Double O-H insertion reactions of cyclic rhodium carbenoids: diastereoselective synthesis of macrocyclic oxindoles

Article abstract of DOI:10.1016/j.tetlet.2009.04.035

Double O-H insertion reactions of cyclic diazo amides 1 and dihydroxy compounds 2 in the presence of rhodium(II) acetate catalyst have been achieved, which ultimately led to the facile synthesis of prototype bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems.

Full text of DOI:10.1016/j.tetlet.2009.04.035

Tetrahedron Letters 50 (2009) 3794–3797
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Double O–H insertion reactions of cyclic rhodium carbenoids: diastereoselective
synthesis of macrocyclic oxindoles
*
Sengodagounder Muthusamy , Pandurangan Srinivasan
School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Double O–H insertion reactions of cyclic diazo amides 1 and dihydroxy compounds 2 in the presence of
rhodium(II) acetate catalyst have been achieved, which ultimately led to the facile synthesis of prototype
bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems. This facile double O–H insertion reaction protocol was
successfully applied to synthesize several C2-symmetric macrocycles having oxindole units incorporated
with complete diastereoselectivity.
Received 11 January 2009
Revised 1 April 2009
Accepted 3 April 2009
Available online 14 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Diazo amides
Oxindoles
O–H insertion
Macrocycle
Rhodium(II) acetate
a
-Diazocarbonyl compounds, which serve as precursors to
a
-
doles) and macrocycles in the presence of rhodium(II) acetate
catalyst.
keto carbenes/carbenoids, have been extensively used in synthetic
organic chemistry.1 To generate an intermediate rhodium carbe-
The required diazo amides 1a–d were synthesized from the 3-
diazooxindole10 according to our earlier work.9 Dihydroxy com-
pounds were used as purchased. Initially, the reaction of 1 equiv
of diazo amide 1a with 0.5 equiv of ethylene glycol in the presence
of a catalytic amount of Rh2(OAc)4 (1 mol %) in dichloromethane
was performed. The reaction was followed by TLC and then chro-
matographic purification of the reaction mixture using column
chromatography furnished product 3a in 59% yield. Compound
3a showed the presence of an amide carbonyl group in IR spec-
trum. A characteristic singlet at d 4.98 ppm for oxindolyl 3,30-pro-
tons in 1H NMR spectrum confirms the O–H insertion. The 13C and
dept-135 spectra of 3a revealed that a single peak for two CH3
groups, a single peak for two 3,30-carbons, four peaks for eight aro-
matic CH carbons, and three peaks for six quaternary carbons
unequivocally confirm the structure11 of 3a. Ethylene glycol is
not completely soluble in dichloromethane. We believed that bet-
ter yields could be achieved if the solubility of the dihydroxy com-
pound is increased. For this purpose, we chose to employ polar
solvents such as THF, DMF, DMSO, or dioxane and these afforded
only dimerization and decomposed products rather than insertion
product 3a. Thus, we have modified the reaction condition using
dichloromethane–DMF (50:2) as a solvent system where the dihy-
droxy compound is completely soluble and the reaction success-
fully yielded 3a with the isolated yield of 82%.
