Divergent Pd(ii) and Au(iii) mediated nitroalkynol cycloisomerizations

Article abstract of DOI:10.1039/c0ob00858c

A new cycloisomerization reaction comprising the simultaneous addition of nitro and alcohol groups across CC leading to skeletally diverse small molecules is documented.

Full text of DOI:10.1039/c0ob00858c

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PAPER
Divergent Pd(II) and Au(III) mediated nitroalkynol cycloisomerizations†
Pitambar Patel and Chepuri V. Ramana*
Received 9th October 2010, Accepted 21st July 2011
DOI: 10.1039/c0ob00858c
A new cycloisomerization reaction comprising the simultaneous addition of nitro and alcohol groups
across C C leading to skeletally diverse small molecules is documented.
Introduction
Domino reactions characterized by several bond formations
through sequential intramolecular transformations address both
molecular complexity and synthetic efficiency.1 This demands
integration of novel reactions and innovative substrate design.
Herein we report a simple domino process comprising an un-
precedented nitroalkynol cycloisomerization. Fig. 1 describes
the general concept and the originating pyridine mediated pho-
tochemical isatogen synthesis (eq.1).2 The reaction mechanism
involves pyridinium betaine intermediate B formation followed
by its spontaneous conversion to isatogen II. We speculated that
if such a transient betaine C is generated by an intramolecular
nucleophilic addition across the alkyne (eq.2),3 it should undergo
post irradiation transformations similar to those of the isatogen
synthesis leading finally either to a N-hydroxy-spiroindolinone
derivative IV or a spirobenzoxazinone derivative V, depending
Fig. 1 Huisgen’s mechanism for photochemical isatogen synthesis and
the projected nitroalkynol cycloisomerizations.
upon the preference of approach of the nucleophile for either the
N or the O of nitroso group (eq. 2) in a stepwise or synchronous
manner4 (1,5- or 1,6- electrocyclizations).
bond with electrophilic Pd(II)-complexes is a rare example, but it
is not unprecedented.10
The exposure of pentynol 1aa to AuCl3 or AuBr3 led to the
formation of a polar mixture, the composition of which could not
be determined. A similar set of catalysts were employed for the
cycloisomerization of the hexynol derivative 1ba (Table 2). The
Results and discussion
With this concept in mind, the nitroalkynols 1aa5b,5c and 1ba5b,5c
were prepared under standard Sonogashira5a conditions. The
feasibility of the proposed cycloisomerization was examined by
screening various Pd(II), Au(III) and Pt(II) complexes.6–8 The
cycloisomerization of 1aa with the majority of the Pd(II) complexes
resulted in the formation of two distinguishable products (Table 1).
Amongst these complexes, the reaction with Pd(CH3CN)2Cl2 was
found to be clean, with a complete conversion of 1aa within
6 h at room temperature. The reaction gave the anticipated
spirobenzoxazinone derivative 3aa along with the spiroindolinone
derivative 2aa9a,9c resulting from the reduction of the anticipated
N-hydroxy indolin-3-one derivative. The breakdown of the N–O
Table 1 Catalysts screened for the nitroalkynol cycloisomerization of 1aa
Entry
Catalyst
Product(s) (2aa : 3aa)a
1
2
PdCl2
PdBr2
1 : 1
1 : 1
3
4
5
6
7
8
9
10
PdI2
No reaction
No reaction
1.1 : 1
No reaction
No reaction
No reaction
Complex mixtureb
Complex mixtureb
Pd(OAc)2
Pd(CH3CN)2Cl2
Pd(PhCN)2Cl2
cis-Pt(CH3CN)2Cl2
cis-Pt(PhCN)2Cl2
AuCl3
National Chemical Laboratory, Dr Homi Bhabha Road, Pune – 411 008,
India. E-mail: vr.chepuri@ncl.res.in; Fax: +91 20 25902629; Tel: +91 20
25902577
AuBr3
† Electronic supplementary information (ESI) available: 1H, 13C NMR and
ESI-MS spectra of all the cycloisomerization products. CCDC reference
numbers 795522, 836106 and 836107. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c0ob00858c
a All the ratios are given on the basis of the NMR of the crude product. b In
dichloromethane also, the starting material decomposed within 5 min.
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Table 2 Catalysts screened for the nitroalkynol cycloisomerization of 1ba
Fig. 2 ORTEP diagram of 3ad.
Entry
Catalyst
Product(s) (2ba : 3ba : 4ba)a
redox via nitroalkyne cycloisomerization. With the alkynol cycloi-
somerization, the formation of proto demetallated intermediates
such as exo-glycals as side products is expected.13 However, no such
side products are observed and we speculate that the reactions are
proceeding with the initial internal nitroalkyne redox. Next, the
internal N–O bond redox could occur either by the 5-exo-dig or
6-endo-dig14–16 mode of nitroalkyne cycloisomerization depending
upon substrate and the metal complex employed.
1
2
3
4
5
6
7
8
PdCl2
5 : 1 : 0
5 : 1 : 0
PdBr2
bPdI2
No reaction
No reaction
No reaction
slow reaction
1 : 0 : 0
No reaction
No reaction
No reaction
Complex mixture
0 : 4 : 3
Complex Mixture
0 : 5 : 6
0 : 3.6 : 1
0 : 4 : 3
Complex mixture
0 : 1.5 : 1
Pd(NO2)3
Pd(OAc)2
Pd(CH3CN)2NO2Cl
Pd(CH3CN)2Cl2
Pd(PhCN)2Cl2
cis-Pt(CH3CN)2Cl2
cis-Pt(PhCN)2Cl2
AuCl3
9
10
11
12
13
14
15
16
17
18
In the first case, which we extend for the Pd[II]-mediated
cyclization,11,12 a 5-exo-dig nitroalkyne cyclization giving D which
upon internal N–O bond redox, leads to the intermediate metal
carbene F (Fig. 3, eq.3). This metal carbene F could undergo a
nucleophilic addition either by the nitrogen of the nitroso-group
or by the oxygen of the –OH group. With the pentynol substrates,
where both these additions lead to 5-membered heterocycles, it
seems to be that both the cyclizations are competing equally
leading to two different products. The addition of the nitrogen
to the metal carbene (Fig. 3, path a) leads to the isatogens II which
subsequently undergo an intramolecular addition of the –OH
group to the imine carbon proceeded or preceded by the N–O bond
reduction and thus give the indolinone 2. Whereas the addition
of –OH to the metal carbene followed by the proto-depalladation
(Fig. 3, path b) leads to the enol L, which subsequently undergoes
a 6n-electrocyclization resulting in benzoxazinone 3 (Fig. 3, eq.4).
When the addition of the –OH forms a 6-membered ring, which
is the case with hexynols and propargyl glycols, the cyclization
is energetically more demanding, and the addition of nitrogen of
the nitroso-group to the metal carbene is the exclusive path thus
providing the indolinones only.
