J. Org. Chem. 1992,57,5047-5049
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gated possibility is that for amide If (Table I), the 5,6cis-substituents do not isomerize because the blocking I N-methyl group precludes the possibility of a [1,5]hydrogen shift. In addition to lf, the formation of a @-hydroxy amide (a single diastereoisomer) is consistent with an acid-catalyzed aldol condensation of an enol p b p h a t e intermediate with benzaldehyde. A Prins reactionla to account, for example, for the deconjugated amide 8a cannot be rigorously excluded; however, @-protonationof OP(O)(OR)OH OP(O)(OR)OH intermediate 6 appears more plausible. I I 2,2-Dimethyl-3-pentenamide failed to react with benzaldehyde in PPE at 40 "C, presumably because enolization cannot occur. PPE evidently favors the formation of enol phosphates, and hence bladams via 6x ring cloeure, unless steric factors prevent coplanarity of the substituents. 6 7 with Thus, condensation of (E)-N-benzyl-3-pentenamide benzaldehyde in PPE (35 OC, 24 h) gave exclusively the N-benzyl derivative (52?%) of the indano-fused ylactam previously obtained from a condensation in PPA." A medium of PPA or MeSOSH-P2O5generally favors the formation of the 7-lactam, presumably via N-acyliminium cations. However, where this mode would proceed via a primary cartmation, the alternative ring cloeure operates to give a blactam,e.g, la. Thus,the size of the lactam ring can be controlled exclusively by selection of the acidic catalysts or stabilizing or activating groups. medium. In no case studied here was a mixture of y- and Condensation of a variety of 3-alkenamides with al6-lactams isolated. dehydes in PPE21affords a general route to substituted In summary, efficient, highly stereocontrolled one-pot 5,6-dihydro-2(lH)-pyridinoneswhose stereochemistry can syntheses of substituted unsaturated 6-lactams by the be rationalized by assuming that (i)such cyclizations do condensation of 3-alkenamides with aldehydes in media not always proceed solely, or at all, through N-acylof phosphoric acids or esters, principally PPE, have been iminium species; in certain cases, enol phosphate interdemonstrated. Condensations proceed under mild conmediates are involved, ( i i ) the formation of a cis-5,6-diditions and can be effected in multigram quantities; acsubstituted-5,6-dihydro-2(lH)-pyridinone ring is the retivating or stabilizing groups are not required. The result of a thermal 6x electrocyclic disrotatory ring-closure,22,23 and (iii) trans-5,6-disubstituted-5,6-dihydro-2- action medium can critically determine whether a ylactam'' or a 6-lactam is formed. Pathways and synthetic (1H)-pyridinone rings are formed from the cis-isomers (or applications are under investigation. their reaction intermediates) by processes which involve a combination of enol phosphate intermediates and Acknowledgment. We thank the Science and Engiequilibration to the trans isomers (as for entries IC, Id, neering Research Council and SmithKline Beecham for l e , and Ig)either by prototropic shifts or by [l,b]siga CASE award (to U.G.). matropic rearrangement of hydrogen.23 An uninvesti-try NO.1%14242226-2;lb, 142422-27-3;IC,142422-284, (21) PPA was purchased from BDH Chemicals La., Poole. For a Id,142422-29-5;le, 142422-30-8;If, 142422-31-9;lg, 142422-32-0; review on PPA see: Rowlands, D. A. In Synthetic Methods; Pizey, J. S., 8a, 142422-33-1; PhCHO, 100-52-7;p-MeOC6H4CHO,123-11-5; Ed.;Wiley: New York, 1985; Vol. 6. p 156. For some uses of PPE in pO2NC6H4CHOp555-16-8;H2MHCHZCONH2, 28446-58-4; synthesis, see: (a) Kanaoaka, Y.; Ban, Y.; Mayashita, K.; Iria, K.; YoH2C=CHCH&ONHCH2Ph, 85390-58-5; (E)-H&CH= nemitau, 0. Chem. Pharm. Bull. 1966,14,934. (b) Kanaoka, Y.; Sato, E.; Yonemitsu, 0.;Ban,Y. Tetrahedron Lett. 1964,35,2419. PPE was CHCH2CONHz,133099-99-7;(E)-H&CH=CHCHzCONHMe, prepared as described by Cava, M. P.; L a k e h m i k a n k Mitchell, M. J. 142422-34-2;(E)-H&CH2CH
