title: Determination of absolute configuration using density functional theory calculation of optical rotation: chiral alkanes.
abstract: The recently developed Gauge-Invariant (Including) Atomic Orbital (GIAO) based Time-Dependent Density Functional Theory (TDDFT) methodology for the calculation of transparent spectral region optical rotations of chiral molecules provides a new approach to the determination of absolute configurations. Here, we discuss the application of the TDDFT/GIAO methodology to chiral alkanes. We report B3LYP/aug-cc-pVDZ calculations of the specific rotations of the 22 chiral alkanes, 2-23, of well-established Absolute Configuration. The average absolute deviation of calculated and experimental [alpha](D) values for molecules 2-22 is 24.8. In two of the molecules 2-23, trans-pinane, 10, and endo-isocamphane, 13, the sign of [alpha](D) is incorrectly predicted. Our results demonstrate that absolute configurations of alkanes can be reliably assigned by using B3LYP/aug-cc-pVDZ TDDFT/GIAO calculations if, but only if, [alpha](D) is significantly greater than 25. In the case of (-)-anti-trans-anti-trans-anti-trans-perhydrotriphenylene, 1, [alpha](D) is -93 and TDDFT/GIAO calculations reliably lead to the absolute configuration R(-).
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, CA 90089-0482, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: McCann
authors.forename: P J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: J R
authors.initials: JR
authors.lastname: Cheeseman