An expeditious enantioselective synthesis of methyl trans-chrysanthemate

Article abstract of DOI:10.1055/s-2002-34388

Methyl trans-chrysanthemate has been prepared in few steps from isopropylidenediphenylsulfurane and methyl (E)-3-(3,3-dimethyloxiran-2-yl)prop-2-enoate. The latter was obtained from methyl 4-oxobutenoate or 3-methylbut-2-en-1-ol. The Sharpless catalytic epoxidation reaction allows an asymmetric version of this transformation.

Full text of DOI:10.1055/s-2002-34388

PAPER
2019
An Expeditious Enantioselective Synthesis of Methyl trans-Chrysanthemate
a
a
b
E
A
nantioselective
S
l
ynthesi
a
s
of Methy
i
l
trans
-
n
Chrysanthemate Krief,* Willy Dumont, Diane Baillieul
a
Laboratoire de Chimie Organique de Synthèse, Département de Chimie, Facultés Universitaires Notre-Dame de la Paix, 61 rue de
Bruxelles, 5000 Namur, Belgium
Fax +32(81)724539; E-mail: alain.krief@fundp.ac.be
b
Fonds pour la Recherche Scientifique dans l’Industrie et l’Agriculture (F.R.I.A.), 5 rue d’Egmont, Bruxelles, 1000, Belgium
Received 21 June 2002
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday with extremely great appreciation for his invaluable
contribution to organic synthesis.
the following advantages: it reaches the (1R)-trans 4 , the
Abstract: Methyl trans-chrysanthemate has been prepared in few
most ‘active’ enantiomer, by taking advantage of the pres-
steps from isopropylidenediphenylsulfurane and methyl (E)-3-(3,3-
ence on 5 of a chiral center close to the site of attack of the
methyl 4-oxobutenoate or 3-methylbut-2-en-1-ol. The Sharpless incoming ylide; and it allows the choice of cyclopropana-
dimethyloxiran-2-yl)prop-2-enoate. The latter was obtained from
catalytic epoxidation reaction allows an asymmetric version of this ting agents such as isopropylidenediphenylsulfurane (2b).
transformation.
Particularly good results have been obtained from , -un-
Key words: sulfur ylides, cyclopropanation, asymmetric induction,
Sharpless epoxidation
3
saturated esters bearing an acetal 5a, a hemi-aminal
3,4f,h
3,4a–e,4g–i
5
5
b,
a protected diol 5c
or a thionocarbonate
5
d in a suitable position (Figure 1).
Good to extremely good asymmetric induction was
achieved using isopropylidenetriphenylphosphorane (2a)
or better, isopropylidenediphenylsulfurane (2b), but it
was found that whereas the former reagent mainly attacks
Several years ago we reported that methyl chrysanthemate
can be synthesized in a single pot from 4-oxobutenoate (1)
and isopropylidenetriphenylphosphorane (2a) (2 equiv,
Scheme 1). It was later established that the reaction
takes place first on the aldehyde carbonyl group (already
at –78 °C) of 1 and that the cyclopropanation occurs
1
a
(
E)-5c from the Si-face (de 72 %), the second one enters
almost exclusively from the Re-face (de >98 %)
Scheme 3).4
(
(
3
around –30 °C) prior to any decomposition of the betaine
.
2
We now disclose two related sequences, which allow an
efficient enantioselective catalytic version of these trans-
formations.
We also described that ‘protection’ of the aldehyde group
as a ‘functionalized ether’ 5 allows inversion of the order
of construction of the carbon-carbon double bond and of Synthesis of Methyl (dl)-trans-Chrysanthemate
the cyclopropane ring (Scheme 2).1,3–5
Following the work described in Scheme 1, we found that
The second approach is less expeditious than the first be- reaction of methyl 4-oxobutenoate (1) and isopropy-
cause it requires a second deprotection step, but it offers lidenediphenylsulfurane (2b) (2 equiv, DME, –78 °C, 2 h
Scheme 1
Scheme 2
Synthesis 2002, No. 14, Print: 07 10 2002.
Art Id.1437-210X,E;2002,0,14,2019,2022,ftx,en;C03502SS.pdf.
