A novel aromatic carbocation-based coupling reagent for esterification and amidation reactions

Abstract

A novel tropylium-based coupling reagent has been developed to facilitate the synthesis of a series of esters, amides, lactones and peptides under mild reaction conditions. Remarkably, this reagent can be used in catalytic amounts in conjunction with a sacrificial reagent, offering a new and efficient method for nucleophilic coupling reactions of carboxylic acids.

Hydroxytropylium chloride: the first crystal structure of an unfunctionalized hydroxytropylium ion

“…In this article, we report the crystal structure of hydroxytropylium chloride, (I), which we obtained serendipitously in our structural studies of halotropylium halides (Jandl et al, 2017). Halotropylium halides are relevant as precursors to carbocyclic carbene complexes and chlorotropylium chloride, in particular, has recently found application as a halogenating agent and activator in Swern-type oxidations (Ö fele et al, 2009;Nguyen & Bekensir, 2014;Nguyen & Hall, 2014;Nguyen & Lyons, 2015). The formation of hydroxytropylium chloride from chlorotropylium chloride also provides an insight into the decomposition pathways of halotropylium halides.…”

Recent Advances in the Synthesis of Carboxylic Acid Esters

“…Photo-irradiated procedure in the presence of PPh 3 with a catalytic amount of flavin and azo compound under O 2 was developed [35]. XtalFluor-E and tropylium-based coupling reagents were found to be effective for the esterification [36,37].…”

Promotion of Organic Reactions by Non‐Benzenoid Carbocyclic Aromatic Ions

“…Upon realizing the potential of tropylium salts in esterification and amidation reactions of carboxylic acids, [23] our group further investigated the application of chlorotropylium chloride (41)a sareagent to couple carboxylic acids. [25] This aromatic cation system effected coupling reactions between several carboxylic acids 51 and alcohol/phenol/amine substrates 52 under mild conditions to facilitate the synthesis of ar ange of esters,a mides,l actones,a nd oligopeptides (53, Scheme 7) via intermediates 54-56. [25] Aliphatic acids were the most reactive substrates,w hile benzoic acids showed the least reactivity.The difference in reactivity is presumably due to the decreased nucleophilicity of the conjugated carboxylic groups,w hich makes them less reactive towards tropylium chloride 41.T he conjugated system can also stabilize the tropyl/tropylium ester intermediates 54/55,thereby rendering them less vulnerable to nucleophilic attack by the chloride anion.…”

“…[25] This aromatic cation system effected coupling reactions between several carboxylic acids 51 and alcohol/phenol/amine substrates 52 under mild conditions to facilitate the synthesis of ar ange of esters,a mides,l actones,a nd oligopeptides (53, Scheme 7) via intermediates 54-56. [25] Aliphatic acids were the most reactive substrates,w hile benzoic acids showed the least reactivity.The difference in reactivity is presumably due to the decreased nucleophilicity of the conjugated carboxylic groups,w hich makes them less reactive towards tropylium chloride 41.T he conjugated system can also stabilize the tropyl/tropylium ester intermediates 54/55,thereby rendering them less vulnerable to nucleophilic attack by the chloride anion. Interestingly,t his coupling method also allowed protected oligopeptides to be obtained in good yields from amino acids with low levels of racemization.…”