Next, considering the available information, for the cycliza-
tions with the Au[III]-complex, we extend a 6-endo-dig mode of
nitroalkyne cycloisomerization and the formation of the alkenyl-
Au[III] species E. The intermediate E can undergo either an internal
redox forming the regiomeric metal carbene G (Fig. 3, path c)
or a protodemetallation giving nitronate H (Fig. 3, path d). The
intermediate H upon hydration gives the nitroso-ene-diol I. This
path is in parallel to the mechanism that has been extended
by Yamamoto for nitroalkyne cycloisomerizations leading to
isatogens and/or anthranils.7 The resulting ene-diol I could be
trapped by the internal OH nucleophile to provide the intermediate
L. The intermediate L should undergo a 6n-electocyclization
to give the benzoxazinone 3 (Fig. 3, eq.6). The formation of
benzoxazinones either as the major or as exclusive products
indicates that with AuBr3, the protodemetallation seems to be
more facile than the metallocarbene formation. The formation of
anthranil side products could be explained by the internal addition
of oxygen of nitroso group to the metal carbene M (formed via the
dehydration of the metal carbene G) resulting in N, which upon
protodemetallation followed by deprotonation forms the anthranil
4 (Fig. 3, eq.5). As a control, the benzoxazinone 3bc was exposed
to AuBr3 (5 mol%, CH3CN, rt, 3 h) and found to be intact. This
cAuCl3
HAuCl4
cHAuCl4
AuBr3
cAuBr3
(PPh3)3(O)Au3BF4
c(PPh3)3(O)Au3BF4
a All the ratios are given on the basis of the NMR of crude product. b PdI2
is sparingly soluble in majority of the solvents used and in DMSO it has
good solubility. However, the attempted cycloisomerization with Pd(II)I2
in this solvent gave an intractable complex mixture c Dichloromethane was
used as a solvent.
cycloisomerization of 1ba with Pd(CH3CN)2Cl2 gave exclusively
the spiroindolinone 2ba9b,9c in good yield. With the three Au(III)
salts, the outcome of the reaction was solvent dependent. Whilst
the cycloisomerization of 1ba with AuBr3 in acetonitrile gave
predominantly the spirobenzoxazinone 3ba and anthranil 4ba
as a minor product, the reactions with AuCl3 and HAuCl4 in
acetonitrile resulted in immediate disappearance of alkynol and
gave untractable polar mixtures. When the solvent was changed
to CH2Cl2, a mixture of spirobenzoxazinone 3ba and anthranil
4ba were obtained in moderate yields with AuCl3 and HAuCl4.
After a preliminary screening of various metal complexes, further
generalization of this novel reaction has been carried out using
Pd(CH3CN)2Cl2 and AuBr3 in acetonitrile. Table 3 provides the
scope and the product divergence of the Pd(II) and Au(III) mediated
nitroalkynol cycloisomerization. With the pentynols 1aa (a = a–
d), the palladium catalyzed cycloisomerizations in general gave
a ~1 : 1 mixture of 2aa and 3aa. The constitution of one of the
benzoxazinones 3ad was confirmed with the help of single crystal
X-ray structural analysis (Fig. 2). With all the hexynols 1ba (a =
a–d), as well as with the propargyl glycol derivatives 1ca (a = a–d),
the indolin-3-one derivatives were isolated exclusively in good to
excellent yields. Formation of substantial amounts of anthranil
derivatives 4ba along with the benzoxazinones 3ba was noticed in
the reactions of hexynols 1ba with AuBr3. The AuBr3 catalyzed
cyclization of propargyl glycol derivatives 1ca afforded exclusively
the benzoxazinone derivatives 3ca.
Mechanism
A plausible mechanism for the palladium- and gold-mediated
cyclizations is given in Fig. 3. Primarily, two competing path
ways exist—(a) the alkynol cycloisomerization and (b) the internal
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Table 3 Product divergence in Pd(II) and Au(III) mediated nitroalkynol cycloisomerizations
Products (Yield %)
Entry
1a
Nitroalkynol
Pd(CH3CN)2Cl2, CH3CN, rt
AuBr3, CH3CN, rt
NA
2
NA
3
Complex mixture
4
6
7
8
9
10
11
a 1ab was slowly converting to the cycloisomerization products on standing in CDCl3 which might be due to traces of [Pd]-present.
control experiment indicated that both the benzoxazinone and
anthranil are formed independently.
in a variety of natural products,17,18 the latter 2,3-benzoxazinone
unit is rare and present in important antitumor, antibiotic natural
products FR90048219 and FR6697920 (structurally related to the
anticancer drug mitomycin C, with more potent DNA cross-
linking activity and decreased toxicity). The present transforma-
tion therefore can find an important application in the synthesis
of related small molecule libraries. Further investigations dealing
with the details of the mechanism and the scope of these reactions
are in progress.
Conclusions
In summary, the intramolecular addition of nitro and alcohol
units across the alkyne leading to spiro-indolin-3-one and spiro-
benzoxazin-4-one derivatives was revealed by employing palla-
dium and gold catalysts. Whilst the former units can be found
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Fig. 3 The possible modes of cyclization and possible mechanism for the product divergence with Pd(II) and Au(III)-mediated nitroalkynol
cycloisomerization (for clarity of the figures the acetonitrile ligands on the Pd(II)-complex have not been shown).
C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.85; H, 6.33; N,
6.67.
Experimental
General procedure for cycloisomerization with Pd[CH3CN]2Cl2 or
AuBr3
Compound 2ac. Yellow solid, Mp. 136 ◦C, 32% yield. IR
(CHCl3): n 3019, 2985, 1714, 1610, 1580, 1454, 1316, 1215, 1066,
To a degassed solution of alkynol 1 (0.5 mmol) in CH3CN (15 mL)
928, 755 cm-1. 1H NMR (200 MHz, CDCl3): d 1.96–2.09 (m, 2H),
was added Pd(CH3CN)2Cl2 or AuBr3 (5 mol%) and the contents
2.21–2.31 (m, 2H), 4.00–4.15 (m, 2H), 5.06 (br s, 1H), 6.69 (d,
stirred under argon for 4 h or 6 h at rt. The reaction mixture was
concentrated and the residue obtained was purified by column
chromatography (ethyl acetate in petroleum ether) to afford 2/3
or 3/4.
J = 1.6 Hz, 1H), 6.75 (dd, J = 1.6, 8.1 Hz, 1H), 7.45 (d, J = 8.2
Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 25.6 (t), 33.9 (t),
69.3 (t), 95.3 (s), 112.0 (d), 117.3 (s), 120.2 (d), 126.0 (d), 144.3 (s),
160.0 (s), 199.5 (s) ppm. ESI-MS: m/z 246.2 (100%, [M+Na]+).
HRMS: Found: 222.0321 ([M - H]+), Calcd.: 222.0322 ([M - H]+).
