Tris(pentafluorophenyl)borane-catalyzed alkylation of 1,3-dicarbonyl compounds with benzylic alcohols: Access to oxygenated heterocycles

Article abstract of DOI:10.1055/s-0030-1258214

Tris(pentafluorophenyl)borane has found to be an effective catalyst for the alkylation of 1,3-dicarbonyl compounds using benzylic alcohols as alkylating agents. Various 1,3-dicarbonyl compounds reacted cleanly with different benzylic alcohols to provide t

Full text of DOI:10.1055/s-0030-1258214

PAPER
3715
Tris(pentafluorophenyl)borane-Catalyzed Alkylation of 1,3-Dicarbonyl
Compounds with Benzylic Alcohols: Access to Oxygenated Heterocycles
A
lkylation of 1,3-
h
Dicarbonyl
a
Compound
d
s
with Benzy
a
lic
A
lcohols Raji Reddy,*a Jonnalagadda Vijaykumar,a René Gréeb
a
Organic Division – I, Indian Institute of Chemical Technology, Hyderabad 500607, India
Fax +91(40)27160512; E-mail: rajireddy@iict.res.in
b
Université de Rennes 1, Laboratoire CPM, CNRS UMR 6510 and Laboratoire SCR, CNRS UMR 6226,
Avenue du Général Leclerc, 35042 Rennes Cedex, France
Received 29 June 2010; revised 9 July 2010
transition metal/MW.6 However, most of the above cata-
lysts are strong acids and/or require either high tempera-
tures or longer reaction times that limit their utility in
complex molecule synthesis. Furthermore, the compati-
Abstract: Tris(pentafluorophenyl)borane has found to be an effec-
tive catalyst for the alkylation of 1,3-dicarbonyl compounds using
benzylic alcohols as alkylating agents. Various 1,3-dicarbonyl com-
pounds reacted cleanly with different benzylic alcohols to provide
the corresponding monoalkylated products in good yield. In addi- bility of acid-labile protecting groups has not been ex-
tion tris(pentafluorophenyl)borane efficiently promoted the C3
plored in the alkylation of 1,3-dicarbonyl compounds.
alkylation of 4-hydroxycoumarins. Further, several oxygenated het-
Thus, both the development of a milder acid catalyst and
erocycles such as furans, 4H-chromenes, and furanocoumarins have
the demonstration of the stability of various protecting
been prepared using the described methodology as the key step.
groups are highly desirable.
Key words: tris(pentafluorophenyl)borane, 1,3-dicarbonyl com-
In this context, we decided to explore the utility of
tris(pentafluorophenyl)borane as a milder acid catalyst for
the alkylation of 1,3-dicarbonyl compounds using alco-
hols as the alkylating agents. Tris(pentafluorophenyl)bo-
rane is a commercially available nonconventional Lewis
acid. Although, it has been known since 1963, for many
years it only found application as a polymerization cata-
lyst.7 Over the last decade, tris(pentafluorophenyl)borane
has proved to be a useful Lewis acid catalyst because it is
water tolerant and air and thermally stable. It has found
various applications such as in hydride abstraction reac-
tions, aldol reactions, acetylide reactions, hydrosilylation
reactions, allylstannation of aldehydes, allylation of sec-
ondary benzylic acetates, aziridine ring-opening, hydro-
genation of imines, reduction of alcohols, ethers, aliphatic
carbonyls to hydrocarbons etc.8,9 We have also success-
fully demonstrated the utility of tris(pentafluorophe-
nyl)borane as a Lewis acid in the opening of epoxides,
Ferrier glycosylation, tritylation of alcohols, N-alkylation
of hydrazones, reductive alkylation of alkoxybenzenes,
reduction of carbonyl to methylene, and Hantzsch reac-
tion.10 However, it has not previously been utilized for the
alkylation of 1,3-dicarbonyl compounds with benzylic al-
cohols.
pound, benzylic alcohol, alkylation, heterocycle
The alkylation of 1,3-dicarbonyl compounds represents
one of the most useful methodologies for C–C bond-form-
ing reactions.1 Usually, alkyl halides are employed as the
alkylating agents in the presence of a stoichiometric
amount of base.2 The drawback of this method is the gen-
eration of waste salts in large quantities, the use of toxic
materials, and lengthy reaction procedures. Therefore, to-
wards sustainable chemistry, an alkylation reaction with
environmental compatibility would be the use of alcohols
as the alkylating agents, wherein water is the only byprod-
uct; in addition, alcohols can be obtained more easily than
the corresponding halides. Nevertheless, hydroxy groups
usually require pre-activation due to their poor leaving
ability.3 This can be achieved by transforming the hy-
droxy group into good leaving groups such as carboxy-
lates, phosphonates, carbonates etc.4 However, either a
promoter or high reaction temperatures are required. Sub-
sequently, the alcohols have been used directly in the
presence of transition-metal-based catalysts such as palla-
dium, copper, or cobalt salts, which are mostly useful for
allylic alcohols, but not with benzylic alcohols.5 Very re-
cently, the pre-activation of alcohols (allylic or benzylic)
has been achieved by using various Lewis and Brønsted
acids for the alkylation of 1,3-dicarbonyl compounds. The
catalysts used include BF3·OEt2, InCl3, Bi(OTf)3, metal
triflates (Sc, Yb, La, Hf), PTSA, FeCl3, I2, AuCl3/AgSbF6,
phosphotungstic acid (PWA), H-montmorillonite, TfOH,
Cu(OTf)2, EMIOTf, Re-catalyst, PMA/SiO2 formic acid,
InBr3, Mo(VI)-catalyst, ZnCl2/TMSCl, NaAuCl4, and
In light of the success in demonstrating that benzylic alco-
hols are alkylating agents under acid catalysis,10c,d,11 we
decided to extend our studies to the alkylation of 1,3-di-
carbonyl compounds. Initially, benzhydrol (1a) was cho-
sen as the alkylating agent for the alkylation of
acetylacetone (2a). This model reaction was carried out in
dichloromethane in the presence of tris(pentafluorophe-
nyl)borane, but produced no adduct even after eight hours
at room temperature. When the temperature was raised to
reflux, complete disappearance of the starting materials
was observed providing the desired alkylated product 3a
in 91% yield (Scheme 1).
SYNTHESIS 2010, No. 21, pp 3715–3723
x
x.
x
x
.
