Stereoselective synthesis of trisubstituted tetrahydrofurans by radical cyclisation reaction using a hypophosphite salt. Application to the total synthesis of (±)-dihydrosesamin

Article abstract of DOI:10.1016/S0040-4020(02)00113-8

The stereoselective synthesis of tetrahydrofurans has been achieved from bromoalkynes and bromoalkenes by intramolecular radical cyclisation using a hypophosphite salt. This radical cyclisation strategy has successfully been applied to the total synthesis

Full text of DOI:10.1016/S0040-4020(02)00113-8

TETRAHEDRON
Pergamon
Tetrahedron 58 12002) 2435±2439
Stereoselective synthesis of trisubstituted tetrahydrofurans by
radical cyclisation reaction using a hypophosphite salt.
Application to the total synthesis of ꢀ6)-dihydrosesamin
Subhas Chandra Roy,a,p Chandrani Guin,a Kalyan Kumar Ranaa and Gourhari Maitib
aDepartment of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
bDepartment of Chemistry, Jadavpur University, Jadavpur, Calcutta 700 032, India
Received 26 July 2001; revised 2 January 2002; accepted 24January 2002
AbstractÐThe stereoselective synthesis of tetrahydrofurans has been achieved from bromoalkynes and bromoalkenes by intramolecular
radical cyclisation using a hypophosphite salt. This radical cyclisation strategy has successfully been applied to the total synthesis of a
naturally occurring bioactive furanolignan, dihydrosesamin. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
N-bromosuccinimide and propargyl alcohol at 2158C to
room temperature under nitrogen atmosphere.5 Compound
7a was prepared from 3,4-dihydro-2H-pyran under identical
reaction conditions. For the preparation of compound 8a,
allyl alcohol was used instead of propargyl alcohol. The
bromo-ethers were found to be a mixture of threo and
erythro isomers in a ratio of 1:1. The ratio was determined
from the only distinguishable signals in 1H NMR spectra for
the methylene protons adjacent to the triple bond as two
double doublets at d 3.87 1Jˆ16 and 2.4Hz) and at d
4.12 1Jˆ16 and 2.4Hz) for 1a and two double doublets at
d 9.93 1Jˆ16.2 and 2.4Hz) and at d 4.15 1Jˆ16.1 and
2.4Hz) for 2a. No such distinguishable signals were
The formation of carbon±carbon bonds by radical cyclisa-
tion has become an invaluable synthetic tool in organic
chemistry especially in the total synthesis of complex
natural products.1 The majority of radical reactions are
based on tributyltin hydride as the reducing agents, mainly
tri-n-butyl tin hydride. However, organo-tin compounds are
toxic and the separation of tin residues from the products
can be laborious. Organo-silanes such as tris1trimethylsilyl)-
silane2 are good alternatives to tin hydrides. Although
silanes are much less toxic, the development of a more
ecofriendly and cost effective alternative to n-Bu3SnH
would allow much more industrial applications of radical
methodology. Hypophosphorus acid and its salts mainly,
1-ethylpiperidine hypophosphite 1EPHP),3 are effective
radical reducing agents for organic halides. We report
here a successful application of EPHP in the radical cyclisa-
tion of various haloalkenes and haloalkynes leading to the
stereoselective synthesis of trisubstituted tetrahydrofurans,
the important intermediates in the synthesis of natural
products such as lignans.4 This radical cyclisation method-
ology has also been applied to the total synthesis of a
furanolignan, 1^)-dihydrosesamin.
