Synthesis of 1-Indanols and 1-Indanamines by Intramolecular Palladium(0)-Catalyzed C(sp3)H Arylation: Impact of Conformational Effects

• Published in: Chemistry : a European journal Vol. 20; no. 35; pp. 11084 - 11090
• Main Authors: Janody, Simon, Jazzar, Rodolphe, Comte, Arnaud, Holstein, Philipp M., Vors, Jean-Pierre, Ford, Mark J., Baudoin, Olivier
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 25.08.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Chemistry; Chemistry, Multidisciplinary; conformation analysis; Conformational analysis; Correlation; CC coupling; CH activation; palladium; Physical Sciences; Science & Technology; Strain; Synthesis; X-rays; C-C coupling; FUNCTIONALIZATION; conformation analysis; C-H activation; MECHANISM; SILYL ENOL ETHERS; HYDROXYLATION; palladium; ALKANE ARYLATION; BOND; ACCESS; CH activation; CC coupling
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201402907

A range of valuable 1‐indanols and 1‐indanamines containing a tertiary C1 atom were synthesized by intramolecular palladium(0)‐catalyzed C(sp3)H arylation, despite unfavorable steric interactions. The efficiency of the reaction was found to correlate with the degree of substitution at C2, as expected from the Thorpe–Ingold effect. Additionally, the nature of the heteroatomic substituent at C1 had a marked influence on the diastereoselectivity at C1 and C2; indeed, 1‐indanols and 1‐indanamines were obtained with the opposite relative configuration. Analysis of the X‐ray and DFT‐optimized structures of the corresponding reactive intermediates provided useful insights into the subtle conformational effects induced by these substituents. Overcoming strain: A range of valuable 1‐indanols and 1‐indanamines containing a tertiary C1 atom were synthesized by intramolecular palladium(0)‐catalyzed C(sp3)H arylation (see scheme; PivOK=potassium pivalate). Reactivity and diastereoselectivity differences among the different substrates can be rationalized by conformational analysis.