William M. Horspool

A new photochemical synthesis of cyclopropanecarboxylic acids present in pyrethroids by the aza-di-π-methane rearrangement

Abstract A novel synthetic route to chrysanthemic acid, 2-cyclopentylidenmethyl-3,3-dimethylcyclopropanecarboxylic acid, fluorenespiro-2,2-dimethylcyclopropanecarboxylic acid and indenespiro-2,2-dimethylcyclopropanecarboxylic acid, all of them present in pyrethroids of known insecticidal activity, is described. The key step in the synthesis is the aza-di-n-rnethane rearrangement of some 1-aza-1,4,6-trienes and some 1-aza-1,4-dienes, using triplet sensitization.

A novel photochemical synthesis of 5,6-dihydro-4H-1,2-oxazines by DCA-sensitized irradiation of γδ-unsaturated oximes

On DCA-sensitized irradiation 6,6-diphenylhex-5-en-2-one oxime 5a, 5,5-diphenylpent-4-enal oxime 5b and 2,2-dimethyl-5-phenylpent-4-enal oxime 5c undergo a novel photochemical cyclization yielding 3-methyl-6-diphenylmethyl-5,6-dihydro-4H-1,2-oxazine 9a, 6-diphenylmethyl-5,6-dihydro-4H-1,2-oxazine 9b and 6-benzyl-4,4-dimethyl-5,6-dihydro-4H-1,2-oxazine 9c, respectively.

Extension of the aza-di-π-methane reaction to stable derivatives. Photochemical cyclization of β,γ-unsaturated oxime acetates

The successful sensitized photochemical conversion of oxime acetates of some β,γ-unsaturated aldehydes and of one ketone into cyclopropane derivatives by the aza-di-π-methane (ADPM) rearrangement has been carried out. Thus, for example, the acetophenon-sensitized irradiation of the oxime acetate of 2,2-dimethyl-4,4-diphenylbut-3-enal affords the oxime acetate of 2,2-dimethyl-3,3-diphenylcyclopropanecarboxaldehyde in 86% yield and with a quantum yield of 0.12. The first report of the successful ADPM rearrangement with all-alkyl substitution is described.

Steric and electronic effects on the photochemical reactivity of oxime acetates of β,γ-unsaturated aldehydes

A general synthesis of 5-substituted N-acetoxy 3,3-dimethyl-1-azapenta-1,4-dienes starting from 2-(1,3-dithian-2-yl)-2-methylpropanal is described. The influence of 5-phenyl, 4-phenyl, 5-cyclohexyl, 5-tert-butoxycarbonyl and 5,5-dicyclohexyl substitution on the outcome of the photochemical reactions of the oxime acetates of β, γ-unsaturated aldehydes has been studied with a view to proving or disproving the operation of a deactivating free rotor in the aza-di-π-methane rearrangement. The results obtained show that if the radical formed at C-5 can be stabilized by conjugation with an aryl group or by certain types of disubstitution then the aza-di-π-methane rearrangement takes place successfully. In any other situation the reaction fails. These results clearly show that the free rotor effect is not responsible for the failure of C-5 monosubstituted 1-aza-1,4-dienes to undergo the aza-di-π-methane rearrangement.

Chemically efficient aza-di-π-methane photoreactivity with novel stable derivatives of β,γ-unsaturated carbonyl compounds

The syntheses of new stable derivatives of β,γ-unsaturated carbonyl compounds such as 2,2-dimethyl-4,4-diphenylbut-3-enal 6 and 3,3-dimethyl-5,5-diphenylpent-4-en-2-one 7 are described. The majority of these derivatives undergo efficient aza-di-π-methane rearrangement on short, acetophenonesensitized, irradiation to afford the corresponding derivatives of the cyclopropane carbonyl compound in good to excellent yield; for example, the photoconversion of the oximino trifluoro acetate of the aldehyde 6 affords 2,2-dimethyl-3,3-diphenylcyclopropane-1-carbonitrile 16 in 80% yield. This is of synthetic value since β,γ-unsaturated nitriles do not undergo the aza-di-π-methane reaction. The study has also indicated some limits to the type of derivative that can be used. Thus with a methyl ketone derivative where the functional group can undergo SET from the triplet 1,1-diphenylvinyl moiety; an alternative fragmentation path can be operative in a novel reaction not seen previously in such systems.

