P2O5-promoted efficient and diastereoselective synthesis of substituted 5-methylene-dihydropyran-2,6-diones and 3-methylene-3,4-dihydropyran-2-ones

Article abstract of DOI:10.1080/00397910802028879

A simple, efficient, and diastereoselective synthesis of 5-methylene-dihydropyran-2,6-diones and 3-methylene-3,4-dihydropyran-2-ones from substrates afforded by the SN2 reaction between the acetyl derivatives of the Baylis-Hillman adducts and methylacetoa

Full text of DOI:10.1080/00397910802028879

Synthetic Communications1, 38: 2113–2124, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802028879
P2O5-Promoted Efficient and Diastereoselective
Synthesis of Substituted
5-Methylene-dihydropyran-2,6-diones and
3-Methylene-3,4-dihydropyran-2-ones
Vijay Singh, Sudharshan Madapa, and Sanjay Batra
Medicinal and Process Chemistry Division, Central Drug Research Institute,
Lucknow, India
Abstract: A simple, efficient, and diastereoselective synthesis of 5-methylene-
dihydropyran-2,6-diones and 3-methylene-3,4-dihydropyran-2-ones from sub-
strates afforded by the SN2 reaction between the acetyl derivatives of the
Baylis–Hillman adducts and methylacetoacetate or acetylacetone or benzoyl
acetone via saponification followed by P2O5-mediated cyclization is described.
Keywords: Baylis–Hillman; 5-methylene-dihydropyran-2,6-diones; 3-methylene-
3,4-dihydropyran-2-ones; P2O5
Over the past couple of years, growth in synthetic applications of the
Baylis–Hillman adducts and their derivatives for the construction of a
variety of heterocycles is noteworthy.[1] Particularly, the derivatives
of the SN2 reaction between the acetyl derivatives and appropriately
substituted carbon nucleophiles serve as appropriate substrates for
the synthesis of a heterocyclic architecture incorporating an exocyclic
methylene group. We have demonstrated the synthesis of a variety of such
structural motifs including 3-methylene-d-valerolactone, 3-methylene-
2-pyrrolidinone, 3-methylene-pyrimidin-2,6-dione, and 3-methylene-1,3,4,5-
tetrahydro-benzo[b][1,4] diazepin-2-ones.[2] In continuation of our efforts
Received August 21, 2007
CDRI Communication No. 7444.
Address correspondence to Sanjay Batra, Medicinal and Process Chemistry
Division, Central Drug Research Institute, PO Box 173, Lucknow 226001, India.
E-mail: batra_san@yahoo.co.uk
2113

2114
V. Singh, S. Madapa, and S. Batra
in this direction, we now report the synthesis of 5-methylene-
dihydropyran-2,6-diones and 3-methylene-3,4-dihydropyran-2-ones.
Recently, we have achieved the synthesis of quinolines from the
substrates derived from the SN2 reaction between the acetate of the
Baylis–Hillman adducts of 2-nitro benzaldehyde and an acetyl group
containing carbon nucleophiles.[3] Based on these studies, it occurred
to us that analogous compounds derived from other aldehydes could
serve as substrates for the generation of a pyranone system. The pres-
ence of pyran-2,6-diones and pyran-2-ones as structural components
of several complex natural products makes them attractive synthetic
targets.[4] In addition, glutaric anhydride derivatives serve as useful
synthetic intermediates,[5] whereas 3-methylene-pyran-2,6-diones have
been useful in polymer chemistry.[6] But there exist only a few reports
that describe the synthesis of pyranone systems containing an exocyclic
double bond. In principle, the products afforded from SN2 reaction of
methylacetoacetate with the acetate of the Baylis–Hillman adduct of
acrylate, upon saponification, would lead to a 1,5-pentane dicarboxylic
acid that could be readily cyclized in the presence of a dehydrating
agent to yield such pyranones. A careful literature survey revealed that
several workers have reported the dehydaration of diacids in the pres-
ence of trifluoroacetic anhydride (TFAA).[7] In the context of Baylis–
Hillman chemistry, Basavaiah and Satyanarayana reported the synthesis
of [4.4.3] and [4.4.4] propellano-bislactones from the acetates of Baylis–
Hillman adducts wherein the final dehydration was carried out in the
presence of TFAA too.[8] More recently, Kim et al. also reported the
synthesis of a-pyranone from the acetate of the Baylis–Hillman adducts
via cyclization with TFAA.[9] However, to effect dehydration, we
decided to examine other dehydrating agents because TFAA requires
specialized handling procedures. Gratifyingly, treatment of 1,5-pentane
dicarboxylic acid with P2O5, which happens to be one of the cheapest
dehydrating agents in a chemical laboratory and was earlier utilized
to effect anhydride formation,[10] successfully yielded the desired pyra-
nones in excellent yields. This communication describes the results of
this synthetic achievement.
Initially the Baylis–Hillman adducts 1a–d were generated following
literature procedure.[11] Acetylating 1a–d with acetyl chloride in the pres-
ence of pyridine furnished the respective acetyl derivatives 2a–d in good
yields. The SN2 reaction of methyl acetoacetate in the presence of
DABCO in a THF–H2O system yielded substituted 1,5-dipentanoate
3a–d in 78–88% yields as diastereoisomeric mixtures. The saponification
of 3a–d with NaOH in the presence of methanol afforded the substituted
1,5-pentane dicarboxylic acid 4a–d in quantitative yields. Although the
formation of 4a was confirmed by mass spectroscopy, these diacids were