noid, the reaction of
a-diazocarbonyl compounds in the presence
of rhodium(II) carboxylate is a well-described method, which can
undergo an assortment of reactions such as C–H or heteroatom-H
insertion, cyclopropanation, and ylide formation.2,3 As an efficient
method of construction of complex architectures from simple,
readily available precursors, the catalytic insertion of
a-diazocar-
bonyl compounds into X–H (X = C, N, O, S, etc.) bonds was widely
utilized in organic synthesis. Oxygen–hydrogen insertion reactions
by the metallo-carbenoids got significant interest among organic
chemists as it provides a pathway for C–O bond formation provid-
ing a simple access to a-alkoxy or a-aryloxy ketones and esters as
well as chiral oxygen containing molecular systems.3,4 Initially,
Casanova and Reichstein have observed in 1950 that heating of a
steroidal diazo ketone in methanol in the presence of copper(II)
oxide gave the corresponding methoxy ketone.5 Later, Teyssié
and co-workers have introduced6 rhodium(II) acetate in 1973 as
the best catalyst for effecting the O–H insertion process. The rho-
dium(II) carboxylates have been found to be the current catalysts
of choice for many carbenoid transformations.7 We have been
extensively involved in developing new synthetic strategies,8 C-
alkylation9 using diazocarbonyl compounds. In continuation of
these efforts, we herein report an efficient double O–H insertion
reaction to synthesize various synthetically useful bis(3-alkoxyin-
Subsequently, under the optimized reaction conditions,
a
variety of dihydroxy compounds were examined by employing
various N-alkylated diazo amides. Thus, we investigated the
rhodium(II)-catalyzed reaction of cyclic diazo amide 1a with
* Corresponding author. Tel.: +91 431 2407053; fax: +91 431 2407045.
E-mail address: muthu@bdu.ac.in (S. Muthusamy).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.035

S. Muthusamy, P. Srinivasan / Tetrahedron Letters 50 (2009) 3794–3797
3795
propane-1,3-diol, butane-1,4-diol, or hexane-1,6-diol to furnish
the bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems 3b–d, respec-
tively, in moderate to good yield (Table 1) as a result of double
O–H insertion reaction. Similarly, reactions of other diazo amides
1b–d with the appropriate dihydroxy compounds furnished the
corresponding double O–H insertion products 3e–p.
3-diazooxindoles was used for the expediency and their stoichiom-
etry was not optimized. The presence of an excess amount of diazo
amide led to the diazo dimerization reaction to provide the corre-
sponding dimerized products under our experimental conditions,
which were readily purified by column chromatography. It is rele-
vant to mention that only one related report exists where the reac-
tion of simple acyclic diazocarbonyl compounds12 was studied
with polyethylene glycols in the presence of Cu(acac)2 catalyst.
We have not obtained any other product resulting from the poten-
tial competitive cyclopropanation reaction13 (when R = allyl, prop-
argyl) of the diazo amides 1.
After obtaining the above encouraging results, we further envis-
aged to apply this intermolecular double O–H insertion reaction
methodology to construct macrocyclic oxindoles. Our strategy for
the construction of macrocycles was to employ rhodium(II) ace-
tate-mediated insertion reaction using bis(3-diazo-2-oxindoles)
4. It was envisaged that the resulting bis(rhodium(II) carbenoids)
would undergo double O–H insertion reaction with a dihydroxy
compound to result the formation of macrocyclic oxindoles.
Thus, the required bis(diazooxindole) 4a was synthesized using
2 equiv of 3-diazooxindole and 1,4-dibromobutane in the presence
of a catalytic amount of tetrabutylammonium iodide as phase
transfer catalyst. Treatment of bis(diazo amide) 4a and 1,3-pro-
panediol in the presence of 1 mol % of Rh2(OAc)4 led to the inter-
esting macrocyclic oxindole14 5a in 75% yield via the double O–H
insertion methodology using DCM/DMF (50:2) solvent system.
There was the possibility for the formation of a mixture of two dia-
stereomers, but we obtained only one diastereomer based on the
crude 1H NMR spectrum. The structure of macrocycle 5a was also
confirmed using single-crystal X-ray analysis (Fig. 1). Interestingly,
the crystal structure analysis revealed that the C2-symmetry hav-
ing Ha,Hb protons is in anti-fashion.
