Mechanistic Aspects of the Boron Trifluoride Catalyzed, Intermolecular Diels-Alder Cycloaddition of an Unactivated 2-Aza 1,3-Diene with Electron-Donating-Substituted Dienophiles

Article abstract of DOI:10.1021/jo00350a049

The boron trifluoride etherate catalyzed, intermolecular cycloaddition reactions of (1E,3E)- and (1E,3Z)-phenyl-2-aza-1,3-pentadiene (13E and 13Z) with various dienophiles including n-butyl vinyl ether, benzyl vinyl ether, tetrahydropyran, 1-(trimethylsiloxy)cyclohexene, cis-propenyl benzyl ether, trans-propenyl benzyl ether, and 1-morpholinocyclopentene have been explored.All reactions were carried out at 25 deg C in benzene solutions and were followed by reductive workup with sodium borohydride.The piperidine products 18-25, along with the reduced aza diene, N-propyl-N-benzylamine (16), and the aza diene dimers 17, were separated and characterized by use of a combination of spectroscopic and X-ray crystallographic methods.The yields of cycloadduct 18-25 formation range from 5 to 39percent while those for amine 16 and aza diene dimer 17 production are 10-50percent and 5-15percent, respectively.Only the 1(E),3(E) stereoisomer 13E is reactive under these conditions.All piperidine products were found to possess the cis-2-phenyl-5-methyl relative stereochemistry.The all-cis-2-phenyl-4-alkoxy-5-methyl stereoisomers 18 and 19 are produced exclusively in reactions of 13 with n-butyl and benzyl vinyl ether.Reactions of 13 with cis- and trans-propenyl benzyl ether give the corresponding cis- and trans-3-methyl-4-(benzyloxy)piperidines, 22 and 23, respectively.No noncyclic products resulting from addition of 1-(trimethylsiloxy)cyclohexene to the imine function of 13 have been detected.In addition, this enol ether fails to undergo boron trifluoride catalyzed addition to N-propylbenzaldimine.Electronically neutral and electron-poor dienophiles including cyclohexene and dimethyl acetylenedicarboxylate do not cycloadd to 13 under these Lewis acid catalysis conditions.The cycloaddition stereochemistry and regiochemistry, the lack of 1(E),3(Z) aza diene 13Z reactivity, the role of secondary interactions in controlling endo vs. exo preferences, as well as other features are discussed in terms of concerted reaction mechanisms via ?2s + ?4s pericyclic transition states for these cycloaddition reactions.