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ISSN 0039-7881

2
020
A. Krief et al.
PAPER
Figure 1 The structures of protected substrates 5a–d
Scheme 3
then 20 °C, 1 h) leads to the racemic methyl epoxychrys- Interestingly, a different diastereoisomer (dl)-6e , result-
anthemate (dl)-6e in good yield (70 %) and reasonably ing from the attack of (dl)-5e from the other face, is ob-
good stereocontrol at the three stereogenic centers (de 80 tained in modest yield if the reaction is performed instead
%
) (Scheme 4).
with isopropylidenetriphenylphosphorane (2a) (THF, 0
C, 1 h, then 20 °C, 1 h, 28 % yield; 6e /6e = 9:91, de
°
The same process can be carried out stepwise providing
first methyl (E)-3-(3,3-dimethyloxiran-2-yl)prop-2-
enoate [(dl)-(E)-5e] by reaction of the first equivalent of
ylide 2b with 1 (DME, –78 °C, 2 h, then 20 °C, 1 h, 73%
yield) followed by subsequent reaction of a second equiv-
alent of the same ylide (DME, –78 °C, 2 h, then 20 °C, 1
h) with (dl)-5e to give (dl)-6e in 88 % yield (de 94 %,
Scheme 5, entry a).
4
8
2%, Scheme 5, entry b). Therefore (dl)-5e behaves as
the other members of the -alkoxy- , -unsaturated esters
family 5c,d since all these compounds provide cyclopro-
pyl esters 6 in which the relative stereochemistry is simi-
lar within the same family of reagents but different
3
–5
between the two families (2a and 2b, Scheme 3).
We have unambiguously confirmed the trans-relationship
1
of (dl)-6e and (dl)-6e by comparing their H NMR data
The higher relative stereocontrol systematically obtained
in the stepwise reaction suggests that the cyclopropana-
tion might take place, at least in part, on the betaine pre-
cursor of (dl)-(E)-5e.
to those of 6e obtained as a stereoisomeric mixture (dl)-
6
e /(dl)-6e = 54:46) by epoxidation of methyl (dl)-trans-
chrysanthemate [(dl)-trans-4] with m-CPBA (1.5 equiv,
CH Cl , 20 °C, 1 h, 87 % yield).
2
2
Scheme 4
Scheme 5
Synthesis 2002, No. 14, 2019–2022 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Enantioselective Synthesis of Methyl trans-Chrysanthemate
2021
Scheme 6
Finally, reduction of (dl)-6e to methyl (dl)-trans-chrysan- Almost complete stereocontrol of methyl (E)-3-[(2R)-3-3-0
themate [(dl)-trans-4] has been effectively achieved by re- dimethyloxiran-2-yl]prop-2-enoate {5e*; ee >98%, [ ]D2
action with P I (1.2 equiv, CS , pyridine, reflux, 5 h, 72 –30.64 (c = 1.155, CHCl )}, methyl epoxychrysanthemate
2
4
2
3
6
20
%
, de 100 %, Scheme 6). It is interesting to note that {6e*; ee 98%; [ ]D +16.02 (c = 0.945, CHCl )} and me-
SmI which is usually able to reduce epoxides to olefins,
3
7
20
thyl trans-chrysanthemate {(1R)-trans-4*; ee 98%; [ ]D
2
,
does not provide even a trace of the desired product but in- +20.28 (c = 1.140, CHCl )} was nevertheless achieved by
3
stead the allyl alcohol 7 resulting from reductive cyclo- a single crystallization from diethyl ether of the nitroben-
propane ring opening (Scheme 6).8
zoate of 9e* from which the enantiopure (S)-(3,3-dim-
ethyloxiran-2-yl)methanol (9e*) was obtained by biphasic
ester hydrolysis using a phase transfer catalyst (4.1 equiv
of an aq 9.6 N KOH solution, 0.2 equiv benzyltributylam-
monium chloride, CH Cl , 20 °C, 12 h).
9b,c
Enantioselective Synthesis of Methyl (1R)-trans-Chrysan-
themate [(1R)-4*]
An enantioselective version of this reaction was achieved
from the trans- , -epoxy- , -unsaturated ester (E)-5e*
prepared, using the Sharpless asymmetric epoxidation re-
2
2
1
Spectroscopic data (IR, H NMR) of methyl (1R)-trans-
chrysanthemate [(1R)-trans-4*] obtained in this work are
identical to those of an authentic sample.4d
9
action, from 3-methylbut-2-en-1-ol (8) and (l)-diisopro-
pyl tartrate to produce first the required (S)-(3,3-
dimethyloxiran-2-yl)methanol (9*) (Scheme 7).
