Effects of Brønsted acid cocatalysts on the activities and selectivities of charge‐enhanced thiourea organocatalysts in Friedel–Crafts and oxa‐Pictet–Spengler reactions

Abstract

Charge-enhanced chiral thioureas were used in the organocatalysis of the Friedel-Crafts alkylation of indole with trans-β-nitrostyrene and the oxa-Pictet-Spengler reaction of tryptophol and benzaldehyde. The effects of substoichiometric Brønsted acidic additives on the reaction conversions and enantiomeric ratios of these transformations were examined, and the role of these species in the mechanism of the latter reaction was explored using variable time normalization kinetics to elucidate the reaction order of the catalyst, cocatalyst, and reagents. A proposed pathway for the oxa-Pictet-Spengler cyclization that involves matched and mismatched catalyst and cocatalyst pairs and an off-cycle racemization of the latter species is provided.

Anion-Activated Bases and Nucleophiles Characterized by Photoelectron Spectroscopy

“…Electric fields can impact bond energies and a wide range of chemical transformations. − One general application that has been explored over the past decade is the incorporation of a positively charged substituent into a neutral Brønsted acid so as to enhance its acidity and catalytic abilities. − Conversely, one would expect that a negatively charged substituent can be used to increase the basicity and nucleophilicity of a noncharged Brønsted base since a positive charge builds up at the basic or nucleophilic site. Given the tremendous importance of bases and nucleophiles in biological and industrial processes including the synthesis of pharmaceutical and agrochemicals, − we decided to investigate these species.…”

Mechanism of a Dually Catalyzed Enantioselective Oxa-Pictet–Spengler Reaction and the Development of a Stereodivergent Variant

“…Oxa-Pictet–Spengler reactions represent an attractive method for accessing various cyclic ethers including isochromans and tetrahydropyrano­[3,4- b ]­indoles, compounds of significant interest in synthetic and medicinal chemistry . Although the first oxa-Pictet–Spengler reaction was published already in 1935, progress in developing catalytic enantioselective variants has been slow and remains limited to relatively few examples . In contrast, many variants of catalytic enantioselective Pictet–Spengler reactions have been developed .…”