γ-Lactonizations of 2H-chromenes via cyclopropanation

Article abstract of DOI:10.1016/j.tetlet.2010.05.059

A two-step synthesis of tetrahydro-2H-furochromenones from 2H-chromenes is reported. The reaction of a series of tert-butyl 2-diazoacetate derivatives with 2H-chromenes, catalyzed by Rh₂(OAc)₄, generated cyclopropane intermediates that rearranged to γ-lactones on treatment with Sn(OTf)₂.

Full text of DOI:10.1016/j.tetlet.2010.05.059

Tetrahedron Letters 51 (2010) 4003–4006
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
c-Lactonizations of 2H-chromenes via cyclopropanation
*
Sean Stokes, Ben Spears, Cameron Laseter, Bobby Barker, Keith T. Mead
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A two-step synthesis of tetrahydro-2H-furochromenones from 2H-chromenes is reported. The reaction of
a series of tert-butyl 2-diazoacetate derivatives with 2H-chromenes, catalyzed by Rh2(OAc)4, generated
Received 20 April 2010
Revised 11 May 2010
Accepted 13 May 2010
Available online 21 May 2010
cyclopropane intermediates that rearranged to
c
-lactones on treatment with Sn(OTf)2.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
c
-Lactones
Cyclopropanation
-Diazocarbonyls
a
2H-Chromenes
Oxidative
c
-lactonizations of alkenes with potassium methyl
ing that stabilization of both benzylic radical and carbocation
intermediates would provide single isomer products analogous to
dihydropyrans.7 However, all attempts failed, presumably because
of competing oxidation of the 2H-chromene to the corresponding
chromenylium ion (Eq. 3), as suggested by the immediate purple
color formed on contact with CAN.
malonate (PMM), first introduced by Fristad et al.,1 have found
widespread application in synthesis as a simple and efficient route
to a-carbomethoxy c
-lactones.2–6 These one-pot reactions are be-
lieved to involve, in addition to the alkene, an oxidatively gener-
ated PMM radical, and in many cases they occur with a high
degree of regio- and stereoselectivity. Our group, for example,
has used this method to lactonize substituted dihydropyrans (Eq.
1) and used the fused ring products as templates for the stereocon-
trolled synthesis of C-alkyl and C-aryl pyranosides.4–6
Inspired by the groups of Theodorakis and co-workers8 and Da-
vies and Hu9 who have independently reported formations of
c-lac-
tones from cyclopropyl esters, we considered a two-step approach
involving cyclopropane intermediates that avoids the use of
strongly oxidizing conditions (Scheme 1). Prior to the onset of this
study, we were aware of only one other example of a cyclopropana-
tion of a 2H-chromene with a diazo ester.10 Cyclopropanations of
R
R
CO2Me
PMM
CAN
ð1Þ
ð2Þ
O
alkenes with
a-diazocarbonyls initiated by a variety of catalysts
O
O
are well documented11 and applied to 2H-chromenes, we reasoned
that subsequent acid-induced cyclopropane ring cleavage should
occur regioselectively to generate an oxy-stabilized benzyl carbo-
cation. By using substituted tert-butyl diazoacetates we hoped to
O
O
O
CO2Me
PMM
X
maximize the rate of rearrangement and achieve selective c-lac-
CAN
tone formation even in the presence of other potential donors (X).
Moreover, several alpha-substituted tert-butyl acetates, from
which these diazoacetates could be made, are commercially avail-
able. Based on our previous work preparing fused ring bicyclic lac-
tones from dihydropyrans, a single diastereomeric lactone was
predicted with the substituent X exo to the fused ring system.
To test the feasibility of the cyclopropanation step, a variety of
methoxy-substituted 2H-chromenes were reacted with three dif-
ferent diazo esters (Table 1). Our first reaction involved compound
1a (entry 1) with diazoester 2a in the presence of catalytic
Rh2(OAc)4, which gave the cyclopropane derivative 3a as a mixture
of diastereomers, along with a minor product identified as the
insertion adduct 4a. The 2H-chromenes 1b and 1c gave similar
O
O
[O]
O
ð3Þ
MeO2C
CO2K
PMM =
With an interest in extending the scope of these reactions, as
well as preparing novel flavan ring structures, we recently tried
to apply oxidative c-lactonization to 2H-chromenes (Eq. 2), reason-
* Corresponding author. Tel.: +1 662 325 3584; fax: +1 662 325 1618.