Anal. Calcd for C11H10ClNO2: C, 59.07; H, 4.51; Cl, 15.85; N, 6.26.
Found: C, 59.20; H, 4.63; Cl, 15.69; N, 6.09.
Compound 2aa. Yellow liquid, 29% yield. IR (CHCl3): n 3022,
1
2926, 1717, 1608, 1526, 1469, 1348, 1235, 1048 cm-1. H NMR
(200 MHz, CDCl3): d 1.93–2.16 (m, 2H), 2.21–2.32 (m, 2H), 4.02–
4.18 (m, 2H), 4.83 (br s, 1H), 6.74 (d, J = 8.1 Hz, 1H), 6.81 (t, J =
7.4 Hz, 1H), 7.41 (ddd, J = 1.3, 7.3, 8.4 Hz, 1H), 7.56 (d, J = 7.7
Hz, 1H), ppm. 13C NMR (50 MHz, CDCl3): d 25.7 (t), 33.9 (t),
69.2 (t), 95.0 (s), 112.1 (d), 119.0 (s), 119.6 (d), 125.0 (d), 137.8
(d), 159.6 (s), 200.9 (s) ppm. ESI-MS: m/z 190.2 (100%, [M+H]+).
HRMS: Found: 190.0856 ([M+H]+); Calcd.: 190.0868 ([M+H]+).
Anal. Calcd for C11H11NO2: C, 69.83; H, 5.86; N, 7.40. Found: C,
69.67; H, 5.82; N, 7.35.
Compound 2ad. Yellow liquid, 38% yield. IR (CHCl3): n 3012,
2998, 1715, 1702, 1608, 1568, 1508, 1474, 1466, 1316, 1263, cm-1.
1H NMR (200 MHz, CDCl3): d 1.99–2.14 (m, 2H), 2.23–2.33 (m,
2H), 3.91 (s, 3H), 4.05–4.15 (m, 2H), 4.93 (br s, 1H), 7.39 (br s,
1H), 7.46 (dd, J = 1.3, 7.9 Hz, 1H), 7.60 (d, J = 7.9 Hz, 1H) ppm.
13C NMR (100 MHz, CDCl3): d 25.7 (t), 33.9 (t), 52.5 (q), 69.3 (t),
95.3 (s), 113.1 (d), 120.5 (d), 122.1 (s), 124.9 (d), 138.1 (s), 159.1
(s), 166.3 (s), 200.7 (s) ppm. ESI-MS: m/z 270.1 (100%, [M+Na]+).
HRMS: Found: 246.0317 ([M - H]+), Calcd.: 246.0202 ([M - H]+).
Anal. Calcd for C13H13NO4: C, 63.15; H, 5.30; N, 5.67. Found: C,
63.01; H, 5.17; N, 5.52.
◦
Compound 2ab. Yellow colour solid, Mp. 133 C, 36% yield.
IR (CHCl3): n 3017, 2915, 2888, 1712, 1616, 1587, 1459, 1324,
1216, 1111, 1021, 755 cm-1. 1H NMR (200 MHz, CDCl3): d 1.91–
2.12 (m, 2H), 2.20–2.34 (m, 2H), 2.28 (s, 3H), 4.05–4.13 (m, 2H),
4.91 (br s, 1H), 6.51 (s, 1H), 6.60 (d, J = 7.9 Hz, 1H), 7.43 (d,
J = 7.9 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 22.3 (q),
25.6 (t), 33.9 (t), 69.1 (t), 95.2 (s), 112.3 (d), 116.6 (s), 121.0
(d), 124.6 (d), 149.5 (s), 160.1 (s), 200.1 (s) ppm. ESI-MS: m/z
202.1(100%, [M - H]+), 204.1 (50%, [M+H]+). HRMS: Found:
204.1039 ([M+H]+), Calcd.: 204.1025 ([M+H]+). Anal. Calcd for
Compound 2ba. Yellow solid, Mp. 112 ◦C, 55% yield. IR
(CHCl3): n 2985, 2924, 1713, 1625, 1489, 1455, 1307, 1268, 1118,
1
1077 cm-1. H NMR (200 MHz, CDCl3): d 1.50–1.85 (m, 4H),
1.94–2.11 (m, 2H), 3.74–3.86 (m, 1H), 4.05–4.15 (m, 1H), 5.13 (br
s, 1H), 6.08–6.87 (m, 2H), 7.44 (dt, J = 1.22, 8.2 Hz, 1H), 7.59 (dd,
J = 1.1, 7.9 Hz, 1H), ppm. 13C NMR (50 MHz, CDCl3): d 19.2 (t),
24.7 (t), 30.5 (t), 63.7 (t), 87.5 (s), 112.7 (d), 119.8 (s), 120.0 (d),
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125.4 (d), 137.8 (d), 159.4 (s), 198.9 (s) ppm. ESI-MS: m/z 226.3
(100%, [M+Na]+). HRMS: Found: 226.0904 ([M+Na]+), Calcd.:
226.0844 ([M+Na]+). Anal. Calcd for C12H13NO2: C, 70.92; H,
6.45; N, 6.89. Found: C, 70.77; H, 6.39; N, 6.72.
[M+Na]+). HRMS: Found: 242.2808 ([M+Na]+), Calcd. 242.0793
([M+Na]+). Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39.
Found: C, 65.68; H, 5.78; N, 6.22.
Compound 2cc. Yellow liquid, 78% yield. IR (CHCl3): n 2946,
◦
1
Compound 2bb. Brown colour solid, Mp. 128 C, 79% yield.
2895, 1718, 1604, 1550, 1439, 1314, 1212, 1067 cm-1. H NMR
IR (CHCl3): n 3015, 1711, 1616, 1570, 1459, 1323, 1289, 1021, 756
cm-1. 1H NMR (200 MHz, CDCl3): d 1.47–1.83 (m, 4H), 1.93–2.11
(m, 2H), 2.32 (s, 3H), 3.72–3.84 (m, 1H), 4.03–4.13 (m, 1H), 5.12
(br s, 1H), 6.62 (s, 1H), 6.64 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.0 Hz,
1H), ppm. 13C NMR (50 MHz, CDCl3): d 19.2 (t), 22.4 (q), 24.7
(t), 30.6 (t), 63.7 (t), 87.8 (s), 112.8 (d), 117.4 (s), 121.5 (d), 125.1
(d), 149.5 (s), 159.9 (s), 198.2 (s) ppm. ESI-MS: m/z 218.2 (100%,
[M+Na]+). HRMS: Found: 218.1168 ([M+H]+), Calcd.: 218.1181
([M+H]+). Anal. Calcd for C13H15NO2: C, 71.87; H, 6.96; N, 6.45.
Found: C, 71.79; H, 6.82; N, 6.33.
