Transition metal catalyzed cross-coupling of 1-halo-1-haloalkene compounds
AssigneeReplidyne, Inc.
InventorsJoseph W. Guiles, Jian Qiu, Theodore M. Tarasow
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Abstract
Methods for introducing a 1-halo-1-haloalkene compound onto an aromatic or heteroaromatic ring are provided, including processes for the production of certain 1-halovinyl aryl or heteroaryl derivatives in which the 1-halovinyl group is either 1-fluoro or 1-chlorovinyl and the aromatic species phenyl or thiophene, the processes including coupling an arylmagnesium species with a dihalo olefin in the presence of a nickel or iron catalyst.
Claims15
A method of introducing a 1-haloalkene functionality into an organic molecule comprising:
- a) providing a substituted or unsubstituted aromatic or heteroaromatic Grignard reagent of the formula ArMgX, wherein Ar is a substituted or unsubstituted C4-C20 aromatic or heteroaromatic compound, and X is a halogen;
- and
- b) reacting the substituted or unsubstituted aromatic or heteroaromatic Grignard reagent with a 1-halo-1-haloalkene of the formula R1X1X2, wherein R1 is an C2-C20 substituted or unsubstituted alkene and X1 and X2 are halogens, in the presence of a transition metal catalyst M, to give a 1-haloalkene substituted aromatic or heteroaromatic compound of the formula X1R1Ar.
A method for preparing 4-bromo-2-dimethoxymethyl-5-(1-fluorovinyl)-3-methylthiophene comprising:
- a) reacting with a Grignard reagent of the formula RMgX to form 3-bromo-5-dimethoxymethyl-4-methylthiophenyl magnesium chloride;
- and
- b) reacting the 3-bromo-5-dimethoxymethyl-4-methylthiophenyl magnesium chloride with a compound selected from the group consisting of 1-bromo-1-fluoro-etheylene, 1-chloro-1-fluoroethylene, 1,1-difluoroethylene, wherein the transition metal catalyst M is NiCl2 or FeCl2 to form 3-bromo-5-dimethoxymethyl-2-(1-fluorovinyl)-4-methylthiophene.
A method for preparing 4-bromo-2-dimethoxymethyl-5-(1-chlorovinyl)-3-methylthiophene comprising:
- a) reacting with a Grignard reagent of the formula RMgX to form 3-bromo-5-dimethoxymethyl-4-methylthiophenyl magnesium chloride;
- and
- b) reacting the 3-bromo-5-dimethoxymethyl-4-methylthiophenyl magnesium chloride with a compound selected from the group consisting of 1,1-dichloroethylene wherein the transition metal catalyst M is NiCl2 or FeCl2 to form 3-bromo-5-dimethoxymethyl-2-(1-chlorovinyl)-4-methylthiophene.
Dependencies are inferred from the claim text.