Synthesis of methyl (R)-2-O-propargylglycerate, a precursor to analogues of the 2-O-alkylglycerate part of the moenomycins

Article abstract of DOI:10.1002/ejoc.200300052

Conditions allowing optically active methyl glycerate to be converted, without racemization, into the 2-O-propargyl derivative, via the 2-O-allyl derivative, are reported. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300052

FULL PAPER
Synthesis of Methyl (R)-2-O-Propargylglycerate, a Precursor to Analogues of
the 2-O-Alkylglycerate Part of the Moenomycins
Madina Mansourova,[a] Katja Rohr,[a] Lothar Hennig,[a] Matthias Findeisen,[a]
Ramona Oehme,[a] Sabine Giesa,[a] and Peter Welzel*[a]
Keywords: Alcohols / Allylation / Alkynes
Conditions allowing optically active methyl glycerate to be
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
converted, without racemization, into the 2-O-propargyl de- Germany, 2003)
rivative, via the 2-O-allyl derivative, are reported.
Introduction
be used to prepare an array of new 2-O-alkylglycerates by
cross metathesis followed by catalytic hydrogenation.[8]
Here we wish to describe the synthesis of methyl 2-O-
propargylglycerate (4b). This compound should also allow
various 2-O-substituted glycerates to be prepared by
known methods.
The antibiotic activity of the moenomycin antibiotics [see
moenomycin A (1), Scheme 1] and structural analogues has
been shown to be critically dependent on the presence of a
suitable lipid component attached to the 2-position of the
glyceric acid moiety.[1,2] Synthesis of structural analogues
with modified lipid chains has been hampered by the incon-
venience of access to 2-O-alkyl glycerates.[3Ϫ7]
Results
The only efficient procedure so far reported is the silver
oxide-promoted reaction between a suitably protected
Direct treatment of 2 with propargyl bromide failed.[9] It
glycerate 2 and allyl bromide, which gives the 2-O-allylated is known, however, that nucleophilic reagents such as elec-
derivative 4 in very high yield (Scheme 2) and without tron-rich aromatic compounds,[10] β-dicarbonyl com-
measurable racemization. The 2-allyl derivative could then pounds,[11] allylsilanes,[12] enols[13] and alcohols react with
Scheme 1
α-[alkynyl-hexacarbonyldicobalt]carbenium ions to give the
corresponding substitution products (Nicholas reaction).[14]
The activating [Co2(CO)6] moieties can be efficiently intro-
[a]
Universität Leipzig, Fakultät für Chemie und Mineralogie,
Johannisallee 29, 04103 Leipzig, Germany
2656
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300052
Eur. J. Org. Chem. 2003, 2656Ϫ2660

Synthesis of Methyl (R)-2-O-Propargylglycerate
FULL PAPER
Scheme 2
duced (by treatment of the alkyne with octacarbonyldicob- remove the dimethoxytrityl group and then to release the
alt) and removed (by treatment with ceriumammonium ni- triple bond with ceriumammonium nitrate. Mosher ester
trate).[15,16] The reaction between 2 and 6 in the presence analysis[19] performed both with 4b (sample obtained from
of several Lewis acids as promoters, at Ϫ20 to 0 °C, was 7b) and with 7b revealed that the Nicholas reaction between
unsuccessful.[17] When, however, the OH group of 5 was 2 and 7 was accompanied by substantial racemization, the
activated as a trichloroacetimidate,[18] the thus formed 6 ratio of the two stereoisomers being about 1:1.6. The analy-
gave the desired ether 7a in a BF3-mediated reaction in sis showed that racemization occurred in the coupling step
yields of 30Ϫ40%. Careful optimization of the reaction con- rather than during cleavage of the cobalt complex. Analysis
ditions (i.e., reduction both of the excess of trichloroaceton- of the Mosher esters 7c obtained by making use of other
itrile used in the formation of 6 and of the amount of Lewis acids in the substitution step revealed somewhat bet-
BF3Ϫdiethyl ether used in the formation of 7a) increased ter stereoisomer ratios (19F NMR).
the yield of 6 to 91% and that of 7a to 78% (Scheme 3).