2
0
1
0
Advanced online publication: 13.08.2010
DOI: 10.1055/s-0030-1258214; Art ID: Z16710SS
© Georg Thieme Verlag Stuttgart · New York

3716
C. R. Reddy et al.
PAPER
Table 1 Tris(pentafluorophenyl)borane-Catalyzed Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcoholsa
Entry
1
Alcohol
1,3-Dicarbonyl compound Time (h)
Productb
Yieldc (%)
O
O
O
O
OEt
1a
0.75
88
82
90
OEt
Ph
3b
O
Ph
2b
O
O
O
EtO
OEt
2
3
1a
1a
2
EtO
OEt
Ph
Ph
2c
3c
O
O
O
O
Cl
OEt
0.5
Cl
OEt
Ph
Ph
2d
3d
O
O
O
O
OEt
4
1a
2
89
OEt
Ph
Ph
2e
2a
3e
O
O
OH
5
6
0.5
0.5
79
87
Ph
Ph
Ph
3f
O
Ph
O
1b
OEt
1b
2b
2a
Ph
3g
O
Ph
O
OH
Ph
7
8
0.5
0.5
94
79
Ph
O
Ph
Ph
3h
O
1c
OEt
1c
1c
2b
Ph
Ph
3i
O
OH
O
9
5
1
91
80
O
O
Ph
2f
Ph
3j
Ph
Ph
OH
O
10
2a
N
N
Ts
Ts
1d
3k
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

PAPER
Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcohols
3717
Table 1 Tris(pentafluorophenyl)borane-Catalyzed Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcoholsa (continued)
Entry
11
Alcohol
1,3-Dicarbonyl compound Time (h)
Productb
Yieldc (%)
O
Ph
O
1d
2b
1
93
EtO
N
Ts
3l
OH
CN
O
12
2a
6
74
CN
MeO
MeO
O
1e
3m
a Reaction conditions: 2a–f (1 mmol), 1a–e (1 mmol), B(C6F5)3 (5 mol%), CH2Cl2 (5 mL), reflux.
b All products were characterized by 1H and 13C NMR and MS.
c Isolated yields.
O
O
After this positive result, the scope of the protocol was ex-
amined for various alcohols and 1,3-dicarbonyl com-
pounds (Table 1). The alkylation of ethyl acetoacetate
(2b), diethyl malonate (2c), and ethyl chloroacetoacetate
(2d) was successfully achieved using 1a as the alkylating
agent to obtain the corresponding alkylated products
3b–d in good yields (entries 1–3). Furthermore, a sterically
hindered 1,3-dicarbonyl compound 2e gave an excellent
OH
O
O
B(C6F5)3 (5 mol%)
+
CH2Cl2, reflux
0.5 h, 91%
Ph
Ph
1a
2a
Ph
Ph
3a
Scheme 1 Alkylation of acetylacetone with benzhydrol
Table 2 Tris(pentafluorophenyl)borane-Catalyzed Alkylation of Dimedone (2g)a
Entry
Alcohol
Time (h)
Productb
Yieldc (%)
OH
O
OH
1
0.5
65
OTBS
MeO
OTBS
1f
MeO
3n
OH
O
OH
2
0.5
76
OTHP
MeO
OTHP
1g
MeO
3o
OH
O
OH
3
0.5
62
OPMB
MeO
OPMB
1h
MeO
3p
a Reaction conditions: 2g (1 mmol), 1f–h (1 mmol), B(C6F5)3 (5 mol%), CH2Cl2 (5 mL), reflux.
b All products were characterized by 1H and 13C NMR and MS.
c Isolated yields.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

3718
C. R. Reddy et al.
PAPER
yield of 3e in two hours by reaction with benzhydrol (1a) argyl alcohol, was treated with dimedone (2g) in the pres-
(entry 4). This indicates the sterically hindered substrates ence of tris(pentafluorophenyl)borane. Interestingly, the
can also be alkylated using benzylic alcohols as the alky- reaction proceeded smoothly at reflux temperature to pro-
lating agents. Allylic benzyl alcohol 1b and propargylic vide the alkylated product 3n in 65% yield, without affect-
benzyl alcohol 1c were also used as alkylating agents for ing the tert-butyldimethylsilyl protection (entry 1).
the alkylation of 2a and 2b to give the corresponding alky-
lated compounds 3f–i (entries 5–8). Cyclic 1,3-carbonyl
compound 2f underwent the alkylation reaction with 1c to
provide 3j in 91% yield (entry 9). Indole benzylic alcohol
Likewise, two other similar substrates having different
acid labile protecting groups, such as tetrahydropyran-2-
yl (THP) and 4-methoxybenzyl (PMB), 1g and 1h, respec-
tively, also participated in the alkylation reaction of dime-
1d also reacted nicely with 2a and 2b under the described
done (2g) to give the corresponding alkylated products 3o
protocol to provide 3k and 3l (entries 10 and 11).While all
and 3p in good yields keeping the protecting groups intact
the benzylic alcohols used gave the expected benzylated
(entries 2 and 3).
products during the alkylation, the benzylic alcohol gen-
Later, we chose to test the alkylation of 4-hydroxycou-
marin (4-hydroxy-2H-chromen-2-one, 4), because this
type of heterocyclic compound has also a 1,3-dicarbonyl
structure. Further, 3-alkylated 4-hydroxycoumarins have
erated from the Baylis–Hillman reaction 1e provided the
corresponding allylated product 3m in 74% yield with ex-
clusive Z-selectivity via allylic alkylation (entries 12).
To check the mildness of the present protocol, we have
useful applications in medicinal chemistry12 and some of
tested the benzylic alcohol substrate containing different
the methods available for obtaining these compounds
protecting groups as the alkylating agent. To the best of
involve alcohols as an alkylating agent under acid cataly-
our knowledge, this type of alcohol has not been used for
sis.13 Thus, the catalytic activity of tris(pentafluorophe-
the alkylation of 1,3-dicarbonyl compounds. Having
nyl)borane was tested for the C3 alkylation of 4-
functionality in the alcohol part will be certainly helpful
hydroxycoumarin (4) using benzhydrol (1a) as the alky-
lating agent (Table 3). For this test experiment, acetoni-
trile was used as the solvent and the reaction was
performed at reflux temperature. Gratifyingly, we found
for the further diversification of the alkylated products
(Table 2). Accordingly, benzylic alcohol 1f, derived from
anisaldehyde and tert-butyldimethylsilyl-protected prop-
Table 3 Tris(pentafluorophenyl)borane-Catalyzed C3-Alkylation of 4-Hydroxycoumarin (4)a
Entry
Alcohol
Time (h)
Productb
Yieldc (%)
86
OH Ph
Ph
1
1a
2
O
O
5a
Ph
OH
O
2
3
1c
0.25
89
94
Ph
O
5b
5c
OH Ph
1d
0.5
N
O
O
Ts
Ph
HO
Ph
OH
O
4
0.25
88
N
N
Ts
O
Ts
1i
5d
a Reaction conditions: 4 (1 mmol), 1a,c,d,i (1 mmol), B(C6F5)3 (5 mol%), MeCN, reflux.
b All products were characterized by 1H and 13C NMR and MS.
c Isolated yields.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

PAPER
Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcohols
Table 5 Synthesis of Substituted Furansa
3719
that the reaction proceeded smoothly to give the desired
product 5a in 86% yield (entry 1). Furthermore, a few
more benzylic alcohols including phenylacetylene-substi-
tuted 1c and indole-substituted alcohols 1d and 1i were
explored for the alkylation of 4 under tris(pentafluorophe-
nyl)borane catalysis, affording the corresponding alkylat-
ed products 5b–d in excellent yields (entries 2–4). It
should be mentioned that primary benzyl alcohol and non-
benzylic alcohols did not undergo the alkylation of 1,3-di-
carbonyl compounds.
