Diastereoselective synthesis of macrocycles incorporating the spiro-indolofurans and -indolodioxolanes

Article abstract of DOI:10.1016/j.tet.2011.12.020

Generation of intramolecular macrocyclic carbonyl ylides from aldehyde group tethered to diazoamides in the presence of rhodium(II) acetate and their successful [3+2]-cycloaddition afforded the corresponding macrocycles incorporating spiro-indolofurans, -indolofuropyrroles, -indolofurofurans, and -indolodioxolanes in moderate to good yield with complete diastereoselectivity. The competition between the electrocyclization and [3+2]-cycloaddition reactions of macrocyclic carbonyl ylides was also demonstrated.

Full text of DOI:10.1016/j.tet.2011.12.020

Tetrahedron 68 (2012) 1443e1451
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Diastereoselective synthesis of macrocycles incorporating the spiro-indolofurans
and -indolodioxolanes
*
Sengodagounder Muthusamy , Thangaraju Karikalan
School of Chemistry, Bharathidasan University, Tiruchirappalli 620024, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Generation of intramolecular macrocyclic carbonyl ylides from aldehyde group tethered to diazoamides
in the presence of rhodium(II) acetate and their successful [3þ2]-cycloaddition afforded the corre-
sponding macrocycles incorporating spiro-indolofurans, -indolofuropyrroles, -indolofurofurans, and
-indolodioxolanes in moderate to good yield with complete diastereoselectivity. The competition be-
tween the electrocyclization and [3þ2]-cycloaddition reactions of macrocyclic carbonyl ylides was also
demonstrated.
Received 1 November 2011
Received in revised form 6 December 2011
Accepted 10 December 2011
Available online 14 December 2011
Keywords:
1,3-Dipolar cycloaddition
Diazoamides
Ó 2011 Elsevier Ltd. All rights reserved.
Macrocycles
Rhodium(II) acetate
Spiro-oxindoles
1. Introduction
rhodium(II) acetate afforded the spiro-indolooxiranes 2 via gener-
ation of macrocyclic carbonyl ylide followed by a conrotatory elec-
Diazocarbonyl compounds find widespread applications in or-
ganic chemistry1 especially in tandem processes and natural prod-
uct synthesis.2 The continual upsurge in molecular complexity and
diversity in the natural product systems urges chemist to increase
tools of their arsenal. The 1,3-dipolar cycloaddition reactions are
appropriate potential tools for synthetic chemists to increase the
efficacy, atom economy, selectivity, and complexity in a particular
process. Metallocarbenoids can be generated from diazocarbonyl
compounds that react with a series of functional groups,3 whereby
subsequent reactions can occur. The intramolecular generation of
carbonyl ylides and their subsequent reactions are studied well,
which constituted an important method for tetrahydrofuran sys-
tems and also applied for the synthesis of many natural products.2a,4
Heterocyclic spiro compounds5 occupy a key place among the var-
ious classes of organic molecules. Especially, the oxindole moiety
constitutes a key structural element in several natural products,6
including the antibiotic speradine7 and the cytostatic welwista-
tin.8 Consequently, the development of novel synthetic strategies
leading to 3,3-disubstituted oxindole derivatives is of paramount
importance. Synthesis of macrocycles via cyclopropanation9 or in-
sertion10 reactions has been explained but there is no report11
for the formation of macrocycles via carbonyl ylide as a dipole.
Aromatic aldehyde tethered to diazoamides 1 in the presence of
trocyclization11 process (Scheme 1). As a part of our ongoing
research on the carbonyl ylides12 and supramolecular systems,13 we
herein demonstrate the new macrocycles incorporating spiro-
indolofurans, -indolofuropyrroles, -indolofurofurans, and -indolo-
dioxolanes by trapping the macrocyclic carbonyl ylides with alkyne,
alkene or aldehyde as a dipolarophile.
Scheme 1. Synthesis of macrocyclic spiro-oxiranes 2.
2. Results and discussion
Initially, the substrates having aldehyde functionality tethered
to diazo functional group were planned. Toward this, O-alkylation
* Corresponding author. Tel.: þ91 431 2407053; fax: þ91 431 2407045; e-mail
address: muthu@bdu.ac.in (S. Muthusamy).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.020

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S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
of 2-hydroxybenzaldehyde with 1,9-dibromononane was per-
formed to furnish the corresponding bromobenzaldehyde 5a.
Subsequent N-alkylation of 3-diazooxindoles 6 with 5a in the
presence of potassium carbonate/DMF afforded the corresponding
cyclic diazoamide 7a in very good yield.
diazoamide 7b yielded the macrocycle 2 incorporating spiro-
indolooxirane via electrocyclization11 when propargyl bromide
(8b) was used as the dipolarophile. Based on the above study, the
electron-deficient dipolarophile favor the formation of spiro-
indolofuran 9.
Reaction of diazoamide 7a and dimethyl acetylenedicarboxylate
(DMAD, 8a) in the presence of 1.3 mol % of rhodium(II) acetate in
dry DCM under argon atmosphere smoothly afforded the corre-
sponding macrocycle 9a in 60% yield as a single diastereomer
(Scheme 2, entry a, Table 1). No other byproducts were observed.
The 1H NMR spectrum of 9a revealed the presence of a singlet at
After demonstrating the generation of macrocyclic carbonyl
ylides and their successful trapping experiments with DMAD, the
use of alkenes as a dipolarophile was planned. Toward this, a variety
of alkenes, such as N-phenylmaleimide (NPM), maleic anhydride or
cyclooctadiene were employed to afford the corresponding mac-
rocyclic compounds incorporating the spiro-indole unit. Reaction of
diazoamide 7b (see the Table 2) and NPM in the presence of
1.3 mol % of rhodium(II) acetate in dry DCM under argon atmo-
sphere furnished macrocycle 10a incorporating the spiro-
indolofuropyrrole in 65% as a single isomer (Scheme 3). 1H, 13C-
Spectra confirm the formation of spiro-indolofuropyrrole ring
system. A variety of spacers and substituents were made on diaz-
oamides 7d,h,i under similar conditions furnished the corre-
sponding macrocycles 10bed in moderate yield (Table 2). The
reaction of diazoamides 7 was planned with maleic anhydride to
furnish the corresponding macrocycles 11 incorporating spiro-
d
6.97 ppm for OCH proton. Furthermore, 13C and DEPT-135 ex-
periments disclosed the presence of a characteristic quaternary
carbon (C2) at 89.29 ppm and a CH (C5) signal at 81.71 ppm,
d
which unequivocally confirms the formation of the spiro-
indolofuran unit. All other signals in 13C spectrum are due to nine
CH2 carbons and eight CH carbons present (due to symmetry) with
the assigned structure. The above reaction was carried out using
different solvents, such as DCM, benzene or toluene at room tem-
perature or reflux conditions and optimized using dry DCM at room
temperature condition to afford the macrocycle 9a.
Scheme 2. Synthesis of macrocycles incorporating spiro-indolofurans 9.
Stimulated by this result, spacer length modifications between
diazo and aldehyde functionalities were planned. Thus, compounds
5b,c having the respective spacer length (n¼7,8) underwent N-al-
kylation to yield the corresponding diazoamides 7b,c. Reaction of
diazoamides 7b,c and DMAD (8a) in the presence of rhodium(II)
acetate catalyst as described above afforded the corresponding
macrocycles 9b,c in moderate yield as a single diastereomer. Next,
reaction of diazoamides 7def having electron-donating or -with-
drawing substituent was performed under similar conditions to
obtain the macrocycles 9def in moderate yield. The presence of
electron-donating substituent on diazoamide gave better yield
than -withdrawing substituent and the results are illustrated in
Table 1. Representatively, the structure of spiro-macrocyclic com-
pound 9e was confirmed by the single crystal X-ray analysis14
(Fig. 1) and observed that the alkyl chain having C11e17 atoms
have high thermal vibration. Based on the stereochemistry of 9e,
the similar stereochemistry was tentatively assigned for other
products obtained in this reaction. Reaction of diazoamides having
meta-substituted benzaldehyde 7g or ortho-substituted nap-
thaldehyde 7h,i furnished products in moderate yield. Reaction of
indolofurofuran unit. Thus, reaction of diazoamides 7b,h with
maleic anhydride furnished the macrocycles 11a,b (Table 2).
However, reaction of 7b and electron-rich cyclooctene as a dipo-
larophile afforded the spiro-indolooxirane 2.
Next, our effort was invested to examine the trapping of mac-
rocyclic carbonyl ylides with carbonyl group as a dipolarophile.
