Enantioselective synthesis of 1(R)-trans-Chrysanthemic acid

Article abstract of DOI:10.1016/S0040-4039(02)01918-4

1(R)-trans-Chrysanthemic acid has been prepared in four steps from methyl 5-methyl-2,4-hexadienoate and isopropylidene diphenylsulfurane.

Full text of DOI:10.1016/S0040-4039(02)01918-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7881–7882
Enantioselective synthesis of 1(R)-trans-chrysanthemic acid
Alain Krief,a,* Laurent Provinsa,† and Alexandre Froidbisea,b
aLaboratoire de Chimie Organique de Synthe`se, 61 rue de Bruxelles, Namur B-5000, Belgium
bFond pour la Recherche Scientifuque dans l’Industrie et l’Agriculture (F.R.I.A.), 5 rue d’Egmont, Bruxelles B-1000, Belgium
Received 10 February 2002; revised 28 February 2002; accepted 6 September 2002
Abstract—1(R)-trans-Chrysanthemic acid has been prepared in four steps from methyl 5-methyl-2,4-hexadienoate and isopropyl-
idene diphenylsulfurane. © 2002 Elsevier Science Ltd. All rights reserved.
We report a short and efficient enantioselective synthe-
sis of methyl 1(R)-trans-chrysanthemate (d)-1, whose
corresponding acid is the constituent of one of the most
active natural pyrethroid insecticides.1 This has been
achieved in four steps from methyl 5-methyl-2,4-hexa-
dienoate 22 and isopropylidene diphenylsulfurane 33
which provide the complete carbon skeleton (7+3)
present on methyl chrysanthemate (Scheme 1).
(e.e. 94%) which has been then transformed to the
corresponding thionocarbonate 5r on reaction with
thiophosgene (DMAP, 0°C, 2 h, 95%).6
Cyclopropanation went smoothly from 5r and isopro-
pylidene diphenyl sulfurane [prepared from isopropyl-
diphenyl sulfonium tetrafluoroborate and LDA (1.2
equiv.), DME, −78°C, 0.5 h in the presence of
dichloromethane (DCM, 1.2 equiv.)] and affords the
functionalized cyclopropyl ester 6r in good yield and
with almost complete asymmetric induction (68% yield
d.e.>98%).
Interestingly our approach uses the same starting mate-
rials and the same key step (cyclopropanation of an
a,b-unsaturated ester) as originally described by Corey
for the synthesis of the racemate (Scheme 2)3 and can
therefore be viewed as one of its asymmetric versions.
The proposed transformation takes into account (i) the
high propensity of AD-mix b to perform the enantiose-
lective dihydroxylation of C,C double bond using cata-
lytic amounts of its chiral ligand,4 (ii) the high
asymmetric induction which is usually associated to the
cyclopropanation of chiral g-alkoxy-a,b-unsaturated
esters by sulfur ylides,1,5 and (iii) the proper choice of
the thiono carbonate which plays the role of ‘the diol
protecting group’ in the cyclopropanation step and
delivers the trisubstituted C,C double bond present on
methyl chrysanthemate 1 on further reductive elimina-
tion reaction.6
Scheme 1. Synthesis of 1(R)-trans-chrysanthemic acid using
isopropylidene diphenyl sulfurane. (i) (a) AD-mix b, t-BuOH/
H2O (1/1); (b) MeSO2NH2, 20°C, 20 h; (ii) Cl2CꢀS, DMAP,
CH2Cl2, 0°C, 2 h; (iii) Me2CꢀSPh2 3, LiBF4, DME, −78°C, 2
h, −78°C to 20°C, 1 h; (iv) (CH2NMe)2P-Ph, neat, 40°C, 6 h.
The reaction between methyl 5-methyl-2,4-hexadienoate
2 and AD-mix b4 leads to a 8/2 mixture of regioiso-
meric diols in 88% overall yield. Purification affords
2,3-dihydroxy-5-methyl-2-hexenoate 4r in 51% yield
* Corresponding author. Tel.: +32 81 724539; fax: +32 81 724536;
e-mail: alain.krief@fundp.ac.be
† Present address: UCB-Pharma, Chemical Research, R4; Chemin du
Foriest, Braine-L’Alleud B-1420, Belgium.
Scheme 2. Synthesis of (R,S)-trans-chrysanthemic acid as
originally described by E.J. Corey.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01918-4

