Morita-Baylis-Hillman reactions between conjugated nitroalkenes or nitrodienes and carbonyl compounds

Article abstract of DOI:10.1002/ejoc.200900475

Morita-Baylis-Hillman (MBH) reactions between conjugated nitroalkenes or nitrodienes and various carbonyl compounds such, as glyoxylate, trifluoropyruvate, pyruvaldehyde, oxomalonate, ninhydrin, and formaldehyde have been extensively investigated. The rea

Full text of DOI:10.1002/ejoc.200900475

FULL PAPER
DOI: 10.1002/ejoc.200900475
Morita–Baylis–Hillman Reactions Between Conjugated Nitroalkenes or
Nitrodienes and Carbonyl Compounds
Indubhusan Deb,[a] Pramod Shanbhag,[a] Shaikh M. Mobin,[b] and
Irishi N. N. Namboothiri*[a]
Dedicated to Professor D. Basavaiah[‡]
Keywords: Alkenes / α-Hydroxyalkylation / C–C coupling / Nitroalkenes / Morita–Baylis–Hillman (MBH) reaction / Syn-
thetic methods
Morita–Baylis–Hillman (MBH) reactions between conjugated
nitroalkenes or nitrodienes and various carbonyl compounds
such as glyoxylate, trifluoropyruvate, pyruvaldehyde, oxo-
malonate, ninhydrin, and formaldehyde have been exten-
sively investigated. The reactions proceeded smoothly in the
presence of DMAP (40–100 mol-%) in acetonitrile and in
some cases also in that of imidazole (100 mol-%) in CHCl3 or
THF, to provide the multifunctional adducts in good to excel-
lent yields. The reactions catalyzed by DMAP in acetonitrile
were superior to the imidazole-catalyzed reactions both in
terms of the rate of reaction and in terms of the isolated yields
of the MBH adducts. The catalytic roles played by DMAP
lysts such as DABCO, are attributed primarily to resonance
stabilization of the initial zwitterionic intermediates.
Whereas the E isomers are the major or exclusive products
in the cases of glyoxylate, pyruvaldehyde, and formalde-
hyde, the Z isomers predominate in the cases of trifluoropy-
ruvate and ninhydrin. Interestingly, oxomalonate forms E iso-
mers with aromatic nitroalkenes and Z isomers with aliphatic
ones. These selectivities and the formation of unusual decon-
jugated products in the case of certain β-alkyl-nitroethylenes
have been explained.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
and imidazole in these reactions, vis-à-vis other MBH cata- Germany, 2009)
as aldehydes, activated ketones/imines/alkenes/azo com-
Introduction
pounds, and iminium salts have been successfully employed
The Morita–Baylis–Hillman (MBH) reaction[1,2] has
emerged in recent years as an attractive strategy for the
quick generation of multifunctional molecules and as a key
step in syntheses of complex bioactive natural products and
designed molecules.[3] The method involves introduction of
a substituent at the α-position of an activated alkene in a
one-pot, room-temperature, and atom-economical fashion
through the Lewis base mediated reaction between an acti-
vated alkene and a carbon- or heteroatom-centered electro-
phile.[4] Various activated alkenes such as enones, enals, ac-
rylates, acrylamides, acrylonitrile, and vinyl sulfoxides/sulf-
ones/sulfonates/phosphonates, as well as electrophiles such
in MBH reactions.[3]
Numerous amines, phosphanes, and other nucleophilic
Lewis bases have been found to catalyze MBH reactions.[3]
Substantial rate acceleration for this eminently sluggish re-
action has been achieved through addition of co-catalysts
and application of new reaction media and conditions.[5]
Recent successes in the intramolecular[6] and asymmetric[7]
versions of this reaction has further transformed it into a
reaction of exceptional topical interest.
Although several activated alkenes, as mentioned above,
have been employed as substrates in MBH reactions, conju-
gated nitroalkenes have not received much attention until
recently. This is despite the fact that Baylis and Hillman, in
their patent, reported the synthesis of α-hydroxyethylated
nitroethylene through the reaction between nitroethylene
and acetaldehyde in the presence of DABCO.[2] The fact
that the superior Michael acceptor abilities of nitroalkenes
[a] Department of Chemistry, Indian Institute of Technology Bom-
bay
Mumbai 400076, India
Fax: +91-22-2572-3480
E-mail: irishi@iitb.ac.in
[b] National Single Crystal X-ray Diffraction Facility, Indian Insti-
tute of Technology Bombay
have been extensively investigated in recent decades[8,9]
–
Mumbai 400076, India
E-mail: xray@chem.iitb.ac.in
and that the first step in the MBH reaction is the Michael-
type addition of the catalyst[4] – has also not evoked suf-
ficient interest for nitroalkenes to have become widely em-
ployed as substrates in MBH reactions.
[‡] On account of his pioneering contributions to Morita–Baylis–
Hillman chemistry
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900475.
Eur. J. Org. Chem. 2009, 4091–4101
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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FULL PAPER
In the above scenario, our endeavors to achieve reactions
between nitroalkenes and various electrophiles such as
formaldehyde,[10–11] activated carbonyl compounds[12]
/
imines[13]/alkenes,[14] and azodicarboxylates[15] in the pres-
ence of imidazole or DMAP as the catalyst have met with
success in recent years. The anti-cancer activities exhibited
by many MBH adducts of nitroalkenes at low micromolar
concentrations, through targeting of tubulins/microtu-
bules,[11,13,14] and the potential application of MBH adducts
as valuable intermediates in the synthesis of amino alcohols,
amino acids, and heterocycles encouraged us to expand the
scope of the MBH reaction by introducing aliphatic nitro-
alkenes and aromatic nitrodienes as substrates for the first
time. This report is the full version of our preliminary com-
munication relating to the reactions between aromatic ni-
troalkenes and various activated non-enolizable carbonyl
compounds.[12] The well-documented reactivities of acti-
vated aldehydes[16] and activated ketones[17–19] as electro-
philes with various activated alkenes such as vinyl ketones,
acrylates, and acrylonitrile also encouraged us to investigate
the reactivities of such electrophiles with conjugated nitro-
alkenes in detail.
Scheme 1.
Our optimization studies suggested that both DMAP
(40 mol-%) and imidazole (100 mol-%) would be suitable
catalysts for this reaction.[12] Whereas acetonitrile was
found to be the best solvent for the DMAP-catalyzed reac-
tion, both chloroform and THF were suitable for the imid-
azole-catalyzed reaction.