E-mail address: kmead@ra.msstate.edu (K.T. Mead).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.059

4004
S. Stokes et al. / Tetrahedron Letters 51 (2010) 4003–4006
Table 2
X
X
CO2t-Bu
Ring expansions of cyclopropane products
CO2t-Bu
N2
R
R
O
catalyst
R2
R2
X
O
O
t
O
CO2 Bu
R1
H3CO
R1
H3CO
X
Lewis acid
CH2Cl2, rt
H+
O
O
3a-d
5a-d
O
O
X
Entry R1
R2
X
Substrate Lewis
acid
Product Yield
(%)
R
O
a
b
b
a
b
b
1
2
3
4
5
6
7
8
9
H
H
H
H
H
CO2CH3 3a
CO2CH3 3a
BF3ꢀOEt2
Sn(OTf)2
Sn(OTf)2
BF3ꢀOEt2
Sn(OTf)2
5a
5a
5b
5c
5c
5c
5c
5d
5d
5d
5d
45
72
57
65
71
27
24
63
40
29
31
OCH3 CO2CH3 3b
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
H
H
H
H
H
H
H
H
CO2CH3 3c
CO2CH3 3c
CO2CH3 3c
CO2CH3 3c
O
Cu(OTf)2
b
Sn(OTf)3
Sn(OTf)2
BF3ꢀOEt2
O
b
a
b
CN
CN
CN
CN
3d
3d
3d
3d
X
R
10
11
Cu(OTf)2
b
O
Sn(OTf)2
a
0.3 equiv.
0.5 equiv.
Scheme 1.
b
decomposition, even at ꢁ78 °C. However, we were delighted to
find better results with Sn(OTf)2 at room temperature (entry 2). In-
deed, this Lewis acid proved to be the reagent of choice for other
substrates (see entries 3, 5, and 8).14 Both Cu(OTf)2 and Sc(OTf)3
proved to be disappointing, while protic acids such as TFA and p-
results with diazoesters 2a and 2b (entries 2–4). Compounds 3b
and 3c were also formed as a mixture of diastereomers, but the cy-
ano-substituted cyclopropane 3d formed as a single isomer. Use of
AgSbF6 or Cu(OTf)2 instead of Rh2(OAc)4 resulted in no cyclopro-
pane product formation. Best yields were obtained by the addition
of an excess (2 equiv) of the diazo compound via a syringe pump to
a stirred solution of the 2H-chromene and catalyst (2 mol %) over
5 h followed by overnight stirring.12 Notably, the extent of inser-
tion relative to cyclopropanation decreased with the dimethoxy-
substituted derivatives 1b and 1c (compare entries 2–4 with entry
1). Unfortunately, all attempts to react diazophosphoryl derivative
2c were unsuccessful.13
Next we studied Lewis acid-induced rearrangements of these
cyclopropane substrates (Table 2). Beginning with the monometh-
oxy-substituted compound 3a (entry 1), we found that BF3ꢀOEt2
provided a very clean reaction, as monitored by tlc, but gave a dis-
appointingly low yield of the product 5a. On the other hand, stron-
ger Lewis acids such as TiCl4 and SnCl4 caused immediate
Figure 1. X-ray structure of compound 5c.
Table 1
Cyclopropanations of 2H-chromenesa
CO2tBu
X
X
R2
R2
R2
CO2tBu
+
R1
R1
R1
N2
2a-c
CO2t Bu
Rh2(OAc)4
H3CO
O
H3CO
O
H3CO
O
1a-c
3a-e
4a-e
X
Entry
R1
R2
Chromene
X
Product
Yield (%)
Product
Yield (%)
1
2
3
4
5
H
H
OCH3
OCH3
OCH3
H
OCH3
H
H
H
1a
1b
1c
1c
1c
CO2CH3 (2a)
CO2CH3 (2a)
CO2CH3 (2a)
CN (2b)
3a
3b
3c
3d
3e
62
78
83
74
0
4a
4b
4c
4d
4e
12
5
7
4
0
PO(OEt)2 (2c)
a
Reaction conditions: 2H-chromene 1 (1 equiv), diazoester 2 (2 equiv), Rh2(OAc)4 (2 mol %), CH2Cl2, 25 °C.