The results called for a more suitable method for the
Use of other Lewis acids (see Table 1) gave lower yields. On preparation of stereohomogeneous 4b. It is known that al-
the pathway to 4b it turned out to be advantageous first to dehydes can be converted into terminal alkynes by use of
Scheme 3
Table 1. Reaction between 2 and 7[17]]
Lewis-acid
Yield of 7a
Reaction
temperature
Amount of promoter
Ratio of stereoisomers
7c (19F NMR)
BF3·Et2O
Sc(OTf)3
TfOH
TfOSiMe3
B(C6F5)3
78%
35%
23%
Ͻ10%
Ͻ10%
Ϫ20 °C
Ϫ10 °C
0 °C
Ϫ20 °C
Ϫ20 °C
0.33 equiv.
0.10 equiv.
0.20 equiv.
0.10Ϫ0.50 equiv.
0.10Ϫ0.50 equiv.
1:1.6
1:2.23
1:1.86
not determined
not determined
[19]
[20]
Eur. J. Org. Chem. 2003, 2656Ϫ2660
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2657

M. Mansourova, K. Rohr, L. Hennig, M. Findeisen, R. Oehme, S. Giesa, P. Welzel
FULL PAPER
Ϫ 6CO]ϩ·, 555 (3) [7a Ϫ 3CO Ϫ ArOMe]ϩ, 471 (20) [7a Ϫ 6CO Ϫ
ArOMe]ϩ, 460 (9) [7a Ϫ Co2(CO)6]ϩ·, 353 (14) [7a Ϫ Co2(CO)6 Ϫ
ArOMe]ϩ·, 303 (100) [4,4Ј-dimethoxytrityl]ϩ.
the Ohira-Bestmann modification[22,23] of a reaction disco-
vered by Colvin and Hamill.[24] In the event, treatment of
the anion of dimethoxy(diazomethyl)phosphonate with the
aldehyde obtained from 3 on treatment with OsO4/NaIO4
afforded alkyne 4a in 84% yield (Scheme 2). 2-O-Propar-
Methyl
(R)-3-O-(4,4Ј-Dimethoxytrityl)-2-O-propargyl-glycerate
(4a). a) From 7a: Ceriumammonium nitrate (CAN, 660 mg,
gylglycerate 4b was converted into the corresponding 1.20 mmol) was added at 0 °C to a solution of 7a (300 mg,
0.40 mmol) in acetone (8 mL). After the mixture had been stirred
at 0 °C for 10 min, evolution of CO was no longer observed and
TLC (toluene/acetone, 10:1) indicated completion of the reaction.
Solvent evaporation, addition of water and usual workup (diethyl
ether), followed by FC (CH2Cl2/acetone, 20:1) provided 4a
(103 mg, 56%) as a pink oil slightly contaminated with DMT-OH.
Rf ϭ 0.54 (CH2Cl2/acetone, 25:1). IR (KBr): ν˜ ϭ 1747, 1608, 1508,
Mosher ester 4c. NMR revealed that no racemization had
occurred under these conditions.
Thus, as well as the allyl ether 3, the new building block
4a is now available for the preparation of glycerates with
different substituents connected to the 2-position through
an ether linkage.
1248, 1176, 1101, 1034, 785, 762 cmϪ1
.
