Rhodium(II) acetate catalysed intramolecular cyclopropanation followed by ring opening of furan toward oxindole incorporated macrocycles

Article abstract of DOI:10.1016/j.tet.2016.02.032

Intramolecular cyclopropanation followed by ring opening of remotely placed furan was demonstrated using rhodium(II) catalysed cyclic diazoamides tethered on furan to produce 12- to 23-membered oxindole incorporated macrocycles. The length of the spacer i

Full text of DOI:10.1016/j.tet.2016.02.032

Tetrahedron 72 (2016) 1749e1757
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Rhodium(II) acetate catalysed intramolecular cyclopropanation
followed by ring opening of furan toward oxindole incorporated
macrocycles
,
a
b
Sengodagounder Muthusamya , Alagesan Balasubramani , Eringathodi Suresh
*
a School of Chemistry, Bharathidasan University, Tiruchirappalli, 620 024, India
b Analytical Discipline and Centralized Instrumentation Facility, Central Salt & Marine Chemicals Research Institute, Bhavnagar, 364 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Intramolecular cyclopropanation followed by ring opening of remotely placed furan was demonstrated
using rhodium(II) catalysed cyclic diazoamides tethered on furan to produce 12- to 23-membered ox-
indole incorporated macrocycles. The length of the spacer is an important factor to decide the stereo-
selectivity of the product.
Received 7 November 2015
Received in revised form 8 February 2016
Accepted 15 February 2016
Available online 17 February 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Diazoamide
Macrocycle
Rhodium(II) acetate
Ring opening
Stereoselectivity
1. Introduction
carbenes to remotely placed furan to form 13e17 membered
macrocyclic lactones/ketones as a mixture of inseparable isomers
The transition-metal catalysed decomposition of diazo com-
pounds is an effective method for the generation of electrophilic
metal carbenes.1 Rhodium(II) acetate has been the superior catalyst
for the generation of transient electrophilic rhodium-carbenoids
and then converted into a single isomer using molecular iodine. The
intermolecular reaction of diazoamides with furans using rhodiu-
m(II) acetate as a catalyst afforded8 a variety of furan ring opened
products 3 in a regio- and stereoselective manner and the stereo-
selectivity was controlled based on the slow addition of diazo-
amides (Scheme 1). With a curiosity to extend this reaction with
the remotely placed furan ring systems on diazoamides, study of
the intramolecular version in the presence of rhodium(II) acetate as
a catalyst under the slow addition as well as controlled concen-
tration of diazoamide was planned.
from
a-diazocarbonyl compounds. Subsequently, these undergo
an array of reactions which led to a variety of CeC, CeX bond for-
mations that are important for the creation of basic skeleton of the
organic structure.2 Generally, copper or rhodium catalysed reaction
of diazocarbonyl compounds with olefins is an efficient method for
the preparation of cyclopropane derivatives.3 The intramolecular
cyclopropanation reactions are limited4 only to simple precursors
like acyclic diazo ketones or diazo esters. Generally, transition
metal catalysed reaction of diazo compounds with furan was re-
ported5 to furnish the detectable cyclopropane intermediates
which rearrange to a mixture of ring-opened or ring-enlarged
products. Interestingly, there is scarcity of report6 available on the
reaction of 3-diazopiperidin-2-one and furan furnishing the cor-
responding cyclopropane products without ring opening. Doyle
and co-workers reported7 the intramolecular addition of metal
2. Results and discussion
In order to test the intramolecular furan ring opening reactions,
we assembled a variety of furan tethered on diazoamides 6aed.
Towards this, the esterification of salicylic acid using furfuryl al-
cohol in the presence of DCC/DMAP in dichloromethane afforded
the corresponding ester 4. Further, the O-alkylation of 4 using
dibromoalkanes in the presence of K2CO3/TBAI in DMF afforded the
corresponding bromo compounds 5. Subsequent N-alkylation of 3-
diazooxindoles 1 with bromo compounds 5 in the presence of
K2CO3/TBAI afforded the corresponding furan tethered on diazo-
amides 6aed in 80e87% yield (Scheme 2).
* Corresponding author. Tel.: þ91 431 2407053; fax: þ91 431 2407045; e-mail
address: muthu@bdu.ac.in (S. Muthusamy).
http://dx.doi.org/10.1016/j.tet.2016.02.032
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

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S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
Scheme 1. Ring opening reactions of furan with rhodium(II) carbenoids.
Scheme 2. Synthesis of furan tethered on diazoamides 6aed.
In our ongoing efforts to construct9 the functionalized macro-
NMR spectra of 7a and 8a exhibited a characteristic singlet reso-
cycles, we investigated the metal-catalysed decomposition re-
actions with slow addition as well as controlled concentration of
diazoamides 6 to produce oxaza-macrocycles via intramolecular
cyclopropanation followed by the ring opening of furan. Based on
our earlier studies,8 furan tethered on diazoamide 6a was added
with the flow rate of 1.5 mL/h to 1 mol % of rhodium(II) acetate
dimer as a catalyst to afford a mixture of products 7a/8a via intra-
molecular cyclopropanation followed by the ring opening of furan
in 32% yield in the ratio of 50:50. Based on this observation, the
flow rate of the diazoamide 6a was decreased to 1.0 mL/h to give
65% yield of macrocycles 7a/8a. There is no improvement in the
yield as well as ratio of the products 7a/8a (Table 1) when the flow
rate kept as 0.5 mL/h. It was found that CuOTf and Cu(CH3CN)4PF6
catalyst was also effective to furnish the ring opened products 7a/8a
but Cu(acac)2 was not suitable for this transformation. The products
7a/8a were separated by the column chromatography and the 1H
nance at d 4.90 and 5.12 ppm for Hd protons, respectively. The ratio
of stereoisomers was determined based on the 1H NMR spectrum of
the crude reaction mixture. The stereochemistry of the product was
confirmed based on the coupling constant of the Hb proton in 8a
appeared as a double of doublets at
based on the literature.8 The Hb proton in 7a appeared as a non-first
order spectral pattern at 8.16. To identify the importance of slow
d
9.14 (J1¼16.0, J2¼11.6 Hz)
d
addition, the above reaction was performed with the simultaneous
addition of diazoamide and catalyst to yield a trace amount of 7a/8a
along with the complex mixture. It indicates that the concentration
of the diazoamide in the reaction mixture is important for
obtaining the products.
Under these optimized reaction conditions, we next focused our
attention on exploring the scope of the reaction for various ring
sizes to study using different dibromo compounds. Reaction of 6b
underwent intramolecular cyclopropanation followed by the ring

S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
1751
Table 1
Optimization of reaction conditions for 7a/8a
Entry
Catalyst (1 mol %)
Flow ratea mL/h
Yieldb
%
Ratio of 7a/8ad
1
2
3
4
5
6
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
CuOTf
Cu(acac)2
Cu(CH3CN)4PF6
1.5
1.0
0.5
1.0
1.0
1.0
32
65
40
45
ndc
23
50:50
50:50
45:55
50:50
d
50:50
a
The compound 6a (0.01 mmol) was dissolved in 5 mL of dry CH2Cl2.
Isolated yield.
b
c
Not detected.
d
Ratio of isomers was determined by 1H NMR spectra of crude sample.
opening furnished a mixture of macrocycles 7b/8b in 43% yield.
Similarly, diazo compounds 6c and 6d yielded the corresponding
macrocycles 7c/8c and 7d/8d in moderate yield. The results are
summarized in Scheme 3. These products were identified as Z/Z and
E/Z isomers based on the coupling pattern of Hb proton. In order to
confirm the stereochemistry of the double bond present in mac-
rocycles 7, the single-crystal analysis of 7c was carried out (Fig. 1).
