Highly enantioselective catalytic hetero-diels-alder reaction with inverse electron demand

Article abstract of DOI:10.1002/(SICI)1521-3773(19980918)37:17<2404::AID-ANIE2404>3.0.CO;2-D

Valuable substrates for the synthesis of natural products, compounds 3 (R¹ = alkyl, aryl, alkoxy; R², R³ = alkyl) are formed from β,γ-unsaturated α-keto esters 1 and vinyl ethers 2 by the title reaction [Eq. (1)]. Copper(II) bisozaxolines act as catalysts, and in many cases enantiomeric excesses higher than 99.5% are achieved.

Full text of DOI:10.1002/(SICI)1521-3773(19980918)37:17<2404::AID-ANIE2404>3.0.CO;2-D

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[10] M. Moscherosch, J. S. Field, W. Kaim, S. Kohlmann, M. Krejcik, J.
Chem. Soc. Dalton Trans. 1993, 211.
Keywords: azo compounds ´ bond order ´ copper ´ EPR
spectroscopy ´ radical ions
‡
[11] An alternative formulation would be the ªtriple ionº description Cu /
‡
.
(abcp )/Cu ; see H. Bock, H.-F. Herrmann, J. Am. Chem. Soc. 1989,
111, 7622. See also H. Bock, K. Ruppert, C. Näther, Z. Havlas, H.-F.
Herrmann, C. Arad, I. Bögel, A. John, J. Meuret, S. Nick, A.
Rauschenbach, W. Seitz, T. Vaupel, B. Solouki, Angew. Chem. 1992,
104, 564; Angew. Chem. Int. Ed. Engl. 1992, 31, 550.
[1] A. F. Holleman, E. Wiberg, N. Wiberg, Lehrbuch der Anorganischen
Chemie, 101st ed., de Gruyter, Berlin, 1995, pp. 508, 1555, 1624, and
references therein.
[2] a) C. S. Johnson, R. Chang. J. Chem. Phys. 1965, 43, 3183; b) U.
Krynitz, F. Gerson, N. Wiberg, M. Veith, Angew. Chem. 1969, 81, 745;
Angew. Chem. Int. Ed. Engl. 1969, 8, 755; c) T. Shida, Adv. Radiat. Res.
Phys. Chem. 1973, 2, 469; d) R. Sustmann, R. Sauer, J. Chem. Soc.
Chem. Commun. 1985, 1248; e) G. A. Russell, R. Konaka, E. T. Strom,
W. C. Danen, K. Chang, G. Kaupp, J. Am. Chem. Soc. 1968, 90, 4646;
f) F. A. Neugebauer, H. Weger, Chem. Ber. 1975, 108, 2703; g) W.
Kaim, S. Kohlmann, Inorg. Chem. 1986, 25, 3442; h) T. Shida,
Electronic Absorption Spectra of Radical Ions, Elsevier, Amsterdam,
1988, p. 194.
[12] Note added in proof (July 24, 1998): The molecular structure of Ru
complexes of azoaromatic radical anions will be reported by A.
Chakravorty et al.
Highly Enantioselective Catalytic Hetero-
Diels ± Alder Reaction with Inverse Electron
Demand**
[3] Cf. H. Zollinger, Color Chemistry, 2nd ed., VCH, Weinheim,
1991.
[4] W. Kaim, R. Reinhardt, J. Fiedler, Angew. Chem. 1997, 109, 2600;
Angew. Chem. Int. Ed. Engl. 1997, 36, 2493.