b) From 4a: A catalytic amount of OsO4 (0.05 mL) in water (1 mL)
was added to a solution of 4a (400 mg, 0.85 mmol) in diethyl ether
(10 mL). After the reaction mixture had turned black (15 min),
NaIO4 (370 mg, 2 equiv.) in water (5 mL) was added. After 18 h
the reaction mixture was diluted with diethyl ether, and the organic
layer was separated and washed with water, dried with NaSO4 and
concentrated. TLC showed only one substance. Because of its very
low stability the aldehyde was used in the next step without any
purification. A solution of dimethoxy(diazomethyl)phosphonate
(210 mg, 1.5 equiv.) and the crude aldehyde (350 mg) in dry meth-
anol (5 mL) and THF (3 mL) was added at 0 °C under argon to a
suspension of K2CO3 (250 mg, 2.2 equiv.) in THF (1 mL). The re-
action mixture was stirred at 0 °C for 30 min and at room tempera-
ture for 6 h. After addition of aqueous saturated NH4Cl (5 mL),
petroleum ether (10 mL) and diethyl ether (10 mL), the organic
layer was separated, dried with Na2SO4 and concentrated. The
crude product was purified by FC on silica gel, eluted with toluene/
acetone (50:1), to give 4a (290 mg, 84% after two steps). Rf ϭ 0.45
(toluene/acetone, 9:1). [α]2D5 ϭ ϩ9 (c ϭ 0.1, CHCl3). IR (film): ν˜ ϭ
1743 cmϪ1 (CO). 1H NMR (200 MHz, HH COSY, CDCl3): δ ϭ
7.49Ϫ7.16 (m, 9 H, Ar H), 6.89Ϫ6.83 (m, 4 H, Ar H), 4.39Ϫ4.34
(m, 3 H, OCH2I, 2-HH), 3.81 (s, 6 H, 2 ϫ ArϪOϪCH3), 3.71 (s, 3
H, OCH3), 3.44 (d, J3,2 ϭ 4.4 Hz, 2 H, 3-CH2H), 2.46 (broad s, 1
H, ϵCH) ppm. 13C NMR (50.3 MHz, HETCOR, CDCl3):
δ ϭ 170.86 (COOCH3), 158.69 (p-methoxyphenyl-C), 144.83
(C-1phenyl), 139.68 (CЈ-1methoxyphenyl), 135.98 (C-1methoxyphenyl),
130.22 (C-3methoxyphenyl), 129.28, 129.15 (2 ϫ C-3phenyl), 128.32,
127.91 (2 ϫ C-2phenyl), 125.43 (C-4phenyl), 113.35, 113.19 (2 ϫ C-
2methoxyphenyl), 86.33 (CAr3), 79.10 (CϵCH), 77.10 (C-2H), 75.42
(CϵCH), 64.28 (C-3H), 57.87 (OCH2), 55.34 (2 ϫ ArϪOϪCH3),
52.09 (COOCH3) ppm. C28H28O6 (460.52, 460.19), ESI MS: m/z ϭ
[M ϩ Na]ϩ calcd. 483.17781; found 483.17804.
Experimental Section
General Methods: see ref.[25]
NMR spectra: The protons and carbons of the glyceric acid unit
H
I
are labelled as and those of the 2-O-substituent as , according
to moenomycin nomenclature (see Scheme 1).
Propargyl Trichloroacetimidate Hexacarbonyldicobalt Complex (6):
Trichloroacetonitrile (2.7 mL, 26.8 mmol) and DBU (dropwise,
4.47 mmol, 700µL) were added at Ϫ10 °C to a solution of the hexa-
carbonyldicobalt complex of propargyl alcohol (5,[26] 6.10 g,
17.89 mmol) in dry dichloromethane (60 mL). After completion of
the reaction (monitoring by TLC) the mixture was quickly filtered
through silica gel. Washing with dichloromethane and solvent evap-
oration furnished crude 6 as a red oil (7.98 g, 91%), which was
unstable and was used without further purification. Rf ϭ 0.60
(CH2Cl2/acetone, 25:1). IR (KBr): ν˜ ϭ 1707, 1514, 1230, 824 cmϪ1
.
1H NMR (300 MHz, CDCl3): δ ϭ 8.45 (br. s, 1 H, NH), 6.10 (s, 1
H, ϵCH), 5.45 (s, 2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 199.1 (br. s, 6 ϫ CϵO), 162.8 (CϭNH), 91.3 (CCl3), 87.3
(CϵCH), 72.3 (ϵCH), 70.5 (CH2) ppm. C11H4Cl3Co2NO7 (486.38,
484.772), FAB MS: m/z (%) ϭ 429 (65) [8 Ϫ 2CO]ϩ·, 401 (29) [8
Ϫ 3CO]ϩ·, 325 (84), 317 (35) [8 Ϫ 6CO]ϩ·, 297 (100), 269 (45),
241 (31).
Methyl
(R)-3-O-(4,4Ј-Dimethoxytrityl)-2-O-propargylglycerate
Hexacarbonyldicobalt Complex (7a): BorontrifluorideϪdiethyl
ether (142 mg, 127 µL, 1 mmol) was slowly added at Ϫ20 °C to a
solution of 2 (1.267 g, 3 mmol) and 6 (1.703 g, 3.5 mmol) in dry
dichloromethane (60 mL). The mixture was stirred at Ϫ20 °C for
2 h. With vigorous stirring, the reaction mixture was then added
to an ice-cold saturated aqueous solution of NaHCO3 (100 mL).