P2O5-Promoted Synthesis of Methylene Dihydrophranones
2115
Scheme 1. Reagents and conditions: (i) AcCl, pyridine, rt, 3 h; (ii) DABCO,
methyl acetoacetate, THF–H2O, rt, 3 h; (iii) NaOH, MeOH–H2O, rt, 4 h; (iv)
P2O5, dry toluene, rt, 1 h; (v) DABCO, acetyl acetone or benzoyl acetone,
THF–H2O, rt, 3 h.
not subjected to detailed spectral analysis and were used further without
any purification. Notably the molecular ion peak corresponded to a
product where the presence of an acetyl group was indicated. Generally,
it was observed that during the saponification, the loss of the acetyl group
takes place. Subsequent treatment of the 1,5-pentane dicarboxylic acid
4a–d with P2O5 in anhydrous toluene at room temperature furnished
the substituted 3-methylene-pyran-2,6-dione 5a–d in excellent yields.
Interestingly, the spectral data show the presence of single isomer. The
nuclear overhauser effect spectroscopy (NOESY) experiment led us to
assign the trans stereochemistry to these products. Significantly, this
methodology worked very well even at a higher scale.
Once the objective to obtain the desired pyranones from the
substrates of methyleacetoacetate was accomplished, to extend the utility
of our strategy we directed our attention to similar substrates afforded
from acetylacetone and benzoyl acetone. Thus, compounds 6a–d were
readily obtained via the SN2 reaction between compounds 2a–d and
acetyl acetone, whereas 7a–b were afforded from the reaction of 2a–b
with benzoyl acetone. Unlike 3a–d, saponification of 6a–d and 7a–b in
the presence of NaOH furnished the products 8a–d and 9a–b, respect-
ively, where the acetyl group was lost. Without any purification, these
products were treated with P2O5 in the presence of dry toluene to afford
10a–d and 11a–b. The formation of 3-methylene-3,4-dihydropyran-
2-ones implies that mechanistically in the first step of this reaction
keto-enol tautomerization occurs, followed by dehydration of the
intermediate.
In summary, we have demonstrated an efficient and practical
synthesis of substituted 5-methylene-dihydropyran-2,6-diones and 3-
methylene-3,4-dihydropyran-2-ones in excellent yields.

2116
V. Singh, S. Madapa, and S. Batra
EXPERIMENTAL
Melting points are uncorrected and were determined in capillary tubes on
an apparatus containing silicon oil. Infrared (IR) spectra were recorded
using Perkin-Elmer’s Spectrum RX I fourier transformed infrared
1
(FTIR) spectrophotometer. H NMR spectra were recorded either on
Bruker DPX-200 FT or Bruker Avance DRX-300 spectrometers, using
tetramethylsilane (TMS) as an internal standard (chemical shifts in d
values, J in hertz). The electronspray mass spectroscopy (ESMS) were
recorded on a Micromass LCMS system, and fast atomic bombardment
mass spectroscopy (FABMS) were recorded on a Jeol=SX-102 spec-
trometer. Elemental analyses were performed on Carlo Erba’s 108 or
Elementar’s Vario EL III microanalyzer. Synthesis and spectral data
for 6a–d have been published earlier.[2b]
General Procedure for the Preparation of Compounds 4a–d, and 7a–b
To a stirred solution of compounds from 2a–d (2.0 mmol) in tetrahydro-
furan (THF)–H2O (10 mL, 50:50, v=v), 1,4-diazabicyclo[2.2.2]ocatane
(DABCO) (3.0 mmol) was added at room temperature, and the reaction
was allowed to continue for 20 min. Thereafter, an appropriate nucleophile
(2.4 mmol) was added, and the reaction was continued at room temperature
for 3 h. The THF was removed from the reaction mixture via rotary evap-
oration, and the residue was diluted with water (100 mL) and extracted with
EtOAc (3 ꢀ 40 mL). The organic layers were pooled, washed with brine
(50 mL), dried (anhyd. Na2SO4), and evaporated to yield a residue, which
was purified via silica-gel chromatography employing hexane–EtOAc
(90:10, v=v) to afford products 3a–d or 7a–b as oils or solids.
Data
Dimethyl 2-Acetyl-4-methylene-3-phenylpentanedioate (3a)
1
Yield 92% as colorless oil; nmax (neat)1721 (CO and CO2Me) cmꢁ1; H
NMR (300 MHz, CDCl3) d ¼ 1.98 (s, 3H, CH3), 2.29 (s, 3H, CH3),
3.49 (s, 3H, CO2CH3), 3.69 (s, 3H, CO2CH3), 3.70 (s, 3H, CO2CH3),
3.72 (s, 3H, CO2CH3), 4.39 (d, 1H, J ¼ 6.3 Hz, CHAr), 4.43 (d, 1H,
J ¼ 6.3 Hz, CHAr), 4.47–4.76 (m, 2H, 2 ꢀ CHCO), 5.72 (d, 1H, J ¼
=
=
=
0.6 Hz, CH), 5.77 (s, 1H, J ¼ 0.7 Hz, CH), 6.29 (s, 1H, CH), 6.31
=
(s, 1H, CH), 7.21–7.25 (m, 10H, 2 ꢀ 5ArH); MS (FABþ) m=z 291
(Mþ þ 1). Anal. calcd. for C16H18O5: C, 66.19; H, 6.25. Found: C,
66.48; H, 6.02.

