 128.72, 129.09, 129.25, 129.73,
139.85, 141.69, 143.78, 152.73, 180.21; MS m/z 299 (Mþ, 100). Anal.
Calcd C21H17NO: C, 84.25; H, 5.72; N, 4.68. Found: C, 84.10; H, 5.74;
N, 4.69.
(500 MHz, CDCl3)
d
2.08 (s, 3H), 2.91 (s, 1H), 7.17 (d, J¼1.8 Hz, 1H),
7.24 (dd, J¼7.8, 1.8 Hz, 1H), 7.30e7.36 (m, 6H); 13C NMR (125 MHz,
CDCl3)
d 14.45, 87.28, 120.64, 124.29, 124.70, 128.17, 128.79, 129.60,
132.36, 137.56, 144.92, 151.55, 187.35; MS m/z 257 (Mþ, 100). Anal.
Calcd C15H12ClNO: C, 69.91; H, 4.69; N, 5.43. Found: C, 69.74; H,
4.94; N, 5.20.
3.3.4. 2-(3-Chlorophenyl)-3-phenyl-3H-indol-3-ol (2d). A pale-yel-
low solid; mp 200e203 ꢀC (hexaneeEt2O); IR (KBr) 3169 cmꢁ1; 1H
NMR
d
3.06 (s, 1H), 7.14 (td, J¼7.3, 0.9 Hz, 1H), 7.17 (dd, J¼7.3, 1.4 Hz,
1H), 7.21 (t, J¼7.8 Hz, 1H), 7.24 (tt, J¼7.3, 1.4 Hz, 1H), 7.28 (dd, J¼7.3,
1.4 Hz, 2H), 7.31e7.36 (m, 4H), 7.54 (d, J¼7.8 Hz, 1H), 7.83 (dd, J¼7.8,
3.3.11. 5-Chloro-2,3-diphenyl-3H-indol-3-ol (2k)6. A white solid;
mp 224e227 ꢀC (hexaneeEt2O) (lit.,6 mp 223e223.5 ꢀC); IR (KBr)
1.4 Hz, 1H), 8.09 (t, J¼1.8 Hz, 1H); 13C NMR
d
87.29, 121.36, 122.85,
3117 cmꢁ1; 1H NMR
d
3.12 (s, 1H), 7.13 (d, J¼2.3 Hz, 1H), 7.23e7.26
124.15, 127.24, 127.37, 127.77, 128.80, 128.85, 129.49, 129.89, 131.11,
132.63, 134.40, 139.01, 143.81, 152.22, 179.04; MS m/z 319 (Mþ, 100).
Anal. Calcd C20H14ClNO: C, 75.12; H, 4.41; N, 4.38. Found: C, 74.96;
H, 4.53; N, 4.41.
(m, 2H), 7.28e7.32 (m, 4H), 7.36 (d, J¼7.3 Hz, 2H), 7.39 (tt, J¼7.3,
1.4 Hz, 1H), 7.46 (d, J¼7.8 Hz, 1H), 7.99 (dd, J¼7.8, 1.4 Hz, 2H); 13C
NMR
d 87.35, 121.99, 123.49, 124.09, 127.92, 128.39, 128.93, 129.26,
129.74, 130.41, 131.46, 132.52, 138.93, 145.37, 150.83, 180.61.
3.3.5. 2-(4-Chlorophenyl)-3-phenyl-3H-indol-3-ol (2e). A palꢁe1-yel-
3.3.12. 5-Chloro-2,3-diethyl-3H-indol-3-ol (2l). A pale-yellow oil; Rf
low solid; mp 174e177 ꢀC (hexaneeEt2O); IR (KBr) 3200 cm
;
1H
0.28(1:2 Et2OeC6H6); IR (neat) 3219 cmꢁ1; 1H NMR
d
0.57 (t, J¼7.3 Hz,
NMR
d
3.84 (s, 1H), 7.09 (t, J¼7.3 Hz, 1H), 7.14 (d, J¼7.3 Hz, 1H),
3H),1.34(t, J¼7.3 Hz, 3H), 1.82e1.89(m,1H), 2.02e2.09(m,1H), 2,12(s,
1H), 2.42e2.50 (m,1H), 2.65e2.73 (m,1H), 7.30 (d, J¼2.3 Hz,1H), 7.34
7.19e7.27 (m, 6H), 7.32 (dd, J¼7.8, 1.4 Hz, 2H), 7.42 (d, J¼7.8 Hz, 1H),
7.91 (d, J¼8.7 Hz, 2H); 13C NMR
d
87.18, 121.12, 122.89, 124.15,
(d, J¼8.2 Hz, 1H), 7.38 (dd, J¼8.2, 2.3 Hz, 1H); 13C NMR
d 7.18, 9.81,
126.95, 127.68, 128.59, 128.80, 129.37, 129.82, 130.44, 137.36, 139.33,
143.87, 152.37, 179.38; MS m/z 319 (Mþ, 100). Anal. Calcd
C20H14ClNO: C, 75.12; H, 4.41; N, 4.38. Found: C, 74.90; H, 4.59;
N, 4.40.
