Acylnitrilium ions, generated by the exposure of tu-ketoimidoyl chlorides to AgBF, readily engage suitably disposed sites of molecular unsaturation in cyclization reactions leading to heterocyclic ring systems. This novel method for annulation is applicable to the construction of 5, 6, and 7 membered rings and is particularly useful for the synthesis of poiyfunctional heterocycles possessing quaternary sites in the @-position to nitrogen.
G. LUEDTKE et al.
RESULTS
A.
Acylnitdium Ion-Silylaxyaikene ~clizations. Applications to the Synthed of A'-plrrolines. Dendrobine (la) : R = H Dendramine (lb) : R q OH
As part of a unified synthetic approach to the Orchidaceae alkaloids", we required large quantities of the A'-pyrroline 2g. It was predicted that 2g and related A'-pyrrolines might be synthesized in a highly convergent mamer by the silver ion induced cyclization of cu-ketoimidoyl chlorides (e.g., 4a-f)
formed by the direct combination of acyl chlorides with isocyanomethylsilyl enol ethers (e.g., 5a-e)."
The requisite isocyanomethylsilyl enol ethers 5as, in turn, were expected to be available, at least in principle, by sequential 1,4-addition of isocyanomethylithium ( )19 to the corresponding cu,/3-unsaturated ketones 7a-e followed by enolate silylation. Curiously, there were no reports detailing the reactions of isocyanomethyllithium ( ) or its organometallic derivatives with enones present in the literature at the time we began our investigations. Accordingly, we conducted a detailed study of the parameters which govern 1,2-vs 1,4-regioselectivity for this nucleophilic addition reaction. It was ultimately determined that reasonable to excellent selectivity favoring the desired 1,4-mode of addition could optimally be