Having validated our strategy toward the synthesis of a macrocy-
clic oxindole via O–H insertion methodology, attention then turned
in assessing the feasibility of various ring sizes. Hence, the reactions
of bis(diazo amides) 4a–b and aliphatic dihydroxy compounds 2
were performed in the presence of rhodium(II) acetate catalyst. All
these reactions successfully yielded the corresponding macrocyclic
oxindoles14 5b–d. We have chosen benzene-1,2-dimethanol instead
of aliphatic dihydroxy compound to yield macrocycle 5e in 65%
yield. The anti-stereochemistry is tentatively assigned for other
macrocycles based on the structure of 5a. It is notable that the
product due to the dimerization of diazo groups was not observed.
This methodology represents the synthesis of macrocycles incorpo-
rating indole units in a diastereoselective manner. The reason for the
diastereoselectivity might be the second O–H insertion reaction
preferred to form only the thermodynamically more stable
C2-symmetric macrocyclic system (Scheme 2, Table 2).
We further extended our studies to the double O–H insertion
reaction methodology using dihydroxy compound having the aro-
maticspacer. Thus, thereactionofcyclicdiazoamide1aand1,4-ben-
zenedimethanol in DCM/DMF (50:2) in the presence of Rh2(OAc)4
furnished the corresponding double O–H insertion product 3q. Reac-
tions of other diazo amides 1 were performed under a similar exper-
imental condition to afford the corresponding insertion products
3r–t (entries r–t, Scheme 1, Table 1). Furthermore, we embarked
on the synthesis of bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems
using the readily available 1,5-decalinediol. Similar experimental
condition was used for the successful acquisition of products 3u–x
with the prolonged reaction time (entries u–x, Scheme 1, Table 1).
All the above reactions were completed in less than an hour (Ta-
ble 1) at room temperature in a facile manner to afford the bis(3-
oxy-1,3-dihydro-2H-indol-2-one) systems 3. An excess amount of
N2
X
O
+
OH
HO
N
R
2
1a; R = methyl
1b; R = benzyl
1c; R = allyl
Rh2(OAc)4
1d; R = propargyl
CH2Cl2:DMF(50:2), rt
5
4
5'
4'
6
H
3
2
H
6'
7'
O
O
3a
3'a
X
3'
7
7a N1
R
7'a
N
2'
O
O
1' R
3
Scheme 1. Intermolecular double O–H insertion reaction of diazo amides with
various dihydroxy compounds.
Table 1
Reactions of cyclic diazo amides 1a–d with dihydroxy compounds 2
Entry
R
Spacer (X)
Reaction time (min)
Yield of 3a (%)
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
CH3
CH3
CH3
CH3
CH2Ph
CH2Ph
CH2Ph
CH2Ph
Allyl
–CH2CH2–
10
12
15
10
10
12
10
05
10
15
10
12
15
12
10
10
32
38
35
36
40
44
48
40
82
80
84
86
84
80
75
78
75
78
74
72
73
80
82
76
75
77
70
75
68
70
65
75
–CH2CH2CH2–
–CH2(CH2)2–CH2–
–CH2(CH2)4–CH2–
–CH2CH2–
–CH2CH2CH2–
–CH2(CH2)2–CH2–
–CH2(CH2)4–CH2–
–CH2CH2–
–CH2CH2CH2–
–CH2(CH2)2–CH2–
–CH2(CH2)4–CH2–
–CH2CH2–
–CH2CH2CH2–
–CH2(CH2)2–CH2–
–CH2(CH2)4–CH2–
–o-Xylenyl–
–o-Xylenyl–
–o-Xylenyl–
–o-Xylenyl–
1,5-Decalenyl
1,5-Decalenyl
1,5-Decalenyl
1,5-Decalenyl
Allyl
Allyl
Allyl
Propargyl
Propargyl
Propargyl
Propargyl
CH3
CH2Ph
Allyl
Propargyl
CH3
s
t
u
v
w
x
CH2Ph
Allyl
Propargyl
a
Yields (unoptimized) refer to isolated and chromatographically pure com-
pounds 3.
Figure 1. ORTEP view of compound 5a.

