Highly diastereoselective synthesis of pyrido[2,1-b][1,3]oxazin-4(6H)-one by intramolecular anodic oxidation

This paper describes a method for the intramolecular anodic oxidation of ω-hydroxyl amides. Products were obtained in acceptable yields from different starting materials using various applied currents, charge, and reactant concentrations. Compounds 1a and 1d afforded a single diastereomer in 67% yield when the applied current and reactant concentration were 100 mA and 0.04 M.

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(1S,2R,4R)-N,N-Diethyl-2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptane-1-carboxamideC14H25NO2Ee >99%[α]D = −18.7 (c 1.38, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,2R,4R)

(1S,2R,4R)-2-Hydroxy-7,7-dimethyl-N,N-dipropylbicyclo[2.2.1]heptane-1-carboxamideC16H29NO2Ee >99%[α]D = −0.3 (c 2.84, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,2R,4R)

(1S,8S,10R,12R)-15,15-Dimethyl-2-oxo-3-aza-9-oxo-tetracyclo[10.2.1.01,10.03,8]pentadecaneC15H23NO2Ee >99%[α]D = −47.7 (c 2.99, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,8S,10R,12R)

(1S,4S,6R,8R)-3-Ethyl-4,11,11-trimethyl-5-oxa-3-aza-tricyclo[6.2.1.01,6]undecan-2-oneC14H23NO2Ee >99%[α]D = −23.8 (c 3.53, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,4S,6R,8R)

(1S,4S,6R,8R)-3-Ethyl-4,11,11-trimethyl-5-oxa-3-aza-tricyclo[6.2.1.01,6]undecan-2-oneC14H23NO2Ee >99%[α]D = −10.3 (c 1.99, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,4R,6R,8R)

(1S,4S,6R,8R)-3-Propyl-4-ethyl-11,11-dimethyl-5-oxa-3-aza-tricyclo[6.2.1.01,6]undecan-2-oneC16H27NO2Ee >99%[α]D = −46.45 (c 2.28, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,4S,6R,8R)

(1S,4R,6R,8R)-3-Propyl-4-ethyl-11,11-dimethyl-5-oxa-3-aza-tricyclo[6.2.1.01,6]undecan-2-oneC16H27NO2Ee >99%[α]D = +23.5 (c 2.50, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,4R,6R,8R)

(1S,7S,9R,11R)-14,14-Dimethyl-2-oxo-3-aza-8-oxo-tetracyclo[9.2.1.01,9.03,7]tetradecaneC14H21NO2Ee >99%[α]D = +12.0 (c 2.18, CHCl3)Source of chirality: (1S)-ketopinic acidAbsolute configuration: (1S,7S,9R,11R)