P2O5-Promoted Synthesis of Methylene Dihydrophranones
2117
Dimethyl 2-Acetyl-4-methylene-3-(4-methylphenyl)pentanedioate (3b)
Yield 89% as colorless oil; nmax (neat) 1721 (CO), 1733 (CO2Me) cmꢁ1
;
1H NMR (300 MHz, CDCl3) d ¼ 1.99 (s, 3H, CH3), 2.29 (s, 3H, CH3),
2.30 (s, 6H, 2 ꢀ ArCH3), 3.51 (s, 3H, CO2CH3), 3.70 (s, 3H, CO2CH3),
3.71 (s, 3H, CO2CH3), 3.72 (s, 3H, CO2CH3), 4.37 (d, 1H, J ¼ 4.8 Hz,
CHAr), 4.41 (d, 1H, J ¼ 4.8 Hz, CHAr), 4.68 (d, 1H, J ¼ 4.8 Hz,
=
CHCO), 4.72 (d, 1H, J ¼ 4.8 Hz, CHCO), 5.70 (s, 1H, CH), 5.76 (s,
=
=
=
1H, J ¼ 0.6 Hz CH), 6.27 (s, 1H, CH), 6.29 (s, 1H, CH), 7.07–7.17
(m, 8H, 2 ꢀ 4ArH); 13C NMR (50 MHz, CDCl3) d ¼ 29.4, 31.0, 46.5,
46.6, 52.4, 52.5, 52.9, 53.1, 124.7, 125.6, 127.0, 127.7, 127.8, 128.6,
128.9, 129.1, 138.9, 139.2, 141.0, 141.7, 166.7, 166.8, 168.4, 168.4,
201.7, 201.8; MS (FABþ) m=z 305 (Mþ þ 1). Anal. calcd. for C17H20O5:
C, 67.09; H, 6.62. Found. C, 67.39; H, 6.77.
2-Acetyl-3-(4-chloro-phenyl)-4-methylene-pentanedioic Acid Dimethyl
Ester (3c)
Yield 86% as colorless oil; nmax (neat)1721 (CO), 1734 (CO2Me) cmꢁ1
;
1H NMR (300 MHz, CDCl3) d ¼ 2.03 (s, 3H, CH3), 2.29 (s, 3H, CH3),
3.53 (s, 3H, CO2CH3), 3.70 (s, 3H, CO2CH3), 3.71 (s, 3H, CO2CH3),
3.73 (s, 3H, CO2CH3), 4.37 (d, 1H, J ¼ 4.1 Hz, CHAr), 4.41 (d, 1H,
J ¼ 4.1 Hz, CHAr), 4.68 (d, 1H, J ¼ 1.4 Hz, CHCO), 4.72 (d, 1H,
=
J ¼ 1.4 Hz, CHCO), 5.72 (s, 1H, CH), 5.77 (d, 1H, J ¼ 0.5 Hz,
=
=
=
CH), 6.30 (s, 1H, CH), 6.31 (s, 1H, CH), 7.19–7.28 (m, 8H,
2 ꢀ 4ArH); MS (FAB þ ) m=z 325 (Mþ þ 1). Anal. calcd. for C16H17ClO5:
C, 59.17; H, 5.28. Found. C, 59.43; H, 5.01.
Dimethyl 2-Acetyl-3-(2-chlorophenyl)-4-methylenepentanedioate (3d)
Yield 91% as colorless oil; nmax (neat) 1723 (CO), 1730 (CO2Me) cmꢁ1
;
1H NMR (300 MHz, CDCl3) d ¼ 2.09 (s, 3H, CH3), 2.32 (s, 3H, CH3),
3.53 (s, 3H, CO2CH3), 3.70 (s, 3H, CO2CH3), 3.71 (s, 3H, CO2CH3),
3.73 (s, 3H, CO2CH3), 4.64 (d, 1H, J ¼ 10.5 Hz, CHAr), 4.68 (d, 1H,
J ¼ 10.4 Hz, CHAr), 5.15 (d, 1H, J ¼ 10.5 Hz, CHCO), 5.17 (d, 1H,
=
J ¼ 10.3 Hz, CHCO), 5.85 (s, 1H, CH), 5.91 (d, 1H, J ¼ 0.5 Hz,
=
=
CH), 6.32 (s, 1H, CH), 6.36 (s, 1H, CH), 7.16–7.22 (m, 4H,
=
2 ꢀ 2ArH), 7.35–7.48 (m, 4H, 2 ꢀ 2ArH); MS (FABþ) m=z 325
(Mþ þ 1). Anal. calcd. for C16H17ClO5: C, 59.17; H, 5.28. Found: C,
58.97; H, 5.01.