3796
S. Muthusamy, P. Srinivasan / Tetrahedron Letters 50 (2009) 3794–3797
5. Casanova, R.; Reichstein, T. Helv. Chim. Acta 1950, 33, 417.
N2
N2
N
6. Paulissen, R.; Reimlinger, H.; Hayez, E.; Hubert, A. J.; Teyssié, P. Tetrahedron Lett.
1973, 37, 2233.
X
O
O
7. (a) Jones, K.; Toutounji, T. Tetrahedron 2001, 57, 2427; (b) Kettle, J. G.; Faull, A.
W.; Fillery, S. M.; Flynn, A. P.; Hoyle, M. A.; Hudson, J. A. Tetrahedron Lett. 2000,
41, 6905; (c) Shi, G.-Q.; Cao, Z.-Y.; Cai, W.-L. Tetrahedron 1995, 51, 5011.
8. (a) Muthusamy, S.; Gnanaprakasam, B. Tetrahedron Lett. 2008, 49, 475; (b)
Muthusamy, S.; Gnanaprakasam, B. Tetrahedron Lett. 2007, 48, 6821; (c)
Muthusamy, S.; Krishnamurthi, J. Tetrahedron Lett. 2007, 48, 6692; (d)
Muthusamy, S.; Gnanaprakasam, B.; Suresh, E. Org. Lett. 2005, 7, 4577; (e)
Muthusamy, S.; Krishnamurthi, J.; Nethaji, M. Chem. Commun. 2005, 3862; (f)
Muthusamy, S.; Gunanathan, C.; Nethaji, M. J. Org. Chem. 2004, 69, 5631.
9. (a) Muthusamy, S.; Gunanathan, C. Synlett 2002, 1783; (b) Muthusamy, S.;
Gunanathan, C.; Babu, S. A.; Suresh, E.; Dastidar, P. Chem. Commun. 2002, 824.
10. Cava, M. P.; Little, R. L.; Naipier, D. R. J. Am. Chem. Soc. 1958, 80, 2257.
11. General procedure for the synthesis of bis(3-alkoxyoxindoles) 3: 1.0 mol % of
Rh2(OAc)4 was added to a stirred solution of diazo amides 1 (3 mmol) and
OH OH
N
( )n
4a, n = 1; 4b, n = 2
2
Rh2(OAc)4 CH2Cl2/DMF
50:2, rt
O
X
O
N
Ha
Hb
O
O
N
( )n
dihydroxy compounds
2 (1.0 mmol) in a freshly distilled 50 mL of dry
dichloromethane. To this solution, 2 mL of freshly prepared dry DMF
(distilled over CaH2, stored over 5 Å molecular sieves under the argon
balloon) was added for the better solubility of dihydroxy compounds. The
reaction was monitored by TLC. After completion of the reaction, the solvent
was evaporated under reduced pressure and the residue was purified by flash
column chromatography over silica gel.
5
Scheme 2. Synthesis of macrocyclic oxindoles via double O–H insertion reaction
methodology.
All new compounds exhibited spectral data consistent with their structures.
Selected spectral
dihydro-2H-indol-2-one) (3a): Red thick oil. IR (CH2Cl2): 2935, 1716, 1614,
1493, 1470, 1421, 1374, 1265, 1093, 1024, 896, 738 cmꢀ1 1H NMR (200 MHz,
data: 3,30-[Ethane-1,2-diylbis(oxy)]bis(1-methyl-1,3-
Table 2
.
