Direct synthesis of 8-aryl tetrahydroquinolines via pd-catalyzed ortho-arylation of arylureas in water

Abstract

An efficient protocol for the direct synthesis of 8-arylated tetrahydroquinolines via Pd-catalyzed ortho-arylation of aryl ureas with aryl iodides was developed. The reaction proceeded smoothly in water under ligand-free and surfactant-free conditions, providing the desired products in high yields with remarkable functional group tolerance.

Progress in the Chemistry of Tetrahydroquinolines

“…Fan and co-workers developed a Pd-catalyzed ortho-arylation of tetrahydroquinoline derivatives 1568 that allowed the synthesis of the corresponding 8-aryl derivatives 1570 (Scheme 423). 643 Thus, the aryl iodides 1569 underwent ready orthoarylation with aryl ureas 1568 in water, in the presence of Pd(OTs) 2 (MeCN) 2 as catalyst and under ligand-free conditions, to yield compounds 1570 in high yields, with remarkable functional group tolerance.…”

Transition-Metal-Catalyzed Directed C8–H Carbon–Carbon Bond Formation in Quinolines and 1,2,3,4-Tetrahydroquinolines

“…Further, an amide DG guided Pd-catalyzed C-H arylation with aryl iodides has been achieved at the C8-position of THQs (Scheme 19D). 61 The reaction in water under mild reaction conditions 62 works well with ample functional groups. Further, the arylation of the enantiomerically pure THQs can be achieved with retaining the stereoselectivity.…”

The ortho effect in directed C–H activation

“…We also indicate if literature precedents are available for such C-H functionalisation regardless of the incoming substituent. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] In fact literature examples have not been found any of the substrates predicted to be unreactive. We have also considered bis-functionalisations when equivalent ortho-positions and sites are available.…”

“…Similar to the aromatic NH amides, methyl phenylcarbamate (16), tert-butyl phenylcarbamate (17) and N,Ndimethyl-N 0 H-N 0 -phenylurea (18) feature coplanar structures and zero torsional energy which suggest mild reaction conditions and a possible twofold C-H activation, which are supported by experimental results. [30][31][32] However, the presence of an N-methyl group in N,N-dimethyl-N 0 -methyl-N 0 -phenylurea (19) 33 induces structural distortion and a larger DG 0 rot implying a slower reaction. Hence, we propose an elevated reaction temperature.…”