(200 MHz, CDCl3): d 3.60 (d, J = 11.5 Hz, 1H), 3.80–3.97 (m,
3H), 3.87 (d, J = 11.5 Hz, 1H), 3.99–4.11 (m, 1H), 5.74 (br s, 1H),
6.84 (dd, J = 1.6, 8.2 Hz, 1H), 6.88 (d, J = 1.6 Hz, 1H), 7.52 (d, J =
8.2 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 62.4 (t), 66.4 (t),
70.8 (t), 86.8 (s), 113.1 (d), 118.4 (s), 121.2 (d), 126.4 (d), 144.7 (s),
159.9 (s), 194.5 (s) ppm. ESI-MS: m/z 262.2 (100%, [M+Na]+).
HRMS: Found: 240.0542 ([M+H]+), Calcd.: 240.0427 ([M+H]+).
Anal. Calcd for C11H10ClNO3: C, 55.13; H, 4.21; Cl, 14.79; N, 5.84.
Found: C, 55.23; H, 4.18; Cl, 14.57; N, 5.71.
◦
Compound 2cd. Yellow colour solid, Mp. 171 C, 82% yield.
Compound 2bc. Low melting solid, 82% yield. IR (CHCl3): n
IR (CHCl3): n 3018, 2951, 1727, 1715, 1624, 1587, 1495, 1454,
1322, 1263, 1161, 1002 cm-1. 1H NMR (200 MHz, CDCl3): d 3.61
(d, J = 11.5 Hz, 1H), 3.84–3.98 (m, 3H), 3.89 (d, J = 11.5 Hz, 1H),
3.93 (s, 3H), 4.02–4.15 (m, 1H), 5.66 (br s, 1H), 7.52 (dd, J = 1.2,
8.7 Hz, 1H), 7.56 (s, 1H), 7.65 (d, J = 8.7 Hz, 1H) ppm. 13C NMR
(50 MHz, CDCl3): d 52.6 (q), 62.4 (t), 66.4 (t), 70.7 (t), 86.7 (s),
114.2 (d), 121.2 (d), 123.1 (s), 125.3 (d), 138.5 (s), 159.1 (s), 166.1
(s), 195.8 (s) ppm. ESI-MS: m/z 279.4 (100%, [M+Na]+). HRMS:
Found: 263.1181 ([M]+), Calcd.: 263.0794 ([M]+). Anal. Calcd for
C13H13NO5: C, 59.31; H, 4.98; N, 5.32. Found: C, 59.20; H, 4.85;
N, 5.23.
1
3018, 3945, 1718, 1604, 1457, 1314, 1215, 1045 cm-1. H NMR
(200 MHz, CDCl3): d 1.50–1.85 (m, 4H), 1.94–2.16 (m, 2H), 3.71–
3.83 (m, 1H), 4.06–4.16 (m, 1H), 5.20 (br s, 1H), 6.79 (dd, J =
1.6, 8.2 Hz, 1H),6.82 (s, 1H), 7.51 (dd, J = 1.6, 7.2 Hz, 1H), ppm.
13C NMR (50 MHz, CDCl3): d 19.1 (t), 24.6 (t), 30.5 (t), 63.8 (t),
87.7 (s), 112.5 (d), 118.1 (s), 120.6 (d), 126.4 (d), 144.1 (s), 159.7
(s), 197.4 (s) ppm. ESI-MS: m/z 240.3 (100%, [M+Na]+). HRMS:
Found: 260.0871 ([M+Na]+), Calcd.: 260.0454 ([M+Na]+). Anal.
Calcd for C12H12ClNO2: C, 60.64; H, 5.09; Cl, 14.92; N, 5.89.
Found: C, 60.58; H, 5.20; Cl, 14.77; N, 5.71.
Compound 2bd. Yellow solid, Mp. 162 ◦C, 84% yield. IR
(CHCl3): n 3032, 2945, 1715, 1702, 1615, 1568, 1527, 1480, 1466,
1345, 1210, 1018 cm-1. 1H NMR (200 MHz, CDCl3): d 1.52–1.84
(m, 4H), 1.94–2.17 (m, 2H), 3.73–3.85 (m, 1H), 3.90 (s, 3H), 4.05–
4.15 (m, 1H), 5.30 (br s, 1H), 7.44–7.48 (m, 2H), 7.62 (d, J = 8.3 Hz,
1H) ppm. 13C NMR (50 MHz, CDCl3): d 19.0 (t), 24.6 (t), 30.4 (t),
52.5 (q), 63.7 (t), 87.7 (s), 113.7 (d), 120.5 (d), 122.7 (s), 125.2 (d),
138.0 (s), 158.9 (s), 166.2 (s), 198.73 (s) ppm. ESI-MS: m/z 284.2
(100%, [M+Na]+). HRMS: Found: 284.3364 ([M+Na]+); Calcd:
284.0899 ([M+Na]+). Anal. Calcd for C14H15NO4: C, 64.36; H,
5.79; N, 5.36. Found: C, 64.22; H, 5.58; N, 5.29.
Compound 3aa. Yellow liquid, 27% yield. IR (CHCl3): n 3019,
1
1695, 1645, 1599, 1448, 1215, 1078 cm-1. H NMR (200 MHz,
CDCl3): d 1.93–2.19 (m, 3H), 2.70–2.85 (m, 1H), 4.05–4.24 (m,
2H), 6.85 (d, J = 8.2 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 7.43 (ddd,
J = 1.4, 7.3, 8.3 Hz, 1H), 7.94 (dd, J = 1.4, 7.9 Hz, 1H) ppm (The N–
H proton is missing in the spectrum). 13C NMR (50 MHz, CDCl3):
d 24.7 (t), 31.2 (t), 71.0 (t), 107.5 (s), 114.7 (d), 117.7 (s), 122.4 (d),
127.7 (d), 134.8 (d), 150.4 (s), 185.1 (s) ppm. ESI-MS: m/z 228.2
(100%, [M+Na]+). HRMS: Found: 228.0597 ([M+Na+]), Calcd.:
228.0637 ([M+Na+]). Anal. Calcd for C11H11NO3: C, 64.38; H,
5.40; N, 6.83. Found: C, 64.42; H, 5.31; N, 6.72.
◦
Compound 2ca. Yellow liquid, 64% yield. IR (CHCl3): n 3016,
2964, 2925, 1709, 1619, 1486, 1471, 1321, 1234, 1121, 1081 cm-1.
1H NMR (200 MHz, CDCl3): d 3.61 (d, J = 11.5 Hz, 1H), 3.78–
3.99 (m, 3H), 3.89 (d, J = 11.5 Hz, 1H), 4.03–4.16 (m, 1H), 5.53
(br s, 1H), 6.85-6.92 (m, 2H), 7.50 (dt, J = 1.3, 7.2 Hz, 1H), 7.6
(d, J = 7.7 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 62.4
(t), 66.5 (t), 71.0 (t), 86.6 (s), 113.2 (d), 120.2 (s), 120.6 (d), 125.4
(d), 138.2 (d), 159.6 (s), 195.9 (s) ppm. ESI-MS: m/z 228.1 (100%,
[M+Na]+). HRMS: Found: 228.0598 ([M+Na]+), Calcd.: 228.0637
([M+Na]+). Anal. Calcd for C11H11NO3: C, 64.38; H, 5.40; N, 6.83.
