Imidazolidine Hydride Donors in Palladium-Catalyzed Alkyne Hydroarylation

Abstract

Aldehyde-derived imidazolidines participate as hydride donors in intramolecular reductive Heck-type reactions. N,N'-Diphenylimidazolidines prepared from ortho-alkynyl benzaldehydes underwent regio- and stereoselective palladium-catalyzed hydroarylation followed by formal 1,5-hydride transfer and reductive elimination to afford substituted alkenes and imidazolium moieties, the latter conveniently converted in situ to ring-opened benzanilides to simplify product isolation. Internal alkynes were converted to trisubstituted alkenes via a syn hydroarylation process, while a terminal alkyne was converted to a cis alkene via a formal trans hydroarylation reaction. Benzanilide products could be converted to carboxylic acid derivatives under basic conditions, resulting in the net conversion of alkynyl aldehydes to alkenyl carboxylic acids. A styrene derivative with an attached N,N'-dimethylbenzimidazoline hydride donor was also found to undergo an analogous hydroarylation/benzimidazoline oxidation to give a diarylethane product.

Scheme 1. Mechanistic Overview of Alkyne Hydroarylation under Reductive Heck Conditions

Scheme 2. Benzimidazolines as Hydride Sources

Scheme 3. Reductive Dehalogenation of a 2-Iodophenyl Imidazolidine

Scheme 4. Preparation of Alkynyl Aminal 3c and Postulated Hydroarylation Sequence

Figure 1

Line drawing and X-ray crystal structure of phenanthrene 5.

Scheme 5. Plausible Sequence Leading to 5

Figure 2

Partial atom connectivity map of 4c derived from 2D NMR data.

Scheme 6. Control Experiments

Scheme 7. Scope of Pd-Catalyzed Alkyne Hydroarylation

Scheme 8. trans Hydroarylation of Terminal Alkyne 3s

Figure 3

Unreactive hydroarylation substrates.

Scheme 9. Anilide Saponification

Scheme 10. Benzimidazoline-Mediated Alkene Hydroarylation