It is important to note that, whereas the DMAP-cata-
lyzed reactions required only Յ30 min for completion, the
imidazole-catalyzed reactions were slower, requiring up to
48 h (Table 1). In general, aromatic nitroalkenes 1a–e re-
acted with ethyl glyoxylate (2) to provide the MBH adducts
3a–e in excellent yields under all conditions tested (En-
tries 1–5), particularly with DMAP as the catalyst [En-
tries 1(a)–5(a), Table 1]. Whereas the yields of MBH ad-
ducts 3h–i derived from nitroalkenes 1h–i were low to mod-
erate under all three sets of conditions (Entries 8–9), other
aromatic (1f–g and 1j–l, Entries 6–7 and 10–12, respec-
Results and Discussion
Reactions between various carbonyl electrophiles and tively) and heteroaromatic (1n–r, Entries 13–17) nitro-
aromatic or heteroaromatic nitroalkenes were investigated alkenes delivered the MBH adducts in moderate to good
by initially taking 4-methoxy-α-nitrostyrene (1a) as the yields (Table 1).
model substrate and ethyl glyoxylate (2) as the model elec-
The E geometries of the glyoxylate adducts 3 were con-
trophile (Scheme 1).
firmed by detailed NMR analysis and X-ray crystallogra-
Table 1. MBH reactions between nitroalkenes 1a–r and ethyl glyoxylate (2)[a] in the presence variously of DMAP in CH3CN or of
imidazole in CHCl3 or THF at room temperature.
Entry
1
Ar
DMAP/CH3CN (a)
Time
Imidazole/CHCl3 (b)
Time
Imidazole/THF (c)
Time
Yield [%][b]
Yield [%][b]
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
a
b
c
d
e
f
g
h
i
j
k
l
n
o
p
q
r
4-MeOC6H4
2,4-(MeO)2C6H3
2,5-(MeO)2C6H3
4-Me2NC6H4
3,4-(MeO)2C6H3
3,4-(OCH2O)C6H3
3-MeO-4-HOC6H3
4-ClC6H4
10 min
5 min
5 min
81
95
99
98
89
65
60
45
33
52
69
90
63
64
60
60
65
3 h
13 h
7 h
24 h
7 h
10 h
30 h
24 h
5 h
2 h
2 h
8 h
7 h
73
80
78
83
72
50
49
38
31
52
62
65
67
68
60
68
55
16 h
33 h
30 h
36 h
14 h
24 h
48 h
40 h
21 h
23 h
25 h
20 h
25 h
30 h
5 h
68
70
71
80
65
50
40
43
25
48
53
55
65
65
55
76
48
20 min
10 min
15 min
10 min
15 min
30 min
15 min
20 min
10 min
5 min
Ph
2-propargyloxyC6H4
2-allyloxyC6H4
3,4,5-(OMe)3C6H2
2-furyl
2-thienyl
3-furyl
3-thienyl
3-indolyl
5 min
6 h
6 h
6 h
8 h
10 min
20 min
30 min
8 h
15 h
[a] 4 equiv. as 50% solutions in toluene both for DMAP- and for imidazole-catalyzed reactions. [b] Isolated yields of 3 after silica gel
column chromatography. The low to moderate yields in some cases are presumably due to polymerization of nitroalkenes. No other side
reactions were observed in any of the cases.
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Morita–Baylis–Hillman Reactions of Conjugated Nitroalkenes and Nitrodienes
Table 2. MBH reactions between nitroalkenes 1 and aldehydes 4a–c[a] in the presence either of DMAP in CH3CN or of imidazole in
CHCl3 at room temperature.
Entry
1
Ar
4
R
5
DMAP/CH3CN (a)
Time
Imidazole/THF (b)
Time
Yield [%][b]
Yield [%][b]
1
2
3
4
5
6
7
a
a
b
c
n
p
a
4-MeOC6H4
4-MeOC6H4
2,4-(MeO)2C6H3
2,5-(MeO)2C6H3
2-furyl
3-furyl
4-MeOC6H4
a
b
b
b
b
b
c
H
a
b
c
d
e
f
7 d
2 d
2 d
2 d
2 d
2 d
7 d
–
7 d
2 d
2 d
2 d
2 d
2 d
7 d
–
CH3
CH3
CH3
CH3
CH3
Ph
26 (50)
32 (50)
30 (40)
33 (40)
35 (25)
–
20 (52)
30 (35)
28 (30)
25 (45)
36 (35)
–
g
[a] 4 equiv. for both DMAP- and imidazole-catalyzed reactions. [b] Isolated yields of 5 after silica gel column chromatography; amount
(%) of recovered 1 in parentheses.
phy. In general, for compounds 3a–l and 3n–r, the styrenic trifluoropyruvate 6c was treated with various aromatic (1a,
protons appeared as singlets in the δ = 8.00–8.70 ppm range 1c–d) and heteroaromatic (1p) nitroalkenes in the presence
(Table S1, Supporting Information). Further, the NOE in- of DMAP as the catalyst (Table 3). Although low yields and
teraction between the aromatic protons and the CH part of prolonged reaction times were encountered when only
the CHOH group and the absence of any such interaction 40 mol-% of DMAP was used as the catalyst (Entry 1,
between the styrenic proton and the CHOH group or the Table 3), increasing of the amount of the catalyst to
Et group in the representative compound 3d was indicative 100 mol-% not only reduced the reaction times, but also
of the E geometries of the styrenic double bonds in com- substantially improved the yields (Entries 1–4).
pounds 3. The structure and stereochemistry were further
unambiguously established by a single-crystal X-ray diffrac-
tion analysis of 3d.[12]
The above reaction conditions were also applied, with
minor modifications, to MBH reactions between nitro-
alkenes and other activated carbonyl compounds. Reactions
between various aromatic (1a–c) or heteroaromatic (1n–p)
nitroalkenes and activated aldehydes such as glyoxal (4a),
pyruvaldehyde (4b), and phenylglyoxal (4c) were therefore
investigated (Table 2). Interestingly, whereas glyoxal (4a)
and phenylglyoxal (4c) remained unreactive even after 7 d
(Entries 1 and 7), pyruvaldehyde (4b) reacted with aromatic
nitroalkenes 1a–c and heteroaromatic ones 1n–p to afford
the MBH adducts 5b–f in low to moderate yields (Table 2).
