Vilsmeier-Hack formylation

Friedlander condensation of 5-aminopyrazole-4-carboxaldehydes 319 with dimedone furnished pyrazolo[3,4- ]quinolines 320. Subsequent Vilsmeier Hack formylation and sequential cyclocondensation with phenylhydrazine gave Ws-pyrazolo[3,4-b 4,3-/]quinolines (06JHC1169). 

Construction of the 2,5-disubstituted pyrrole 79 commenced with a one-pot acylation amidation protocol, whereby a Vilsmeier-Hack formylation furnished 74 in two steps in moderate yields. Assembly of the more complicated a-bromoketone was achieved by the use of 81, which was synthesized from the L-diethyl tartrate in four steps using a known procedure. The halide 82 was obtained through a one-pot Appel bromination/DlBAlH reduction of the ester. Protection of the primary alcohol followed by reaction with dithiane 83 led to 84. The yields of this reactimi were highly dependent upon the use of 2.0 equiv. of NaH, 2.0 equiv. of 83, and a catalytic amount of tBuOH. Any divergence from these conditions resulted in decreased yields. Subsequent reduction and removal of the dithiane provided 85 which was crai-verted to the desired a-bromoketone 78 (Scheme 28). 

Two new methods of formation of C-C bond at C-2 of glycals, with retention of the glycal double bond, have been published recently. Vilsmeier-Hack reaction is involved in the formylation of glycals [180], A Friedel-Crafts reaction of acyl chlorides with glycals, in the presence of aluminium chloride, is required for the C-2 acylation of glycals (Scheme 49) [181]. 

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