My process for synthesizing these isoxazolines was very similar to what the research suggests
Step 1: Grignard Reaction
Step 2: Oxidation Reaction
Step 3: Oxime Reaction
Step 4.a: Nickel-Catalyzed Cyclization Reaction
Step 4.b:Palladium-Catalyzed Cyclization Reaction
- P-anisaldehyde was reacted with allylmagnesium chloride to form the alcohol 1-(4-methoxyphenyl)-3-buten-1-ol.
- This reaction lengthened the carbon chain on p-anisaldehyde.
- This chain was the binding site for the isoxazole ring.
Step 2: Oxidation Reaction
- 1-(4-methoxyphenyl)-3-buten-1-ol was reacted pyridinium chlorochromate to form the ketone 1-(-4-methoxyphenyl)-3-buten-1-one.
- This reaction essentially removed a hydrogen from the hydroxyl group located on the alcohol and formed a double bond in its place.
Step 3: Oxime Reaction
- 1-(4-methoxyphenyl)-3-buten-1-one was reacted with hydroxylamine hydrochloride to form the oxime (IE)-N-hydroxy-1-(4-methoxyphenyl)-3-buten-1-imine.
- This reaction formed the base of the isoxazole ring.
Step 4.a: Nickel-Catalyzed Cyclization Reaction
- (IE)-N-hydroxyl-1-(4-methoxyphenyl)-3-buten-1-imine was reacted with nickel (II) chloride and copper (II) chloride to form the first variation of isoxazoline.
- The nickel derivative fell off of the isoxazoline at the end of the reaction.
Step 4.b:Palladium-Catalyzed Cyclization Reaction
- (IE)-N-hydroxyl-1-(4-methoxyphenyl)-3-buten-1-imine was reacted with palladium (II) chloride and copper (II) chloride to from the second variation of isoxazoline.