Thus the stereochemistry of Z,Z/S-trans for the isomer 7 and Z,E for
the isomer 8 was cautiously assigned based on the crystal structure
and our previous report.8
Next, it was planned to reduce the ring size as minimum as
possible thereby the reaction will lead to an intermolecular di-
merization process. To demonstrate this, furan tethered on diazo-
amides having shorter chain length were assembled via
esterification of bromoacids 9 using furfuryl alcohol in the presence
of DCC/DMAP to afford the corresponding bromo ester 10. Further,
N-alkylation of 3-diazooxindoles 1 with bromoester 10 in the
presence of K2CO3/TBAI afforded the corresponding furan tethered
on diazoamides 6eeg in 85e91% yield (Scheme 4).
The diazoamides 6eeg having shorter chain length were further
examined for intramolecular cyclopropanation followed by ring
opening of furan under the above optimized reaction conditions. To
our surprise, reaction of diazoamide 6e in the presence of rhodiu-
m(II) acetate as a catalyst produced only 7e as a single isomer in
65% yield (Scheme 5). Similar reaction of diazoamides 6f and 6g
afforded the corresponding macrocycles 7f and 7g in good yield.
Interestingly, the reaction proceeded towards a single isomer when
the chain length shortened.
the isomers 7aed was fixed as Z,Z/S-trans based on the crystal
structure (Fig. 1) whereas the stereochemistry of the isomers 7eeh
was tentatively assigned as Z,Z/S-cis based on the MM2 minimum
energy calculations11 as shown in Schemes 5 and 7.
The plausible mechanism is proposed as shown in Scheme 8 for
the formation of macrocycles from furan tethered on diazoamides 6
in the presence of rhodium(II) acetate as a catalyst under slow
addition as well as controlled concentration of diazoamide. The
transient rhodium(II) carbenoids 13 derived from diazoamides
6aed having longer spacer might undergo furnishing a mixture of
14a and 14b via an intramolecular cyclopropanation with the less
substituted double bond of furan ring present in the molecule in
two different ways. The labile intermediates 14a and 14b un-
derwent ring-opening to provide macrocycles 7aed and 8aed,
respectively. However, the rhodium(II) carbenoids 13 derived from
diazoamides 6eef having shorter spacer might produce selectively
14a having lower minimization energy11 than 14b affording 7eef in
a diasteroselective manner due to the fixed conformation of the
molecule. In all the above reactions, the proposed cyclopropane
intermediates 14a and 14b could not be isolated. The requirement
of slow addition of diazoamides indicates that the concentration is
an important factor in achieving these macrocycles in a stereo-
selective manner. It may be noted that Doyle’s intramolecular ad-
dition of metal carbenes to remote furan unit furnished7 13e17
macrocyclic lactones/ketones via furan ring opening as a mixture of
inseparable isomers and converted into a single isomer using mo-
lecular iodine. In contrast, the above intramolecular strategy is
applicable in providing separable Z,Z and Z,E isomers. The effort was
made to isomerize 7a and 8a using iodine or Lewis acids, but in
vain.
Further, the scope was extended to synthesize
a-keto ester
containing macrocycles via intramolecular cyclopropanation fol-
lowed by ring opening of furan under the above optimized reaction
conditions. Towards this, esterification of furan carboxylic acid 11
with bromo alcohol in the presence of DCC/DMAP was performed
to afford the corresponding bromoester 12. Further, N-alkylation of
3-diazooxindoles 1 with bromo ester 12 in the presence of K2CO3/
TBAI afforded the corresponding furan tethered on diazoamide 6h
in 84% yield (Scheme 6).
Reaction of diazoamide 6h in the presence of rhodium(II) ace-
tate as a catalyst as described above furnished a-keto ester con-
taining macrocycle 7h (Scheme 7) in good yield. These results
indicate that the presence of shorter chain in diazoamides 6eeh
yielded the formation of only Z/Z isomer. The stereochemistry of
3. Conclusion
In conclusion, we have demonstrated the intramolecular
cyclopropanation followed by ring opening reaction of remotely
placed furan ring in the presence of rhodium(II) acetate catalyst
under slow addition as well as controlled concentration of diazo-
amide to yield oxindole incorporated macrocycles in a stereo-
selective manner. Interestingly, the above products were obtained
under mild reaction conditions via the slow addition of diazo-
amides. The stereoselectivity of the product mainly depends on the

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S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
Scheme 3. Synthesis of macrocycles 7aed/8aed.
spacer length present in the molecule and the concentration of
diazoamides.
isomer in parts per million (
d) relative to tetramethylsilane (d
0.00) and chloroform ( 77.7), respectively. Multiplicities are in-
d
dicated by singlet (s), doublet (d), triplet (t), quartet (q), pentet (p),
multiplet (m). Coupling constants (J) were reported in hertz (Hz).
Carbon types were determined from 13C NMR and DEPT experi-
ments. High resolution mass analyses were performed using
electrospray ionization (ESI) technique. Analytical thin layer
chromatography (TLC) was performed on silica gel and compo-
nents were visualized by observation under iodine or UV-light.
Column chromatography was performed using silica gel
(100e200 mesh). The 3-diazooxindole 1 was prepared by the
literature procedure.10
4. Experimental section
4.1. General
All melting points were uncorrected. IR spectra were recorded
neat on a Bruker Alpha FTIR spectrophotometer using ATR tech-
nique. 1H and 13C NMR spectra were recorded (400 and 100 MHz,
respectively) on a Bruker Avance DPX 400 using CDCl3. Chemical
shifts for proton and carbon resonances are reported for the major

S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
1753
Scheme 5. Synthesis of macrocycles 7eeg.
Fig. 1. ORTEP view of compound 7c (Z,Z/S-trans).
tetrabutylammonium iodide. The progress of the reaction was
monitored using TLC. The mixture was extracted with dichloro-
methane (3ꢂ25 mL) and the combined organic layers were washed
with water (3ꢂ25 mL), brine (2ꢂ25 mL) and dried (anhydrous
Na2SO4). The solvent was removed under reduced pressure and the
resulting residue purified using column chromatography (SiO2,
hexane/ethyl acetate 80:20) to afford the respective bromo com-
pound 5.
4.2. General procedure for the preparation of 4
To an oven-dried flask salicylic acid (2.80 mmol) in dry
dichloromethane (50 mL) was charged under inert atmosphere. To
the above solution, furan-2-ylmethanol (2.55 mmol) was added
and the reaction mixture cooled to 0 ꢀC. To this cooled reaction
mixture, DCC (3.1 mmol) and a catalytic amount of DMAP were
added. Initially, the reaction mixture was homogeneous. The white
solid separates out from the reaction mixture after 2 h duration.
Progress of the reaction was monitored using TLC. After completion
of the reaction the reaction mixture was filtered and concentrated
in vacuo. The residue was subjected to column chromatography
(hexane/EtOAc) to furnish the corresponding ester12 4 in 70% yield.
Compound 5a: Yield 75%; 450 mg; Colourless liquid; IR (neat):
nmax 2089, 1727, 1683, 1681, 1484, 1467, 1298, 1196, 1065 cmꢁ1 1H
;
NMR (400 MHz, CDCl3)
d 1.27e1.41 (m, 12H), 1.68e1.78 (m, 4H),
3.35 (t, 2H, J¼7.2 Hz), 3.94 (t, 2H, J¼6.4 Hz), 5.26 (s, 2H), 6.35e6.36
(m, 1H), 6.46 (d, 1H, J¼3.2 Hz), 6.90e6.94 (m, 2H), 7.39e7.43 (m,
2H), 7.78 (dd, 1H, J1¼8.0, J2¼1.6 Hz); 13C NMR (100 MHz, CDCl3)
IR (neat):
n
3190, 2929, 2854, 1669, 1613, 1484, 1468, 1295, 1153,
750 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
5.25 (s, 1H), 6.31e6.32 (m,
d
25.8 (CH2), 26.9 (CH2), 28.2 (CH2), 29.1 (CH2), 29.2 (CH2), 29.3
(CH2), 33.8 (CH2), 58.2 (CH2), 68.9 (CH2), 108.8 (]CH), 110.4 (]CH),
113.2 (]CH), 119.9 (]CH), 120.2 (quat-C), 131.8 (]CH), 133.5 (]
CH), 143.0 (]CH), 149.8 (quat-C), 158.8 (quat-C), 166.1 (C]O);
HRMS (ESI) Calcd for C22H29BrO [MþH]þ 437.1327; found, 437.1320.
