Palladium catalyzed cyclization reactions of acetylenic lactams

Lactams and oxazolidinones containing a 3-butynyl side chain at the four- a nd the three-position, respectively, have been prepared by reductive alkyla tion of cyclic imides or by S(N)2'-substitution of bromopropadiene with hig hly functionalized enantiopure organozinc reagents. Treatment of these comp ounds with aryl halides and one vinyl bromide using Pd(PPh3)(4) as a cataly st gives rise to a coupling-cyclization reaction, yielding bicyclic enamide s in which the aryl or vinyl moiety is incorporated. Remarkably, these grou ps are transferred stereoselectively cis with respect to the nitrogen nucle ophile onto the triple bond. Structural proof for this unusual stereochemic al outcome has been obtained by crystal structure analysis and NOE-differen ce spectroscopy of the cyclized products. (C) 2001 Elsevier Science B.V. Al l rights reserved.