Entry Substrate Time
(h)
Productb
Yieldc
(%)
O
O
1
3h
3
82
Ph
Ph
8a
Next, we asked ourselves whether the hydroxybenzhydrol
6a would provide the simple alkylated product or the cy-
clized product chromene by reaction with 1,3-dicarbonyl
compounds under the tris(pentafluorophenyl)borane ca-
talysis (Table 4). This type of chromene synthesis proto-
col is less explored.6m,14 In turn, the reaction of 6a with
acetylacetone (2a) in dichloromethane at reflux tempera-
ture in the presence of tris(pentafluorophenyl)borane was
tested, which gave the chromene 7a in 56% yield in four
hours (entry 1). Encouraged by this finding, as the
chromenes are very important scaffolds in several bioac-
tive compounds,15 we decided to explore similar reactions
using different substrates. Accordingly, compound 6a
was treated with cyclic 1,3-dicarbonyl compound 2f to
obtain the corresponding chromene 7b in 62% yield albeit
with a longer reaction time (entry 2). Furthermore, we
have studied another hydroxybenzhydrol substrate 6b,
generated from 2-naphthol, which provided the chromene
7c in 55% yield on reaction with acetylacetone (2a) (entry
3).
O
EtO
O
2
3
3i
3j
2.5
90
84
Ph
Ph
8b
Ph
O
1
Ph
O
8c
Ph
O
4
5d
3
57
N
O
O
Ts
8d
a Reaction conditions: 3h–j, 5d (1.0 mmol), K2CO3, MeCN, reflux.
b All products were characterized by 1H and 13C NMR and MS.
c Isolated yields.
Finally, the application of the obtained alkylated products
from propargylic alcohols for the synthesis of tetrasubsti-
tuted furans was examined. Some of the above obtained
products were treated with potassium carbonate to pro-
vide structurally interesting furan derivatives
(Table 5)6e,k,13d that can be considered as new chemical
entities. Thus, compound 3h was treated with potassium
carbonate (2 equiv) in acetonitrile at reflux temperature to
give the corresponding tetrasubstituted furan 8a in 82%
yield (entry 1).
Table 4 Tris(pentafluorophenyl)borane-Catalyzed Synthesis of Chromenesa
Entry
Alcohol
1,3-Diketones
Time (h)
4
Productb
Yieldc (%)
56
Ph
Ph
O
O
OH
1
2a
OH
O
6a
6a
7a
7b
Ph
2
3
2f
12
5
62
55
O
Ph
Ph
O
O
2a
OH
OH
6b
7c
a Reaction conditions: 2a,f (1 mmol), 6a,b (1 mmol), B(C6F5)3 (5 mol%), CH2Cl2, reflux.
b All products were characterized by 1H and 13C NMR and MS.
c Isolated yields.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

3720
C. R. Reddy et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 7.32–7.16 (m, 10 H, HPh), 4.77 (q,
J = 12.0 Hz, 2 H, COCHCO, Ph2CH), 4.06–3.87 (m, 4 H, ClCH2,
OCH2CH3), 1.00 (t, J = 7.2 Hz, 3 H, CH3CH2).
13C NMR (75 MHz): d = 195.4, 166.6, 140.9, 140.6, 129.0, 128.6,
127.7, 127.5, 127.2, 127.0, 61.8, 61.4, 50.9, 48.6, 13.6.
HRMS (ESI): m/z [M + Na]+ calcd for C19H19ClNaO3; 353.0915;
found: 353.0908.
Cyclization of 3i gave 8b in good yield as well (entry 2).
Reaction of 3j, derived from a cyclic 1,3-dicarbonyl com-
pound, produced the fused furan derivative 8c in 84%
yield (entry 3). A more fascinating furan derivative 8d,
having indole and fused coumarin as substituents, was ob-
tained from the cyclization of 7c in 57% yield (entry 4).
Significantly, it is worthy of note that the tetrasubstituted
furans can also be obtained in a one-pot reaction from the
propargylic alcohol and 1,3-dicarbonyl compound.16 This
was demonstrated by the reaction of 1c with 2a in the
presence of tris(pentafluorophenyl)borane in acetonitrile
followed by the addition of potassium carbonate to obtain
8a in 73% yield (Scheme 2).
2-(1,3-Diphenylprop-2-ynyl)-3-hydroxycyclohex-2-enone (3j)
Colorless solid; mp 170–172 °C.
IR (KBr): 2953, 1601, 1489, 1450, 1373 cm–1.
1H NMR (300 MHz, CDCl3): d = 10.61–10.35 (br s, OH), 7.56–7.38
(m, 4 H, HPh), 7.36–7.10 (m, 6 H, HPh), 5.57 (s, 1 H, PhCH,), 2.62–
2.28 (m, 4 H, COCH2, =COHCH2), 2.00–1.88 (m, 2 H,
CH2CH2CO).
13C NMR (75 MHz): d = 194.8, 172.2, 140.2, 130.4, 127.1, 126.7,
126.4, 126.2, 124.7, 123.1, 114.8, 89.8, 80.2, 35.5, 29.3, 28.4, 19.5.
O
OH
i) B(C6F5)3 (5 mol%)
O
O
MeCN, reflux, 20 min
O
HRMS (ESI): m/z [M + H]+ calcd for C21H19O2: 303.1380; found:
303.1391.
+
Ph
ii) K2CO3, reflux
3 h
Ph
Ph
1c
2a
Ph
8a (73%)
‘one-pot’
3-[Phenyl(1-tosyl-1H-indol-3-yl)methyl]pentane-2,4-dione (3k)
White solid; mp 150–153 °C.
IR (KBr): 3106, 1737, 1597, 1492, 1447 cm–1.