Although substantial amounts of nitroalkenes were reco-
vered from these reactions, the possible application of pyru-
valdehyde (4b) as an electrophile in the MBH reaction has
to the best of our knowledge been demonstrated here for
the first time.[20]
The E geometries of the double bonds in the MBH ad-
ducts 5b–f were confirmed by correlating the 1H NMR
chemical shifts of the styrenic protons with those of com-
pounds 3. As in the case of 3, the styrenic protons in 5b–f
appeared as singlets in the δ = 8.00–8.60 ppm range
(Table S2, Supporting Information).
Figure 1. α-Oxo esters.
Table 3. MBH reactions between nitroalkenes 1 and oxo ester 6c[a]
in the presence of DMAP in CH3CN at room temperature.
Entry
1
1
a
Ar
7
a
DMAP/CH3CN
Time
Yield [%][b]
4-MeOC6H4
2 d
3 h
4 h
10 h
30 min
40[c]
70[d]
71[d]
80[d,e]
63[d]
2
3
4
c
d
p
2,5-(MeO)2C6H3
4-Me2NC6H4
3-furyl
b
c
d
[a] 4 equiv. [b] Isolated yields of 7a–d after silica gel column
chromatography. [c] 40% of DMAP was used. [d] 100% of DMAP
was used. [e] 5% of 1d was recovered.
Our attempts to obtain reactions between oxo esters –
Unlike in the cases of the glyoxylate adducts 3 and the
namely, pyruvate 6a and phenylglyoxylate 6b (Figure 1) – pyruvaldehyde adducts 5, the styrenic protons of which res-
and various nitroalkenes in the presence of DMAP or imid- onated in the δ = 8.00–8.70 ppm range, the styrenic protons
azole as catalyst were unsuccessful. However, we were ple- of the MBH adducts of trifluropyruvates 7a–d were rela-
ased to observe the formation of MBH adducts 7a–d when tively shielded (δ = 7.20–7.90 ppm, Table S3, Supporting In-
Eur. J. Org. Chem. 2009, 4091–4101
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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I. Deb, P. Shanbhag, S. M. Mobin, I. N. N. Namboothiri
FULL PAPER
formation), suggesting that the geometries of their styrenic in other cases mixtures of E and Z isomers with preferences
double bonds could be Z. This was confirmed by a single- for the former (Entries 2 and 5, Table 4). The fact that that
crystal X-ray analysis of the representative compound 7c the major or the exclusive isomers could be the E isomers
(Table S4, Supporting Information).[21]
was verified by comparison of the 1H NMR chemical shifts
Treatment of various nitroalkenes with a ketone activated of the styrenic protons (Table S5, Supporting Information).
by two ester groups – namely, oxomalonate 8 – in the pres- This was further corroborated by a single-crystal X-ray
ence of DMAP as the catalyst led to the formation of the analysis of the representative compound 9a (Table S6, Sup-
MBH adducts 9–10 in moderate to good yields (Table 4). porting Information).
These reactions were complete in 20 min, and in some cases
Having succeeded in obtaining reactions between various
the products were single E isomers (Entries 1, 3, and 4) and nitroalkenes and open-chain multi-carbonyl compounds as
electrophiles, we turned our attention to cyclic multi-car-
bonyl compounds in anticipation that the strain inherent in
Table 4. MBH reactions between nitroalkenes 1 and diethyl oxo-
such compounds should make them react with nitroalkenes
malonate (8a) at room temperature in the presence of DMAP in
under the MBH conditions. We therefore examined the elec-
CH3CN.
trophilicity of ninhydrin (11), and we were pleased to isolate
the MBH adducts 12 and 13 in good yields in most cases
(Table 5). As in the reactions between nitroalkenes 1 and
glyoxylate 2 (Table 1), the reactions between 1 and ninhyd-
rin (11) were catalyzed both by DMAP and by imidazole.
As before, the DMAP-catalyzed reactions were also faster
in this case, providing the products in moderate to good
yields in Յ30 min [Entries 1(a)–9(a), Table 5]. On the other
Entry
1
Ar
9/10
DMAP/CH3CN
Time
Yield [%][b] (9/10)
hand, the imidazole-catalyzed reactions required 5–22 h for
completion. Nevertheless, greater selectivities in favor of the
E isomers were in many cases observed in the imidazole-
catalyzed reactions (Entries 1–3, 5 and 9, Table 5).
1
2
3
4
5
a
d
e
l
4-MeOC6H4
4-Me2NC6H4
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2
2-furyl
a
b
c
d
e
20 min
20 min
20 min
20 min
20 min
85 (100:0)
55 (78:22)
65 (100:0)
43 (100:0)
53 (71:29)[c]
Clear distinctions between the Z isomers 12 and the E iso-
1
mers 13 could be made on the basis of their IR, H NMR,
n
and 13C NMR characteristics. First of all, the IR peaks for
the OH groups in the Z isomers in general appeared at higher
frequencies (3404–3434 cm–1) than those in the E isomers
(3125–3370 cm–1, Supporting Information). The general
chemical shift range observed for the styrenic protons in the
[a] 4 equiv. [b] Isolated yield of 9 + 10 after silica gel column
chromatography. The diastereomeric ratios of products 9 and 10
were determined by 1H NMR spectroscopy. The moderate yields
in some cases are presumably due to polymerization of nitro-
alkenes. No other side reactions were observed in any cases. [c] In-
separable mixture.
Table 5. MBH reactions between nitroalkenes 1 and ninhydrin (11)[a] in the presence of DMAP in CH3CN and imidazole in THF at
room temperature.
Entry
1
Ar
DMAP/CH3CN (a)
Yield [%][b] (12/13)
Imidazole/CHCl3 (b)
Time
Time
Yield [%][b] (12/13)
1
2
3
4
5
6
7
8
9
a
d
h
i
k
m
n
o
p
4-MeOC6H4
4-Me2NC6H4
4-ClC6H4
Ph
2-allyloxyC6H4
2-O2NC6H4
2-furyl
15 min
2 h
64 (55:45)
53 (65:35)
43 (62:38)
49 (67:33)
71 (59:41)
75 (100:0)
78 (100:0)
72 (100:0)
64 (56:44)
22 h
24 h
20 h
16 h
9 h
6 h
5 h
63 (69:31)[c]
56 (79:21)[c]
55 (67:33)
59 (64:36)[c]
68 (63:37)
79 (100:0)
73 (100:0)
75 (100:0)
67 (69:31)
15 min
15 min
30 min
15 min
30 min
30 min
30 min
2-thienyl
3-furyl
6 h
5 h
[a] 3 equiv. for both DMAP- and imidazole-catalyzed reactions. [b] Isolated yield of 12 + 13 after purification by silica gel column
1
chromatography. The diastereomeric ratio of 12 and 13 was determined by H NMR spectroscopy. The moderate yields in some cases
are presumably due to polymerization of nitroalkenes. No other side reactions were observed in any of the cases. [c] Inseparable mixture.