1
observed in H NMR spectra of 3a±8a. Two isomers in
1a±8a could not be separated by usual chromatographic
methods and hence the crude mixture of isomers were
used in the next step for the radical cyclisation. Treatment
of the bromoalkyl propargyl ethers or bromoalkyl allyl
ethers with EPHP in the presence of AIBN in re¯uxing
benzene furnished the corresponding trisubstituted tetra-
hydrofuran derivatives 1Scheme 1). Thus, a series of
bromoalkyl allyl ethers and bromoalkyl prapargyl ethers
1a±8a were subjected to radical cyclisation and the results
are summarised in Table 1. The cyclisation of bromoalkyl
propargyl ethers 1a±6a was found to be highly stereo-
selective. The substituents at C-2 and C-3 in the products
1b±6b are in trans orientation as expected from our
earlier studies4 and by invoking well-known conformational
effects in the intermediates.6 The cyclised compound 8b was
found to be a mixture of two compounds in a 5:1 ratio. The
2. Results and discussion
The radical precursors 1a±6a4b were prepared from the
corresponding cinnamyl compounds by treatment with
1
ratio of the two diastereomers was determined from the H
NMR spectrum of the crude cyclised product. The only
distinguishable signal of the benzylic methine proton
appeared as a doublet at 5.19 1d, Jˆ7.7 Hz) for the major
isomer and at d 5.05 1Jˆ8.7 Hz) for the minor isomer. The
Keywords: stereoselective; radical cyclisation; hypophosphite salt; furano-
lignan.
Corresponding author. Tel.: 191-33-473-4971; fax: 191-33-473-2805;
e-mail: ocscr@mahendra.iacs.res.in
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020102) 00113-8

2436
S. C. Roy et al. / Tetrahedron 58 +2002) 2435±2439
Scheme 1.
Table 1. Radical cyclisation of bromoalkynes and bromoalkenes with EPHP
Entry Substrate Product
Reaction time 1h)
Yield 1%)
1
480
2
5
78
3
489
4
5
3
75
87
2.5
6
7
3
3
81
63
8
3
84

S. C. Roy et al. / Tetrahedron 58 +2002) 2435±2439
2437
Scheme 2.
1
two isomers could not be separated by usual chromato-
graphic methods.
are uncorrected. H and 13C NMR were recorded in CDCl3
on 300 and 75 MHz spectrometer 1Bruker), respectively and
IR were recorded using a Shimadzu FT IR-8300 instrument.
Diethyl ether, tetrahydrofuran and benzene were dried over
sodium and were freshly distilled from calcium hydride.
Dichloromethane was freshly distilled from phosphorus
pentoxide. Petroleum ether of boiling range 60±808C and
silica gel of 60±120 mesh was used for column chromato-
graphy.
This radical cyclisation strategy was then applied to the
stereoselective total synthesis of a naturally occurring
bioactive furanolignan 1^)-dihydrosesamin. Dihydro-
sesamin is one of the representative biologically active
furanolignans with two identical aromatic moieties, which
was isolated from Daphne tangutica Maxim. and has been
used in the treatment of rheumatism and toothache.7 Thus,
the bromo-alcohol 94d on treatment with EPHP in the
presence of AIBN in re¯uxing benzene for 72 h afforded a
mixture of two diastereomers in a 5:3 ratio in 70% isolated
yield 15.5% of starting material 9 recovered) 1Scheme 2).
The ratio of the two diastereomers was determined from the
1H NMR spectrum of the crude cyclised product. The C-2
benzylic proton appeared as doublet at d 4.78 1Jˆ6.5 Hz)
for the major isomer and at d 4.57 1Jˆ8.0 Hz) for the minor
isomer. The major diastereomer was separated by prepara-
tive TLC 120% ethyl acetate in petroleum ether) in 50%
isolated yield and the spectral data of 10 was identical
with those of dihydrosesamin.4d,6 The minor isomer or
derivatives formed by reaction of its hydroxy group, such
as benzoate and acetate, could not be separated by prepara-
tive TLC in pure form, always contaminated with the major
isomer. So the stereochemistry of the minor isomer remains
uncertain.