Jacob Thorhauge, Mogens Johannsen, and
Karl Anker Jùrgensen*
[5] a) Synthesis of abcp: A solution of lithium hypochlorite (50 g,
0.856 mol) in water (300 mL) was cooled until it began to solidify
(external bath temperature 30oC). A solution of 2-aminopyrimidine
(5 g, 52.5 mmol) in H2O (100 mL) was then added slowly and
carefully. After completion, the orange-red reaction mixture was
warmed to room temperature and extracted several times with
dichloromethane. The organic phase was then purified by chromatog-
raphy on silica gel (CH2Cl2/Et2O, 2/1) to yield the separated red mono-
and dichlorinated azo compounds. The ligand abcp was obtained in a
yield of 1.20 g (18%). Correct C,H,N analysis; 1H NMR (250 MHz,
300 K, CDCl3): d ˆ 8.93 (s). b) Synthesis of 1-PF6: The ligand abcp
(51 mg, 0.20 mmol) and [Cu(PPh3)4](PF6) (503 mg, 0.40 mmol) were
treated for two hours at 708C in dichloromethane (10 mL). The
addition of Et2O after the mixture had warmed to room temperature
precipitated the dark blue product, which was then redissolved in THF
(10 mL). Careful addition of Et2O (about 1 mL) produced a dark blue,
partially crystalline material (178 mg, 54%). We attribute the
reduction to the presence of excess PPh3 (see J. W. Hershberger,
R. J. Klingler, J. K. Kochi, J. Am. Chem. Soc. 1983, 105, 61). EPR
(CH2Cl2, 298 K or 110 K): g ˆ 2.0077; UV/Vis (CH2Cl2, 300 K): lmax
(e) ˆ 700 (1560), 560 (2350), 403 (6400), 373 (6270) nm (m 1 cm 1);
cyclic voltammetry (CH2Cl2/0.1m Bu4NPF6): Epa(ox) ˆ 1.42 V,
The hetero-Diels ± Alder reaction of a,b-unsaturated car-
bonyl compounds with electron-rich alkenes gives excellent
access to substituted 3,4-dihydro-2H-pyrans that are very
useful precursors for the synthesis of carbohydrates and
natural products.[1] The reaction is controlled by the LUMO of
the a,b-unsaturated carbonyl compound and the HOMO of
the dienophile; electron-withdrawing substituents on the
former greatly enhances the reactivity.[1, 2]
Although the reaction usually is highly regioselective,
Lewis acids can improve both regioselectivity and reaction
rate.[1c] A variety of different achiral Lewis acids, such as
EtAlCl2,[3] Me2AlCl,[3] ZnCl2,[3] TiCl4,[3] Eu(fod)3,[4] Yb-
(fod)3,[5] LiClO4,[6] Mg(ClO4)2,[6] and SnCl4[7] have been shown
to catalyze inverse hetero-Diels ± Alder reactions (fod ˆ
6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadiene).
Although much work has been devoted to the diastereo-
selective hetero-Diels ± Alder reaction with inverse electron
demand,[3a, b, 8] the enantioselective addition of electron-rich
alkenes to a,b-unsaturated carbonyl compounds with chiral
Lewis acids as catalysts is still a relatively unexplored field and
only very few reactions have been reported. Examples include
the intramolecular cycloaddition of an oxadiene with a
diisopropylideneglucose ± titanium complex as catalyst (33 ±
88% ee for the tetracyclic product),[9] and a reaction catalyz-
ed by trans-(4,5-dihydro-4,5-diphenyloxazole) ± Mg(ClO4)2
which yields both ene and hetero-Diels ± Alder products in a
89:11 ratio (89% ee for the ene product).[1c] Kanemasa has
reported an intermolecular hetero-Diels ± Alder reaction with
inverse electron demand in which the enantioselective
addition of (E)-oxo-phenylsulfonyl-3-alkenes to enol ethers
‡
E1/2(red1) ˆ 0.06 V, E1/2(red2) ˆ 0.75 V versus Fc /Fc0 at a scan rate
1
of 100 mVs
.
[6] Crystal structure analysis of 1-(PF6) ´ 2THF: C80H64Cl2Cu2F6N6P5 ´
2C4H8O, Mr ˆ 1720.50 gmol 1, crystal size 0.4  0.3  0.6 mm, triclinic,
Å
space group P1, a ˆ 11.5353(9), b ˆ 14.4228(10), c ˆ 14.8086(11) Š,
a ˆ 88.040(5), b ˆ 70.643(6), g ˆ 66.855(5)8, Vˆ 2124.2(3) Š3, Z ˆ 1,
1calcd ˆ 1.439 g cm 3, 3.088 < 2q < 508; 8694 reflections (7472 indepen-
dent; h ˆ 14 to 14, k ˆ 17 to 18, l ˆ 18 to 19) were collected at
908C, 7198 reflections were used for the refinement. R ˆ 0.0578 [I >
2s(I)], wR2 ˆ 0.1748; Siemens P4 diffractometer with graphite
monochromator and MoKa radiation (0.71073 Š). The structure was
solved by direct methods (Siemens SHELXS-86) and refined with full-
matrix least-square methods (SHELXL-93). Two solvent molecules
had to be included, one of which was disordered. Anisotropic thermal
parameters were refined for all non-hydrogen atoms. Hydrogen atoms
were introduced at calculated positions and refined freely (riding
model). Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion no. CCDC-101074. Copies of the data can be obtained free of
charge on application to The Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: (‡44)1223-336-033; e-mail: depos-
it@ccdc.cam.ac.uk).
