Direct C–H Alpha Arylation of Enones with ArI(O2CR)2 Reagents

Abstract

Herein, we report the metal-free direct C–H arylation of enones mediated by hypervalent iodine reagents. The reaction proceeds via a reductive iodonium Claisen rearrangement of <i>in situ </i>b-pyridinium silyl enol ethers. The aryl groups are derived from ArI(O<sub>2</sub>CCF<sub>3</sub>)<sub>2</sub> reagents, which are readily accessed from the parent iodoarenes. It is tolerant of a wide range of substitution patterns and the incorporated arenes maintain the valuable iodine functional handle. Mechanistic investigations implicate arylation via an umpoled “enolonium” species and that the presence of a b-pyridinium moiety is critical for desired C–C bond formation.

Electrochemical strategies for C–H functionalization and C–N bond formation

“…Synthetic applications of these versatile reagents include, for example, aminations, C-C bond-forming reaction manifolds, halogenations, oxidations, rearrangements, and various dual catalytic activation modes. [962][963][964][965][966][967][968][969] In this context, hypervalent iodine species electrochemically generated from the corresponding iodoarenes have been applied for the synthesis of various heterocyclic frameworks, such as carbazoles 970 (Scheme 127), pyrroloindoles, 971 quinolinone derivatives 972 (Scheme 128) and spirocycles (Scheme 129). 973,974 The utility of electrochemically generated hypervalent iodine reagents has also been demonstrated in the synthesis of glycozoline 970 and tetrahydropyrroloiminoquinone alkaloids.…”

Diaryliodonium Salt-Based Synthesis of N-Alkoxyindolines and Further Insights into the Ishikawa Indole Synthesis

“…1 H HMR spectra were recorded at 400 or 500 MHz with tetramethylsilane as an internal standard on a JEOL JNM-ECS400 (400 MHz), JEOL JNM-ECZ400 (400 MHz), or JEOL JNM-ECA500 (500 MHz) spectrometer unless otherwise noted. 13 C{ 1 H} NMR spectra were recorded at 100 or 125 MHz. High-resolution mass spectra (HRMS) were measured by the electrospray ionization (ESI) mode (TOF analyzer) on a Waters LCT Premier XE spectrometer.…”

“…The residue was purified by column chromatography on silica gel (EtOAc/hexane, 1:19−1:2) to provide 1.39 g (quant.) of S2a as a white solid: TLC R f 0.74 (EtOAc/ hexane, 1:6); IR (neat) 1584, 1515, 1335, 846, 831, 694 cm −1 ; 1 H NMR (500 MHz, CDCl 3 ) δ 8.07 (d, 1H, J = 8.0 Hz), 7.52 (d, 1H, J = 8.0 Hz), 7.52 (s, 1H), 7.21 (s, 2H), 7.07 (s, 1H), 2.69 (s, 3H), 2.40 (s, 6H); 13 2-(1-Nitronaphthalen-2-yl)ethan-1-ol (S3a).…”

“…The combined extracts were washed with saturated brine (50 mL), dried, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/hexane, 1:10) to provide 6.44 g (78%) of 2a as a colorless oil: TLC R f 0.46 (EtOAc/hexane, 1:10); IR (neat) 3356, 2957, 2926, 1464, 1377, 1217, 1045, 757, 667 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.42 (dd, 1H, J = 6.8, 0.9 Hz), 7.30−7.24 (m, 2H), 7.19 (td, 1H, J = 7.2, 2.0 Hz), 3.83 (q, 2H, J = 6.8 Hz), 2.87 (t, 2H, J = 6.8 Hz), 1.54−1.44 (m, 6H), 1.39−1.29 (m, 6H), 1.16−0.99 (m, 6H), 0.89 (t, 9H, J = 7.2 Hz); 13 (11 mL) was added n-BuLi (2.69 M solution in hexane, 4.10 mL, 11.0 mmol). The mixture was stirred at −78 °C for 0.5 h, and n-Bu 3 SnCl (1.75 mL, 6.45 mmol) was added.…”

Organocatalytic Group Transfer Reactions with Hypervalent Iodine­ Reagents

“…Despite having downhill thermodynamics, many of the reactions with hypervalent iodine group transfer reagents require catalysis to facilitate their progress or to steer them toward the formation of the desired products. In the majority of cases metal catalysts have been used for this purpose, 5,6 which to some extent mitigates the above-mentioned environmental and economic benefits provided by the hypervalent iodine compounds. However, in recent years reports of the application of organocatalysts to promote reactions with hypervalent iodine reagents has begun to emerge.…”