Aza-Friedel-Crafts alkylation

As a true testament to the potential long-term impact of H-bonding activation, a number of ureas, thioureas, and acid catalysts are now finding broad application in a large number of classical and modem carbon-carbon bond-forming processes. On one hand, Johnston s chiral amidinium ion 28 was elegantly applied to the asymmetric aza-Henry reactions (Scheme 11.12d). On the other hand, chiral phosphoric acids (e.g., 29 and 30), initially developed by Akiyama and Terada, have been successfully employed in Mannich reactions, hydrophosphonylation reac-tions, aza-Friedel-Crafts alkylations (Scheme 11.12e), and in the first example... 

Uraguchi D, Sorimachi K, Terada M (2004) Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. J Am Chem Soc 126 11804-11805 Uraguchi D, Terada M (2004) Chiral Brpnsted acid-catalyzed direct Mannich reactions via electrophilic activation. J Am Chem Soc 126 5356-5357 Vachal P, Jacobsen EN (2000) Enantioselective catalytic addition of HCN to ketoimines. Catalytic synthesis of quaternary amino acids. Org Lett 2 867-870... 

Terada and co-workers reported the aza-Friedel-Crafts alkylation of furans to aldimines by means of 2 mol% of 21h (Scheme 10.39) [82, 83]. 

SCHEME 5.14 Asymmetric oiganocatalyzed aza-Friedel-Crafts alkylations of phenols, naphthols, and sesamols. 

For selected pioneering examples, see (a) D. Uraguchi, K. Sorimachi, M. Terada, J. Am. Chem. Soc. 2004, 126, 11804-11805. Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. (b) T. Akiyama, H. Morita, J. Itoh, K. Fuchibe, Org. Lett. 2005, 7, 2583-2585. Chiral Br0nsted acid catalyzed enantioselective hydrophosphonylation of imines asymmetric synthesis of a-amino phosphonates. 

A-Sulfinyl aldimines undergo Friedel-Crafts reaction with indoles in up to 99% ee, using a copper(II)-bis(oxazoline) catalyst. An organocatalytic asymmetric aza- 0 Friedel-Crafts alkylation of naphthols with A-sulfonylimines has been developed, giving yields and ees up to 99% 0... 

Scheme 7.56 Performance of 31 in Friedel-Crafts alkylation and aza-ttenry reaction...

In 2009, Cai et al. reported a cascade olefin cross-metathesis/intramolecular Friedel-Crafts alkylation for the construction of polycyclic indoles 133 (Scheme 5.89) [90], A Ru complex (134)/chiral Brpnsted acid [(S)-135] binary system was used in this relay catalysis. Recently, the same group reported an enantioselective intramolecular aza-Michael addition of indoles using a similar binary catalyst system (Scheme 5.90) [91]. 

While its precise role remains unclear, the catalyst 3m is supposed not only to activate the electrophile (26), but also to lower the nucleophilicity of the amide nitrogen atom (Fig. 5). The latter interaction may account for a chemoselective Friedel-Crafts-type alkylation versus an aza-Darzens reaction. 

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