title: Three-component Ag-catalyzed enantioselective vinylogous mannich and Aza-Diels-Alder reactions with alkyl-substituted aldehydes.
abstract: Efficient protocols for three-component catalytic enantioselective vinylogous Mannich (VM) reactions of alkyl-substituted aldimines (including those bearing heteroatom-containing substituents) and readily available siloxyfurans are presented. High efficiency and stereoselectivity is achieved through the use of o-thiomethyl-p-methoxyaniline-derived aldimines. Reactions, performed under an atmosphere of air and in undistilled THF, can be promoted in the presence of as little as 1 mol % of easily accessible amino acid-based chiral ligands and commercially available AgOAc. The desired products are obtained in 44 to 92% yield, and in up to >98:<2 diastereomer and >99:<1 enantiomer ratio (>98% ee). Removal of the N-activating group is performed through a one-vessel oxidation/hydrolysis operation, which proceeds via a stable aza-quinone (characterized by X-ray crystallography). Evidence is presented indicating that reactions with chiral nonracemic aldehydes are subject to catalyst control: both substrate enantiomers react to afford the desired product diastereomers in high stereoselectivity. Aryl- and alkynyl-substituted o-thiomethyl-p-methoxyaniline-derived aldimines undergo Ag-catalyzed enantioselective VM reactions more efficiently and with higher selectivity than the corresponding o-anisidyl substrates. Additionally, Ag-catalyzed aza-Diels-Alder reactions of the alkyl-substituted aldimines bearing the structurally modified N-aryl unit afford enantiomerically enriched (up to 95% ee) products in up to 88% yield.
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College Chestnut Hill, Massachusetts 02467, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mandai
authors.forename: Kyoko
authors.initials: K
authors.lastname: Mandai
authors.forename: Marc L
authors.initials: ML
authors.lastname: Snapper
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hoveyda
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry; D002384:Catalysis; D005663:Furans / Q000737:chemistry*; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D011809:Quinones / Q000737:chemistry; D012834:Silver / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D001372:Aza Compounds; D005663:Furans; D007097:Imines; D011809:Quinones; D012834:Silver