Synthesis of Synthetic Pyrethroids - ACS Symposium Series (ACS

Chapter 17 Synthesis of Synthetic Pyrethroids Stereoselection in the Synthesis of Cyclopropane Carboxylates William A. Kleschik

Downloaded by UNIV LAVAL on May 9, 2016 | http://pubs.acs.org Publication Date: November 3, 1987 | doi: 10.1021/bk-1987-0355.ch017

Agricultural Products Department, Dow Chemical Company, Walnut Creek, CA 94598

A discussion of approaches to the stereoselective synthesis of3-(dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid through intramolecular alkylation of an enolate ion is presented. Principles for achieving good control of the relative stereochemistry about the cyclopropane ring will be described. The control of the absolute stereochemistry on the ring was accomplished through the use of a chiral enolate. The synthetic pyrethroids represent an important class of compounds for insect control i n modern agriculture (1). These materials ewe their success to their high insecticidal activity combined with their lew mammalian toxicity. Some examples of these compounds include permethrin (2), cypermethrin (2), DOWOO 417 (3) and deltamethrin (2) shewn i n Figure 1. A key structural element of these materials i s the 3- (dihalovinyl) -2,2-dimetftylcycloprOpanecarboxylic acid. The relative and absolute stereochemistry about the cyclopropane ring influences both the level and spectrum of insecticidal activity exhibited by these compounds (1,2). In general the c i s diastereamers are more active than the trans, and the component of the racemate of R-configuration at the carboxyl stereccenter i s the more active. Consequently, methods for the stereoselective synthesis of these cyclopropanecarboxylic acids are highly desirable. We chose 1R, 3R-3- (dichlorovinyl) -2,2-dimethylcycloprOpanecarboxylic acid as cur i n i t i a l synthetic target. A number of imaginative approaches to the synthesis of pyrethroid cyclopropanecarboxylic acids have been reported (4). Conceptually, one of the simplest approaches to these materials involves an intramolecular alkylation of an enolate anion to form the cyclopropane ring as illustrated i n Figure 2. The starting materials for such approaches are readily available through methodology based on [3,3] sigmatropic rearrangements followed by free radical initiated addition of polyhaloalkanes to olefins. We chose to reexamine this route from the standpoint of stereocontrol. 0097-6156/87/0355-0189$06.00/0 © 1987 American Chemical Society

Baker et al.; Synthesis and Chemistry of Agrochemicals ACS Symposium Series; American Chemical Society: Washington, DC, 1987.