Toward this, reaction of diazoamide 7b (see the Table 1) and p-
nitrobenzaldehyde in the presence of 1.3 mol % of Rh2(OAc)4 was
carried out to give the corresponding macrocycle 13a having spiro-
indolodioxolane unit in moderate yield as a single isomer with
complete diastereoselectivity (Scheme 4). The stereochemistry of
the macrocyclic compound 13a was confirmed by the single crystal
X-ray analysis14 (Fig. 2) and observed that the alkyl chain having
C11e17 atoms have high thermal vibration. Similarly, other de-
rivatives of macrocycles 13b,c were also synthesized and the results
are illustrated in Table 3. It is interesting to note that the opposite
diasteroisomer12a of spiro-dioxolanes 13 was obtained via intra-
molecular carbonyl ylides.
Mechanistically, it is proposed that the electron-deficient car-
benoid carbon of rhodium(II) carbenoids 14 reacts with the

S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
1445
Table 1
Trapping of macrocyclic carbonyl ylides with DMAD
Entry
Aldehyde 3
n
R1
R2
Diazoamide 7
Product 9
Yielda (%)
O
O
O
O
O
1
2-Hydroxybenzaldehyde
6
H
H
7a
60
O
N
O
9a
O
O
O
O
O
2
2-Hydroxybenzaldehyde
7
H
H
7b
65
O
N
O
9b
O
O
O
O
O
O
3
2-Hydroxybenzaldehyde
8
H
H
7c
63
N
O
9c
O
O
O
O
O
O
4
2-Hydroxybenzaldehyde
7
4-OCH3
H
7d
70
O
N
O
9d
O
O
O
NO
O
O
5
2-Hydroxybenzaldehyde
7
3-NO2
H
7e
62
O
N
O
9e
O
O
O
Cl
O
O
6
2-Hydroxybenzaldehyde
7
H
Cl
7f
63
O
N
O
9f
O
O
O
O
O
7
3-Hydroxybenzaldehyde
7
H
H
7g
65
O
N
O
9g
(continued on next page)

1446
S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
Table 1 (continued )
Entry
Aldehyde 3
n
R1
R2
Diazoamide 7
Product 9
Yielda (%)
O
O
O
O
O
8
2-Hydroxynaphthaldehyde
7
H
H
7h
68
O
N
O
9h
O
O
O
O
O
O
9
2-Hydroxynaphthaldehyde
9
H
H
7i
62
N
O
9i
O
H
O
N
10b
2-Hydroxybenzaldehyde
7
H
H
7b
70
O
2
a
Isolated yield.
b
Propargyl bromide was used as a dipolarophile; reactions were performed by addition of diazoamide 7 (1 equiv) and DMAD 8 (1.3 equiv) in the presence of 1.3 mol % of
Rh2(OAc)4 in dry DCM (15 mL) at room temperature 15e20 min duration.
Scheme 3. Synthesis of spiro-indolofuropyrroles 10 and -indolofurofurans 11.
Fig. 1. Crystal structure of spiro-indolofuran 9e.
Table 2
Trapping of macrocyclic ylides with alkenes
Scheme 4. Synthesis of spiro-indolodioxolanes 13.
Entry
Diazoamide 7
Dipolarophile
Product (yielda %)
1
2
3
4
5
6
7
7b
7d
7h
7i
7b
7h
7b
NPM
NPM
NPM
NPM
Maleic anhydride
Maleic anhydride
Cyclooctene
10a (65%)
10b (68%)
10c (65%)
10d (60%)
11a (59%)
11b (56%)
2 (70%)
remotely placed oxygen atom of the aromatic aldehyde function-
ality affording the interesting macrocyclic carbonyl ylides 15
(Scheme 5) in an intramolecular manner. From the observed ste-
reochemistry of the products, the conformation of the most fa-
vorable carbonyl ylide intermediate 15 was proposed. Thus, the
carbonyl ylide 15 might be stabilized by intramolecular hydrogen
bonding interaction forming a six-membered12a transition state.
Subsequently, 1,3-dipolar cycloaddition reaction of carbonyl ylides
a
Isolated yield. Reactions were performed by addition of diazoamide 7 (1 equiv)
and NPM/maleic anhydride (1.3 equiv) in the presence of 1.3 mol % of Rh2(OAc)4 in
dry DCM (15 mL) at room temperature 15e25 min duration.

S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
1447
Fig. 2. Crystal structure of spiro-indolodioxolane 13a.
Table 3
Trapping of macrocyclic ylides with aldehydes
Entry
Diazoamide
ArCHO
Product (yielda %)
1
2
3
7b
7d
7b
p-Nitrobenzaldehyde (12a)
p-Nitrobenzaldehyde (12a)
m-Bromobenzaldehyde (12b)
13a (55%)
13b (59%)
13c (50%)
a
Isolated yield. Reactions were performed by addition of diazoamide 7 (1 equiv)
and aromatic aldehyde 12 (1.3 equiv) in the presence of 1.4 mol % of Rh2(OAc)4 in
dry DCM (15 mL) at room temperature 25e30 min duration.
15 with electron-deficient alkyne, alkene or aldehyde functional
groups furnished the macrocycles 16 incorporating spiro-indoles
with diasteroselectivity. It is noteworthy to mention that the ab-
sence11 of dipolarophile or electron-rich dipolarophile resulted in
the electrocyclization process.
Scheme 5. Plausible mechanism.
mass analyses were performed using electrospray ionization
technique on a Waters QTof-micro mass spectrometer. All solvents
were purified by distillation following standard procedure. Thin
layer chromatography was performed on silica or alumina plates
and components visualized by observation under iodine/UV light at
254 nm. Column chromatography was performed on silica gel
(100e200 mesh). All the reactions were conducted in oven-dried
glassware under a positive pressure of argon with magnetic stir-
ring. Reagents were added via syringes through septa.
3. Conclusions
In conclusion, the generation of macrocyclic intramolecular
carbonyl ylides and their subsequent intermolecular [3þ2]-cyclo-
addition reactions in the presence of rhodium(II) acetate as a cata-
lyst were demonstrated. Based on this concept, the successful
synthesis of new macrocycles incorporating spiro-indolofurans,
-indolofuropyrroles, -indolofurofurans, and -indolodioxolanes was
established with complete diastereoselectivity. This research work
represents the first paradigm for the trapping of macrocyclic car-
bonyl ylides.
4.2. Synthesis of macrocycle 9a
A solution of aromatic aldehyde tethered to diazoamide 7a
(100 mg, 0.24 mmol) and dimethyl acetylenedicarboxylate (45 mg,
0.31 mmol), rhodium(II) acetate (1.42 mg, 1.3 mol %) in dichloro-
methane (15 mL) was stirred at room temperature for 20 min. The
reaction mixture was concentrated in vacuo and purified on silica
(hexane/EtOAc, 65:35) to give 9a (60%). Colorless solid; mp
210e212 ꢀC; IR (neat): nmax 2931, 2857, 1724, 1614, 1490, 1467, 1437,
4. Experimental section
4.1. General remarks
Melting points were determined on a capillary melting point
apparatus and are uncorrected. IR spectra were recorded using ATR
technique on a Bruker Alpha FTIR spectrophotometer. Proton nu-
clear magnetic resonance (1H NMR) spectra were recorded on
1252, 1161, 1019, 991, 729 cmꢁ1
;
1H NMR (400 MHz, CD2Cl2)
d
¼1.22e1.25 (m, 7H, CH2), 1.36e1.37 (m, 3H, CH2), 1.66e1.73 (m, 4H,
CH2), 3.34 (dt, 1H, J1¼14 Hz, J2¼4 Hz, NeCH2), 3.56 (s, 3H, OCH3),
3.68 (s, 3H, OCH3), 3.86 (td, 1H, J1¼9.4 Hz, J2¼2.4 Hz, NeCH2),
4.00e4.05 (m, 1H, OCH2), 4.09e4.17 (m, 1H, OCH2), 6.71 (d, 1H,
J¼7.6 Hz, ArH), 6.77 (d, 1H, J¼7.6 Hz, ArH), 6.88e6.92 (m, 2H, ArH),
6.97 (s, 1H, CHO), 7.11 (dd, 1H, J1¼7.6 Hz, J2¼1.2 Hz, ArH), 7.17e7.24
(m, 2H, ArH), 7.36 (dd, 1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH); 13C NMR
a Bruker Avance 400 at 400 MHz using CDCl3 in parts per million (
d)
related to tetramethylsilane (
d
¼0.00) as an internal standard and
are reported as follows; chemical shift (ppm), multiplicity
(br¼broad, s¼singlet, d¼doublet, m¼multiplet), coupling constant
(Hz) and integration. Carbon-13 nuclear magnetic resonance (13C
NMR) spectra were recorded at 100 MHz in CDCl3. Chemical shifts
(100 MHz, CD2Cl2)
d 26.40 (CH2), 26.52 (CH2), 27.87 (CH2), 28.00
(CH2), 28.39 (CH2), 29.54 (CH2), 30.82 (CH2), 39.14 (CH2), 52.50
(OCH3), 52.66 (OCH3), 69.16 (CH2), 81.71 (CH, observed in DEPT-90
NMR), 89.29 (quat-C), 109.12 (]CH), 112.20 (]CH), 120.63 (]CH),
122.88 (]CH), 125.32 (]CH), 126.22 (quat-C), 127.27 (quat-C),
are reported in delta (d) units, parts per million (ppm) relative to
the center of the triplet at 77.7 ppm for CDCl3. Carbon types were
determined from 13C NMR and DEPT experiments. High resolution

1448
S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
128.51 (]CH), 130.64 (]CH), 135.30 (quat-C), 144.64 (quat-C),
145.92 (quat-C), 157.35 (quat-C), 161.22 (quat-C), 163.19 (quat-C),
173.35 (quat-C); HRMS (ESI) calcd for C30H33NO7 [MþNa]þ
542.5758; found, 542.5766.
