Selective O-methylations of 3-[(triphenylphosphoranylidene)acetyl]tetronic and -tetramic acids

Article abstract of DOI:10.1016/j.tet.2013.03.004

Tetronic and tetramic acids react with the cumulated ylide Ph ₃PCCO to afford 3-[(triphenylphosphoranylidene)acetyl] derivatives 4 and 5. These can be selectively methylated with Meerwein's salt, Me ₃O⁺BF₄, eith

Full text of DOI:10.1016/j.tet.2013.03.004

Tetrahedron 69 (2013) 3677e3682
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Selective O-methylations of 3-[(triphenylphosphoranylidene)acetyl]
tetronic and -tetramic acids
,
Marina Harras a, Tobias Bauer b, Rhett Kempe b, Rainer Schobert a
*
a Organic Chemistry Laboratory, University Bayreuth, Universitaetsstr. 30, D-95440 Bayreuth, Germany
b Inorganic Chemistry Laboratory, University Bayreuth, Universitaetsstr. 30, D-95440 Bayreuth, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Tetronic and tetramic acids react with the cumulated ylide Ph3PCCO to afford 3-[(triphenylphosphor-
anylidene)acetyl] derivatives 4 and 5. These can be selectively methylated with Meerwein’s salt,
Me3OþBF4ꢀ, either at the 4-O atom of the heterocycle or, in the presence of 1,8-bis(dimethylamino)
naphthalene (proton sponge), at the O-atom of the acyl ylide. While the 4-methoxy ylides 6 and 7 un-
dergo Wittig reactions with aldehydes to give the corresponding 3-enoyltetronates and -tetramates as
occurring in natural products, the 10-methoxy isomers 8 and 9 are typically unreactive bisacyl ylides. This
was rationalised by an X-ray structural analysis and ab initio calculations. However, the formal Wittig
products of 8 and 9 are accessible in two steps via Wittig olefination of ylides 4/5 followed by 10-O
methylation of the resulting alkenes.
Received 12 February 2013
Accepted 4 March 2013
Available online 13 March 2013
Keywords:
Tetronic acids
Tetramic acids
Phosphorus ylides
Wittig olefination
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
their 10-O atom,12 4-O atom,13 or even the 2-O atom14 alkylated.
Unfortunately, most standard protocols for the alkylation of
Tetronic acids (i.e., dihydrofuran-2,4-diones) 1 and tetramic
acids (i.e., pyrrolidine-2,4-diones) 2 are common metabolites of
marine and terrestrial organisms such as bacteria, algae, sponges,
fungi and lichens.1e3 The vast majority of these compounds feature
a 3-acyl residue and as a consequence are highly polar and exist
as mixtures of numerous tautomers. They are also frequently
of considerable biological activity. 3-Acyltetramic and -tetronic
acids are customarily prepared either directly by base-induced
3-acyltetronic and -tetramic acids such as the one using diazo-
methane lead to mixtures of these regioisomers.15
LaceyeDieckmann cyclisation4 of N-(
b-ketoacyl)-a-amino esters
or O-( -ketoacyl)-
b
a
-hydroxy esters, respectively,5 or in two steps
by 3-acylation of preformed tetramic or tetronic acids. Such
a 3-acylation can be achieved by reaction with the respective acyl
chlorides and BF3ediethyl etherate acc. to Jones,6 or with carboxylic
acids and various condensation agents acc. to Yoshii,7 Yoda8 or
Moloney,9 or with the cumulated phosphorus ylide Ph3PCCO (3).10
The ylides 4 or 5 resulting from the last mentioned method (Fig. 1)
may be deprotonated by potassium tert-butoxide in THF to give an
anionic species that undergoes Wittig alkenation reactions with
aromatic and aliphatic aldehydes including highly unsaturated
ones. We found this to be the method of choice for the synthesis
of delicate 3-oligoenoyltetramic and -tetronic acids.11 There is also
a subclass of acyltetronic and acyltetramic acids that have either
* Corresponding author. Tel.: þ49 921 55 2679; fax: þ49 921 55 2671; e-mail
Fig. 1. Syntheses and structures of 3-[(triphenylphosphoranylidene)acetyl]tetronic and-
tetramic acids 4 and 5.
address: Rainer.Schobert@uni-bayreuth.de (R. Schobert).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.004

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M. Harras et al. / Tetrahedron 69 (2013) 3677e3682
We were also interested in selective O-alkylations of
3-acyltetramic and -tetronic acids for a mechanistic reason. We
had observed that the 3-(triphenylphosphoranylidene)acetyl de-
rivatives 4 and 5 did not enter into Wittig olefinations due to the
tris-b-keto system dissipating the electron density away from the
ylidic carbon atom C-20. There is even a betaine tautomer present
in equilibrium with the ylide tautomer for compounds 4 and 5.10
We were keen to see whether replacement of the hydrogen by
methyl would be possible in a regioselective manner and would
result in compounds as Wittig-active as the anions that we had
previously obtained by deprotonation of 4/5 with potassium tert-
butoxide.
2. Results and discussion
5-Mono- or -disubstituted furandiones 4 and pyrrolidinediꢀones
5 reacted with an excess of Meerwein’s salt Me3OþBF4 in
dichloromethane at room temperature to give exclusively the cor-
responding methyl 3-[(triphenylphosphoranylidene)acetyl]-tetro-
nates 6 or -tetramates 7, respectively (Scheme 1). When the acyl
ylides 4 or 5 were treated with equimolar amounts of Me3OþBF4
ꢀ
in the presence of 1,8-bis(dimethylamino)naphthalene (‘proton
sponge’) under otherwise identical conditions the isomeric 3-[1-
methoxy-2-(triphenylphosphoranylidene)ethenyl]-furan[5H]-2,4-
diones 8 or -pyrrolidine-2,4-diones 9 were formed (Table 1). It
should be noted that reaction of the ylides 4 or 5 first with KtBuO
and then with the soft methylating agent MeI had earlier been
found to afford derivatives alkylated at the ylidic carbon atom C-
20.16 Single crystals were grown of the 5,5-dimethyl derivative 8a
suitable for an X-ray diffraction structural analysis the result of
which is depicted in Fig. 2.
Fig. 2. Molecular structure of 3-[1-methoxy-2-(triphenylphosphoranylidene)ethenyl]-
5,5-dimethyl-furan[5H]-2,4-dione 8a, as thermal ellipsoid representations at 50%
probability level showing the atomic numbering schemes (H-atoms omitted). Selected
bond lengths [A] and angles [ ]: P1eC1 1.7419, C1eC2 1.3595, C2eO1 1.3603, C2eC3
1.4240, C3eC4 1.4154, C3eC8 1.4316, C4eO4 1.2352, C8eO3 1.2193, C8eO2 1.3764,
C5eO2 1.4531, C4eC5 1.5247, P1eC1eC2 121.03, C1eC2eC3 124.12, O1eC2eC3 121.52,
C2eO1eC9 120.18, P1eC1eC2eC3 ꢀ168.43, P1eC1eC2eO1 13.27, C1eC2eC3eC4
19.35, C3eC2eO1eC9 41.64, C1eC2eO1eC9 ꢀ140.01.
