Enantioselective fluorination of β-ketoesters using tartrate derived bidentate bioxazoline-Cu(II) complexes

Enantioselective fluorination of aliphatic cyclic and acyclic β-ketoesters was achieved in excellent yield (up to 98%) with moderate to good enantioselectivities (up to 86% ee) using tartrate derived bidentate bioxazoline-Cu(II) complexes. This is the first report of a bioxazoline which forms a 5-membered chelate inducing enantioselectivity in the asymmetric fluorination of β-ketoesters.

Figure optionsDownload as PowerPoint slide

(R)-Ethyl 1-fluoro-2-oxocyclopentanecarboxylateC8H11FO3ee = 86%[α]D25=+73.2 (c1.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 1-fluoro-2-oxocyclopentanecarboxylateC7H9FO3ee = 72%[α]D25=+69.7 (c1.2, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-tert-Butyl 1-fluoro-2-oxocyclopentanecarboxylateC10H15FO3ee = 83%[α]D25=+61.4 (c0.25, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 1-fluoro-2-oxocyclohexanecarboxylateC9H13FO3ee = 52%[α]D25=+39.6 (c1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-fluoro-2-methyl-3-oxobutanoateC7H11FO3ee = 70%[α]D25=-62.1 (c0.70, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-fluoro-1-oxo-2,3-dihydro-1H-indene-2-carboxylateC12H11FO3ee = 34%[α]D25=-5.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-Ethyl 2-fluoro-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylateC13H13FO3ee = 16%[α]D25=-2.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)