Rh(III)-Catalyzed [3 + 2] Annulation via C–H Activation: Direct Access to Trifluoromethyl-Substituted Indenamines and Aminoindanes

Abstract

The rhodium(III)-catalyzed direct C−H addition and annulation of benzimidates and aldimines with β-(trifluoromethyl)-α,β-unsaturated ketones is described. This protocol provides the facile and efficient formation of various trifluoromethyl-containing indenamines or aminoindanes in moderate to high yields.I ndenes and indanes are very important carbocyclic derivatives that are found in various natural products and pharmaceutically active molecules. 1 Moreover, they find application in organometallics and material science. 2 In particular, aminoindene/indane derivatives have shown important biological activities, 3 such as glutamate receptor antagonist, calcium antagonist, and anti-Parkinson. In addition, trifluoromethyl-containing indane acts as a selective CB2 ligand (Figure 1). 4

Rhodium‐Catalyzed Cascade Annulation of Benzimidates and Nitroalkenes for the Synthesis of Difunctionalized Indenes

“…On the basis of the preliminary mechanistic studies and previous literature reports, a plausible reaction mechanism is proposed as outlined in Scheme . Initially, the active catalyst Cp*Rh(AdCOO) 2 A is generated through ligand exchange between [Cp*RhCl 2 ] 2 and AdCOOK, which underwent coordination with 1 a and C−H metallation process to form rhodacycle complex B with the loss of AdCOOH.…”

Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

“…Thus, looking into this aspect and in continuation of their exploration of directing group assisted coupling with β-CF 3 -substituted enones, Sharma and coworkers reported the first synthesis of trifluoromethyl-containing 1 H -indene-3-amines 299 with the help of Rh( iii ) catalysis that involved [3 + 2] C–H annulation between benzimidates 298 and 283 in good to high yields. 203 In addition, the coupling reaction was also found to be applicable for aldimines that produced trifluoromethylated amino indanes in moderate yields. Since degradation of aldimine was observed in ethyl acetate, DCE was used as a solvent in the case of aldimines.…”

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

“…The feasibility of aldimines 140 as a coupling partner was also studied to give the desired amino-trifluoromethylated indanes 141 as shown in scheme 41. [86] In continuation of their work, Sharma et al very recently, reported an efficient method to synthesize 3trifluoromethylindanone 145 derivatives through coupling of N-methoxybenzamides 142 with β-CF 3 -enones 3 via Rh(III)-catalysis. [87] As indanones are naturally occurring and valuable scaffolds for various applications, [88] the modification of the indanone core with substituting trifluoromethyl may lead to a pharmaceutically potential candidate.…”

“…To incorporate the trifluoromethyl group in aminoindane scaffold, recently Sharma and coworkers reported the first synthesis of the 1‐(trifluoromethyl)‐1 H ‐inden‐3‐amine scaffolds 139 using Rh(III)‐catalysed [3+2] C−H annulation reaction of benzimidates 138 with β ‐(trifluoromethyl)‐ α , β ‐unsaturated ketones 3 . The feasibility of aldimines 140 as a coupling partner was also studied to give the desired amino‐trifluoromethylated indanes 141 as shown in scheme 41 [86] …”