Reactions of bis(diazo amides) 4 with dihydroxy compounds 2
CDCl3): d 3.16 (6H, s, N–CH3), 3.88–4.11 (4H, m, OCH2), 4.98 (2H, s, OCH), 6.79
(2H, d, J = 7.3 Hz), 7.07 (2H, t, J = 7.5 Hz), 7.33 (2H, t, J = 7.4 Hz), 7.44 (2H, d,
J = 7.2 Hz). 13C NMR (50.3 MHz, CDCl3): d 26.6 (CH3), 68.8 (CH2), 68.0 (CH2),
76.5 (CH), 108.8 (CH), 125.6 (quat-C), 126.1 (CH), 130.1 (CH), 144.8 (quat-C),
175.1 (quat-C). MS: m/z = 352 (M+). Anal. Calcd for C20H20N2O4: C, 68.17; H,
5.72; N, 7.95. Found: C, 68.41; H, 5.70; N, 7.96. 3,30-[Hexane-1,6-
diylbis(oxy)]bis(1-methyl-1,3-dihydro-2H-indol-2-one) (3d): Yellow solid.
Mp 109–111 °C (hexane/CHCl3). IR (KBr): 2932, 1715,1614, 1493, 1469, 1373,
Entry
n
X
Reaction time (min)
Yield of 5a (%)
a
b
c
d
e
2
2
1
1
1
–(CH2)2–
–CH2–
–(CH2)4–
–(CH2)6–
p-Xylenyl
40
44
45
48
55
75
78
70
72
65
1350, 1264, 1113, 1046, 739 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.31–1.42 (4H,
.
a
Yields (unoptimized) refer to isolated and chromatographically pure com-
m), 1.55–1.66 (4H, m), 3.16 (6H, s, N–CH3), 3.53–3.63 (2H, m, OCH2), 3.71–3.82
(2H, m, OCH2), 5.05 (2H, s, OCH), 6.79 (2H, d, J = 7.6 Hz), 7.07 (2H, t, J = 7.2 Hz),
7.28–7.39 (4H, m). 13C NMR (50.3 MHz, CDCl3): d 26.4 (CH2), 26.6 (N–CH3), 30.4
(CH2), 69.5 (OCH2), 76.5 (OCH), 108.9 (CH), 123.5 (CH), 125.8 (CH), 125.9 (quat-
C), 130.5 (CH), 144.9 (quat-C), 175.3 (quat-C). MS: m/z = 408 (M+, 15.6), 190
(3.5), 162 (100), 146 (63), 91 (12.8). Anal. Calcd for C24H28N2O4: C, 70.57; H,
6.91; N, 6.86. Found: C, 70.73; H, 6.94; N, 6.87. 3,30-[Propane-1,3-
diylbis(oxy)]bis(1-allyl-1,3-dihydro-2H-indol-2-one) (3j): Red thick oil. IR
pounds 5.
In conclusion, we have demonstrated a facile double O–H inser-
tion reaction methodology using the diazo amides in the presence
of rhodium(II) acetate catalyst. This approach furnished an assort-
ment of prototype bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems
by forming two C–O bonds in a single synthetic step. This facile
double O–H insertion reaction protocol was successfully applied
to synthesize several C2-symmetric macrocycles with oxindole
units incorporated in a diastereoselective manner. Further study
to find the reason for the high diastereoselectivity is in progress.
(CH2Cl2): 2987, 1723 1613, 1489, 1468, 1362, 1265, 1182, 1107, 742 cmꢀ1
.
1H NMR (200 MHz, CDCl3): d 1.91 (2H, t, J = 6.1 Hz), 3.67–3.74 (2H, m, OCH2),
3.81–3.88 (2H, m, OCH2), 4.15–4.30 (4H, m, N–CH2), 4.84 (2H, s, OCH), 5.11–
5.28 (4H, m, C = CH2), 5.67–5.81 (2H, m, CH = C), 6.26 (2H, d, J = 7.6 Hz), 7.08
(2H, t, J = 7.1 Hz), 7.21–7.33 (4H, m). 13C NMR (50.3 MHz, CDCl3): d 21.3 (CH2),
42.5 (N–CH2), 66.1 (OCH2), 66.2 (OCH2), 76.3 (OCH), 109.6 (CH), 118.1 (CH2),
123.2 (CH), 125.6 (quat-C), 125.8 (CH), 130.1 (CH), 131.6 (CH), 134.3 (quat-C),
174.7 (quat-C). MS: m/z = 418 (M+). Anal. Calcd for C25H26N2O4: C, 71.75; H,
6.26; N, 6.69. Found: C, 71.59; H, 6.27; N, 6.67. 3,30-[1,4-
Phenylenebis(methyleneoxy)])]bis(1-methyl-1,3-dihydro-2H-indol-2-one)
(3q): Red solid. Mp 137–139 °C (hexane/CHCl3). IR (KBr): 2936, 1713, 1613,
Acknowledgments
1493, 1470, 1374, 1350, 1264, 1108, 1052, 753 cmꢀ1 1H NMR (200 MHz,
.
