Catalytic Asymmetric Friedel-Crafts Alkylations 1st ..
In this communication, we report an asymmetric Friedel−Crafts reaction of indoles with imines catalyzed by a bifunctional cinchona alkaloid catalyst. This is the first efficient organocatalytic asymmetric Friedel−Crafts reaction of indoles with imines. This reaction is operationally simple and, unprecedentedly, affords high enantioselectivity for a wide range of indoles and both aryl and alkyl imines. This establishes a direct, convergent, and versatile approach to optically active 3-indolyl methanamines, a structural motif embedded in numerous indole alkaloids and synthetic indole derivatives.
catalytic asymmetric Friedel-Crafts alkylations ..
Yi-Xia Jia, , Yun Yang, Qi-Lin Zhou*, Asymmetric Friedel-Crafts alkylations of indoles with nitroalkenes catalyzed by Zn(II)-bisoxazoline complexes, J.
Over the intervening years many other Lewis acids including BF3, BeCl2, TiCl4, SbCl5 or SnCl4 have been described as catalysts for the FC alkylation. Furthermore, strong Brønsted-acids including sulfuric acid, hydrofluoric acid or super acids such as HF•SbF5 and HSO3F•SbF5 have also been shown to accelerate this transformation. Despite the great importance of the Friedel–Crafts alkylation for organic synthesis it has major drawbacks since stoichiometric or super stoichiometric amounts of a Lewis acid or Brønsted acid and toxic alkyl halides have to be utilized leading to vast amounts of salt side products. With the need for more environmentally and economically benign processes, the development of FC reactions using only catalytic amounts of a metal or acid catalyst would be highly desirable. In addition, the substitution of the alkyl chlorides by other, less toxic, alkylating reagents such as alcohols would be a major improvement as water would be the only side product. Beyond this, the use of activated double bonds and styrenes would be even more efficient as no side products are to be expected. However, good ideas always need time to develop and grow and thus it is not surprising that it took more than 100 years from the initial invention of Friedel and Crafts in 1887 until the first catalytic FC alkylations with alcohols and styrenes as alkylating reagents were developed. Initial attempts in 1996 using Sc(OTf)3 and soon after with Mo(CO)6 as Lewis acid catalysts were consequently followed by a multitude of new methods employing a variety of Lewis- and Brønsted acids with decreasing catalyst loadings and in consequence increasing efficiencies ().