Unexpected influence of mono-phenyl substitution on the photochemistry of β,γ-unsaturated oxime acetates

On irradiation the oxime acetate of trans-2,2-dimethyl-4-phenylbut-3-enal (5) undergoes stereospecific aza-di-π-methane rearrangement to the oxime acetate of trans-2,2-dimethyl-3-phenylcyclopropanecarbaldehyde (7), while surprisingly the irradiation of the oxime acetate of 2,2-dimethyl-3-phenylbut-3-enal (10) follows a different reaction path and affords the oxime acetate of 4-methyl-3-phenylpent-3-enal (13) by a novel 1,3-migration pathway.

A new photochemical synthesis of dihydropyrazoles. Novel mode of photocyclization of some 1-iuminobut-3-enes derivatives

While some hydrazine derivatives 3 of 2,2-dimethyl-4,4-diphenylbut but-3-enal undergo both the aza-di-π-methane (ADPM) rearrangement and a novel cyclization to afford dihydropyrazole derivatives 5 in varying yields, the tosylhydrazone derivative of 3,3-dimethyl-5,5-diphenylpent-4-en-d-one 7 gives exclusively an excellent yield of the corresponding dihydropyrazole 8, in a reaction that is proposed to involve an electron transfer process.

A study on the scope of the photochemical 1,3-migration of oximino groups in β,γ-unsaturated oximes and oxime derivatives

While the aza-di-π-methane rearrangement is the normal photoreactive behaviour of β,γ-unsaturated imines and oxime acetates, the results obtained in this study show that 1,3-migrations of acetoxyimino groups in β,γ-unsaturated oxime acetates takes place only when all the parameters are correct. The rearrangement takes place when there is a quaternary carbon separating the two π-systems and when one of the radical centres in the intermediate cyclobutyl 1,4-biradical is stabilized by conjugation with a phenyl ring. Suppression of the free rotor effect also helps to promote the reaction. These criteria are fulfilled in compounds 1a and 7a. The reaction was extended to the β,γ-unsaturated oximes l b and 7b where again the 1,3-migration of the oximino group took place.

Novel photochemical behaviour of the oximes and hydrazones of β,γ-unsaturated carbonyl compounds

A study of the photochemical reactivity of a series of β,γ-unsaturated oximes and hydrazone derivatives under triplet sensitized conditions has been carried out. The oximes 3c, 4a and 4c cyclize to the corresponding dihydroisoxazoles 5c, 6a and 6c while the tosyl hydrazone 8a affords the dihydropyrazole 9a. An intramolecular single electron-transfer mechanism from the alkene moiety to the oximino group, in the case of the oximes 3c, 4a and 4c, and to the tosyl group for the tosyl hydrazone 8a, is proposed to account for these results. Oximes and hydrazine derivatives from aldehydes behave differently. Thus, the oxime 3d yields the cyclopropyl oxime 10 by an aza di-π-methane (ADPM) rearrangement while the aldoxime 3e gives a mixture of the corresponding dihydroisoxazole 5d and cyclopropane 11a resulting from an ADPM process. Irradiation of the hydrazine derivatives 8b, 8c and 8d gives a mixture of the corresponding dihydropyrazoles 9b, 9c and 9d and the cyclopropanes 11b, 11c and 11d, respectively. However, under the same experimental conditions, dihydronaphthalene derivatives such as the oxime 12a and the tosyl hydrazone 12b undergo ADPM rearrangements exclusively, affording the cyclopropanes 13a and 13b, respectively. Sensitized irradiation of the tosyl hydrazone 12c yields the cyclopropane 13c, as the major product. In this instance a small amount of the hexahydrophenanthroline 14, resulting from an endo cyclization is also formed. The influence of substitution on the outcome of the reaction is discussed.

Reaction of anions from monoimines of benzil with alkylating agents. Photochemical reactivity of some 4-alkoxy-2-aza-1,3-dienes

The reaction of benzil benzhydrylmonoimine 6a with methyl iodide or dimethyl sulphate as the electrophile affords 4-alkoxy-2-aza-1,3-dienes resulting from an O-alkylation. When benzyl chloride is employed, products of O-alkylation, C-alkylation and cyclization are produced, while with toluene-p-sulphonyl chloride only cyclization to a dihydro-oxazole takes place. Benzil α-phenylethylmonoimine 6b yields only products of C- and/or O-alkylation. In one case, when a large excess of dimethyl sulphate is used, cyclization affords N-methyl-2,3,5-triphenylpyrrole. Irradiation of the O-alkylated compounds (E)- and (Z)-4-methoxy-1,1,3,4-tetraphenyl-2-azabuta-1,3-diene and (E)-4-benzyloxy-1,1,3,4-tetraphenyl-2-azabuta,-1,3-diene in the presence of perchloric acid yields isoquinoline derivatives by a photo-Mannich reaction.