3.1. Typical procedure for the preparation of the
bromoalkyl propargyl/allyl ethers 1a±8a
3.1.1. Preparation of ethyl-2-bromo-3-ꢀ3,4-methylene-
dioxyphenyl)-3-ꢀprop-2-ynyloxy)propanoate 1a. To a
stirred solution of N-bromosuccinimide 13.0 g, 17 mmol)
and propargyl alcohol 13.3 mL, 57 mmol) in dry CH2Cl2
115 mL) at 2158C 1ice±salt bath) was added dropwise a
solution of cinnamic ester 1c 12.5 g, 12 mmol) in dry
CH2Cl2 110 mL) under nitrogen for 30 min. The reaction
mixture was stirred for 2 h at that temperature and left over-
night at room temperature. It was then diluted with CH2Cl2
130 mL), washed successively with 1N aqueous NaOH
120 mL) and brine 110 mL), then dried 1Na2SO4). Solvent
was removed under reduced pressure and the residue
obtained was puri®ed by column chromatography over
silica gel 125% ethyl acetate/petroleum ether) to afford
1a4b 13.2 g, 79%) as a viscous oil.
Although the tin hydride-mediated cyclisations of 1a, 2a, 7a
and 9 have been previously reported4a±d to furnish the tetra-
hydrofuran derivatives 1b, 2b, 7b and 10 respectively, the
use of EPHP reagent offers certain advantages over tin
hydride. The reagent is non-toxic in nature, no reduction
products were isolated, the reaction time was reduced and
above all the pure products were isolated in high yield with-
out much effort. Although similar EPHP-mediated cyclisa-
tions have been reported recently,3d,g,h to our knowledge we
have demonstrated here for the ®rst time the EPHP-
mediated cyclisation of bromoalkyl allyl esters to form
tetrahydrofurans.
3.1.2. Preparation of ethyl-2-bromo-3-ꢀ3,4-dimethoxy-
phenyl)-3-ꢀprop-2-ynyloxy)propanoate 2a. Compound
2a 10.69 mg, 88%, colourless crystals, mp 818C)4b was
prepared from 2c 10.5 g, 2.12 mmol) by following the
same procedure as described for 1a.
3.1.3. Preparation of ethyl-2-bromo-3-ꢀ3-methoxy-4-
benzyloxyphenyl)-3-ꢀprop-2-ynyloxy)propanoate
3a.
Compound 3a 10.57 g, 80%, viscous oil) was prepared
from 3c 10.5 g, 1.6 mmol) by following the same procedure
as described for 1a. [Found: C, 59.17; H, 5.18. C22H23O5Br
requires C, 59.06; H, 5.19%]; nmax 1neat) 3286, 2981, 2937,
1739, 1595, 1514, 1463, 1454, 1421, 1371, 1261 cm21; dH
In conclusion, tetrahydrofuran derivatives have been
prepared stereoselectively and in good yield by radical
cyclisation using EPHP salt. This methodology was
successfully applied to the synthesis of a natural furano-
lignan, dihydrosesamin.
1300 MHz, CDCl3) 1.241t,
Jˆ7.2 Hz, 3H), 2.341t,
Jˆ2.4Hz, 1H), 3.76 1dd, Jˆ15.6, 2.4Hz, 1H), 4.01 1dd,
Jˆ15.6, 2.4Hz, 1H), 3.79 1s, OC H3), 4.17 1d, Jˆ10.2 Hz,
1H), 4.17±4.25 1m, 2H), 4.78 1d, Jˆ10.2 Hz, 1H), 5.05 1s,
OCH2Ph), 6.79±6.82 1m, 3H, ArH), 7.20±7.36 1m, 5H,
ArH); dC 175 MHz, CDCl3) 14.4, 48.0, 56.4, 56.7, 62.6,
71.2, 75.5, 79.1, 81.2, 111.0, 113.5, 121.9, 127.7, 128.3,
128.9, 137.3, 149.3, 150.1, 169.0.
