Improved schmidt conversion of aldehydes to nitriles using azidotrimethylsilane in 1,1,1,3,3,3-Hexafluoro-2-Propanol

The Schmidt reaction of aromatic aldehydes using a substoichiometric amount (40 mol %) of triflic acid is described. Low catalyst loading was enabled by a strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP). This improved protocol tolerates a broad scope of aldehydes with diverse functional groups and the corresponding nitriles were obtained in good to high yields without the need for aqueous work up

An Interrupted Schmidt Reaction: C-C Bond Formation Arising from Nitrilium Ion Capture

The rerouting of the nitrilium ion formed in the Schmidt reaction of ketones and TMSN 3 to encompass C-C bond formation with an electron-rich aromatic group is reported. Thus, when the reaction is carried out in HFIP using AlCl 3 or AlBr 3 as the promoter, imines, iminium ions, or enamide derivatives are obtained through one-pot procedures. The scope and possible mechanisms of these new transformations are considered

Hexafluoroisopropanol and Acetyl Chloride Promoted Catalytic Hydroarylation with Phenols

We report a catalytic hydroarylation method to convert phenols to dihydrocoumarins in hexafluoroisopropanol (HFIP) using acid generated from sub-stoichiometric amounts of acetyl chloride as catalyst. Attractive elements include easy set-up and isolation, and applicability to a range of phenols including natural product substrates

Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction

A method for carrying out the intramolecular Schmidt reaction of alkyl azides and ketones using a substoichiometric amount of catalyst is reported. Following extensive screening, the use of the strong hydrogen-bond-donating solvent hexafluoro-2-propanol was found to be consistent with low catalyst loadings, which ranged from 2.5 mol % for favorable substrates to 25 mol % for more difficult cases. Reaction optimization, broad substrate scope, and preliminary mechanistic studies of this improved version of the reaction are described