CDCl3): d 3.17 (6H, s, N–CH3), 4.83 (2H, s, OCH), 4.90 (4H, d, J = 14.8 Hz), 6.80
(2H, d, J = 7.8 Hz), 7.07 (2H, t, J = 7.6 Hz), 7.27–7.43 (8H, m). 13C NMR
(50.3 MHz, CDCl3): d 26.6 (N–CH3), 71.1 (O–CH2), 75.3 (OCH), 108.9 (CH),
123.5 (CH), 123.2 (CH), 125.9 (CH), 127.6 (quat-C), 129.0 (CH), 130.5 (CH),
137.8 (quat-C), 144.8 (quat-C), 175.3 (quat-C). MS: m/z = 428 (M+). Anal. Calcd
for C26H24N2O4: C, 72.88; H, 5.65; N, 6.54. Found: C, 72.69; H, 5.64; N, 6.55.
12. Kulkowit, S.; McKervey, M. A. J. Chem. Soc., Chem. Commun. 1981, 616.
13. (a) Hu, W.; Timmons, D. J.; Doyle, M. P. Org. Lett. 2002, 4, 901; (b) Doyle, M. P.;
Hu, W. Synlett 2001, 1364; (c) Davies, H. M. L.; Townsend, R. J. J. Org. Chem.
2001, 66, 6595.
This research was supported by the Department of Science and
Technology, New Delhi. We thank DST, New Delhi and AvH founda-
tion, Germany for NMR and IR facilities, respectively. We thank Dr.
E. Suresh for the X-ray analysis. P.S. thanks CSIR, New Delhi, for a
fellowship.
References and notes
14. General procedure for the synthesis of macrocycles 5: 1.0 mol % of Rh2(OAc)4 was
added to a stirred solution of bis(diazo amides) 4 (1.0 mmol) and dihydroxy
compounds 2 (1.0 mmol) in a freshly distilled 50 mL of dry dichloromethane
and 2 mL of dry DMF at room temperature under nitrogen atmosphere. The
reaction was monitored by TLC. After completion of the reaction, the solvent
was evaporated under reduced pressure and the residue purified by flash
column chromatography over silica gel. All new compounds exhibited spectral
data consistent with their structures. 5a: IR (CH2Cl2): 3064, 2929, 2871, 1710
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds from Cyclopropanes to Ylides; Wiley
Interscience: New York, 1998.
2. (a) Muthusamy, S.; Krishnamurthi, J.. In Topics in Hetereocyclic Chemistry;
Hassner, A., Ed.; Springer, 2008; Vol. 12, pp 147–192; (b) Mehta, G.;
Muthusamy, S. Tetrahedron 2002, 58, 9477; (c) Davies, H. M. L.; Beckwith, R.
E. J. Chem. Rev. 2003, 103, 2861; (d) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998,
98, 911; (e) Padwa, A.; Weingarten, M. D. Chem. Rev 1996, 96, 223; (f) Ye, T.;
McKervey, M. A. Chem. Rev 1994, 94, 1091; (g) Doyle, M. P. Chem. Rev. 1986, 86,
919.
1611, 1486, 1466, 1351, 1299, 1222, 1159, 1116, 1093, 1048, 732, 699 cmꢀ1 1H
.
