3-aza-Cope rearrangement of quaternary N-allyl enammonium salts. Stereospecific 1,3 allyl migration from nitrogen to carbon on a tricyclic template

N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3 -aza-Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction in volving 1,3 allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts, exemplified by benzo[alpha]quinolizine 8 and pyrrolo[2,1 -alpha]isoquinoline 13, with an interest in stereochemistry and mechanism. Salts 8 and 13 were accessed, respectively, through stereospecific allylati on of hydroxy amines 4 and 11a/11b to give 7 and 12a/12b, which were dehydr ated with trifluoroacetic acid. Allylic migration in these tricyclic tetrah ydroisoquinolines occurred with high stereospecificity, with the major prod ucts 9 (from 8) and 15a (from 13) apparently deriving from a concerted supr afacial [3,3] rearrangement. The rearrangement of 8 to 9 was facile at 23 d egrees C (t(1/2) = ca. 5 h) and was >98% stereospecific, whereas the rearra ngement of 13 to 15a/15b required heating between 50 and 100 degrees C, wit h ca. 90-95% stereospecificity (t(1/2) = ca. 0.3 h at 100 degrees C). A deu terium-labeling experiment with 21 (H-2-13) confirmed that allylic inversio n accompanies the 1,3 migration en route to major isomer 22a (H-2-15a), sup porting the predominance of a concerted [3,3] sigmatropic mechanism. Howeve r, the 5-10% loss of stereospecificity in the rearrangements of the pyrrolo isoquinolines 13 and 21, reflected by formation of minor isomers 15b and 22 b, respectively, indicates a minor nonconcerted reaction pathway.