S. Stokes et al. / Tetrahedron Letters 51 (2010) 4003–4006
4005
X
X
O
H
t
CO2 Bu
O
CO2tBu
Sn(OTf)2, DCM
H
X
MeO
MeO
MeO
MeO
MeO
MeO
N2
Rh2(OAc)4, DCM
O
O
O
1c
8 X = NO2, 64%
9 X = CN, 72%
X = H, 0%
6 X = NO2, 98%
7 X = CN, 77%
Scheme 2.
1H), 3.75 (s, 3H), 3.59 (s, 3H), 2.76 (d, J = 9.5 Hz, 1H), 2.41 (ddd, J = 9.5, 2.1 and
0.9 Hz, 1H), 1.47 (s, 9H); 13C NMR (300 mHz): d 169.8, 158.4, 155.5, 129.7, 119.5,
105.7, 100.3, 82.4, 68.7, 55.8, 52.2, 37.2, 29.8, 28.7, 28.3. 1-tert-Butyl 1-methyl
5,7-dimethoxy-1a,2-dihydrocyclopropa[c]chromene-1,1(7bH)-dicarboxylate (3b).
Yellow oil (296 mg, 78%); 1H NMR (300 MHz, CDCl3): d 6.15 (s, 1H), 5.90 (s,
1H), 4.12 (dd, 10.1 and 1.3 Hz, 1H), 3.97 (dd, 10.1 and 0.8 Hz, 1H), 3.82 (s, 3H),
3.81 (s, 3H), 3.79 (s, 3H), 2.50 (d, 9.0 Hz, 1H), 2.36 (dd, 9.0, 1.3 and 0.8 Hz), 1.35
(s, 9H); 13C NMR (300 mHz): d 170.0, 160.8, 157.9, 156.5, 104.4, 92.6, 91.8, 82.4,
68.6, 56.1, 55.8, 52.2, 37.5, 30.1, 28.5, 22.4. 1-tert-Butyl 1-methyl 5,6-dimethoxy-
1a,2-dihydrocyclopropa[c]chromene-1,1(7bH)-dicarboxylate (3c). Yellow oil
(315 mg, 83%); 1H NMR (300 MHz, CDCl3): d 6.85 (s, 1H), 6.41 (s, 1H), 4.05
(dd, J = 10.9 and 1.0 Hz, 1H), 3.93 (dd, J = 10.9 and 2.5 Hz, 1H), 3.83 (s, 3H), 3.80
(s, 3H), 3.76 (s, 3H), 2.70 (d, J = 9.2 Hz, 1H), 2.42 (ddd, J = 9.2, 2.5, and 1.0 Hz,
1H), 1.50 (s, 9H); 13C NMR (300 mHz): d 168.2, 147.8, 141.2, 120.5, 107.5,
100.2, 82.5, 68.4, 56.1, 52.5, 36.8, 29.5, 28.9, 28.2. tert-Butyl 1-cyano-5,6-
dimethoxy-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylate (3d). White
solid (248 mg, 74% before recrystallized; 190 mg, 55% after recrystallization with
hexane and ethyl acetate); mp: 147–149 °C; 1H NMR (300 MHz, CDCl3): d 6.79
(s, 1H), 6.47 (s, 1H), 4.48 (dd, J = 12.2 and 2.0 Hz, 1H), 4.33 (dd, J = 12.2 and
3.6 Hz, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.00 (d, J = 9.5 Hz, 1H), 2.61 (ddd,
J = 9.5,3.6, and 2.0 Hz, 1H), 1.54 (s, 9H); 13C NMR (300 mHz): d 165.0, 150.1,
147.1, 144.1, 115.0, 112.3, 107.2, 101.6, 84.5, 60.6, 56.4, 55.9, 30.7, 29.8, 27.9,
27.7. tert-Butyl 5,6-dimethoxy-1-(4-nitrophenyl)-1,1a,2,7b-tetrahydrocyclopropa
[c]chromene-1-carboxylate (6). Yellow oil (436 mg, 98%); 1H NMR (300 MHz,
CDCl3): d 7.99 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 6.89 (s, 1H), 5.98 (s,
1H), 4.39 (d, J = 11.7 Hz, 1H), 4.05 (dd, J = 11.8 and 2.2 Hz, 1H), 3.93 (s, 3H), 3.70
TsOH (not shown) gave complex mixtures of products and were
not analyzed further. All products 5a–d formed as single isomers
(see Fig. 1).