NMR (200 MHz, CDCl3): d 1.58–1.48 (4H, m), 1.75–1.67 (4H, m), 2.75–2.70 (2H,
m), 3.33–3.27 (4H, m), 3.98–3.91 (2H, m), 4.84 (2H, s, OCH), 6.76 (2H, d,
J = 7.6 Hz), 7.02 (2H, t, J = 7.6 Hz), 7.32–7.25 (4H, m). 13C NMR (50.3 MHz,
CDCl3): d 24.7 (CH2), 25.4 (CH2), 39.5 (N–CH2), 63.9 (OCH2), 75.5 (OCH), 108.8
(CH), 122.9 (CH), 124.3 (quat-C), 125.9 (CH), 130.1 (CH), 143.6 (quat-C), 174.9
(C = O). MS: m/z = 406 (M+). Anal. Calcd for C24H26N2O4: C, 70.92; H, 6.45; N,
6.89. Found: C, 70.97; H, 6.38; N, 6.92. X-ray Crystal data for compound 5a.
3. For an excellent review on O–H insertion reactions: Miller, D. J.; Moody, C. J.
Tetrahedron 1995, 51, 10811.
4. (a) Liu, B.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 12616; (b) Maier,
T. C.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 4594; (c) Jiang, N.; Wang, J.; Chan, A.
S. C. Tetrahedron Lett. 2001, 42, 8511; (d) Cenini, S.; Cravotto, G.; Giovenzana, G.
B.; Palmisano, G.; Penoni, A.; Tollari, S. Tetrahedron Lett. 2002, 43, 3637; (e)
Jiang, N.; Wang, J.; Chan, A. S. C. Tetrahedron Lett. 2001, 42, 8511; (f) Creger, P. L.
J. Org. Chem. 1965, 30, 3610.
3
ꢀ
C24H26N2O4, M = 406.47, 0.30 ꢁ 0.24 ꢁ 0.12 mm , triclinic, P1, a = 7.8002(14) Å,
b = 11.382(2) Å, c = 12.097(2) Å,
a = 94.574(3)°, b = 90.416(3)°, c = 101.248(3)°,
V = 1049.7(3) Å3, T = 293(2) K, R1 = 0.0766, wR2 = 0.1927, on observed data,

S. Muthusamy, P. Srinivasan / Tetrahedron Letters 50 (2009) 3794–3797
3797
z = 2, Dcalcd = 1.286 mg/m3, F(0 0 0) = 432, absorption coefficient = 0.091 mmꢀ1
k = 0.71073 Å, 7575 reflections were collected on a Bruker Smart Apex CCD
,
71.44; H, 6.68; N, 6.61. 5d: IR (CH2Cl2): 2931, 1719, 1614, 1467, 1260, 1237,
1198, 1168, 1091, 1025, 908, 751 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.63–1.14
.
spectrometer, 3679 observed reflections (I > 2
r
(I)). The largest difference peak
(12H, m), 2.21–2.08 (2H, m), 3.37–3.46 (4H, m), 3.75–3.64 (2H, m), 4.09–3.98
(2H, m), 4.89 (2H, s, OCH), 6.89 (2H, d, J = 7.6 Hz), 7.09 (2H, t, J = 6.8 Hz), 7.35–
7.27 (2H, m), 7.43 (2H, d, J = 7.6 Hz). 13C NMR (50.3 MHz, CDCl3): d 19.2 (CH2),
24.9 (CH2), 25.6 (CH2), 28.0 (CH2), 29.2 (CH2), 36.6 (CH2), 67.7 (OCH2), 75.2
(OCH), 108.2 (CH), 122.9 (CH), 125.4 (quat-C), 125.9 (CH), 130.0 (CH), 143.2
(quat-C), 174.6 (C = O). MS: m/z = 448 (M+). Anal. Calcd for C27H32N2O4: C,
72.30; H, 7.19; N, 6.25. Found: C, 72.24; H, 7.21; N, 6.32. Compound 5e: IR
(CH2Cl2): 3431, 3059, 2925, 2852, 1712, 1612, 1488, 1467, 1298, 1188, 1169,
and hole = 0.533 and ꢀ0.349 eAꢀ3, respectively. Crystallographic data for this
compound have been deposited15 with the Cambridge Crystallographic Data
Center as supplementary publication number CCDC 711953. Compound 5b: IR
(CH2Cl2): 3064, 2929, 2866, 1707, 1613, 1487, 1466, 1349, 1214, 1161, 1087,
965, 876, 750, 732, 700, 651 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.60–1.53 (2H,
.