ꢁ
ꢀ
The molecular structure of 8a corroborates the qualitative as-
sumption of a phosphorus ylide considerably stabilised by two
carbonyl groups withdrawing electron density from the ylidic car-
bon atom C-20. The bond between the latter and C-10 (or C1 and C2
0
ꢀ
in the notation of Fig. 2) is 1.36 A short while those between C-1 /C-
ꢀ
3, C-3/C-4 and C-2/C-3 are all ca.1.42 A long. In solution compounds
8 and 9 exist exclusively as ylides rather than as mixtures with
zwitterionic vinylphosphonium salts. This was confirmed by in-
dicative signals around 15 ppm in their 31P NMR spectra and at
d
>120 ppm for the ipso-C-atoms of the aryl rings of the PPh3 group
in the 13C NMR spectra.10
We also carried out a single point ab initio (MP2) energy cal-
culation for the geometry obtained by this X-ray structural analysis
using the Gamess (2011) programme, a 6-31þG(2d,p) basis set, and
RHF wave functions in the SCF procedure. The HOMO energy was
calculated to be ꢀ0.273 eV, the LUMO energy 0.082 eV. The HOMO
was found to have its largest orbital coefficients mainly at C-3 and
C-20. However, the electron density when mapped on the molecular
electrostatic potential surface was found concentrated on the ox-
ygen atoms and only to a lesser extent on C-3 and C-20 (cf.
Supplementary data file). In keeping with these results from the
X-ray diffraction analysis and the ab initio calculation ylides of
types 8 and 9 did not enter into Wittig reactions even with strongly
electrophilic aldehydes such as p-nitrobenzaldehyde due to the
parallel deactivating effect of the two carbonyl groups. In this re-
spect they are reminiscent of the inertness of the parent systems 4
and 5. As a workaround, 3-(1-methoxyalkylidene)furandiones and
-pyrrolidinediones, the formal Wittig products of ylides 8 or 9, were
accessible by first olefinating an appropriate aldehyde with the
anionic species resulting from deprotonation of ylides 4 or 5 with
KtBuO and then regioselectively methylating the 10-O atom of the
3-enoyl intermediate thus obtained with Me3OBF4/proton sponge.
Scheme 1. Reagents and conditions: (i) Me3OBF4, CH2Cl2, rt, 24 h; (ii) Me3OBF4, 1,8-
bis(dimethylamino)naphthalene, CH2Cl2, rt.
Table 1
Methoxy ylides 6e9 prepared as shown in Scheme 1
X
Ra
Rb
Yield [%]
6a
6b
7a
8a
8b
9a
9b
O
O
NBoc
O
O
Me
H
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
42
36
30
52
31
40
62
NBoc
NBoc
Me
H

M. Harras et al. / Tetrahedron 69 (2013) 3677e3682
3679
Table 2
Scheme 2 demonstrates this approach for the synthesis of pyrro-
lidinedione 11 from ylide 5b.
3-Enoyltetronate 14a and -tetramates 15
X
Ra
Rb
R1
Yield [%]
14a
15a
15b
15c
O
Me
Me
Me
Me
Me
Me
Me
Me
p-NO2C6H4
p-NO2C6H4
C5H11
65
72
54
50
NBoc
NBoc
NBoc
C6H6
3. Conclusion
Meerwein’s salt Me3OþBF4ꢀ is a ‘hard’ alkylant with a bias for the
nucleophilic oxygen atoms in 3-acyltetronic and -tetramic acids.
Independent of the nature of the 3-acyl residue, it methylates the 4-
O atom when applied in CH2Cl2 solution. In the presence of an excess
of proton sponge, 3-acyltetronic and -tetramic acids with an
electron-rich residue attached to the 3-keto group as in the ylides 4
and 5 or in the enoyl derivative 10 are methylated exclusively at the
oxygen atom of this group. In contrast, 3-acetyl-5,5-dimethyl dihy-
drofuran-2,4-dione 12 featuring acidic a-H atoms next to the 3-keto
Scheme 2. Reagents and conditions: (i) KOtBu, PhCHO, THF, 24 h, 80 ꢁC, 50%; (ii)
Me3OBF4, 1,8-bis(dimethylamino) naphthalene, CH2Cl2, 24 h, rt, 25%.
group is methylated at the 4-O atom under these conditions. A
plausible explanation is that the favourable six-membered OeHeO
chelate persists in derivatives of the latter type when treated with
proton sponge. This base does not carry a metal cation suitable for
replacing the chelated H-atom and so will rather abstract an acidic
It is worthy of note that 3-acetyltetramic and -tetronic acids
such as 12, readily accessible by basic hydrolysis of ylides 4 and 5,17
were methylated by Meerwein’s salt exclusively at 4-O even in the
presence of proton sponge. Since the methyl group is relatively
acidic in these 3-acetyl derivatives1a the H-chelate is likely to re-
main intact even under basic conditions, rendering 4-O the most
basic oxygen atom in the molecule (Scheme 3).
a-H atom leading to anions with a high electron density on 4-O as
indicated in Scheme 3. While the 4-methoxy substituted ylides 6a
and 7a show a Wittig reactivity typical of monoacyl ylides, their 10-
OMe isomers 8 and 9 represent bisacyl ylides where two carbonyl
groups drain too much electron density off the ylidic carbon atom to
enter into Wittig olefinations with even the most activated alde-
hydes. This observation is in line with the results of the X-ray
structural analysis of ylide 8a and ab initio calculations based
thereupon. In summary, we are now in a position to prepare op-
tionally either the 4-methoxy or the 10-methoxy substituted 3-enoyl
derivatives of tetramic and tetronic acids in only three steps. Both
structural motifs were found in natural products.
4. Experimental
4.1. General
Melting points (uncorrected): Electrothermal 9100 melting
point apparatus. IR: PerkineElmer Spectrum One FT-IR spectro
photometer with ATR sampling unit. NMR: if not indicated other-
wise, measured in CDCl3 at 300 MHz (1H), 75.5 MHz (13C) or
121.5 MHz (31P) on a Bruker Avance 300 spectrometer. Chemical
Scheme 3. Reagents and conditions: (i) 2 M NaOH, THF, 2 h, rt, 52%; ii) Me3OBF4, 1,8-
bis(dimethylamino) naphthalene, CH2Cl2, 24 h, rt, 90%.
shifts are given in parts per million (d) downfield from Me4Si as
internal standard for 1H and 13C. Mass spectra: Finnigan MAT 8500
(EI, 70 eV). HRMS: UPLC/Q-TOF MS system in ESI mode. Elemental
analyses: Carlo Erba Elemental Analyzer Model 1106. Optical rota-
In contrast to the bisacyl ylides 8 and 9, the monoacyl ylides 6
and 7 reacted with aliphatic and aromatic aldehydes. However,
acceptable yields of pure E-configured 3-enoyltetronates and tet-
ramates 14 and 15, respectively, were obtained only for the 5,5-
disubstituted ylides 6a and 7a (Scheme 4, Table 2). This reaction
nicely complements the synthesis of 10-O-methylated isomers, e.g.,
Compound 11.
tions: PerkineElmer Polarimeter 343 (
l
¼589 nm). For column
chromatography Merck silica gel 60 (230e400 mesh) was used.