Compound 5b: Yield 82%; 480 mg; Colourless liquid; IR (neat):
1H), 6.43 (d, 1H, J¼3.2 Hz), 6.75e6.79 (m, 1H), 6.89 (dd, 1H,
J1¼8.4 Hz, J2¼0.8 Hz), 7.34e7.75 (m, 2H), 7.77 (dd, 1H, J1¼8.4 Hz,
J2¼2.0 Hz), 10.59 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 58.7 (CH2),
110.7 (]CH), 111.4 (]CH),112.2 (quat-C), 117.6 (]CH), 119.2 (]CH),
130.1 (]CH), 135.9 (]CH), 143.6 (]CH), 148.8 (quat-C), 161.7 (C]
O), 169.8 (C]O).
nmax 2093, 1718, 1683, 1601, 1400, 1299, 1264, 1128, 729 cmꢁ1
;
1H
NMR (400 MHz, CDCl3)
d 1.30e1.41 (m, 10H), 1.68e1.76 (m, 4H),
3.36 (t, 2H, J¼6.8 Hz), 3.96 (t, 2H, J¼6.4 Hz), 5.26 (s, 2H), 6.35 (d, 1H,
J¼1.6 Hz), 6.45 (br, 1H), 6.91e6.93 (m, 2H), 7.38e7.42 (m, 2H), 7.78
4.3. General procedure for the preparation of 5
(m, 1H); 13C NMR (100 MHz, CDCl3)
d 26.1 (CH2), 27.3 (CH2), 28.1
(CH2), 29.1 (CH2), 29.2 (CH2), 29.4 (CH2), 34.8 (CH2), 58.3 (CH2), 68.9
(CH2), 108.9 (]CH), 110.6 (]CH), 113.2 (]CH), 120.0 (quat-C), 120.1
(]CH), 131.8 (]CH), 133.5 (]CH), 143.1 (]CH), 149.8 (quat-C),
158.8 (quat-C), 166.1 (C]O); HRMS (ESI) Calcd for C21H27BrO4
[MþH]þ 423.1171; found, 423.1175.
To an oven-dried flask, a solution containing the ester 4
(1.37 mmol) and potassium carbonate (3.34 mmol) in dry DMF was
taken under argon atmosphere. To this reaction mixture, a solution
of appropriate dibromo compound (1.65 mmol) in dry DMF was
slowly added over a period of 30 min and then a catalytic amount of
Scheme 4. Synthesis of furan tethered on diazoamides 6eeg.

1754
S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
N2
O
O
1
DCC/DMAP
Br
( )2
N
OH
O
+
HO
O
O
O
( )2
Br
CH2Cl2, 30 °C
( )2
K2CO3 / TBAI
DMF, 30 °C
O
O
O
6h (84%)
11
12
Scheme 6. Synthesis of furan tethered on diazoamide 6h.
113.2 (]CH), 119.9 (quat-C), 120.3 (]CH), 131.9 (]CH), 133.6 (]
CH), 143.2 (]CH), 149.7 (quat-C), 158.6 (quat-C), 166.0 (C]O));
HRMS (ESI) Calcd for
353.0392.
C
16H18BrO4 [MþH]þ 353.0388; found,
4.4. General procedure for the preparation of 10
Scheme 7. Synthesis of macrocycle 7h.
To an oven-dried flask bromoacid 9 (1.79 mol) in dry dichloro-
methane (50 mL) was charged under inert atmosphere. To the
above solution, furan-2-ylmethanol (1.79 mmol) was added and the
reaction mixture cooled to 0 ꢀC. To this cooled reaction mixture,
DCC (2.15 mmol) and a catalytic amount of DMAP were added.
Initially, the reaction mixture was homogeneous. The white solid
separates out from the reaction mixture after 2 h duration. Progress
of the reaction was monitored using TLC. After completion of the
reaction the reaction mixture was filtered and concentrated in
vacuo. The residue was subjected to column chromatography
(hexane/EtOAc) to furnish the corresponding ester 10.
Compound 5c: Yield 83%; 415 mg; Colourless liquid; IR (neat):
nmax 2930, 1730, 1710, 1658, 1615, 1485, 1275, 1075, 725 cmꢁ1 1H
;
NMR (400 MHz, CDCl3) 1e1.60 (m, 2H), 1.72e1.79 (m, 2H),
1.83e1.90 (m, 2H), 3.38 (t, J¼7.2 Hz, 2H), 3.96 (t, J¼6.4 Hz, 2H), 5.26
(s, 2H), 6.35e6.36 (m,1H), 6.46 (d, J¼3.2 Hz,1H), 6.88e6.93 (m, 2H),
7.37e7.42 (m, 2H), 7.78 (dd, J1¼7.6, J2¼1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3)
d 24.7 (CH2), 28.3 (CH2), 32.5 (CH2), 33.7 (CH2),
58.3 (CH2), 68.4 (CH2), 110.5 (]CH), 110.7 (]CH), 113.1 (]CH),
120.0 (quat-C), 120.1 (]CH), 131.8 (]CH), 133.6 (]CH), 143.2 (]
CH), 149.8 (quat-C), 158.6 (quat-C), 166.0 (C]O); HRMS (ESI) Calcd
for C17H20BrO4 [MþH]þ 367.0545; found, 367.0543.
Compound 10a: Yield 85%; 400 mg; Colourless oil; IR (neat):
nmax 1745, 1660, 1604, 1475, 1389, 1345, 1156, 1022, 924 cmꢁ1 1H
;
NMR (400 MHz, CDCl3)
J¼7.2 Hz), 3.45 (t, 2H, J¼6.4 Hz), 5.08 (s, 2H), 6.37 (s,1H), 6.41 (s,1H),
7.42 (s,1H); 13C NMR (100 MHz, CDCl3)
27.7 (CH2), 32.3 (CH2), 32.6
d
2.17 (quint, 2H, J¼6.8 Hz), 2.53 (t, 2H,
Compound 5d: Yield 78%; 380 mg; Colourless liquid; IR (neat):
d
nmax 2943, 2095, 1755, 1715, 1614, 1475, 1255, 1112, 725 cmꢁ1 1H
;
(CH2), 58.2 (CH2), 110.6 (]CH), 110.8 (]CH), 143.4 (]CH), 149.3
(quat-C), 172.2 (C]O); HRMS (ESI) Calcd for C9H12BrO3 [MþH]þ
246.9969; found, 246.9967.
NMR (400 MHz, CDCl3) 1.81e1.95 (m, 4H), 3.37 (t, J¼6.4 Hz, 2H),
4.03 (t, J¼6.0 Hz, 2H), 5.23 (s, 2H), 6.34e6.35 (m, 1H), 6.43 (d,
J¼3.2 Hz, 1H), 6.91e6.97 (m, 2H), 7.39e7.44 (m, 2H), 7.78 (dd,
Compound 10b: Yield 79%; 375 mg; Colourless oil; IR (neat):
J1¼7.6, J2¼0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 24.9 (CH2), 27.2
(CH2), 33.5 (CH2), 58.3 (CH2), 67.9 (CH2),110.5 (]CH), 110.6 (]CH),
nmax 3125, 2941, 1745, 1695, 1605, 1465, 1382, 1165, 735 cmꢁ1 1H
;
NMR (400 MHz, CDCl3) 3.83 (s, 2H), 5.13 (s, 2H), 6.36 (s, 1H), 6.44 (s,
Scheme 8. Mechanism for the formation of macrocycles 7/8.