Work is now in progress to adapt the reported strategy to
the synthesis of deltamethrin.
The most straightforward synthesis of (E)-5e* entails the
direct ‘Parikh–von Doering oxidation’ of the crude mix-
ture obtained from the Sharpless epoxidation reaction (1.2
1
0
equiv pyridine SO , Et N, DMSO, 20 °C, 3 h) leading to Methyl (E)-3-[(2R)-3,3-dimethyloxiran-2-yl]prop-2-enoate
3
3
(5e*)
the crude aldehyde 10* which is in turn subjected, without
purification, to the Wittig olefination reaction using
methoxycarbonyltriphenylphosphorane in DMSO (1
Method 1: Crushed, activated 3 Å molecular sieves (1.5 g) were in-
troduced into a flame-dried flask filled with argon. CH Cl (100
mL) was added and the flask was cooled to –20 °C. D-(–)-Diisopro-
pyl tartrate (702 mg, 3.0 mmol), 3-methylbut-2-en-1-ol (8; 4.3 g,
-
2
2
4
d,11
equiv, DMSO, 20 °C, 4 h, 59%).
A single chromato-
graphic purification (silica gel, pentane–Et O, 80:20 v/v)
2
50.0 mmol, stored over molecular sieves), and Ti(i-PrO) (710 mg,
4
allows, separation of the small amount (4%) of the Z-ste- 2,5 mmol) were added sequentially. The stirring was maintained for
reoisomer (Z)-5e* concomitantly produced. The enantio- 0.5 h at –20 °C, whereupon a 3.7 M solution of tert-butyl hydroper-
oxide (TBHP) in toluene (27 mL, 100 mmol) was added via a sy-
ringe and the stirring was continued for a further 3 h at the same
temperature. Careful quenching of the excess TBHP was accom-
plished by the slow addition of dimethyl sulfide (12.4 g, 200 mmol),
meric excess recorded for methyl epoxy-trans-
chrysanthemate [(1R)-trans-6e*] resulting from the reac-
tion of isopropyldiphenylsulfonium tetrafluoroborate was
rather moderate (74 %) due to the modest enantiomeric
taking care that the temperature did not rise above –20 °C. After
stirring at –20 °C, for 0.7 h, CH Cl was evaporated under vacuum
9
excess with which 9* is obtained (75%).
2
2
Scheme 7 (i) TBHP, Ti(OPr-i) , (l)-DIPT, CH Cl , –20 °C, 3 h, Me S; (ii) Pyridine SO , Et N, DMSO, 20 °C, 3 h; (iii) Ph P=CHCO Me,
4
2
2
2
3
3
3
2
2
0 °C, 4h; (iv) Me C=SPh , LiBF , DME, –78 °C, 2 h then 20 °C, 1 h; (v) P I , CS , pyridine, 5 h, reflux
2
2
4
2
4
2
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022
A. Krief et al.
PAPER
(
15 mbar, under 20 °C). The resulting mixture, still containing some
chromatography on silica gel (pentane–Et O, 85:15 v/v, R 0.49) to
2
f
CH Cl , was dissolved in DMSO (60 mL) and Et N (55 mL) and
yield 266 mg (89 %) of 6e*.
2
2
3
subjected to the ‘Parikh–von Doering oxidation’ reaction using a
IR (film): 2991, 2957, 2931, 1730, 1441, 1403, 1381, 1341, 1287,
solution of pyridine SO complex (9.54 g, 60 mmol) in DMSO (70
–1
3
1
225, 1174, 1118, 1061, 1027, 997 cm .
mL) which was slowly added (3 h) at 20 °C temperature. Olefina-
tion reaction of the crude aldehyde was carried out with -methox-
1
H NMR (400 MHz, CDCl ): = 1.26–1.37 (m, 13 H, 4 CH , 3 s at
3
3
1
1
1.37, 1.33 and 1.26 with 3 H each and 1 H, m, CHCHCO Me), 1.54
ycarbonyltriphenylphosphorane (16.7 g, 50 mmol) at r.t. After
2
(
d, J = 5.2 Hz, 1 H, CHCO Me), 2.51 (d, J = 8.4 Hz, 1 H,
2
stirring the resulting mixture for 4 h at r.t., H O (20 mL) was added
2
Me COCH), 3.70 (s, 3 H, CO CH ).
and the mixture was extracted twice with Et O, washed with H O
2
2
3
2
2
and dried (Na SO ). The solvent was removed under reduced pres-
2
4
Methyl trans-Chrysanthemate [(1R)-trans-4*]
A solution of 6e* (297 mg, 1.5 mmol) and pyridine (1.5 mL) in CS2
sure and the crude material was purified by column chromatography
on silica gel (pentane–Et O, 80:20 v/v, R 0.38) to yield 4.27 g
2
f
(
3 mL) was added at 20 °C to a solution of P I (1.026 g, 1.8 mmol)
(
55%) of (E)-5e*.
