Pestic. Sci. 1986, 17, 701-707

The Pyrethrins and Related Compounds. Part XXIX" : Haloallylbenzyl Esters

Michael Elliottb, Richard L. Elliottc, Norman F. Janes and Bhupinder P. S. Khambay

Department of Insecticides and Fungicides, Rorhams ted Experimental Station, Harpenden, Herts. AL5 2JQ

(Revised manuscript received 4 December 1985)

Synthesis and bioassay of a series of esters based on pyrethroidal acids established that the activity of halosubstituted allylbenzyl esters depends on the position and stereochemistry of substitution in the ally1 side-chain, on the substitution pattern on benzyl, on the esterifying acid, and, to a lesser extent, on the nature of the halogen substituent itself. The most powerful combination of the first four parameters for activity against houseflies is in (Z)-3-haloallylbenzyI esters of the (lR)-ci.s 3-(2,2- dibromovinyl) acid. Other combinations have moderate to low activity. Some aspects of the variation conform to previously recognised patterns, others define more pre- cisely the requirements for the side-chain to confer activity. The pattern of response of activity to cyano-substitution at the a-position, noted earlier, persists in the current compounds, and is here analysed quantitatively.

1. Introduction

The preceding paper' describes the examination of alkenylbenzyl chrysanthemates (Figure 1, R2=truns-2-methylprop-l-enyl) and analogues (R2=cis-2,2-dibromovinyl) in which the side-chains (R') are related to those present in the natural pyrethrins. It is possible that variations similar to those found to be effective in the acid side-chain might also be advantageous in the alcohol side-

cyH:c,o, CH /@ II I R2 Figure 1. Basic structure of esters: R'=alkenyl;

Y=H or CN. O Y

chain. For instance, mono- and di-halovinyl groups are particularly effective on the acid side,2, so it was considered attractive to examine the effect of mono- and di-haloallyl groups in alcohols. A few relevant compounds have already been des~r ibed ,~ . but for these the associated insecticidal data are difficult to assess comparatively. The present work reports a series of compounds synthesised and tested to establish structure-activity relationships in this area.

2. Experimental methods 2.1. General The procedures and techniques described in the previous paper' were used, including those for converting aldehydes to the corresponding benzyl and a-cyanobenzyl alcohols and esters. In addi-

'Part XXVIII: Pestic Sci. 1986, 17, 691-700. bPresent address: Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, 115. Wellman

'Present address: Beecham Pharmaceutical Research Division, Animal Health Research Centre, Walton Oaks, Dorking Hall, University of California, Berkeley. California, 94720, USA.

Road, Tadworth. Surrey, KT20 7NT.

70 1

702 Michael Elliott el al.

tion, a Perkin Elmer 251 Autoannular Still was used for spinning-band distillations. Supporting experimental data are recorded as supplementary material. As previously, IH and I3C nuclear magnetic resonance (n.m.r.) spectroscopy were used to confirm the structure and purity of inter- mediates and final products. The effects noted in the previous paper again applied consistently throughout the present series, so that complete assignment of all peaks was possible (see Table S3 in the supplementary material to this paper)."

2.2. Procedure A: copper-catalysed coupling to introduce side-chain The Grignard reagent from bromobenzaldehyde ketal (43.7 mmol) and magnesium (1.15 g, 47.3 mmol) in dry tetrahydrofuran (40 ml) was added to a stirred solution of the haloallyl halide (65 mmol) and finely-ground catalyst (8.3 mmol) in tetrahydrofuran (150 ml) at -20°C. For allyl bromides, the catalyst was copper (I) bromide, and for allyl chlorides, an equimolar mixture of lithium chloride and copper (I) chloride. The mixture was stirred at 20°C for 16 h, then decomposed with saturated aqueous ammonium chloride (ca. 100 ml). The tetrahydrofuran layer and diethyl ether extracts of the inorganic layer were combined and evaporated on a rotary evaporator. The residue, redissolved in tetrahydrofuran (100 ml), was treated with aqueous hydrochloric acid ( 3 M , 50 ml) at 20°C for 1 h, diluted with water and diethyl ether, and the ether layer processed as usual. The residue was chromatographed on florisil, eluting with diethyl ether+light petroleum (15+85 by vol), to give a fraction (typically 15% yield) shown by n.m.r. and g.1.c. to be the required product (purity: 98%). When (E/Z)-l,3-dibromopropene was used, h.p.1.c. purification (cf. procedure C of previous paper') afforded a clear separation of the product mixture into the required E and Z isomers.

