Photochemically catalyzed cyclizations and intramolecular [2+2] cycloadditions of allenes

[ M. Jovanović]

159 str.

Hemija - Organska hemija / Chemistry - Organic Chemistry

U okviru ove doktorske disertacije razvijene su nove sintetičke metodologije zasnovane na fotohemijski katalizovanim transformacijama alena. Istraživanje je podeljeno u dva dela. U prvom delu razvijena je blaga metoda za aktivaciju C(sp²)–I i C(sp³)–I veza pri čemu nastali alkil/vinil/aril radikal ciklizuje na alenski fragment. U reakciji se koristi [Ir(ppy)₂(dtbbpy)]PF₆ (1 mol%) kao fotokatalizator, DIPEA-u kao aditiv i plava svetlost (λ = 465 nm), pri čemu nastaju ciklizacioni proizvodi u prinosima od 23% do 78%. Mehanizam se odvija putem jednoelektronskog transfera (SET), gde se inicijalno redukuje C–I veza, nakon čega sledi intramolekulska adicija na alenski fragment. Reakcija je regioselektivna, i odvija se isključivo na proksimalnoj dvostrukoj vezi alena, i pokazuje visoku dijastereoselektivnost (do 95:5 u korist trans-proizvoda) kod hiralnih supstrata. Kao proizvodi u reakciji nastaju, 3-vinil indoli i 3-vinil pirolidini. Metodologija je takođe uspešno primenjena i za formiranje šestočlanih prstenova. U drugom delu doktorske disertacije razvijena je blaga metoda za intramolekulsku [2+2] cikloadiciju enalenilamida u prisustvu plave svetlosti (λ = 465 nm) uz upotrebu Ir(ppy)₃ kao fotokatalizatora. Reakcija otpočinje procesom transfera energije (EnT), kojim se selektivno aktivira dvostruka veza cimetamidnog fragmenta koja potom selektivno napada distalnu dvostruku vezu alena formirajući isključivo trans-biciklo[4.2.0]oktanske derivate. Reakcija se odvija pod blagim uslovima i predstavlja komplementaran pristup postojećim termičkim metodama, uz znatno bolje prinse. Ustanovljeno je da supstituenti na aromatičnom prstenu značajno utiču na prinos reakcije, pa tako supstrati sa elektron-donorskim grupama daju bolje prinose (60–88%) u poređenju sa supstratima sa elektron-privlačnim grupama (39–50%). Mehanizam reakcije dodatno je potkrepljen kompjuterskim modelovanjem i analizom ključnih intermedijernih stanja korišćenjem teorije funkcionala gustine (DFT - Density functional theory).

Within this doctoral dissertation, novel synthetic methodologies based on photochemically catalyzed transformations of allenes have been developed. The research is divided into two parts. In the first part, a mild method for the activation of C(sp²)–I and C(sp³)–I bonds was developed, leading to the formation of alkyl/vinyl/aryl radicals that cyclize onto the allene fragment. The reaction employs [Ir(ppy)₂(dtbbpy)]PF₆ (1 mol%) as a photocatalyst, DIPEA as an additive, and blue light (λ = 465 nm), yielding cyclized products in 23% to 78% yields. The mechanism proceeds via a single electron transfer (SET) process, where the C–I bond is initially reduced, followed by intramolecular addition to the allene fragment. The reaction is regioselective, occurring exclusively at the proximal double bond of the allene, and exhibits high diastereoselectivity (up to 95:5 in favor of the trans product) for chiral substrates. The products formed include 3-vinyl indoles and 3-vinyl pyrrolidines. The methodology was also successfully applied to the formation of six-membered rings. In the second part of the dissertation, a mild method for the intramolecular [2+2] cycloaddition of enallenylamides was developed under blue light irradiation (λ = 465 nm) using Ir(ppy)₃ as a photocatalyst. The reaction starts with an energy transfer (EnT) process where the double double bond of the cinnamamide fragment is selectively activated. The formed intermediate then attacks the distal double bond of the allene, exclusively forming trans-bicyclo[4.2.0]octane derivatives. The reaction proceeds under mild conditions and represents a complementary approach to existing thermal methods, with significantly improved yields. It was found that substituents on the aromatic ring significantly influence the reaction yields, with substrates bearing electron-donating groups affording higher yields (60–88%) compared to those with electron-withdrawing groups (39–50%). The reaction mechanism was further supported by computational modeling and analysis of key intermediate states using density functional theory (DFT).

fotohemija, aleni, radikalska ciklizacija, [2+2] cikloadicija, iridijum, dijastereoselektivnost, jednoelektronski transfer, transfer energije

photochemistry, allenes, radical cyclization, [2+2] cycloaddition, iridium, diastereoselectivity, single-electron transfer, energy transfer

544.52:66.095.5(043.3)

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