A single-crystal X-ray structure of compound 5c confirmed the
assigned stereochemistry of the lactone products, showing the
substituent X, in this case methyl ester, to be exo to the fused ring
system.15
A number of routes to
One commonly used method involves the
vated
-lactone using toxic lead- and mercury-based reagents.16c–e
To see if we could prepare these derivatives using our two-step
protocol, 2H-chromene 1c was reacted with three different
aryl- -diazo tert-butyl acetates to form cyclopropane intermedi-
a-aryl
c
-lactones have been reported.16
-arylation of an -acti-
a
a
c
a
-
a
ates (Scheme 2). Not surprisingly, our results indicated a direct
relationship between the yield of cyclopropane product and the
electron deficiency of the aryl ring on the diazo reagent and sug-
gested a need for the presence of an electron-withdrawing group
for the reaction to proceed. Notably, there was no evidence of an
insertion product in either of the successful cyclopropanations.
Moreover, both cyclopropane products 6 and 7 rearranged to
tones 8 and 9, respectively, on treatment with Sn(OTf)2.
c-lac-
(s, 3H), 2.96 (d, J = 9.7 Hz, 1H), 2.64 (dd, J = 9.7 and 1.4 Hz, 1H), 1.35 (s, 9H); 13
C
NMR (300 mHz): d 164.8, 147.8, 147.6, 145.6, 145.1, 141.2, 129.0, 123.7, 120.5,
107.5, 100.2, 82.7, 68.9, 55.9, 36.8, 36.6, 36.2, 28.7. tert-Butyl 1-(4-cyanophenyl)-
5,6-dimethoxy-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-1-carboxylate (7). Yellow
oil (326 mg, 77%); 1H NMR (300 MHz, CDCl3): d 8.22 (d, J = 9.0 Hz, 2H), 7.65 (d,
J = 9.0 Hz, 2H), 6.90 (s, 1H), 5.99 (s, 1H), 4.39 (d, J = 11.1 Hz, 1H), 4.06 (d,
J = 11.1 Hz, 1H), 3.94 (s, 3H), 3.69 (s, 3H), 2.96 (d, J = 8.7 Hz, 1H), 2.64 (dd,
J = 8.7 and 1.0 Hz, 1H), 1.36 (s, 9H); 13C NMR (300 mHz): d 164.5, 147.8, 147.6,
143.8, 141.2, 132.0, 128.8, 120.5, 118.6, 109.8, 107.5, 100.2, 82.5, 68.7, 56.2,
36.9, 36.5, 36.1, 28.3.
A useful method for effecting successful c-lactonizations of 2H-
chromenes has been described, which avoids the use of strongly
oxidizing conditions. We hope to use these intermediates as tem-
plates for targeting novel flavan ring structures.
References and notes
13. For examples of cyclopropanations of alkenes with
a-trifluoromethyldiazo-
1. Fristad, W. E.; Peterson, J. R.; Ernst, A. B. J. Org. Chem. 1985, 50, 3143–3148.
2. del Rosario-Chow, M.; Ungwitayatorn, J.; Currie, B. L. Tetrahedron Lett. 1991, 32,
1011–1014.
3. (a) D’Annibale, A.; Trogolo, C. Tetrahedron Lett. 1994, 35, 2083–2086; (b)
Allegretti, M.; D’Annibale, A.; Trogolo, C. Tetrahedron 1993, 49, 10705–10714.
4. Cakir, S. P.; Mead, K. T.; Smith, L. Tetrahedron Lett. 2003, 44, 6355–6358.
5. Cakir, S. P.; Mead, K. T. J. Org. Chem. 2004, 69, 2203–2205.
6. Cakir, S. P.; Mead, K. Heterocycl. Commun. 2005, 11, 471–474.
phosphonate, see: Titanyuk, I. D.; Beletskaya, I. P.; Peregudov, A. S.; Osipov, S.
