Sc(OTf)₃-Catalyzed Synthesis of Symmetrical Dithioacetals and Bisarylmethanes Using Nitromethane as a Methylene Source

Abstract

Use of nitromethane as an electrophilic methylene source for the synthesis of symmetrical dithioacetals and bisarylmethanes has been showcased using Sc­(OTf)3 as a catalyst. The procedure allows straightforward access to the densely functionalized dithioacetals and bisarylmethanes under mild conditions. Additionally, the method has been applied for the synthesis of antimalarial tetramethyl mellotojaponin C and anticancer dimeric phloroglucinol derivative.

Highly Selective and Catalytic C–N Bond Cleavage of Tertiary Sulfonamides: Scope and Mechanistic Insight

“…Bis­(3,4-dimethoxy-phenyl)­methane ( 8a ): 45% yield; brown thick oil; 1 H NMR (CDCl 3 , 400 MHz): δ 9.84 (s, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.41­(s, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.79 (d, J = 8.0 Hz, 8H), 6.70 (d, J = 10.4 Hz, 1H), 3.96 (s, 3H), 3.93 (s, 3H), 3.87 (s, 8H), 3.84 (s, 24H), 3.82 (s, 24H); 13 C NMR (CDCl 3 , 100 MHz): δ 149.0 (2C). 147.4 (2C), 134.0 (2C), 120.8 (2C), 112.2 (2C), 111.3 (2C), 56.0 (2C), 55.9 (2C), 41.1; HRMS (ESI) + calcd for C 17 H 21 O 4 , 289.1440 m / z (M + H) + ; found, 289.1433 m / z.…”

Lewis Acid-Promoted Typical Friedel–Crafts Reactions Using DMSO as a Carbon Source

“…21,21 The title compound was prepared following GP2 using 1,3,5-trimethoxybenzene (1.0 mmol, 168 mg), 2-methylfuran (1.0 mmol, 89 μL), TMSOTf (0.5 mmol, 92.5 μL), and DMSO (0.5 mL): yield 144 mg (55%); pale white solid; R f = 0.6 (SiO 2 , 8:2 hexane/EtOAc); 1 H NMR (500 MHz, CDCl 3 ) δ 6.17 (m, 2H), 5.79 (s, 1H), 5.62 (s, 1H), 3.89 (s, 2H), 3.82 (s, 3H), 3.80 (m, 2H), 2.25 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 157. 8,157.0,151.8,147.6,105.4,103.8,102.9,88.7,53.8,53.3,27.7,11.6. 2,4,aniline (4g).…”

“…21 The title compound was prepared following GP2 using 2,6-dimethylphenol (1.0 mmol, 122 mg), anisole (1.0 mmol, 108 μL), TMSOTf (0.5 mmol, 92.5 μL), and DMSO (0.5 mL): yield 140 mg (58%); pale white solid; R f = 0.6 (SiO 2 , 8:2 hexane/EtOAc); 1 H NMR (500 MHz, CDCl 3 ) δ 6.17 (m, 2H), 5.79 (s, 1H), 5.62 (s, 1H), 3.89 (s, 2H), 3.82 (s, 3H), 3.80 (m, 2H), 2.25 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 156. 8,149.4,133.0,132.2,128.7,127.96,122.0,112.8,54.3,39.2,. 21 The title compound was prepared following GP2 using 2,6-dimethylphenol (1.0 mmol, 122 mg), 1,3-dimethoxybenzene (1.0 mmol, 131 μL), TMSOTf (0.5 mmol, 92.5 μL), and DMSO (0.5 mL): yield 146 mg (54%); pale white solid; R f = 0.6 (SiO 2 , 8:2 hexane/EtOAc); 1 H NMR (500 MHz, CDCl 3 ) δ 6.72 (m, 2H), 6.38 (m, 2H) .…”

“…In addition, using benzyl azides as the C 1 source, Tummatorn and co-workers reported the synthesis of diarylmethanes. Recently, Dherange and co-workers developed an elegant protocol for the synthesis of diarylmethanes using Sc­(OTf) 3 as a catalyst and nitromethane as a methylene source. Subsequently, employing polyethylene glycol (PEG-400) as a methylene spacer, Adimurthy et al reported a metal-free reaction protocol for the synthesis of diarylmethanes (Scheme ).…”

Site‐Selective 1,4‐Difunctionalization of Nitrogen Heteroaromatics for Constructing Vinylidene Heterocycles

“…Methyl and methylene compounds with electronwithdrawing groups, e. g., acetophenone, nitromethane, and 1,3-dicarbonyl compounds, are commonly used as nucleophilic coupling reagents in organic reactions such as Henry, Michael addition, and cross dehydrogenation coupling reactions. [11] Vinyl-substituted heterocycles, because of their C=C double-bond structure, which has unique reactivity and structural modification potential, are widely used in pharmaceutically active molecules and materials. [12] We therefore hoped to achieve vinylidene functionalization of quinoline Nheterocycles in one pot by using active methyl/methylene compounds and alkyl bromides.…”