190

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

Sane measures of stereocontrol had previously been observed in approaches to pyrethroid acids involving intramolecular enolate alkylation. As outlined in Figure 3, workers at Sumitomo have investigated the cyclization of a methyl ketone enolate (5). They obtained a 9:1 ratio of cis:trans products upon ring closure initiated by sodium hydroxide. The methyl ketone was subsequently converted to the corresponding carboxylic acid via the haloform reaction. An additional example (Figure 4) of stereochemical control was observed by workers at FMC i n cyclization of ester enolates (6). Cyclization of the ethyl ester initiated by sodium t-butoxide i n hexane produced a 12:88 ratio of cis:trans cyclopropanes. Repeating this experiment in the presence of the polar aprotic solvent, HMPA, reversed the stereoselection in the ring closure. The ratio of cis:trans isomers was 74:26. One obvious interpretation of these results can be derived from observations of Ireland regarding the influence of HMPA on the stereoselection in the formation of ester enolates (7). Based on Ireland s work, i n hexane the E-enolate would be formed preferentially and in the presence of HMPA the Z-enolate would be the major diastereomeric intermediate. I t follows that E-enolates cyclize selectively to form trans cyclopropanes, and Z-enolates selectively produce c i s products (Figure 5). We chose to explore the intramolecular alkylation of amide enolates as a potential stereoselective route to c i s pyrethroid cyclopropane carboxylates. If the relationship between the stereoselection i n enolate formation and ring closure i s operable, amide enolates would be an excellent means of developing a stereoselective synthesis of çis products (8). Furthermore, recent progress i n achieving enantioselection i n the intermolecular alkylation of chiral amide enolates would provide a means of obtaining optically active pyrethroid acids (Figure 6) (9-13). Our i n i t i a l efforts were aimed at examining the stereoselection of the cyclization of enolates from simple Ν,Ν-dialkyl amides. To this end we prepared N,N,3,3-tetramethyl4-pentenamide i n 77% yield using the Meerwein-Eschenmoser variant of the Claisen rearrangement (Figure 7) (14). However, we met with considerable difficulty upon attempts to functionalize the olefin. Repeated attempts at free radical initiated addition of OCI4 or CBrCl^ under standard conditions resulted i n recovery of starting material. Upon going to more vigorous conditions the formation of a lactone was observed (15). The lactone presumably arises from an intramolecular alkylation of the i n i t i a l OCI4 addition product. We also attempted epoxidation as a means of functional iz ing the olefin. Again we observed a lack of reactivity. Ultimately we found that reaction occurred with 2 -hydroperoxyhexafluoro-2 prcpanol (16), but again a lactone derived from intramolecular epoxide opening was the product. After our i n i t i a l attempts to test our idea i n a model compound met with failure, we chose to examine a system which more closely resembled one of interest for cur ultimate goal. We prepared the product of the Claisen rearrangement of 3-methyl-2buten-l-ol adduct with triethylorthoacetate (Figure 8). The resulting unsaturated ester was hydrolized to the œrresponding 1


17.

Permethrin Cypermethrln OOWCO 417 Decamethrln


Figure 1.

191

Synthesis of Synthetic Pyrethroids

KLESCHICK

A = C H , X=CI, Y=H A = C H , X=CI. Y=CN A=N, X=CI, Y = C N A - C H . X=Br, Y=CN (1R. 3R. a S)

Some examples of synthetic pyrethroid insecticides

HOO

^

1

CH»CCI

CH CCI

2

2

Figure 2.

CH CC1

CH3OC

ROI

ROi

2

N

q

3

0

H

3

Retrosynthetic analysis

)

CHjOC*

CH3OC CH CCI 2

CI

CH2CCI3

3

cis: t r a n s »

9:1

Figure 3. Stereoselecticn i n the cyclization of the methyl ketone enolate

Et0 C

CH CCI 2

2

N 3

O

Q

B

U

^ , solvent

CI

Et0

+

3

CH CCI 2

2

CH CCI 2

3

cis: trons

solvent hexane hexane-HMPA

Figure 4. enolate

3

Et0 (

12:88 74:26

Stereoselection i n the cyclization of the ester



192


F i g u r e 5. S t e r e o s e l e c t i o n i n c y c l o p r o p a n e f u n c t i o n of e n o l a t e s t e r e o c h e m i s t r y

f o r m a t i o n as a

Figure 6. Retrosynthetic analysis for the asymmetric synthesis


IT.

KLESCHICK


193

MeaOCHCHjOH lcH C(0Me) NMe

2

||CF C0CF3, H 0

2

3


CuBr. C B r C l

Me hT " ^ ^ C H C C I a

2

3

2

3

2

Λ

3

10 !H

I

JH O 2

Figure 7 .

a

Attempted synthesis v i a the Ν,Ν-dimethylamide

Cl

CH CCI 2

CH CCI

3

2

85:15

3

g or h (Q) C H j C i O E t J j . (b) NQOH. (c) SOCI* (d) NaH. 2-oxQzolidInone. (e) F e t C O ) * CCI*, (f) NaH. (g) 1. KOH. 2. HCI. 3. KOH. (h) 1. LiOMe,

HOOi

ÎH-CCU

2

'