3. Experimental
Melting points were determined in open capillary tubes and

2438
S. C. Roy et al. / Tetrahedron 58 +2002) 2435±2439
3.1.4. Preparation of 3-bromo-4-ꢀ3,4-dimethoxyphenyl)-
4-ꢀprop-2-ynyloxy)butan-2-one 4a. Compound 4a 10.41 g,
78%, viscous oil) was prepared from 4c 10.30 g, 1.46 mmol)
by following the same procedure as described for 1a.
[Found: C, 52.71; H, 5.05. C15H17O4Br requires C, 52.79;
H, 5.02%]; nmax 1neat) 3286, 3003, 2937, 2906, 2837, 1720,
1595, 1517, 1464, 1421, 1359, 1313, 1232 cm21; dH
1300 MHz, CDCl3) 2.43 1s, 3H), 2.48 1t, Jˆ2.4Hz, 1H),
3.83 1dd, Jˆ16.2, 2.4Hz, 1H), 3.89 1s, 3H), 3.90 1s, 3H),
4.05 1dd, Jˆ16.2, 2.4Hz, 1H), 4.25 1d, Jˆ10.1 Hz, 1H),
4.88 1d. Jˆ10.1 Hz, 1H), 6.86±6.98 1m, 3H, ArH); dC
125 MHz, CDCl3) 25.9, 55.3, 56.3, 56.4, 75.8, 78.9, 80.7,
110.4, 111.1, 122.0, 128.5, 149.7, 150.1, 201.2.
3.2. Typical procedure for the radical cyclisation of the
bromoethers 1b±8b
3.2.1. Preparation of ethyl ꢀ2R,3R)-2-ꢀ3,4-methylendioxy-
phenyl)-4-methylenetetrahydrofuran-3-carboxylate 1b.
A solution of the bromoether 1a 1150 mg, 0.42 mmol) and
EPHP 1380 mg, 2.11 mmol) in dry benzene 112 mL) was
re¯uxed in the presence of AIBN 110 mg, added in two
portions at an interval of 30 min) under nitrogen. After
completion of the reaction 1monitoring by TLC) the reaction
mixture was allowed to come to room temperature and was
diluted with ether 150 mL). The organic part was separated,
washed successively with 2N HCl 110 mL), saturated
aqueous NaHCO3 12£10 mL) and dried 1Na2SO4). Solvent
was removed under reduced pressure and the residue
obtained was puri®ed by column chromatography over
silica gel 130% ethyl acetate/petroleum ether) to afford the
cyclised product 1b4b 193 mg, 80%) as a viscous oil.
3.1.5. Preparation of methyl-2-bromo-3-ꢀ4-methoxy-
phenyl)-3-ꢀprop-2-ynyloxy)propanoate 5a. Compound
5a 10.53 g, 79%, viscous oil) was prepared from 5c
10.40 g, 2.08 mmol) by following the same procedure as
described for 1a. [Found: C, 51.06; H, 4.71. C14H15O4Br
requires C, 51.38; H, 4.65%]; nmax 1neat) 3288, 3003,
2954, 2906, 2839, 1745, 1612, 1514, 1434, 1305, 1251,
1174cm 21; dH 1300 MHz, CDCl3) 2.43 1t, Jˆ2.4Hz, 1H),
3.76 1s, 3H, OCH3), 3.79 1s, 3H, OCH3), 3.93 1q, Jˆ5.6 Hz,
2H), 4.25 1d, Jˆ9.9 Hz, 1H), 4.87 1d, Jˆ9.9 Hz, 1H), 6.87
1d, Jˆ8.1 Hz, 2H, ArH), 7.27 1d, Jˆ8.4Hz, 2H Ar H). dC
175 MHz, CDCl3) 47.7, 53.4, 55.6, 56.6, 75.6, 79.1, 80.8,
114.3, 128.2, 129.9, 160.6, 169.4.
3.2.2. Preparation of ethyl ꢀ2R,3R)-2-ꢀ3,4-dimethoxy-
phenyl)-4-methylenetetrahydrofuran-3-carboxylate 2b.
