Borane-catalyzed cascade Friedel–Crafts alkylation/[1,5]-hydride transfer/Mannich cyclization to afford tetrahydroquinolines

An unprecedented redox-neutral annulation reaction of tertiary anilines with electron-deficient alkynes was developed that proceeds through a cascade Friedel–Crafts alkylation/[1,5]-hydride transfer/Mannich cyclization sequence. Under B(C6F5)3 catalysis, a range of functionalized 1,2,3,4-tetrahydroquinolines were facilely constructed in moderate to good yields with exclusive 3,4-anti-stereochemistry. The commercial availability of the catalyst and the high atom and step economy of the procedure, together with metal-free and external oxidant-free conditions, make this an attractive method in organic synthesis.


Crossover experiment
To a Schlenk tube equipped with a dried stir bar was added B(C 6 F 5 ) 3

Kinetic isotope effect
To a Schlenk tube equipped with a dried stir bar was added B(C 6 F 5 ) 3

Role of TMSOTf
Additive TMSOTf was found to be able to improve the reaction efficiency. We have tried to use other acid as catalyst or additive, such as Lambert salt or Brookhart's acid. However, they produced no desired product when used alone. When they were used in combination with B(C 6 F 5 ) 3 , diminished yields of 3a and 4a were observed.

S29
We surmised that TMSOTf could coordinate with B(C 6 F 5 ) 3 to increase the Lewis acidity (Int S1). However, 19 F NMR measurement of 1:1 ratio of TMSOTf and B(C 6 F 5 ) 3 showed no obvious change in chemical shift and implied this hypothesis is likely not operative. Alternatively, we hypothesized that TMSOTf may coordinate with substrate 2a (e.g., through the ester moiety) to further increase its electrophilicity (Int S2).

X-Ray crystallography data
Thermal ellipsoids are drawn on 50% probability level The single-crystal diffraction data were collected on a Rigaku XtaLAB synergy four-circle diffractometer with Cu-Kα radiation (λ=1.54184Å), with the CrysAlisPro software (version 1.171.39.34b) for data reduction and analysis. The crystal was kept at 100 K during data collection. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimisation. All non-hydrogen atoms were refined with anisotropic displacement parameters. All hydrogen atoms were generated geometrically.

Thermal ellipsoids are drawn on 50% probability level
The single-crystal diffraction data were collected on a Rigaku XtaLAB synergy four-circle diffractometer with Cu-Kα radiation (λ=1.54184Å), with the CrysAlisPro software (version 1.171.39.34b) for data reduction and analysis. The crystal was kept at 100 K during data collection. Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimisation. All non-hydrogen atoms were refined with anisotropic displacement parameters. All hydrogen atoms were generated geometrically.