Solvents were dried and distilled (diethyl ether and THF over Na/K,
CH2Cl2 over CaH2) and stored under argon. Starting compounds
were bought from the usual sources and used without further
purification. (5S)-5-Methyl-3-[(triphenylphosphoranylidene)ace-
tyl]dihydrofuran-2,4-dione (4b) was prepared as published.11
4.2. Synthesis and characterisation
4.2.1. 5,5-Dimethyl-3-[(triphenylphosphoranylidene)acetyl]
dihy-
drofuran-2,4-dione (4a). A solution of 5,5-dimethyltetronic acid
(1a)18 (5.28 g, 41.21 mmol) inTHF (550 mL) was stirred at gentle reflux
and treated over a period of 20 min with a solution of Ph3PCCO (3)
(12.50 g, 41.21 mmol) in the same solvent (50 mL). Heating was
Scheme 4. Wittig alkenations with ylides 6 and 7.

3680
M. Harras et al. / Tetrahedron 69 (2013) 3677e3682
continued for a further 16 h. The solvent was then removed under
reduced pressure and the resulting residue was purified by column
chromatography (ethyl acetate) to leave 17.70 g (99%) of 4a as a faintly
was added, the layers were separated, the aqueous one extracted
with CH2Cl2 (2ꢃ30 mL), and the combined organic phases were
first washed with brine, then dried over Na2SO4 and finally con-
centrated under vacuum. The crude product was purified by col-
umn chromatography (silica gel; ethyl acetate/hexane, 2:1þ5%
methanol) to leave tetronate 6a (0.22 g, 42%) as a faintly yellow
crystalline solid of mp 191 ꢁC; Rf 0.68 (CH2Cl2/acetone, 1:1); nmax
yellow solid of mp 146 ꢁC (decomp.); nmax 1732,1607,1584,1427 cmꢀ1
;
dH 1:3 mixture of ylide (a) and betaine (b): 1.16 and 1.36 (each 3H, s,
CH3b), 1.20 and 1.25 (each 3H, s, CH3b), 5.02 (2H, d, JHP 13.3 Hz, PCH2),
5.14 (1H, d, JHP 19.1 Hz, P]CH), 7.41e7.82(15H, m, PPh3),11.38 (1H, brs,
OH); dC ylide: 23.6 (CH3), 55.6 (d, JPC 107.2 Hz, P]CH), 82.9 (C-5), 95.0
(C-3),123.7 (d,JPC 92.6Hz,PeCipso),173.3 (C-2),179.0(C-10),199.4(C-4);
betaine: 23.8 (CH3), 34.6 (d, JPC 53.6 Hz, PCH2), 82.3 (C-5), 95.4 (C-3),
119.1 (d, JPC 88.3 Hz, PeCipso), 173.4 (C-2), 179.1 (C-10), 200.6 (C-4);
further unassignable phenyl signals of both isomers: 128.2, 128.4,
129.1, 129.3, 129.4, 129.6, 129.8, 130.2, 131.8, 132.8, 132.9, 133.0, 133.1,
133.3,133.5,133.7,133.8,134.4; dP ylide: 15.5; betaine: 22.7; m/z(%) 430
(100, Mþ), 344 (15), 316 (35), 262 (25, PPh3þ), 227 (33), 183 (45), 131
(7); HRMS: m/z calcd for C26H24O4P [MHþ]: 431.1412; found: 431.1425.
1740, 1636, 1516, 1034 cmꢀ1
; dH (CD3OD) 1.45 (6H, s, 5-CH3), 4.14
(3H, s, OCH3), 7.48e7.80 (15H, m, PPh3); dC (CD3OD) 24.6 (5-CH3),
61.4 (OCH3), 82.5 (C-5), 106.0 (d, JPC 17.9 Hz, C-3), 126.8 (d, JPC
91.5 Hz, PeCipso), 130.0, 130.3, 130.5, 131.6, 131.7, 133.1, 133.2, 133.5,
133.9, 134.0, 134.1, 134.4, 134.5 (Car), 173.6 (C-2), 179.6 (C-4), 180.2
(C-10); dP (CD3OD) 14.1; m/z (%) 444 (14, Mþ), 303 (15), 262 (100),
201 (7), 183 (20, M ꢀ PPh3þ), 108 (7). HRMS: m/z calcd for
C27H26O4P [MHþ]: 445.1569; found: 445.1581.
4.2.5. (ꢀ)-(5S)-4-Methoxy-5-methyl-3-[(triphenylphosphor-
anylidene)acetyl]furan[5H]-2-one (6b). Analogously to 6a, ylide 6b
(37 mg, 36%) was obtained as a clear viscous oil from 4b (100 mg,
0.24 mmol) and Me3OBF4 (71 mg, 0.48 mmol); Rf 0.59 (CH2Cl2/ace-
4.2.2. N-tert-Butoxycarbonyl-5,5-dimethyl-3-[(triphenylphosphor-
anylidene)acetyl]pyrrolidine-2,4-dione (5a). Analogously to 4a,
ylide 5a (4.39 g, 92%) was obtained as a yellow solid of mp 181 ꢁC
(decomp.) from N-tert-butoxycarbonyl-5,5-dimethylpyrrolidine-
2,4-dione (2a)19 (1.88 g, 8.27 mmol) and ylide 3 (2.50 g, 8.27 mmol);
tone, 1:1); ½a 2D3
ꢂ
e2.2 (c 0.5, CHCl3); nmax 1743, 1631, 1518, 1437,
1109 cmꢀ1
; dH (CD3CN) 1.38 (3H, d, JHH 6.7 Hz, 5-CH3), 4.11 (3H, s,
nmax 1751, 1631, 1550, 1438, 1316 cmꢀ1
;
dH 3:1 mixture of ylide (a)
OCH3), 4.72 (1H, q, JHH 6.7 Hz, 5-H), 7.48e7.75 (15H, m, PPh3); dC
(CD3CN) 18.3 (5-CH3), 53.3 (d, JPC 109.0 Hz, P]CH), 61.4 (OCH3), 74.5
(C-5), 101.7 (C-3), 127.5 (d, JPC 91.0 Hz, PeCipso), 129.7, 129.8, 130.0,
130.2, 130.8, 131.0, 132.7, 132.8, 133.1, 133.6, 133.9, 134.1, 134.9, 135.1
(Car),172.7 (C-2),177.8 (C-4),187.5 (C-10); dP (CD3CN) 14.1; m/z (%) 430
(2, Mþ),416(52), 301(28),262(45), 201(7),183(64),152(18),108(15).
