Synthesis of 3-alkyl spiro[4,5]trienones by copper-catalyzed oxidative ipso-annulation of activated alkynes with unactivated alkanes

Abstract

A Cu-catalyzed oxidative ipso-annulation of activated alkynes with unactivated alkanes for the synthesis of 3-alkyl spiro[4,5]trienones is described. This method allows the formation of two carbon-carbon bonds and one carbon-oxygen bond in a single reaction through a sequence of C-H oxidative coupling, ipso-carbocyclization and dearomatization.

The Persistent Radical Effect in Organic Synthesis

“…[59] Furthermore,m ore complex cascades were developed along those lines. [60,61] Another beautiful sequence taking advantage of the PRE with peroxyl radicals as in situ generated scavengers is shown in Figure 14 a. Thee sters and amides 44 derived from propiolic acid derivatives and anilines or phenols were used as radical acceptors.I nt he first step,at ransient radical generated by ar edox reaction adds regioselectively to the CÀCt riple bond of 44 to give av inyl radical 45.I ts ipso cyclization onto the arene of the aniline or phenol moiety leads to cyclohexadienyl radical 46,w hich is trapped by tertbutylperoxyl to give peroxide 47,which can undergo aK ornblum-DeLaMare rearrangement [62] to finally provide ketone 48.T his sequence was successfully conducted with various radicals RC using different radical precursors.A lkyl radicals derived from ethers, [63] ketones, [64] or alkanes, [65] acyl radicals from aldehydes, [66] CF 3 radicals from the Langlois reagent, [67] SCF 3 radicals from AgSCF 3 , [68] silyl radicals from silanes, [69] and sulfonyl radicals from sulfonylhydrazides engage in this spirocyclization cascade. [70] Recently,t he groups of Wu and Zhong presented an oxidative cyclization of ethylene-bridged aminoindoles 48 to afford peroxypyrroloindolines 49 with t-BuOOH as the oxidant in combination with TBAI ( Figure 14 b).…”

“…a) Radical spirocyclization with the tert-butylperoxyl radical as atrapping reagent. [63][64][65][66][67][68][69][70] b) Oxidative indole functionalization to access peroxypyrroloindolenines 49. [71] Figure 15.…”

Der “Persistent Radical Effect” in der organischen Chemie

“…Diese Sequenz wurde mit einer Vielzahl verschiedener Radikale RC durchgeführt. In dieser spiro-Cyclisierung wurden Alkyl-Radikale von Ethern, [63] Ketonen [64] bzw.A lkanen, [65] Acyl-Radikale von Aldehyden, [66] CF 3 -Radikale vom Langlois-Reagenz, [67] SCF 3 -Radikale vom AgSCF 3 , [68] Silyl-Radikale von Silanen [69] und Sulfonyl-Radikale von Sulfonylhydraziden [70] eingesetzt.…”

Copper‐Catalyzed Alkylarylation of Unactivated Alkenes: Synthesis of 3‐Alkyl Indolines from N‐Allyl Anilines and Alkanes

“…[3] CÀHf unctionalization is considered an ideal process in terms of step-anda tom-economy, and in this regard, directf unctionalization of inert alkanic CÀH bonds remains as ignificant challenge due to their intrinsic low acidity and high bond-dissociation energy. [4] Nonetheless,s ignificant progress has been made recently towards C(sp 3 )ÀH functionalization of simple alkanes with arenes, [5] heteroarenes, [6] CO, [7] carbenes, [8] alkynes, [9] isonitriles, [10] heteroatoms, [11] activateda liphatic carbons, [12] or activated olefins, [13][14][15] etc. [16] In sharp contrast, coupling/addition of simple alkanes across unactivated alkenes is rarely reported( Scheme 1a), [17] probably because of polarity mismatching.…”

“…[18,19] Unactivated alkyl radicals are weakly nucleophilic, and they tend to reactw ith electrondeficients pecies. [5][6][7][8][9][10][11][12][13][14] 16] Dehydrogenativec oupling of simple alkanes with nucleophiless uch as unactivated alkenes is far more difficult. Aryl [17a] /alkynyl migration [17b] or ac yclization process [17c] could facilitate such ap olarity-mismatched reaction, and an elegant anti-Markovnikov hydroalkylation of unactivat-Scheme1.Literature examplesa nd this work.[a] Prof.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.…”