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

TCE

The Chemical Educator

ISSN: 1430-4171 (electronic version)

Table of Contents

Abstract Volume x Issue x (2006) pp 262-266

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

John W. Keller

Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK 99775-6160, ffjwk@uaf.edu
Received January 10, 2006. Accepted May 25, 2006.

Published online: 23 June 2006

Abstract. 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.

Key Words: Laboratories and Demonstrations; upper-division undergraduate; organic chemistry; synthesis; laboratory instruction; problem solving; chromatography; conformational analysis; asymmetric synthesis; Lewis acids; molecular modeling; NMR spectroscopy; stereochemistry; Diels–Alder; HSQC; HMBC

(*) Corresponding author. (E-mail: ffjwk@uaf.edu)

Article in PDF format (467 KB) HTML format

Supporting Materials:

Supporting materials include guidelines and procedure for students; a grading rubric; a list of supplies; and additional figures: 8 (DEPT), 9 (GC-MS), 10 (mass spectra), 11 (full HMBC), and 12 (full HSQC). (853 KB).