and betaine (b): 1.38 (6H, s, CH3b), 1.41 (6H, s, CH3a), 1.42 (9H, s,
tBub), 1.45 (9H, s, tBua), 5.09 (2H, d, JHP 12.6 Hz, PCH2), 5.49 (1H, d,
JHP 19.9 Hz, P]CH), 7.33e7.71 (15H, m, PPh3), 12.69 (1H, br s, OH);
dC ylide: 22.9 (5-CH3), 28.0 (Me3C), 55.8 (d, JPC 108.1 Hz, P]CH),
65.7 (C-5), 81.2 (CMe3), 92.1 (C-3), 123.9 (d, JPC 92.8 Hz, PeCipso),
149.4 (O]CN), 172.7 (C-10), 174.7 (C-2), 194.1 (C-4); betaine: 22.6
(5-CH3), 27.9 (Me3C), 35.1 (d, JPC 54.6 Hz, PCH2), 63.5 (C-5), 80.7
(CMe3), 89.8 (C-3), 119.5 (d, JPC 87.8 Hz, PeCipso), 150.1 (O]CN),
173.6 (C-10), 175.7 (C-2), 197.6 (C-4); further unassignable phenyl
signals of both isomers: 127.9, 128.9, 129.1, 129.5, 129.6, 129.9, 130.1,
130.2, 131.8, 132.7, 132.9, 133.5, 133.7, 133.9, 134.1, 134.9; dP ylide:
14.9; betaine: 22.4; m/z (%) 529 (72, Mþ), 430 (100), 345 (51), 316
(27), 301 (95), 277 (41), 201 (20), 183 (47), 165 (20), 154 (11), 108
(12), 99 (17); HRMS: m/z calcd for C31H32NNaO5P [MNaþ]:
552.1916; found: 552.1990.
4.2.6. N-tert-Butoxycarbonyl-4-methoxy-5,5-dimethyl-3-[(triphenyl-
phosphoranylidene)acetyl]-3-pyrrolin-2-one (7a). Analogously to 6,
ylide 7a (185 mg, 30%) was obtained as a clear viscous oil from 5a
(600 mg, 1.13 mmol) and Me3OBF4 (201 mg, 1.36 mmol); Rf 0.64
(CH2Cl2/acetone, 1:1); vmax 1753, 1634, 1522, 1438, 1315, 1151, 1106,
1058 cmꢀ1 dH (CD3CN) 1.47 (6H, s, 5-CH3),1.48 (9H, s, tBu), 4.10 (3H,
;
s, OCH3), 7.48e7.73 (15H, m, PPh3); dC (CD3CN) 23.8 (5-CH3), 28.4
(Me3C), 59.3 (d, JPC 104.0 Hz, P]CH), 61.4 (OCH3), 63.3 (C-5), 84.0
(CMe3), 111.1 (C-3), 126.8 (d, JPC 88.3 Hz, PeCipso), 129.4, 129.7, 129.8,
130.1, 130.3, 130.6, 130.8, 131.2, 132.7, 132.8, 133.1, 133.7, 133.8, 134.1,
135.0 (Car), 150.7 (O]CN), 170.5 (C-2), 175.7 (C-4), 180.0 (C-10); dP
(CD3CN) 13.8; m/z (%) 443 (18), 428 (7), 303 (19), 277 (33), 262
(100), 201 (11), 183 (18), 108 (5); HRMS: m/z calcd for C32H35NO5P
[MHþ]: 544.2253; found: 544.2277.
4.2.3. (þ)-(5S)-N-tert-Butoxycarbonyl-5-methyl-3-[(triphenylphos-
phoranylidene)acetyl]pyrrolidine-2,4-dione (5b). Analogously to 4a,
ylide 5b (7.47 g, 99%) was obtained as an orange solid of mp 167 ꢁC
(decomp.) from (5S)-N-tert-butoxycarbonyl-5-methyl pyrrolidine-
2,4-dione (2b)19 (3.1 g, 14.54 mmol) and ylide
3
(4.40 g,
14.54 mmol); ½a 2D0
ꢂ
19.5 (c 1.0, CHCl3); nmax 1749, 1620, 1554, 1437,
4.2.7. 3-[10-Methoxy-20-(triphenylphosphoranylidene)ethen-10-yl]-
5,5-dimethyldihydrofuran-2,4-dione (8a). A solution of 4a (100 mg,
0.23 mmol) in dry CH2Cl2 (8 mL) was treated with 1,8-
bis(dimethylamino)naphthalene (300 mg, 1.39 mmol) and the
resulting mixture was stirred at room temperature for 20 min.
Meerwein’s salt Me3OBF4 (210 mg, 1.39 mmol) was added and
stirring continued for another 24 h. Saturated aqueous NH4Cl so-
lution was added (15 mL), the layers were separated, the aqueous
one was extracted with CH2Cl2 (2ꢃ30 mL), and the combined or-
ganic phases were first washed with brine, then dried over Na2SO4
and finally concentrated under vacuum. The crude product was
purified by column chromatography (silica gel; ethyl acetate/hex-
ane, 2:1þ5% methanol) to leave ylide 8a (55 mg, 52%) as colourless
crystals of mp 231 ꢁC; (Found: C, 72.85; H, 5.68. C27H25O4P requires
C, 72.96; H, 5.67%); Rf 0.64 (CH2Cl2/acetone, 1:1); nmax 1715, 1630,
1309 cmꢀ1
; dH 1:3 mixture of ylide (a) and betaine (b): 1.41 (3H, d,
JHH 6.7 Hz, 5 ꢀ CH3a), 1.43 (3H, d, JHH 6.8 Hz, 5 ꢀ CH3b), 1.46 (9H, s,
tBua), 1.49 (9H, s, tBub), 3.75 (1H, q, JHH 6.7 Hz, 5-Ha), 3.96 (1H, q, JHH
6.8 Hz, 5-Hb), 5.12 (2H, d, JHP 12.8 Hz, PCH2b), 5.43 (1H, d, JHP
18.8 Hz, PeCHa), 7.36e7.78 (15H, m, PPh3), 12.47 (1H, br s, OH); dC
ylide: 16.7 (5-CH3), 25.2 (Me3C), 55.2 (d, JPC 109.7 Hz, P]CH), 57.5
(C-5), 80.3 (CMe3), 100.8 (C-3), 123.7 (d, JPC 92.1 Hz, PeCipso), 149.3
(O]CN), 172.3 (C-2), 178.9 (C-10), 191.2 (C-4); betaine: 17.5 (5-CH3),
27.9 (Me3C), 35.1 (d, JPC 54.8 Hz, PCH2), 58.3 (C-5), 80.8 (CMe3),101.4
(C-3), 118.7 (d, JPC 88.6 Hz, PeCipso), 150.1 (O]CN),173.4 (C-2), 178.9
(C-10), 194.8 (C-4); further unassignable phenyl signals of both
isomers: 128.1, 128.3, 128.4, 129.1, 129.2, 129.5, 129.6, 130.0, 130.2,
131.6, 131.7, 132.7, 132.8, 132.9, 133.5, 133.6, 134.1, 134.8, 134.9; dP
ylide: 14.7; betaine: 23.6; m/z (%) 515 (13, Mþ), 501 (63), 415 (29),
344 (6), 262 (18), 183 (26), 166 (10). HRMS: m/z calcd for
C30H31NO5P [MHþ]: 516.1940; found: 516.1940.