Found: C, 64.21; H, 5.29; N, 6.71.
Compound 3ab. Brown colour solid, Mp. 118 C, 34% yield.
IR (CHCl3): n 3012, 2981, 1685, 1613, 1459, 1340, 1294, 1019 cm-1.
1H NMR (200 MHz, CDCl3): d 1.92–2.17 (m, 3H), 2.32 (s, 3H),
2.69–2.83 (m, 1H), 4.04–4.22 (m, 2H), 6.63 (s, 1H), 6.85 (dd, J =
0.7, 8.1 Hz, 1H), 7.41 (br s, 1H), 7.82 (d, J = 8.1 Hz, 1H) ppm.
13C NMR (50 MHz, CDCl3): d 22.0 (q), 24.7 (t), 31.2 (t), 71.0
(t), 107.6 (s), 114.6 (d), 115.6 (s), 123.9 (d), 127.7 (d), 146.2 (s),
150.5 (s), 184.9 (s) ppm. ESI-MS: m/z 242.2 (100%, [M+Na]+).
HRMS: Found: 220.0960 ([M+H]+), Calcd.: 220.0974 ([M+H]+).
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C,
65.79; H, 5.79; N, 6.27.
◦
Compound 2cb. Yellow liquid, 80% yield. IR (CHCl3): n 3018,
Compound 3ac. Yellow colour solid, Mp. 118 C, 31% yield.
2947, 1718, 1611, 1581, 1452, 1314, 1215, 1066 cm-1. H NMR
IR (CHCl3): n 2923, 1682, 1613, 1452, 1313, 1270, 1056 cm-1. 1H
NMR (200 MHz, CDCl3): d 1.92–2.23 (m, 3H), 2.68–2.83 (m,
1H), 4.04–4.23 (m, 2H), 6.85 (d, J = 1.8 Hz, 1H), 6.99 (dd, J =
1.8, 8.6 Hz, 1H), 7.55 (s, 1H), 7.85 (d, J = 8.6 Hz, 1H) ppm. 13C
NMR (50 MHz, CDCl3): d 24.6 (t), 31.1 (t), 71.1 (t), 107.5 (s),
114.3 (d), 115.9 (s), 122.9 (d), 129.3 (d), 141.0 (s), 151.1 (s), 184.2
(s) ppm. ESI-MS: m/z 240.2 (100%, [M+H]+). HRMS: Found:
1
(200 MHz, CDCl3): d 2.36 (s, 3H), 3.59 (d, J = 11.5 Hz, 1H),
3.83–3.98 (m, 3H), 3.88 (d, J = 11.5 Hz, 1H), 4.01–4.15 (m, 1H),
5.48 (br s, 1H), 6.69 (s, 1H), 6.71 (d, J = 8.5 Hz, 1H), 7.49 (d, J =
8.5 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 22.5 (q), 62.4
(t), 66.4 (t), 71.1 (t), 86.9 (s), 113.3 (d), 118.0 (s), 122.2 (d), 125.1
(d), 150.2 (s), 160.1 (s), 195.1 (s) ppm. ESI-MS: m/z 242.1 (100%,
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240.0420 ([M+H]+), Calcd.: 240.0427 ([M+H]+). Anal. Calcd for
C11H10ClNO3: C, 55.13; H, 4.21; Cl, 14.79; N, 5.84. Found: C,
55.01; H, 4.09; Cl, 14.58; N, 5.79.
63.5 (t), 98.7 (s), 114.0 (d), 114.9 (s), 123.7 (d), 128.1 (d), 145.9 (s),
150.6 (s), 185.0 (s) ppm. ESI-MS: m/z 256.3 (100%, [M+Na]+).
Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C,
66.74; H, 6.32; N, 5.87.
o
Compound 3ad. Yellow colour solid, Mp. 123 C. 34% yield.
Compound 3bc. Low melting solid, 38% yield. IR (CHCl3):
IR (CHCl3): n 3020, 1729, 1684, 1618, 1590, 1435, 1301, 1215,
1
n 3020, 1683, 1614, 1453, 1314, 1216, 1058, 919 cm-1. H NMR
1
1090 cm-1. H NMR (400 MHz, CDCl3): d 1.99–2.05 (m, 1H),
(200 MHz, CDCl3): d 1.62–1.73 (m, 2H), 1.78–1.86 (m, 3H), 2.27–
2.43 (m, 1H), 3.88–3.92 (m, 2H), 6.87 (d, J = 1.8 Hz, 1H), 6.99 (dd,
2.10–2.21 (m, 2H), 2.73–2.81 (m, 1H), 3.91 (s, 3H), 4.08–4.14 (m,
1H), 4.16–4.22 (m, 1H), 7.55 (s, 1H), 7.57 (br s, 1H), 7.65 (dd,
J = 1.4, 8.1 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3): d 24.7 (t), 31.2 (t), 52.6 (q), 71.3 (t), 107.4 (s),
116.4 (d), 120.3 (s), 122.6 (d), 128.1 (d), 135.3 (s), 150.2 (s), 165.8
(s), 184.6 (s) ppm. ESI-MS: m/z 270.1 (100%, [M+Na]+). HRMS:
Found: 263.0849 ([M]+), Calcd.: 263.0794 ([M]+). Anal. Calcd for
C13H13NO5: C, 59.31; H, 4.98; N, 5.32. Found: C, 59.27; H, 4.89;
N, 5.22.
J = 1.8, 8.5 Hz, 1H), 7.26 (s, 1H), 7.87 (d, J = 8.5 Hz, 1H) ppm. 13
C
NMR (50 MHz, CDCl3): d 17.8 (t), 24.4 (t), 25.4 (t), 63.6 (t), 98.8
(s), 113.76 (d), 115.2 (s), 122.7 (d), 129.7 (d), 140.8 (s), 151.1 (s),
184.2 (s) ppm. ESI-MS: m/z 276.1 (100%, [M+H]+). Anal. Calcd
for C12H12ClNO3: C, 56.81; H, 4.77; Cl, 13.98; N, 5.52. Found: C,
56.99; H, 4.71; Cl, 13.75; N, 5.41.