Aqueous workup (CH2Cl2) and FC (toluene/acetone, 30:1) fur-
nished 7a (1.747 g, 78% based on 2) as a dark red oil. Rf ϭ 0.63
(CH2Cl2/acetone, 25:1). IR (KBr): ν˜ ϭ 1749, 1606, 1506, 1250,
Methyl 2-O-Propargylglycerate (4b)
a) Mixture of Enantiomers Obtained by the Nicholas Route:
1178, 1132, 1034, 829 cmϪ1 1H NMR (300 MHz, CDCl3): δ ϭ
.
aa) A solution of 4a (80 mg, 0.174 mmol) in aqueous acetic acid
(80%, 5 mL) was stirred at 20 °C for 48 h. Azeotropic solvent re-
moval [toluene (5 mL) and pyridine (1 mL)] and subsequent FC
(CH2Cl2/acetone, 10:1) provided 4b (15 mg, 55%) as a pink oil.
7.45Ϫ7.41 (d, 2 H, Ar H), 7.34Ϫ7.16 (m, 7 H, Ar H), 6.84Ϫ6.79
(d, 4 H, Ar H), 6.09 (s, 1 H, ϵCH), 4.92 and 4.75 (AB system,
JAB ϭ 13.0 Hz, 2 H, OCH2), 4.34Ϫ4.28 (m, 1 H, 2-Hglyc), 3.84 (s,
6 H, 2 ϫ Ar-OCH3), 3.79 (s, 3 H, OCH3), 3.53 (m, 2 H, CH2-3glyc
)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 200.0 (br. s, 6 ϫ CϵO),
171.1 (ϪCOOCH3), 158.7 (2 ϫ C-4methoxyphenyl), 144.9 (C-1phenyl),
136.0 (2 ϫ C-1methoxyphenyl), 130.3 (4 ϫ C-2methoxyphenyl), 128.4 (2 ϫ
C-2phenyl), 128.1 (2 ϫ C-3phenyl), 127.0 (CAr-4phenyl), 113.3 (4 ϫ C-
ab) Compound 7a (312 mg, 0.703 mmol) was treated with CAN
(1.156 g, 2.11 mmol) as described above. Workup and FC (CH2Cl2/
acetone, 10:1) furnished 4b (64 mg, 58%) as a pink oil.
b) Compound 4b Obtained by the Ohira؊Bestmann Route:
3
methoxyphenyl), 90.7 (CCq o complex), 86.4 [C(Ar)3], 78.9 (C-2glyc), 71.9
(ϵCHCo complex), 71.2 (ϪCH2ϪCϵ), 64.4 (C-3glyc), 55.3 (2 ϫ A solution of 4a (35 mg, 0.08 mmol) in acetic acid (80%, 3 mL)
ArylϪOCH3), 52.0 (ϪCOOCH3) ppm. C34H28Co2O12 (746.46,
was stirred at 20 °C for 4 h. The reaction mixture was then diluted
with a pyridine/water mixture and the solvents were evaporated.