1510, 1054 cmꢀ1
; dH (CD3OD) 1.37 (6H, s, 5-CH3), 3.17 (3H, s, OCH3),
5.54 (1H, d, JHP 20.7 Hz, P]CH), 7.61e7.81 (15H, m, PPh3); dC
(CD3OD) 24.6 (5-CH3), 58.9 (OCH3), 73.7 (d, JPC 104.1 Hz, P]CH),
84.3 (C-5), 87.3 (d, JPC 10.8 Hz, C-3), 124.6 (d, JPC 92.6 Hz, PeCipso),
130.2, 130.4, 130.8, 131.0, 134.0, 134.3, 134.6, 135.0 (Car), 175.3 (C-10),
176.3 (C-2), 198.8 (C-4); dP (CD3OD) 15.4; m/z (%) 444 (44, Mþ),
400 (24), 353 (47), 330 (89), 262 (100), 243 (19), 202 (19), 183
4.2.4. 4-Methoxy-5,5-dimethyl-3-[(triphenylphosphoranylidene)
acetyl] furan[5H]-2-one (6a). A mixture of 4a (0.5 g, 1.16 mmol),
Meerwein’s salt Me3OBF4 (0.21 g, 1.39 mmol) and dry CH2Cl2
(15 mL) was stirred at room temperature for 24 h. Water (15 mL)

M. Harras et al. / Tetrahedron 69 (2013) 3677e3682
3681
(68, M ꢀ PPh3þ), 145 (25), 108 (12). HRMS: m/z calcd for C27H26O4P
[MHþ]: 445.1569; found: 445.1552.
thus obtained was heated at reflux for another 12 h. The solution
was chilled to room temperature and concentrated under vacuum.
The residue was filtered through a column (2e5 cm) charged with
Dowex MPWA anion exchanger resin to remove most of the
byproduct phosphine oxide. The resin was rinsed several times
with 50 mL each of ethyl acetate, methanol, THF and CH2Cl2. Finally,
the product was recovered from the column by eluting it first with
a mixture of 1 M aq KHSO4/methanol (1:1; 100 mL), then with neat
methanol. The combined eluates were concentrated and the
remaining aqueous phase was extracted several times with CH2Cl2.
The extracts were dried with Na2SO4, filtered and concentrated in
vacuum to leave 200 mg (50%) of product 10 as an orange viscous
Crystal data for 8a: C27H25O4P, M¼444.44, orthorhombic, space
ꢀ
group P2(1ꢁ)2(1)2(1), a¼8.5710(3), b¼15.5010(5), c¼17.4060(6) A,
3
ꢀ
ꢀ
m
a¼
b¼
g
¼90 , V¼2312.55(14) A , Z¼4,
l
¼0.71069 A,
¼0.150 mme1
,
T¼133 K; 27,955 reflections, 3856 unique; final refinement to
convergence on F2 gave R¼0.0267 and Rw¼0.0720, GOF¼1.060.
CCDC 902297 (for full details cf. Supplementary data file).
4.2.8. (ꢀ)-(5S)-3-[10-Methoxy-20-(triphenylphosphoranylidene)
ethen-10-yl]-5-methyldihydrofuran-2,4-dione (8b). A mixture of 4b
(300 mg, 0.72 mmol), 1,8-bis(dimethylamino)naphthalene
(232 mg, 1.08 mmol), Me3OBF4 (160 mg, 1.08 mmol) and CH2Cl2
(7 mL) was irradiated in a CEM microwave oven (300 W) at 70 ꢁC for
1 h and then worked up as described for 8a. Yield: 95 mg (31%) of
8b as slowly solidifying faintly yellowish foam of mp 131 ꢁC; Rf 0.52
oil; Rf 0.40 (ethyl acetate/hexane, 4:1); ½a D20
ꢂ
26 (c 1.0, CHCl3); nmax
dH 1.46 (3H, d, JHH
1710, 1625, 1581, 1369, 1338, 1297, 1150 cmꢀ1
;
6.9 Hz, 5-CH3), 1.52 (9H, s, tBu), 4.16 (1H, q, JHH 6.9 Hz, 5-H),
7.29e7.50 (3H, m, Har), 7.53e7.70 (2H, m, Har), 7.80 (1H, d, JHH
15.8 Hz, CHPh), 7.89 (1H, d, JHH 15.8 Hz, CHCOH), 11.48 (1H, br s,
OH); dC 17.0 (5-CH3), 27.9 (Me3C), 61.2 (C-5), 83.6 (Me3C), 99.8 (C-3),
117.4 (CHPh), 126.8, 128.8, 129.1, 129.3, 130.5, 134.0, 146.5 (CHCOH),
148.5 (O]CN), 173.3 (C-2), 176.7 (C-10), 192.9 (C-4); m/z (%) 343 (6,
Mþ), 243 (22), 215 (100), 201 (69), 171 (6), 131 (16), 103 (9); HRMS:
m/z calcd for C19H21NNaO5 [MNaþ]: 366.1317; found: 366.1326.
(CH2Cl2/acetone, 1:1); ½a D21
ꢂ
e6.3 (c 0.5, CHCl3); nmax 1714, 1625,
dH (CD3CN) 1.29 (3H, d, JHH
1513, 1455, 1437, 1411, 1107, 1042 cmꢀ1
;
6.6 Hz, 5-CH3), 3.20 (3H, s, CH3O), 4.27 (1H, q, JHH 6.6 Hz, 5-H), 5.59
(1H, d, JHP 22.3 Hz, P]CH), 7.58e7.78 (15H, m, PPh3); dC (CD3CN)
18.6 (5-CH3), 59.7 (OCH3), 68.8 (d, JPC 106.9 Hz, P]CH), 77.9 (C-5),
102.4 (C-3), 125.4 (d, JPC 92.2 Hz, PeCipso), 130.9, 131.1, 134.4, 134.5,
134.9 (Car), 175.1 (C-10), 176.6 (C-2), 195.3 (C-4); dP (CD3CN) 15.4; m/
z (%) 430 (46, Mþ), 415 (5), 386 (48), 339 (42), 303 (10), 262 (100),
183 (63), 165 (10), 145 (21), 108 (14).
