Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-10-16
2002-07-02
Richter, Johann (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06414165
ABSTRACT:
The present invention relates a process for making cyclopropane esters useful in the synthesis of pyrethroids which are useful as pesticides, and to intermediates useful in said process.
Esters of cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylic acid with for example 3-phenoxybenzyl alcohol, &agr;-cyano-3-phenoxybenzyl alcohol and 2-methyl-3-phenylbenzyl alcohol are important insecticidal and acaricidal products, and esters of this acid are important intermediates in the manufacture of such products. These products are all chiral and it is preferred to manufacture such products as single enantiomers or in enantiomerically enriched form.
An asymmetric synthesis of single enantiomers of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one involving a trans- to cis-isomerisation step from a hydroxyester precursor is described in
Tet. Lett.,
1983, 24, 103. The conversion of the resulting 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one to deltamethrin is also described.
The use of L-proline as a chiral auxiliary for the asymmetric synthesis of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one (I) from methyl 4,5-epoxy-3,3-dimethylpentanoate to give a mixture of cis- and trans-cyclopropyl isomers is described in
Heterocycles,
1985, 23, 2859. This methodology does not enable the geometry of the cyclopropyl ring to be controlled. This reference also describes rearrangement of epoxyester (IIIa) to lactone (I) and trans-hydroxyester (VIa) but, under the reaction conditions, (VIa) cannot be rearranged to form (I), viz:
Thus, it is desirable to prepare cis-pyrethroid acids (see, for example, pyrethroid acids of formula (V) in Scheme 1) using a process under which any trans-isomer formed will be rearranged to the cis-form.
The present invention provides a process for the preparation of cis-6,6-dimethyl-3-oxa-bicyclo[3.1.0]hexan-2-one which comprises either:
a) reacting a sulphonic ester of &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone with a compound of formula M(C
1-6
alkoxide)
y
, in a suitable solvent; or
b) reacting a C
1-4
alkyl ester of 4,5-epoxy-3,3-dimethylpentanoic acid with M(C
1-6
alkoxide)
y
, in a suitable solvent;
wherein M is a suitable cation and y fulfills valency requirements.
It is preferred that the C
1-6
alkoxide is an alkoxide that can function both as a base and a nucleophile, such as tert-butoxide.
It is preferred that M is an alkali metal salt (especially sodium or potassium), an alkaline earth metal (especially calcium or magnesium) or an organic cation (especially a quaternary ammonium such as NH
4
or N(CH
3
)
4
). It is especially preferred that M is sodium or potassium.
Alkyl esters of 4,5-epoxy-3,3-dimethylpentanoic acid are preferably the methyl or ethyl esters of that acid.
Sulphonic esters of &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone include C
1-4
alkylsulphonyl and phenylsulphonyl (wherein phenyl is optionally substituted with C
1-4
alkyl) esters, such as the mesyl and tosyl esters.
In one aspect the present invention provides a process for the preparation of cis-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one which comprises either:
a) forming a sulphonic ester of &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone; and,
b) reacting the sulphonic ester with a compound of formula M(C
1-6
alkoxide)
y
, in a suitable solvent; or
reacting a C
1-4
alkyl ester of 4,5-epoxy-3,3-dimethylpentanoic acid with M(C
1-4
alkoxide)
y
, in a suitable solvent;
wherein M is a suitable cation and y fulfills valency requirements.
Sulphonic esters of &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone can be formed, for example, by adaptation of literature methods or by reacting an appropriate hydroxymethyl lactone with a suitable sulphonyl chloride in the presence of a suitable base or mixture of bases (such as a tri(C
1-4
alkyl)amine or a di(C
1-4
alkyl)aminopyridine) in a suitable solvent.
In yet another aspect the present invention provides a sulphonic ester of &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone.
One of the advantages of the present invention is that any entiomeric excess present in &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone is preserved and, thus, the process of the present invention also allows the preparation of enantiomerically enriched cis-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one which, in turn, can be used to prepare enantiomerically enriched pyrethroid acids.
Thus, in another aspect the present invention provides a process for the preparation of enantiomerically enriched cis-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one which comprises:
a) forming enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone;
b) forming a sulphonic ester of the enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone; and,
c) reacting the sulphonic ester with a compound of formula M(C
1-6
alkoxide)
y
, in a suitable solvent;
wherein M is a suitable cation and y fulfills valency requirements.
In a further aspect the present invention provides a process for the preparation of enantiomerically enriched cis-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one which comprises:
a) performing a Sharpless asymmetric dihydroxylation on a C
1-4
alkyl ester of 3,3-dimethyl-4-pentenoate to form enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone;
b) forming a sulphonic ester of the enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone; and,
c) reacting the sulphonic ester with a compound of formula M(C
1-6
alkoxide)
y
, in a suitable solvent;
wherein M is a suitable cation and y fulfills valency requirements.
6,6-Dimethyl-3-oxabicyclo[3.1.0]hexan-2-one produced according to the present invention is preferably enantiomerically enriched and has an enantiomeric excess greater than 90%, preferably greater than 98%.
The term “enantiomeric excess” is defined as:
(% major enantiomer)−(% minor enantiomer)
(% major enantiomer)+(% minor enantiomer)
Enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone can be prepared by Sharpless asymninetric dihydroxylation of a C
1-4
alkyl ester of 3,3-dimethyl-4-pentenoate (see, for example, H C Kolb, M S Vannieuwenhze & K B Sharpless,
Chemical Reviews,
(1994) 94(8) 2483-2547, or H Becker & K B Sharpless,
Angew. Chem. Int. Ed. Eng.
(1996) 35 448-451); or by bioresolution (see, for example S M Robert, K Wiggins & G Casy (eds.) “Preparative Biotransfornations—Whole cells and isolated enzymes in organic synthesis” John Wiley & Sons, (1993)).
In a further aspect the present invention provides a process for the preparation of a compound of formula (VI):
in enantiomerically enriched form, wherein X and Y are, independently, halogen, C
1-3
alkyl or C
1-3
haloalkyl, which comprises:
a) forming enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone (such as by Sharpless asymmetric dihydroxylation or bioresolution);
b) forming a sulphonic ester of the enantiomerically enriched &bgr;,&bgr;-dimethyl-&ggr;-(hydroxymethyl)-&ggr;-butyrolactone;
c) reacting the sulphonic ester with a compound of formula M(C
1-4
alkoxide)
y
, in a suitable solvent to form enantiomerically enriched 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one;
d) reducing the enantiomerically enriched 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one under suitable conditions (such as using DIBAL in the presence of a solvent at low temperature) to provide a compound of formula (VII) in enantiomerically enriched form; and,
e) ring opening said compound of formula (VII) (such as by adaptation of methodologies described in S Takano, M Tanaka, K Seo, M Hirama & K Ogasawara,
J. Org. Chem.
(1985) 50 931-936 or J Tessier
Chem Ind
(1984) 199 which describe the conversion of a lactol to a dimethylvinyl cyclopropane derivative);
wherein M is a suitable cation and y fulfills vale
Greeves Nicholas
Guy Jonathan
Levin Daniel
Hale and Dorr LLP
Richter Johann
Sackey Ebenezer
Syngenta Limited
LandOfFree
Preparation of cis-6,... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preparation of cis-6,..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preparation of cis-6,... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2918120