746.025), FAB MS: m/z (%) ϭ 662 (20) [7a Ϫ 3CO]ϩ·, 578 (53) [7a
2658
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Eur. J. Org. Chem. 2003, 2656Ϫ2660

Synthesis of Methyl (R)-2-O-Propargylglycerate
FULL PAPER
Dry pyridine (2 mL) was added and the solvent was removed under
Methyl
2-O-Propargyl-3-O-{[(R)-3,3,3-trifluoro-2-methoxy-2-
reduced pressure. FC (CH2Cl2/acetone, 50:1) provided 4b (10 mg, phenyl]propionyl}glycerate Hexacarbonyldicobalt Complex (7c, Mix-
84%) as a colourless oil. Rf ϭ 0.25 (CH2Cl2/acetone, 9:1). [α]2D5
ϭ
ture of Stereoisomers): Complex 7b was converted into 7c as de-
ϩ176.5 (c ϭ 0.1, CHCl3). IR (film): ν˜ ϭ 3380 (OH), 1743 cmϪ1 scribed for 4b. FC (CH2Cl2/acetone, 10:1) furnished 7c (not com-
(CO). 1H NMR (200 MHz, HH COSY, CDCl3): δ ϭ 4.43 (dd, pletely pure, 20 mg, 84%) as a red oil. 1H NMR (200 MHz, C6D6):
J1,3 ϭ 2.6, J1,1Ј ϭ 16.1 Hz, 1 H, 1-HI), 4.25 (dd, J1,3 ϭ 2.5, J1Ј,1
16.1 Hz, 1 H, 1-HЈI), 4.29 (m, 1 H, 2-HH), 3.92 (dd, J3,2 ϭ 3.6,
ϭ
δ ϭ 7.78Ϫ7.65 (dd, 2 H, 2-HAr), 7.16Ϫ7.08 (m, 3 H, 3-HAr, 4-HAr),
5.40 (s, 1 H, ϵCH), 4.42, 4.09 (2 ϫ d, 2J1I,1ЈI ϭ 12.3 Hz, 2 H, OCH
J3,3Ј ϭ 11.7 Hz, 1 H, 3-HH), 3.82 (dd, J3Ј,2 ϭ 5.5, J3Ј,3 ϭ 11.7 Hz, 2I), 4.51Ϫ4.43 (dd, J3,3Ј ϭ 11.7, J3,2 ϭ 3.7 Hz, 1 H, 3-HH),
1 H, 3-HЈH), 3.78 (s, 3 H, OCH3), 2.50 (t, J3I,1I ϭ 2.6 Hz, 1 H, 4.38Ϫ4.29 (dd, J3Ј,3 ϭ 11.7, J3Ј,2 ϭ 5.1 Hz, 1 H, 3-HЈH), 3.82Ϫ3.78
CϵCH), 2.30 (s, 1 H, OH) ppm. 13C NMR (50.3 MHz, HETCOR, (dd, J2,3 ϭ 3.7, J2,3Ј ϭ 5.1 Hz, 1 H, 2-HH), 3.47 (br. s, 3 H,
CDCl3): δ ϭ 171.23 (COOCH3), 79.33 (CϵCH), 78.43 (C-2H),
CquatϪOCH3), 3.20, 3.18 (2 ϫ s, ratio 1:1.67, 3 H, COOCH3) ppm.
76.44 (CϵCH), 64.02 (C-3H), 58.60 (OCH2), 52.97 (COOCH3) 1H NMR (200 MHz, CDCl3): δ ϭ 7.65Ϫ7.41 (m, 5 H, Ar H), 5.99
ppm. C7H10O4 (158.15, 158.06), ESI MS: m/z ϭ 159.0 [M ϩ H]ϩ,
278.9 [M ϩ Na]ϩ.
(s, 1 H, ϵCH), 4.87 (d, J1I,1ЈI ϭ 12.3 Hz, 1 H, 1-HI), 4.69Ϫ4.56
2
(m, 3 H, CH2H, 1-HЈI), 4.41 (m, 1 H, 2-HH), 3.68 (br. s, 3 H,
CquatϪOCH3), 3.81, 3.54 (2 ϫ s, ratio 1:1.65, 3 H, COOCH3) ppm.
13C NMR (75 MHz, C6D6): δ ϭ 199.9 (br. s, 6 ϫ CϵO), 168.9
(COOCH3), 164.6 (CquatϪCOO), 132.7, 129.8 (CAr, the other sig-
nals were hidden by the benzene signals), 124.1 (q, 1JC,F ϭ 288 Hz,
CF3), 90.8 (CϵCH), 76.5 (C-2H), 71.3 (ϵCH), 70.9 (OCH2), 65.7
(C-3H), 55.5, 55.1 (OCH3), 51.7 (COOCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 199.4 (br. s, 6 ϫ CϵO), 169.6 (COOCH3),
166.4 (CquatϪCOO), 132.1 (C-1Ar), 130.0, 129.8 (C-4Ar), 128.8,
128.6 (C-3Ar), 127.5, 127.4 (C-2Ar), 123.3 (q, 1JF,C ϭ 289 Hz, CF3),
90.0 (CϵCH), 76.5 (C-2H), 71.4 (ϵCH, OCH2), 66.0 (C-3H), 55.8,
55.6 (OCH3), 52.4 (COOCH3) ppm. 19F NMR (282 MHz, C6D6):
two CF3 signals δ ϭ 4.82, 4.53 ppm [ratio 1:1.7] (CF3COOH as
standard).