2118
V. Singh, S. Madapa, and S. Batra
Methyl 2-(2-Benzoyl-3-oxo-1-phenylbutyl)acrylate (7a)
Yield 83% as a white solid, mp 99–100ꢂC; nmax (KBr) 1715 (CO and
CO2Me) cmꢁ1
2.21 (s, 3H, CH3), 3.66 (s, 3H, CO2CH3), 3.73 (s, 3H, CO2CH3), 5.06
;
1H NMR (300 MHz, CDCl3) d ¼ 1.99 (s, 3H, CH3),
(d, 2H, J ¼ 12.0 Hz, 2 ꢀ CHAr), 5.46–5.61 (m, 2H, 2 ꢀ CHCO), 5.63
=
(d, 1H, CH), 5.91 (s, 1H, CH), 6.13 (s, 1H, CH), 6.39 (s, 1H,
=
=
=
CH), 7.08–7.18 (m, 6H, 2 ꢀ 3ArH), 7.24–7.32 (m, 6H, 2 ꢀ 3ArH),
7.36–7.54 (m, 6H, 2 ꢀ 3ArH), 7.89 (d, 2H, J ¼ 7.2 Hz, ArH); MS
(ES þ ) m=z 337.1 (Mþ þ 1). Anal. calcd. for C21H20O45: C, 74.98; H,
5.99. Found. C, 75.13; H, 5.91.
Methyl 2-[2-Benzoyl-1-(4-methylphenyl)-3-oxobutyl]acrylate (7b)
Yield 85% as a white solid, mp 100–102ꢂC; nmax (KBr) 1719 (CO and
1
CO2Me) cmꢁ1; H NMR (300 MHz, CDCl3) d ¼ 2.00 (s, 3H, COCH3),
2.20 (d, 6H, J ¼ 1.4 Hz, COCH3 and ArCH3), 2.32 (s, 3H, ArCH3),
3.66 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 5.02 (t, 2H, J ¼ 12.0 Hz,
=
=
2 ꢀ CH), 5.46–5.60 (m, 3H, CH and 2 ꢀ CH), 5.90 (s, 1H, CH), 6.11
=
=
(s, 1H, CH), 6.36 (s, 1H, CH), 6.96 (d, 2H, J ¼ 8.0 Hz, ArH), 7.11–
7.15 (m, 4H, ArH), 7.26 (d, 2H, J ¼ 8.0 Hz, ArH), 7.40 (t, 2H,
J ¼ 7.9 Hz, ArH), 7.49–7.54 (m, 3H, ArH), 7.60–7.62 (m, 1H, ArH),
7.87–7.90 (m, 2H, ArH), 8.09–8.12 (m, 2H, ArH); 13C NMR (75 MHz,
CDCl3) d ¼ 19.6, 19.8, 26.1, 27.0, 45.3, 45.4, 50.7, 50.8, 66.0, 66.4,
123.0, 124.6, 127.0, 127.2, 127.4, 127.6, 127.7, 127.9, 128.2, 132.3,
132.6, 134.3, 134.5, 135.3, 135.4, 135.5, 135.8, 139.6, 140.1, 165.1,
165.3, 192.6, 192.9, 201.1, 201.9; MS (ES þ ) m=z 351.2 (Mþ þ 1). Anal.
calcd. for C22H22O4: C, 75.41; H, 6.33. Found: C, 75.33; H, 6.11.
General Procedure for the Preparation of Compounds 5a–d, 10a–d, and
11a–b.
To a stirred solution of appropriate compound from 3a–d, 6a–d, and 7a–b
(1.0 mmol) in methanol (10 mL), aqueous NaOH (2 mL, 50% w=v) was
added and the reaction was allowed to proceed for 4 h at room tempera-
ture. Thereafter, methanol was evaporated, and the reaction mixture was
acidified with conc. HCl (up to pH 3–4). The compound was extracted
with EtOAc (3 ꢀ 40 mL), and the solvent was evaporated to yield crude
products, which were utilized further without any purification. To a
stirred solution of appropriate crude product (4a–d, 8a–d, 9a–b) in dry
toluene (10 mL), P2O5 (0.7 g, 5.0 mmol) was added, and the reaction mix-
ture was allowed to proceed at room temperature for 1 h. On completion,

P2O5-Promoted Synthesis of Methylene Dihydrophranones
2119
as evident by thin-layer chromotography (TLC) analysis and also by
change in color of the reaction mixture to brown or red, the toluene
was removed via rotary evaporation. The residue was diluted with EtOAc
(50 mL) and filtered. The filtrate was evaporated to yield a crude pro-
duct, which was purified via silica-gel chromatography employing
hexane–EtOAc (90:10, v=v) to afford products 5a–d, 10a–d, and 11a–b
as oils or solids
Data
3-Acetyl-5-methylene-4-phenyldihydro-2H-pyran-2,6(3H)-dione (5a)
Yield 83% as a pale yellow solid, mp 71–73ꢂC; nmax (KBr) 1734 (CO)
1
cmꢁ1; H NMR (300 MHz, CDCl3) d ¼ 2.00 (s, 3H, CH3), 4.35 (d, 1H,
J ¼ 4.3 Hz, CHAr), 5.11 (d, 1H, J ¼ 4.3 Hz, CHCO), 5.55 (s, 1H,
=
=
CH), 6.51 (s, 1H, CH), 7.20–7.27 (m, 2H, ArH), 7.29–7.36 (m, 3H,
ArH); 13C NMR (50 MHz, CDCl3) d ¼ 19.4, 44.2, 103.8, 127.8, 128.0,
129.4, 130.9, 136.7, 142.7, 148.5, 163.3; MS (ESþ) m=z 245.1 (Mþ þ 1).
Anal. calcd. for C14H12O4: C, 68.85; H, 4.95. Found: C, 68.48; H, 5.07.
3-Acetyl-5-methylene-4-(4-methylphenyl)dihydro-2H-pyran-2,6(3H)-
dione (5b)
Yield 79% as a pale yellow solid, mp 128–130ꢂC; nmax (KBr)1722 (CO)
1
cmꢁ1; H NMR (300 MHz, CDCl3) d ¼ 1.99 (s, 3H, CH3), 2.35 (s, 3H,
ArCH3), 4.31 (d, 1H, J ¼ 4.2 Hz, CHAr), 5.09 (d, 1H, J ¼ 4.2 Hz,
=
=
CHCO), 5.53 (s, 1H, CH), 6.49 (s, 1H, CH), 7.11 (d, 2H, J ¼ 8.0 Hz,
ArH), 7.16 (d, 2H, J ¼ 8.0 Hz, ArH); 13C NMR (50 MHz, CDCl3)
d ¼ 19.4, 21.4, 43.8, 104.0, 127.8, 130.1, 130.8, 130.9, 136.9, 137.4,
139.8, 148.3, 161.7, 163.5; MS (FABþ) m=z 259 (Mþ þ 1). Anal. calcd.
for C15H14O4: C, 69.76; H, 5.46. Found: C, 70.09; H, 5.23.
3-Acetyl-4-(4-chlorophenyl)-5-methylenedihydro-2H-pyran-2,6(3H)-
dione (5c)
1
Yield 81% as pale yellow oil; nmax (neat) 1724 (CO) cmꢁ1; H NMR
(300 MHz, CDCl3) d ¼ 1.99 (s, 3H, CH3), 4.32 (d, 1H, J ¼ 4.2 Hz,
CHAr), 5.07 (d, 1H, J ¼ 4.2 Hz, CHCO), 5.53 (d, 1H, J ¼ 1.5 Hz,
=
=
CH), 6.54 (t, 1H, J ¼ 0.8 Hz, CH), 7.15 (d, 2H, J ¼ 8.0 Hz, ArH),
7.31 (d, 2H, J ¼ 8.0 Hz, ArH); 13C NMR (50 MHz, CDCl3) d ¼ 19.3,
43.5, 103.3, 129.4, 129.5, 131.0, 133.5, 136.4, 141.1, 148.9, 164.5; MS