Scheme 2 One-pot synthesis of a substituted furan
1H NMR (300 MHz, CDCl3): d = 7.93 (d, J = 8.1 Hz, 1 H, HAr), 7.66
(d, J = 8.3 Hz, 2 H, HAr), 7.34 (d, J = 7.9 Hz, 1 H, HAr), 7.27–7.08
(m, 10 H, HAr, =CHN), 4.88 (d, J = 12.3 Hz, 1 H, PhCH), 4.53 (d,
J = 12.1 Hz, 1 H, COCHCO), 2.34 (s, 3 H, Ts-CH3), 1.90 (s, 3 H,
CH3CO), 1.84 (s, 3 H, CH3CO).
13C NMR (75 MHz): d = 202.7, 202.4, 144.9, 139.1, 135.3, 134.7,
129.8, 128.8, 128.0, 127.3, 126.7, 125.2, 123.5, 123.1, 119.6, 113.9,
In conclusion, we have developed a mild method for the
alkylation of 1,3-dicarbonyl compounds and 4-hydroxy-
coumarins using benzylic alcohols as the alkylating
agents. The stability of acid labile groups (e.g., TBS,
THP, PMB) is significant for the present method. Follow-
ing this reaction, syntheses of interesting oxygenated het-
erocycles such as 4H-chromenes, furans, and furano- 42.4, 31.3, 27.4, 21.5.
HRMS (ESI): m/z [M + NH4]+ calcd for C27H29N2O4S: 477.1843;
found: 477.1869.
coumarins were easily achieved in good to excellent
yields.
Ethyl 3-Oxo-2-[phenyl(1-tosyl-1H-indol-3-yl)methyl]bu-
tanoate (3l)
Viscous liquid.
IR (neat): 3432, 1745, 1599, 1494, 1449 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.88 (t, J = 7.2 Hz, 1 H, HAr), 7.66
(t, J = 6.6 Hz, 2 H, HAr), 7.55–7.04 (m, 11 H, HAr, =CHN), 4.87 (t,
J = 12.1 Hz, 1 H, PhCH), 4.32 (dd, J = 11.7 Hz, 1 H, COCHCO),
3.93 (q, J = 7.2 Hz, 2 H, CH2OCO), 2.34 (s, 3 H, Ts-CH3), 2.00 (d,
J = 21.7 Hz, 3 H, CH3CO), 1.02–0.89 (m, 3 H, CH3CH2O).
13C NMR (75 MHz): d = 201.2, 167.4, 144.8, 139.3, 135.3, 134.8,
129.7, 128.7, 128.5, 128.2, 128.1, 127.2, 126.6, 124.9, 123.4, 123.2,
122.9, 122.1, 119.9, 119.8, 113.8, 113.5, 65.9, 61.5, 30.8, 28.5,
21.5, 13.7.
1H and 13C NMR spectra were recorded in CDCl3 solvent on a 300,
500, or 75 MHz spectrometer at r.t. with TMS as internal standard.
FT-IR spectra were recorded as KBr thin films or neat. All the re-
agents and solvents were reagent grade and used without further pu-
rification unless specified. Technical grade EtOAc and petroleum
ether (PE) used for column chromatography was distilled prior to
use. Column chromatography was carried out using silica gel (60–
120 mesh) packed in glass columns. All reactions were performed
under an N2 atmosphere in oven-dried glassware with magnetic stir-
ring.
2-Alkyl-1,3-dicarbonyl 3a–p; General Procedure
A mixture of 1,3-dicarbonyl compound 2a–f (1.0 mmol), benzylic
alcohol 1a–h (1.0 mmol), and B(C6F5)3 (5 mol%) in CH2Cl2 (5 mL)
was stirred at reflux temperature until complete consumption of the
starting material (Tables 1 and 2). The mixture was cooled to r.t.,
diluted with H2O (10 mL) and extracted with CH2Cl2 (2 × 15 mL).
The combined organic layers were dried (anhyd Na2SO4), concen-
trated in vacuo, and purified by column chromatography (silica gel)
to afford pure 3a–p. The products obtained were characterized by
IR, 1H and 13C NMR, and mass spectroscopy. The 1H NMR, IR and
mass spectral data of known compounds 3a,6p 3b,6o 3c,17a 3e,6u 3f,5i
3g,17b 3h,13d and 3i13d were identical with those of authentic sam-
ples.
HRMS (ESI): m/z [M + Na]+ calcd for C28H27NNaO5S: 512.1502;
found: 512.1506.
(Z)-4-Acetyl-2-(4-methoxybenzylidene)-5-oxohexanenitrile
(3m)
Viscous liquid. Based on the 1H and 13C NMR, this product exists
in the enolic form; Z-selectivity was supported by NOE experi-
ments.
IR (KBr): 2927, 2208, 1707, 1606, 1514, 1465, 1440 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 8.7 Hz, 2 H, HAr), 6.90
(d, J = 8.9 Hz, 2 H, HAr), 6.72 (s, 1 H, ArHC=), 3.84 (s, 3 H, OCH3),
3.34 [d, J = 1.1 Hz, 2 H, =C(CN)CH2], 2.17 (s, 6 H, 2 CH3CO).
13C NMR (75 MHz): d = 192.3, 161.1, 142.2, 130.4, 125.8, 119.0,
114.2, 106.0, 105.0, 55.3, 33.4, 23.2.
Ethyl 2-Benzhydryl-4-chloro-3-oxobutanoate (3d)
Colorless solid; mp 115–118 °C.
IR (KBr): 2976, 1744, 1592, 1494, 1453 cm–1.
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Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcohols
3721
HRMS (ESI): m/z [M + Na]+ calcd for C16H17NNaO3: 294.1101;
found: 294.1091.
4-Hydroxy-3-[phenyl(1-tosyl-1H-indol-3-yl)methyl]-2H-
chromen-2-one (5c)
White solid; mp 204–206 °C.
2-[4-(tert-Butyldimethylsilyloxy)-1-(4-methoxyphenyl)but-2-
ynyl]-3-hydroxy-5,5-dimethylcyclohex-2-enone (3n)
Viscous liquid.
IR (neat): 3406, 2957, 1725, 1601, 1510, 1463 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.62 (br s, 1 H, OH), 7.27 (d,
J = 8.7 Hz, 2 H, HAr), 6.80 (d, J = 8.7 Hz, 2 H, HAr), 5.35 (s, 1 H,
CHAr), 4.38 (d, J = 1.9 Hz, 2 H, CH2OTBS), 3.77 (s, 3 H, OCH3),
2.41–2.21 (m, 4 H, CH2CO, CH2C=), 1.10 [s, 3 H, C(CH3)2], 1.00
[s, 3 H, C(CH3)2], 0.91 [s, 9 H, C(CH3)3], 0.11 [s, 6 H, Si(CH3)2].
