NMR Crystallography Comparative Studies of Chiral (1R,2S,3R,5R)‑3- Amino-6,6-dimethylbicyclo[3.1.1]heptan-2-ol and Its p‑Toluenesulfonamide Derivative Magdalena Jaworska,* ,† Tomasz Pawlak, † Rafal Kruszyń ski, ‡ Marta C ́ wikliń ska, § and Marek Krzemiń ski § † Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland ‡ Department of X-ray Crystallography and Crystal Chemistry, Institute of General and Ecological Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland § Department Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University, Gagarina 7, 87-100 Torun, Poland * S Supporting Information ABSTRACT: The crystal structure of (1R,2S,3R,5R)-3- amino-6,6-dimethyl-2-hydroxybicyclo[3.1.1]heptane 1 was de- termined and it is presented in reference to the structure of (1 R ,2 S ,3 R ,5 R )-3-( p -tosylamino)-6,6-dimethyl-2- hydroxybicyclo[3.1.1]heptane 2. 1 H and 13 C chemical shifts parameters for both structures and for whole unit cells were calculated by using the GIPAW (gauge including projector augmented waves) method. Theoretically calculated chemical shift tensor parameters were verified by 13 C CP MAS, 2D PASS, and 13 C- 1 H FSLG HETCOR results to obtain a full structural assignment for 13 C and 1 H resonances in the solid-state. PISEMA MAS experiment was performed to determine the molecular dynamics of aminoalcohol 1. The comparison of two structures, obtained after all-atom positions optimization after the GIPAW calculations, revealed small conformational differences consistent with the single-crystal X-ray diffaction results. 1. INTRODUCTION Nowadays, pure chiral aminoalcohols play a key role in many branches of human life since they are widely applied as starting materials for the total syntheses of natural products or drugs. Moreover, a large number of them exhibit a wide range of bioactivities, such as antimalarial, 1 antiplasmodial, 2 antiprolifer- ative, 2 antileishmanial, 3 and antimicrobial. 4 Recent studies have also showed a potential ability of aminoalcohols to be the anticancer agents. 5 However, optically active aminoalcohols and their derivatives have been utilized successfully in widespread modern asymmetric syntheses, including the asymmetric addition of diethylzinc to aldehydes, 6,7 the enantioselective Michael addition, 8 the catalytic asymmetric transfer hydro- genation, 9 and the asymmetric synthesis of sulfonamides. 10 This class of compounds is also used as a main source of chirality in the structure of organoboron catalysts, such as oxazaborolidines 11,12 and spiroborate esters 13,14 used in asymmetric borane reduction of CO 12-15 and CN double bonds. 15 Several strategies for the synthesis of chiral aminoalcohols have been reported in the literature, for instance, the addition of α-hydroxy ketones to imines, 16 aminohydroxylation of olefins, 17 aminolytic kinetic resolution of racemic terminal/ trans aromatic epoxides, 18,19 and asymmetric ring-opening of meso-epoxides. 20 However, there is still a large requirement to expand knowledge about new aminoalcohol structures and spatial arrangements, which can help find the proper applications. NMR crystallography approach has recently become a very important method for structures elucidation. 21 Solid-state NMR spectroscopy combined with the X-ray diffraction (XRD) method and supported by gauge-including projector augmented waves (GIPAW) theoretical calculations has proven to be a powerful tool for the crystal structures determination of biologically active compounds, 22 glasses, 23 and minerals. 24 CP MAS (cross-polarization magic angle spinning) NMR is an ideal method for determining a number of independent molecules in the asymmetric unit cell (Z′) via comparison between the number of 13 C or 15 N resonances and the number of chemically different atoms in the crystal. 25 Although, it should be emphasized that the complete structural assignments of observed 13 C resonances to their positions in a crystal structure is still a challenging task. The growing interest in the NMR crystallography method has proven that this method can be used in classical organic chemistry for crystal structure determination, especially when single crystals for classical X-ray diffraction measurements are difficult to obtain. However, it can also be treated as a kind of experimental verification of crystal structures obtained by diffraction methods. 26 In this article, the structural investigations of (1R,2S,3R,5R)- 3-amino-6,6-dimethylbicyclo[3.1.1]heptan-2-ol are presented (pinane aminoalcohol, 1) using NMR crystallography method, Received: July 9, 2012 Revised: November 9, 2012 Published: November 14, 2012 Article pubs.acs.org/crystal © 2012 American Chemical Society 5956 dx.doi.org/10.1021/cg300940k | Cryst. Growth Des. 2012, 12, 5956-5965