4.2.12. (5S)-N-tert-Butoxycarbonyl-3-[(E)-10-methoxy-30-phenyl-
allylidene]-5-methylpyrrolidine-2,4-dione (11). Analogously to 9,
methyl enol ether 11 (26 mg, 25%) was obtained as a yellow viscous
oil from 10 (100 mg, 0.29 mmol), 1,8-bis(dimethylamino)naphtha-
lene (125 mg, 0.58 mmol), and Me3OBF4 (86 mg, 0.58 mmol); Rf 0.64
4.2.9. N-tert-Butoxycarbonyl-3-[10-methoxy-20-(triphenylphosphor-
anylidene)ethen-10-yl]-5,5-dimethylpyrrolidine-2,4-dione
(9a). Analogously to 8b, ylide 9a (184 mg, 40%) was obtained as
white crystals of mp 177 ꢁC from 5a (450 mg, 0.85 mmol), 1,8-
bis(dimethylamino)naphthalene (273 mg, 1.27 mmol), and
Me3OBF4 (189 mg, 1.27 mmol); Rf 0.42 (CH2Cl2/acetone, 1:1); nmax
(ethyl acetate/cyclohexane, 1:1); ½a D21
ꢂ
11 (c 1.0, CHCl3); nmax 1773,
1929, 1607, 1323, 1155 cmꢀ1
; dH 1.53 (3H, d, JHH 6.6 Hz, 5-CH3), 1.54
(9H, s, tBu), 4.02 (3H, s, OCH3), 4.42 (1H, q, JHH 6.6 Hz, 5-H), 7.33e7.37
(3H, m, Har), 7.40 (1H, d, JHH 16.0 Hz, CHPh), 7.54e7.62 (2H, m, Har),
7.61 (1H, d, JHH 16.0 Hz, CHCOMe); dC 17.7 (5-CH3), 28.1 (Me3C), 55.5
(C-5), 62.1 (OCH3), 83.2 (CMe3), 108.8 (C-3), 126.1 (CHPh), 128.80,
128.85 130.6, 134.6 (Car),144.0 (CHCOMe),149.1 (O]CN), 166.5 (C-2),
178.4 (C-10), 187.2 (C-4); m/z (%) 357 (15, Mþ), 284 (7), 257 (38), 214
(8), 173 (6), 140 (90), 131 (64), 58 (100); HRMS: m/z calcd for
C20H23NNaO5 [MNaþ]: 380.1474; found: 380.1478.
1711, 1655, 1606, 1524, 1437, 1337, 1154, 1100, 1032 cmꢀ1
; dH
(CD3OD) 1.47 (6H, s, 5-CH3), 1.58 (9H, s, tBu), 3.17 (3H, s, CH3O), 5.64
(1H, d, JHP 20.8 Hz, P]CH), 7.59e7.86 (15H, m, PPh3); dC (CD3OD)
24.1 (5-CH3), 28.7 (Me3C), 59.0 (OCH3), 66.2 (C-5), 76.1 (d, JPC
103.1 Hz, P]CH), 85.4 (Me3C), 92.6 (C-3), 124.4 (d, JPC 92.6 Hz,
PeCipso), 131.0, 131.2, 134.6, 134.7, 135.3 (Car), 153.2 (O]CN), 173.1
(C-10), 174.5 (C-2), 196.0 (C-4); dP (CD3OD) 15.3; m/z (%) 443 (6), 330
(8), 277 (100), 262 (76), 199 (16), 183 (42), 152 (8), 108 (9); HRMS:
m/z calcd for C32H35NO5P [MHþ]: 544.2253; found: 544.2253.
4.2.13. 3-Acetyl-5,5-dimethyltetronic acid (12).4a A solution of ylide
4a (1.3 g, 3.48 mmol) in THF (30 mL) was treated dropwise with
aqueous 2 M NaOH solution while stirring at room temperature.
Stirring was continued for 2 h and then 50 mL of aqueous HBr
solution were slowly added. The resulting mixture was extracted
with ethyl acetate (2ꢃ50 mL), the combined organic layers were
washed with water (50 mL), dried over Na2SO4 and concentrated in
vacuum. The crude product was purified by sublimation which
afforded tetronic acid 12 (305 mg, 52%) as white crystals of mp
68 ꢁC; Rf 0.51 (ethyl acetate/hexane, 2:1þ5% methanol); nmax 1747,
4.2.10. (þ)-(5S)-N-tert-Butoxycarbonyl-3-[10-methoxy-20-(triphenyl-
phosphoranylidene)ethen-10-yl]-5-methylpyrrolidine-2,4-dione
(9b). Analogously to compound 8b, ylide 9b (632 mg, 62%) was
obtained as a slowly solidifying faintly yellowish foam of mp 101 ꢁC
from 5b (1.00 g, 1.94 mmol), 1,8-bis(dimethyl amino)naphthalene
(1.25 g, 5.28 mmol), and Me3OBF4 (0.86 g, 5.82 mmol); Rf 0.58
(CH2Cl2/acetone, 1:1); ½a D
ꢂ
20 5.4 (c 1.0, CH3OH); nmax 1618, 1500, 1309,
dH (CD3OD) 1.43 (3H, d, JHH 6.7 Hz, 5-CH3), 1.54 (9H,
1154, 1103 cmꢀ1
;
1655, 1594, 1187, 1017 cmꢀ1
; dH 5:6-mixture of two tautomers a and
s, tBu), 3.16 (3H, s, CH3O), 3.97 (1H, q, JHH 6.7 Hz, 5-H), 5.61 (1H, d, JHP
21.1 Hz, P]CH), 7.57e7.82 (15H, m, PPh3); dC (CD3OD) 18.7 (5-CH3),
28.6 (Me3C), 58.9 (OCH3), 59.8 (C-5), 74.3 (d, JPC 104.8 Hz, P]CH),
83.0 (Me3C), 94.3 (d, JPC 10.5 Hz, C-3), 124.7 (d, JPC 92.3 Hz, PeCipso),
130.7, 130.8, 131.0, 134.5, 134.6, 134.8, 135.0 (Car),151.6 (O]CN),172.4
(C-10), 174.9 (C-2), 192.9 (C-4); dP (CD3OD) 15.4; m/z (%) 529 (7, Mþ),
428 (29), 385 (9), 329 (24), 302 (9), 262 (100), 183 (59), 165 (9).
HRMS: m/z calcd for C31H33NO5P [MHþ]: 530.2091; found: 530.2096.
b: 1.45 (6H, s, 5 ꢀ CH3a), 1.49 (6H, s, 5 ꢀ CH3b), 2.52 (3H, s, CH3C]
Oa), 2.53 (3H, s, CH3C]Ob), 10.60 (2H, br s, OHaþb); dC 19.4 (CH3C]
Oa), 21.0 (CH3C]Ob), 23.4 (5 ꢀ CH3a), 23.6 (5-CH3b), 83.3 (C-5b),
89.1 (C-5a), 96.5 (C-3a), 99.1 (C-3b), 171.6 (OCOa), 175.1 (OCOb), 188.7
(CH3C]Oa), 194.3 (CH3C]Ob), 197.4 (C-4a), 202.8 (C-4b); m/z (%)
170 (35, Mþ), 150 (37), 142 (15), 100 (14), 44 (100); HRMS: m/z calcd
for C8H11O4 [MHþ]: 171.0657; found: 171.0679.
