Palladium catalyzed cyclization reactions of acetylenic lactams

Lactams and oxazolidinones containing a 3-butynyl side chain at the four- and the three-position, respectively, have been prepared by reductive alkylation of cyclic imides or by SN2′-substitution of bromopropadiene with highly functionalized enantiopure organozinc reagents. Treatment of these compounds with aryl halides and one vinyl bromide using Pd(PPh3)4 as a catalyst gives rise to a coupling-cyclization reaction, yielding bicyclic enamides in which the aryl or vinyl moiety is incorporated. Remarkably, these groups are transferred stereoselectively cis with respect to the nitrogen nucleophile onto the triple bond. Structural proof for this unusual stereochemical outcome has been obtained by crystal structure analysis and NOE-difference spectroscopy of the cyclized products.