NeCH2), 3.54 (s, 3H, OCH3), 3.66 (s, 3H, OCH3), 3.77 (s, 3H, OCH3),
3.78e3.82 (m, 1H, NeCH2), 3.99e4.04 (m, 1H, OCH2), 4.06e4.13 (m,
1H, OCH2), 6.35 (d, 1H, J¼2.4 Hz, ArH), 6.45 (dd, 1H, J1¼8.4 Hz,
J2¼2.4 Hz, ArH), 6.70 (d,1H, J¼7.6 Hz, ArH), 6.89e6.92 (m, 2H, ArH &
CHO), 7.14e7.21 (m, 2H, ArH), 7.30 (d, 1H, J¼8.4 Hz, ArH); 13C NMR
4.3. Synthesis of macrocycle 9b
(100 MHz, CD2Cl2) d 24.90 (CH2), 25.79 (CH2), 26.09 (CH2), 27.36
(CH2), 27.99 (CH2), 28.19 (CH2), 28.28 (CH2), 29.94 (CH2), 39.07
(CH2), 52.40 (OCH3), 52.57 (OCH3), 55.35 (OCH3), 68.95 (CH2), 81.54
(CH, observed in DEPT-90 NMR), 89.19 (quat-C), 100.13 (]CH),
105.31 (]CH), 108.70 (]CH), 119.20 (quat-C), 122.73 (]CH),
125.32 (]CH), 127.30 (quat-C), 129.57 (]CH), 130.58 (]CH), 134.89
(]CH), 144.17 (quat-C), 145.91 (quat-C), 158.86 (quat-C), 161.20
(quat-C), 161.70 (quat-C), 163.23 (quat-C), 173.69 (quat-C); HRMS
(ESI) calcd for C32H37NO8 [MþNa]þ 586.6279; found, 586.6265.
A solution of diazoamide 7b (100 mg, 0.23 mmol) and DMAD
(44 mg, 0.30 mmol), rhodium(II) acetate (1.4 mg, 1.3 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
18 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9b (65%). Colorless
solid; mp 202e204 ꢀC; IR (neat): nmax 2927, 2856, 1715, 1652, 1610,
1599, 1488, 1433, 1246, 1122, 1016, 986, 760 cmꢁ1
;
1H NMR
¼1.18e1.50 (m, 11H, CH2), 1.69e1.73 (m, 5H,
(400 MHz, CD2Cl2)
d
CH2), 3.32 (dt, 1H, J1¼14.4 Hz, J2¼4.4 Hz, NeCH2), 3.55 (s, 3H, OCH3),
3.65 (s, 3H, OCH3), 3.88 (td, 1H, J1¼9.4 Hz, J2¼2.4 Hz, NeCH2),
4.02e4.10 (m, 2H, OCH2), 6.70 (d, 2H, J¼8.0 Hz, ArH), 6.80 (d, 1H,
J¼8.4 Hz, ArH), 6.89e6.95 (m, 2H, ArH), 7.00 (s, 1H, CHO), 7.15e7.25
(m, 2H, ArH), 7.38 (dd, 1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH); 13C NMR
4.6. Synthesis of macrocycles 9e
A solution of diazoamide 7e (100 mg, 0.21 mmol) and DMAD
(40 mg, 0.28 mmol), rhodium(II) acetate (1.26 mg, 1.32 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9e (62%) Colorless
solid; mp 182e185 ꢀC; IR (neat): nmax 2930, 2856, 1723, 1660, 1613,
(100 MHz, CD2Cl2)
d 24.89 (CH2), 25.78 (CH2), 26.09 (CH2), 27.34
(CH2), 27.94 (CH2), 28.91 (CH2), 28.30 (CH2), 29.00 (CH2), 39.07
(CH2), 52.57 (OCH3), 52.57 (OCH3), 69.03 (CH2), 89.48 (CH, observed
in DEPT-90 NMR), 89.48 (quat-C), 108.75 (]CH), 113.12 (]CH),
120.84 (]CH), 122.78 (]CH), 125.39 (]CH), 126.60 (quat-C), 127.11
(quat-C), 128.67 (]CH), 130.64 (]CH), 130.67 (]CH), 135.48 (quat-
C), 144.17 (quat-C), 145.38 (quat-C), 157.68 (quat-C), 161.22 (quat-C),
163.00 (quat-C), 173.57 (quat-C); HRMS (ESI) calcd for C31H35NO7
[MþNa]þ 556.6019; found, 556.6032.
1593, 1519, 1489, 1263, 1017, 992, 760 cmꢁ1
;
1H NMR (400 MHz,
CDCl3)
d
¼1.09e1.23 (m, 8H, CH2), 1.31e1.38 (m, 2H, CH2), 1.47e1.49
(m, 1H, CH2), 1.59e1.76 (m, 4H, CH2), 1.77e1.81 (m, 1H, CH2), 3.33
(dt, 1H, J1¼14 Hz, J2¼4.4 Hz, NeCH2), 3.58 (s, 3H, OCH3), 3.69 (s, 3H,
OCH3), 3.95 (td, 1H, J1¼10.8 Hz, J2¼3.2 Hz, NeCH2), 4.06e4.13 (m,
1H, OCH2), 4.13e4.20 (m, 1H, OCH2), 6.73 (d, 1H, J¼8.0 Hz, ArH),
6.87 (d, 1H, J¼9.2 Hz, ArH), 6.93e6.97 (m, 2H, ArH, CHO), 7.17 (d, 1H,
J¼8.0 Hz, ArH), 7.21e7.25 (m, 1H, ArH), 8.18 (dd, 1H, J1¼8.6 Hz,
J2¼2.4 Hz, ArH), 8.31 (d, 1H, J¼2.4 Hz, ArH); 13C NMR (100 MHz,
4.4. Synthesis of macrocycle 9c
A solution of diazoamide 7c (100 mg, 0.23 mmol) and DMAD
(42 mg, 0.29 mmol), rhodium(II) acetate (1.32 mg, 1.3 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated in vacuo and puri-
fied on silica (hexane/EtOAc, 65:35) to give 9c (63%) Colorless solid;
mp 210e212 ꢀC; IR (neat): nmax 2930, 2856, 1724, 1653, 1615, 1508,
CDCl3) d 24.87 (CH2), 25.80 (CH2), 25.94 (CH2), 27.26 (CH2), 28.06
(CH2), 28.13 (CH2), 28.14 (CH2), 28.74 (CH2), 39.14 (CH2), 52.63
(OCH3), 52.77 (OCH3), 60.66 (CH2), 80.60 (CH, observed in DEPT-90
NMR), 89.91 (quat-C), 108.98 (]CH), 112.19 (]CH), 123.09 (]CH),
124.83 (]CH), 125.46 (]CH), 126.16 (quat-C), 126.77 (]CH), 127.81
(quat-C), 131.07 (]CH), 137.46 (quat-C), 141.27 (quat-C), 142.62
(quat-C), 144.19 (quat-C), 161.09 (quat-C), 162.37 (quat-C), 162.51
(quat-C), 173.06 (quat-C); HRMS (ESI) calcd for C31H34N2O9
[MþNa]þ 601.5994; found, 601.5979. Crystal data for the compound
1466, 1436, 1263, 1018, 992, 73 cmꢁ1 1H NMR (400 MHz, CD2Cl2)
;
d
¼1.16e1.49 (m,12H, CH2),1.71e1.74 (m, 6H, CH2), 3.24e3.30 (dt,1H,
J1¼14 Hz, J2¼4 Hz, NeCH2), 3.51 (s, 3H, OCH3), 3.59 (s, 3H, OCH3),
3.85e3.89 (td, 1H, J1¼9 Hz, J2¼2.1 Hz, NeCH2), 4.02e4.09 (m, 2H,
OCH2), 6.67 (d, 2H, J¼8.0 Hz, ArH), 6.76 (d, 1H, J¼8.4 Hz, ArH),
6.84e6.91 (m, 2H, ArH), 6.99 (s, 1H, CHO), 7.11e7.22 (m, 2H, ArH),
7.36 (dd, 1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH); 13C NMR (100 MHz, CD2Cl2)
9e: (CCDC 851590) C31H34N2O9, M¼578.60, 0.27ꢂ0.14ꢂ0.09 mm,
ꢀ
Monoclinic,
space
group
Pꢁ21
ꢀ
with
¼90.00,
a¼14.0885(3) A,
ꢀ
b¼10.6655(2) A,
c¼20.5109(4) A,
a
b
¼98.6460(10),
3
ꢀ
g
¼90.00, V¼3046.96(10) A , T¼293(2) K, R1¼0.0694, wR2¼0.1775
d
24.83 (CH2), 25.75 (CH2), 26.01 (CH2), 27.30 (CH2), 27.94 (CH2),
on observed data, z¼4, Dcalcd¼1.261 mg cmꢁ3, F(000)¼1224, Ab-
ꢀ
28.05 (CH2), 28.19 (CH2), 28.79 (CH2), 29.10 (CH2), 39.01 (CH2), 52.46
(OCH3), 52.51 (OCH3), 69.01 (CH2), 89.41 (CH, observed in DEPT-90
NMR), 89.47 (quat-C), 108.70 (]CH), 112.67 (]CH), 119.81 (]CH),
121.58 (]CH),124.89 (]CH),125.90 (quat-C),126.41 (quat-C),127.57
(]CH), 130.14 (]CH), 130.37 (]CH), 134.58 (quat-C), 143.12 (quat-
C), 145.28 (quat-C), 156.28 (quat-C), 161.12 (quat-C), 162.00 (quat-C),
171.57 (quat-C); HRMS (ESI) calcd for C32H37NO7 [MþNa]þ
570.6285; found, 570.6276.
