Catalytic Asymmetric Intramolecular Hydroarylations of ω‐Aryloxy‐ and Arylamino‐Tethered α,β‐Unsaturated Aldehydes

Abstract

Economical approach: The first organocatalytic asymmetric intramolecular hydroarylation of phenol- and aniline-derived enals offers one of the most straightforward and atom-economic approaches to enantioriched chromans and tetrahydroquinolines (up to 96% ee; see scheme).

Asymmetric Organocatalysis

“…When a, b-unsaturated ketones were exploited, a primary-secondary diamine 62 was able to catalyze the transformation with excellent results [73]. Xiao and co-workers have shown two successful examples of asymmetric intramolecular Friedel-Crafts reaction (Scheme 19) [74,75]. The intramolecular ringclosing Friedel-Crafts-type alkylation of indolyl a,b-unsaturated aldehydes provided an enantioselective synthesis of tetrahydropyrano [3,4-b]indoles (THPIs) and tetrahydro-b-carbolines (THBCs) in the presence of a MacMillan catalyst [74].…”

“…The intramolecular ringclosing Friedel-Crafts-type alkylation of indolyl a,b-unsaturated aldehydes provided an enantioselective synthesis of tetrahydropyrano [3,4-b]indoles (THPIs) and tetrahydro-b-carbolines (THBCs) in the presence of a MacMillan catalyst [74]. The other intramolecular hydroarylations of w-aryloxy-and arylamino-tethered a,b-unsaturated aldehydes enabled a straightforward access to optically active functional chromans and tetrahydroquinolines [75].…”

Catalytic, Enantioselective, Intramolecular Sulfenoamination of Alkenes with Anilines

“…Finally, for disconnection (4), Lu and co-workers reported an enantioselective Friedel–Crafts alkylation using a prolinol silyl ether catalyst. 8 …”

Asymmetric Construction of Polycyclic Indoles through Olefin Cross‐Metathesis/Intramolecular Friedel–Crafts Alkylation under Sequential Catalysis

“…In general, electron-rich indolyl enones ( Table 2, entries 2 and 3) were more reactive than electron-deficient substrates ( Table 2, entries [4][5][6]. Excellent yields and enantioselectivities were observed for aryl indolyl enones with a variety of aryl groups (97-99 % yield, 96-98 % ee; Table 2, entries [8][9][10][11]. Single-crystal X-ray analysis of enantiomerically pure 2 d revealed the absolute configuration to be R. [12,13] Following the success of the asymmetric intramolecular Friedel-Crafts alkylation, we investigated the sequential catalysis of olefin cross-metathesis and asymmetric Friedel-Crafts alkylation.…”

“…[7] Despite considerable efforts devoted to asymmetric intramolecular Friedel-Crafts-type Michael addition reactions, there are few successful examples. [8] Most notably, the tedious procedure for the preparation of substrates for the intramolecular Friedel-Crafts reaction limits its synthetic applications.…”