Catalytic enantioselective conjugate addition of dialkylzinc reagents to N-substituted-2,3-dehydro-4-piperidones

Abstract

The first, highly enantioselective, copper/phosphoramiditecatalyzed conjugate addition of dialkylzinc reagents to N-substituted 2,3-dehydro-4-piperidones is described.

Phosphoramidites: Privileged Ligands in Asymmetric Catalysis

“…[178,179] Conjugate addition reactions of dialkyl zinc reagents to cyclic nitrogen-containing Michael acceptors, such as lactams 72 and piperidones 74, have recently been disclosed (Scheme 21). [180,181] The addition products 73 and 75 are important intermediates in alkaloid syntheses. The reaction of diethylzinc and a,b-unsaturated lactams in the presence of phosphoramidite ligand ent-L2a (see Figure 4) gave the heterocyclic products 73 with ee values of up to 95 % (Scheme 21 a).…”

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[178,179] Weiterhin wurden konjugierte Additionen von Dialkylzinkreagentien an cyclische stickstoffhaltige Michael-Akzeptoren wie die Lactame 72 und die Piperidone 74 beschrieben (Schema 21 a und b). [180,181] [183] Die Addition von weniger reaktivem Dimethylzink an die von Chalkon abgeleiteten, a,b-ungesättigten (Pyridyl)sulfonylimine 81 wurde ebenfalls untersucht (Schema 24 a). [184] In Gegenwart eines Katalysators mit dem PhosphoramiditLiganden ent-L2b (siehe Abbildung 4) wurden die Enamide 82 in guten Ausbeuten (bis 91 %), ee-Werten bis 80 % und Z/E-Verhältnissen > 83:17 erhalten.…”

Synthesis of Novel Iminosugar Derivatives Based on a 2-Azabi­cyclo[4.1.0]heptane Skeleton

“…7-ethyl 5-hydroxy-2azabicyclo[4.1.0]heptane-2,7-dicarboxylate, 2b: From 4.0 mL (40.0 mmol) of 4-methoxy pyridine, 6.38 g (27.6 mmol, 69%) of benzyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate 1b were obtained, following the procedure described in the literature except that NaBH4 was used as the reducing agent. 14 The synthesis was continued as for compound 2a using 10.0 g (43.75 mmol) of (2-ethoxy-2-oxoethyl)dimethylsulfonium bromide in 45 mL of CHCl3 and 7 mL (46.00 mmol) of DBU. After the cyclopropanation step, 7.0 g of crude (1R*,6R*,7R*)-2-benzyl 7-ethyl 5oxo-2-azabicyclo[4.1.0]heptane-2,7-dicarboxylate were treated in 70 mL of methanol with 1.024 g (27.1 mmol) of NaBH4 giving, after isolation and flash column chromatography (Hexane:EtOAc (2:1) →Hexane:EtOAc (1:2)) 3.67 g (14.35 mmol, 52% yield from 1b, Rf=0.1 in Hexane/EtOAc, 1:1) of 2b as a colorless oil.…”

“…(1R*,5S*,6R*,7R*)-Diethyl 5-hydroxy-2-azabicyclo[4.1.0]heptane-2,7-dicarboxylate, 2a: From 4 mL (40.0 mmol) of 4-methoxypyridine, 4.53 g (26.8 mmol, 67%) of ethyl 4-oxo-3,4-dihydropyridine-1(2H)carboxylate 1a were obtained following the procedure described in the literature except that NaBH4 was used as the reducing agent. 14 To a solution of 10.22 g (44.6 mmol) of (2-ethoxy-2oxoethyl)dimethylsulfonium bromide in 41 mL of CHCl3, 6.75 mL (45.18 mmol) of DBU were added. After 30 minutes of stirring, 4.53 g of 1a were added and the reaction mixture was heated up to 70 o C through microwave irradiation during 10 min.…”