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Morita–Baylis–Hillman Reactions of Conjugated Nitroalkenes and Nitrodienes
1H NMR spectra of the Z isomers was δ = 7.54–8.18 ppm,
The comparable chemical shifts (δ = 7.10 and 7.25 ppm)
whereas for the E isomers it was δ = 8.50–8.91 ppm (Table S7, observed for the olefinic protons in 16a and 16e, together
Supporting Information). In the 13C NMR spectra, the with the appearance of the olefinic proton signal in the
CHOH carbon atoms of the Z isomers resonated at higher minor isomer 17a at δ = 5.95 ppm, suggested the E geome-
field (δ = 75.9–76.9 ppm) than those of the E isomers (δ = tries for 16a and 16e (Table S1, Supporting Information).
1
1
76.9–78.3 ppm, Supporting Information). Since H,1H 2D- This was further confirmed by H,1H 1D-NOE examina-
NOESY experiments did not provide satisfactory results, the tion of 16a, in which irradiation of the CH in the CHOH
above assignment was unambiguously supported by a single- group caused an NOE enhancement of 8.3% for the signal
crystal X-ray analysis of the representative system 12p.[12]
of the allylic proton on the cyclohexane ring (see the Sup-
Encouraged by the results obtained from the reactions porting Information).
between β-aryl- and β-heteroaryl-nitroethylenes and various
carbonyl electrophiles such as glyoxylate 2, pyruvaldehyde
(4b), trifluoropyruvate 6c, oxomalonate 8 and ninhydrin
(11), we decided to investigate the reactivities of selected
β-alkyl-nitroethylenes 14a–d (Figure 2) with some of these
electrophiles.
In contrast with the formation of E isomers in the reac-
tions between 14a or 14b and glyoxylate 2, the Z isomers
17b and 17g were the major or exclusive products in the
reactions between 14a or 14b and trifluoropyruvate 6c (En-
tries 2 and 7, Table 6). The selectivities observed in these
cases were again consistent with those observed in the cases
of aromatic nitroalkenes 1 (see Table 3, see also Table S3,
1
Supporting Information, for correlation of the H NMR
chemical shifts of the β-H moieties). The structure of 17b
was confirmed by X-ray analysis (Table S8, Supporting In-
formation).
The reactions between 14a or 14b and oxomalonate 8
(Entries 3 and 8, Table 6) exhibited selectivity opposite to
that observed for the aromatic nitroalkenes 1 (see Table 4).
The DMAP- and imidazole-catalyzed reactions between ni-
troalkene 14a and oxomalonate 8 provided the MBH ad-
Figure 2. Aliphatic nitroalkenes.
Initially, 14a and 14b were screened for their reactivities ducts 16c + 17c in 80% and 53% yields, respectively, with
towards these electrophiles, as well as towards the smallest a common E/Z ratio of 28:72 (Entry 3, Table 6). The similar
carbonyl electrophile, formaldehyde (15, Table 6). Needless reactions between 14b and 8 afforded the MBH adducts 16h
to mention, the nitroalkenes 14a and 14b exhibited similar + 17h in 75% and 66% yields, respectively, with a common
reactivities towards the electrophiles we screened. Treat- E/Z ratio of 31:69 (Entry 8, Table 6). The E and Z geome-
1
ment of 14a or 14b with glyoxylate 2, for instance, provided tries for the two isomers were assigned from the H NMR
the E isomers 16a and 16e of the MBH adducts as the chemical shifts of the key olefinic protons in the two iso-
major or exclusive products (Entries 1 and 5, Table 6), as in mers. Whereas in the minor E isomers 16c and 16h, the
the case of the aromatic nitroalkenes 1 (see Table 1).
signals of the olefinic protons appeared at δ = 7.03 and
Table 6. MBH reactions between nitroalkenes 14a or 14b and various electrophiles[a] in the presence of DMAP in CH3CN and imidazole
in CHCl3 at room temperature.
Entry
14
R
Electrophile
R1
R2
16 + 17
DMAP/CH3CN (a)
Time
Imidazole/CHCl3 (b)
Time
Yield [%][b] (16/17)
Yield [%][b] (16/17)
1
2
3
4
5
6
7
8
9
a
a
a
a
b
b
b
b
b
Cy
Cy
Cy
Cy
iPr
iPr
iPr
iPr
iPr
2
6c
8
15
2
H
CF3
CO2Et
CO2Me
a
b
c
d
e
f
g
h
i
5 min
5 min
5 min
5 min
5 min
10 min
5 min
5 min
5 min
88 (92:8)
85 (3:97)
15 min
10 min
10 min
24 h
10 min
15 min
10 min
10 min
24 h
45 (92:8)
41 (3:97)
CO2Et CO2Et
H
H
H
CF3
CO2Et CO2Et
H
80 (28:72)[c]
61 (91:9)[d]
73 (100:0)[f]
40 (87:13)[c]
80 (0:100)
75 (31:69)[c]
45 (88:12)
53 (28:72)[c]
[e]
H
–
CO2Et
COMe
CO2Me
55 (100:0)[f]
35 (87:13)[c]
62 (0:100)
4b
6c
8
66 (31:69)[c]
[e]
15
H
–
[a] 4 equiv. for both DMAP- and imidazole-catalyzed reactions. [b] Isolated yield of 16 + 17 after silica gel column chromatography. The
diastereomeric ratio of 16 and 17 was determined by 1H NMR spectroscopy. The moderate yields observed in some cases are presumably
due to polymerization of nitroalkenes. No other side reactions were observed in any of the cases. [c] Inseparable mixture. [d] The major
isomer was isolated in pure form. [e] Complex mixture including substantial amount of starting material. [f] Crude 16e was acetylated
for the purpose of characterization, due to its instability.