Compound 2b 10.09 g, 78%, viscous oil),4b was prepared
from 2a 10.15 g, 0.40 mmol) by the same procedure as
described for 1b.
3.2.3. Preparation of ethyl ꢀ2R,3R)-2-ꢀ3-methoxy-4-
benzyloxyphenyl)-4-methylenetetrahydro-furan-3-car-
boxylate 3b. Compound 3b 10.11 g, 89%, viscous oil) was
prepared 3a 10.15 g, 0.34mmol) by the same procedure as
described for 1b. [Found: C, 71.41; H, 6.73. C22H24O5
requires C, 71.72; H, 6.57%]; nmax 1neat) 3064, 3031,
2979, 2935, 2871, 1732, 1664, 1593, 1515, 1463, 1421,
1371, 1340, 1263, 1232 cm21; dH 1300 MHz, CDCl3) 1.25
1t, Jˆ7.4 Hz, 3H), 3.45±3.49 1m, 1H), 3.88 1s, 3H, OCH3),
4.12±4.27 1m, 2H), 4.57 1q, Jˆ13.0 Hz, two peaks further
split, Jˆ2.1 Hz, 2H), 4.47 1dd, Jˆ13.0, 2.2 Hz, 1H), 4.62
1dd, Jˆ13.0, 2.2 Hz, 1H), 5.09 1d, Jˆ2.1 Hz, 1H), 5.141s,
2H, OCH2Ph), 5.14±5.18 1m, 2H), 6.84 1s, 2H, ArH), 6.96
1s, 1H, ArH), 7.25±7.43 1m, 5H, ArH). dC 175 MHz, CDCl3)
14.6, 56.4, 57.4, 61.5, 71.4, 71.9, 83.8, 106.7, 110.0, 114.0,
119.0, 127.6, 128.3, 129.0, 133.3, 137.5, 147.0, 148.4,
150.1, 171.2.
3.1.6. Preparation of 3-bromo-4-ꢀ2-methoxyphenyl)-4-
ꢀprop-2-ynyloxy)butan-2-one 6a. Compound 6a 10.43 g,
82%, viscous oil) was prepared from 6c 10.30 g,
1.70 mmol) by following the same procedure as described
for 1a. [Found: C, 54.06; H, 4.99. C14H15O3Br requires C,
54.02; H, 4.86%]; nmax 1neat) 3290, 3078, 3004, 2941, 2839,
1720, 1600, 1492, 1463, 1438, 1357, 1286, 1247,
1211 cm21; dH 1300 MHz, CDCl3) 2.41 1t, Jˆ2.4Hz, 1H),
2.42 1s, 3H), 3.86 1s, 3H, OCH3), 3.93 1dd, Jˆ15.7, 2.4Hz,
1H), 4.08 1dd, Jˆ15.7, 2.4Hz, 1H), 4.53 1d, Jˆ8.8 Hz, 1H),
5.41 1d, Jˆ8.8 Hz, 1H), 6.90±7.05 1m, 2H, ArH), 7.29±7.36
1m, 2H, ArH). dC 175 MHz, CDCl3) 26.3, 53.8, 55.5, 56.4,
74.9, 75.1, 78.9, 111.1, 120.8, 128.3, 130.1, 131.7, 158.2,
200.9.
3.1.7. Preparation of 3-bromo-2-ꢀprop-2-ynyloxy)tetra-
hydro-2H-pyran 7a. Compound 7a 11.04g, 80%, viscous
oil)3d,e was prepared from 3,4-dihydro-2H-pyran 10.5 g,
5.95 mmol) by following the same procedure as described
for 1a.
3.2.4. Preparation of 1-[ꢀ2R,3R)-2-ꢀ3,4-dimethoxy-
phenyl)-4-methylenetetrahydrofuran-3-yl] ethanone 4b.
