Base‐Mediated Reductive Coupling of Indole‐3‐tosylhydrazone with Thiols/Boronic Acids: Facile Synthesis of 3‐(phenylthio)methyl/benzyl Indole Derivatives

Abstract

A transition‐metal free base‐mediated reductive coupling of indole‐3‐tosylhydrazone with thiols/boronic acids to afford biologically important 3‐(phenylthio)methyl/benzyl indole derivatives has been developed. A number of advantages such as low cost, broad substrates scope and operational simplicity make it a potential method for the synthesis of 3‐ phenylthiomethyl/benzyl indole derivatives. Further, six derivatives were selected based on their electronic effects to study the photophysical properties in different solvents. The studied compounds exhibited strong solvatochromic shift and faces solvent dependent polarity in UV‐Visible absorption as well as in fluorescence emission techniques. In addition, one derivative having –CN functionality exhibited most astonishing observation in fluorescence such as significant bathochromic shifting in the emission peak position as well as enhancing the fluorescence quantum yield in CH3CN compared to water.

Recent Update on Alkylation of Indole and Its Derivatives Using N‐Tosylhydrazone

“…The synthesis of 3‐(phenylthio)methyl/benzyl indole substituents 3 have been achieved by Maity and co‐workers through the reductive combination of indole‐3‐tosylhydrazone ( 1 ) and thiols/boronic acids 2 , under transition‐metal free conditions (scheme 1). [25] The highlighted advantages of this protocol involve high product yields (up to 92 % yield), broad substrate scope without interference of C‐2 and N‐1 positions, and without any requirement of diazo substituents and transition metal free reaction conditions. The optimized conditions for the synthesis of 3 and 5 from reaction 1 with 2 and 4 required K‐ t‐ OBu and K 2 CO 3 as the base, respectively, in 1, 4‐dioxane at 100 °C as depicted in Scheme 2.…”

Emerging Trends in N‐Tosylhydrazone Mediated Transition‐Metal‐Free Reactions

“…Recently, an interesting transition‐metal free base concentrated of Indole‐3‐tosylhydrazone 105 and thiols/boronic acid has been developed by khan et al [102] . to construct 3‐benzyl‐ 1H ‐indole 104 and 3‐phenylthiomethyl 106 frameworks.…”

“…Recently, an interesting transition-metal free base concentrated of Indole-3-tosylhydrazone 105 and thiols/boronic acid has been developed by khan et al [102] to construct 3-benzyl-1Hindole 104 and 3-phenylthiomethyl 106 frameworks. This elegant transformation of C 3 -functionalization of indole proceeded via one-pot reaction in presence of K 2 CO 3 base and subsequent reductive coupling using a 1,4-dioxane solvent.…”

Coupling Reactions of Anhydro-Aldose Tosylhydrazones with Boronic Acids

“…These couplings resulted in low to good yields of drug-like molecules, bicyclic products, with a methylene linker between the rings ( Scheme 2 b) [ 25 ]. This type of coupling of indole-3-carbaldehyde tosylhydrazone with boronic acids was used for the synthesis of biologically important 3-benzyl indole derivatives ( Scheme 2 b) [ 26 ]. Ley and coworkers used the procedure for the metal-free coupling of 4-, 5-, and 6-membered saturated heterocyclic p -methoxyphenyl (PMP) sulfonylhydrazones with (het)aryl boronic acids to form sp 2 −sp 3 linked bicyclic building blocks, including oxetanes, piperidines, and azetidines, from their parent ketones ( Scheme 2 c) [ 27 ].…”

“…Molecules 2022, 27, 1795 29 of 31 (26) and (Z)-1,2-Dideoxy-3,4,5,7-Tetra-O-Methoxymethyl-1-Phenyl-D-gluco-Hept-1-Enitol (27) Isolated from a reaction of tosylhydrazone 24 (0.10 g, 0.19 mmol), phenylboronic acid (1.5 equiv., 0.03 g, 0.28 mmol), and K3PO4 (3 equiv., 0.12 g, 0.56 mmol) according to General procedure I by column chromatography (1:6 EtOAc-hexane) to yield 19 mg white amorphous solid containing 26 and 27 in 100:1 ratio. Rf: 0.29 (1:2 EtOAc-hexane), [α]D + 1 (c 0.30, CH2Cl2).…”