3892
S. Stokes et al. / Tetrahedron Letters 53 (2012) 3890–3893
In every case, the 1,1-cyclopropane diester formed as a single
diastereomer, and not surprisingly the X-ray crystal structure of
7a showed that cyclopropanation occurred anti to the C2-aryl sub-
stituent (Fig. 2). As an added note, because Rh2(S-TBSP)4 is chiral,
we checked for enantiomeric enrichment in the products formed
in the presence of this catalyst. However, we found no evidence
of kinetic resolution in these reactions.
As expected, cyclopropanes substituted with a tert-butyl ester
group rearranged to
c-lactone on treatment with Sn(OTf)2
(Table 4). In comparison, the corresponding 1,1-dimethyl ester
derivatives gave multiple products on treatment with a variety of
Lewis acids (TiCl4, BF3, Sc(OTf)3, Sn(OTf)2). We are currently investi-
gating the use of these lactones in the synthesis of biflavonoid
natural products.
In conclusion, iodonium ylides and a-diazo derivatives of dial-
kyl malonates serve complimentary roles in the formation of 1,1-
cyclopropane esters from 2-aryl-2H-chromenes. Diazo compounds
are the preferred reagents for forming tetrahydro-2H-furochrome-
nones, because of the need for a tert-butyl ester group to facilitate
the rearrangement step. However, the choice of catalyst is critical.
In contrast, superior yields of gem-dimethyl esters are obtained
using the iodonium ylide 2a (see Table 3). These donor–acceptor
cyclopropanes should lend themselves to a multitude of transfor-
mations, hopefully yielding a variety of novel aryl-substituted
chroman structures.17
Figure 2. The X-ray crystal structure of 7a.
Table 4
Sn(OTf)2 initiated rearrangement of cyclopropane diesters 6 to
c
-lactones 8
O
O
CO2Me
R1
R1
H
CO2t-Bu
H
CO2Me
Acknowledgements
Sn(OTf)2
DCM
MeO
O
MeO
O
The NMR data were made possible through NSF CRIF Award
0840220 which supported the acquisition of the 600 MHz NMR.
We are indebted to Jonathan R. Frisch and the X-ray Crystallo-
graphic Laboratory at Mississippi State University for the crystal
structure of 7a.
R2
R2
6
8
Entry
Cyclopropane
R1
R2
Product
Yield (%)
1
2
3
4
6a
6b
6c
6f
H
OMe
H
OMe
OMe
Me
8a
8b
8c
8f
75
53
66
74
Supplementary data
H
H
The crystallographic data was deposited with the Cambridge
Crystallographic Data Centre (deposition number CCDC 876447)
Supplementary data associated with this article can be found, in
Rh2(OAc)4 gave disappointing results, as did three other catalysts
(entries 1–4). However, Rh2(S-TBSP)4 gave a satisfactory yield of
the desired product (entry 5). In addition to the 1,1-cyclopropane
diester product 6a, formation of the carbene dimer was an
unavoidable by-product which fortunately could be separated by
column chromatography. In order to achieve complete cycloprop-
anation of 4a, 3 equiv of 5b were required.
References and notes
1. (a) Gupta, A.; Mandal, S. K.; Leblanc, V.; Descoteaux, C.; Asselin, E.; Berube, G.
Bioorg. Med. Chem. Lett. 2008, 18, 3982–3987; (b) Constantinou, A. I.;
Husband, A. Anticancer Res. 2002, 22, 2581–2585; (c) LaLonde, R. T.;
Ramdayal, F.; Sarko, A.; Yanai, K.; Zhang, M. J. Med. Chem. 2003, 46, 1180–
1190.
2. Gafner, S.; Bergeron, C.; Villinski, J. R.; Godejohann, M.; Kessler, P.; Cardellina, J.
H.; Ferreira, D.; Feghali, K.; Grenier, D. J. Nat. Prod. 2011, 74, 2514–2519.
3. Sawadjoon, S.; Kittakoop, P.; Kirtikara, K.; Vichai, V.; Tanticharoen, M.;
Thebtaranonth, Y. J. Org. Chem. 2002, 67, 5470–5475.
4. (a) Luan, Yi.; Sun, H.; Schaus, S. E. Org. Lett. 2011, 13, 6480–6483; (b)
Devakaram, R.; Black, D. StC.; Andrews, K. T.; Fisher, G. M.; Davis, R. A.; Kumar,
N. Bioorg. Med. Chem. 2011, 19, 5199–5206.
5. Deng, J.-Z.; Starck, S. R.; Li, S.; Hecht, S. M. J. Nat. Prod. 2005, 68, 1625–1628.
6. For recent activity in this area, see Ref.4 and Korotaev, V. Yu.; Sosnovskikh, V.
Ya.; Barabanov, M. A.; Yasnova, E. S.; Ezhikova, M. A.; Kodess, M. I.; Slepukhin,
P. A. Tetrahedron 2010, 66, 1404–1409.
7. For an enantioselective route to 2-aryl-2H-chromenes, see: Moquist, P. N.;
Kodama, T.; Schaus, S. E. Angew. Chem., Int. Ed 2010, 49, 7096–7100.
8. Stokes, S.; Spears, B.; Laseter, C.; Barker, B.; Mead, K. T. Tetrahedron Lett. 2010,
51, 4003–4006.
9. For examples, see: (a) Fristad, W. E.; Peterson, J. R.; Ernst, A. B. J. Org. Chem.
1985, 50, 3143–3148; (b) del Rosario-Chow, M.; Ungwitayatorn, J.; Currie, B. L.
Tetrahedron Lett. 1991, 32, 1011–1014; (c) D’Annibale, A.; Trogolo, C.
Tetrahedron Lett. 1994, 35, 2083–2086; (d) Allegretti, M.; D’Annibale, A.;
Trogolo, C. Tetrahedron 1993, 49, 10705–10714.
These conditions were found to be general for most reactions
studied (Table 3, entries 1–6). The exceptions were compounds 4d
and 4e which failed to react with diazo derivative 5b (entries 7
and 8). As noted earlier, these trimethoxyaryl-substituted chrom-
enes were found to be highly susceptible to decomposition and
were used immediately. However, we suspected that their lack of
reactivity might have been due to their higher rate of decomposition
relative to cyclopropane formation which required 12–16 h to com-
plete. The chromenes 4d and 4e were equally unreactive to reagent
5a, suggesting the reaction duration was a factor in these reactions.
Indeed, the faster reacting iodonium ylide 2a gave cyclopropane
products with both 4d and 4e, albeit in moderate yield (Table 3, en-
tries 11 and 12). In these cases, we surmise that reactions were able
to progress significantly before substantial decomposition of the
chromene occurred. Moreover, reactions with ylide 2a in general
gave higher yields of cyclopropane products than their diazo coun-
terparts (Table 2, entries 9 and 10). To our surprise, however, no
reaction was observed when reagent 2b was used, in which one of
the ester groups was tert-butyl (Table 3, entries 13–15). This was
somewhat disappointing, in light of the fact that the iodonium ylide
of ditert-butyl malonate has been shown to add to styrene.11
10. For related reaction sequences, see: (a) Kim, C.; Brady, T.; Kim, S. H.;
Theodorakis, E. A. Synth. Commun. 2004, 34, 1951–1965; (b) Davies, H. M. L.;
Hu, B. J. Org. Chem. 1992, 57, 4309–4312.