Compound 4b 146 mg, 75%, viscous oil) was prepared from
4a 180 mg, 0.24mmol) by the same procedure as described
for 1b. [Found: C, 68.48; H, 6.98. C15H18O4 requires C,
68.68; H, 6.92%]; nmax 1neat) 2999, 2937, 2837, 1710,
1593, 1520, 1465, 1419, 1357, 1263, 1236 cm21; dH
1300 MHz, CDCl3) 2.02 1s, 3H), 3.43±3.46 1m, 1H), 3.62
1s, 3H, OCH3), 3.641s, 3H, OC H3), 4.54 1q, Jˆ13.2 Hz, two
peaks further split, Jˆ2.1 Hz, 2H), 4.86 1dd, Jˆ16.8,
2.1 Hz, 2H), 4.97 1d, Jˆ6.9 Hz, 1H), 6.54±6.65 1m, 3H,
ArH). dC 175 MHz, CDCl3) 29.7, 55.9, 65.8, 72.0, 83.4,
107.6, 109.4, 111.4, 118.8, 133.2, 147.2, 149.3, 149.6,
205.9.
3.1.8. Preparation of ethyl-3-ꢀallyloxy)-2-bromo-
propanoate 8a. Compound 8a 10.38 g, 80%, viscous oil)
was prepared from 2c 10.30 g, 1.27 mmol) and allyl alcohol
by following the same procedure as described for 1a.
[Found: C, 51.42; H, 5.69. C16H21O5Br requires C, 51.47;
H, 5.67%]; nmax 1neat) 3078, 2981, 2935, 2837, 1743, 1595,
1515, 1465, 1421, 1371, 1336, 1261, 1240 cm21; dH
1300 MHz, CDCl3) 1.36 1t, Jˆ7.2 Hz, 3H), 3.76±3.82 1m,
1H), 3.87±3.98 1m, 1H), 3.89 1s, 6H, 2£OCH3), 4.23 1d,
Jˆ10 Hz, 1H), 4.29±4.37 1m, 2H), 4.67 1d, Jˆ10 Hz, 1H),
5.12±5.21 1m, 2H), 5.75±5.80 1m, 1H), 6.85±6.95 1m, 3H,
ArH). 13C NMR d 14.4, 48.3, 56.2, 56.4, 62.4, 70.8, 82.0,
110.5, 111.1, 117.8, 121.6, 129.9, 134.4, 149.5, 149.8,
169.3.
3.2.5. Preparation of methyl ꢀ2R,3R)-2-ꢀ4-methoxy-
phenyl)-4-methylenetetrahydrofuran-3-carboxylate 5b.
Compound 5b 10.1 g, 87%, viscous oil) was prepared
from 5a 10.15 g, 0.46 mmol) by the same procedure as
described for 1b. [Found: C, 67.24; H, 6.81. C14H16O4

S. C. Roy et al. / Tetrahedron 58 +2002) 2435±2439
2439
requires C, 67.73; H, 6.50%]; nmax 1neat) 2999, 2952, 2912,
1735, 1612, 1515, 1458, 1436, 1301, 1249 cm21; dH
1300 MHz, CDCl3) 3.84±3.541m, 1H), 3.741s, 3H,
OCH3), 3.80 1s, 3H, OCH3), 4.55 1q, Jˆ12.0 Hz, two
peaks further split, Jˆ3.0 Hz, 2H), 5.10 1dd, Jˆ18.0,
3.0 Hz, 2H) 5.17 1d, Jˆ6.0 Hz, 1H), 6.84±6.92 1m, 2H,
ArH), 7.26±7.33 1m, 2H, ArH). dC 175 MHz, CDCl3)
52.7, 55.7, 57.4, 71.9, 83.7, 106.8, 114.3, 127.9, 132.2,
146.9, 159.9, 171.7.
4.78 1d, Jˆ6.5 Hz, 1H, C2±H), 5.93 1s, 2H, OCH2O), 5.94
1s, 2H, OCH2O), 6.62±6.83 1m, 6H, ArH); dC 175 MHz,
CDCl3) 33.4, 42.4, 52.5, 60.8, 72.8, 82.8, 100.7, 100.9,
106.4, 108.1, 108.3, 108.8, 119.1, 121.5, 134.3, 137.0,
145.8, 146.7, 147.8, 147.8.
