Iodine(III)‐Promoted Ring Expansion Reactions: A Metal‐Free Approach toward Seven‐Membered Heterocyclic Rings

Abstract

A metal‐free approach for the synthesis of seven‐membered heterocycles (chromane, thiochromane) or rings fused with heterocycles (furan, indole, pyrrole, and thiophene) is described. The salient feature of the strategy is based on the ring expansion of methylenic heterocycles mediated by the iodine(III) reagent HTIB (PhI(OH)OTs) in aqueous acetonitrile.

Reactivity and Stability of (Hetero)Benzylic Alkenes via the Wittig Olefination Reaction

“…During our study of heterocyclic ring expansion reactions using hypervalent iodine, we observed that some of the substrates prepared via Wittig olefination were easily isolated. However, some ketones were decomposed during the work-up process or obtained in very low yields upon exposure to the Wittig reaction [ 23 , 24 ]. To investigate the reason, we decided to observe the decomposition behavior of the expected alkenes via a series of heterocyclic substrates.…”

“…After the unsuccessful isolation of the expected olefinic product for 4n, our subsequent goal was to capture the intermediate (olefinic product) before decomposition in the work-up process. Our strategy was to generate the resulting methylene product but using a minimal amount of Wittig reagent (1.2 equiv) with the aim of minimizing any complexation in the subsequent step, where the reaction mixture was directly exposed (without work-up and isolation process) to an iodine(III) reagent (Hydroxy(tosyloxy)iodobenzene (HTIB) dissolved in CH3CN:H2O (9:1 v/v)), with the potential to induce rearrangement and incorporate the exo-methylenic carbon into the ring (Scheme 5) [23]. After the study of protected (EWG) indole derivatives, we extended our investigation to pyridine derivatives (such as isoquinolinones) to determine the stability of the resulting methylene products.…”

“…Yield: 66% (0.139 g, 0.66 mmol). Sample appearance: Brown solid Milting Point: 207 4-Methylene-9-tosyl-2,3,4,9-tetrahydro-1H-carbazole (5f) [23].…”

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review

“…Khan et al reacted ketone 78 with potassium tert -butoxide, Ph 3 PCH 3 Br and diethyl ether, which resulted in the synthesis of chromane intermediate 79 . The synthesized chromane was then treated with HTIB catalyst in the presence of acetonitrile and water as solvent to synthesize seven-membered heterocycle 80 in a good yield ( Scheme 24 ) [ 54 ].…”

Iodine(III)-Mediated Ring-Contraction Reactions Using Halogenated and Non-halogenated Solvents

“…[18][19][20] HTIB has garnered significant interest among researchers because of its economic viability and commercial availability. [21][22][23] The conversion process from 1,2-dihydronaphthalene (1) derivatives into the corresponding indane derivatives using HTIB is highly efficient and straightforward. 2 In our previous work, we utilized 1,2-dihydronaphthalene derivatives as substrates with HTIB to achieve ring-contracted products (indanes) with different functionalities.…”