4.2.14. 4-Methoxy-5,5-dimethyl-3-acetylfuran[5H]-2-one
(13). A
4.2.11. (þ)-(5S)-N-tert-Butoxycarbonyl-3-[(E)-10-hydroxy-30-phenyl-
allylidene]-5-methylpyrrolidine-2,4-dione (10). Under an inert at-
mosphere a solution of ylide 5b (600 mg, 1.16 mmol) in dry THF
(60 mL) was treated with potassium tert-butoxide (140 mg,
1.28 mmol) and the resulting mixture was heated at reflux for
20 min. A solution of freshly distilled benzaldehyde (140 mg,
1.28 mmol) in dry THF (5 mL) was added dropwise and the mixture
mixture of tetronic acid 12 (52 mg, 0.31 mmol), Me3OBF4 (138 mg,
0.93 mmol), 1,8-bis(dimethylamino)naphthalene (200 mg,
0.93 mmol) and CH2Cl2 (2 mL) was stirred at room temperature for
24 h. Water (5 mL) was added, the layers were separated, the
aqueous one extracted with CH2Cl2 (2ꢃ30 mL), and the combined
organic phases were washed with brine, then dried over Na2SO4
and finally concentrated under vacuum. The crude product was

3682
M. Harras et al. / Tetrahedron 69 (2013) 3677e3682
purified by column chromatography (silica gel; ethyl acetate/hex-
ane, 1:7) to leave tetronate 13 (51 mg, 90%) as colourless crystals of
mp 39 ꢁC; Rf 0.59 (ethyl acetate/hexane, 1:1); nmax 1750, 1689, 1611,
crude product was purified via column chromatography (ethyl ac-
etate/hexane, 1:9) to leave tetramate 15c (13 mg, 50%) as a clear
viscous oil; Rf 0.68, 0.67* (ethyl acetate/cyclohexane, 1:1); nmax
(ATR) 1771, 1727, 1612, 1314, 1154, 971 cmꢀ1; 92:8 mixture (NMR) of
E(*) and Z isomers: dH 1.46 (6H, s, 5-CH3), 1.54 (9H, s, tBu), 1.56* (9H,
s, tBu), 1.59* (6H, s, 5-CH3), 3.97 (3H, s, OCH3), 4.01* (3H, s, OCH3),
6.72 (1H, d, JHH 12.5 Hz, 30-H), 6.97 (1H, d, JHH 12.5 Hz, 20-H),
7.27e7.38 (3H, m, Har), 7.33e7.39 (3H, m, Har), 7.39* (1H, d, JHH
16.2 Hz 30-H), 7.57e7.62 (2H, m, Har), 7.60* (1H, d, JHH 16.2 Hz, 20-H);
dC 23.1 (5-CH3), 23.4* (5-CH3), 28.2/28.2* (Me3C), 62.4* (OCH3), 62.5
(C-5), 62.6 (OCH3), 63.0* (C-5), 83.0/83.0* (CMe3),105.8 (C-3),107.2*
(C-3), 126.5* (CHCHC]O), 128.0*, 128.8* (Car), 129.1 (CHCHC]O),
129.8, 130.6, 134.6* (CHCHCipso), 135.5 (CHCHCipso), 142.3 (CHC]O),
143.9* (CHC]O), 149.3/149.3* (O]CN), 166.2 (C-2), 166.6* (C-2),
180.7 (C-4), 180.9* (C-4), 187.9* (CHC]O), 188.4 (CHC]O); m/z (%)
371 (57, Mþ), 298 (16), 271 (79), 256 (41), 214 (11), 180 (33), 154
(59), 131 (71), 103 (44), 77 (22), 58 (100); HRMS: m/z calcd for
C21H25NNaO5 [MNaþ]: 394.1630; found: 394.1636.
1349, 1286 cmꢀ1
; dH 1.44 (6H, s, 5-CH3), 2.53 (3H, s, CH3C]O), 4.11
(3H, s, OCH3); dC 24.4 (5-CH3), 30.6 (CH3C]O), 63.6 (OCH3), 81.2
(C-5), 103.2 (C-3), 169.3 (C-2), 185.0 (CH3C]O), 195.3 (C-4); m/z (%)
184 (44, Mþ), 169 (33), 151 (19), 127 (29), 112 (7), 101 (44), 44 (100);
HRMS: m/z calcd for C9H13O4 [MHþ]: 185.0814; found: 185.0837.
4.2.15. 4-Methoxy-5,5-dimethyl-3-[(E)-(p-nitro)cinnamoyl]
furan
[5H]-2-one (14a). A mixture of ylide 6a (108 mg, 0.24 mmol),
p-nitrobenzaldehyde (40 mg, 0.27 mmol) and dry THF (12 mL) was
stirred and heated under reflux for 8 h. The volatiles were removed
under reduced pressure and the crude product was purified by
column chromatography (ethyl acetate/hexane, 1:5) to leave tetr-
onate 14a (50 mg, 65%) as yellow crystals of mp 159 ꢁC; Rf 0.42
(ethyl acetate/hexane, 1:2); nmax 1746, 1668, 1613, 1519, 1344, 1287,
1038 cmꢀ1; 92:8 mixture (GC) of E(*) and Z isomers: dH 1.44 (6H, s,
5-CH3), 1.51* (6H, s, 5-CH3), 4.10 (3H, s, OCH3), 4.18* (3H, s, OCH3),
6.97 (2H, s, 20-H, 30-H), 7.63* (2H, s, 20-H, 30-H), 7.64 (2H, d, JHH
8.5 Hz, Hortho), 7.73* (2H, d, JHH 8.5 Hz, Hortho), 8.14 (2H, d, JHH 8.5 Hz,
Acknowledgements
H
meta), 8.21* (2H, d, JHH 8.5 Hz, Hmeta); dC 24.4 (5-CH3), 63.7 (OCH3),
Financial support by the Deutsche Forschungsgemeinschaft
(grant Scho 402/9-2) is gratefully acknowledged. We are indebted
to Dr. Holger Schmidt, Department of Plant Physiology, University
Bayreuth for high resolution mass spectra.
81.7 (C-5), 102.4 (C-3), 124.1 (Cmeta), 128.7 (CHC]O), 129.2 (Cortho),
140.3 (CHCHC]O), 140.7 (CHCipso), 148.6 (CNO2), 169.3 (C-2), 185.2
(CHC]O), 186.6 (C-4); m/z (%) 317 (80, Mþ), 302 (100), 274 (15), 176
(54), 155 (47), 102 (52). HRMS: m/z calcd for C16H16NO6 [MHþ]:
318.0978; found: 318.0982.
Supplementary data
4.2.16. N-tert-Butoxycarbonyl-4-methoxy-5,5-dimethyl-3-[(E)-p-ni-
trocinnamoyl]-3-pyrrolin-2-one (15a). Analogously to 14a, tetra-
mate 15a (55 mg, 72%) was obtained as a yellow crystalline solid of
mp 66 ꢁC from ylide 7a (100 mg, 0.18 mmol) and p-nitro-
benzaldehyde (30.6 mg, 0.20 mmol); Rf 0.65 (ethyl acetate/cyclo-
hexane, 1:1); nmax 1767, 1721, 1613, 1594, 1520, 1343, 1311, 1152,
1105, 1089, 967 cmꢀ1; 94:6 mixture (GC) of E(*) and Z isomers: dH
1.54 (9H, s, tBu), 1.55* (9H, s, tBu), 1.53 (6H, s, 5-CH3), 1.59* (6H, s, 5-
CH3), 3.97 (3H, s, OCH3), 4.06* (3H, s, OCH3), 6.94 (2H, s, 20-H, 30-H),
7.60* (2H, s, 20-H, 30-H), 7.65 (2H, d, JHH 8.9 Hz, Hortho), 7.72* (2H, d,
JHH 8.9 Hz, Hortho), 8.14 (2H, d, JHH 8.9 Hz, Hmeta), 8.20* (2H, d, JHH
8.9 Hz, Hmeta); dC 23.4 (5-CH3), 28.2 (Me3C), 63.0 (OCH3), 63.2 (C-5),
83.2 (CMe3), 106.8 (C-3), 124.0 (Cmeta), 129.2 (Cortho), 129.7 (CHC]
O), 139.6 (CHCHC]O), 141.0 (CHCipso), 148.5 (CNO2), 149.0 (O]CN),
166.7 (C-2), 182.5 (C-4), 186.5 (CHC]O); m/z (%) 416 (18, Mþ), 360
(15), 343 (16), 316 (57), 299 (31),176 (23),154 (23), 57 (100); HRMS:
m/z calcd for C21H24N2NaO7 [MNaþ]: 439.1481; found: 439.1482.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.03.004.