Eur. J. Org. Chem. 2009, 4091–4101
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FULL PAPER
6.98 ppm, respectively, in the major Z isomers 17c and 17h 144.1 ppm, respectively, in 18b. The geometries of the
1
the signals of the olefinic protons appeared at δ = 6.15 and double bonds were confirmed to be E from the H NMR
6.14 ppm, respectively (Table S5, Supporting Information). spectra (J values for the olefinic protons of 12.8 Hz in 18a
Reactions between nitroalkenes 14a or 14b and formalde- and 11.4 Hz in 18b).
hyde (15) were feasible only with DMAP as the catalyst
It appears that the formation of unusual products of type
(Entries 4a and 9a, Table 6). The MBH adducts 16d + 17d 18a or 18b is observed only when oxomalonate 8 is used as
were isolated in 61% yield with an E/Z ratio of 91:9 (En- the electrophile. For instance, when trifluoropyruvate 6c
try 4a, Table 6). Similarly, 16i + 17i were isolated in moder- was treated with nitroalkene 14d under DMAP-catalyzed
ate yield (45%) with an E/Z ratio of 88:12 (Entry 9a, conditions, the only product isolated was the MBH adduct
Table 6). Surprisingly, the reactions between 14a or 14b and 19c, albeit in low yield (37%, Entry 3, Table 7).
formaldehyde (15) under the imidazole-catalyzed conditions
The formation of β,γ-unsaturated nitro compounds 18a
[Entries 4(b) and 9(b), Table 6] were not satisfactory. The E or 18b instead of the expected MBH adducts 19a or 19b in
stereochemistries were assigned for 16d and 16i from the the reactions between nitroalkenes 14c or 14d and oxoma-
fact that the olefinic protons in these major isomers (δ = lonate 8 (Entries 1–2, Table 7) can be interpreted in terms
7.09 and 7.05 ppm) were deshielded by ca. 1 ppm in relation of the two elimination pathways available to the zwitterionic
to those in the minor isomers 17d and 17i (δ = 5.96 and intermediate arising from addition of nitronate I to the elec-
5.93 ppm, Table S9, Supporting Information).
trophile 8 (Scheme 2). If the intermediate were to undergo
Finally, the reaction between nitroalkene 14b and pyru- elimination through α-hydrogen abstraction by the alk-
valdehyde (4b) provided the MBH adducts 16f + 17f in oxides, as shown in II, the product formed would be the
moderate yield [40%, Method (a) and 35%, Method (b)] α,β-unsaturated compound 19, which is not observed.[22]
with an E/Z ratio of 87:13 (Entry 6, Table 6). The styrenic On the other hand, elimination through γ-hydrogen ab-
proton in the E isomer 16f was deshielded by ca. 1.2 ppm straction by the alkoxide as shown in III would result in
relative to that in the Z isomer 17f (Table S2, Supporting the β,γ-unsaturated nitro compound 18, which is the only
Information).
product isolated. It is proposed that the γ-hydrogen abstrac-
The products formed in the MBH reactions discussed so tion by the alkoxide as shown in III is facilitated by the
far possess the double bond in conjugation with the nitro chair-like conformation adopted by III. Although such a
group. Interestingly, in the reactions between aliphatic ni- chair-like conformation might also be possible for the zwit-
troalkenes possessing γ-methylene groups, such as 14c or terionic intermediates arising from 14a or 14b, such a con-
14d, and oxomalonate 8, the β,γ-unsaturated nitro com- formation is either destabilized due to 1,3-diaxial interac-
pounds 18a and 18b were isolated instead of the expected tion as in IV or the γ-hydrogen atom is not appropriately
α,β-unsaturated nitro compounds (Table 7). This was con- oriented to undergo abstraction by the alkoxide as in V
firmed by 1H, 13C, and 13C-DEPT spectra (see the Support- (Scheme 3).
ing Information). Whereas the signals of the α- and β-pro-
Subsequent to our studies on the MBH reactions be-
tons (with respect to the NO2 group) overlapped (δ = 5.60– tween aromatic, heteroaromatic, or aliphatic nitroalkenes
1
5.80 ppm) in the H NMR spectra of 18a and 18b, the γ-H and various carbonyl electrophiles, similar reactions be-
protons each appeared as a ddd at δ = 6.00 ppm. This was tween the nitrodienes 20a–c (Figure 3),[23] prepared through
1
confirmed by a H,1H 2D-COSY experiment on 18b (see Henry reactions of substituted cinnamaldehydes, and se-
the Supporting Information). Analysis of the 13C NMR lected electrophiles such as glyoxylate 2, trifluoropyruvate
spectra of 18a and 18b with the aid of DEPT spectra fur- 6c, and formaldehyde (15) were investigated (Table 8).
ther confirmed the above assignment in that the α-, β-, and
As observed in previous instances, the DMAP-catalyzed
γ-methine carbon atoms appear at δ = 90.4, 115.7 and reactions were much faster than the imidazole-catalyzed re-
150.4 ppm, respectively, in 18a and at δ = 90.4, 118.2 and actions and provided the products in better yields, but there
Table 7. MBH reactions of nitroalkenes 14c or 14d and oxomalonate 8[a] in the presence of DMAP in CH3CN and imidazole in CHCl3
at room temperature.
Entry
14
R
6c, 8
E, R1
18/19
DMAP/CH3CN (a)
Yield [%][b] (18/19)
Imidazole/CHCl3 (b)
Time
Time
Yield [%][b] (18/19)
1
2
3
c
d
d
iPr
nPent
nPent
8
8
6c
CO2Et, Et
CO2Et, Et
CF3, Me
a
b
c
5 min
5 min
45 min
45 (100:0)
57 (100:0)
37 (0:100)[c]
5 min
5 min
–
40 (100:0)
48 (100:0)
[d]
–
[a] 4 equiv. for both DMAP- and imidazole-catalyzed reactions. [b] Isolated yield of 18 after silica gel column chromatography. The
moderate yields are presumably due to polymerization of nitroalkenes. No other side reactions were observed. [c] Z isomer. [d] No
reaction.
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Morita–Baylis–Hillman Reactions of Conjugated Nitroalkenes and Nitrodienes
Figure 3. Aromatic nitrodienes.
der the DMAP-catalyzed conditions [Entries 1(a)–3(a)], for
the imidazole-catalyzed reactions the yields were moderate
(60–68%), and they required 5–12 h to go to completion
[Entries 1(b)–3(b), Table 8].
