Syntheses of Phencyclone Analogues. Applications for NMR Studies of Hindered Rotations and Magnetic Anisotropy in Crowded Diels–Alder Adducts

Undergraduate organic chemistry special laboratory projects based upon the synthesis of phencyclone, 1 (a potent Diels-Alder diene), and the preparation of a series of highly hindered Diels-Alder adducts of the phencyclone, were described earlier. Details of the synthesis of an analogue of 1 are presented here as an extension of these projects. The analogue, 3,6-dibromophencyclone, 2, and adducts from a wide range of dienophiles, can be prepared by undergraduate organic chemistry students. These adducts (from 1 or 2) are eminently suitable for student characterization by NMR to examine aspects of hindered rotation, magnetic anisotropy, and dynamic NMR spectroscopy, using modern one- and two-dimensional multinuclear methods with a medium-field instrument (7 T), to observe 1H, 13C, and 19F. Use of 2 effectively doubles the range of potential target compounds for students. The Diels-Alder adducts (and their precursors) have been studied by molecular modeling methods. This present paper describes the reaction of 2 with 4, the dienophile N-(4-dimethylamino-3,5-dinitrophenyl)maleimide (“Tuppy’s maleimide”), to form the adduct 5. Compound 5 has been well-characterized by 1D and 2D 1H and 13C NMR, and is illustrative of the wide range of adducts that can be made from 2 by students. The structure of 5, as determined by geometry optimization at the semiempirical (AM-1) level, is included here.