S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
1755
1H), 7.42 (s,1H); 13C NMR (100 MHz, CDCl3)
110.7 (CH), 111.0 (CH), 111.4 (CH), 143.6 (CH), 148.6 (quat-C), 166.8
(C]O); HRMS (ESI) Calcd for C7H8BrO3 [MþH]þ 218.9656; found,
218.9661.
d
25.9 (CH2), 59.5 (CH2),
120.0 (quat-C), 120.1 (]CH), 121.9 (]CH), 125.4 (]CH), 131.8 (]
CH), 133.5 (]CH), 133.9 (]CH), 143.1 (quat-C), 149.8 (quat-C), 158.8
(quat-C), 166.1 (C]O), 166.7 (C]O); HRMS (ESI) Calcd for
C
29H31N3O5 [MþNa]þ 524.2161; found, 524.2172.
Compound 6c: Yield 82%; 230 mg; Deep red gel; IR (neat): nmax
4.5. General procedure for the preparation of 12
2925, 2098, 1736, 1700, 1669, 1605, 1469, 1264, 1099, 732 cmꢁ1; 1H
NMR (400 MHz, CDCl3) 1.54e1.56 (m, 2H), 1.72e1.84 (m, 4H), 3.84
(t, J¼7.2 Hz, 2H), 3.98 (t, J¼6.4 Hz, 2H), 5.25 (s, 2H), 6.36e6.37 (m,
1H), 6.46 (d, J¼3.2 Hz, 1H), 6.89e6.96 (m, 3H), 7.07 (td, J1¼7.6,
J2¼0.8 Hz, 1H), 7.15e7.20 (m, 2H), 7.39e7.43 (m, 2H), 7.78 (dd,
To an oven-dried flask furan-2-carboxylic acid 11 (1.78 mmol) in
dry dichloromethane (50 mL) was charged under inert atmosphere.
To the above solution, 3-bromo-1-propanol (1.78 mmol) was added
and the reaction mixture cooled to 0 ꢀC. To this cooled reaction
mixture, DCC (2.14 mmol) and a catalytic amount of DMAP were
added. Initially, the reaction mixture was homogeneous. The white
solid separates out from the reaction mixture after 2 h duration.
Progress of the reaction was monitored using TLC. After completion
of the reaction the reaction mixture was filtered and concentrated
in vacuo. The residue was subjected to column chromatography
(hexane/EtOAc) to furnish the corresponding ester 12.
J1¼7.6, J2¼1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 23.3 (CH2), 27.7
(CH2), 28.7 (CH2), 40.6 (CH2), 58.3 (CH2), 68.5 (CH2), 108.9 (]CH),
110.6 (]CH), 110.6 (]CH), 113.2 (]CH), 116.9 (quat-C), 118.3 (]
CH), 120.0 (quat-C), 120.1 (]CH), 121.9 (]CH), 125.4 (]CH), 131.9
(]CH), 133.6 (]CH), 133.8 (quat-C), 143.2 (]CH), 149.8 (quat-C),
158.7 (quat-C), 166.0 (C]O), 166.8 (C]O); HRMS (ESI) Calcd for
C
25H23N3O5 [MþH]þ 446.1716; found, 446.1720.
Compound 6d: Yield 87%; 235 mg; Deep red gel; IR (neat): nmax
Compound 12: Yield 84%; 350 mg; Yellow liquid; IR (neat): nmax
2943, 2095, 1755, 1715, 1614, 1475, 1255, 1112, 725 cmꢁ1 1H NMR
;
2974, 1727, 1668, 1365, 1174, 922, 714 cmꢁ1
;
1H NMR (400 MHz,
(400 MHz, CDCl3) 1.81e1.95 (m, 4H), 3.88 (t, J¼6.4 Hz, 2H), 4.05 (t,
J¼6.0 Hz, 2H), 5.23 (s, 2H), 6.34e6.35 (m, 1H), 6.43 (d, J¼3.2 Hz, 1H),
6.91e6.97 (m, 3H), 7.07 (t, J¼7.6 Hz, 1H), 7.17 (t, J¼7.6 Hz, 2H),
7.39e7.44 (m, 2H), 7.78 (dd, J1¼7.6, J2¼0.8 Hz, 1H); 13C NMR
CDCl3) 2.31 (quint, J¼6.4 Hz, 2H), 3.53 (t, J¼6.8 Hz, 2H), 4.45 (t,
J¼6.0 Hz, 2H), 6.52e6.53 (m, 1H), 7.19e7.20 (m, 1H), 7.59e7.60 (m,
1H); 13C NMR (100 MHz, CDCl3)
d 29.2 (CH2), 31.8 (CH2), 62.6 (CH2),
111.9 (CH), 118.1 (CH), 144.4 (quat-C), 146.5 (CH), 158.5 (C]O);
HRMS (ESI) Calcd for C8H10BrO3 [MþH]þ 232.9813; found,
232.9820.
(100 MHz, CDCl3) d 24.5 (CH2), 26.3 (CH2), 40.1 (CH2), 58.3 (CH2),
67.9 (CH2), 109.1 (]CH), 110.6 (]CH), 110.6 (]CH), 113.2 (]CH),
116.8 (quat-C), 118.3 (]CH), 119.9 (quat-C), 120.2 (]CH), 122.0 (]
CH),125.5 (]CH),131.9 (]CH),133.6 (]CH),133.8 (]CH),143.2 (]
CH), 149.7 (quat-C), 158.6 (quat-C), 166.0 (C]O), 166.8 (C]O);
4.6. General procedure for the preparation of furan tethered
on diazoamides 6aeh
HRMS (ESI) Calcd for
432.1562.
C
24H21N3O5 [MþH]þ 432.1559; found,
To an oven-dried flask, a solution containing the 3-diazoox-
indole 1 (1.25 mmol) and potassium carbonate (3.14 mmol) in dry
DMF was taken under argon atmosphere. To this reaction mixture,
a solution of appropriate bromo furan 5 (1.35 mmol) in dry DMF
was slowly added over a period of 30 min and then a catalytic
amount of tetrabutylammonium iodide. The progress of the re-
action was monitored using TLC. The mixture was extracted with
dichloromethane (3ꢂ25 mL) and the combined organic layers were
washed with water (3ꢂ25 mL), brine (2ꢂ25 mL) and dried (anhy-
drous Na2SO4). The solvent was removed under reduced pressure
and the resulting residue purified using column chromatography
(SiO2, hexane/ethyl acetate 80:20) to afford the respective diazo-
amides 6.
Compound 6e: Yield 88%; 180 mg; Red solid; mp 158e159 ꢀC; IR
(neat): nmax 2087, 1731, 1675, 1609, 1467, 1399, 1345, 1148, 1015,
917 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
2.03 (quin, 2H, J¼7.2 Hz),
2.43 (t, 2H, J¼7.2 Hz), 3.87 (t, 2H, J¼7.2 Hz), 5.07 (s, 2H), 6.36e6.37
(m, 1H), 6.41e6.42 (m, 1H), 6.96 (d, 1H, J¼8.0 Hz), 7.05e7.10 (m, 1H),
7.15e7.19 (m, 2H), 7.41e7.42 (m, 1H); 13C NMR (100 MHz, CDCl3)
d
23.1 (CH2), 30.7 (CH2), 36.7 (CH2), 58.1 (CH2), 108.9 (]CH), 110.6
(]CH), 110.7 (]CH), 116.7 (quat-C), 118.3 (]CH), 122.1 (]CH),
125.5 (]CH), 133.6 (quat-C), 143.3 (]CH), 149.3 (quat-C), 166.7
(C]O), 172.4 (C]O); HRMS (ESI) Calcd for C17H15N3O4 [MþNa]þ
348.0960; found, 348.0968.