Compound 3bd. Yellow solid, Mp. 153 ◦C, 40% yield. IR
(CHCl3): n 2951, 1727, 1703, 1615, 1580, 1438, 1286, 1229, 1092,
752 cm-1. 1H NMR (200 MHz, CDCl3): d 1.62–1.86 (m, 5H), 2.27–
2.43 (m, 1H), 3.90–4.00 (m, 2H), 3.91 (s, 3H), 7.36 (br s, 1H), 7.54
(d, J = 1.3 Hz, 1H), 7.63 (dd, J = 1.3, 8.2 Hz, 1H), 7.99 (d, J =
8.2 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 17.9 (t), 24.4 (t),
25.4 (t), 52.6 (q), 63.6 (t), 98.7 (s), 115.6 (d), 119.5 (s), 122.3 (d),
128.4 (d), 135.0 (s), 150.2 (s), 165.9 (s), 184.6 (s) ppm. ESI-MS:
m/z 278.2 (100%, [M+H]+). HRMS: Found: 278.1007 ([M+H]+),
Calcd.: 278.1028 ([M+H]+). Anal. Calcd for C14H15NO5: C, 60.64;
H, 5.45; N, 5.05. Found: C, 60.52; H, 5.28; N, 4.88.
X-Ray crystallographic data21. X-ray intensity data of com-
pound 3ad† was collected on
a Bruker SMART APEX
CCD diffractometer with graphite-monochromatized (Mo-Ka =
˚
0.71073 A) radiation at room temperature. Data were collected
with w scan width of 0.3◦ and with four different settings of j (0◦,
90◦, 180◦ and 270◦) keeping the sample-to-detector distance fixed
at 6.145 cm and the detector position (2q) fixed at -28◦. The X-
ray data collection was monitored by SMART program (Bruker,
2003).22a All the data were corrected for Lorentzian, polarization
and absorption effects using Bruker’s SAINT and SADABS
programs.22a SHELX-9722b was used for structure solution and
full-matrix least-squares refinement on F2. Hydrogen atoms were
included in the refinement as per the riding model. The overall
quality of the diffraction data was very poor due to the poor
quality of the crystals which is reflected in its high R-value.
Crystal data for 3ad (C13H13N1O5): M = 263.24, crystal dimen-
Compound 3ca. Yellow liquid, 51% yield. IR (CHCl3): n 2927,
2857, 1682, 1605, 1478, 1348, 1086, 1057, 918, 752 cm-1. 1H NMR
(200 MHz, CDCl3): d 3.72 (d, J = 11.1 Hz, 1H), 3.81–3.87 (m,
2H), 3.84 (d, J = 12.6 Hz, 1H), 4.18–4.36 (m, 1H), 4.30 (d, J = 12.6
Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 6.98–7.06 (m, 1H), 7.44 (ddd,
J = 1.5, 7.2, 8.3 Hz, 1H), 7.61 (br s, 1H), 7.91 (dd, J = 1.5, 7.9 Hz,
1H) ppm. 13C NMR (50 MHz, CDCl3): d 61.3 (t), 65.6 (t, 2C),
95.4 (s), 113.6 (d), 116.5 (s), 122.1 (d), 127.9 (d), 135.0 (d), 150.5
(s), 183.7 (s) ppm. ESI-MS: m/z 244.3 (100%, [M+Na]+). HRMS:
Found: 221.0753 ([M]+), Calcd.: 221.0688 ([M]+). Anal. Calcd for
C11H11NO4: C, 59.73; H, 5.01; N, 6.33. Found: C, 59.59; H, 4.95;
N, 6.19.
sions 0.22 ¥ 0.16 ¥ 0.06 mm3, monoclinic, space group P21/n, a =
3
˚
˚
14.478(8), b = 5.258(3), c = 17.353(10) A, V = 1315.8(13) A , Z = 4;
rcalcd = 1.329 gcm-3, m(Mo-Ka) = 0.103 mm-1, F(000) = 552, 2qmax
=
50.00◦, 7556 reflections collected, 1815 unique, 1346 observed (I >
2s(I)) reflections, 173 refined parameters, R value 0.1249, wR2 =
0.3022 (all data R = 0.1520, wR2 = 0.3159), S = 1.241, minimum and
maximum transmission 0.9780 and 0.9934 respectively, maximum
-3
˚
and minimum residual electron densities +0.495 and -0.374 e A .
Compound 3cb. Yellow liquid, 72% yield. IR (CHCl3): n 3019,
2980, 2928, 1687, 1615, 1453, 1381, 1321, 1215, 1115, 1068 cm-1.
1H NMR (200 MHz, CDCl3): d 2.30 (s, 3H), 3.69 (d, J = 11.2 Hz,
1H), 3.79–3.90 (m, 2H), 3.83 (d, J = 12.6 Hz, 1H), 4.16–4.34 (m,
1H), 4.27 (d, J = 12.6 Hz, 1H), 6.62 (s, 1H), 6.81 (dd, J = 0.7,
8.1 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H) ppm. 13C NMR (50 MHz,
CDCl3): d 22.0 (q), 61.2 (t), 65.6 (t, 2C), 95.3 (s), 113.3 (d), 114.2
(s), 123.5 (d), 127.7 (d), 146.5 (s), 150.6 (s), 183.5 (s) ppm. ESI-MS:
m/z 236.2 (100%, [M+H]+). Anal. Calcd for C12H13NO4: C, 61.27;
H, 5.57; N, 5.95. Found: C, 61.30; H, 5.41; N, 5.76.
Compound 3ba. Yellow solid, Mp. 121 ◦C, 57% yield. IR
(CHCl3): n 3020, 2930, 1725, 1605, 1550, 1461, 1302, 1217, 1108,
1080, 756 cm-1. 1H NMR (200 MHz, CDCl3): d 1.61–1.75 (m, 2H),
1.80–1.87 (m, 3H), 2.33–2.42 (m, 1H), 3.87–3.97 (m, 2H), 6.86 (d,
J = 8.2 Hz, 1H), 7.04 (ddd, J = 1.0, 7.3, 8.0 Hz, 1H), 7.27 (s, 1H),
7.43 (ddd, J = 1.5, 7.3, 8.5 Hz, 1H), 7.95 (dd, J = 1.0, 8.0 Hz, 1H)
ppm. 13C NMR (50 MHz, CDCl3): d 17.9 (t), 24.4 (t), 25.6 (t),
63.5 (t), 98.8 (s), 114.0 (d), 116.9 (s), 122.2 (d), 128.1 (d), 134.5 (d),
150.5 (s), 185.2 (s) ppm. ESI-MS: m/z 242.2 (100%, [M+Na]+).
HRMS: Found: 220.1017 ([M+H]+), Calcd.: 220.0974 ([M+H]+).
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: :
C, 65.85; H, 5.76; N, 6.25.
Compound 3cc. Yellow liquid, 67% yield. IR (CHCl3): n 3019,
2927, 2855, 1694, 1600, 1442, 1215, 1045, 758, 668 cm-1. 1H NMR
(200 MHz, CDCl3): d 3.72 (d, J = 11.1 Hz, 1H), 3.80–3.87 (m,
2H), 3.84 (d, J = 12.7 Hz, 1H), 4.16–4.37 (m, 1H), 4.29 (d, J =
12.7 Hz, 1H), 6.88 (d, J = 1.6 Hz, 1H), 6.99 (dd, J = 1.6, 8.5
Hz, 1H), 7.62 (br s, 1H), 7.84 (d, J = 8.5 Hz, 1H) ppm. 13C
NMR (50 MHz, CDCl3): d 61.3 (t), 65.4 (t), 65.6 (t), 95.3 (s),
113.3 (d), 114.8 (s), 122.7 (d), 129.5 (d), 141.4 (s), 151.0 (s), 182.8
(s) ppm. ESI-MS: m/z 256.3 (100%, [M+H]+). HRMS: Found:
Compound 3bb. Sticky liquid, 35% yield. IR (CHCl3): n 3019,
2948, 2855, 1686, 1614, 1580, 1454, 1310, 1270, 1215, 1045 cm-1.
