Triflic Acid Mediated Dealkylative Lactonisation via NMR‐Observable Alkyloxonium Intermediates

Abstract

Trifluoromethanesulfonic acid (TfOH) efficiently induces the dealkylative cyclisation of pent-4-enoates to generate ?-lactones with high selectivity. For primary alkyl esters bearing an additional alkene, only monolactonisation occurs, even in the presence of excess TfOH. The kinetics of the reaction have been studied by 1H NMR spectroscopy, which reveal that the TfOH acid undergoes a self-catalysed reaction with the pent-4-enoate to generate an oxonium triflate intermediate (rate ˜ kobsd.[TfOH]2[ester]1), possibly via the dimer (TfOH)2. The oxonium triflate intermediate then evolves to the ?-lactone according to unimolecular kinetics, liberating MeOTf in an SNi reaction. 2H-labelling experiments with TfOD suggest that the acid protonates the carbonyl moiety of the ester, with subsequent intramolecular delivery of D+ to the alkene. The resulting carbocation is transient, being rapidly captured intramolecularly to generate the oxonium species. Reversibility in this step mediates equilibration of diastereomeric oxonium intermediates via the carbocation

Access to Polycyclic Derivatives by Triflate‐Catalyzed Intramolecular Hydroarylation

“…This dealkylative lactonisation process has already been observed for other examples, [25] and high selectivity was observed for the lactonisation of 4-methylpentenoates via alkyloxonium intermediates, which were observable by NMR spectroscopy. [26] In contrast with the results for 1j-1l, the analogous olefin 1m underwent carbocyclisation to form the fused six-membered ring 2m in yields of 53 and 35 % with the Bi III and In III catalysts, respectively ( Table 4, Entry 4). The lactone 3m was also formed as a byproduct (Bi III ) or as the main product (In III ).…”

Comparison of homogeneous and heterogeneous Ga(III) catalysis in the cycloisomerization of 1,6-enynes

“…Product 5f, already described in Hg(OTf) 2 -catalyzed carbocyclization of 1,6-enynes (47), is presumably formed upon the nucleophilic attack of the double bond on the π-activated triple bond of intermediate A via a 6-exo-dig ring-closure forming intermediate B, featuring a stabilized tertiary carbenium ion. The latter intermediate undergoes in a second step the attack an ester group of the tether leading to intermediate C further converted to D by dealkylation (48)(49)(50). The hydrolysis of one ester followed by an intramolecular hydrocarboxylation could not be discarded, although no hydrolysis product was isolated during this study.…”

Silver‐Free Two‐Component Approach in Gold Catalysis: Activation of [LAuCl] Complexes with Derivatives of Copper, Zinc, Indium, Bismuth, and Other Lewis Acids

“…Although the Au/Cu mixture proved versatile and superior to the Au/Ag system in hydroalkylations of unactivated olefins with β‐dicarbonyls, we noticed a limitation with α‐ketones (Scheme ). Using either [(JohnPhos)AuCl] ( A ) or [(IPr)AuCl] ( C ) and Cu(OTf) 2 as catalytic mixtures with compound 20 gave rise to lactone 21 (full conversion), presumably after retro‐Michael and cyclization of dimethyl 2‐allylmalonate 28. On the other hand, the cyclization of 20 into 22 has been described with a Au/Ag system 24c.…”