sorption coefficient¼0.093 mmꢁ1
,
l
¼0.71073 A, 7283 reflections
were collected on a smart apex CCD single crystal diffractometer
4087 observed reflections (Iꢃ2
s (I)). The largest difference peak
ꢀꢁ3
and hole¼0.733 and ꢁ0.366 e A , respectively. The structure was
solved by direct methods and refined by full-matrix least squares
on F2 using SHELXL-97 software.
4.7. Synthesis of macrocycles 9f
4.5. Synthesis of macrocycles 9d
A solution of diazoamide 7f (100 mg, 0.22 mmol) and DMAD
(40 mg, 0.28 mmol), rhodium(II) acetate (1.3 mg, 1.3 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9f (63%) Colorless
solid; mp 205e207 ꢀC; IR (neat): nmax 2931, 2857, 1724, 1659, 1611,
A solution of diazoamide 7d (100 mg, 0.22 mmol) and DMAD
(41 mg, 0.28 mmol), rhodium(II) acetate (1.3 mg, 1.32 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
15 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9d (70%) Colorless
solid; mp 201e203 ꢀC; IR (neat): nmax 2927, 2852, 1718, 1609, 1510,
1485, 1455, 1433, 1263, 1020, 990, 730 cmꢁ1
CDCl3)
;
1H NMR (400 MHz,
d¼1.19e1.318 (m, 8H, CH2), 1.39e1.49 (m, 2H, CH2), 1.51e1.58
1464, 1437, 1252, 1094, 1014, 984, 761 cmꢁ1
CD2Cl2)
¼1.16e1.87 (m, 8H, CH2), 1.34e1.37 (m, 2H, CH2), 1.44e1.48
(m, 1H, CH2), 1.55e1.74 (m, 5H, CH2), 3.31 (dt, 1H, J1¼14 Hz, J2¼4 Hz,
;
1H NMR (400 MHz,
(m, 1H, CH2), 1.66e1.72 (m, 4H, CH2), 1.76e1.86 (m, 1H, CH2),
3.35e3.39 (m, 1H, NeCH2), 3.66 (s, 3H, OCH3), 3.75 (s, 3H, OCH3),
3.91e3.92 (m, 1H, NeCH2), 4.12e4.19 (m, 2H, OCH2), 6.72 (d, 1H,
d

S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
1449
J¼8.0 Hz, ArH), 6.89 (d, 1H, J¼8.4 Hz, ArH), 7.03 (td, 1H, J1¼7.6 Hz,
4.10. Synthesis of macrocycles 9i
J2¼0.8 Hz, ArH), 7.08 (s, 1H, CHO), 7.18 (d, 1H, J¼2.0 Hz, ArH), 7.25
(dd, 1H, J1¼8.0 Hz, J2¼2.4 Hz, ArH), 7.32 (td, 1H, J1¼7.6 Hz, J2¼1.6 Hz,
ArH), 7.46 (dd, 1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH); 13C NMR (100 MHz,
A solution of diazoamide 7i (100 mg, 0.20 mmol) and DMAD
(37 mg, 0.26 mmol), rhodium(II) acetate (1.2 mg, 1.34 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9i (62%) Colorless
solid; mp 218e220 ꢀC; IR (neat): nmax 2923, 2853, 1714, 1611, 1595,
CDCl3)
d 24.86 (CH2), 25.75 (CH2), 25.98 (CH2), 27.30 (CH2), 27.93
(CH2), 28.09 (CH2), 28.24 (CH2), 28.96 (CH2), 39.32 (CH2), 52.58
(OCH3), 52.69 (OCH3), 68.89 (CH2), 82.18 (CH, observed in DEPT-90
NMR), 89.14 (quat-C), 109.75 (]CH), 113.04 (]CH), 120.94 (]CH),
125.86 (]CH), 126.03 (quat-C), 128.07 (quat-C), 128.63 (]CH),
128.83 (quat-C), 130.56 (]CH), 130.91 (]CH), 134.35 (quat-C),
142.78 (quat-C), 146.30 (quat-C), 157.64 (quat-C), 160.89 (quat-C),
162.93 (quat-C), 173.28 (quat-C); HRMS (ESI) calcd for C31H34ClNO7
[MþNa]þ 591.0469; found, 519.0455.
1514, 1464, 1293, 1014, 988, 749 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d¼1.31 (br, s, 14H, CH2), 1.44 (br, s, 2H, CH2), 1.58e1.65 (m, 2H, CH2),
1.68e1.74 (m, 1H, CH2), 1.76e1.79 (m, 1H, CH2), 3.28e3.35 (m, 1H,
NeCH2), 3.50 (s, 3H, OCH3), 3.55 (s, 3H, OCH3), 3.95e4.03 (m, 2H,
NeCH2,OCH2), 4.12e4.15 (m, 1H, OCH2), 6.76 (d, 1H, J¼8.0 Hz, ArH),
6.74 (td, 1H, J1¼7.8 Hz, J2¼0.8 Hz, ArH), 7.17 (d, 1H, J¼9.6 Hz, ArH),
7.23e7.32 (m, 2H, ArH), 7.50e7.57 (m, 2H, ArH), 7.69e7.77 (m, 3H,
ArH, CHO), 8.51 (d, 1H, J¼8.8 Hz, ArH); 13C NMR (100 MHz, CDCl3)
4.8. Synthesis of macrocycles 9g
A solution of diazoamide 7g (100 mg, 0.23 mmol) and DMAD
(44 mg, 0.30 mmol), rhodium(II) acetate (1.4 mg, 1.3 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
17 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/EtOAc, 65:35) to give 9g (65%) Colorless
solid; mp 218e220 ꢀC; IR (neat): nmax 2929, 2858, 1726, 1617, 1603,
d 24.75 (CH2), 25.88 (CH2), 26.05 (CH2), 26.79 (CH2), 26.96 (CH2),
27.27 (CH2), 27.78 (CH2), 28.24 (CH2), 28.51 (CH2), 29.49 (CH2),
39.32 (CH2), 52.36 (OCH3), 52.39 (OCH3), 70.72 (CH2), 80.77
(CH, observed in DEPT-90 NMR), 88.77 (quat-C), 108.65 (]CH),
115.17 (]CH), 116.30 (quat-C), 122.80 (]CH), 123.62 (]CH),
124.18 (]CH), 125.47 (]CH), 126.40 (]CH), 126.74 (quat-C), 128.79
(]CH), 129.68 (quat-C), 130.87 (]CH), 131.97 (]CH), 133.44 (quat-
C), 134.97 (quat-C),144.52 (quat-C), 148.50 (quat-C), 156.71 (quat-C),
161.60 (quat-C), 162.75 (quat-C), 173.38 (quat-C); HRMS (ESI) calcd
for C37H41NO7 [MþNa]þ 634.7137; found, 634.7127.