[*] K. A. Jùrgensen, J. Thorhauge, M. Johannsen
Center for Metal Catalyzed Reactions
Department of Chemistry, Aarhus University
Langelandgade 140, DK-8000 Aarhus C (Denmark)
Fax : (‡ 45)8619-6199
[7] W. Kaim, S. Kohlmann, J. Jordanov, D. Fenske, Z. Anorg. Allg. Chem.
1991, 598/599, 217.
E-mail: kaj@kemi.aau.dk
[8] H. S. Freeman, S. A. McIntosh, P. Singh, Dyes Pigm 1997, 35, 11.
[9] A. F. Holleman, E. Wiberg, N. Wiberg, Lehrbuch der Anorganischen
Chemie, 101st ed., de Gruyter, Berlin, 1995, pp. 661, 672.
[**] The work was made possible by a grant from the Danish National
Science Foundation. Thank are expressed to Professor R. G. Hazell
for performing the X-ray analysis.
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gives dihydropyran adducts in good yields (77 ± 96%) and
with enantioselectivities of 59 ± 97% with TiBr2 ± TADDO-
Late as the catalyst (TADDOL ˆ tetraphenyl-1,3-dioxolan-
4,5-dimethanol).[4b, 10] During the writing of this paper, we
became aware of recent work by Evans et al., who have
studied the copper(ii) bis(dihydrooxazole) catalyzed hetero-
Diels ± Alder reaction between a,b-unsaturated acylphos-
phonates and vinyl ethers.[11]
We report here a novel and highly diastereo- and enantio-
selective catalytic hetero-Diels ± Alder reaction of b,g-unsa-
turated a-keto esters 1, substituted in the g position with alkyl,
aryl, and alkoxy substituents, with the electron-rich alkenes 2
to give very attractive dihydropyran adducts 3 [Eq. (1)]. The
products thus formed are very useful precursors for the
synthesis of carbohydrates and natural products.
the hetero-Diels ± Alder product 3a with 95.6% ee (Table 1,
entry 1). This is improved to 97.5% when the reaction
temperature is reduced to 788C (entry 2). The use of THF
as solvent leads to a further improvement; 3a is obtained with
99.0% ee at 458C, and at 788C it is isolated in 89% yield
and with 99.7% ee (entries 3 and 4). A high conversion is also
observed with nitromethane as the solvent, but the ee value
drops to 75.8% (entry 5). The two phenyl-substituted cop-
per(ii) bis(dihydrooxazole)s 4c, d also catalyze the reaction of
1a with 2a, but although high conversion is obtained, the ee
value of 3a is only moderate (entries 6 and 7). Catalysts 4e, f
are much less effective than 4a, c, d, and only a low ee value
of 3a is observed (entries 8 and 9).
The absolute stereochemistry of the hetero-Diels ± Alder
product 3a is dependent on the catalyst; both 4a and 4c give
the same enantiomer of 3aÐan opposite stereochemistry in
the ligand leads to the same absolute stereochemistry in the
product.[13] In contrast, 4d and 4 f give opposite absolute
stereochemistries of 3a.
The scope and the potential of the hetero-Diels ± Alder
reaction catalyzed by the copper(ii) bis(dihydrooxazole)s 4a,b
are demonstrated for the reaction of various g-substituted b,g-
unsaturated a-keto esters 1a ± c with the electron-rich alkenes
2a, b [Eq. (1)] and 2c [Eq. (2)]. The results for the reactions
are presented in Table 2.
The results of the [4‡2] cycloaddition reaction of 1a with
2a in the presence of various copper(ii) catalysts 4a, c ± f[12]
are presented in Table 1 (OTf ˆ trifluoromethylsulfonate).
Table 1. Results of the reaction 1a ‡ 2a !3a in the presence of the
catalysts 4a, c ± f (10 mol%).