2.3. Intermediates for procedure A 3-Bromo-, 4-bromo-, and 4-bromo-2,6-dimethyl-benzaldehyde ethylene ketals were available from previous work.' Spinning-band distillation of commercial 1,3-dichloropropene gave an early fraction containing, among other impurities, 1,2-dichIoropropane, then two major fractions, b.p. 101-108°C and 108-1 12°C. Separate redistillation of these fractions gave (Z)-1,3-dichloropropene [ng' 1.4679, n.m.r. peaksat4.3 (d, J=7 Hz), 6.1 (dt, 7, J=7 Hz;, 6.3 (6 , J=7 Hz)] and (E)-1,3-dichloropropene, [ng 1.4747, n.m.r. peaks at 4.2 (d, J=7 Hz), 6.2 (dt, 14, J=7 Hz), 6.5 (d, J=14 Hz)]. 1,3- Dibromopropene was used as a mixture of E and Z isomers, prepared as described previously.h

2.4. 3-(3,3-Dichloroallyl)-and 3-(3-chloro-3-fluoroaIlyl)-benzaldehydes Ozone-rich oxygen was passed into 3-allylbenzaldehyde ethylene ketall (2.0 g, 10.5 mmol) in dichloromethane (40 ml) at -78°C until a blue colour appeared (ca. 20 min), followed by oxygen (3 min) then nitrogen (10 niin). Triphenylphosphine (2.0 g, 11.1 mmol) in dichloromethane (10 ml) was added and the mixture was allowed to warm to 20°C. After removal of solvent the residue of the crude phenylacetaldehyde and triphenylphosphine (5.24 g, 20 mmol) in dry acetonitrile (15 ml) was treated dropwise with stirring at 15°C with carbon tetrachloride (3 ml, 28.5 mmol) then stirring was continued for 16 h. Solvents were removed by evaporation, and the residue extracted with diethyl ether+light petroleum (1+1 by vol). The extract, after removal of solvents, was hydrolysed in aqueous hydrochloric acid-tetrahydrofuran (as in section 2.2). Purification by chromatography on florisil gave 3-(3,3-dichloroallyl)benzaldehyde (0.62 g), ng 1.5654, n.m.r. peaks at 3.7 (d, 2H, J=7 Hz), 6.2 (t, l H , J=7 Hz), 7.4-8.1 (m, 4H), 10.2 (s, 1H).

Alternatively, the above 3-(2-oxoethyl)-benzaldehyde ethylene ketal(l.4 g, 9.2 mmol) dissolved in a mixture of dry heptane ( 5 ml) and dry diethyl ether (10 ml) was added to a reagent prepared at 0°C by adding a solution of dichlorofluoromethane (2 g, 19.4 mmol) in heptane (10 ml) over 30 min to a stirred suspension of triphenylphosphine (2.6 g, 10.0 mmol) and potassium tert-butoxide (1.86 g, 16.6 mmol) under an atmosphere of nitrogen, and the mixture was allowed to warm up to room temperature over 2 h. Saturated aqueous ammonium chloride solution was added and the mixture extracted with diethyl ether (three times), dried and the solvent evaporated. Purification by

"Spectral data are available as supplementary material deposited with the British Library (Lcnding Division). Boston Spa, Wetherby. W. Yorkshire LS23 7BQ as SUP no. 11002 (7 pages).

The pyrethrins and related compounds 103

flash chromatography on silica gave (E/Z)-3-(3-chloro-3-fluoroallyl)benzaldehyde ethylene ketal (0.4 g), ng 1.5273.

This product (0.35 g, 1.73 mmol) was added to a stirred solution of sodium dihydro-bk(2- methoxyethoxy)aluminohydride (SDA) (2 g, 9.9 mmol) in dry toluene (20 ml) and the mixture was refluxed under an atmosphere of nitrogen for 2 h. Saturated aqueous ammonium chloride solution was added cautiously and the product was extracted with diethyl ether. The extracts were concen- trated to ca. 30 ml and added to 20% aqueous hydrochloric acid. The mixture was stirred for 30 min, extracted with diethyl ether (three times), dried and the solvent was evaporated to give (E/Z)-3-(3- fluoroally1)benzaldehyde (0.11 9).