2120
V. Singh, S. Madapa, and S. Batra
(FABþ) m=z 279 (Mþ þ 1). Anal. calcd. for C14H11ClO4: C, 60.34; H,
3.98. Found: C, 60.38; H, 4.19.
3-Acetyl-4-(2-chlorophenyl)-5-methylenedihydro-2H-pyran-2,6(3H)-
dione (5d)
1
Yield 78% as pale yellow oil; nmax (neat) 1731(CO) cmꢁ1; H NMR
(300 MHz, CDCl3) d ¼ 1.99 (s, 3H, CH3), 4.91 (q, 1H, J ¼ 4.2 Hz,
CHAr), 5.07 (d, 1H, J ¼ 4.2 Hz, CHCO), 5.65 (q, 1H, J ¼ 0.6 Hz,
=
=
CH), 6.56 (t, 1H, J ¼ 2.0 Hz, CH), 7.19–7.26 (m, 3H, ArH), 7.31–
7.46 (m, 1H, ArH); 13C NMR (50 MHz, CDCl3) d ¼ 19.4, 40.7, 102.5,
128.0, 129.0, 129.7, 130.4, 131.3, 133.6, 135.1, 140.3, 149.0, 163.1. MS
(FABþ) m=z 279 (Mþ þ 1). Anal. calcd. for C14H11ClO4: C, 60.34; H,
3.98. Found: C, 60.57; H, 4.11.
6-Methyl-3-methylene-4-phenyl-3,4-dihydro-2H-pyran-2-one (10a)
Yield 93% as a pale yellow solid, mp 77–78ꢂC; nmax (KBr) 1721 (CO)
1
cmꢁ1; H NMR (300 MHz, CDCl3) d ¼ 2.00 (s, 3H, CH3), 4.35 (q, 1H,
J ¼ 1.9 Hz, CHAr), 5.11 (d, 1H, J ¼ 4.2 Hz, CHCO), 5.55 (q, 1H,
=
=
J ¼ 0.8 Hz, CH), 6.51 (t, 1H, J ¼ 0.8 Hz, CH), 7.20–7.23 (m, 2H,
ArH), 7.26–7.38 (m, 3H, ArH); 13C NMR (50 MHz, CDCl3) d ¼ 19.4,
44.2, 103.8, 127.8, 128.0, 129.4, 130.9, 136.7, 142.7, 145.5, 163.3; MS
(FABþ) m=z 201 (Mþ þ 1). Anal. calcd. for C13H12O2: C, 77.98; H,
6.04. Found: C, 77.16; H, 6.16.
6-methyl-3-methylene-4-(4-methylphenyl)-3,4-dihydro-2H-pyran-2-one (10b)
Yield 82% as a pale yellow solid, mp 145–148ꢂC; nmax (KBr) 1725 (CO)
1
cmꢁ1; H NMR (300 MHz, CDCl3) d ¼ 1.98 (s, 3H, CH3), 2.35 (s, 3H,
ArCH3), 4.31 (q, 1H, J ¼ 2.0 Hz, CHAr), 5.09 (d, 1H, J ¼ 4.0 Hz,
=
=
CHCO), 5.54 (s, 1H, CH), 6.49 (s, 1H, CH), 7.10 (d, 2H, J ¼ 8.1 Hz,
ArH), 7.16 (d, 2H, J ¼ 8.1 Hz, ArH); 13C NMR (75 MHz, CDCl3)
d ¼ 17.6, 19.7, 42.1, 102.3, 126.1, 126.8, 128.4, 128.9, 135.3, 135.7,
138.1, 146.7, 161.7; MS (ESþ) m=z 215.1 (Mþ þ 1). Anal. calcd. for
C14H14O2: C, 78.48; H, 6.59. Found: C, 78.21; H, 6.73.
4-(4-Chlorophenyl)-6-methyl-3-methylene-3,4-dihydro-2H-pyran-
2-one (10c)
1
Yield 91% as pale yellow oil; nmax (neat) 1711 (CO) cmꢁ1; H NMR
(200 MHz, CDCl3) d ¼ 1.98 (s, 3H, CH3), 4.32 (s, 1H, CHAr), 5.06