2 4
in CS (5 mL). The resulting dark brown solution was refluxed for
2
Method 2: Alternatively oxidation of 8 was performed similarly, but
5
h, hydrolysed with H O (5 mL) and extracted with Et O. The or-
2
2
with TBHP in CH Cl (15 mL of a 6.8 M solution, 100 mmol). The
2
2
ganic extracts were washed with aq sat. solution of Na S O prior to
the usual workup. Purification by column chromatography on silica
2
2
3
reaction mixture was stirred at –20 °C for 2.5 h, then the excess of
TBHP was reduced by trimethyl phosphite (19 mL, 75.0 mmol) in
gel (pentane–Et O, 90:10 v/v, R 0.78) afforded the methyl trans-
2
f
0
.75 h taking care that the temperature did not rise above –20 °C.
1
chrysanthemate [(1R)-trans-4*] in 72 % yield. Its IR and HNMR
spectrum were identical to those of an authentic sample.
The synthesis of the related nitrobenzoate was achieved by adding
4d
Et N (8.5 mL, 60 mmol) followed by a solution of p-nitrobenzoyl
3
chloride (9.3 g, 50 mmol) in CH Cl (15 ml). This mixture was
2
2
stirred at 0 °C for 1 h, filtered through a pad of Celite, and the filtrate
was washed with 10% aq tartaric acid (2 15 mL), aq sat. NaHCO3
References
(
1) (a) Krief, A.; Bayet, P.; Hevesi, L.; Devos, M.-J.
Tetrahedron Lett. 1976, 3911. (b) Krief, A.; Hevesi, L.;
Sevrin, M. Tetrahedron Lett. 1976, 3918.
(
3
15 mL), and brine (2 15 mL). The organic phase was dried
(
Na SO ), filtered and concentrated. The solid was recrystallized
2
4
twice from Et O to give [(2R)-3,3-dimethyloxiran-2-yl] 4-nitroben-
2
(
(
(
2) (a) Krief, A.; Devos, M.-J. Tetrahedron Lett. 1979, 1511.
zoate, as fine pale yellow needles (3.62 g; 31%; ee >98%; 3.12 g;
(
b) Krief, A.; Devos, M.-J. Tetrahedron Lett. 1979, 1518.
2
9
6%; ee >90%). An aq solution of NaOH (2.69 g in 5 mL of H O,
.6 N, 48 mmol) containing benzyltributylammonium chloride (700
2
3) Krief, A.; Lecomte, P.; Demoute, J. P.; Dumont, W.
Synthesis 1990, 275.
4) (a) Mulzer, J.; Kappert, M. Angew. Chem., Int. Ed. Engl.
mg, 2.4 mmol) was added dropwise at 20 °C to the [(2R)-3,3-dime-
thyloxiran-2-yl] 4-nitrobenzoate (2.89 g, ee >98%, 11.5 mmol) dis-
solved in CH Cl (30 mL). After stirring for 12 h at 20 °C, the
1983, 22, 63. (b) Krief, A.; Dumont, W.; Pasau, P.