2.5. 4-(3,3-Dichloroallyl)benzyl esters The tetrahydropyranyl ether of 4-allylbenzyl alcohol' was also subjected to ozonolysis, Wittig reaction and hydrolysis, as described in section 2.4, to give a mixture containing 4-(3,3- dichloroally1)benzyl alcohol and the corresponding benzyl chloride. Separation was best achieved by

Table 1. Synthesis and bioloeical DroDerties of esters investieated

Insecticidal activity* Structure of estep (lR)-?rans chrysanthemate (lR)-cis DBDCG

Entry Method of number R' at Y synthesis HF MB HF MB

I n Iu N V VI w MI M X XI xu xm XIV xv

XVI X W xvm XIX xx

XXI xxn

XXIII X X N XXV

XXVl XXVII

XXWI XXIX xxx XXXI

XXXII

2-Chloroallyl 2-Chloroallyl 2-Chloroallyl 2-Chloroallyl 2-Bromoallyl 2-Bromoallyl 2-Bromoallyl 2-Bromoallyl

(Z)-3-Chloroallyl (Z)-3- ChloroaUyl (Z)-3-Chloroallyl (Z)-3-Chloroallyl (Z)-3-Chloroallyl (E)-3-ChloroaUyl (E)J-Chloroallyl (E)-3-Chloroallyl (E)-3-Chloroallyl (Z)-3-BromoaIlyl (Z)-3-Bromoallyl (E)-3-Bromoallyl (E)-3-Bromoallyl 3,3-Dichloroallyl 3,3-Dichloroallyl 3,3-Dichloroallyl 3,3-Dichloroallyl 3,3-Difluoroallyl (Z)-3-Fluoroallyl (E)-3-Ruoroallyl

(E/Z)-3-Fluoroallyl (E/Z)-3-Chloro-3-fluoroallyl (E/Z)-3-Chloro-3-fluoroallyl (E/Z)-3-Chloro-3-fluoroallyl

3 3 4 4 3 3 4 4 3 3 4 4 4e 3 3 4 4 3 4 3 4 3 3 4 4 4 3 3 4 3 3 4

H CN H CN H CN H CN H CN H CN H H CN H CN H H H H H CN H CN H H H H H CN

A A A A A A A A A A A A A A A A A

A+h.p.l.c. A+h.p.l.c. A+h.p.l.c. A+h.p.l.c.

Special Special Special Special Special

Special+h.p.l.c. Special+h.p.l.c.

Special Special Special

H Special

5.1 0.8 9.2 6

64 2.4 2.1 ca 0.2 5.0 0.6 4.2 2.9

12 0.9 0.8 N T d

5.1 3.0 28 13 46 8.9 0.5 ca 0.1 7.3 6.3 5.0 ca 1

13 ca 6 6.2 ca 1 NT NT 3.2 0.8

10 3.8 1.8 ca 0.3 3.2 0.8 2.8 1.6 5.6 9.8 1.2 ca 0.6

NT NT 24 1.7

11 0.8

31 29

240

82

89

74 11

380

53 15 9

93 3

35 230 11 32

74 13

ca 0.2 100 25 15 50 52

150 37

1.7

8.3

0.9

5.2

3.2

6.9 17 9 1.2 4.4 6.4 5

ca 0.6 14 60 15

57 ca 7

17 ca 6 ca 1

1.9

7.2 4.1 5.0 4.6 2.2

12 4.5

NT 6.6 5.5 3.3 4.0 1.6 3.0 4.9

'For basic structure, see Figure 1 bActivity relative to bioresmethrin (=100) by topical application tests using measured drops in acetone. HF=Houseflies

(Musca domestica L.); MB=mustard beetles (Phaedon cochleariae Fab.). c( 1R)-c~-3-(2,2-Dibromovinyl)d,2-dimethylcyclopropanecarboxylate. dNT=non-toxic. c2,6-Dimethyl substituted.

47

704 Michael Elliott el al.

oxidising the alcohol with pyridinium dichromate (Procedure J of preceding paper'). Preparative h.p.1.c. on silica, eluting with diethyl ether+light petroleum (5+95 by volume) then gave 4-(3,3- dichloroal1yl)benzyl chloride, [ng 1.5603, n.m.r. peaks at 3.6 (d, 2H, J=7 Hz), 4.6(s, 2H), 6.1 (t, l H , 7 Hz), 7.2-7.8 (AzB2, 4H)] and 4-(3,3-dichloroallyl)-benzaldehyde, (ng 1.5621, n.m.r. peaks at 3.7 (d, 2H, J=7 Hz), 6.2 (1, lH , J=7 Hz), 7.4-8.1 (A2B2, 4H) 10.2 (s, 1 H)]. The benzyl chloride was reacted with the silver salts of the two acids in refluxing carbon tetrachloride' to give the two esters described in Table 1 (XXIV).