1H NMR (200 MHz, CDCl3): d 1.58–1.74 (m, 2H), 1.76–1.84 (m,
3H), 2.28–2.51 (m, 1H), 2.33 (s, 3H), 3.88–3.94 (m, 2H), 6.64 (s,
1H), 6.85 (dd, J = 0.8, 8.1 Hz, 1H), 7.83(d, J = 8.1 Hz, 1H) ppm.
13C NMR (50 MHz, CDCl3): d 17.9 (t), 22.0 (q), 24.5 (t), 25.6 (t),
7332 | Org. Biomol. Chem., 2011, 9, 7327–7334
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256.0373 ([M+H]+), Calcd.: 256.0377 ([M+H]+). Anal. Calcd for
C11H10ClNO4: C, 51.68; H, 3.94; Cl, 13.87; N, 5.48. Found: C,
51.55; H, 3.89; Cl, 13.62; N, 5.39.
nation. Financial support from UGC (New Delhi) in the form of
a research fellowship to PP is gratefully acknowledged.
Notes and references
◦
Compound 3cd. Yellow colour solid, Mp. 168 C, 85% yield.
IR (CHCl3): n 2924, 1726, 1693, 1619, 1506, 1438, 1298, 1228,
1 L. F. Tietze, G. Brasche and K. Gericke, Domino Reactions in Organic
Synthesis, Wiley-VCH, Weinheim, 2006.
2 (a) P. N. Preston and G. Tennant, Chem. Rev., 1972, 72, 627–677; (b) R.
Huisgen, Angew Chem., Int. Ed., 1963, 2, 565–598.
1
1094, 1055, 918, 752 cm-1. H NMR (200 MHz, CDCl3): d 3.69
(d, J = 10.9 Hz, 1H), 3.81–3.97 (m, 2H), 3.85 (d, J = 12.7 Hz, 1H),
3.92 (s, 3H), 4.17–4.36 (m, 1H), 4.31 (d, J = 12.7 Hz, 1H), 7.58 (d,
J = 1.4 Hz, 1H), 7.62 (dd, J = 1.4, 8.2 Hz, 1H), 7.84 (br s, 1H), 7.95
(d, J = 8.2 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 52.7 (q),
61.3 (t), 65.4 (t), 65.6 (t), 95.2 (s), 115.3 (d), 119.0 (s), 122.2 (d),
128.2 (d), 135.5 (s), 150.2 (s), 165.8 (s), 183.2 (s) ppm. ESI-MS:
m/z 279.4 (100%, [M]+). HRMS: Found: 279.0936 ([M]+), Calcd.:
279.0743 ([M]+). Anal. Calcd for C13H13NO6: C, 55.91; H, 4.69; N,
5.02. Found: C, 55.85; H, 4.73; N, 5.12.
3 Selected reviews: (a) Z. Li, C. Brouwer and C. He, Chem. Rev., 2008,
108, 3239–3265; (b) A. S. K. Hashmi, Chem. Rev., 2007, 107, 3180–
3211; (c) G. Zeni and R. C. Larock, Chem. Rev., 2004, 104, 2285–2309;
(d) F. Alonso, M. Yus and I. P. Beletskaya, Chem. Rev., 2004, 104,
3079–3159; (e) J. Muzart, Tetrahedron, 2005, 61, 5955–6008.
4 (a) O. A. Attanasi, G. Favi, P. Filippone, G. Giorgi, S. Lillini, F.
Mantellini and F. R. Perrulli, Synlett, 2006, 2731–2734; (b) A. G. Leach,
K. N. Houk and I. W. Davies, Synthesis, 2005, 3463–3467; (c) Z. Wro´bel
and M. Ma˛kosza, Tetrahedron, 1997, 53, 5501–5514; (d) E. N. Marvell,
ed., Thermal Electrocyclic Reactions, Academic Press, New York,
1980.
Compound 4bb. Yellow liquid, 30% yield. IR (CHCl3): n 3019,
2927, 2855, 1729, 1626, 1557, 1440, 1300, 1215, 1045, 759 cm-1.
1H NMR (400 MHz, CDCl3): d 1.96–2.00 (m, 2H), 2.28–2.32 (m,
2H), 2.35 (s, 3H), 4.24 (t, J = 5.1 Hz, 2H), 5.88 (t, J = 4.3 Hz, 1H),
6.75 (d, J = 9.1 Hz, 1H), 7.20 (s, 1H), 7.65(d, J = 9.1 Hz, 1H) ppm.
13C NMR (100 MHz, CDCl3): d 20.4 (t), 22.0 (t), 22.4 (q), 66.6 (t),
104.7 (d), 112.1 (d), 113.1 (s), 121.4 (d), 127.2 (d), 141.2 (s), 144.4
(s), 158.0 (s), 159.8 (s) ppm. ESI-MS: m/z 216.2 (100%, [M+H]+).
HRMS: Found: 216.1022 ([M+H]+), Calcd. 216.1025 ([M+H]+).
Anal. Calcd for C13H13NO2: C, 72.54; H, 6.09; N, 6.51. Found: C,
72.59; H, 6.23; N, 6.45.
5 (a) K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975,
16, 4467–4470; (b) K. Hiroya, S. Itoh and T. Sakamoto, J. Org. Chem.,
2004, 69, 1126–1136; (c) K. Hiroya, S. Itoh, M. Ozawa, Y. Kanamori
and T. Sakamoto, Tetrahedron Lett., 2002, 43, 1277–1280.
6 For nitroalkyne cycloisomerizations in the presence of Pd(II)-complexes
see: (a) B. C. G. Soderberg, S. P. Gorugantula, C. R. Howerton, J.
L. Petersen and S. W. Dantale, Tetrahedron, 2009, 65, 7357–7363;
for an apparent nitro-alkyne cycloisomerization in the presence of
Pd(II) see: (b) G. M. Rosen, P. Tsai, E. D. Barth, G. D. Dorey, P.
Casara, M. Spedding and H. J. Halpern, J. Org. Chem., 2000, 65, 4460–
4463.
¨
7 For AuBr3 mediated nitroalkyne cycloisomerisation see: N. Asao, K.
Sato and Y. Yamamoto, Tetrahedron Lett., 2003, 44, 5675–5677.