1489, 1468, 1454, 1246, 1159, 995, 745 cmꢁ1
CD2Cl2)
;
1H NMR (400 MHz,
¼1.17e1.53 (m, 12H, CH2), 1.62e1.79 (m, 4H, CH2),
d
3.29e3.36 (dt, 1H, J1¼14 Hz, J2¼4 Hz, NeCH2), 3.59 (s, 3H, OCH3),
3.64 (s, 3H, OCH3), 3.93e3.97 (m, 1H, NeCH2), 4.10e4.14 (m, 2H,
OCH2), 6.69e6.72 (m, 2H, ArH), 6.81 (t, 1H, J¼8.4 Hz, ArH),
6.85e6.90 (m, 2H, ArH), 7.05 (s, 1H, CHO), 7.11e7.20 (m, 2H, ArH),
7.26 (dd, 1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH); 13C NMR (100 MHz, CD2Cl2)
4.11. Synthesis of macrocycles 10a
d
24.80 (CH2), 25.73 (CH2), 26.05 (CH2), 27.29 (CH2), 27.89 (CH2),
A solution of diazoamide 7b (100 mg, 0.23 mmol) and N-phe-
nylmaleimide (53 mg, 0.30 mmol), in dry dichloromethane (15 mL)
was allowed to react with rhodium(II) acetate (1.4 mg, 1.3 mol %) at
room temperature for 18 min. The reaction mixture was concen-
trated in vacuo and purified on silica (hexane/EtOAc, 65:35) to
furnish 10a (65%). Colorless solid; mp 228e230 ꢀC; IR (neat): nmax
28.85 (CH2), 28.94 (CH2), 29.02 (CH2), 38.95 (CH2), 52.17 (OCH3),
52.37 (OCH3), 68.85 (CH2), 88.68 (CH, observed in DEPT-90 NMR),
89.18 (quat-C), 108.25 (]CH), 112.11 (]CH), 119.81 (]CH),
121.28 (]CH), 124.29 (]CH), 125.55 (quat-C), 126.51 (quat-C),
128.17 (]CH), 130.24 (]CH), 130.57 (]CH), 135.38 (quat-C), 144.07
(quat-C), 145.18 (quat-C), 157.38 (quat-C), 161.02 (quat-C), 162.59
(quat-C), 172.57 (quat-C); HRMS (ESI) calcd for C31H35NO7 [MþNa]þ
556.6019; found, 556.6036.
2931, 2857, 1715, 1614, 1491, 1468, 1374, 1264, 1192, 1042, 729 cmꢁ1
1H NMR (400 MHz, CDCl3)
¼1.03e1.05 (m, 3H, CH2), 1.15e1.20 (m,
;
d
5H, CH2), 1.27e1.38 (m, 4H, CH2), 1.60e1.64 (m, 2H, CH2), 1.76e1.85
(m, 2H, CH2), 3.34 (dt, 1H, J1¼14 Hz, J2¼4 Hz, NeCH2), 3.68 (d, 1H,
J¼8.0 Hz, CH), 3.96e4.07 (m,1H, NeCH2), 4.14e4.26 (m, 2H, OCH2 &
CH), 4.27e4.30 (m, 1H, OCH2), 6.65 (d, 1H, J¼8.4 Hz, ArH), 6.81 (d,
1H, J¼8.0 Hz, ArH), 6.86e6.90 (m, 2H, ArH), 7.02 (td, 1H, J1¼7.6 Hz,
J2¼0.8 Hz, ArH), 7.16e7.37 (m, 9H, ArH); 13C NMR (100 MHz, CDCl3)
4.9. Synthesis of macrocycles 9h
A solution of diazoamide 7h (100 mg, 0.21 mmol) and DMAD
(39 mg, 0.27 mmol), rhodium(II) acetate (1.25 mg, 1.32 mol %) in
dichloromethane (15 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated in vacuo and puri-
fied on silica (hexane/EtOAc, 65:35) to give 9h (68%) Yellow solid;
mp 263e265 ꢀC; IR (neat): nmax 2926, 2855, 1718, 1613, 1512, 1488,
d
24.76 (CH2), 25.71 (CH2), 26.64 (CH2), 26.90 (CH2), 28.10 (CH2),
28.60 (CH2), 28.99 (CH2), 29.31 (CH2), 37.57 (CH2), 49.90 (]CH),
50.98 (]CH), 69.43 (CH2), 74.86 (CH, observed in DEPT-90 NMR),
83.42 (quat-C), 109.17 (]CH), 112.96 (]CH), 120.54 (]CH), 122.74
(]CH),124.14 (quat-C),125.85 (]CH), 126.20 (]CH), 127.38 (]CH),
128.34 (quat-C), 128.62 (]CH), 129.18 (]CH), 129.44 (]CH), 131.01
(]CH), 131.72 (quat-C), 143.88 (quat-C), 156.36 (quat-C), 173.43
(quat-C), 173.60 (quat-C), 174.74 (quat-C); HRMS (ESI) calcd for
C35H36N2O5 [MþNa]þ 587.6605; found, 587.6616.
1465, 1246, 1013, 988, 733 cmꢁ1; 1H NMR (400 MHz, CD2Cl2)
d
¼1.18
(br, 8H, CH2), 1.43e1.52 (m, 4H, CH2), 1.61e1.69 (m, 3H, CH2),
1.76e1.81 (m, 1H, CH2), 3.33 (dt, 1H, J1¼14 Hz, J2¼4.4 Hz, NeCH2),
3.50 (s, 3H, OCH3), 3.57 (s, 3H, OCH3), 3.93e3.99 (m, 1H, NeCH2),
4.10e4.17 (m, 1H, OCH2), 4.21e4.26 (m, 1H, OCH2), 6.95 (d, 1H,
J¼8.0 Hz, ArH), 6.95 (td, 1H, J1¼7.6 Hz, J2¼0.8 Hz, ArH), 7.22 (d, 1H,
J¼8.8 Hz, ArH), 7.24 (td,1H, J1¼8.0 Hz, J2¼1.2 Hz, ArH), 7.28e7.32 (m,
1H, ArH), 7.50e7.55 (m, 2H, ArH), 7.69 (d, 2H, J¼7.2 Hz, ArH, CHO),
7.74 (d, 1H, J¼8.8 Hz, ArH), 8.51 (d, 1H, J¼8.8 Hz, ArH); 13C NMR
4.12. Synthesis of macrocycles 10b
A solution of diazoamide 7d (100 mg, 0.22 mmol) and NPM
(50 mg, 0.28 mmol), in dry dichloromethane (15 mL) was allowed
to react with rhodium(II) acetate (1.3 mg, 1.3 mol %) at room tem-
perature for 15 min. The reaction mixture was concentrated in
vacuo and purified on silica (hexane/EtOAc, 65:35) to furnish 10b
(68%). Colorless solid; mp 273e275 ꢀC; IR (neat): nmax 2920, 2853,
(100 MHz, CD2Cl2)
d 24.79 (CH2), 24.28 (CH2), 25.13 (CH2), 26.14
(CH2), 26.43 (CH2), 26.82 (CH2), 26.87 (CH2), 27.78 (CH2), 28.68
(CH2), 37.83 (CH2), 51.38 (OCH3), 51.42 (OCH3), 69.87 (CH2), 79.42
(CH, observed in DEPT-90 NMR), 87.74 (quat-C), 107.88 (]CH),
115.55 (]CH), 115.84 (quat-C), 121.88 (]CH), 122.67 (]CH), 123.04
(]CH),124.44 (]CH),125.48 (]CH),125.77 (quat-C),127.83 (]CH),
128.77 (quat-C), 129.86 (quat-C), 131.03 (]CH), 132.43 (]CH),
133.66 (quat-C), 143.44 (quat-C), 147.92 (quat-C), 155.73 (quat-C),
160.61 (quat-C), 161.72 (quat-C), 172.35 (quat-C); HRMS (ESI) calcd
for C35H37NO7 [MþNa]þ 606.6606; found, 606.6621.
1715, 1612, 1504, 1495, 1468, 1380, 1198, 1025, 756 cmꢁ1
(400 MHz, CDCl3)
;
1H NMR
d
¼1.17e1.20 (m, 6H, CH2), 1.12e1.32 (m, 2H, CH2),
1.35e1.39 (m, 3H, CH2), 1.58e1.63 (m, 3H, CH2), 1.74e1.84 (m, 2H,
CH2), 3.31e3.36 (dt, 1H, J1¼14 Hz, J2¼3.6 Hz, NeCH2), 3.67e3.73 (m,
5H, CH2 & OCH3), 3.94 (td, 1H, J1¼9.6 Hz, J2¼2.4 Hz, NeCH2),

1450
S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
4.12e4.18 (m, 2H, OCH2 & CH), 4.20e4.24 (m, 1H, OCH2), 6.39e6.43
(m, 1H, ArH), 6.59 (d, 1H, J¼8.4 Hz, ArH), 6.80 (d, 2H, J¼7.6 Hz, ArH),
7.01 (t, 1H, J¼7.6 Hz, ArH), 7.16e7.23 (m, 3H, ArH), 7.27e7.33 (m, 2H,
123.11 (quat-C), 124.34 (]CH), 125.93 (]CH), 126.18 (]CH), 127.10
(]CH),128.36 (]CH),128.91 (]CH),129.17 (]CH),129.45 (quat-C),
130.78 (]CH), 130.90 (]CH), 131.65 (quat-C), 132.91 (quat-C),
143.77 (quat-C), 155.83 (quat-C), 173.26 (quat-C), 173.36 (quat-C),
175.32 (quat-C); HRMS (ESI) calcd for C41H42N2O5 [MþNa]þ
665.7723; found, 665.7713.