N. J. Fluorine Chem. 2007, 128, 723–728.
14. General procedure for the preparation of the lactones: methyl 7-methoxy-2-oxo-
3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromene-3-carboxylate (5a). In
a 5-mL
round-bottomed flask, solution of compound 3a (50 mg, 0.15 mmol) in
a
3 mL of dry DCM was cooled to 0 °C and tin(II) triflate (31 mg, 0.075 mmol) was
added. The reaction vessel was purged with argon and stirred overnight, slowly
allowing the solution to warm to room temperature. The reaction was
quenched with a few drops of water and then dried over MgSO4. The solvent
was removed under reduced pressure and then the crude product was purified
using flash column chromatography using mixtures of hexane and ethyl
acetate as the eluting solvents. Off-white solid (30 mg, 72%); 1H NMR
(300 MHz, CDCl3): d 7.28 (d, J = 8.6 Hz, 1H), 6.62 (dd, J = 8.6 and 2.4 Hz, 1H),
6.41 (d, J = 2.4 Hz, 1H), 5.68 (d, J = 7.3 Hz, 1H), 4.21 (dd, J = 11.8 and 3.4 Hz, 1H),
4.01 (dd, J = 11.8 and 6.2 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.61 (d, J = 7.4 Hz,
1H), 3.43–3.35 (m, 1H); 13C NMR (300 mHz): d 171.0, 169.9, 158.1, 155.8,
128.7, 120.0, 108.6, 99.7, 81.1, 68.5, 55.8, 51.9, 49.5, 32.6. Methyl 7,9-
dimethoxy-2-oxo-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromene-3-carboxylate
(5b). Off-white solid (24 mg, 57%); 1H NMR (300 MHz, CDCl3): d 6.17 (s, 1H),
5.98 (s, 1H), 5.62 (d, J = 7.0 Hz, 1H), 4.19 (dd, J = 11.3 and 3.8 Hz, 1H), 3.99 (dd,
J = 11.3 and 6.0 Hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.83 (s, 3H), 3.63 (d, J = 7.5 Hz,
1H), 3.47–3.38 (m, 1H); 13C NMR (300 mHz): d 172.6, 165.3, 158.1, 146.2,
142.6, 111.78, 109.9, 100.3, 78.4, 65.1, 55.4, 55.0, 53.2, 48.6, 39.7. Methyl 7,8-
dimethoxy-2-oxo-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromene-3-carboxylate
(5c). White solid (30 mg, 71%); mp: 149–150 °C; 1H NMR (300 MHz, CDCl3): d
6.79 (s, 1H), 6.42 (s, 1H), 5.67 (d, J = 7.4 Hz, 1H), 4.18 (dd, J = 11.8 and 3.3 Hz,
1H), 4.01 (dd, J = 11.8 and 5.9 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H),
3.64 (d, J = 7.8 Hz, 1H), 3.43–3.35 (m, 1H); 13C NMR (300 mHz): d 170.6, 167.3,
151.1, 149.2, 144.7, 111.7, 109.2, 100.7, 73.8, 64.2, 56.3, 56.0, 53.4, 47.6, 38.2.
7,8-Dimethoxy-2-oxo-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromene-3-carbonitrile
7. For previous routes to related 6,6,5-tricyclic
c-lactones, see: (a) Bentley, J.;
Nilsson, P. A.; Parsons, A. F. J. Chem. Soc., Perkin Trans. 1 2002, 12, 1461–1469;
(b) Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
4424–4431; (c) Szczepanik, M.; Obara, R.; Szumny, A.; Gabrys, B.; Halarewicz-
Pacan, A.; Nawrot, J.; Wawrzenczyk, C. J. Agric. Food. Chem. 2005, 53, 5905–
5910.
8. Kim, C.; Brady, T.; Kim, S. H.; Theodorakis, E. A. Synth. Commun. 2004, 34, 1951–
1965.