Compound 6f: Yield 91%; 170 mg; Red solid; mp 162e164 ꢀC; IR
(neat): nmax 2085, 1730, 1671, 1615, 1475, 1395, 1341, 1144, 1018,
Compound 6a: Yield 80%; 260 mg; Red solid; mp 184e186 ꢀC; IR
(neat): nmax 2089, 1727, 1683, 1681, 1484, 1467, 1298, 1196,
914 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
2.00 (quin, 2H, J¼7.2 Hz),
2.42 (t, 2H, J¼7.2 Hz), 3.85 (t, 2H, J¼7.2 Hz), 5.07 (s, 2H), 6.36e6.37
(m, 1H), 6.41e6.42 (m, 1H), 6.88 (d, 1H, J¼8.4 Hz), 7.11e7.14 (m, 1H),
7.17e7.18 (m, 2H), 7.42e7.43 (m, 1H); 13C NMR (100 MHz, CDCl3)
1065 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.28e1.41 (m, 12H),
1.68e1.77 (m, 4H), 3.80 (t, 2H, J¼7.2 Hz), 3.98 (t, 2H, J¼6.4 Hz), 5.26
(s, 2H), 6.35e6.36 (m,1H), 6.46 (d,1H, J¼3.2 Hz), 6.90e6.94 (m, 3H),
7.04 (td, 1H, J1¼7.6, J2¼0.8 Hz), 7.15e7.19 (m, 2H), 7.39e7.43 (m, 2H),
d
23.0 (CH2), 30.9 (CH2), 39.9 (CH2), 58.2 (CH2), 109.7 (]CH), 110.6
(]CH), 110.8 (]CH), 118.2 (]CH), 118.3 (quat-C), 125.5 (]CH),
127.4 (quat-C), 132.2 (quat-C), 143.4 (]CH), 149.3 (quat-C), 166.1
(C]O), 172.3 (C]O); HRMS (ESI) Calcd for C17H14ClN3O4 [MþH]þ
360.0751; found, 360.0756.
7.78 (dd, 1H, J1¼8.0, J2¼1.6 Hz); 13C NMR (100 MHz, CDCl3)
d 25.9
(CH2), 26.9 (CH2), 28.1 (CH2), 29.1 (CH2), 29.3 (CH2), 29.4 (CH2), 40.8
(CH2), 58.3 (CH2), 68.9 (CH2), 108.9 (]CH), 110.5 (]CH), 113.2 (]
CH), 116.9 (quat-C), 118.3 (]CH), 119.9 (]CH), 120.1 (quat-C), 121.8
(]CH), 125.4 (]CH), 131.8 (]CH), 133.5 (]CH), 134.0 (quat-C),
143.1 (]CH), 149.8 (quat-C), 158.8 (quat-C), 166.1 (quat-C), 166.7
(C]O); HRMS (ESI) Calcd for C30H33N3O5 [MþH]þ 516.2498; found,
516.2505.
Compound 6g: Yield 85%; 158 mg; Red solid; mp 146e149 ꢀC; IR
(neat): nmax 3127, 2936, 2082, 1739, 1680, 1602, 1465, 1391, 1334,
1272, 1172, 923, 747 cmꢁ1 1H NMR (400 MHz, CDCl3) 4.19 (t,
;
J¼5.6 Hz, 2H), 4.54 (t, J¼5.6 Hz, 2H), 6.46e6.47 (m, 1H), 7.06e7.09
(m, 3H), 7.15e7.20 (m, 2H), 7.55 (s, 1H); 13C NMR (100 MHz, CDCl3)
Compound 6b: Yield 85%; 268 mg; Red solid; mp 175e177 ꢀC; IR
(neat): nmax 2093, 1718, 1683, 1601, 1400, 1299, 1264, 1128,
d 39.6 (CH2), 62.3 (CH2), 109.2 (CH), 111.9 (CH), 116.7 (quat-C), 118.4
(CH), 118.6 (CH), 122.3 (CH), 125.4 (CH), 133.8 (quat-C), 144.0 (quat-
C), 146.7 (CH), 158.3 (C]O), 166.8 (C]O); HRMS (ESI) Calcd for
729 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.30e1.41 (m, 10H),
1.68e1.76 (m, 4H), 3.81 (t, 2H, J¼6.8 Hz), 3.97 (t, 2H, J¼6.4 Hz), 5.26
(s, 2H), 6.35 (d, 1H, J¼1.6 Hz), 6.45 (br, 1H), 6.91e6.93 (m, 3H),
7.04e7.08 (m, 1H), 7.15e7.19 (m, 2H), 7.38e7.42 (m, 2H), 7.78 (m,
C
15H11N3O4 [MþH]þ 298.0827; found, 298.0831.
Compound 6h: Yield 84%; 164 mg; Red solid; mp 156e158 ꢀC; IR
(neat): nmax 2965, 2098, 1715, 1685, 1358, 1185, 1125, 915, 885,
755 cmꢁ1; 1H NMR (400 MHz, CDCl3) 2.17 (quin, J¼6.4 Hz, 2H), 3.99
(t, J¼6.8 Hz, 2H), 4.35 (t, J¼6.0 Hz, 2H), 6.51e6.52 (m, 1H), 6.96 (d,
J¼8.0 Hz, 1H), 7.06 (t, J¼7.6 Hz, 1H), 7.14e7.20 (m, 3H), 7.58 (d,
1H); 13C NMR (100 MHz, CDCl3)
d 25.8 (CH2), 26.9 (CH2), 28.1 (CH2),
29.1 (CH2), 29.2 (CH2), 29.4 (CH2), 40.8 (CH2), 58.3 (CH2), 68.9 (CH2),
108.9 (]CH), 110.6 (]CH), 113.2 (]CH), 116.9 (]CH), 118.3 (]CH),

1756
S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
J¼0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
27.3 (CH2), 37.6 (CH2),
(quat-C), 120.0 (]CH), 121.4 (]CH), 122.1 (]CH), 127.0 (]CH),
62.1 (CH2), 108.7 (CH), 111.9 (CH), 116.8 (quat-C), 118.1 (CH), 118.4
(CH), 122.1 (CH), 125.5 (CH), 133.6 (quat-C), 144.5 (quat-C), 146.4
(CH), 158.4 (C]O), 166.7 (C]O); HRMS (ESI) Calcd for C16H13N3O4
[MþNa]þ 334.0803; found, 334.0805.
129.6 (]CH), 130.6 (]CH), 131.3 (]CH), 132.1 (]CH), 132.7 (quat-
C), 133.8 (quat-C),133.9 (]CH) 137.5 (]CH), 143.0 (quat-C), 158.5
(quat-C), 162.3 (CONR), 166.9 (COO), 196.8 (C]O); HRMS (ESI) Calcd
for C29H31NO5 [MþH]þ 474.2280; found, 474.2270.
Compound 8b: Yield 17%; 15 mg; Red solid; mp 171e173 ꢀC; IR
(neat): nmax 3061, 2929, 2858, 1699, 1598, 1462, 1366, 1295, 1247,
4.7. General procedure for the preparation of macrocycles 7
and 8
1171, 1127, 1087, 989, 751 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
0.86e0.88 (m, 2H), 1.38e1.44 (m, 6H), 1.68e1.77 (m, 6H), 3.81 (t,
J¼5.6 Hz, 2H), 3.97 (t, J¼6.0 Hz, 2H), 5.12 (s, 2H), 6.53 (d, J¼16.4 Hz,
1H), 6.80 (d,1H, J¼8.0 Hz), 6.91e7.03 (m, 4H), 7.16 (d, J¼11.6 Hz,1H),
7.29e7.31 (m, 1H), 7.41e7.47 (m, 2H), 7.79 (m, 1H), 9.16 (dd, J1¼16.0,
In an oven-dried flask rhodium(II) acetate dimer (1 mol %) in
10 mL of dry dichloromethane was degasified under an argon at-
mosphere. To this reaction mixture, 5 mL solution of 6 (100 mg,
0.19 mmol) in dry dichloromethane was added for the flow rate of
1.0 mL/h via syringe pump under an argon atmosphere at 25 ꢀC. The
reaction mixture was further allowed to stir at the same tempera-
ture and followed by TLC till the disappearance of the starting
material. The solvent was removed under reduced pressure and
chromatographic purification (Hexane/EtOAc, 80:20) of the residue
to afford a separable macrocycle 7 (Z,Z) and 8 (Z,E) based on the
newly formed two double bonds.