21.63, 29.29, 87.18, 120.90, 123.09, 129.52, 131.59, 141.42, 151.83,
189.94; MS m/z 223 (Mþ, 100). Anal. Calcd C12H14ClNO: C, 64.43; H,
6.31; N, 6.26. Found: C, 64.36; H, 6.48; N, 6.48.
3.3.13. 3-(4-Chlorophenyl)-2,2-dimethylindolin-3-ol (3a). A yellow
3.3.6. 2-(3-Methoxyphenyl)-3-phenyl-3H-indol-3-ol (2f). A paꢁle1-
oil; Rf 0.29 (1:5 THFehexane); IR (neat) cmꢁ1 1H NMR
; d 0.72 (s,
yellow solid; mp 212e215 ꢀC (hexaneeTHF); IR (KBr) 3169 cm
;
3H), 1.32 (s, 3H), 2.14 (br s, 1H), 3.61 (br s, 1H), 6.66 (d, J¼7.8 Hz, 1H),
6.74 (dd, J¼7.8, 7.3 Hz, 1H), 7.04 (d, J¼7.8 Hz, 1H), 7.12 (dd, J¼7.8,
7.3 Hz, 1H), 7.25 (d, J¼8.7 Hz, 2H), 7.37 (d, J¼8.7 Hz, 2H); 13C NMR
1H NMR
d
3.18 (s, 1H), 3.74 (s, 3H), 6.90 (dd, J¼8.2, 2.3 Hz, 1H), 7.11
(dd, J¼7.8, 7.3 Hz, 1H), 7.15 (d, J¼7.3 Hz, 1H), 7.18 (t, J¼8.2 Hz, 1H),
7.21 (t, J¼7.3 Hz, 1H), 7.25e7.30 (m, 3H), 7.36 (dd, J¼7.3, 1.4 Hz, 2H),
7.52 (d, J¼7.8 Hz, 1H), 7.55 (d, J¼8.2 Hz, 1H), 7.58 (s, 1H); 13C NMR
d
21.29, 27.16, 68.27, 85.13, 110.93, 119.31, 125.39, 127.86, 128.98,
129.91, 132.47, 133.30, 138.93, 149.80; MS m/z 273 (Mþ, 7.3), 255
(100). Anal. Calcd C16H16ClNO: C, 70.20; H, 5.89; N, 5.12. Found: C,
70.28; H, 6.08; N, 5.06.
d
55.22, 87.38, 113.14, 118.18, 121.25, 122.03, 122.81, 124.16, 126.91,
127.62, 128.78, 129.29, 129.84, 132.23, 139.65, 143.94, 152.68,
159.35, 180.09; MS m/z 315 (Mþ, 100). Anal. Calcd C21H17NO2: C,
79.98; H, 5.43; N, 4.44. Found: C, 79.73; H, 5.52; N, 4.44.
3.3.14. 3-(4-Methoxyphenyl)-2,2-dimethylindolin-3-ol (3b). A yel-
low oil; Rf 0.42 (1:8 AcOEteC6H6); IR (neat) 3343, 1609 cmꢁ1 1H
;
3.3.7. 2-(3,4-Dimethoxyphenyl)-3-phenyl-3H-indol-3-ol (2g). A pale-
yellow solid; mp 214e216 ꢀC (hexaneeTHF); IR (KBr) 3140,
NMR
d 0.79 (s, 3H), 1.41 (s, 3H), 2.11 (s, 1H), 3.71 (br s, 1H), 3.83
(s, 3H), 6.75 (d, J¼7.8 Hz, 1H), 6.81 (dd, J¼7.8, 7.3 Hz, 1H), 6.89 (d,

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K. Kobayashi et al. / Tetrahedron 66 (2010) 7961e7964
J¼8.7 Hz, 2H), 7.17 (d, J¼7.8 Hz, 1H), 7.19 (dd, J¼7.8, 7.3 Hz, 1H), 7.43
References and notes
(d, J¼8.7 Hz, 2H); 13C NMR
d 21.13, 27.33, 55.19, 68.27, 85.15, 110.85,
1. (a) Kobayashi, K.; Yoneda, K.; Miyamoto, K.; Morikawa, O.; Konishi, H. Tetrahe-
dron 2004, 60, 11639e11645; (b) Kobayashi, K.; Okamura, Y.; Konishi, H. Synthesis