13C NMR (75 MHz): d = 196.3, 171.2, 158.3, 130.0, 127.8, 114.8,
113.8, 84.7, 83.9, 55.1, 51.6, 50.0, 45.8, 29.6, 28.9, 25.6, 18.1, 17.9,
–3.6, –5.2.
IR (KBr): 3025, 1670, 1604, 1548, 1491, 1448 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.97 (d, J = 8.3 Hz, 1 H, HAr), 7.67
(d, J = 8.3 Hz, 3 H, HAr), 7.53 (t, J = 8.5 Hz, 1 H, HAr), 7.41–7.12
(m, 13 H, HAr, =CHN), 5.99 (s, 1 H, PhCH), 2.38 (s, 3 H, Ts-CH3).
13C NMR (75 MHz): d = 162.9, 161.4, 152.7, 145.2, 138.6, 135.9,
132.4, 130.0, 129.5, 129.0, 128.9, 128.1, 126.7, 125.7, 125.0, 124.0,
123.7, 123.2, 120.3, 120.0, 116.5, 115.6, 114.0, 105.4, 38.9, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C31H24NO5S: 522.1370;
found: 522.1386.
4-Hydroxy-3-[3-phenyl-1-(1-tosyl-1H-indol-3-yl)prop-2-ynyl]-
2H-chromen-2-one (5d)
Light-green solid; mp 111–114 °C.
HRMS (ESI): m/z [M + H]+ calcd for C25H37O4Si: 429.2456; found:
429.2474.
IR (KBr): 3061, 1699, 1622, 1566, 1491, 1447 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.92 (d, J = 8.3 Hz, 1 H, HAr), 7.83
(dd, J = 7.5, 1.5 Hz, 1 H, HAr), 7.72 (d, J = 8.3 Hz, 3 H, HAr), 7.65
(d, J = 1.5 Hz, 1 H, HAr), 7.55–7.46 (m, 2 H, HAr), 7.38–7.12 (m, 10
H, HAr, =CHN), 5.86 (s, 1 H, CHC=CN), 2.33 (s, 3 H, Ts-CH3).
13C NMR (75 MHz): d = 162.0, 161.7, 152.7, 145.1, 134.8, 132.6,
131.8, 129.9, 129.2, 128.5, 126.8, 125.3, 124.1, 123.4, 120.3, 116.5,
113.7, 102.7, 86.8, 85.0, 25.6, 21.5.
3-Hydroxy-2-[1-(4-methoxyphenyl)-4-(tetrahydro-2H-pyran-2-
yloxy)but-2-ynyl]-5,5-dimethylcyclohex-2-enone (3o)
Viscous liquid.
IR (neat): 3448, 2926, 1717, 1604, 1510, 1461 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.56 (br s, 1 H, OH), 7.26 (d,
J = 8.6 Hz, 2 H, HAr), 6.77 (d, J = 8.2 Hz, 2 H, HAr), 5.35 (s, 1 H,
OCHO), 4.75 (s, 1 H, CHAr), 4.31 (s, 2 H, THP-OCH2), 3.84–3.73
(m, 4 H, CH3O, CH2O), 3.53–3.45 (m, 1 H, CH2O), 2.42–2.17 (m,
4 H, CH2CO, CH2C=), 1.67–1.47 (m, 6 H, OCHCH2CH2CH2), 1.09
[s, 3 H, C(CH3)2], 0.96 [s, 3 H, C(CH3)2].
13C NMR (75 MHz): d = 196.3, 171.1, 158.3, 131.6, 127.8, 114.7,
113.8, 97.2, 85.2, 81.7, 62.0, 55.0, 54.5, 50.0, 43.0, 30.1, 29.5, 28.9,
28.7, 25.1, 19.0, 18.9.
HRMS (ESI): m/z [M + Na]+ calcd for C33H23NNaO5S, 568.1189;
found: 568.1202.
4H-Chromenes 7a–c; General Procedure
To a stirred soln of 1,3-dicarbonyl compound 2a,f (1.0 mmol), ben-
zylic alcohol 6a,b (0.75 mmol), and B(C6F5)3 (5 mol%) in CH2Cl2
(5 mL) was stirred at reflux temperature for the given time (see
Table 4). The mixture was cooled to r.t., diluted with H2O (10 mL),
and extracted with CH2Cl2 (2 × 15 mL). The combined organic lay-
ers were dried (anhyd Na2SO4), concentrated in vacuo, and purified
by column chromatography (silica gel) to afford pure 7a–c.
HRMS (ESI): m/z [M + Na]+ calcd for C24H30NaO5: 421.1985;
found: 421.1989.
3-Hydroxy-2-[5-(4-methoxybenzyloxy)-1-(4-methoxyphe-
nyl)pent-2-ynyl]-5,5-dimethylcyclohex-2-enone (3p)
Viscous liquid.
IR (neat): 2925, 1712, 1608, 1465, 1511, 1461 cm–1.
IR, 1H NMR, and MS data of known compounds 7a and 7b14 were
identical with those of authentic samples.
1-(3-Methyl-1-phenyl-1H-benzo[f]chromen-2-yl)ethanone (7c)
Colorless solid; mp 128–131 °C.
IR (KBr): 3063, 2923, 1639, 1595, 1455 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.01 (d, J = 8.5 Hz, 1 H, HAr), 7.72
(q, J = 8.1 Hz, 2 H, HAr), 7.48–7.02 (m, 8 H, HAr), 5.66 (s, 1 H,
CHPh), 2.47 (s, 3 H, CH3C=), 2.38 (s, 3 H, CH3CO).
13C NMR (75 MHz): d = 198.2, 158.5, 147.5, 145.0, 131.2, 130.8,
128.6, 128.5, 128.4, 128.1, 126.8, 126.5, 124.6, 122.9, 116.9, 38.3,
30.8, 20.4.
1H NMR (300 MHz, CDCl3): d = 8.06–7.98 (br s, 1 H, OH), 7.27–
7.20 (m, 4 H, HAr), 6.82 (d, J = 7.69 Hz, 2 H, HAr), 6.73 (d, J = 7.7
Hz, 2 H, HAr), 5.26 (d, J = 25.0 Hz, 1 H, CHAr), 4.47 (q, J = 19.2 Hz,
2 H, OCH2Ar), 3.79 (s, 3 H, CH3OC6H4CH2O), 3.75 (s, 3 H,
CH3OC6H4), 3.55 (t, J = 6.7 Hz, 2 H, CH2OPMB), 2.55 (t, J = 6.7
Hz, 2 H, CH2CH2OPMB), 2.40–2.17 (m, 4 H, CH2CO, CH2C=),
1.09 [s, 3 H, C(CH3)2], 0.96 [s, 3 H, C(CH3)2].