J2¼11.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 25.1 (CH2), 26.0 (CH2),
26.3 (CH2), 27.7 (CH2), 28.1 (CH2), 29.5 (CH2), 29.6 (CH2), 37.9 (CH2),
66.1 (OCH2), 68.9 (OCH2), 108.6 (]CH), 112.9 (]CH), 120.0 (]CH),
120.0 (quat-C), 120.9 (]CH), 122.0 (]CH), 122.4 (quat-C), 130.8 (]
CH), 130.9 (]CH), 131.2 (]CH), 132.3 (quat-C), 133.4 (]CH), 134.1
(]CH), 138.5 (]CH), 143.3 (quat-C), 158.6 (quat-C), 166.2 (CONR),
166.8 (COO), 194.8 (C]O); HRMS (ESI) Calcd for C29H31NO5 [MþH]þ
474.2280; found, 474.2273.
Reaction of 6a was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7a (Z,Z) and 8a (Z,E) isomers with 47:53 ratio.
Reaction of 6c was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7c (Z,Z) and 8c (Z,E) isomers with 58:42 ratio.
Compound 7a: Yield 39%; 37 mg; Red solid; mp 178e181 ꢀC; IR
(neat): nmax 3062, 2927, 2855, 1702, 1600, 1463, 1365, 1296, 1248,
Compound 7c: Yield 31%; 29 mg; Red solid; mp 172e174 ꢀC; IR
(neat): nmax 2925, 2855, 1736, 1700, 1669, 1605, 1469, 1264, 1099,
732 cmꢁ1; 1H NMR (400 MHz, CDCl3) 1.47e1.51 (m, 2H), 1.63e1.69
(m, 2H), 1.72e1.76 (m, 2H), 3.86 (br, 4H), 4.69 (s, 2H), 6.52 (dd,
J1¼12.0, J2¼1.2 Hz, 1H), 6.77 (d, J¼8 Hz, 1H), 6.89e6.95 (m, 2H), 7.03
(t, J¼7.6 Hz, 1H), 7.24e7.28 (m, 1H), 7.43e7.47 (m, 1H), 7.52 (d,
J¼7.6 Hz, 1H), 7.80e7.84 (m, 2H), 8.00 (m, 1H); 13C NMR (100 MHz,
1171, 1129, 1089, 984, 752, 706 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
1.12e1.17 (m, 10H), 1.70e1.78 (m, 6H), 3.86 (t, J¼5.6 Hz, 2H), 4.02 (t,
J¼7.2 Hz, 2H), 4.90 (s, 2H), 6.84 (d, 1H, J¼7.6 Hz), 6.98e7.05 (m, 3H),
7.15 (d, J¼15.2 Hz, 1H), 7.29e7.33 (m, 2H), 7.51 (t, J¼7.6 Hz, 1H), 7.75
(d, J¼7.6 Hz, 1H), 7.86 (d, J¼7.6 Hz, 1H), 8.16 (m, 1H); 13C NMR
(100 MHz, CDCl3)
d
25.7 (CH2), 25.8 (CH2), 25.9 (CH2), 27.6 (CH2),
CDCl3) d 24.7 (CH2), 26.8 (CH2), 28.6 (CH2), 39.2 (CH2), 69.5 (CH2),
28.1 (CH2), 28.7 (CH2), 28.7 (CH2), 29.3 (CH2), 39.4 (CH2), 68.8
(OCH2), 69.2 (OCH2), 109.2 (]CH), 113.0 (]CH), 119.0 (quat-C),
120.1 (]CH), 121.3 (quat-C), 122.4 (]CH), 125.1 (]CH), 130.8 (]
CH), 131.1 (]CH), 132.2 (]CH), 132.2 (]CH), 133.4 (quat-C), 134.2
(]CH), 136.7 (]CH), 144.1 (quat-C), 158.7 (quat-C), 166.4 (CONR),
167.8 (COO), 195.5 (C]O); HRMS (ESI) Calcd for C30H33NO5
[MþNa]þ 510.2251; found, 510.2248.
69.8 (CH2), 108.4 (]CH), 113.0 (]CH), 118.2 (quat-C), 119.6 (]CH),
121.1 (]CH), 122.2 (]CH), 123.2 (quat-C), 129.7 (]CH), 129.9 (]
CH), 130.4 (quat-C), 131.3 (]CH), 132.0 (]CH), 134.3 (]CH), 134.5
(]CH), 142.0 (quat-C), 159.8 (quat-C), 164.3 (quat-C), 167.5 (COO),
199.4 (C]O). HRMS (ESI) Calcd for C25H23NO5 [MþH]þ 418.1654;
found, 418.1656. Crystal data (CCDC 1422674):
C25H23NO5,
M¼417.44, 0.30ꢂ0.16ꢂ0.07 mm, Monoclinic, space group P21/n
Compound 8a: Yield 26%; 25 mg; Red solid; mp 174e176 ꢀC; IR
(neat): nmax 3061, 2926, 2856, 1700, 1600, 1466, 1369, 1298, 1250,
with a¼14.3134(12) A, b¼9.0775(8) A, c¼16.0429(13) A, ¼90.00,
a
ꢀ
ꢀ
ꢀ
3
ꢀ
b
¼100.5050(10), ¼90.00, V¼2049.5(3)A , T¼273 (2) K, R1¼0.0393,
g
1170, 1130, 1086, 999, 751 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
wR2¼0.0931 on observed data, z¼4, Dcalcd¼1.353 mg cmꢁ3, F(000)¼
880, Absorption coefficient¼0.094 mmꢁ1
,
l
¼0.71073 A, 4018 re-
ꢀ
1.22e1.42 (m, 10H), 1.59e1.73 (m, 6H), 3.83 (t, J¼6.0 Hz, 2H), 3.97 (t,
J¼6.0 Hz, 2H), 5.12 (s, 2H), 6.59 (d, 1H, J¼16.0 Hz), 6.80 (d, 1H,
J¼8.0 Hz), 6.94e7.03 (m, 3H), 7.16 (d, 1H, J¼11.6 Hz), 7.26e7.31 (m,
1H), 7.43e7.47 (m, 2H), 7.88 (dd, J1¼7.6, J2¼1.6 Hz, 1H), 9.14 (dd,
flections were collected on a smart apex CCD single crystal dif-
fractometer 3407 observed reflections (Iꢃ2
s (I)). The largest
ꢀꢁ3
difference peak and hole¼0.256 and ꢁ0.168 eA , respectively. The
structure was solved by direct methods and refined by full-matrix
least squares on F2 using SHELXLe 97 software.
J1¼16.0, J2¼11.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 25.7 (CH2),
26.6 (CH2), 26.6 (CH2), 27.9 (CH2), 29.0 (CH2), 29.7 (CH2), 29.8 (CH2),
30.3 (CH2), 38.4 (CH2), 66.6 (OCH2), 69.2 (OCH2), 108.8 (]CH), 113.3
(]CH), 119.7 (quat-C), 120.1 (]CH), 120.8 (quat-C), 122.0 (]CH),
122.4 (]CH), 130.9 (]CH), 131.1 (]CH), 131.7 (]CH), 132.2 (quat-
C), 133.1 (quat-C), 133.7 (]CH), 138.0 (]CH), 143.3 (quat-C), 159.0
(quat-C), 165.9 (CONR), 166.7 (COO), 194.3 (C]O); HRMS (ESI) Calcd
for C30H33NO5 [MþNa]þ 510.2251; found, 510.2245.
