title: Effect of Bronsted Acids and Bases, and Lewis Acid (Sn(2+)) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-β-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisomeric 1H-Pyrrolo[3,2-b]pyridines.
abstract: Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-β-diketones gave γ-1H-pyrrolo[3,2-b]pyridines via reaction at the less reactive carbonyl group. The trifluoromethyl group increased the electrophilicity of the adjacent carbonyl group and decreased the basicity of the hydroxyl group of the CF3 amino alcohol formed. This amino alcohol was formed faster, but its subsequent dehydration to the β-enaminone was slow resulting in the preferential formation of the γ-regioisomer. Reaction of 4,4,4-trifluoro-1-phenyl-1,3-butadione with 3-aminopyrrole was carried out using a series of 6 amine buffers. Yields of the α-1H-pyrrolo[3,2-b]pyridine increased as the pKa of the amine buffer decreased. Surprisingly the yield went down at higher pKas. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-β-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-β-diketone) the α-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn(2+). Similar α-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-β-diketones was carried out in the presence of base and tin(II) acetate.
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: De Rosa
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: David
authors.initials: D
authors.lastname: Arnold
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hartline
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Truong
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Roman
authors.initials: R
authors.lastname: Verner
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Penn State Brandywine , 25 Yearsley Mill Road, Media, Pennsylvania 19063, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Westin