9. Davies, H. M. L.; Hu, B. J. Org. Chem. 1992, 57, 4309–4312.
10. Blanchard, L. A.; Schneider, J. A. J. Org. Chem. 1986, 51, 1372–1374.
11. For a review, see: Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1.
12. General procedure for formation of the cyclopropanes: 1-tert-butyl 1-methyl 5-
methoxy-1a,2-dihydrocyclopropa[c]chromene-1,1(7bH)-dicarboxylate (3a). In a 5-
mL round-bottomed flask, 7-methoxy-2H-chromene (200 mg, 1.2 mmol) was
dissolved in 2 mL of dry DCM. Once dissolution was achieved, Rh2(OAc)4 (11 mg,
0.024 mmol) was added and the reaction vessel was purged with argon. This
mixture was stirred for 5 min and then 1-tert-butyl 3-methyl 2-diazomalonate
(480 mg, 2.4 mmol) dissolved in 1 mL of dry DCM was added via a syringe pump
over 5 h. The solvent was removed under reduced pressure and the crude
product was purified by flash column chromatography using mixtures of hexane
and ethyl acetate as the eluting solvents. Yellow oil (253 mg, 63%); 1H NMR
(300 MHz, CDCl3): d 7.21 (d, J = 8.4 Hz, 1H), 6.54 (dd, J = 8.4 and 2.6 Hz, 1H), 6.34
(d, J = 2.5 Hz, 1H), 4.52 (dd, J = 11.3 and 0.9 Hz, 1H), 3.98 (dd, J = 11.3 and 2.1 Hz,

4006
S. Stokes et al. / Tetrahedron Letters 51 (2010) 4003–4006
(5d). Off-white solid (27 mg, 63%); 1H NMR (300 MHz, CDCl3): d 6.82 (s, 1H),
174.4, 148.1, 147.8, 143.8, 141.7, 131.7, 129.8, 121.6, 119.7, 112.2, 108.5, 100.7,
82.3, 69.9, 56.7, 56.3, 53.4, 40.5.
6.40 (s, 1H), 5.57 (d, J = 7.2 Hz, 1H), 4.20 (dd, J = 11.2 and 3.0 Hz, 1H), 4.00 (dd,
J = 11.2 and 6.1 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.59 (d, J = 7.6 Hz, 1H), 3.45–
3.37 (m, 1H); 13C NMR (300 mHz): d 165.3, 148.1, 147.5, 143.4, 120.5, 116.8,
113.9, 99.7, 81.3, 68.5, 56.2, 55.9, 35.8, 32.6. 7,8-Dimethoxy-3-(4-nitrophenyl)-
3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromen-2-one (8). Off-white solid (28 mg,
64%); 1H NMR (300 MHz, CDCl3) d 8.29 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.7 Hz,
2H), 6.88 (s, 1H), 6.42 (s, 1H), 5.46 (d, J = 4.7 Hz, 1H), 4.21 (dd, J = 12.3 and
2.5 Hz, 1H), 4.10 (dd, J = 12.3 and 2.4 Hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.60 (d,
J = 7.4 Hz, 1H), 3.33–3.23 (m, 1H); 13C NMR (300 mHz): d 174.2, 148.2, 147.3,
144.8, 143.4, 143.0, 129.5, 123.1, 120.4, 111.7, 100.5, 82.7, 67.8,56.5, 56.3,53.5, 38.9.
4-(7,8-Dimethoxy-2-oxo-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]chromen-3-yl)benzoni-
trile (9). Off-white solid (31 mg, 72%); 1H NMR (300 MHz, CDCl3): d 7.89 (d,
J = 8.2 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 6.87 (s, 1H), 6.44 (s, 1H), 5.49 (d, J = 4.3 Hz,
1H), 4.24 (dd, J = 12.1 and 2.1 Hz, 1H), 4.15 (dd, J = 12.1 and 2.0 Hz, 1H), 3.89 (s,
3H), 3.86 (s, 3H), 3.63 (d, J = 7.2 Hz, 1H), 3.39–3.27 (m, 1H); 13CNMR (300 mHz): d
15. Crystal data for 5c: C15H16O7, Mw = 308.28, crystal size: 0.06 ꢂ 0.16 ꢂ 0.19 mm,
crystal system: orthorhombic, space group:
b = 7.2968(7) Å, c = 23.947(2) Å,
P b c a, a = 15.7986(15) Å,
a = b = c
= 90°, U = 2760.6(5) Å3, Z = 8,
T = 100(2) K, reflections collected 23670, 2144 independent (Rint = 0.0681),
R1 = 0.0405, wR2 = 0.1115. The crystallographic data were deposited with the
Cambridge Crystallographic Data Centre (deposition number CCDC 774002).
The data can be obtained free of charge from www.ccdc.cam.ac.uk.
16. (a) Spielvogel, D. J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 3500–3501; (b)
Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122,
1360–1370; (c) Sakaguchi, K.; Kitamura, T.; Shiomi, Y.; Koden, M.; Kuratate, T.
Chem. Lett. 1991, 1383–1386; (d) Pinhey, J. T.; Rowe, B. A. Aust. J. Chem. 1980,
33, 113–120; (e) Deng, H.; Konopelski, J. P. Org. Lett. 2001, 3, 3001–3004; (f)
Gong, J.; Lin, G.; Li, C.-c.; Yang, Z. Org. Lett. 2009, 11, 4770–4773.