Determination of the Absolute Configuration of Six-Membered-Ring Ketones by ¹³C NMR

The diastereotopic splitting of the 13C NMR signals of the (2R,3R)-2,3-butanediol acetals of 39 chiral six-membered-ring ketones, including 2- and 3-substituted cyclohexanones, 2-alkyltetrahydropyran-4-ones, and 2- and 3-alkyltetrahydrothiopyran- 4-ones, has been studied. The stereodifferentiation of the six-membered-ring carbon atoms was shown to follow a very regular pattern, which is independent of substituents or of heteroatoms in the ring. Hence, an empirical rule could be deduced which allows the assignment of the absolute configuration of the original ketones from the 13C NMR spectrum of their acetals. The rule is only valid for six-membered-ring ketones having the chair form as the preferred conformation in the acetal. As shown for 11 examples, this rule is not valid for acyclic ketones, cyclopentanones, cycloheptanones, or cyclohexanones and cyclohexenones not having the chair form as the preferred conformation. The rule also permits the interpretation of the 13C NMR spectrum of the (2R,3R)-2,3-butanediol acetals of achiral cyclohexanones (seven examples). The stereodifferentiation is almost exclusively determined by the centers of chirality in the dioxolane ring. © 1987, American Chemical Society. All rights reserved.

Duke Scholars

Author Eric John Toone Chemistry