Synthesis of alkyl-substituted six-membered lactones through ring-closing metathesis of homoallyl acrylates. An easy route to pyran-2-ones, constituents of tobacco flavor.
The ring-closing metathesis (RCM) reactions of homoallylic acrylates bearing alkyl substituents on various positions of their skeleton afford the corresponding pentenolides in the presence of carbene ruthenium catalysts. For R3 = R4 = H, or R3 = Me, R4 = H, the reactions are catalyzed by complex [RuCl2(PCy3)2(=CHPh)], while a second-generation Grubbs catalyst is required when R3 = H and R4 = Me, R3 = R4 = Me, or R3 = i-Pr and R4 = H. Alkyl substitution at the homoallylic carbon (R1, R2) increases the yield of the reaction when both the acrylic and/or homoallylic double bonds are methyl-substituted. The interaction of the catalyst with the substrate in the initiation stage involves the homoallylic double bond rather than the acrylic moiety, and the resulting alkylidene species from the first-generation Grubbs catalyst can be observed by 1H and 31P NMR. The racemic tobacco constituents 4-isopropyl-5,6-dihydropyran-2-one and 4-isopropyltetrahydropyran-2-one are prepared via a short reaction sequence, involving the RCM reaction as the key transformation.
D'Annibale
Andrea
A
Dipartimento di Chimica, and Istituto CNR di Chimica Biomolecolare, Sezione di Roma, Università degli Studi La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy. andrea.dannibale@uniroma1.it
Ciaralli
Laura
L
Bassetti
Mauro
M
Pasquini
Chiara
C
D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D006838:Hydrocarbons / Q000737:chemistry; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D011714:Pyrans / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D014026:Nicotiana / Q000737:chemistry* / Q000378:metabolism*
D006838:Hydrocarbons; D007783:Lactones; D011714:Pyrans; C030011:carbene; D002244:Carbon; D012428:Ruthenium; D008697:Methane