P2O5-Promoted Synthesis of Methylene Dihydrophranones
2121
=
=
(d, 1H, J ¼ 3.3 Hz, CHCO), 5.52 (s, 1H, CH), 6.50 (s, 1H, CH), 7.13
(d, 2H, J ¼ 8.2 Hz, ArH), 7.31 (d, 2H, J ¼ 8.3 Hz, ArH); 13C NMR
(50 MHz, CDCl3) d ¼ 19.3, 43.5, 103.3, 129.4, 129.5, 129.9, 131.1,
133.6, 136.4, 141.1, 148.9, 163.0; MS (ESþ) m=z 235.2 (Mþ þ 1). Anal.
calcd. for C13H11ClO2: C, 66.53; H, 4.72. Found: C, 66.61; H, 5.02.
4-(2-Chlorophenyl)-6-methyl-3-methylene-3,4-dihydro-2H-pyran-
2-one (10d)
1
Yield 87% as pale yellow oil; nmax (neat) 1716 (CO) cmꢁ1; H NMR
(300 MHz, CDCl3) d ¼ 1.97 (s, 3H, CH3), 4.90 (q, 1H, J ¼ 1.8 Hz,
CHAr), 5.06 (d, 1H, J ¼ 3.9 Hz, CHCO), 5.63 (d, 1H, J ¼ 1.0 Hz,
=
=
CH), 6.53 (s, 1H, CH), 7.19–7.26 (m, 3H, ArH), 7.37–7.40 (m, 1H,
ArH); 13C NMR (75 MHz, CDCl3) d ¼ 17.7, 39.1, 100.8, 126.3, 127.3,
128.0, 128.7, 129.7, 131.9, 133.4, 138.7, 147.3; MS (ESþ) m=z 235.0
(Mþ þ 1). Anal. calcd. for C13H11ClO2: C, 66.53; H, 4.72. Found: C,
66.39; H, 4.59.
3-Methylene-4,6-diphenyl-3,4-dihydro-2H-pyran-2-one (11a)
Yield 85%as yellow oil; nmax (neat) 1716 (CO) cmꢁ1 1H NMR
;
(200 MHz, CDCl3) d ¼ 4.56 (d, 1H, J ¼ 1.9 Hz, CHAr), 5.53 (q, 1H,
=
J ¼ 0.8 Hz, CH), 5.90 (d, 1H, J ¼ 4.3 Hz, CHCO), 6.56 (s, 1H,
CH), 7.22–7.38 (m, 8H, ArH), 7.68 (d, 2H, J ¼ 4.3 Hz, ArH); 13C
=
NMR (50 MHz, CDCl3) d ¼ 42.9, 102.1, 123.4, 123.5, 126.2, 126.3,
126.9, 127.7, 127.8, 1218.0, 128.5, 129.9, 131.0, 135.1, 140.5, 162.5; MS
(FABþ) m=z 263 (Mþ þ 1). Anal. calcd. for C18H14O2: C, 82.42; H,
5.38. Found: C, 82.29; H, 5.59.
3-Methylene-4-(4-methylphenyl)-6-phenyl-3,4-dihydro-2H-pyran-
2-one (11b)
1
Yield 79% as pale yellow oil; nmax (neat) 1719 (CO) cmꢁ1; H NMR
(300 MHz, CDCl3) d ¼ 2.36 (s, 3H, CH3), 4.54 (t, 1H, J ¼ 2.2 Hz,
=
CHAr), 5.61 (d, 1H, J ¼ 1.3 Hz, CH), 5.90 (d, 1H, J ¼ 4.5 Hz, CHCO),
=
6.56 (d, 1H, J ¼ 0.9 Hz, CH), 7.15–7.18 (m, 4H, ArH), 7.38–7.43 (m,
3H, ArH), 7.68–7.71 (m, 2H, ArH); 13C NMR (75 MHz, CDCl3)
d ¼ 19.8, 42.5, 102.3, 123.4, 126.2, 127.0, 127.7, 127.9, 128.0, 128.3,
128.5, 129.2, 129.9, 131.0, 135.1, 136.0, 138.1, 147.4, 161.4; MS (ESþ)
m=z 277.2 (Mþ þ 1). Anal. calcd. for C19H16O2: C, 82.58; H, 5.84. Found:
C, 82.81; H, 5.99.