2.6 4-(3,3-Difluoroallyl)benzaldehyde A solution of 4-allylbromobenzene (25.0 g, 127 mmol)8 in dichloromethane (400 ml) at -30°C was treated with ozone as in section 2.4. After flushing, the mixture was treated (vigorous stirring) with acetic acid (200 ml) containing water (20 ml) at -3O"C, followed by zinc powder (140 g). The mixture was allowed to warm to 20°C during 1.5 h, then filtered, and shaken with water (1 litre) and diethyl ether (500 ml). The organic layer, combined with a further ether extract, was processed as usual, then distilled to give 4-bromophenylacetaldehyde, (16.9 g) b.p. 95-10OoC/0. 1 mm, ng 1.5741, n.m.r. peaks at 3.6 (d, 2 H, J=2 Hz), 6.9-7.5 (AzB2, 4 H), 9.6 (t, 1 H, J=2 Hz).

A solution of triphenylphosphine (26 g, 100 mmol) in dimethylacetamide (12 ml) was added to a mixture of dibromodifluoromethane (21 g, 100 mmol) and the above aldehyde (10 g, 50 mmol) in dimethylacetamide (12 ml) at 0°C over 30 min under nitrogen, then the mixture was allowed to warm to 20°C during 30 min. Zinc dust (6.55 g, 100 mmol) was added, and the mixture was stirred at 100°C for 1 h. After recooling and filtering, the mixture was shaken with water and ether, and the organic layer was processed as usual. The residue was distilled to give 4-bromo-(3,3-difluoroallyl)benzene (5.2 g) b.p. 50-51°C/0.2 mm, ng 1.5330, n.m.r. peaks at 3.2 (broad d, 2H, J=7 Hz), 4.3 (ddt, 1H.

This intermediate (0.5 g, 2.1 rnmol) in diethyl ether (5 ml) at -78°C under nitrogen was treated with tert-butyl-lithium in hexane (1.38 ml of 1.4 M, 1.9 mmol) then the mixture was allowed to warm to 20°C during 30 min. N-Piperidinecarboxaldehyde (0.27 g, 2.39 mmol) in diethyl ether (5 ml) was added at 20"C, and stirring was continued for 30 min. Saturated aqueous ammonium chloride was added, followed by ether and water, and the organic layer was processed as usual. Purification of the residue by preparative h.p.1.c. gave 4-(3,3-difluoroallyl)benzaldehyde (0.21 g) ng 1.5179, n.m.r. peaks at 3.4 (broad d, 2H, J=7 Hz), 4.4 (ddt, lH , J=24,2 ,7 Hz), 7.1-7.9 (A2B2, 4H), 9.9 (s, 1H).

2.7. ( E / Z ) ,4-( 3-Fluoroall y l) benzy 1 alcohol Phenyl-lithium (46 ml of 2.0 M, 92 mmol) was added to a stirred suspension of (methoxy- methy1)triphenyl phosphonium chloride (31.3 g, 91.5 mmol) in dry diethyl ether (250 ml), cooled in a water bath, over 10 min. After 35 min a solution of 4-methoxycarbonylbenzaldehyde (10 g, 64.9 mmol) in dry diethyl ether (70 ml) was added over 5 min and the mixture was stirred at room temperature for 3 days. Saturated aqueous ammonium chloride was added and the mixture extracted with diethyl ether (three times), dried and the solvent evaporated. The residue was extracted with light petroleum and eluted from a column of silica with diethyl ether+light petroleum (15+85 by volume) to give methyl (E/Z)-4-(2-methoxyvinyl)benzoate (9.8 g) as a semi-solid.

This enol ether (3 g) was dissolved in a mixture of tetrahydrofuran (100 ml) and concentrated hydrochloric acid (15 ml) and stirred at room temperature for 1.5 h. Water (50 ml) was added and the mixture was concentrated under reduced pressure, extracted with diethyl ether (three times), dried and the solvent evaporated to give methyl 4-(2-oxoethyl)benzoate (2.1 g) ng 1.5468.

This aldehyde (1.8 g) was then converted to methyl 4-(3,3-difluoroallyl) benzoate (yield 0.35 g, ng 1.5050) by the procedure described in section 2.6 for 4-bromo-(3,3-difluoroallyl)benzene and reduced with excess SDA in 4 h by the procedure described in section 2.4 to the required alcohol (0.22 g), n$? 1.5486.

