Copper-Catalyzed Synthesis of Indol-3-yl α-(Difluoromethyl)-α-(trifluoromethyl)carbinols: Construction of Difluoromethylated sp³ Carbon Centers

Abstract

An efficient copper-catalyzed synthesis of indol-3-yl α-(difluoromethyl)-α-(trifluoromethyl)carbinols is developed. The reaction proceeds in good to excellent yields through a Friedel-Crafts-type mechanism, and a variety of indoles with commonly occurring functional groups such as formyl, cyano, nitro, alkyloxide, and halogen are well tolerated. In addition, these carbinol products are readily transformed into diversified difluoromethylated dinitrile indol-3-yl derivatives. This strategy provides a general synthetic method for ready construction of difluoromethylated sp carbon centers.

Regioselective C3-Fluoroalcoholation of Indoles with Heptafluoroisopropyl Iodide via Palladium-Catalyzed C(sp2)–C(sp3) Cross-Coupling in the Presence of O2

“…11a,18 Reduction of 4a using Cs 2 CO 3 in the solvent CH 3 CN gave product 5f in 87% yield. 18 Fipronil analogue 5g was achieved with moderate to good yield under mild conditions. 19 We turned our attention to the plausible pathway for the C3 regioselective C−H hexafluoroisopropanolization of N-unprotected indoles.…”

“…Treatment of product 4a with 2 equiv of acetic anhydride and 0.65 equiv of NaOAc afforded corresponding product 5a in 56% yield . The straightforward deprotonation of 4a by NaHMDS (1 mol/mL) was trapped by the acid chloride ( 5b ) . Adding K 2 CO 3 at room temperature, 4a can react with different equivalents of benzyl bromide to produce mono- or di-substituted products ( 5c – 5e ). , Reduction of 4a using Cs 2 CO 3 in the solvent CH 3 CN gave product 5f in 87% yield .…”

Delivering 2-Aryl Benzoxazoles through Metal-Free and Redox-Neutral De-CF3 Process

“…The deprotonation of 1 by base generated intermediate I , which is a reversible process. The intermediate I then underwent an aromatization driven β-carbon elimination process ,, to deliver 2 and CF 3 – . The latter was further protonated to yield CF 3 H.…”

The ortho‐Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect

“…In agreement with our expectation, none of the desired products ( 4 ab – ae ) were obtained from the reactions . Furthermore, as shown in Equation (2), we considered the substitution on the Ph group in 2 a , including the electron‐donating groups nBu ( 2 f ) and OMe ( 2 g ) and electron‐withdrawing group CF 3 [ 2 h ; note that 2 h can be readily prepared from HFIP (hexafluoroisopropanol)] . 2 h furnished trace amounts of the desired product under the standard reaction conditions.…”