Compound 8c: Yield 22%; 21 mg; Deep red gel; IR (neat): nmax
2895, 2834, 1723, 1712, 1636, 1597, 1413, 1243, 1012, 712 cmꢁ1 1H
;
NMR (400 MHz, CDCl3); 1.40e1.41 (m, 2H), 1.60e1.69 (m, 2H),
1.88e1.90 (m, 2H), 3.77e3.80 (m, 2H), 4.06 (t, J¼5.2 Hz, 2H), 5.11 (s,
2H), 6.25 (d, J¼16.4 Hz, 1H), 6.69 (d, J¼7.6 Hz, 1H), 6.81e6.93 (m,
3H), 7.03 (d, J¼11.2 Hz, 1H), 7.18e7.22 (m, 1H), 7.31e7.36 (m, 2H),
7.68 (dd, J1¼8, J2¼2 Hz, 1H), 8.99 (dd, J1¼16.4, J2¼11.2 Hz, 1H); 13C
Reaction of 6b was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7b (Z,Z) and 8b (Z,E) isomers with 58:42 ratio.
NMR (100 MHz, CDCl3)
d 23.8 (CH2), 27.2 (CH2), 28.2 (CH2), 37.4
(CH2) 65.5 (CH2), 69.2 (CH2), 108.3 (]CH), 113.3 (]CH), 119.5 (quat-
C), 119.7 (]CH), 121.0 (]CH), 121.9 (]CH), 122.4 (quat-C), 130.9 (]
CH), 131.2 (]CH), 131.9 (]CH), 132.1 (quat-C), 133.7 (]CH), 134.1
(]CH), 140.5 (]CH), 143.3 (quat-C), 159.5 (quat-C), 163.0 (CONR),
166.5 (COO), 197.2 (C]O). HRMS (ESI) Calcd for C25H23NO5 [MþH]þ
418.1654; found, 418.1658.
Reaction of 6d was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7d (Z,Z) and 8d (Z,E) isomers with the ratio of 42:58.
Compound 7b: Yield 26%; 25 mg; Red solid; mp 176e178 ꢀC; IR
(neat): nmax 2924, 2857, 1739, 1688, 1602, 1463, 1367, 1323, 1271,
1168, 1089, 1003, 915, 791, 747 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
0.88e0.89 (m, 2H), 1.12e1.17 (m, 8H), 1.68e1.78 (m, 6H), 3.86 (t,
J¼5.6 Hz, 2H), 4.02 (t, J¼7.2 Hz, 2H), 4.90 (s, 2H), 6.84 (d, J¼7.6 Hz,
1H), 6.97e7.03 (m, 3H), 7.13 (d, J¼15.2 Hz, 1H), 7.28e7.30 (m, 2H),
7.48 (t, J¼7.6 Hz, 1H), 7.71 (d, J¼7.6 Hz, 1H), 7.89e7.92 (d, J¼7.6 Hz,
1H), 8.20 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 23.9 (CH2), 25.4
(CH2), 25.5 (CH2), 27.2 (CH2), 28.6 (CH2), 28.9 (CH2), 30.2 (CH2), 37.6
(CH2), 69.2 (OCH2), 69.9 (OCH2), 108.7 (]CH), 112.9 (]CH), 119.9
Compound 7d: Yield 31%; 29 mg; Red gel; IR (neat): nmax 2925,
2855, 1736, 1700, 1669, 1605, 1469, 1264, 1099, 732 cmꢁ1; 1H NMR

S. Muthusamy et al. / Tetrahedron 72 (2016) 1749e1757
1757
(400 MHz, CDCl3) 1.61e1.69 (m, 2H), 1.87e1.90 (m, 2H), 3.78e3.81
(m, 2H), 4.06 (t, J¼5.2 Hz, 2H), 5.11 (s, 2H), 6.65 (dd, J1¼12.0,
J2¼1.2 Hz, 1H), 6.79e6.80 (m 1H), 6.89e6.95 (m, 2H), 7.03 (t,
J¼7.6 Hz, 1H), 7.24e7.28 (m, 1H), 7.43e7.47 (m, 1H), 7.52 (d,
J¼7.6 Hz, 1H), 7.80e7.84 (m, 2H), 8.00 (m, 1H); 13C NMR (100 MHz,
CDCl3) d 41.2 (CH2), 59.3 (CH2), 109.9 (CH), 110.1 (CH), 110.7 (quat-C),
111.4 (CH), 117.8 (quat-C), 124.1 (CH), 125.5 (CH), 138.2 (CH), 143.6
(quat-C), 148.4 (CH), 150.2 (quat-C), 158.0 (CONR), 166.5 (COO),
182.2 (C]O); HRMS (ESI) Calcd for C15H11NO4 [MþNa]þ 292.0585;
found, 292.0581.
Reaction of 6h was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7h (Z,Z) alone as a single isomer.
CDCl3)
d
23.8 (CH2), 28.2 (CH2), 37.4 (CH2), 65.5 (CH2), 69.2 (CH2),
108.3 (]CH), 113.3 (]CH), 119.5 (quat-C), 119.7 (]CH), 121.0 (]
CH), 121.9 (]CH), 122.4 (quat-C), 130.9 (]CH), 131.2 (]CH), 131.9
(quat-C), 132.1 (]CH), 133.7 (]CH), 134.1 (]CH), 140.5 (]CH),
143.3 (quat-C), 159.5 (quat-C), 163.0 (CONR), 166.5 (COO), 197.2 (C]
O). HRMS (ESI) Calcd for C24H21NO5 [MþH]þ 404.1498; found,
404.1488.
Compound 7h: Yield 62%; 56 mg; Red solid; mp 153e154 ꢀC; IR
(neat): nmax 2930, 1731, 1609, 1467, 1357, 1160, 1089, 1016, 965, 923,
881, 820, 752 cmꢁ1; 1H NMR (400 MHz, CDCl3) 2.20 (quin, J¼6.4 Hz,
2H), 3.91 (t, J¼6.8 Hz, 2H), 4.40 (t, J¼6.0 Hz, 2H), 6.58 (qurt,
J¼1.6 Hz, 1H), 6.93 (d, J¼8.0 Hz, 1H), 7.10 (t, J¼7.6 Hz, 1H), 7.16 (dd,
J1¼3.6 J2¼0.8 Hz,1H), 7.54e7.60 (m, 3H); 13C NMR (100 MHz, CDCl3)
Compound 8d: Yield 30%; 28 mg; Red gel; IR (neat): nmax 2927,
2862, 1738, 1705, 1610, 1465, 1268, 1095, 725 cmꢁ1 1H NMR
;
(400 MHz, CDCl3) 1.56e1.60 (m, 2H), 1.76e1.77 (m, 2H), 3.85 (t,
J¼5.6 Hz, 2H), 4.21 (t, J¼6.8 Hz, 2H), 5.05 (s, 2H), 6.29 (d, J¼16.4 Hz,
1H), 6.69 (d, J¼8.0 Hz, 1H), 6.80e6.83 (m, 2H), 6.91 (td, J1¼7.6,
J2¼0.4 Hz. 1H), 7.03 (dd, J1¼11.2, J2¼0.8 Hz, 1H), 7.20 (td, J1¼8.0,
J2¼1.2 Hz, 1H), 7.27e7.32 (m, 1H), 7.36 (d, J¼7.2 Hz, 1H), 7.62 (dd,
J1¼8.0, J2¼6.0 Hz, 1H), 8.90 (dd, J1¼16.4, J2¼11.2 Hz, 1H); 13C NMR
d 26.6 (CH2), 37.5 (CH2), 62.2 (CH2), 109.9 (CH), 112.0 (CH), 117.7
(quat-C), 118.3 (CH), 123.8 (CH), 125.5 (CH), 138.3 (quat-C), 138.4
(CH), 144.3 (quat-C), 146.5 (CH), 150.7 (quat-C), 158.3 (CONR), 158.3
(COO), 183.2 (C]O); HRMS (ESI) Calcd for C16H13NO4 [MþH]þ
284.0922; found, 284.0920.