Acknowledgements
We gratefully acknowledge the ®nancial support from
Department of Science and Technology, New Delhi. C. G.
thanks CSIR, New Delhi for the award of a Junior Research
Fellowship.
3.2.6. Preparation of 1-[ꢀ2R,3R)-2-ꢀ2-methoxyphenyl)-4-
methylenetetrahydrofuran-3-yl]ethanone 6b. Compound
6b 10.09 g, 81%, viscous oil) was prepared 6a 10.15 g,
0.48 mmol) by the same procedure as described for 1b.
[Found: C, 72.11; H, 6.99. C14H16O3 requires C, 72.39; H,
6.94%]; nmax 1neat) 3078, 2999, 2939, 2839, 1712, 1664,
1602, 1490, 1461, 1438, 1357, 1244 cm21; dH 1300 MHz,
CDCl3) 2.23 1s, 3H), 3.43±3.46 1m, 1H), 3.69 1s, OCH3),
4.53 1q, Jˆ12.6 Hz, two peaks further split, Jˆ2.1 Hz, 2H),
4.93 1dd, Jˆ4.2, 2.1 Hz, 1H), 5.04 1dd, Jˆ4.2, 2.1 Hz, 1H),
5.45 1d, Jˆ6 Hz, 1H), 6.76±6.92 1m, 2H, ArH), 7.15±7.21
1m, 1H, ArH), 7.36±7.38 1m, 1H, ArH). dC 175 MHz,
CDCl3) 28.0, 55.2, 65.3, 72.0, 79.4, 107.5, 110.4, 121.0,
125.8, 128.9, 130.0, 147.3, 156.0, 205.7.
References
1. 1a) Giese, B. Radicals in Organic synthesis, Formation of
Carbon±Carbon
Bonds;
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Oxford,
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1b) Ramaiah, M. Tetrahedron 1987, 3541. 1c) Srikrishna, A.
Curr. Sci. 1987, 56, 392. 1d) Curran, D. P. Synthesis 1988,
417 see also p 489. 1e) C-Radikale, Teil 112. Houben-Weyl,
Methoden der Organischen Chemie; Regitz, M., Giese, B.,
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p 715 see also p 779. 1g) Motherwell, W. B.; Crich, D. Free
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Organic Chemistry; Wiley: New York, 1995.
3.2.7. Preparation of 3-methylenehexahydro-4H-
furo[2,3-b]pyran 7b. Compound 7b 10.08 g, 63%, viscous
oil)3d,e was prepared from 7a 10.2 g, 0.91 mmol) by the same
procedure as described for 1b.
2. 1a) Ballestri, M.; Chatgilialoglu, C.; Clark, K. B.; Griller, B.;
Giese, B.; Kopping, B. J. Org. Chem. 1991, 56, 678.
1b) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188.
1c) Kulicke, K. J.; Giese, B. Synlett 1990, 91.
3.2.8. Preparation of ethyl ꢀ2R,3R)-2-ꢀ3,4-dimethoxy-
phenyl)-4-methyltetrahydrofuran-3-carboxylate
8b.
