Enantioselective NHC-Catalyzed Redox [2+2] Cycloadditions with Perfluoroketones: A Route to Fluorinated Oxetanes
The N-heterocyclic carbene (NHC) catalyzed redox formal [2+2] cycloaddition between α-aroyloxyaldehydes and perfluoroketones, followed by ring-opening in situ delivers a variety of perfluorinated β-hydroxycarbonyl compounds in good yield, and excellent diastereo- and enantioselectivity. Through a reductive work-up and subsequent cyclization, this protocol offers access to highly substituted fluorinated oxetanes in two steps and in high ee.
Davies, Alyn T.,Slawin, Alexandra M. Z.,Smith, Andrew D.
supporting information
p. 18944 - 18948
(2016/01/26)
Organocatalytic Aerobic Oxidation of α-Fluoroalkyl Alcohols to Fluoroalkyl Ketones at Room Temperature
The organocatalytic aerobic oxidation of electron-deficient α-fluoroalkyl alcohols at room temperature is described. The resulting fluoroalkyl ketones are versatile synthetic intermediates for a variety of fluorine-containing molecules. This otherwise difficult transformation has now been accomplished by the reaction of α-fluoroalkyl alcohols with N-oxyl radicals, catalytically generated from 9-azabicyclo[3.3.1]nonan-3-one N-oxyl/nitrogen oxide (keto-ABNO/NOx) and oxygen in acetic acid (AcOH), affording the corresponding fluoroalkyl ketones in high yield. This operationally simple reaction can be performed under mild conditions, and was applied to a wide range of alcohols (20 examples), thus demonstrating a high functional group tolerance. Moreover, a modified one-pot protocol based on this method was able to convert an aldehyde to a trifluoromethyl ketone on a gram scale.
New fluorous photoaffinity labels (F-PAL) and their application in V-ATPase inhibition studies
(Trifluoromethyl)diazirines are well established photoaffinity labels (PAL) used in biochemical investigations to create covalent ligand-receptor bonds. Two new diazirinylbenzoic acids 8b, c with perfluorobutyl and perfluorooctyl chains (FPAL) were efficiently prepared from p-bromobenzaldehyde and attached to the highly potent and specific V-ATPase inhibitors 21-deoxyconcanolide A (2) and bafilomycin A1 (5), deriving from the natural product pool from Streptomyces producer strains. The labelled derivatives 17 and 18 were efficiently purified by fluorous solid-phase extraction. Func-tional biochemical assays with the V-ATPase holoenzymes proofed, strong inhibition activities. So far, radioactive isotopes or biotin-tags have mainly been used for tracing compounds in photoaffinity studies. The C4F9- and C 8F17-fluorous tags aim to enable advantageous separation and identification of labelled peptide fragments by fluorous chromatography followed by MS analysis. Therefore, F-PAL represents an innovative new concept for binding site determination and should significantly accelerate and simplify such biochemical investigations.