2.8. Insecticidal activity The activities of the various compounds against housefly (Muscu domesticu L.) and mustard beetle (Phaedon cochleun'ue, Fab.) were determined as described in the previous papers2

J=24,2 ,7 Hz), 6.9-7.5 (AZB2, 4H).

The pyrethrins and related compounds 705

3. Discussion 3.1. Synthesis Many of the compounds listed in Table 1 (I-XXI) were made by adapting the method described in the preceding paper,' (Figure 2, Route 1) as described here in section 2.2. Some of the intermediate haloallyl halides (those for I-VIII) were immediately available, but for others special procedures

Route 1

I 'sub

Route 2 TI

I

p C H H c H 2 D c ' C H o \ Ph,P=CX,X,, or equivalent x2

R R Figure 2. General routes to compounds synthesised.

were necessary. Commercial 1,3-dichloropropene is a mixture of E and 2 isomers, together with a small amount of 1 ,2-dichloropropane; the mixture was separated by spinning band distillation to provide the pure E and Z isomers (for IX-XVII). The corresponding 1,3-dibromopropene was available by synthesis as a Z / E mixture, which was used directly, and the mixed products were separated by h.p.1.c. (XVIII, XX and XIX, XXI). Allylic bromides coupled more readily than the chlorides, so copper (I) bromide was an acceptable coupling catalyst in the former case, but copper chloride was supplemented by lithium chloride to form a more active complex9 in the latter instance.

As in the preceding paper, the aldehydes smoothly gave the benzyl alcohols, the cyanohydrins, and thence the required esters.

For the dihaloallyl side chains, substituted phenylacetaldehydes, (Figure 2, route 2) generated by ozonolysis of substituted allylbenzenes, were subjected to Wittig reactions, using triphenylphosphine and carbon tetrachloride (for XI, X,=Clj, dibromodifluoromethane (for XI, X,=F), or dichlorofluoromethane under special conditionslO.

The detailed descriptions in sections 2.4 to 2.6 illustrate that the route was suitable for a series of aldehyde precursors, all of which were converted to aldehyde after the Wittig step. When R was Br reaction of the lithium derivative with N-piperidinecarboxaldehydel2 was successful. Alternatively, when R was ketal-protected aldehyde, simple hydrolysis was satisfactory. Finally, when R was tetrahydropyranyloxymethyl (the product obtained starting from 4-allylbenzyl alcohol), partial attack of the R group occurred at the Wittig stage, so that after hydrolysis and oxidation with pyridinium dichromate, the reaction product contained the benzyl chloride (R=CH,Cl) as well as the expected aldehyde. The separated benzyl chloride reacted smoothly with silver salts of pyrethroi- dal acids to give the required esters.

For the monofluoroallyl derivatives, reaction of 3,3-dihaloallyl compounds with hydride reducing agents, e.g. SDA, was investigated. Of many combinations of possibilities examined, one proved suitable for each case (substituent at the 3- or 4-position). In the 3-substituted case, R was ketal- protected aldehyde, X,,X, were F, CI and the reducing agent was SDA at 110°C for 2 h, R then remaining unattacked; subsequent separation by h.p.1.c. at the final stage gave the required esters. The corresponding reaction failed in the 4-substituted case, but when R was methoxycarbonyl, Xl,Xz both F, and the reducing agent SDA at 100°C for 4 h, R was reduced to hydroxymethyl, and the desired mixture of alcohols (E/Z ratio 5:l) was obtained directly.

(for XI=F, X,=CI).

706 Michael Elliott el d.

3.2. Insecticidal activity The activities against houseflies and mustard beetles of 59 compounds listed in Table 1 are generally low to moderate compared with typical pyrethroids, but occasionally higher. Esters of the (lR,cis) dibromoacid (listed on the right hand side of Table 1) are significantly more active than those of the (lR,tranr) chrysanthemic acid which is in agreement with earlier studies.l3 Examination of the structures with higher activities reveals a striking pattern. All seven values greater than 80 are for esters of the dibromo acid against houseflies, and all but two have in common also the following features: a substituent at the 4-position of the benzylic ring; no cyano group at the a-position: halogen on C-2', or C-3', in the latter case with Z-stereochemistry.

