New synthetic approach to cyclopenta-fused heterocycles based upon a mild Nazarov reaction.
The Pd-catalyzed coupling reaction of lactam or lactone-derived vinyl triflates and phosphates with alpha-alkoxydienylboronates gives conjugated alkoxytrienes in which one of the double bonds is embedded in a heterocyclic moiety. If subjected to mild acidic hydrolysis, these compounds undergo a 4pi electrocyclization process (Nazarov reaction) which furnishes cyclopenta-fused O- and N-heterocycles in good yields. The scope of the work has been that of closely examining the role and effect of both the heteroatom and the heterocycle ring size on the outcome of the electrocyclization, as well as the torquoselectivity of this process. The presence of the heteroatom was essential in stabilizing the oxyallyl cation intermediate, thus allowing the reaction to occur. The ring size was also a basic parameter in the cyclization step: five-membered azacycles required more drastic conditions to give 5-5 fused systems and did so only after an initial hydrolysis to the corresponding divinyl ketones. As for the torquoselectivity, with both 2-methyl and 4-methyl substituted lactam derivatives steric interactions seem to have a role in forcing the conrotatory process to take place in one sense only: allowing the synthesis of diastereomerically pure compounds to be realized. Because different patterns of substitution on the heterocycle are compatible with the reaction conditions, the methodology developed could be very useful for the synthesis of natural products and biologically active compounds containing cyclopenta-fused O- and N-heterocycle moieties.
Occhiato
Ernesto G
EG
Dipartimento di Chimica Organica "U. Schiff" and ICCOM, Università di Firenze, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Italy. ernesto.occhiato@unife.it
Prandi
Cristina
C
Ferrali
Alessandro
A
Guarna
Antonio
A
Venturello
Paolo
P
D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003517:Cyclopentanes / Q000138:chemical synthesis*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007769:Lactams / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
D001897:Boronic Acids; D003517:Cyclopentanes; D006571:Heterocyclic Compounds; D007769:Lactams; D007783:Lactones; D008698:Mesylates; D010710:Phosphates; D014753:Vinyl Compounds; C437735:vinyl triflate; D010165:Palladium