ArH), 7.37e7.41 (m, 2H, ArH); 13C NMR (100 MHz, CDCl3)
d 24.77
(CH2), 25.69 (CH2), 26.57 (CH2), 26.92 (CH2), 28.05 (CH2),
28.58 (CH2), 28.90 (CH2), 29.16 (CH2), 37.64 (CH2), 49.91 (]CH),
51.00 (]CH), 55.23 (OCH3), 69.29 (CH2), 74.77 (CH, observed in
DEPT-90 NMR), 83.21 (quat-C), 99.99 (]CH), 105.13 (]CH), 109.15
(]CH), 117.34 (quat-C), 122.70 (]CH), 122.90 (quat-C), 126.21 (]
CH), 126.74 (]CH), 126.97 (]CH), 127.31 (]CH), 128.64 (]CH),
129.10 (]CH), 130.96 (]CH), 131.75 (quat-C), 143.87 (quat-C),
157.45 (quat-C), 160.76 (quat-C), 173.51 (quat-C), 173.81 (quat-C),
174.78 (quat-C); HRMS (ESI) calcd for C36H38N2O6 [MþNa]þ
617.6865; found, 617.6849.
4.15. Synthesis of macrocycles 11a
A solution of diazoamide 7b (100 mg, 0.23 mmol) and maleic
anhydride (30 mg, 0.30 mmol), in dry dichloromethane (20 mL)
was allowed to react with rhodium(II) acetate (1.4 mg, 1.33 mol %)
at room temperature for 25 min. The reaction mixture was con-
centrated in vacuo and purified on silica (hexane/EtOAc, 65:35) to
furnish 11a (59%). Colorless solid; mp 255e257 ꢀC; IR (neat): nmax
4.13. Synthesis of macrocycles 10c
2920, 2851, 1715, 1614, 1491, 1467, 1246, 1184, 1039, 913, 735 cmꢁ1
1H NMR (400 MHz, CDCl3)
¼1.01e1.08 (m, 3H, CH2), 1.20e1.24 (m,
;
d
A solution of diazoamide 7h (100 mg, 0.27 mmol) and NPM
(48 mg, 0.27 mmol), in dry dichloromethane (20 mL) was allowed
to react with rhodium(II) acetate (1.25 mg, 1.32 mol %) at room
temperature for 20 min. The reaction mixture was concentrated in
vacuo and purified on silica (hexane/EtOAc, 65:35) to furnish 10c
(65%). Colorless solid; mp 241e243 ꢀC; IR (neat): nmax 2926, 2854,
5H, CH2), 1.31e1.41 (m, 4H, CH2), 1.59e1.71 (m, 2H, CH2) 1.78e1.83
(m, 1H, CH2), 1.87e1.94 (m, 1H, CH2), 3.40 (dt, 1H, J1¼14.4 Hz,
J2¼4 Hz, NeCH2), 3.84 (d, 1H, J¼8.8 Hz, CH), 4.08 (td, 1H, J1¼10 Hz,
J2¼2.4 Hz, NeCH2), 4.18e4.26 (m, 1H, OCH2), 4.28e4.32 (m, 1H,
OCH2), 4.35 (t, 1H, J¼8.4 Hz, CH), 6.68 (d, 1H, J¼8.0 Hz, ArH), 6.88 (d,
1H, J¼7.6 Hz, ArH), 6.94e6.97 (m, 2H, ArH), 7.15 (td, 1H, J1¼7.6 Hz,
J2¼0.8 Hz, ArH), 7.27e7.32 (m, 2H, ArH), 7.34 (d, 1H, J¼6.8 Hz, ArH),
7.39 (td, 1H, J1¼8.0 Hz, J2¼1.2 Hz, ArH); 13C NMR (100 MHz, CDCl3)
1716, 1614, 1596, 1499, 1468, 1375, 1187, 1066, 729 cmꢁ1
;
1H NMR
(400 MHz, CDCl3)
d
¼1.07e1.10 (m, 3H, CH2), 1.16e0.1.28 (m, 5H,
CH2), 1.37e1.41 (m, 2H, CH2), 1.49e1.54 (m, 2H, CH2), 1.68e1.73 (m,
2H, CH2), 1.83e1.88 (m, 2H, CH2), 3.36 (dt, 1H, J1¼14 Hz, J2¼4 Hz,
NeCH2), 3.82 (d, 1H, J¼8.4 Hz, CH), 4.07 (td, 1H, J1¼11 Hz, J2¼3.2 Hz,
NeCH2), 4.15e4.24 (m, 2H, OCH2 & CH), 4.36e4.41 (m, 1H, OCH2),
6.82 (d, 1H, J¼7.6 Hz, ArH), 6.95e6.98 (m, 1H, ArH), 7.07 (td, 2H,
J1¼7.6 Hz, J2¼0.4 Hz, ArH), 7.18e7.33 (m, 7H, ArH), 7.35 (d, 2H,
J¼8.8 Hz, ArH), 7.70 (d, 1H, J¼8.0 Hz, ArH), 7.75 (d, 1H, J¼8.8 Hz,
d 24.69 (CH2), 25.64 (CH2), 26.56 (CH2), 26.78 (CH2), 28.00 (CH2),
28.52 (CH2), 28.88 (CH2), 29.29 (CH2), 37.63 (CH2), 51.01 (]CH),
51.47 (]CH), 69.41 (CH2), 75.00 (CH, observed in DEPT-90 NMR),
83.50 (quat-C), 109.32 (]CH), 112.83 (]CH), 120.85 (]CH),
122.00 (quat-C), 123.09 (]CH), 123.75 (quat-C), 126.06 (]CH),
126.99 (]CH), 129.78 (]CH), 131.49 (]CH), 143.78 (quat-C), 156.05
(quat-C), 168.28 (quat-C), 168.94 (quat-C), 174.03 (quat-C); HRMS
(ESI) calcd for C29H31NO6 [MþNa]þ 512.5493; found, 512.5479.
ArH), 8.53 (d, 1H, J¼8.4 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 24.80
(CH2), 25.92 (CH2), 26.45 (CH2), 26.63 (CH2), 27.78 (CH2),
28.05 (CH2), 28.19 (CH2), 29.60 (CH2), 37.92 (CH2), 49.48 (]CH),
51.11 (]CH), 70.14 (CH2), 76.68 (CH, observed in DEPT-90 NMR),
83.93 (quat-C), 109.23 (]CH), 114.27 (]CH), 115.42 (quat-C),
122.81 (]CH), 123.02 (quat-C), 123.16 (]CH), 124.30 (]CH), 125.90
(]CH), 126.25 (]CH), 127.36 (]CH), 128.35 (]CH), 128.89 (]CH),
129.25 (]CH), 129.49 (quat-C), 130.92 (]CH), 130.98 (]CH), 131.69
(quat-C), 133.08 (quat-C), 143.87 (quat-C), 155.11 (quat-C), 173.45
(quat-C), 173.49 (quat-C), 175.08 (quat-C); HRMS (ESI) calcd for
C39H38N2O5 [MþNa]þ 637.7192; found, 637.7179.