2122
V. Singh, S. Madapa, and S. Batra
ACKNOWLEDGMENTS
Two of the authors (V. S. and S. M.) acknowledge the financial support
from Council of Scientific and Industrial Research (CSIR), New Delhi, in
the form of fellowships. The financial support for this work from Depart-
ment of Science and Technology (DST), New Delhi, is also acknowledged.
REFERENCES
1. (a) Basavaiah, D.; Jaganmohan Rao, A.; Satyanarayana, T. Recent advances
in the Baylis–Hillman reaction and applications. Chem. Rev. 2003, 103, 811;
(b) Pathak, R.; Madapa, S.; Batra, S. Trifluoroacetic acid: A more effective
and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-
quinolin-2-ones and 3-arylmethyl-2-amino-quinolines from Baylis–Hillman
derivatives via Claisen rearrangement. Tetrahedron 2007, 63, 451; (c) Nag,
S.; Yadav, G. P.; Maulik, P. R.; Batra, S. Sodium hydride mediated cascade
reaction towards the synthesis of 1,5-disubstituted uracil from cyanamides
derived from Baylis–Hillman adducts. Synthesis 2007, 911; (d) Zhang, Q.;
Sun, S.; Hu, J.; Liu, Q.; Tan, J. BF3 ꢃ Et2O-catalyzed direct carbon–carbon
bond formation of a-EWG ketene-(S,S)-acetals and alcohols and synthesis
of unsymmetrical biaryls. J. Org. Chem. 2007, 72, 139; (e) Chen, P. Y.; Chen,
H. M.; Chen, L. Y.; Tzeng, J. Y.; Tsai, J. C.; Chi, P. C.; Li, S. R.; Wang, E. C.
Claisen rearrangement=Baylis–Hillman reaction=ring-closing metathesis as
bases for the construction of substituted cyanonaphthalenes. Tetrahedron
2007, 63, 2824; (f) Majhi, T. P.; Neogi, A.; Ghosh, S.; Mukherjee, A. K.;
Chattopadhyay, P. Sequential Baylis–Hillman reaction and radical cycliza-
tion of furanose derivatives: Expeditious approach to enantiopure benzo-
fused nine-membered oxacycles. Tetrahedron 2006, 62,12003; (g) Lee, K. Y.;
Gowrisankar, S.; Lee, Y. J.; Kim, J. N. Synthesis of 2-amino-2,3-dihydro-
benzofurans and fully substituted furans from modified Baylis–Hillman
adducts. Tetrahedron 2006, 62, 8798; (h) Shanmugam, P.; Vaithiyanathan,
V.; Viswambharan, B. Synthesis of functionalized 3-spirocyclopropane-
2-indolones from isomerised Baylis–Hillman adducts of isatin. Tetrahedron
2006, 62, 4342; (i) Basavaiah, D.; Reddy, R. J.; Rao, J. S. Applications of
Baylis–Hillman adducts: A simple, convenient, and one-pot synthesis of
3-benzoylquinolines. Tetrahedron Lett. 2006, 47, 73; (j) Kim, S. C.; Lee,
H. S.; Lee, Y. J.; Kim, J. N. Regioselective construction of polysubstituted
phenols from Baylis–Hillman adducts via formal [4 þ 2] annulation strategy.
Tetrahedron Lett. 2006, 47, 5681; (k) Du, Y.; Feng, J.; Lu, X. A phosphine-
catalyzed [3 þ 6] annulation reaction of modified allylic compounds and tro-
pone. Org. Lett. 2005, 7, 1987; (l) Mix, S.; Blechert, S. Synthesis of cis-fused
carbo-bicycles by domino enyne cross-metathesis=intramolecular Diels–
Alder reaction. Org. Lett. 2005, 7, 2015; (m) Pathak, R.; Batra, S.
Expeditious synthesis of 5,6,7,8-tetrahydro imidazo [1,2-a]pyrimidin-2-ones
and 3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones. Tetrahedron