References and notes
1. Reviews on tetramic acids: (a) Henning, H.-G.; Gelbin, A. Adv. Heterocycl. Chem.
1993, 57, 139e185; (b) Royles, B. J. L. Chem. Rev. 1995, 95, 1981e2001; (c)
Ghisalberti, E. L. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.;
Elsevier: New York, 2003; Vol. 28/1, pp 109e163; (d) Gossauer, A. Monopyrrolic
natural compounds including tetramic acid derivatives In. Progress in the
Chemistry of Organic Natural Products; Springer: Wien, New York, 2003; Vol. 86,
pp 1e188.
2. Reviews on tetronic acids: (a) Tejedor, D.; Garcia-Tellado, F. Org. Prep. Proceed. Int.
2004, 36, 35e59; (b) Zografos, A. L.; Georgiadis, D. Synthesis 2006, 3157e3188.
3. Reviews on tetramic and tetronic acids: (a) Schobert, R. Naturwissenschaften 2007,
94, 1e11; (b) Schobert, R.; Schlenk, A. Bioorg. Med. Chem. 2008, 16, 4203e4221.
4. (a) Lacey, R. N. J. Chem. Soc. 1954, 832e839; (b) Lacey, R. N. J. Chem. Soc. 1954,
850e854.
5. (a) Boeckman, R. K.; Weidner, C. H.; Perni, R. B.; Napier, J. J. J. Am. Chem. Soc.
1989, 111, 8036e8037; (b) Paquette, L. A.; MacDonald, D.; Anderson, L. G.;
Wright, J. J. Am. Chem. Soc. 1989, 111, 8037e8039; (c) Ley, S. V.; Smith, S. C.;
Woodward, P. R. Tetrahedron 1992, 48, 1145e1174; (d) Iwata, Y.; Maekawara, N.;
Tanino, K.; Miyashita, M. Angew. Chem., Int. Ed. 2005, 44, 1532e1536 Angew.
Chem. 2005, 117, 1556e1560; (e) Burke, L.; Dixon, D.; Ley, S. V.; Rodríguez, F. Org.
Lett. 2000, 2, 3611e3613; (f) Hart, A. C.; Phillips, A. J. J. Am. Chem. Soc. 2006, 128,
4.2.17. N-tert-Butoxycarbonyl-4-methoxy-5,5-dimethyl-3-[(E)-hex-
2-enoyl]-3-pyrrolin-2-one (15b). Analogously to 14a, tetramate 15b
(27 mg, 54%) was obtained as a yellow viscous oil from ylide 7a
€
1094e1095; (g) Bohme, R.; Jung, G.; Breitmaier, E. Helv. Chim. Acta 2005, 88,
(75 mg, 0.14 mmol) and hexanal (18.9
acetate/cyclohexane, 1:1); nmax 1768, 1718, 1654, 1621, 1314, 1260,
1152, 1090, 975 cmꢀ1
dH 0.79e0.90 (3H, m, CH2Me), 1.15-1.35 (6H,
m
L, 0.15 mmol); Rf 0.76 (ethyl
2837e2841.
6. (a) Kohl, H.; Bhat, S. V.; Patell, J. R.; Ghandi, N. M.; Nazareth, J.; Divekar, P. V.; de
Souza, N. J.; Berscheid, H. G.; Fehlhaber, H.-W. Tetrahedron Lett. 1974, 15,
983e986; (b) Jones, R. C. F.; Begley, M. J.; Peterson, G. E.; Sumaria, S. J. Chem.
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9. Jeong, Y.-C.; Moloney, M. G. J. Org. Chem. 2011, 76, 1342e1354.
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Soc., Perkin Trans. 1 2000, 1723e1730.
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12. Kasettrathat, C.; Ngamrojanavanich, N.; Wiyakrutta, S.; Mahidol, C.; Ruchirawat, S.;
Kittakoop, P. Phytochemistry 2008, 69, 2621e2622.
13. Gu, Z.; Zakarian, A. Angew. Chem., Int. Ed. 2010, 49, 9702e9705.
14. Zhan, Z.-J.; Jin, J.-P.; Ying, Y.-M.; Shan, W.-G. Helv. Chim. Acta 2011, 94, 1454e1458.
15. Terui, Y.; Sakazaki, R.; Shoji, J. J. Antibiot. 1990, 43, 1245e1253.
16. Kempf, K.; Schobert, R., Unpublished results.
;
m, CH2), 1.24 (6H, s, 5-CH3),1.57 (9H, s, tBu), 2.25e2.38 (2H, m, CH2),
3.98 (3H, s, OCH3), 6.67e6.71 (2H, m, 20-H, 30-H); dC 14.0 (CH2Me),
23.3 (5-CH3), 28.2 (Me3C), 22.6, 29.5, 31.7 (CH2), 49.4 (CHCH2), 62.4
(OCH3), 62.9 (C-5), 82.9 (CMe3), 107.0 (C-3), 131.8 (CHC]O), 150.6
(CHCHC]O), 149.2 (O]CN), 166.5 (C-2), 181.0 (C-4), 188.2 (CHC]
O); m/z (%) 365 (2, Mþ), 309 (3), 294 (5), 265 (100), 250 (8), 222 (10),
194 (6), 168 (13), 141 (6), 58 (32); HRMS: m/z calcd for C20H31KNO5
[MKþ]: 404.1839; found: 404.1871.
4.2.18. N-tert-Butoxycarbonyl-4-methoxy-5,5-dimethyl-3-[(E)-cin-
17. Schobert, R.; Dietrich, M.; Mullen, G.; Urbina-Gonzales, J.-M. Synthesis 2006,
3902e3914.
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Hiemstra, H.; Kellogg, R. M.; Feringa, B. L. J. Org. Chem. 1999, 64, 2567e2570.
namoyl]-3-pyrrolin-2-one (15c). A mixture of ylide 7a (40 mg,
0.07 mmol), benzaldehyde (7.5
mL, 0.07 mmol) and dry toluene
(2 mL) was stirred and heated in a sealed bomb tube at 120 ꢁC for
24 h. The volatiles were removed under reduced pressure and the