K

0

K

Figure 8. Stereoselective synthesis of c i s - 3 (2,2-dichlorovinyl) -2,2-djiiiethylc^clcpropanecarto


acid

194


carboxylic acid (17), and the acid was converted to the acid chloride. Reaction of the acid chloride with the sodium salt of 2-oxazolidinone produced the desired imide. Functionalizing the olefin i n this material also proved d i f f i c u l t . After much experimentation we found that reaction with CC1 catalyzed by iron pentacarbonyl at reflux produced the desired CC1 adduct i n excellent yield. Cyclization of this material was accomplished by treatment with sodium hydride. Other bases could also be used to bring about cyclization, however the desired products were œntaminated with minor products from déhydrohalogenation or oxazolidinone ring opening. The ratio of c i s to trans cyclopropanes was 85:15. The stereochemistry of the major product was confirmed by separation and conversion to a sample of the c i s carboxylic acid. No scrambling of the carboxyl stereocenter was detected during the hydrolysis and déhydrohalogenation reactions involved i n the conversion. Having established the stereoselection i n the cyclization of a simple imide, we began to explore a chiral imide system. The starting material for the ring closure was prepared by a straightforward extension of the route described above (Figure 9). The starting point for this material was R-valine. R-valine was reduced with borane-methyl sulfide to the corresponding amino alcohol without any loss of stereochemical integrity (18). This was verified by conversion of the amino alcohol to the Mosher's amide and examination of the F NMR spectrum and HPLC chromatographic properties (19). The imidazolidinone was prepared by reaction of the amino alcohol with carbonyl diimidazole. In this reaction sequence, OCI4 addition to the olefin produced two diastereomeric products. As expected the stereoselection i n this addition was low due to the great distance between the resident stereocenter and the newly created one. The two CCI4 addition products were nearly identical i n a l l respects. Identification of 4


4

1 9

the s t e r e o s t r u c t u r e of the major d i a s t e r e o m e r was a c c o m p l i s h e d by s i n g l e c r y s t a l X-ray a n a l y s i s . The s t e r e o s e l e c t i o n i n t h e c y c l i z a t i o n of each d i a s t e r e o m e r was examined i n d e p e n d e n t l y . The s t e r e o c h e m i c a l outcome of the c y c l i z a t i o n s h o u l d be p r e d i c t a b l e based on our assumption r e g a r d i n g

the relationship between enolate stereochemistry and cyclopropane stereochemistry, the principles of asymmetric, intermolecular alkylation of optically active amides (9-13) and the assumption that the mechanism of cyclopropane formation involves a straightforward back-side, SJJ2 reaction. In the case of the major diastereomer, the natural tendency of the enolate to produce the cis-cyclopropane w i l l oppose the facial preference for the alkylation of the chiral enolate. Consequently, poorer stereochemical control would be expected i n the ring closure. In the minor diastereomer these two forces are working i n tandem, and high degrees of stereocontrol should result. Cyclization of the major diastereomer produced a mixture of a l l four possible products i n a ratio of 1:23:74:2 (Figure 10). The stereochemical assignment (Figure 10) was based on conversion to dihalovinyl acid. Ratios of c i s to trans products were established by ! H NMR, and assignment of absolute configuration was made based on comparison of the optical rotation with literature



KLESCHICK


(a) BHs-SMea, B F ^ O E t * (b) carbonyldlimidazolβ. (d) ClOCCHaCCCHjJjCH-CHa. (e) Fe(CO)e. C C I *

(c) NaH.

Figure 9. Synthesis of cyclization precursor for the asymmetric synthesis

(a) NaOH

(b) LiOMe

(c) KOH

Figure 10. Stereoselection i n the cyclization of the major diastereomer


195

196


92%, »1R,3R-i J * * 1R.3SH b.c 2^ 1 S . 3 S 4 ^ 5%

VPr


(α) NaOH

(b) LiOMe

H 0 0 C ^

1S.3R-J

C

H

-

C

C

^

[ a i +18.9

(c) KOH

Figure 11. Stereoselection i n the cyclization of the minor diasterecmer M

1/ ROC

Synthesis of Synthetic Pyrethroids - ACS Symposium Series (ACS

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