13C NMR (75 MHz): d = 196.2, 171.1, 159.2, 158.3, 132.5, 130.0,
129.8, 129.3, 129.2, 127.8, 114.9, 113.8, 113.7, 84.0, 80.6, 72.6,
67.6, 55.2, 55.1, 50.2, 43.0, 31.5, 29.1, 28.9, 27.3, 20.2.
HRMS (ESI): m/z [M + H]+ calcd for C22H19O2: 315.138; found:
315.1383.
HRMS (ESI): m/z [M + H]+ calcd for C28H33O5: 449.2323; found:
449.2322.
Tetrasubstituted Furans 8a–d; General Procedure
3-Alkyl-4-hydroxycoumarins 5a–d; General Procedure
To a stirred soln of propargylated 1,3-dicarbonyl compound 3h–j,
5d (1.0 mmol) in MeCN (6 mL) was added K2CO3 (2.0 mmol) and
the mixture was stirred at reflux temperature until complete con-
sumption of the starting material (TLC monitoring, Table 5). The
mixture was cooled to r.t. and MeCN was removed on a rotary evap-
orator. The crude was diluted with CH2Cl2 (15 mL) and washed
with H2O (2 × 10 mL). The organic layer was dried (anhyd
Na2SO4), concentrated in vacuo, and purified by column chroma-
tography (silica gel) to afford 8a–d.
A mixture of 4-hydroxycoumarin (4, 1.0 mmol), benzylic alcohol
1a,c,d,i (1.0 mmol), and B(C6F5)3 (5 mol%) in MeCN (5 mL) was
stirred at reflux temperature until complete consumption of the
starting material (Table 3). The mixture was cooled to r.t. and
MeCN was removed on a rotary evaporator. The crude was diluted
with CH2Cl2 (10 mL) and washed with H2O (2 × 10 mL). The or-
ganic layer was dried (anhyd Na2SO4), concentrated in vacuo, and
purified by column chromatography (silica gel) to afford pure 5a–d.
IR, 1H NMR, and MS data of known compounds 5a and 5b11b were
identical with those of authentic samples.
IR, 1H NMR, and MS data of known compounds 8a and 8b6e were
identical with those of authentic samples.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

3722
C. R. Reddy et al.
PAPER
6, 763. (f) Westermaier, M.; Mayr, H. Org. Lett. 2006, 8,
2-Benzyl-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (8c)
Colorless solid; mp 100–102 °C.
IR (KBr): 2948, 1676, 1574, 1494, 1451 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35–7.08 (m, 10 H, HAr), 3.90 (s,
2 H, PhCH2), 2.79 (t, J = 6.0 Hz, 2 H, CH2CO), 2.41 [t, J = 6.0 Hz,
2 H, =C(O–)CH2], 2.10–2.04 (m, 2 H, CH2CH2CO).
13C NMR (75 MHz): d = 193.9, 166.4, 150.3, 137.9, 131.4, 129.7,
126.4, 128.5, 128.3, 127.9, 127.3, 126.5, 38.5, 32.0, 23.7, 22.4.
HRMS (ESI): m/z [M + H]+ calcd for C21H19O2: 303.1380; found:
303.1392.
4791. (g) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Org.
Lett. 2004, 6, 3199. (h) De La Herran, G.; Segura, A.;
Csaky, A. G. Org. Lett. 2007, 9, 961.
(5) (a) Muzarat, J. Eur. J. Org. Chem. 2007, 3077. (b)Muzarat,
J. Tetrahedron 2005, 61, 4179. (c) Tamaru, Y. Eur. J. Org.
Chem. 2005, 2647. (d) Kayaki, Y.; Koda, T.; Ikaria, T.
J. Org. Chem. 2004, 69, 2595. (e) Kinoshita, H.;
Shinokubo, H.; Oshima, K. Org. Lett. 2004, 6, 4085.
(f) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241.
(g) Kimura, M.; Mukai, R.; Tanigawa, N.; Tanaka, S.;
Tamaru, Y. Tetrahedron 2003, 59, 7767. (h) Ozawa, F.;
Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami, T.;
Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968.
(i) Mukhopadhyay, M.; Iqbal, J. Tetrahedron Lett. 1995, 36,
6761. (j) Baruah, J. B.; Samuelson, A. G. J. Organomet.
Chem. 1989, 361, 57.
2-Benzyl-3-(1-tosyl-1H-indol-3-yl)-4H-furo[3,2-c]chromen-4-
one (8d)
Colorless solid; mp 80–85 °C.
IR (KBr): 3081, 1728, 1649, 1465, 1419 cm–1.
(6) (a) BF3·OEt2: Bisaro, F.; Prestat, G.; Vitale, M.; Poli, G.
Synlett 2002, 1823. (b) InCl3: Yasuda, M.; Somyo, T.; Baba,
A. Angew. Chem. Int. Ed. 2006, 45, 1414. (c) Bi(OTf)3:
Rueping, M.; Nachtsheim, B. J.; Kuenkel, A. Org. Lett.
2007, 9, 825. (d) Metal triflate (Sc, Yb, La, Hf): Noji, M.;
Kouno, Y.; Ishii, K. J. Org. Chem. 2007, 72, 5161.
(e) PTSA: Sanz, T.; Miguel, D.; Martinez, A.; Alvarez-
Gutierrez, J. M.; Rodriguez, F. Org. Lett. 2007, 9, 727.
(f) FeCl3: Jana, U.; Biswas, S.; Maiti, S. Tetrahedron Lett.
2007, 48, 4065. (g) I2: Rao, W.; Tay, A. H. J.; Goh, P. J.;
Choy, J. M. L.; Ke, J. K.; Chan, P. W. H. Tetrahedron Lett.
2008, 49, 122. (h) AuCl3/AgSbF6: Kothandaraman, P.; Rao,
W.; Zhang, X. X.; Chan, P. W. H. Tetrahedron 2009, 65,
1833. (i) PWA: Wang, G.-W.; Shen, Y.-B.; Wu, X.-L. Eur.
J. Org. Chem. 2008, 4999. (j) H-Montmorillonite:
1H NMR (300 MHz, CDCl3): d = 8.01 (d, J = 8.3 Hz, 1 H, HAr),
7.89–7.78 (m, 3 H, HAr), 7.12–7.53 (m, 14 H, HAr, =CN), 4.12 (s, 2
H, PhCH2), 2.35 (s, 3 H, PhCH3).