Entry
Catalyst
Solvent
T [8C]
Conv. [%]
ee [%][a]
1
2
3
4
5
6
7
8
9
4a
4a
4a
4a
4a
4c
4d
4e
4 f
CH2Cl2
CH2Cl2
THF
45
78
45
78
20
78
78
78
78
100
100
100
100 (89)[b]
100
100
95
< 10
10
95.6
97.5
99.0
99.7
75.8
63.8
72.4
< 5
Table 2. Results of the hetero-Diels ± Alder reaction of 1a ± c with 2a ± c in
the presence of the catalysts 4a, b (10 mol%) at 788C in THF.
THF
CH3NO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Entry Catalyst
1
2
Product[a]
Yield[%][b] ee[%]
1
2
3
4
5
6
7
8
4a
4a
4a
4b
4a
4a
4a
4a
1a
1b
1c
1c
1c
1a
1b
1c
2a
2a
2a
2a
2b
2c
2c
2c
3a
3b
3c
3c
3d
3 f
3g
3h
89
95
93
88
61[f]
51[14]
96
> 99.5[c]
99.5[d]
64.9
> 99.5[c]
96.8[c, e]
90.4[c]
[a] Determined by GC on a chiral stationary phase. [b] Yield of isolated
product.
> 99.5[c]
99.5[c]
97.5[c, g]
84
The enantioselectivity induced with 4a is superior to that
induced by 4c ± f. The reaction of 1a and 2a, catalyzed by 4a
in CH2Cl2 at 458C, shows complete conversion, and gives
[a] All de values are greater than 98%, except for 3g (95%). [b] Yield of
isolated product. [c] Determined by GC on a chiral stationary phase.
[d] Determined by HPLC on a chiral stationary phase. [e] CH2Cl2 as
solvent. [f] Two diastereomers: 4:1, <10% ee for the minor diastereomer.
[g] Reaction temperature 458C.
The b,g-unsaturated a-keto esters 1a ± c react with 2a in the
presence of 4a (10 mol%) in THF at 788C to give the
hetero-Diels ± Alder products 3a ± c in high yields and with
very high enantiomeric excess ( ꢀ 99.5% ee; Table 2, en-
tries 1 ± 3). When the anion of the catalyst is changed from
OTf to PF6 , a small decrease in the yield and enantioselec-
tivity of 3c is observed (88%, 96.8% ee, entry 4). The use of
2b as the alkene decreases the diastereoselectivity, as now two
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7.1 Hz, 2H; OCH2CH3), 2.75 (m, 1H; C-3H), 2.01 (m, 2H; C-3aHH), 1.31
(t, J ˆ 7.1 Hz, 3H; OCH2CH3)1.24 (t, J ˆ 7.1 Hz, 3H; OCH2CH3); 13C NMR
(75 MHz, CDCl3): d ˆ 162.1, 141.6, 108.6, 102.2, 70.6, 68.4, 64.3, 61.4, 42.5,
23.7, 15.4, 14.2.
diastereomers are formed in a ratio of 4:1 (60% de). The
hetero-Diels ± Alder product 3d is isolated in 61% yield, and
the major diastereomer has an ee value of 90.4% (entry 5).
The drop in the ee value is probably due to steric repulsion
between the tert-butyl substituent and the chiral catalyst in the
preferred endo transition state for the reaction.
Received: May 13, 1998 [Z11854IE]
German version: Angew. Chem. 1998, 110, 2543 ± 2546
The cyclic enol ether 2c is also an excellent substrate for the
enantioselective reaction catalyzed by 4a. Reaction of 2c with
1a leads to the formation of adduct 3 f in 51% yield,[14] and
only one enantiomer can be detected by GC on a chiral
stationary phase (ee > 99.5%; Table 2, entry 6). The reaction
of 1b is also highly enantioselective, and 3g is isolated in 96%
yield and with 99.5% ee (entry 7). The introduction of an
ethoxy substituent in the substrate, 1c, leads likewise to a very
selective reaction, as 3h is obtained in 84% yield and with
97.5% ee. The endo approach of the alkene was confirmed by
an X-ray analysis of the cycloadduct 3h.
The generality and potential of these highly enantioselec-
tive hetero-Diels ± Alder reactions with inverse electron
demand catalyzed by 4a are evident from the results
presented in Table 2. High yields and very high enantiomeric
excess are obtained with alkyl-, aryl-, and alkoxy-substituted
oxadienes, and both acyclic and cyclic dienophiles can be
used. The reaction thus offers a new and promising method
for the synthesis of natural compounds and novel carbohy-
drates.