2
2
Tetrahedron Lett. 1988, 29, 1079. (c) Krief, A.; Dumont,
W. Tetrahedron Lett. 1988, 29, 1083. (d) Krief, A.;
Dumont, W.; Pasau, P.; Lecomte, P. Tetrahedron 1989, 45,
mixture was extracted with Et O and dried (Na SO ). CH Cl was
evaporated at 20 °C under 15 mbar and the resulting mixture was di-
2
2
4
2
2
luted with DMSO (15 mL) containing Et N (13 mL) and reacted
3
3039. (e) Krief, A.; Surleraux, D.; Dumont, W.; Pasau, P.;
with pyridine SO complex (2.2 g, 13.8 mmol) dissolved in the
3
Lecomte, P. In Strain and Its Application in Organic
Chemistry; de Meijere, A.; Blechert, S., Eds.; Kluwer
Academic Publishers: Dordrecht, 1989, 333. (f) Bernardi,
A.; Scolastico, C.; Villa, R. Tetrahedron Lett. 1989, 30,
same solvent (15 mL). The mixture was stirred at r.t. for 2 h and
subjected to the olefination reaction using the -methoxycarbonyl-
triphenylphosphorane (3.84 g, 11.5 mmol) at 20 °C. After stirring
1
1
at this temperature for 4 h, the mixture was hydrolyzed with H O
2
3733. (g) Krief, A.; Surleraux, D.; Dumont, W.; Pasau, P.;
(
10 mL) and extracted with Et O, washed with H O and dried
2
2
Lecomte, P. Pure Appl. Chem. 1990, 62, 1311. (h)Leonard,
J. Contemp. Org. Synth. 1994, 1, 387. (i) Leonard, J.;
Mohialdin, S.; Reed, D.; Ryan, G.; Swain, P. A. Tetrahedron
(
Na SO ). The solvents were removed under reduced pressure. The
2
4
crude material was purified by column chromatography on silica gel
pentane–Et O, 80:20, R 0.38) to yield 0.933 g (52 %) of (E)-5e*.
(
2
f
1995, 51, 12843.
IR (film): 2999, 2958, 2926, 1725, 1658, 1438, 1381, 1320, 1296,
(
5) Krief, A.; Provins, L.; Froidbise, A. Tetrahedron Lett. 2002,
–
1
1
265, 1194, 1173, 1115, 1042, 981 cm .
in press.
1H NMR (400 MHz, CDCl3): = 1.30 and 1.42 (2 s, 6 H, 2 CH3),
(6) (a) Krief, A.; Denis, J.-N.; Magnane, R.; van Eenoo, M.
Nouv. J. Chim. 1979, 3, 705. (b) Suzuki, H.; Fuchita, T.;
Iwasa, A.; Mishina, T. Synthesis 1978, 905.
3
6
.34 (dd, J = 6.4, 1.2 Hz, 1 H, Me COCH), 3.76 (s, 3 H, CO CH ),
2 2 3
.12 (dd, J = 15.6, 1.2 Hz, 1 H, CHCO Me), 6.85 (dd, J = 6.4, 15.6
2
Hz, HC=CHCO Me).
(7) (a) Molander, G. A. Org. React. 1995, 46, 211. (b) Girard,
P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102,
2693.
(8) Work is in progress to understand the scope and limitation of
this reaction.
2
Methyl trans-3-(3,3-Dimethyloxiran-2-yl)-2,2,dimethylcyclo-
propane Carboxylate (Methyl trans-Epoxychrysanthemate,
6
e*)
A solution of LDA (0.58 N, 3.1 mL) was added dropwise, under ar-
gon and at –78 °C, to a well stirred solution of isopropyldiphenyl-
sulfonium tetrafluoroborate (569 mg, 1.8 mmol) ) in anhyd DME
(9) (a) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
109, 5765. (b) Ko, S. Y.; Masamune, H.; Sharpless, K. B. J.
Org. Chem. 1987, 52, 667. (c) Uchiro, H.; Nagasawa, K.;
Aiba, Y.; Kotake, T.; Hasegawa, D.; Kobayashi, S.
Tetrahedron Lett. 2001, 42, 4531.
(10) (a) Parikh, J. R.; von Doering, W. E. J. Am. Chem. Soc. 1967,
89, 5505. (b) Mancuso, A. J.; Swern, D. Synthesis 1981, 165.
(11) House, H. O.; Jones, V. K.; Frank, G. A. J. Org. Chem. 1964,
29, 3327.
(
10 mL) containing freshly distilled CH Cl (0.12 mL, 1.8 mmol ).
2 2
The resulting yellow solution was then stirred for an additional 0.3
h at –78 °C. A solution of 5e* (234 mg, 1.5 mmol) in DME (1 mL)
was added dropwise to the above mixture. After stirring for 2 h at
–
78 °C and 1 h at 20 °C, the mixture was hydrolyzed by the addition
of aq sat. NH Cl solution, and extracted with Et O. The Et O extract
4
2
2
was washed with brine, dried (Na SO ),and the Et O was removed
2
4
2
under reduced pressure. The crude material was purified by column
Synthesis 2002, No. 14, 2019–2022 ISSN 0039-7881 © Thieme Stuttgart · New York