Iron(III)‐Catalyzed 1,3‐Functional Group Transposition Reactions: Synthetic Protocol to Access 3‐Substituted Indoles

Abstract

An iron(III)-catalyzed 1,3-dihydroisobenzofuran transferring reaction of indoles provides ap ractical synthetic protocol to access 3-substitutedi ndolesu nder mild conditions. This is the first example of a1 ,3-functional group transposition of a N-protected indole to give a3 -substituted indole derivative in good yield. Ap lausible mechanism has been proposed on the basis of deuterium-labeling and control experiments. Furthermore, after as imple oxidation, the obtained product could be easily transformed into 3-phthalide indole, ad rug candidate for treating Alzheimer'sd isease.The indole core is av ery common structuralm otif found in natural products and medicines.[1] Research on the indole alkaloids' biological activities and investigations into indole'sr eactivities have been carriedo ut extensively.[2] The natural products or drugs bearingi ndole cores often have remarkable bioactivities. For example, bioactivity studies showed that dragmacidin (Scheme 1) is at ype of serine/threonine protein phosphatase inhibitor that hasa nti-herpesvirus and anti-HIV effects; indomethacin has been used as aN SAID( nonsteroidal anti-inflammatory drug) for more than fifty years; citrinalin B,atype of prenylated indole alkaloid, had its total synthesis reported recently, [1h] which may help develop ad ifferent approacht o synthesize quinineo rm orphine derivatives. Some other indole-containing compounds have been applied as neuroprotection, anti-cancer compounds, antibiotics, etc.[3] With regard to indole'sr eactivity,i ti sw ell known that the 3-position of indole has the richest electron density and that this carbon site can act as the nucleophile to allow 3-substituted indole derivatives to undergo Friedel-Crafts-type reactions.To the best of our knowledge, the synthesis of 3-substituted indoles has always been as ignificantly demanding task for organic chemists working in indole chemistry.[4] As shown in Scheme 2, the previous methods to achieve this goal include simple Friedel-Crafts-type substitution, transition-metal-catalyzed CÀHb ond activation or cross-coupling, including crossdehydrogenative couplingb yu sing the nucleophilic nature of the 3-position of the indole (Scheme 2). However, 1,3-functionScheme1.Reported indole-based structures for drugs and natural products.Scheme2.Reported methodsfor the synthesis of 3-substituted indoles.

Arylative Ring Expansion of 3‐Vinylazetidin‐3‐Ols and 3‐Vinyloxetan‐3‐Ols to Dihydrofurans by Dual Palladium and Acid Catalysis

“…Hydrogenation of the double bond from the face opposite to the one occupied by the C2‐phenyl substituent followed by hydrogenolysis of the benzylic C−O bond could account for the observed high diastereoselectivity. Oxidation of 4 a with Oxone and KBr furnished 5‐hydroxyfuran‐2(5 H )‐one 15 , [29] while radical‐based dehydrogenation (PhSH, AIBN) afforded furan 16 [30] . Mannich reaction of 4 a with formaldehyde under acidic conditions afforded a tricyclic tetrahydrobenzofuroazepine 17 [31] .…”

Tunable Reaction Mode of Bifunctional Peroxides with Ketones to Access α-Oxacyclic Ketones and Enals

“…However, due to the lower p K a of α-protons in these peroxides and the stronger basicity of KO t Bu, the latter rearrangement pathway should be favorable. Upon release of the aldehyde 59 , the waiting enolate would immediately react with such a reactive intermediate and subsequently cyclize with the allylic bromide to generate the five-membered dihydrofuran product 16 . Alternatively, under Condition A (Scheme , right pathway), an excessive amount of enolate was formed in the solution when premixing 3.0 equiv of ketone and 3.0 equiv of KO t Bu first.…”