N-Acyliminium salts

A comprehensive kinetic study examining the reactivity of N-acylimines/N-acyliminium salts versus imines/iminium salts has not, to date, been published. Spectral data ( C NMR), however, would suggest... 

The a-amidoalkylation reaction, which involves the addition of carbon nucleophiles (primarily aromatic rings, alkenes, cyanides, isocyanides, alkynes, organometallic and active methylene-containing compounds) to substituted amides (89) where X is a leaving group (Scheme 17), has been extensively re-viewed. A variety of organometallic condensations have since been reported which extend the scope of this reaction. The reactive intermediates in these reactions are considered to be N-acylimines (88) or N-acyliminium salts (SKI). Direct displacement of the a-haloalkylamide precursors (89 X = halogen) cannot in certain cases be discounted. 

During the total synthesis of the marine alkaloid (+)-lepadiformine by S.M. Weinreb et al., one of the key bicyclic N-acyliminium salt intermediates was subjected to a nucleophilic attack by an organocuprate. ° The resulting allyidimethylsilyl derivative was then treated under the Fieming-Tamao oxidation conditions to afford the corresponding hydroxymethyl compound in excellent yield. 

Cyclic N-acyliminium salts and related intermediates 00T3817. 

In order to further understand how this overall transformation proceeds, a series of mechanistic experiments have been performed, in which the catalytic cycle has been broken down into individual steps (Scheme 1). Firstly, monitoring the reaction in situ by H and C NMR clearly reveals that imine 2 with acid chloride 3 react immediately upon mixing, prior to the addition of Pd2(dba)3 CHCl3, bipyridine, or carbon monoxide, to form the N-acyliminium salt 6 (Step A, Scheme 1) (10). The stmcture of 6 can be confirmed by its independent synAesis from imine and acid chloride. The conversion of 2 and 3 to this iminium salt is essentially quantitative by H NMR. 

We have previously reported that N-acyliminium salts can undergo rapid oxidative addition to low valent metals to generate metal-chelated amides (11). Similarly, the addition of the catalyst (5 mol% Pd2(dba)3 CHCI3 and 10% bipyridine) to this solution of 6 (Step B, Scheme 1) results in the rapid conversion of the palladium source into a new complex (7). This same conplex 7 can be prepared and isolated upon the stoichiometric reaction of 6, 0.5 equiv. Pd2(dba)3 CHCI3 and... 

Funke, W., Hornig, K., Moller, M.H. and Wiirthwein, E.U., Alkoxy-substituted N-acyliminium salts - synthesis, structure, reactivity, Chem. Ber. 126 (9), 2069-2077 (1993). 

The phosphonite 81 was shown to render a phosphonium salt 84 by interaction with the primarily obtained N-acyliminium salt 83. Deprotonation transformed 84 to the oxaphosphohdine 85, which undergoes l,3-dipolar cycloaddition with the activated alkyne elimination of phosphonate from the adduct 86 gives rise to the pyrrole system 82. In contrast to Mtinchnones (cf. p. 175), the mesoionic 1,3-dipoles of type 85 show high regioselectivity in the cycloaddition process. 

---