Autoxidation of a tetracyclic lactam and its conversion to an enantiopure tertiary alcohol

The reduction of chiral tetracyclic lactams 1, 2 led to new functionalized derivatives 5–8 containing 3 or 5 stereogenic centers. Autoxidation of compound 5 was observed yielding an enantiopure peroxide 9, which in turn slowly converted into tertiary alcohol 10.

Figure optionsDownload as PowerPoint slide

(1R,3R,8R,11R,12S)-10-Oxo-2,9-diazatetracyclo[10.2.1.02.11.03.8]pentadecaneC13H20N2O[α]D20=+98.2 (c 1.12, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3R,8R,11R,12S) (by chemical correlation)

(3R,8R,11R)-10-Oxo-2,9-diazatetracyclo[10.2.2.02.11.03.8]hexadecaneC14H22N2O[α]D20=+18.0 (c 0.25, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (3R,8R,11R) (by chemical correlation)

(1R,4R,6R)-4-Cyclopentyl-3-oxo-2,5-diazabicyclo[4.4.0]decaneC13H22N2O[α]D20=+31.0 (c 0.55, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,4R,6R) (by chemical correlation and 2D NMR NOESY measurement)

(1R,4R,6R)-4-Cyclohexyl-3-oxo-2,5-diazabicyclo[4.4.0]decaneC14H24N2O[α]D20=+20.7 (c 0.53, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,4R,6R) (by chemical correlation and 2D NMR NOESY measurement)

Bis-11,11′-{(1R,3R,8R,11S,12S)-10-oxo-2,9-diazatetracyclo[10.2.1.02.11.03.8]pentadecyl}peroxideC26H38N4O4[α]D20=+58.3 (c 0.57, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3R,8R,11S,12S) (by chemical correlation and X-ray measurement)

(1R,3R,8R,11S,12S)-11-Hydroxy-10-oxo-2,9-diazatetracyclo[10.2.1.02.11.03.8]pentadecaneC13H20N2O2[α]D20=+75.1 (c 0.75, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3R,8R,11S,12S) (by chemical correlation and X-ray measurement)