Keywords: asymmetric catalysis ´ cycloadditions ´ copper ´
Lewis acids ´ synthetic methods
[1] For example, a) G. Desimoni, G. Tacconi, Chem. Rev. 1975, 75, 651;
b) D. L. Boger, S. M. Weinreb, Hetero Diels ± Alder Methodology in
Organic Synthesis, Academic Press, New York, 1987. c) L. F. Tietze, G.
Kettschau in Stereoselective Heterocyclic Synthesis I, Vol. 189 (Ed.: P.
Metz), Springer, Berlin, 1997, pp. 1 ± 120.
[2] For example, J. Sauer, R. Sustmann, Angew. Chem. 1980, 92, 773;
Angew. Chem. Int. Ed. Engl. 1980, 19, 779.
[3] For example, a) D. L. Boger, K. D. Robarge, J. Org. Chem. 1988, 53,
3373; b) L. F. Tietze, C. Schneider, A. Grote, Chem. Eur. J. 1996, 2,
139; c) L. F. Tietze, C. Schneider, A. Montenbruck, Angew. Chem.
1994, 106, 1031; Angew. Chem. Int. Ed. Engl. 1994, 33, 980; d) B. B.
Snider, Q. Zhang, J. Org. Chem. 1991, 56, 4908; e) L. F. Tietze, S.
Brand, T. Pfeiffer, J. Antel, K. Harms, G. M. Sheldrick, J. Am. Chem.
Soc. 1987, 109, 921; f) E. Wada, S. Kanemasa, O. Tsuge, Chem. Lett.
1989, 675.
[4] For example, a) E. Wada, H. Yasuoka, S. Kanemasa, Chem. Lett. 1994,
145; b) E. Wada, W. Pei, H. Yasuoka, U. Chin, S. Kanemasa,
Tetrahedron 1996, 52, 1205.
Â
[5] J.-Y. Merour, L. Chichereau, E. Desabre, P. Gadonneix, Synthesis
1996, 519.
[6] For example, a) G. Desimoni, G. Faita, P. P. Righetti, G. Tacconi,
Tetrahedron 1991, 47, 8399; b) G. Desimoni, G. Faita, P. P. Righetti, L.
Toma, Tetrahedron 1990, 46, 7951; c) A. Corsico Coda, G. Desimoni,
G. Faita, P. P. Righetti, G. Tacconi, Tetrahedron 1989, 45, 775; d) M. A.
Forman, W. P. Dailey, J. Am. Chem. Soc. 1991, 113, 2761.
[7] For example, a) A. Sera, M. Ohara, H. Yamada, E. Egashira, N. Ueda,
J. Setsune, Bull. Chem. Soc. Jpn. 1994, 67, 1912; b) L. F. Tietze, C.
Schneider, Synlett 1992, 755.
[8] For example, a) S. J. Johnson, C. Crasto, S. M. Hecht, Chem. Commun.
1998, 1019; b) G. Dujardin, S. Rossignol, E. Brown, Tetrahedron Lett.
1996, 37, 4007; c) G. Dujardin, S. Rossignol, E. Brown, Synthesis 1998,
763; d) R. R. Schmidt, M. Maier, Tetrahedron Lett. 1985, 26, 2065.
[9] a) L. F. Tietze, P. Saling, Synlett 1992, 281; b) L. F. Tietze, P. Saling,
Chirality 1993, 5, 329.
[10] E. Wada, H. Yasuoka, S. Kanemasa, Chem. Lett. 1994, 1637.
[11] D. A. Evans, J. S. Johnson, J. Am. Chem. Soc. 1998, 120, 4895
[12] a) A. Pfaltz, Acc. Chem. Res. 1993, 26, 339; b) D. A. Evans, S. J. Miller,
T. Lectka, J. Am. Chem. Soc. 1993, 115, 6460; c) D. A. Evans, J. A.
Murry, P. von Matt, R. D. Norcross, S. J. Miller, Angew. Chem. 1995,
107, 864; Angew. Chem. Int. Ed. Engl. 1995, 34, 798; d) A. K. Ghosh, P.
Mathivanen, J. Caprello, Tetrahedron: Asymmetry 1998, 9, 1, and
references therein.
