Aminomethylhydroxylation of alkenes: Exploitation in the synthesis of scaffolds for small molecule libraries.
The application of [4+2] cycloadditions between alkenes and an N-benzoyl iminium species, generated in situ under acidic conditions, is described in the synthesis of diverse molecular scaffolds. The key reaction led to the formation of cyclic imidates in good yield and with high regioselectivity. It was demonstrated that the cyclic imidates may be readily converted into 1,3-amino alcohols. Incorporation of orthogonally-reactive functionality, such as aryl and alkyl bromides, into the cycloaddition substrates enabled the synthesis of additional scaffolds. For one scaffold, the synthesis of exemplar screening compounds was undertaken to demonstrate potential value in small molecule library production.
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
Ignacio
I
Colomer
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
Ololade
O
Adeniji
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
George M
GM
Burslem
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Philip
P
Craven
Edelris, 115 Avenue Lacassagne, F-69003 Lyon, France.
Martin Ohsten
MO
Rasmussen
Edelris, 115 Avenue Lacassagne, F-69003 Lyon, France.
Anthony
A
Willaume
Lead Discovery Center, Otto-Hahn Straße 15, 44227 Dortmund, Germany.
Tuomo
T
Kalliokoski
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Richard
R
Foster
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
Stephen P
SP
Marsden
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address: a.s.nelson@leeds.ac.uk.
Adam
A
Nelson
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D007096:Imidoesters / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000475:Alkenes; D007096:Imidoesters; D054852:Small Molecule Libraries; D010165:Palladium
1,3-Amino alcohols; Cycloaddition; Small molecule libraries