13C NMR (75 MHz): d = 157.5, 157.3, 154.5, 152.5, 145.1, 136.7,
134.9, 130.7, 129.9, 128.8, 128.4, 127.1, 126.9, 126.7, 124.9, 124.4,
123.4, 120.9, 120.5, 117.2, 113.7, 112.1, 111.1, 33.1, 29.6.
HRMS (ESI): m/z [M + H]+ calcd for C33H24NO5S: 546.1370;
found: 546.1361.
Acknowledgment
This work has been carried out as part of the Indo-French ‘Joint La-
boratory for Sustainable Chemistry at Interfaces’. We thank CSIR,
CNRS, and University of Rennes 1 for support.
Motokura, K.; Fujita, N.; Mori, K.; Mizugaki, T.; Ebitani,
K.; Kaneda, K. Angew. Chem. Int. Ed. 2006, 45, 2605.
(k) TfOH: Sanz, R.; Miguel, D.; Martinez, A.; Alvarez-
Gutierrez, J. M.; Rodriguez, F. Org. Lett. 2007, 9, 2027.
(l) Cu(OTf)2: Pan, Y.-M.; Zhao, S.-Y.; Ji, W.-H.; Zhan, Z.-
P. J. Comb. Chem. 2009, 11, 103. (m) EMIOTf: Funabiki,
K.; Komeda, T.; Kubota, Y.; Matsui, M. Tetrahedron 2009,
65, 7457. (n) Re catalyst: Kuninobu, Y.; Ueda, H.; Takue, K.
Chem. Lett. 2008, 37, 878. (o) PMA/SiO2: Yadav, J. S.;
Reddy, B. V. S.; Pandurangam, T.; Rao, K. V. R.; Praneeth,
K.; Kumar, G. G. K. S. N.; Madhavi, C.; Kunwar, A. C.
Tetrahedron Lett. 2008, 49, 4296. (p) Formic acid:
Gullickson, G. C.; Lewis, D. E. Aust. J. Chem. 2003, 56,
385;. (q) InBr3: Yadav, J. S.; Reddy, B. V. S.; Rao, K. V. R.;
Narender, R. Tetrahedron Lett. 2009, 50, 3963. (r) Mo(VI)
catalyst: Yang, H.; Fang, L.; Zhang, M.; Zhu, C. Eur. J. Org.
Chem. 2009, 666. (s) ZnCl2/TMSCl: Liu, C.-R.; Li, M.-B.;
Yang, C.-F.; Tian, S.-K. Chem. Eur. J. 2009, 15, 793.
(t) NaAuCl4: Georgy, M.; Boucard, V.; Debleds, O.; Zotto,
C. D.; Campagne, J.-M. Tetrahedron 2009, 65, 1758.
(u) Transition metal/MW: Babu, S. A.; Yasuda, M.;
Tsukahara, Y.; Yamaguchi, T.; Wada, Y.; Baba, A.
Synthesis 2008, 1717. (v) For alkylation using alcohols in
water, see: Cozzi, P. G.; Zoli, L. Angew. Chem. Int. Ed.
2008, 47, 4162.
References and Notes
(1) (a) House, H. O. Modern Synthetic Research, 2nd ed.;
Benjamin: Menlopark CA, 1972, 492. (b) Prout, F. S.;
Haung, E. P.-Y.; Hartman, R. J.; Korpies, C. J. J. Am. Chem.
Soc. 1954, 76, 1911. (c) Larock, R. C. Comprehensive
Organic Transformations; VCH: New York, 1999.
(d) Tsuji, J.; Minami, I. Acc. Chem. Res. 1987, 20, 140.
(e) Trost, B. M. Acc. Chem. Res. 1980, 13, 385.
(2) (a) Comprehensive Organic Synthesis, Vol. 3; Trost, B. M.;
Fleming, I., Eds.; Pergamon: Oxford, 1991. (b) Marquest,
J.; Moreno-Manas, M.; Pacheco, P.; Vallribera, A.
Tetrahedron Lett. 1988, 29, 1465. (c) Zhu, J.; You, L.;
Zhao, S. X.; White, B.; Chen, J. G.; Skonezny, P. M.
Tetrahedron Lett. 2002, 43, 7585. (d) Brandstrom, A.;
Junggren, U. Acta Chem. Scand. 1969, 23, 2204. (e) Durst,
H. D.; Liebeskind, L. J. Org. Chem. 1974, 39, 3271.
(f) Ranu, B. C.; Bhar, S. J. Chem. Soc., Perkin Trans. 1 1992,
365. (g) Moreno-Manas, M.; Marquet, J.; Vallribera, A.
Tetrahedron 1996, 52, 3377. (h) Lee, H.-S.; Park, J.-S.;
Kim, B. M.; Gellmann, S. H. J. Org. Chem. 2003, 68, 1575.
(3) (a) Adams, J. T.; Abramovitch, B.; Hauser, C. R. J. Am.
Chem. Soc. 1943, 65, 552. (b) Trost, B. M.; Crawley, M. L.
Chem. Rev. 2003, 103, 2921. (c) Ma, S.; Yu, S.; Peng, Z.;
Guo, H. J. Org. Chem. 2006, 71, 9865.
(4) (a) Antonioletti, R.; Bovicelli, P.; Malancona, S.
Tetrahedron 2002, 58, 589. (b) Armugam, S.; McLeod, D.;
Verkade, J. G. J. Org. Chem. 1998, 63, 3677. (c) Lei, A.;
Lu, X. Org. Lett. 2000, 2, 2357. (d) Konno, T.; Takehana,
T.; Ishihara, T.; Yamanaka, H. Org. Biomol. Chem. 2004, 2,
93. (e) Dieter, R. K.; Core, V. K.; Chen, N. Org. Lett. 2004,
(7) (a) Massey, A. G.; Park, A. J.; Stone, F. G. A. Proc. Chem.
Soc., London 1963, 212. (b) Massey, A. G.; Park, A. J.
J. Organomet. Chem. 1964, 2, 245. (c) Massey, A. G.; Park,
A. J. Organometallic Syntheses, Vol. 3; King, R. B.; Eisch,
J. J., Eds.; Elsevier: New York, 1986, 461. (d) Marks, T. J.
Acc. Chem. Res. 1992, 25, 57. (e) Yang, X.; Stern, C. L.;
Mark, T. J. J. Am. Chem. Soc. 1994, 116, 10015.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York

PAPER
Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcohols
3723
(8) For reviews on B(C6F5)3, see: (a) Erker, G. Dalton Trans.