[13] We have previously observed similar change in induction with
copper(ii) bis(dihydrooxazole)s as catalysts for normal hetero-
Diels ± Alder reactions of aldehydes and ketones: M. Johannsen,
K. A. Jùrgensen, J. Org. Chem. 1995, 60, 5979; M. Johannsen, S. Yao,
K. A. Jùrgensen, Chem. Commun. 1997, 2169.
Experimental section
3b: Catalyst (S)-4a was prepared by the addition of Cu(OTf)2 (36 mg,
0.1 mmol) to 2,2'-isopropylidenebis[(4S)-4-tert-butyl-2-oxazoline] (31 mg,
0.105 mmol) dissolved in dry THF (2 mL) under N2, followed by stirring for
1 h. Compound 1b (190 mg, 1.0 mmol) was added to the catalyst solution,
which was then cooled to 788C. Freshly distilled 2a (143 mL, 1.5 mmol)
was added, and the solution was stirred at this temperature for 50 h.
Pentane (2 ml) was then added, and the mixture was filtered through a
silica plug with pentane/Et2O (1/1). The solvent was evaporated, and the
crude product was purified by flash chromatography (pentane/Et2O 90/10)
to give 3b as a pale yellow oil in 95% yield and with 99.5% ee, determined
by HPLC with a chiral OD column (hexane/iPrOH 98/2, 1.0 mLmin 1).
[a]D20 ˆ ‡2.18 (c ˆ 1.06, CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 7.34 ± 7.20
ˆ
(m, 5H; C6H5), 6.16 (dd, J ˆ 3.2, 1.1 Hz, 1H; C CH), 5.16 (dd, J ˆ 7.7,
2.2 Hz, 1H; C-6H), 4.04 (dq, J ˆ 9.3, 7.1 Hz, 1H; OCHHCH3), 3.81 (s, 3H;
OCH3), 3.73 (ddd, J ˆ 9.5, 7.0, 3.2 Hz, 1H; C-4H), 3.63 (dq, J ˆ 9.3, 7.1 Hz,
1H; OCHHCH3), 2.31 (dddd, J ˆ 13.5, 7.0, 2.2, 1.1 Hz, 1H; C-5HH), 1.97
(ddd, J ˆ 13.5, 9.5, 7.7 Hz, 1H; C-5HH), 1.23 (t, J ˆ 7.1 Hz, 3H; OCH2CH3);
13C NMR (75 MHz, CDCl3): d ˆ 163.2, 142.8, 142.3, 128.6, 127.5, 126.8,
114.5, 100.0, 64.7, 52.2, 37.8, 36.0, 15.1. The reaction has also been run on a
gram scale to give 3b in quantitative yield and with high selectivity
(>99% ee, >98% de).
3h: The catalyst was prepared as described above. Compound 1c (172 mg,
1 mmol) was added to the catalyst solution, which was then cooled to
788C and treated with freshly distilled 2c (151 mL, 2 mmol). The solution
was warmed to 458C and stirred for 50 h. Pentane (2 mL) was then
added, and the mixture was filtered through a silica plug with pentane/Et2O
(1/1). After evaporation of the solvent, the crude product was purified by
[14] The reaction gives 100% conversion, but the product is presumably
unstable on the column during purification.[3a]
flash chromatography (pentane/Et2O, 75/25) to give 3h as
a highly
crystalline, colorless solid in 84% yield and with 97.5% ee (determined
by GC with a Chrompack Chirasil-DEX CB column). One recrystallization
from Et2O gave the enantiopure product. X-ray spectroscopy confirmed
the expected endo structure of the product. [a]2D0
ˆ
32.18 (c ˆ 1.06,
CHCl3); 1H NMR (300 MHz, CDCl3): d ˆ 6.01 (dd, J ˆ 2.2, 1.5 Hz, 1H;
ˆ
C CH), 5.66 (d, J ˆ 4.0 Hz, 1H; C-2H), 4.50 (dd, J ˆ 6.6, 2.2 Hz, 1H; C-
4H), 4.26 (dq, J ˆ 4.4, 7.1 Hz, 2H; OCH2CH3), 4.24 (ddd, J ˆ 17.9, 9.2,
3.5 Hz, 1H; C-7aHH), 3.97 (dt, J ˆ 9.2, 8.1 Hz, 1H; C-7aHH), 3.60 (q, J ˆ
2406
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