Lewis Acid-Catalyzed Diels–Alder Reaction of Carvone with Isoprene. Using Two-Dimensional NMR and Molecular Modeling to Solve a Stereo- and Regiochemical Puzzle

Aluminum chloride catalyzes a regio- and stereoselective Diels–Alder reaction between (R)-(‑)-carvone and isoprene, forming one main product whose structure is deduced by a combination of molecular modeling and 1-D and 2-D NMR spectral interpretation. The major bicyclic product, which comprises about 80% of the product isomers, is purified by flash chromatography. Molecular models show that the product of anti addition of isoprene relative to the carvone isopropenyl group contains a C3 ring hydrogen in the equatorial position, while the same hydrogen in the syn product would be axial. The signal for this hydrogen is first identified within the alkyl region of the 1H NMR spectrum using DEPT and HSQC spectra. Then, using the observed spin-spin coupling pattern, the syn or anti configuration can be deduced. Para or meta orientation of the isoprene methyl group relative to the carvone carbonyl is determined by a combination of HSQC and HMBC 2-D spectra. MM2 molecular mechanics optimization is used to analyze the relative energies of the chair conformations of the four isomeric products. The major product, (3R,4aS,8aR)-3-isopropenyl-6,8a-dimethyl-3,4,4a,5,8,8a-hexahydronaphthalen-1(2H)-one (1d), is the least stable isomer.