Compound 8b 10.08 g, 84%, viscous oil) was prepared
from 8a 10.12 g, 0.32 mmol) by the same procedure as
described for 1b. [Found: C, 74.93; H, 7.52. C16H22O5
requires C, 65.29; H, 7.53%]; nmax 1neat) 2968, 2937,
2875, 2837, 1728, 1593, 1517, 1463, 1421, 1377, 1350,
1263, 1236 cm21; dH 1300 MHz, CDCl3) 1.07 1d, Jˆ7 Hz,
3H), 1.27 1t, Jˆ7.2 Hz, 3H), 2.71±2.81 1m, 1H) 3.00 1t,
Jˆ8.4Hz, 1H), 3.65 1dd, Jˆ8.1, 6.7 Hz, 1H), 3.86 1s, 3H,
OCH3), 3.88 1s, 3H, OCH3), 4.11±4.23 1m, 2H), 4.27 1dd,
Jˆ8.1, 6.7 Hz, 1H), 5.05 1d, Jˆ8.7 Hz, 1/5H), 5.19 1d,
Jˆ7.7 Hz, 4/5H), 6.81±6.90 1m, 3H, ArH); dC 175 MHz,
CDCl3) 14.3, 14.7, 37.5, 56.2, 57.0, 60.8, 75.5, 82.1, 84.3,
109.4, 111.5, 118.6, 134.6, 148.9, 149.4, 172.3.
3. 1a) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, C. J. Tetrahedron
Lett. 1992, 33, 5709. 1b) Barton, D. H. R.; Jang, D. O.;
Jaszberenyi, J. C. J. Org. Chem. 1993, 58, 6838. 1c) McCague,
R.; Pritchard, R. G.; Stoodley, R. I.; Williamson, D. S. Chem.
Commun. 1998, 2691. 1d) Graham, S. R.; Murphy, J. A.; Coates,
D. Tetrahedron Lett. 1999, 40, 2415. 1e) Graham, S. R.;
Murphy, J. A.; Kennedy, A. R. J. Chem. Soc., Perkin Trans. 1
1999, 3071. 1f) Tokuyama, H.; Yamashita, T.; Reding, M. T.;
Kaburagi, Y.; Fukuyama, T. J. Am. Chem. Soc. 1999, 121, 3791.
1g) Yorimitsu, H.; Shinokubo, H.; Oshima, K. Bull. Chem. Soc.
Jpn 2001, 74, 225. 1h) Kita, Y.; Nambu, H.; Ramesh, N. G.;
Anilkumar, G.; Matsugi, M. Org. Lett. 2001, 3, 1157.
4. 1a) Adhikari, S.; Roy, S. Tetrahedron Lett. 1992, 33, 6025.
1b) Roy, S. C.; Adhikari, S. Tetrahedron 1993, 49, 8415.
1c) Maiti, G.; Adhikari, S.; Roy, S. C. Tetrahedron Lett. 1994,
35, 3985. 1d) Maiti, G.; Adhikari, S.; Roy, S. C. J. Chem. Soc.,
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3.2.9. Synthesis of dihydrosesamin ꢀ10). The bromo-
alcohol 94d on radical cyclisation reaction under identical
reaction conditions as described for 1b for 72 h afforded a
mixture of two isomers in a ratio of 5:3 in 70% isolated yield
15.5% of starting material 9 recovered). The major isomer
was separated by preparative TLC 120% ethyl acetate/
petroleum ether) to afford 104d,6 in 50% yield. dH
1300 MHz, CDCl3)) 1.60 1br s, OH), 2.32±2.38 1m, 1H
C3±H), 2.55 1dd, Jˆ13.3 and 10.3 Hz, 1H, C04±H),
2.63±2.76 1m, 1H, C4±H), 2.87 1dd, Jˆ13.3 and 5.2 Hz,
5. Okabe, M.; Abe, M.; Tada, M. J. Org. Chem. 1982, 47, 1775.
6. 1a) Beckwith, A. L. J.; Eaton, C. J.; Lawrence, T.; Serelis, A. K.
Aust. J. Chem. 1983, 36, 545. 1b) RajanBabu, T. V. Acc. Chem.
Res. 1991, 24, 139.
7. Lin-Zen, Z.; Seligmann, O.; Lotter, H.; Wagner, H.
Phytochemistry 1983, 22, 265.
1H, C0 ±H), 3.69±3.78 1m, 2H, C03±H), 3.89 1dd, Jˆ10.5
4
and 6.8, 1H, C5±H), 4.04 1dd, Jˆ8.4and 6.5 Hz, 1H, C5±H),