Methyl 2-O-Propargyl-glycerate Hexacarbonyldicobalt Complex
(7b, Mixture of Enantiomers): The dimethoxyltrityl group was re-
moved from 7a (300 mg, 0.402 mmol) as described for 4a. FC
(CH2Cl2/acetone, 15:1) furnished 7b (107 mg, 60%) as a dark red
oil. Rf ϭ 0.31 (CH2Cl2/acetone, 25:1). IR (film): ν˜ ϭ 1525, 1350,
1093, 1038, 804, 731 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ 6.05
(s, 1 H, ϵCH), 4.98 (d, J1,1Ј ϭ 12.8 Hz, 1 H, 1-HI), 4.64 (d, J1Ј,1 ϭ
12.8 Hz, 1 H, 1-HЈI), 4.28Ϫ4.24 (dd, J2,3 ϭ 3.7, J2,3Ј ϭ 5.1 Hz, 1
H, 2-HH), 4.05Ϫ3.96 (dt, J3,3Ј ϭ 11.7, J3,2 ϭ 3.7, J3,OH ϭ 6.2 Hz,
1 H, 3-HH), 3.93Ϫ3.84 (dt, J3Ј,3 ϭ 11.7, J3Ј,2 ϭ 5.1, J3Ј,OH ϭ 7.3 Hz,
1 H, 3-HЈH), 3.80 (s, 3 H, COOCH3), 2.27 (t, J3,OH ϭ 6.2, J3Ј,OH ϭ
7.3 Hz, 1 H, OH) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 200.0
(br. s, 6 ϫ CϵO), 172.8 (COOCH3), 91.94 (CϵCH), 81.2 (C-2H),
73.1 (ϵCH), 72.9 (OCH2), 65.7 (C-3H), 54.2 (COOCH3) ppm.
C13H10Co2O10 (444.08, 443.894), FAB MS: m/z (%) ϭ 467 (2) [7b
ϩ Na]ϩ, 416 (6) [7b Ϫ CO]ϩ·, 388 (52) [7b Ϫ 2CO]ϩ·, 360 (65) [7b
Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft, BC
Biochemie GmbH and the Fonds der Chemischen Industrie is
gratefully acknowledged.
Ϫ 3CO]ϩ·, 332 (100) [7b Ϫ 4CO]ϩ·, 325 (46), 304 (8) [7b Ϫ 5CO]ϩ·
297 (49), 276 (64) [7b Ϫ 6CO]ϩ·, 269 (18), 241 (14).
,
Methyl 2-O-Propargyl-3-O-{[(R)-3,3,3-trifluoro-2-methoxy-2-phenyl]-
propionyl}glycerate (4c)
[1]
N. El-Abadla, M. Lampilas, L. Hennig, M. Findeisen, P. Wel-
zel, D. Müller, A. Markus, J. van Heijenoort, Tetrahedron 1999,
a) Mixture of Stereoisomers Obtained by the Nicholas Route:
DMAP (0.7 mg, 6.3 µmol), triethylamine (18.2 mg, 25 µL,
0.18 mmol) and 3,3,3-trifluoro-2-methoxy-2-phenylpropionyl chlo-
ride (63 mg, 47 µL, 0.24 mmol) were added at 20 °C to a solution
of 4b (20 mg, 0.12 mmol) in dry dichloromethane (2 mL) and the
mixture was stirred at 20 °C overnight. TLC indicated complete
consumption of 4b. Solvent evaporation and FC (toluene/acetone,
25:1) furnished 4c (38.4 mg 83%) as a colourless oil. Rf ϭ 0.56
(toluene/acetone, 10:1). 19F NMR (282 MHz, C6D6): two CF3 sig-
nals, ∆δ ϭ 0.2 ppm [ratio 1:1.6].
55, 699Ϫ722, and references therein.
[2]
A. Anikin, A. Buchynskyy, U. Kempin, K. Stembera, P. Welzel,
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Chem. Lett. 2000, 20, 1963Ϫ1965.