m), 1.75–1.67 (4H, m), 1.92–1.88 (2H, m), 3.57–3.33 (2H, m), 3.77–3.75 (2H,
m), 3.99–3.96 (2H, m), 4.68 (2H, s, OCH), 6.79 (2H, d, J = 7.6 Hz), 7.07 (2H, t,
J = 7.6 Hz), 7.35–7.27 (4H, m). 13C NMR (50.3 MHz, CDCl3): d 25.6 (CH2), 30.1
(CH2), 39.4 (CH2), 63.5 (OCH2), 74.4 (OCH), 108.5 (CH), 122.9 (CH), 125.1 (quat-
C), 126.1 (CH), 130.1 (CH), 144.2 (quat-C), 174.6 (C@O). MS: m/z = 392 (M+).
Anal. Calcd for C23H24N2O4: C, 70.39; H, 6.16; N, 7.14. Found: C, 70.31; H, 6.18;
N, 7.17. Compound 5c: IR (CH2Cl2): 3064, 2934, 2872, 1712, 1613, 1466, 1360,
1092, 1053, 759, 700 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.36–1.26 (2H, m),
.
3.76–3.71 (4H, m), 4.74 (2H, s, OCH), 5.00–4.86 (4H, m, benzylic-H), 6.78–6.75
(2H, m), 7.07 (2H, t, J = 7.6 Hz), 7.44–7.24 (8H, m). 13C NMR (50.3 MHz, CDCl3):
d 25.2 (CH2), 37.7 (CH2), 66.5 (OCH2), 74.5 (OCH), 108.7 (CH), 123.2 (CH), 125.7
(CH), 127.9 (CH), 129.2 (CH), 129.7 (CH), 129.9 (CH), 130.2 (CH), 130.4 (CH),
134.8 (quat-C), 140.8 (quat-C), 142.9 (quat-C), 174.8 (C = O). MS: m/z = 440
(M+). Anal. Calcd for C27H24N2O4: C, 73.62; H, 5.49; N, 6.36. Found: C, 73.67; H,
5.55; N, 6.31.
1297, 1181, 1168, 1050, 750, 698 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.63–1.23
.
(8H, m), 2.15–2.11 (2H, m), 3.50–3.41 (4H, m), 3.73–3.69 (2H, m), 4.06–4.00
(2H, m), 4.81 (2H, s, OCH), 6.85 (2H, d, J = 7.6 Hz), 7.08 (2H, t, J = 6.8 Hz), 7.35–
7.31 (2H, m), 7.45 (2H, d, J = 7.6 Hz). 13C NMR (50.3 MHz, CDCl3): d 24.3 (CH2),
27.0 (CH2), 29.6 (CH2), 37.4 (CH2), 67.0 (OCH2), 74.9 (OCH), 108.3 (CH), 122.9
(CH), 125.2 (quat-C), 125.9 (CH), 129.9 (CH), 143.8 (quat-C), 174.9 (C = O). MS:
m/z = 420 (M+). Anal. Calcd for C25H28N2O4: C, 71.41; H, 6.71; N, 6.66. Found: C,
15. Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 IEZ, UK {fax: +44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk}.