| Abstract: | The classical electrophilic substitution of activated aromatics with the Vilsmeier–Haack reagent N-chloromethylen-N,N-dimethylammonium chloride (Schemes 1 and 2) has been more recently extended to a great variety of aliphatic substrates, mainly due to the work of Arnold. In this review, a collection of representative examples for these henceforth called Vilsmeier–Haack–Arnold (VHA) formylation reaction of aliphatics is given: the reaction of polymethine cyanines, merocyanines, and other vinylogous iminium salts with the VHA reagent gives, after hydrolysis of the primary substitution products, trialdehydes such as triformylmethane (Scheme 3); VHA reaction with ene-diamines and diene-diamines yields N,N-dialkylaminomalonaldehydes and tetraaldehydes such as 1,1,2,2-tetraformylethane, respectively (Schemes 4 and 5); aldehyde acetals, enol ethers, and carboxylic acids deliver with VHA reagents 2-substituted malonaldehydes (Scheme 6), and α-amino acids give derivatives of the unstable aminomalonaldehyde (Scheme 7); alkenes and polyenes react with VHA reagents to give α,β-unsaturated or higher vinylogous aldehydes (Schemes 8 and 9), and alkenes with donor substituents yield alkylidene-malonaldehydes (Scheme 10); enolizable methyl and methylene ketones produce with VHA reagents 3-chlorovinylaldehydes (Scheme 11). Eventually, the VHA reagent can be used for the intermediate preparation of nucleophilic amino-chlorocarbenes (Scheme 12). |