4.16. Synthesis of macrocycles 11b
A solution of diazoamide 7h (100 mg, 0.21 mmol) and maleic
anhydride (27 mg, 0.27 mmol), in dry dichloromethane (15 mL)
was allowed to react with rhodium(II) acetate (1.25 mg, 1.32 mol %)
at room temperature for 25 min. The reaction mixture was con-
centrated in vacuo and purified on silica (hexane/EtOAc, 65:35) to
furnish 11b (56%). Colorless solid; mp 230e232 ꢀC; IR (neat): nmax
2923, 2852, 1723, 1613, 1591, 1488, 1466, 1269, 1081, 818, 749 cmꢁ1
1H NMR (400 MHz, CDCl3)
¼1.10e1.19 (m, 4H, CH2), 1.23e1.31 (m,
;
d
4.14. Synthesis of macrocycles 10d
4H, CH2), 1.38e1.47 (m, 4H, CH2), 1.58e1.70 (m, 2H, CH2), 1.81e1.93
(m, 2H, CH2), 3.39 (dt, 1H, J1¼14 Hz, J2¼4 Hz, NeCH2), 3.87 (d, 1H,
J¼8.2 Hz, CH), 4.10 (td, 1H, J1¼10.2 Hz, J2¼2.8 Hz, NeCH2),
4.21e4.26 (m, 1H, OCH2), 4.30e4.35 (m, 1H, OCH2), 4.37 (t, 1H,
J¼8.4 Hz, CH), 6.39 (t, 1H, J¼8.0 Hz, ArH), 6.71 (d, 1H, J¼7.6 Hz, ArH),
6.83e6.95 (m, 2H, ArH), 7.10e7.17 (m, 1H, ArH), 7.27 (d, 2H,
J¼7.4 Hz, ArH), 7.31e7.35 (m, 2H, ArH), 7.39 (d, 2H, J1¼8.0 Hz, ArH);
A solution of diazoamide 7i (100 mg, 0.20 mmol) and NPM
(45 mg, 0.26 mmol), in dry dichloromethane (15 mL) was allowed
to react with rhodium(II) acetate (1.2 mg, 1.34 mol %) at room
temperature for 20 min. The reaction mixture was concentrated in
vacuo and purified on silica (hexane/EtOAc, 65:35) to furnish 10d
(60%). Colorless solid; mp 220e222 ꢀC; IR (neat): nmax 2922, 2850,
13C NMR (100 MHz, CDCl3)
d 24.20 (CH2), 25.10 (CH2), 26.24 (CH2),
1705, 1613, 1594, 1489, 1465, 1382, 1179, 1022, 737 cmꢁ1
;
1H NMR
26.36 (CH2), 28.12 (CH2), 28.80 (CH2), 28.91 (CH2), 29.32 (CH2),
37.89 (CH2), 51.15 (]CH), 51.53 (]CH), 69.75 (CH2), 75.35 (CH,
observed in DEPT-90 NMR), 85.50 (quat-C), 109.15 (]CH), 112.25
(]CH), 120.35 (]CH), 122.12 (quat-C), 123.19 (]CH), 124.15 (quat-
C), 125.55 (]CH), 126.31 (]CH), 126.54 (]CH), 128.24 (]CH),
129.31 (]CH), 132.34 (]CH), 140.23 (quat-C), 143.78 (quat-
C),152.35 (quat-C), 156.34 (quat-C), 167.65 (quat-C), 167.96 (quat-C),
175.12 (quat-C); HRMS (ESI) calcd for C33H33NO6 [MþNa]þ
562.6080; found, 562.6067.
(400 MHz, CDCl3)
d
¼1.36e1.45 (m, 14H, CH2), 1.70e0.1.86 (m, 5H,
CH2), 1.94e1.98 (m, 1H, CH2), 3.70e3.78 (m, 1H, NeCH2), 3.80e3.83
(m, 1H, NeCH2), 3.86 (d, 1H, J¼8.4 Hz, CH), 4.17 (td, 1H, J1¼8.8 Hz,
J2¼3.6 Hz, OCH2), 4.32 (t, 1H, J¼8.8 Hz, CH), 4.35e4.39 (m, 1H,
OCH2), 6.91 (d, 1H, J¼7.6 Hz, ArH), 6.97e6.99 (m, 2H, ArH), 7.15 (td,
1H, J1¼7.2 Hz, J2¼0.8 Hz, ArH), 7.28e7.35 (m, 4H, ArH), 7.37e7.44
(m, 3H, ArH), 7.47 (d, 1H, J¼8.8 Hz, ArH), 7.79 (d, 1H, J¼7.2 Hz, ArH),
7.84 (d, 1H, J¼9.2 Hz, ArH), 8.74 (d, 2H, J¼8.4 Hz, ArH); 13C NMR
(100 MHz, CDCl3)
d 25.02 (CH2), 25.68 (CH2), 26.30 (CH2), 26.59
(CH2), 27.61 (CH2), 27.96 (CH2), 28.08 (CH2), 28.85 (CH2), 29.36
(CH2), 29.98 (CH2), 38.37 (CH2), 49.14 (]CH), 51.68 (]CH), 69.24
(CH2), 78.07 (CH, observed in DEPT-90 NMR), 84.07 (quat-C), 108.91
(]CH),113.60 (]CH), 115.46 (quat-C), 122.69 (]CH),123.06 (]CH),
4.17. Synthesis of macrocycles 13a
A solution of diazoamide 7b (100 mg, 0.23 mmol) and p-nitro-
benzaldehyde (47 mg, 0.31 mmol), in dry dichloromethane (15 mL)

S. Muthusamy, T. Karikalan / Tetrahedron 68 (2012) 1443e1451
1451
was allowed to react with rhodium(II) acetate (1.5 mg, 1.4 mol %) at
room temperature for 25 min. The reaction mixture was concen-
trated in vacuo and purified on silica (hexane/EtOAc, 65:35) to yield
13a (55%). Colorless solid; mp 240e242 ꢀC; IR (neat): nmax 2923,
(neat): nmax 2929, 2857, 1719, 1606, 1522, 1493, 1467, 1251, 1066,
853, 751 cmꢁ1 1H NMR (400 MHz, CDCl3)
¼1.12e1.32 (m, 10H,
;
d
CH2), 1.61e1.79 (m, 6H, CH2), 3.29 (dt, 1H, J1¼14 Hz, J2¼4 Hz,
NeCH2), 3.79e3.81 (m, 1H, NeCH2), 3.98e4.03 (m, 1H, OCH2),
4.09e4.20 (m, 1H, OCH2), 5.64 (s, 1H, OCH), 6.36e6.3 (m, 1H, ArH),
6.51 (dd, 1H, J1¼8.2 Hz, J2¼1.8 Hz, ArH), 6.59 (d, 2H, J¼7.8 Hz, ArH),
6.61e6.65 (m, 2H, ArH), 6.78 (s, 1H, OCH), 6.87 (td, 1H, J1¼7.8 Hz,
J2¼1.8 Hz, ArH), 7.21 (d, 2H, J¼7.8 Hz, ArH), 7.53 (d, 1H, J¼8.0 Hz,
2852, 1712, 1605, 1522, 1492, 1454, 1247, 1062, 937, 749 cmꢁ1
;
1H
NMR (400 MHz, CDCl3)
d¼1.10e1.37 (m,12H, CH2),1.59e1.82 (m, 4H,
CH2), 3.34 (dt, 1H, J1¼14 Hz, J2¼4.8 Hz, NeCH2), 3.89 (td, 1H,
J1¼11 Hz, J2¼4 Hz, NeCH2), 4.02e4.07 (m, 1H, OCH2), 4.18e4.24 (m,
1H, OCH2), 5.71 (s, 1H, OCH), 6.60e6.68 (m, 2H, ArH), 6.69 (dd, 2H,
J1¼7.6 Hz, J2¼1.2 Hz ArH), 6.86 (d, 1H, J¼8.0 Hz, ArH), 6.93 (s, 1H,
OCH), 6.97e7.05 (m, 2H, ArH), 7.30e7.35 (m, 2H, ArH), 7.88 (dd, 1H,
J1¼7.6 Hz, J2¼1.6 Hz, ArH), 8.00 (d, 2H, J¼7.2 Hz, ArH); 13C NMR
ArH), 7.72e7.86 (m, 2H, ArH); 13C NMR (100 MHz, CDCl3)
d 24.59
(CH2), 25.85 (CH2), 26.45 (CH2), 26.89 (CH2), 27.91 (CH2), 28.23
(CH2), 29.05 (CH2), 29.35 (CH2), 39.45 (CH2), 68.38 (CH2), 80.24
(quat-C), 81.35 (OCH), 99.85 (OCH), 106.65 (]CH), 107.81 (]CH),
118.81 (quat-C), 120.21 (]CH), 121.41 (]CH), 122.13 (]CH),
124.10 (quat-C),125.13 (quat-C),126.02 (]CH),126.11 (]CH),126.26
(]CH), 128.87 (]CH), 132.42 (]CH), 142.23 (quat-C), 143.71 (quat-
C), 147.21 (quat-C), 161.08 (quat-C), 175.72 (quat-C); HRMS (ESI)
calcd for C32H34BrNO4 [MþNa]þ 599.5104; found, 599.5121.
(100 MHz, CDCl3)
d 24.66 (CH2), 25.53 (CH2), 25.96 (CH2), 26.97
(CH2), 27.57 (CH2), 27.62 (CH2), 27.91 (CH2), 28.95 (CH2), 39.10
(CH2), 68.59 (CH2), 83.29 (quat-C), 83.39 (OCH),100.33 (OCH),108.78
(]CH), 112.51 (]CH), 120.51 (]CH), 122.61 (]CH), 123.44 (]CH),
124.10 (quat-C), 125.57 (quat-C), 126.15 (]CH), 126.19 (]CH),
126.36 (]CH), 129.97 (]CH), 131.02 (]CH), 143.13 (quat-C), 143.79
(quat-C), 147.35 (quat-C), 157.83 (quat-C), 175.62 (quat-C); HRMS
(ESI) calcd for C32H34N2O6 [MþNa]þ 565.6119; found, 565.6132.
Crystal data for the compound 13a: (CCDC 851589) C32H34N2O6,
M¼542.61, 0.26ꢂ0.14ꢂ0.09 mm, Monoclinic, space group Pꢁ21
Acknowledgements
This research was supported by Department of Science and
Technology (DST), New Delhi. T.K. thanks UGC-RFSMS, for a re-
search fellowship. We thank DST, New Delhi for providing 400 MHz
NMR and XRD facilities under FIST program.
