title: Unexpected Retroaldol-Aldol Reaction during O-Alkylation of Hydroxylated Vince Lactam Derivatives.
abstract: The unexpected retroaldol-aldol reaction during O-alkylation of a β-hydroxy lactam was found to be highly dependent on the temperature and shows a remarkable solvent effect. In DMF, O-alkylation is faster than retroaldol-aldol rearrangement giving exclusively products with retention of configuration. In THF, O-alkylation is slower than rearrangement, giving selectively products with inversion of stereochemistry. In DMSO, a retroaldol reaction followed by fast intramolecular proton transfer occurs to give the ring-opened aldehyde.
authors.affiliation: Department of Medicinal Chemistry, CVMD iMed, AstraZeneca R&D Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bengtsson
authors.affiliation: Department of Medicinal Chemistry, CVMD iMed, AstraZeneca R&D Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wetzel
authors.affiliation: Department of Medicinal Chemistry, CVMD iMed, AstraZeneca R&D Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Bergman
authors.affiliation: Department of Medicinal Chemistry, CVMD iMed, AstraZeneca R&D Mölndal , Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Brånalt