2009, 1494e1498; (c) Kobayashi, K.; Fujita, S.; Fukamachi, S.; Konishi, H. Syn-
thesis 2009, 3378e3382; (d) Kobayashi, K.; Okamura, Y.; Fukamachi, S.; Konishi,
H. Heterocycles 2010, 81, 1253e1259.
113.04, 119.10, 125.56, 128.70, 129.60, 132.44, 133.07, 149.88, 158.85;
MS m/z (%) 269 (Mþ, 7.3), 251 (100). Anal. Calcd C17H19NO2: C,
75.81; H, 7.11; N, 5.20. Found: C, 75.78; H, 7.05; N, 5.44.
2. For an excellent review: (a) Somei, M.; Yamada, F. Nat. Prod. Rep. 2005, 22,
73e103 For recent reports on isolation: (b) Kam, T.-S.; Choo, Y. M. J. Nat. Prod.
2004, 67, 547e552; (c) Lim, K.-H.; Hiraku, O.; Komiyama, K.; Koyano, T.; Hayashi,
M.; Kam, T.-S. J. Nat. Prod. 2007, 70, 1302e1307.
3. (a) Liu, Y.; McWhorter, W. W., Jr. J. Org. Chem. 2003, 68, 2618e2622; (b) Kimura,
M.; Futamata, M.; Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127, 4592e4593;
(c) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128, 6314e6315; (d) Boy-
arskikh, V.; Nyong, A.; Rainier, J. D. Angew. Chem., Int. Ed. 2008, 47, 5374e5377;
(e) He, Z.; Li, H.; Li, Z. J. Org. Chem. 2010, 75, 4636e4639.
4. Liu, Y.; McWhorter, W. W., Jr.; Hadden, C. E. Org. Lett. 2003, 5, 333e335.
5. Oxidation of 2-aryltryptamine derivatives affording the corresponding 3H-in-
dolo-3-ol derivatives have recently been reported; Movassaghi, M.; Schmidt, M.
A.; Ashenhurst, J. A. Org. Lett. 2008, 10, 4009e4012.
3.3.15. 5-Chloro-2,2-dimethyl-3-phenylindolin-3-ol (3c). Yellow crys-
tals; mp 134e137 ꢀC (hexaneeAcOEt); IR (KBr) 3268, 1605 cmꢁ1; 1H
NMR d 0.79 (s, 3H), 1.41 (s, 3H), 2.13 (br s, 1H), 3.69 (br s, 1H), 6.67 (d,
J¼8.2 Hz,1H), 7.12 (d, J¼1.8 Hz,1H), 7.15 (dd, J¼8.2,1.8 Hz,1H), 7.33 (t,
J¼7.3 Hz, 1H), 7.38 (dd, J¼7.8, 7.3 Hz, 2H), 7.49 (d, J¼7.8 Hz, 2H); 13C
NMR d 21.12, 27.18, 68.94, 85.42,111.78,123.59, 125.69, 127.38,127.66,
127.89, 129.59, 134.72, 139.56, 148.38; MS m/z 273 (Mþ, 7.6), 255
(100). Anal. Calcd C16H16ClNO: C, 70.20; H, 5.89; N, 5.12. Found: C,
70.16; H, 5.84; N, 4.91.
6. We used this eluent because of considerably lower solubility of the crude
products in hexaneeAcOEt.
Acknowledgements
7. Ito, Y.; Kobayashi, K.; Seko, N.; Saegusa, T. Bull. Chem. Soc. Jpn. 1984, 57, 73e84.
8. Lednicer, D.; Emmert, D. E. J. Heterocycl. Chem. 1970, 7, 575e581.
9. Berti, C.; Greci, L.; Marchetti, L. J. Chem. Soc., Perkin Trans. 2 1979, 233e236.
We thank Mrs. Miyuki Tanmatsu of this university for
determining mass spectra and performing combustion analyses.