A pattern of the changes in activity induced in compounds of the structure shown in Figure 1 by changing from a 3-substituted, Y=H compound to a 3-substituted, Y=CN compound, or to a 4-substituted, Y=H or a 4-substituted, Y=CN compound was discerned, as in the previous set of compounds.' The results of quantitative statistical analysis to examine these effects in compounds from both sets gave the results summarised in Figure 3. The small standard errors indicate the persistence of the effect over the whole range of compounds studied. For houseflies, introducing a cyano group into a 3-substituted compound can be seen, in general, to enhance activity slightly less than changing the substituent to the 4-position; for mustard beetles the former effect is one of strong enhancement, but the latter of weak diminution in activity. The most striking observation is the generally devastating effect of introducing a cyano group into a 4-substituted compound.

Clearly, the requirements for activity depend on subtle interactions involving the a-centre, and the detection of this consistent pattern provides valuable additional information. Larger a-groups (even methyl) generally lowered activity compared with the a -H compound,13 so the enhancement by cyano may be associated with a chemical influence from a non-destructive site. One such effect would be increased acidity of the remaining a-H, thereby increasing ability to form a hydrogen bond with the neighbouring ester carboxyl oxygen. If sufficiently strongly favoured, this would impose a fixed conformation at this part of the molecule, contrasting with flexibility in a -H compounds. The imposed conformation might be close to that appropriate for binding at the site of action in the 3-substituted compounds, whereas in 4-substituted compounds, the change in orientation of the side-chain unsaturation might lead to a larger difference between the active and imposed conformations.

0 - - ?! - - 8 a -0.5-

-1.0-

I I I 3-ti 3-CN 4-H 4-CN

Figure 3. Changes in biological activity against (0) M. dornestica and (X) P. cochleariae caused by struc- tural changes. The labels on the horizontal axis refer to the position of substitution for R1 in that group of compounds (3-or 4) followed by the nature of the Y-substituent (H or CN). The 3-H compounds (in each of 24 cases-12 substituentsx 2 acid components) were taken as standard (change=O.O) and the 24 diff- erences [log (relative toxicity of changed com- pound)-log (relative toxicity of 3-H compound)] analysed to give ic and the standard error (both are plotted on the figure) for the 2 x 3 structural changes. Compounds listed as non-toxic in Table 1 were assigned a log (relative toxicity) of -1.0. The 12 sub- stituents analysed were: allyl, 2-methylprop-2-eny1, (Z)-but-2-enyl, (Z)-pent-2-enyl, (Z)-penta-2.4- dienyl, prop-Zynyl, but-2-ynyl (from the previous work'), 2-chloroaUyl. 2-bromoallyl, (Z)-3-chloroallyl, (E)-3-chloroaUyl and 3,3-dichloroallyl (from the pre- sent work).

The pyrethrins and related compounds 707

Acknowledgements The authors thank the British Technology Group for financial support, and the bioassay team (S. Jenkinson and K. O’Dell under the supervision of A. W. Farnham) for sustained enthusiasm in obtaining essential results. Some of the compounds described are the subject of British Patent Applications Nos. 8314514,8317344 and foreign counterparts.

References 1. 2. 3. 4. 5. 6. 7. 8. 9.

10. 11. 12. 13.

Elliott, M.; Elliott, R. L.; Janes, N. F.; Khambay, B. P. S.; Pulman, D. A. Pesfic. Sci. 1986,17,691-700. Elliott, M.; Janes, N. F. Chern. SOC. Rev. 1978,7,473-505. Elliott, M.; Janes, N. F.; Khambay, B. P. S. Pesfic Sci. 1986, 17, 708-714. Brifish Pafenf Application 2 093 830 (1980); to ICI. Japanese Patent 57-18658 (1982); to Kuraray. Miller, B.; Saide, M. R. J . Am. Chem. SOC. 1976,98,2227-2238. Elliott, M.; Janes, N. F.; Pearson, B. C. J . Sci. Food Agric. 1967,18,325-331. Shirley, D. A . Preparafion of Organic Intermediates Wiley, New York, 1951, p. 36. Tamura, M.; Kochi, J . Synthesis 1971,303-305. Hayashi, S.; Nakai, T.; Ishikawa, N.; Burton, D. J.; Naae, D. G. Keoling, H. S. Chem. Len. 1979,983-986. Speziale, A.; Ratts, K. W. J. Am. Chem. SOC. 1982,84,854-859. Olah, G. A,; Arvanaghi, M. Angew. Chem. Int. Ed. Engl. 1981,20,878-879. Elliott, M.; Farnham, A . W.; Janes, N. F.; Khambay, B. P. S. Pesn’c. Sci. 1982, 13,407-414.