(100 MHz, CDCl3)
d 24.7 (CH2), 28.6 (CH2), 39.2 (CH2), 69.5 (CH2),
Acknowledgements
69.8 (CH2), 108.4 (]CH), 113.0 (]CH), 118.2 (quat-C), 119.6 (]CH),
121.1 (]CH), 122.2 (]CH), 123.2 (quat-C), 129.7 (]CH), 129.9 (]
CH), 130.4 (quat-C), 131.3 (]CH), 132.0 (]CH), 134.3 (]CH), 134.5
(]CH), 142.0 (quat-C), 159.8 (quat-C), 164.3 (CONR), 167.5 (COO),
199.4 (C]O). HRMS (ESI) Calcd for C24H21NO5 [MþH]þ 404.1498;
found, 404.1492.
Reaction of 6e was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7e (Z,Z) alone as a single isomer.
This research was supported by the Department of Science and
Technology (DST), New Delhi (No. SR/S1/OC-11/2011(G)) . A. B.
thanks to the University Grants Commission (UGC) for a BSR fel-
lowship. We thank DST, New Delhi, for providing 400 MHz NMR
facility under FIST program.
Supplementary data
Compound 7e: Yield 65%; 59 mg; Red solid; mp 150e153 ꢀC; IR
(neat): nmax 2930, 1731, 1609, 1467, 1357, 1160, 1089, 1016, 965, 923,
881, 820, 752 cmꢁ1; 1H NMR (400 MHz, CDCl3) 2.03 (quin, J¼7.2 Hz,
2H), 2.47 (t, J¼6.0 Hz, 2H), 3.77 (t, J¼7.2 Hz, 2H), 5.09 (s, 2H),
6.37e6.43 (m, 2H), 6.98 (d, 1H, J¼7.6 Hz), 7.12 (d, 3H, J¼7.6 Hz), 7.43
Supplementary data (Copies of representative 1H and 13C NMR
spectra of compounds 6e8.) associated with this article can be
found in the online version, at http://dx.doi.org/10.1016/
j.tet.2016.02.032.
(s, 1H), 7.56e7.61 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 22.3 (CH2),
30.9 (CH2), 39.3 (CH2), 58.3 (CH2), 110.3 (CH), 110.6 (CH), 110.8 (CH),
117.6 (quat-C), 123.7 (CH), 125.5 (CH), 138.5 (CH), 143.4 (CH), 149.2
(quat-C), 150.8 (quat-C), 158.2 (CONR), 172.2 (COO), 183.3 (C]O);
References and notes
1. (a) Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A.
Chem. Rev. 2015, 115, 9981; (b) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds: from Cyclopro-
panes to Ylides; Wiley: New York, NY, 1998.
HRMS (ESI) Calcd for
298.1074.
C
17H15NO4 [MþH]þ 298.1079; found,
Reaction of 6f was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7f (Z,Z) alone as a single isomer.
2. (a) Gillingham, D.; Fei, N. Chem. Soc. Rev. 2013, 42, 4918; (b) Davies, H. M. L.;
Morton, D. Chem. Soc. Rev. 2011, 40, 1857; (c) Mehta, G.; Muthusamy, S. Tetra-
hedron 2002, 58, 9477; (d) Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A.
Chem. Soc. Rev. 2001, 30, 50; (e) Padwa, A.; Weingarten, M. D. Chem. Rev. 1996,
96, 223; (f) Miller, D. J.; Moody, C. J. Tetrahedron 1995, 51, 10811.
3. (a) Bartoli, G.; Bencivenni, G.; Dalpozzo, R. Synthesis 2014, 46, 979; (b) Davies,
H. M. L.; Denton, J. R. Chem. Soc. Rev. 2009, 38, 3061; (c) Caballero, A.; Prieto, A.;
Diaz-Requejo, M. M.; Perez, P. J. Eur. J. Inorg. Chem. 2009, 1137; (d) Davies, H. M.
L.; Manning, J. R. Nature 2008, 451, 417; (e) Reissig, H.-U.; Zimmer, R. Chem. Rev.
2003, 103, 1151; (f) Pellissier, H. Tetrahedron 2008, 64, 7041; (g) Ye, T.; McKer-
vey, M. A. Chem. Rev. 1994, 94, 1091.
Compound 7f: Yield 68%; 63 mg; Red liquid; IR (neat): nmax
2952, 1745, 1607, 1452, 1353, 1165, 1084, 1014, 974, 921, 875, 814,
752 cmꢁ1 1H NMR (400 MHz, CDCl3) 1.97e2.04 (m, 2H), 2.47 (t,
;
J¼6.8 Hz, 2H), 3.77 (t, J¼7.6 Hz, 2H), 5.09 (s, 2H), 6.38e6.39 (m, 1H),
6.43 (d, 1H, J¼3.2 Hz), 6.97 (d, 1H, J¼8.4 Hz), 7.43 (d, 1H, J¼1.2 Hz),
7.53e7.57 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 22.1 (CH2), 30.7
4. (a) Ruppel, J. V.; Cui, X.; Xu, X.; Zhang, X. P. Org. Chem. Front. 2014, 1, 515; (b)
Shen, J.; Zhu, S.; Cai, Y.; Xu, H.; Xie, X.; Zhou, Q. Angew. Chem., Int. Ed. 2014, 53,
13188; (c) Nani, R. R.; Reisman, S. E. J. Am. Chem. Soc. 2013, 135, 7304; (d) Xu, X.;
Lu, H. J.; Ruppel, J. V.; Cui, X.; de Mesa, S. L.; Wojtas, L.; Zhang, X. P. J. Am. Chem.
Soc. 2011, 133, 15292.
5. (a) Shieh, P. C.; Ong, C. W. Tetrahedron 2001, 57, 7303; (b) Wenkert, E.; Khatuya,
H. Helv. Chim. Acta 1998, 81, 2370; (c) Wenkert, E.; Guo, M.; Lavilla, R.; Porter, B.;
Ramachandran, K.; Sheu, J. H. J. Org. Chem. 1990, 55, 6203.
6. Hutchinson, I. S.; Matlin, S. A.; Mete, A. Tetrahedron 2002, 58, 3137.
7. Doyle, M. P.; Chapman, B. J.; Hu, W.; Peterson, C. S.; McKervey, M. A.; Garcia, C. F.
Org. Lett. 1999, 1, 1327.
8. Muthusamy, S.; Azhagan, D. Tetrahedron Lett. 2011, 52, 6732.
9. Muthusamy, S.; Karikalan, T. Org. Biomol. Chem. 2014, 12, 9243.
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11. See supporting information for details.
(CH2), 39.4 (CH2), 58.3 (OCH2), 110.7 (]CH), 110.9 (]CH), 111.6 (]
CH), 118.4 (quat-C), 125.4 (]CH), 129.6 (quat-C), 137.9 (]CH), 143.5
(]CH), 149.0 (quat-C), 149.1 (quat-C), 157.6 (CONR), 172.2 (COO),
182.3 (C]O); HRMS (ESI) Calcd for C17H14ClNO4 [MþH]þ 332.0689;
found, 332.0680.
Reaction of 6g was carried out as per described general pro-
cedure and chromatographic purification of the residue to afforded
7g (Z,Z) alone as a single isomer.
Compound 7g: Yield 66%; 60 mg; Red solid; mp 143e145 ꢀC; IR
(neat): nmax 2928, 1736, 1609, 1470, 1373, 1344, 1185, 930, 865,
752 cmꢁ1 1H NMR (400 MHz, CDCl3) 4.52 (s, 2H), 5.17 (s, 2H),
;
6.38e6.44 (m, 2H), 6.74 (d, J¼8 Hz, 1H), 7.14e7.17 (m, 1H), 7.43 (s,
12. Lavigne, H.; Astoin, J.; Patte, F.; Coullaut, M. F.; Berny, C. M.; Le Bouquin, C. Chim.
Ther. 1969, 4, 453.
1H), 7.57 (t, J¼7.2 Hz 1H), 7.65 (d, J¼7.6 Hz, 1H); 13C NMR (100 MHz,