ꢀ
ꢀ
ꢀ
a
with a¼14.5635(10) A, b¼10.8377(7) A, c¼18.1521(12) A, ¼90.00,
3
ꢀ
b
¼97.7130(10),
g
¼90.00, V¼2839.1(3) A , T¼293(2) K, R1¼0.0907,
wR2¼0.2995 on observed data, z¼4, Dcalcd¼1.270 mg cmꢁ3, F(000)¼
1152, Absorption coefficient¼0.088 mmꢁ1
,
l
¼0.71073 A, 6151 re-
ꢀ
flections were collected on a smart apex CCD single crystal diffrac-
References and notes
tometer 3812 observed reflections (Iꢃ2
s (I)). The largest difference
ꢀꢁ3
peak and hole¼0.864 and ꢁ0.422 e A , respectively. The structure
was solved by direct methods and refined by full-matrix least
squares on F2 using SHELXL-97 software.
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; John Wiley: New York, NY, 1998.
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Cycloaddition Chemistry toward Heterocycles and Natural Products; Padwa, A.,
Pearson, W. H., Eds.; John Wiley: New Jersey, NJ, 2003.
3. (a) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091; (b) Zhang, Z.; Wang, J.
Tetrahedron 2008, 64, 6577.
4.18. Synthesis of macrocycles 13b
4. (a) Mehta, G.; Muthusamy, S. Tetrahedron 2002, 58, 9477; (b) Hodgson, D. M.;
Pierard, F. Y. T. M.; Stupple, P. A. Chem. Soc. Rev. 2001, 30, 50; (c) Padwa, A.;
Weingarten, M. D. Chem. Rev. 1996, 96, 223.
5. (a) Chen, M. H.; Pollard, P. P.; Patchett, A.; Cheng, K.; Wei, L.; Chan, W. W. -S.;
Butler, B.; Jacks, T. M.; Smith, R. G. Bioorg. Med. Chem. Lett. 1999, 9, 1261; (b)
Behera, R. K.; Behera, A. K.; Pradhan, R.; Pati, A.; Patra, M. Synth. Commun. 2006,
36, 3729.
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2001, 261; (b) Lo, M. M.-C.; Neumann, C. S.; Nagayama, S.; Perlstein, E. O.;
Schreiber, S. L. J. Am. Chem. Soc. 2004, 126, 16077; (c) Bignan, G. C.; Battista, K.;
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Chem. Lett. 2005, 15, 5022; (d) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int.
Ed. 2007, 46, 8748; (e) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209.
7. Tsuda, M.; Mugishima, T.; Komatzu, K.; Sone, T.; Tanaka, M.; Mikami, Y.; Shiro,
M.; Hirai, M.; Ohizumii, Y.; Kobayashi, J. Tetrahedron 2003, 59, 3227.
8. Zhang, X.; Smith, C. D. Mol. Pharmacol. 1996, 49, 288.
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Eds.; Pergamon: New York, NY, 1991; Vol. 4, pp 1031e1067; (b) Weathers, T. M.,
Jr.; Wang, Y.; Doyle, M. P. J. Org. Chem. 2006, 71, 8183; (c) Doyle, M. P.; Chapman,
B. J.; Hu, W.; Peterson, C. S.; McKervey, M. A.; Garcia, C. F. Org. Lett. 1999, 1, 1327;
(d) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919.
A solution of diazoamide 7d (100 mg, 0.22 mmol) and p-nitro-
benzaldehyde (44 mg, 0.29 mmol), in dry dichloromethane (15 mL)
was allowed to react with rhodium(II) acetate (1.4 mg, 1.42 mol %)
at room temperature for 25 min. The reaction mixture was con-
centrated in vacuo and purified on silica (hexane/EtOAc, 65:35) to
yield 13b (59%). Colorless solid; mp 227e229 ꢀC; IR (neat): nmax
2926, 2853, 1725, 1675, 1596, 1522, 1467, 1259, 1031, 824, 754 cmꢁ1
1H NMR (400 MHz, CDCl3)
¼1.11e1.37 (m, 12H, CH2), 1.59e1.80 (m,
;
d
4H, CH2), 3.34 (dt, 1H, J1¼14.4 Hz, J2¼4.8 Hz, NeCH2), 3.77 (s, 3H,
OCH3), 3.86 (td, 1H, J1¼11 Hz, J2¼4.0 Hz, NeCH2), 4.00e4.05 (m, 1H,
OCH2), 4.17e4.24 (m, 1H, OCH2), 5.69 (s, 1H, OCH), 6.41 (d, 1H,
J¼2.4 Hz, ArH), 6.55 (dd, 1H, J1¼8.4 Hz, J2¼2.4 Hz, ArH), 6.61 (d, 2H,
J¼8.0 Hz, ArH), 6.66e6.68 (m, 1H, ArH), 6.89 (s, 1H, OCH), 6.99 (td,
1H, J1¼7.6 Hz, J2¼1.6 Hz, ArH), 7.33 (d, 2H, J¼8.4 Hz, ArH), 7.77 (d,
1H, J¼8.4 Hz, ArH), 7.97e8.01 (m, 2H, ArH); 13C NMR (100 MHz,
CDCl3)
d 24.18 (CH2), 25.91 (CH2), 26.75 (CH2), 27.06 (CH2), 28.91
10. (a) Moyer, M. P.; Feldman, P. L.; Rapoport, H. J. Org. Chem. 1986, 50, 5223; (b)
Heslin, J. C.; Moody, C. J.; Slawin, A. M. Z.; Williams, D. J. Tetrahedron Lett. 1986,
27, 1403; (c) Doyle, M. P.; Protopopova, M. N.; Peterson, C. S.; Vitale, J. P.;
McKervey, M. A.; Garcia, C. F. J. Am. Chem. Soc. 1996, 118, 7865; (d) Doyle, M. P.;
Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev. 2010, 110, 704.
11. Muthusamy, S.; Karikalan, T.; Suresh, E. Tetrahedron Lett. 2011, 52, 1934.
12. (a) Muthusamy, S.; Ramkumar, R.; Mishra, A. K. Tetrahedron Lett. 2011, 52, 148;
(b) Muthusamy, S.; Krishnamurthi, J.; Babu, S. A.; Suresh, E. J. Org. Chem. 2007,
72, 1252; (c) Muthusamy, S.; Gnanaprakasam, B.; Suresh, E. Org. Lett. 2005, 7,
4577; (d) Muthusamy, S.; Krishnamurthi, J.; Nethaji, M. Chem. Commun. 2005,
3862; (e) Muthusamy, S.; Krishnamurthi, J.; Suresh, E. Synlett 2005, 3002; (f)
Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Ganguly, B.; Suresh, E.; Dastidar, P.
J. Org. Chem. 2002, 67, 8019.
(CH2), 29.03 (CH2), 29.13 (CH2), 29.24 (CH2), 40.04 (CH2), 55.62
(OCH3), 68.47 (CH2), 77.26 (OCH), 78.61 (quat-C), 98.53 (OCH),
105.79 (]CH), 108.73 (]CH), 119.01 (quat-C), 122.60 (]CH),
122.88 (]CH),125.77 (quat-C),126.50 (]CH), 129.90 (]CH), 130.28
(]CH), 130.37 (]CH), 142.79 (quat-C), 143.47 (quat-C), 147.62
(quat-C), 163.43 (quat-C), 166.23 (quat-C), 175.92 (quat-C); HRMS
(ESI) calcd for C33H36N2O7 [MþNa]þ 595.6379; found, 595.6366.
4.19. Synthesis of macrocycles 13c
13. (a) Muthusamy, S.; Gnanaprakasam, B. Tetrahedron 2007, 63, 3355; (b) Mu-
thusamy, S.; Gnanaprakasam, B.; Suresh, E. J. Org. Chem. 2007, 72, 1495; (c)
Muthusamy, S.; Gnanaprakasam, B.; Suresh, E. Org. Lett. 2006, 8, 1913; (d)
Muthusamy, S.; Azhagan, D. Tetrahedron 2010, 66, 8196; (e) Muthusamy, S.;
Srinivasan, P. Tetrahedron Lett. 2009, 50, 3794.
14. CCDC-851590(for9e),851589(for13a)containthesupplementarycrystallographic
data for this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
A solution of diazoamide 7b (100 mg, 0.23 mmol) and m-bro-
mobenzaldehyde (57 mg, 0.30 mmol), in dry dichloromethane
(15 mL) was allowed to react with rhodium(II) acetate (1.5 mg,
1.4 mol %) at room temperature for 30 min. The reaction mixture
was concentrated in vacuo and purified on silica (hexane/EtOAc,
65:35) to yield 13c (50%). Colorless solid; mp 231e233 ꢀC; IR