With regard to the stereochemistries of 21/22a–c, the
chemical shifts and coupling constants of the hydrogen
atoms α, β, and γ with respect to the nitro groups in the
dienic moieties were analyzed. The appearance of the sig-
nals of the β-protons in 21a–c in the δ = 7.95–8.00 ppm
range suggested that the α,β-double bonds have E configu-
rations (Table S1 in the Supporting Information). Vicinal
coupling constants of J = 11–12 Hz for the couplings be-
tween α-H and β-H in 21a–c further confirmed this assign-
ment. That the γ,δ-double bonds are also E is evident from
the vicinal couplings between γ-H and δ-H, with J values
of 11.9 Hz in 21a, 15.3 Hz in 21b, and 15.4 Hz in 21c. This
Scheme 2.
1
was further supported by a H,1H 2D-NOESY experiment
on the representative compound 21a, in that a strong NOE
was observed between the CH part of the CHOH group
and the γ-H (see the Supporting Information).
As in the cases of aromatic, heteroaromatic, and aliphatic
nitroalkenes, the reaction between nitrodiene 20a and tri-
fluoropyruvate 6 provided the Z isomer as the exclusive
product in high yield both under the DMAP- and under
the imidazole-catalyzed conditions (Entry 4, Table 8). The
Z configuration was assigned to 22d on the basis of corre-
lation of the 1H NMR chemical shift of β-H (δ = 7.60 ppm)
with those in the similar adducts 7a–c and 7e (δ = 7.22–
Scheme 3.
was no appreciable change in the selectivity. Whereas treat- 7.85 ppm, Table S3, Supporting Information). The struc-
ment of nitrodienes 20a–c with glyoxylate 2 provided the ture of 22d was further unambiguously established by X-
MBH adducts 21/22a–c in 80–88% yields in 20–30 min un- ray analysis (Table S10, Supporting Information).
Table 8. MBH reactions between nitrodienes 20 and various electrophiles[a] in the presence of DMAP in acetonitrile or imidazole in
chloroform at room temperature.
Entry
20
X
2, 6, 15
R1, R2
21/22
DMAP/CH3CN (a)
Yield[b] [%] (21/22)
Imidazole/CHCl3 (b)
Time
Time
Yield [%][b] (21/22)
1
2
3
4
5
6
a
b
c
a
a
b
H
OMe
NO2
H
H
OMe
2
2
H, CO2Et
H, CO2Et
H, CO2Et
CF3, CO2Me
H, H
a
b
c
d
e
f
30 min
30 min
40 min
20 min
45 min
45 min
85 (100:0)
88 (92:8)
80 (100:0)
78 (0:100)
70 (100:0)
63 (100:0)
5 h
7 h
12 h
2 h
16 h
16 h
60 (100:0)
63 (90:10)
68 (100:0)
79 (0:100)
50 (100:0)[c]
53 (100:0)[c]
2
6
15
15
H, H
[a] 4 equiv. for both DMAP- and imidazole-catalyzed reactions. [b] Isolated yields of 21 and 22 after silica gel column chromatography.
The diastereomeric ratio of 21 and 22 was determined by 1H NMR spectroscopy. The moderate yields observed in some cases are
presumably due to polymerization of nitroalkenes. No other side reactions were observed in any of the cases. [c] Solvent was THF.
Eur. J. Org. Chem. 2009, 4091–4101
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I. Deb, P. Shanbhag, S. M. Mobin, I. N. N. Namboothiri
FULL PAPER
Finally, the reactions between nitrodienes 20a or 20b and ing electrophile 23 (R2 = R3 = CO2Et), nor on the alkoxide
formaldehyde (15) proceeded well under both DMAP- and group in VII. In contrast, the aliphatic substituent (R1 =
imidazole-catalyzed conditions (Entries 5–6, Table 8). The alkyl), by virtue of its spatial disposition, offers greater re-
stereochemistries of the α-hydroxymethylated nitrodienes sistance to the approaching electrophile 23, and path B
1
21e and 21f were confirmed by correlation of the H NMR leading to the Z isomer 25 is therefore favored.
chemical shifts of the β-protons with those in similar ad-
The superior catalytic roles of DMAP[25] and imid-
azole[26] in the reactions between nitroalkenes or nitrodienes
ducts (Table S9, Supporting Information).[24]
In the reactions between various nitroalkenes or nitro- and various carbonyl electrophiles are amply evident from
dienes and electrophiles such as glyoxylate 2, pyruvaldehyde our experiments. Other amine and phosphane catalysts that
(4b), or formaldehyde (15), in which R2 and/or R3 are/is have been and continue to be routinely employed in MBH
H, the E isomers 24 are the major or exclusive products reactions of various activated alkenes[3] were not effective
(Scheme 4). On the other hand, the Z isomers 25 are the in the case of nitroalkenes. It is interesting to note that,
major or exclusive products in the corresponding reactions whereas imidazole, with a pKa of 7.0, and DMAP, with a
with electrophiles such as trifluoropyruvate 6c and ninhyd- pKa of 9.7, are good catalysts in our reactions, trimeth-
rin 11c in which R2 and R3 ϶ H. The only exception is ylphosphane (TMP) and DABCO, with intermediate pKa
oxomalonate 8, which exhibited opposite selectivities with values (8.7 each), and DBU and tetramethylguanidine
aromatic and aliphatic nitroalkenes, in that, whereas E iso- (TMG), with higher pKa values (12.0 and 13.6, respec-
mers are favored for aromatic and heteroaromatic nitro- tively), are not suitable for our reactions (Figure 4). This
alkenes, Z isomers are the major products in cases of ali- suggests that the catalytic activities of these nucleophilic
phatic nitroalkenes (see Tables 4 and 6). The above selectivi- Lewis bases do not correlate with their basicities.[27]
ties can be explained on the basis of the approach of the
electrophile from the two faces of the nitronate VI and the
relative stabilities of the products 24 and 25 (Scheme 4).
Figure 4. Commonly employed MBH catalysts and their pKa val-
ues.