Monatsh. Chem. 1957, 88, 25. (c) Ahluvalia, V. K.; Arora,
K. K.; Mukherjee, I. Indian J. Chem., Sect. B: Org. Chem.
Incl. Med. Chem. 1985, 298. (d) Huang, W.; Wang, J.; Shen,
Q.; Zhou, X. Tetrahedron 2007, 63, 11636. (e) Lin, X.; Dai,
X.; Mao, Z.; Wang, Y. Tetrahedron 2009, 65, 9233.
(f) Kischel, J.; Mertins, K.; Michalik, D.; Zapf, A.; Beller,
M. Adv. Synth. Catal. 2007, 349, 865. (g) Rueping, M.;
Nachtsheim, B. J.; Sugiono, E. Synlett 2010, 1549.
(14) Fan, J.; Wang, Z. Chem. Commun. 2008, 5381.
(15) (a) Ito, C.; Itoigawa, M.; Kanematsu, T.; Ruangrungsi, N.;
Mukainaka, T.; Tokuda, H.; Nishino, H.; Furukawa, H.
Phytochemistry 2003, 64, 1265. (b) Rukachaisirikul, V.;
Kamkaew, M.; Sukavisit, D.; Phongpaichit, S.;
2005, 1883. (b) Kargbo, R. B. Synlett 2004, 1118.
(c) Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999,
527. (d) Chandrasekhar, S.; Babu, B. N.; Chandrasekhar, G.
eEROS Encyclopedia Reagents in Organic Synthesis 2006,
DOI: 10.1002/047084289X.m00620.
(9) (a) Rottger, D.; Schmuck, S.; Erker, G. J. Organomet. Chem.
1996, 508, 263. (b) Bach, P.; Albright, A.; Laali, K. K. Eur.
J. Org. Chem. 2009, 1961. (c) Rubin, M.; Gevorgyan, V.
Org. Lett. 2001, 3, 2705. (d) Watson, I. D. G.; Yudin, A. K.
J. Org. Chem. 2003, 68, 5160. (e) Hog, D. T.; Oestreich, M.
Eur. J. Org. Chem. 2009, 5047. (f) Gevorgyan, V.; Liu, J.-
X.; Rubin, M.; Benson, S.; Yamamoto, Y. Tetrahedron Lett.
1999, 40, 8919. (g) Bajracharya, G. B.; Nogami, T.; Jin, T.;
Matsuda, K.; Gevorgyan, V. Synthesis 2004, 308.
(10) (a) Chandrasekhar, S.; Reddy, Ch. R.; Babu, B. N.;
Chandrashekar, G. Tetrahedron Lett. 2002, 43, 3801.
(b) Chandrasekhar, S.; Reddy, Ch. R.; Babu, B. N.;
Chandrashekar, G. Tetrahedron Lett. 2004, 45, 6481.
(c) Reddy, Ch. R.; Rajesh, G.; Balaji, S. V.; Chetan, N.
Tetrahedron Lett. 2008, 49, 970. (d) Reddy, Ch. R.;
Jithender, E. Tetrahedron Lett. 2009, 50, 5633.
Sawangchote, P.; Taylor, W. C. J. Nat. Prod. 2003, 66,
1531. (c) Quaglia, W.; Pigini, M.; Piergentili, A.; Giannella,
M.; Marucci, G.; Poggesi, E.; Leonardi, A.; Melchiorre, C.
J. Med. Chem. 1999, 42, 2961. (d) Kemnitzer, W.; Drewe,
J.; Jiang, S.; Zhang, H.; Crogan-Grandy, C.; Labreque, D.;
Bubenick, M.; Attardo, G.; Denis, R.; Lamothe, S.;
Gourdeau, H.; Tseng, B.; Kasibhatla, S.; Cai, S. J. Med.
Chem. 2008, 51, 417. (e) Hardcastle, I. R.; Cockcroft, X. I.;
Curtin, N. J.; El-Murr, M. D.; Leahy, J. J.; Stockley, M.;
Golding, B. T.; Regoreau, L.; Recordson, C.; Smith, G. C.
M.; Grifin, J. J. Med. Chem. 2005, 48, 7829. (f) Kidwai,
M.; Saxena, S.; Khan, M. K. R.; Thukral, S. S. Bioorg. Med.
Chem. Lett. 2005, 15, 4295.
(e) Chandrasekhar, S.; Khatun, S.; Rajesh, G.; Reddy, Ch. R.
Tetrahedron Lett. 2009, 50, 6693. (f) Chandrasekhar, S.;
Reddy, Ch. R.; Babu, B. N. J. Org. Chem. 2002, 67, 9080.
(g) Chandrasekhar, S.; Rao, Y. S.; Mahipal, B.;
Sreelakshimi, L.; Reddy, Ch. R. Synthesis 2008, 1737.
(11) (a) Reddy, Ch. R.; Madhavi, P. P.; Reddy, A. S. Tetrahedron
Lett. 2007, 48, 7169. (b) Reddy, Ch. R.; Srikanth, B.; Rao,
N. N.; Shin, D.-S. Tetrahedron 2008, 64, 11666. (c) Reddy,
Ch. R.; Rao, N. N.; Sudhakar, A. Lett. Org. Chem. 2008, 5,
473.
(12) (a) Raj, G.; Kumar, R.; McKinney, W. P. Am. J. Med. Sci.
1994, 307, 128. (b) Hadler, M. R.; Shadbolt, R. S. Nature
1975, 253, 275. (c) Wang, S.; Milne, G. W. A.; Yan, X.;
Posey, I. J.; Nicklaus, M. C.; Graham, L.; Rice, W. G.
J. Med. Chem. 1996, 39, 2047.
(16) For one-pot synthesis of tetrasubstituted furans, see: (a) ref.
6l. (b) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton,
M. D.; Hidai, M.; Uemura, S. Angew. Chem. Int. Ed. 2003,
42, 2681. (c) Feng, X.; Tan, Z.; Chen, D.; Shen, Y.; Guo,
C.-C.; Xiang, J.; Zhu, C. Tetrahedron Lett. 2008, 49, 4110.
(d) Ji, W.-H.; Pan, Y.-M.; Zhao, S.-Y.; Zhan, Z.-P. Synlett
2008, 3046.
(17) (a) Polivin, Y. N.; Postnov, V. N.; Sazonova, V. A.;
Zagorevski, D. V.; Nekrasov, Y. S.; Kharchevnikov, A. P.
J. Organomet. Chem. 1985, 288, 201. (b) Uozumi, Y.;
Danjo, H.; Hayashi, T. Tetrahedron Lett. 1997, 38, 3557.
(13) (a) Enders, A. Angew. Chem. 1957, 69, 481. (b) Ziegler, R.
Synthesis 2010, No. 21, 3715–3723 © Thieme Stuttgart · New York