8 For [Ir]-catalysed nitroalkyne cycloisomerisation: X. Li, C. D. Incar-
vito, T. Vogel and R. H. Crabtree, Organometallics, 2005, 24, 3066–
3073.
Compound 4bc. Colourless liquid, 32% yield. IR (CHCl3): n
9 For preparation and reactions of spiroindolin-3-one derivatives see:
(a) R. W. Clawson, Jr., R. E. Deavers III, N. G. Akhmedov and B. C.
G. So¨derberg, Tetrahedron, 2006, 62, 10829–10834; (b) M. J. Buller, T.
G. Cook and Y. Kobayashi, Heterocycles, 2007, 72, 163–166; (c) Q. Yin
and S.-L. You, Chem. Sci., 2011, 2, 1344–1348.
10 (a) D. A. Patterson and D. G. Wibberley, J. Chem. Soc., 1965, 1706–
1711; (b) R. N. Fakhretdinov, A. G. Telin and U. M. Dzhemilev, Bull.
Acad. Sci. USSR, Div. Chem. Sci., 1986, 35, 2059–2061; (c) N. A.
Bokach, A. A. Krokhin, A. A. Nazarov, V. Yu. Kukushkin, M. Haukka,
J. J. R. Frafflsto da Silva and A. J. L. Pombeiro, Eur. J. Inorg. Chem.,
2005, 3042–3048; (d) K. V. Luzyanin, A. G. Tskhovrebov, M. da Silva,
M. Haukka, A. J. L. Pombeiro and V. Y. Kukushkin, Chem. Eur. J.,
2009, 15, 5969–5978.
3018, 2926, 1723, 1609, 1506, 1461, 1323, 1217, 1117, 756, 666
1
cm-1. H NMR (200 MHz, CDCl3): d 1.93–2.04 (m, 2H), 2.27–
2.36 (m, 2H), 4.25 (t, J = 5.1 Hz, 2H), 5.95 (t, J = 4.3 Hz, 1H), 6.85
(dd, J = 1.6, 9.2 Hz, 1H), 7.49 (dd, J = 0.9, 1.6 Hz, 1H), 7.74 (dd, J =
0.9, 9.2 Hz, 1H) ppm. 13C NMR (50 MHz, CDCl3): d 20.4 (t), 21.9
(t), 66.7 (t), 105.8 (d), 112.8 (s), 113.2 (d), 123.7 (d), 125.6 (d), 137.3
(s), 144.1 (s), 157.5 (s), 161.1 (s) ppm. ESI-MS: m/z 236.0 (100%,
[M+H]+). HRMS: Found: 236.0461 ([M+H]+), Calcd. 236.0478
([M+H]+). Anal. Calcd for C12H10ClNO2: C, 61.16; H, 4.28; Cl,
15.04; N, 5.94. Found: C, 61.21; H, 4.19; Cl, 14.94; N, 5.77.
11 For a general Pd(II)-catalyzed isatogen synthesis see: C. V. Ramana, P.
Patel, K. Vanka, B. Miao and A Degterev, Eur. J. Org. Chem., 2010,
5955–5966.
12 For comprehensive compilation of isatogen synthesis and reactions see:
S. P. Hiremath and M. Hooper, Adv. Heterocycl. Chem., 1978, 22, 123–
181.
13 Selected examples on the alkynol-cycloisomerizations involving o-
(arylalkynyl)-nitrobenzenes where the nitro-group is a spectator group:
(a) C. V. Ramana, R. Mallik and R. G. Gonnade, Tetrahedron, 2008,
64, 219–233; (b) E. C. Y. Woon, A. Dhami, M. F. Mahonb and M.
D. Threadgill, Tetrahedron, 2006, 62, 4829–4837; (c) A. Padwa, E.
K. Krumpe and M. D. Weingarten, J. Org. Chem., 1995, 60, 5595–
5603.
14 For [Au]-mediated internal N–O redox of oximes see: (a) H.-S. Yeom,
J.-E. Lee and S. Shin, Angew. Chem., Int. Ed., 2008, 47, 7040–7043;
(b) H.-S. Yeom, Y. Lee, J.-E. Lee and S. Shin, Org. Biomol. Chem.,
2009, 7, 4744–4752.
Compound 4bd. Off white solid, Mp. 131 ◦C 35% yield. IR
(CHCl3): n 3022, 2958, 2922, 1710, 1695, 1608, 1568, 1527, 1480,
1466, 1345, 1216 cm-1. 1H NMR (200 MHz, CDCl3): d 1.94–2.05
(m, 2H), 2.28–2.37 (m, 2H), 3.94 (s, 3H), 4.27 (t, J = 5.1 Hz, 2H),
5.97 (t, J = 4.3 Hz, 1H), 7.49 (dd, J = 1.1, 9.1 Hz, 1H), 7.83 (dd, J =
1.1, 9.1 Hz, 1H), 8.28 (t, J = 1.1 Hz, 1H) ppm. 13C NMR (50 MHz,
CDCl3): d 20.4 (t), 22.0 (t), 52.6 (q), 66.7 (t), 105.7 (d), 115.2 (s),
118.7 (d), 122.6 (d), 122.8 (d), 132.8 (s), 144.2 (s), 157.1 (s), 161.2
(s), 166.3 (s) ppm. ESI-MS: m/z 282.3 (100%, [M+H]+). Found:
260.0508 ([M+H]+), Calcd. 260.0923 ([M+H]+). Anal. Calcd for
C14H13NO4: C, 64.86; H, 5.05; N, 5.40. Found: C, 64.72; H, 5.19;
N, 5.29.
15 For [Au]-mediated internal S–O redox of sulfoxides see: (a) N. D.
Shapiro and F. D. Toste, J. Am. Chem. Soc., 2007, 129, 4160–4161;
(b) G. Li and L. Zhang, Angew. Chem., Int. Ed., 2007, 46, 5156–5159;
(c) P. W. Davies and S. J.-C. Albrecht, Angew. Chem., Int. Ed., 2009, 48,
8372–8375.
16 During the revision of this manuscript, gold mediated cycloisomeriza-
tion of 2-(ynol)aryl carbonyl compounds was reported: L.-P. Liu and
G. B. Hammond, Org. Lett., 2010, 12, 4640–4643.
Acknowledgements
We thank the Ministry of Science and Technology for funding
through the Department of Science and Technology under the
Green Chemistry Program (NO. SR/S5/GC-20/2007). We thank
Dr R. G. Gonnade for the single crystal X-ray structure determi-
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21 The crystallographic data of compounds 3ad, 2bb, and 2bd have
been deposited with the Cambridge Crystallographic Data Centre as
deposition Nos. CCDC 795522 CCDC 836106, and CCDC 836107
respectively.† Copies of the data can be obtained, free of charge, on
application to the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[fax:+44(1223)336033; e-mail: deposit@ccdc.cam. ac.uk].
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7334 | Org. Biomol. Chem., 2011, 9, 7327–7334
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