T. Schubert, F. Kunisch, P. Welzel, Tetrahedron 1983, 39,
2211Ϫ2217.
U. Peters, W. Bankova, P. Welzel, Tetrahedron 1987, 43,
3803Ϫ3816.
U. Eichelberger, I. Neundorf, L. Hennig, M. Findeisen, S.
Giesa, D. Müller, P. Welzel, Tetrahedron 2002, 58, 545Ϫ559.
S. Vogel, K. Stembera, L. Hennig, M. Findeisen, S. Giesa, P.
Welzel, M. Lampilas, Tetrahedron 2001, 57, 4139Ϫ4146.
S. Vogel, K. Stembera, L. Hennig, M. Findeisen, S. Giesa, P.
Welzel, C. Tillier, S. Bonhomme, M. Lampilas, Tetrahedron
2001, 57, 4147Ϫ4160.
U. Eichelberger, M. Mansourova, L. Hennig, M. Findeisen, S.
[3]
[4]
b) Compound 4c Obtained by the Ohira؊Bestmann Route: A mix-
ture of 4b (10 mg, 0.06 mmol), 3,3,3-trifluoro-2-methoxy-2-phenyl-
propionyl chloride (40 µL, 0.30 mmol, 5 equiv.), triethylamine (40
µL) and a catalytic amount of 4-(dimethylamino)pyridine in
CH2Cl2 (0.5 mL) was stirred under argon for 15 h. The solvents
were evaporated. Purification by FC (petroleum ether/ethyl acetate,
[5]
[6]
[7]
1
3:1) furnished 4c (18 mg, 85%). H NMR (200 MHz, CDCl3): δ ϭ
[8]
7.68Ϫ7.63 (m, 2 H, Ar H), 7.07Ϫ6.94 (m, 3 H, Ar H), 4.42 (dd,
Giesa, D. Müller, P. Welzel, Tetrahedron 2001, 57, 9737Ϫ9742.
J
3,2 ϭ 3.3, J3,3Ј ϭ 11.4 Hz, 1 H, 3-HH), 4.08 (dd, J3Ј,2 ϭ 5.1, J3Ј,3 ϭ
[9]
M. Mansourova, Dissertation, University of Leipzig, 2002.
11.4 Hz, 1 H, 3-HЈH), 4.23Ϫ4.15 (dd, J2,3 ϭ 3.3, J2,3Ј ϭ 5.1 Hz, 1
H, 2-HH), 3.96 (t, J1,3 ϭ 2.6 Hz, 2 H, CH2I), 3.42 (q, J ϭ 1.0 Hz, 3
H, OCOCOCH3), 3.07 (s, 3 H, COOCH3), 1.86 (t, J3I,1I ϭ 2.6 Hz,
1 H, CϵCH) ppm. 19F NMR (188.3 MHz, CDCl3): δ ϭ 4.46
(CF3COOH as standard) ppm. 19F NMR (188.3 MHz, C6D6): δ ϭ
4.50 (CF3COOH as standard) ppm.
[10]
K. M. Nicholas, R. F. Lockwood, Tetrahedron Lett. 1977, 48,
4163Ϫ4166.
[11]
K. M. Nicholas, H. D. Hodes, Tetrahedron Lett. 1978, 45,
4349Ϫ4352.
K. M. Nicholas, J. E. O’Boyle, Tetrahedron Lett. 1980, 21,
1595Ϫ1598.
[12]
Eur. J. Org. Chem. 2003, 2656Ϫ2660
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2659

M. Mansourova, K. Rohr, L. Hennig, M. Findeisen, R. Oehme, S. Giesa, P. Welzel
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E. W. Colvin, B. J. Hamill, J. Chem. Soc., Perkin Trans. 1 1977,
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A. Buchynskyy, K. Stembera, L. Hennig, M. Findeisen, S.
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H. W. Sternberg, H. Greenfield, R. A. Friedel, J. Wotiz, R.
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Received January 29, 2003
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´
´
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41, 9993Ϫ9996.
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K. Rohr, Diploma thesis, University of Leipzig, 2002.
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hedron 1996, 52, 11163Ϫ11176.
J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34,
2543Ϫ2549.
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2660
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2656Ϫ2660