Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters

Abstract

A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N'-dioxide-Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.

Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle–Kirmse Reaction of α-Diazo Pyrazoleamides

“…We next evaluated metal salts used for both metallocarbene formation and Lewis acid activation (entries 2–8). We examined Rh­(II), Ag­(I), Cu­(I), Fe­(II), and Ni­(II) as the metal ions, and one exception was Rh 2 (OAc) 4 , which led to the gradual decomposition of the diazo substrate but none of the desired product (entry 2), with a completely different capability for the reaction of the α-diazoester . The same result was observed with the AgOTf system (entry 3).…”

“…Initially, chiral N,N′ -dioxide L 3 -PiPr 2 synthesized from l -pipecolic acid and 2,6-diisopropylaniline was used to recognize the metal salts. Rare-earth metal salts, such as Sc­(OTf) 3 and Yb­(OTf) 3 , which showed excellent performance with chiral N,N′ -dioxide ligands in several asymmetric catalytic reactions of α,β-unsaturated pyrazoleamides, were ineffective in this case (entry 1). − ,, Thus, thermal- and Lewis acid-activated decomposition of the α-diazo pyrazoleamide into a carbene at this condition was excluded. We next evaluated metal salts used for both metallocarbene formation and Lewis acid activation (entries 2–8).…”

Homologation Reaction of Ketones with Diazo Compounds

“…Recently, the same group reported the catalytic intramolecular version of the same reaction resulting in preparation of cyclopentanones promoted by chiral N,N ′-dioxide-Sc­(OTf) 3 complex formed by combination of the metal salt with ligand 150 (Scheme ). This method provides a construction of α-aryl- and α-alkyl-substituted 2-oxocyclopentanecarboxylates with a chiral all-carbon quaternary center in up to 96% yield and ee . After the intramolecular nucleophilic addition of the diazo moiety to the carbonyl group, a 1,2-aryl shift extrudes molecular nitrogen, providing the β-keto esters using catalyst loadings as low as 0.5 mol % in a moisture- and oxygen-tolerant process.…”

α-Diazoacetamides in Sc(OTf)3-Catalyzed Tiffeneau–Demjanov Ring Expansion: Application towards the Synthesis of Rare Bicyclic Pyrazoles

“…-Tetralone also failed to undergo Sc(OTf) 3 -catalyzed ring expansion with 4a, which is unsurprising considering that the only example of similar ring expansion reported in the literature (also Sc(OTf) 3 -catalyzed) involves intramolecular addition of -diazocarbonyl side chain onto -tetralone moiety. 16 It should also be noted that Sc(OTf) 3 -catalyzed ring-expansion reactions of cyclic ketones using diazoalkanes have been reported by the Kingsbury group. 17…”