P2O5-Promoted Synthesis of Methylene Dihydrophranones
2123
2007, 63, 9448; (n) Nag, S.; Madapa, S.; Batra, S. Application of primary
allyl amines afforded by the Baylis–Hillman adducts for heterocyclic
synthesis: Generation of 5-benzyl-4(3H)-pyrimidinones and 2-benzylidene-
2,3-dihydro-pyrrolizin-1-ones. Synthesis 2008, 101; (o) Singh, V.; Yadav, G.
P.; Maulick, P. R.; Batra, S. Synthesis of substituted 3-methylene-2-pyridones
from Baylis–Hillman derivatives and its application for the generation of
2-pyridone susbtituted spiroisoxazolines. Tetrahedron 2008, 64, 2979.
2. (a) Pathak, R.; Nag, S.; Batra, S. A facile synthesis of 3-methylene-4-aryl-
1,3,4,5-tetrahydrobenzo[b][1,4]diazepin-2-ones and 3-arylmethylene-4,5-dihy-
dro-3H-benzo[b][1,4]diazepin-2-ylamines. Synthesis 2006, 4205; (b) Singh, V.;
Batra, S. Convenient synthesis of substituted a-methylene-d-valerolactones in
aqueous medium using Baylis–Hillman chemistry. Synthesis 2006, 63; (c)
Singh, V.; Kanojiya, S.; Batra, S. Studies on the reduction of the nitro group
in 3-aryl-2-methylene-4-nitro-alkanoates afforded by the Baylis–Hillman
adducts: Synthesis of 4-aryl-3-methylene-2-pyrrolidinones and 3-(1-alkoxy-
carbonyl-vinyl)-1H-indole-2-carboxylates. Tetrahedron 2006, 62, 10100; (d)
Singh, V.; Yadav, G. P.; Maulik, P. R.; Batra, S. Studies toward the
construction of substituted piperidine-2-ones and pyridine-2-ones from
Baylis–Hillman adducts: Discovery of a facile synthesis of 5-methyl-4-oxo-6-
aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates. Tetrahedron 2006, 62, 8731.
3. Madapa, S.; Singh, V.; Batra, S. An alternate approach to quinoline architec-
ture via Baylis–Hillman chemistry: SnCl2-mediated tandem reaction toward
synthesis of 4-(substituted vinyl)-quinolines. Tetrahedron 2006, 62, 8740.
4. (a) Brownbridge, P.; Chan, T. H.; Brook, M. A.; Kang, G. J. Chemistry of
enol silyl ethers: A general synthesis of 3-hydroxyhomophthalates and a
biomimetic synthesis of sclerin. Can. J. Chem. 1983, 61, 688; (b) Ayer, W. A.;
Hoyano, Y.; Pedras, M. S.; Altena, I. V. Metabolites produced by the scler-
oderris canker fungus, Gremmeniella abietina, part 1. Can. J. Chem. 1986, 64,
1585; (c) Asaoka, M.; Sonoda, S.; Fujii, N.; Takei, H. Diastereoselective 1,4-
addition of various nucleophiles to 5-trimethylsilyl-2-cyclohexenone:
Synthesis of (þ)-ramulosin. Tetrahedron 1990, 46, 1541; (d) Boulet, C. A.;
Poulton, G. A. Pentaketide metabolite from Potebniamyces gallicola n. sp.
Can. J. Chem. 1983, 61, 2285; (e) Fried, J.; Richard, W. T.; Klingsberg, A.
Oxidation of steroids by micro organisms, III: Side chain degradation, ring
D-cleavage and dehydrogenation in ring A. J. Am. Chem. Soc. 1953, 75,
5764; (f) Peterson, D. H.; Eppstein, S. H.; Meister, P. D.; Murray, H. C.;
Leigh, H. M.; Weintraub, A.; Reineke, L. M. Microbiological transforma-
tions of steroids, IX: Degradation of C21 steroids to C19 ketones and to tes-
tololactone. J. Am. Chem. Soc. 1953, 75, 5768.
5. (a) Loos, V.; Jozef, L. M.; Roest, B. C. a-Methyleneglutaric acid anhydride.
Neth. Appl. NL 72-14550-19721027, 1974; Chem. Abstr. 1974, 81, 63161w;
(b) Stewart, W. W. Synthesis of 3,6-disulfonated 4-aminonaphthalimides.
J. Am. Chem. Soc. 1981, 103, 7615.
6. (a) Berlin, A. Y. Condensation and polymerization of a-b-unsaturated alde-
hydes and acids, IV: Condensation of a-methyleneglutaric acid anhydride
with butadiene. J. Gen.Chem. 1944, 14, 116; Chem. Abstr. 1945, 39, 915;

2124
V. Singh, S. Madapa, and S. Batra
(b) Semon, W. L.; Jones, J. F. Polymers containing anhydryde groups. Ger.
1,086,892, 1960; Chem. Abstr. 1961, 55, 22913f.
7. A few representative references only: (a) Keen, S. P.; Cowden, C. J.; Bishop,
B. C.; Brands, K. M. J.; Davies, A. J.; Dolling, U. H.; Lieberman, D. R.;
b
Stewart, G. W. Practical asymmetric synthesis of a non-peptidic av 3 antag-
onist. J. Org. Chem. 2005, 70; 1771; (b) Boger, D. L.; Hong, J.; Hikota,
M.; Ishida, M. Total synthesis of phomazarin. J. Am. Chem. Soc. 1999,
121, 2471; (c) Kim, H. O.; Ji, X.; Melman, N.; Olah, M. E.; Stiles, G. L.;
Jacobson, K. A. Structure–activity relationships of 1,3-dialkylxanthine deri-
vatives at rat A3 adenosine receptors. J. Med. Chem. 1994, 37, 3373; (d)
Boger, D. L.; Baldino, C. M. d,l- and meso-isochrysohermidin: Total syn-
thesis and interstrand DNA crosslinking. J. Am. Chem. Soc. 1993, 115,
11418.
8. Basavaiah, D.; Satyanarayana, T. A novel and facile synthesis of functiona-
lized [4.4.3] and [4.4.4]propellano-bislactones using acetates of the Baylis–
Hillman adducts. Org. Lett. 2001, 3, 3619.
9. Kim, S. J.; Lee, H. S.; Kim, J. N. Synthesis of 3,5,6-trisubstituted a-pyrones
from Baylis–Hillman adducts. Tetrahedron Lett. 2007, 48, 1069.
10. A few representative references only: (a) Sugiyama, A; Shibanuma, T. Process
for producing fluorocarboxylic anhydrides. U.S. Patent 6,903,236, 2005; (b)
Bourne, E. J.; Stacey, M.; Tatlow, J. C.; Tedder, J. M. Studies on trifluoroa-
cetic acid, part I: Trifluoroacetic anhydrides as a promoter of ester formation
between hydroxyl compounds and carboxylic acids. J. Chem. Soc. 1949, 2976;
(c) Prichard, W. W.; Del, W. Cyclic anhydrides of aromatic dicarboxylic
acids. U.S. Patent 2,680,751, 1954; Chem. Abstr. 1955, 49, 6308; (d) March
J. (Ed). Advanced Organic Chemistry, 4th ed.; John Wiley & Sons, Singapore,
2003; p. 401.
11. Patra, A.; Batra, S.; Kundu, B.; Joshi, B. S.; Roy, R.; Bhaduri, A. P.
5-Isoxazolecarboxaldehyde: A novel substrate for fast Baylis–Hillman reac-
tion. Synthesis 2001, 276.