Asymmetric Organocatalytic Synthesis of Fluorinated β-Hydroxy Diazenes

The nucleophilic addition of formaldehyde tert-butyl hydrazone to fluoromethyl ketones provides a valuable tool for the synthesis of highly functionalized beta-hydroxy beta-tri- and difluoromethyl diazenes. Excellent reactivities and moderate to good enantioselectivities (up to 90 % ee) were achieved by H-bonding activation exerted by tert-Leucine derived H-bonding (squaramide or thiourea) organocatalysts. Subsequent derivatizations in one-pot fashion provide synthetically useful intermediates for target-oriented synthesis: tri- and di-fluoromethylated azoxy compounds, beta-amino alcohols, alpha-hydroxy aldoximes and derivatives thereof.