Attempts on the Synthesis of the Pheromone Component Lineatin

Abstract

poorly achieved. Direct alkylation on the alkenal V with 8-methallylmagnesium chloride followed by oxidative cleavage of 2,5,5-trimethylocta-l,7-diene-4-ol (VIlI) and methylenation via a Wittig reaction gave an improved yield of the alkylated product, 4,4-dimethyl-5-(2-methyl-2-propenyl)oxacyclopentan-2-one (IX). This compound and its precursors showed a strong tendency to cyclize and it was therefore difficult to prepare aketene precursor. Blocking the c 4-0H of compound VIII before oxidising the C-C double bonds was considered as one way of reducing this cyclization tendency. However, protection of the c 4-oH of VIII as a methyl ether followed by ozonolysis under reductive conditions (CH2cl 2/DMS) gave unexpectedly the cyclic product, 4,4-dimethyl-2-methoxy-5-(2-opropyl)oxalane (X) in which the methoxy group had migrated. Attempted halogenation of VIII resulted in (3~)-2,5,5-trimethyl-l,3,7-octatriene (XI).Selective oxidation of the c 4-oH of VIII to 2,5,5-trimethyll,7-octadiene-4-one (XII) was achieved with chromic acid in ether, but the strong tendency to isomerize to the a,S-unsaturated isomer before protection of the c 4 carbonyl group could be achieved precluded further manipulations on VIII.In a different attempt to prepare the ketene precursor the alkenal V was oxidised to 2,2-dimethyl-4-pentenoic acid (XIII)which was converted into its methyl ester XIV. Upon ozonolysis under reductive conditions (CH 2cl 2/DMS), XIV furnished 3,3-dimethyl-5-methoxyoxacyclopentan-2-one (XV) in which the methoxy group had migrated as well. A discussion of a mechanism of zonolysis under reductive conditions in aprotic and protic media is presented to account for the intramolecular alkoxy migration. These strategies and other related ones proved futile as routes to suitable precursors for the intramolecular ketene cyclization. In one of the strategies aimed at the bicyclic oxaketone III,the anticipated Michael addition of the alkoxy anion of 3-methyl-3-buten-l-ol (XVI) on sec-butyl and tert~butyl 3-methyl-2-butenoates (XVII) to give the potential ketene precursor, furnished instead, the ester exchange product 3-methyl-3-butenyl 3-methyl-2-butenoate (XVIII) . On the other hand, the reaction of the homoallylic alcohol XVI with NBS in the presence of acid catalyst gave 3-bromomethyl-3,7-dimethyl-4-oxa-7-octen-l-ol (XIX) . Attempted debromination of XIX led to the formation of 2-methyl-2-(3-methyl-3-butenoxy)oxalane (XX). By protection of the bromoalcohol XIX as a trimethyl silyl ether and debromination with tributyltinhydride followed by Jones oxidation, 3,3,7-trimethyl-4-oxa-7-octenoic acid (XXI) was obtained in good overall yield. The corresponding acid chloride XXII was prepared by the reaction with oxalyl chloride in benzene and pyridine. The acid chloride was unstable and could not be purified without decomposition. Reaction of the crude acid chloride XXII with base did not give any bicyclic oxaketone III. Hence terminating our synthetic efforts of lineatin by an intramolecular ketene-ene cycloaddition approach.The reaction of NBS with allyl and methallyl alcohols also gave the "dimerized" products, hence the reaction seems to be a general one. A mechanism for this reaction is discussed.