The above observation encouraged us to implicate the
relative steric requirements of nucleophilic Lewis bases in
their conjugate additions to β-substituted nitroalkenes and
the relative stabilities of the zwitterionic intermediates aris-
ing from such addition. It has been reported that conjugate
additions of amines to nitroalkenes are reversible
(Scheme 5a).[28,29] Because MBH reactions are equilibrium-
controlled, the reversibility in the first step is a major im-
pediment that makes certain catalysts such as DABCO inef-
Scheme 4.
fective. However, the zwitterionic intermediates 30a/30b or
It turns out that approach of the electrophile 23 from the 31a/31b arising from initial conjugate addition of imidazole
hindered side (path A) is tolerated if there is no severe steric or DMAP are resonance-stabilized and therefore less prone
interaction (i.e., when R2 and/or R3 are/is H) between the to undergo reverse reaction (Scheme 5b,c). It is important
alkoxide and the β-substituent (R1) in the transition state to note that the positive charge on the amine nitrogen atom
leading to intermediate VII and product 24 (E isomer). Al- is stabilized without violating the aromaticity of the imid-
ternatively, path B, involving approach of the electrophile azole moiety in 30a or 30b, or of the DMAP moiety in one
23 from the less hindered side, is favored when R2 and R3 of the contributing structures (31b).
are not H. This approach avoids any possible steric interac-
Another important feature of the MBH reactions of ni-
tion between the alkoxide and the β-substituent (R1) in the troalkenes is that β-substituents do not inhibit the reaction.
transition state leading to intermediate VIII and product 25 This is in stark contrast with the behavior of other activated
(Z isomer). In the case of oxomalonate 8, the E isomer 24 alkenes containing β-substituents, which either do not react
is favored (path A) for aromatic nitroalkenes (R1 = Ar), pre- or react very sluggishly.[3] The fact that the reactions be-
sumably because the planar aromatic ring in nitronate VI tween nitroalkenes and most of the carbonyl electrophiles
does not exert any severe steric hindrance on the approach- reported here take place in less than 60 min, particularly
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Eur. J. Org. Chem. 2009, 4091–4101

Morita–Baylis–Hillman Reactions of Conjugated Nitroalkenes and Nitrodienes
followed by the activated carbonyl compound 2 (4 equiv.), and the
reaction mixture was stirred at room temperature. After the com-
pletion of the reaction (monitored by TLC), the reaction mixture
was diluted with water (5 mL), the aqueous layer was extracted
with ethyl acetate (3ϫ5 mL), and the combined organic layers were
washed with brine (10 mL), dried with anhydrous Na2SO4, and
concentrated in vacuo. The crude residue was purified by silica gel
column chromatography by elution with EtOAc/hextroalkenes
(Procedure B): Imidazole (34 mg, 100 mol-%) was added to a
stirred solution of the nitroalkene 1 (0.5 mmol) in dry CHCl3 or
THF (1 mL), followed by the activated carbonyl compound 2, and
the reaction mixture was stirred at room temperature. After the
completion of the reaction (monitored by TLC), the reaction mix-
ture was diluted with water (5 mL), the aqueous layer was extracted
with ethyl acetate (3ϫ5 mL), and the combined organic layers were
washed with brine (10 mL), dried with anhydrous Na2SO4, and
concentrated in vacuo. The crude product was purified by silica gel
column chromatography by elution with EtOAc/hexane (gradient
elution).
Scheme 5.
Representative experimental data (see the Supporting Information
for complete data).[30]
under the DMAP-catalyzed conditions, suggests superior
reactivities of nitroalkenes as MBH substrates vis-à-vis
other activated alkenes. Our investigations of the possible
reactivity of the parent nitroethylene with various electro-
philes under controlled conditions will be reported in due
course.
Diethyl (E)-2-Hydroxy-2-[2-(4-methoxyphenyl)-1-nitrovinyl]malon-
ate (9a): Yellow crystalline solid. Yield 150 mg (85%). m.p. 88 °C.
1H NMR (400 MHz, CDCl3): δ = 1.07 (t, J = 7.1 Hz, 6 H), 3.85
(s, 3 H), 3.96 (ABqd, J = 10.8, 7.1 Hz, 4 H), 4.76 (s, 1 H), 6.94 (dd,
J = 6.8, 2.2 Hz, 2 H), 7.51 (dd, J = 6.8, 2.2 Hz, 2 H), 8.31 (s, 1 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 13.4, 55.4, 63.6, 77.4,
114.2, 123.1, 132.0, 140.3, 145.7, 162.0, 167.4 ppm. IR (film): ν =
˜
3465 (br. m), 2979 (w), 1761 (s), 1639 (m), 160 (s), 1515 (m), 1322
Conclusions
(m), 1264 (s), 1140 (m) cm–1. MS (70 eV): m/z (%) = 376 (50) [M
+
Na]+, 342 (100), 336 (30). HRMS (70 eV) calcd. for
The reactivities of conjugated nitroalkenes, both aro-
matic and aliphatic, and nitrodienes with various carbonyl
electrophiles under the Morita–Baylis–Hillman conditions
have been thoroughly investigated. The studies have shown
that aldehydes such as glyoxylate and pyruvaldehyde, as
well as formaldehyde, oxo esters such as trifluoropyruvate
and oxomalonate, and a cyclic polycarbonyl compound
such as ninhydrin, are suitable electrophiles for the α-hy-
droxyalkylation of nitroalkenes and nitrodienes. Quite re-
markably, DMAP and imidazole are the only two nucleo-
philic Lewis bases that were found to catalyze this reaction,
presumably because of the smaller steric requirement and,
more importantly, the resonance stabilization of the zwitter-
ionic intermediates arising from the Michael-type additions
of these catalysts. Formation of E and Z isomers of the
MBH adducts with preference for E isomers was observed
when R1 and/or R2 of the electrophile (R1COR2) was H
and with preference for Z isomers when R1 and R2 ϶ H.
Unusual γ-hydrogen abstractions in the elimination step,
C16H19NO8Na [M + Na]+ 376.1008; found 376.1005.
Selected X-ray Data for 9a (CCDC-728134): C16H19NO8, M =
¯
353.32, triclinic, space group P1, a = 6.798(2) Å, b = 10.1396(14) Å,
c = 12.700(5) Å, α = 74.61(7), β = 85.56(3), γ = 79.315(18)°, V =
829.0(6) Å3, Dc = 1.415 Mgm–3, Z = 2, F(000) = 372, λ =
0.71073 Å, µ = 8.152 mm–1. Total/unique reflections = 10056/4175
[R(int) = 0.0306], T = 293(2) K, θ range = 3.08–30.12°. Final R
[IϾ2σ(I)]: R1 = 0.0354, wR2 = 0.0718; R (all data): R1 = 0.0916,
wR2 = 0.0791.
