Stereochemistry of alkylated isoquinoline Reissert compounds

• Published in: Tetrahedron Vol. 70; no. 35; pp. 5904 - 5918
• Main Authors: Gibson, Harry W., Berg, Michael A.G., Price, Terry L., Niu, Zhenbin, Lee, Minjae, Rouser, Mason A., Slebodnick, Carla
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 02.09.2014; Elsevier
• Subjects: Alkylated isoquinoline Reissert compounds; Alkylation; Amide isomers; Atropisomers; Bonding; Chemistry; Chemistry, Organic; Crystallography; Isomers; NMR spectroscopy; NOESY; Physical Sciences; Rotamers; Science & Technology; Stereochemistry; Tetrahedrons; X-ray structures; X-rays; Alkylated isoquinoline Reissert compounds; Amide isomers; NOESY; Rotamers; Atropisomers; X-ray structures; ASYMMETRIC-SYNTHESIS; SUBSTITUENTS; INTERNAL-ROTATION; BARRIERS; CATALYST; MAGNETIC RESONANCE; NMR; CH/PI HYDROGEN-BONDS; CHEMISTRY; STRAIN
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.06.027

A series of alkylated isoquinoline Reissert compounds (2-acyl-1-alkyl-1,2-dihydroisoquinoline-1-nitriles) with either 3-H (3) or 3-CH3 (4) substituents was examined by 1H, 13C, and 19F NMR spectroscopies and X-ray crystallography. In all cases the trans-amide conformation, with reference to the carbonyl oxygen and the 3-position of the isoquinoline ring, exists exclusively in the solid state, and predominates in solution. As expected the 1-alkyl groups (isopropyl, isobutyl, benzyl) are nearly pseudo-axial or axial in all cases. In N-aroyl compounds the larger ortho-aroyl substituent lies syn to the 1-alkyl moiety in nine of the 11 cases, as revealed by X-ray crystallographic studies. In solution NMR results show that atropisomerism about the Ar/CO bond is usually rapid at room temperature, but slow at −50 °C and usually favors the syn isomer. CH⋯π interactions of the 3-methyl protons of 4 with the N-aroyl moieties appear to influence the atropisomerism. [Display omitted]