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A. Krief et al. / Tetrahedron Letters 43 (2002) 7881–7882
Scheme 3. Proposed alternative route to 1(R)-trans-chrysanthemic acid using isopropylidene triphenyl phosphorane. (i) AD-mix
a; (ii) (a) Cl2CꢀO; (b) acetone, H+; (iii) Me2CꢀPPh3; (iv) H3O+; (v) (CH2NMe)2PPh.
Removal of the thiocarbonate moiety has been
achieved under mild conditions using trisaminophos-
phine (3 equiv., neat, 40°C, 6 h)6a to produce methy1
1(R)-trans-chrysanthemate 1 (89% yield, e.e. 95%, com-
pared to an authentic sample).5a,7
quite lengthy route (seven instead of four steps) which
will produce 1 with poor enantioselection (e.e. <56%=
75×75) and will offer no advantages over the route
reported in Scheme 1. We have not pursued our work
towards these lines.
The synthesis reported here could appear as trivial since
each of the individual steps was previously known. We
will now show that successful synthesis of 1 requires
adequate synthetic planning and proper choice of
reagents.
References
1. (a) Krief, A. Synthesis of optically active pyrethroids—
strategy and practice: synthesis of non-racemic cyclo-
propane carboxylic acids. In Stereocontrolled Organic
Synthesis. A Chemistry for the 21st Century Monograph;
International Union of Pure and Applied Chemistry,
Trost, B. M., Ed.; Blackwell Scientific Publications, 1994,
pp. 337–397; (b) Krief, A. Pestic. Sci. 1994, 41, 237.
2. (a) Chiusoli, G. P. Angew. Chem., Int. Ed. 1967, 6, 124; (b)
Devos, M.-J.; Hevesi, L.; Bayet, P.; Krief, A. Tetrahedron
Lett. 1976, 3911.
3. Corey, E. J.; Jautelat, M. J. Am. Chem. Soc. 1967, 89,
3912.
4. Kolb, H. C.; Vannieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483.
5. (a) Krief, A.; Dumont, W.; Pasau, P.; Lecomte, Ph. Tetra-
hedron 1989, 45, 3039; (b) Krief, A.; Lecomte, P.;
Demoute, J. P.; Dumont, W. Synthesis 1990, 275; (c)
Krief, A.; Surleraux, D.; Dumont, W.; Pasau, P.; Lecomte,
Ph. Pure Appl. Chem. 1990, 62, 1311; (d) Krief, A.;
Lecomte, P. Tetrahedron Lett. 1993, 34, 2695.
6. (a) Corey, E. J.; Hopkins, P. B. Tetrahedron Lett. 1982, 23,
1979; (b) Provins, L. Dissertation doctorale, 1998,
FUNDP, Namur.
What would have happened if we had made a different
choice? Let us look at a different scenario which would
have taken place if isopropylidene triphenyl phospho-
rane would have been used in place of its sulfur
analogue.1,5
AD-mix a is now required since phosphoranes and
sulfuranes are known to react by the opposite face with
g-alkoxy-E-a,b-unsaturated esters.1,5 Stereocontrol is
much poorer at both the dihydroxylation stage4 (e.e.
76% instead of 94% with AD-mix b) and at the cyclo-
propanation reaction5,8 (d.e. 75% instead of 98% with
AD-mix b, compare Scheme 3 to Scheme 1). Moreover
isopropylidene triphenyl phosphorane leads, on reac-
tion with the unsaturated the thionocarbonate 5% (1.2
equiv., THF, 0°C to 20°C), to an intractable mixture of
compounds in which the cyclopropyl ester 6% is missing.
The synthesis of methyl 1(R)-trans-chrysanthemate 1
could have been nevertheless achieved from the diol 4s
using the dioxolane protecting group as already
described for a related case1,5,7 (5s, Scheme 3). This is a
7. [h]D +20 (20°C, c 0.985, CHCl3).
8. Mulzer, J. Angew. Chem., Int. Ed. 1983, 22, 63.