Methyl (E)-4-Cyclohexyl-2-hydroxy-3-nitro-2-(trifluoromethyl)but-
3-enoate (16b) and Methyl (Z)-4-Cyclohexyl-2-hydroxy-3-nitro-2-
(trifluoromethyl)but-3-enoate (17b): White crystalline solid. Yield
85% (132 mg) (3:97 ratio, Method A); 41% (64 mg) (3:97 ratio,
Method B); major isomer 17b (obtained in pure form by silica gel
1
column chromatography of the mixture); m.p. 36–37 °C. H NMR
(400 MHz, CDCl3): δ = 1.16–1.39 (m, 6 H), 1.68–1.79 (m, 4 H),
2.55–2.69 (m, 1 H), 3.97 (s, 3 H), 4.52 (s, 1 H), 6.20 (d, J = 9.8 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.8, 24.9, 25.4, 31.3,
31.9, 38.0, 55.2, 76.37 (q, J = 31.3 Hz), 121.2 (q, J = 286.0 Hz),
leading to the formation of α-hydroxyalkylated β,γ-nitro- 140.7, 143.5, 167.4 ppm. 19F NMR (CDCl3, 376 MHz): δ =
–74.7 ppm. IR (film): ν = 3434 (br. vs), 2934 (m), 2858 (w), 1757
˜
alkenes, were observed in the reactions between oxomalon-
ate and nitroalkenes possessing γ-CH2 groups.
(m), 1655 (m), 1541 (m), 1444 (w), 1364 (w), 1299 (m) cm–1. MS
(70 eV): m/z (%) = 334 (100) [M + Na]+, 268 (35). HRMS (70 eV)
calcd. for C12H16F3NO5Na [M + Na]+ 334.0878; found 334.0867.
Experimental Section
Selected X-ray Data for 17b (CCDC-728136): C12H16F3NO5, M =
311.26, monoclinic, space group P21/c, a = 11.4463(7) Å, b =
General methods are provided in the Supporting Information.
12.3752(9) Å,
c
=
10.3759(7) Å,
β
=
102.057(6)°,
V
=
DMAP-Catalyzed MBH Reactions of Nitroalkenes (Procedure A): 1437.33(17) Å3, Dc = 1.438 Mgm–3, Z = 4, F(000) = 648, λ =
DMAP (25 mg, 40 mol-% or 62.5 mg, 100 mol-%) was added to a
stirred solution of the nitroalkene 1 (0.5 mmol) in MeCN (1 mL),
0.71073 Å, µ = 0.135 mm–1. Total/unique reflections = 6477/2490
[R(int) = 0.0494], T = 150(2) K, θ range = 3.29–24.99°. Final R
Eur. J. Org. Chem. 2009, 4091–4101
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I. Deb, P. Shanbhag, S. M. Mobin, I. N. N. Namboothiri
FULL PAPER
Lloyd-Jones, Angew. Chem. Int. Ed. 2005, 44, 1706–1708; f)
L. S. Santos, C. H. Pavam, W. P. Almeida, F. Coelho, M. N.
Eberlin, Angew. Chem. Int. Ed. 2004, 43, 4330–4333; g) K. E.
Price, S. J. Broadwater, B. J. Walker, D. T. McQuade, J. Org.
Chem. 2005, 70, 3980–3987; h) P. Buskens, J. Klankermayer, W.
Leitner, J. Am. Chem. Soc. 2005, 127, 16762–16763; i) J. S. Hill,
N. S. Isaacs, Tetrahedron Lett. 1986, 27, 5007–5010.
[IϾ2σ(I)]: R1 = 0.0788, wR2 = 0.1569; R (all data): R1 = 0.1174,
wR2 = 0.1729.
Methyl
(3Z,5E)-2-Hydroxy-3-nitro-6-phenyl-2-(trifluoromethyl)-
hexa-3,5-dienoate (22d): Yellow crystalline solid. Yield 78%
1
(129 mg) (Method A), 79% (131 mg) (Method B); m.p. 122 °C. H
NMR (400 MHz, CDCl3): δ = 3.95 (s, 3 H), 4.57 (br. s, 1 H), 7.05
(d, J = 10.9 Hz, 1 H), 7.17 (d, J = 15.6 Hz, 1 H), 7.39–7.40 (m, 3
H), 7.53–7.55 (m, 2 H), 7.60 (dd, J = 15.5, 10.9 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 55.1, 77.1 (q, J = 30.5 Hz), 120.7,
122.2 (q, J = 282.9 Hz), 128.2, 129.0, 130.7, 134.9, 135.6 (q, J =
2.3 Hz), 140.8, 148.3, 167.5 ppm. 19F NMR (CDCl3, 376 MHz): δ
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= –74.1 ppm. IR (neat): ν = 3429 (br. vs), 2925 (w), 1748 (m), 1635
˜
(s), 1529 (m), 1384 (m) cm–1. MS (70 eV): m/z (%) = 332 (75) [M
+ H]+, 264 (80), 254 (100). HRMS (70 eV) calcd. for C14H13NO5F3
[M + H]+ 332.0746; found 332.0736.
Selected X-ray Data for 22d (CCDC-728135): C28H24F6N2O10, M
= 662.49, monoclinic, space group P21/n, a = 13.6872 (5) Å, b =
7.4396 (3) Å,
c = 29.5302 (10) Å, β = 102.147(4)°, V =
2939.66(19) Å3, Dc = 1.497 Mgm–3, Z = 4, F(000) = 1360, λ =
0.71073 Å, µ = 0.137 mm–1. Total/unique reflections = 19177/5161
[R(int) = 0.0221], T = 150(2) K, θ range = 3.04–25.00°. Final R
[IϾ2σ(I)]: R1 = 0.0319, wR2 = 0.0762; R (all data): R1 = 0.0435,
wR2 = 0.0804.
[6]
CCDC-728134-728137 contain the supplementary crystallographic
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.
Supporting Information (see footnote on the first page of this arti-
cle): NMR, X-ray data tables, NMR spectra, and general methods.
Acknowledgments
The authors thank the Department of Science and Technology
(DST), India, for financial assistance (Grant SR/S1/OC-19/2006),
the Sophisticated Analytical Instruments Facility (SAIF), Indian
Institute of Technology Bombay, for selected NMR spectroscopic
data, and Dr. Mamta Dadwal for selected experimental data. I. D.
and P. S. thank the Council of Scientific and Industrial Research
(CSIR) for a senior research fellowship.
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1
All new compounds were characterized by IR, H NMR, 13C
[30]
NMR spectroscopy, and mass spectrometry, including HRMS
data. These compounds were in general not amenable to com-
bustion (CHN) analysis as they underwent degradation during
repeated purification.
Received: May 4, 2009
Published Online: July 14, 2009
Eur. J. Org. Chem. 2009, 4091–4101
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4101