Maria Luisa Navacchia

A Study of Vinyl Radical Cyclization onto the Azido Group by Addition of Sulfanyl, Stannyl, and Silyl Radicals to Alkynyl Azides☆

Thermal radical reactions of azidoalkynes 2, 8, 14, and 21a–c with thiols 1a–c afford 2-sulfanylvinyl radicals by selective addition of sulfanyl radicals to the triple bond. 1-Phenylvinyl radicals 23 and 30a, as well as vinyl radical 30b, undergo fast 5-cyclization onto the aromatic azide function to give cyclized indoles. In contrast, both 1-phenyl (15, 17) and 1-alkyl (3a,b, 9) vinyl radicals fail to add to their aliphatic azido substituents and exclusively undergo cyclization onto the aromatic sulfanyl ring and H transfer from the thiol precursor. Azidoalkynes 14 and 21a react with Bu3SnH and TMSS under radical conditions to give instead the corresponding amines as a result of preferential attack of Bu3Sn · and (TMS)3Si · radicals on the azido group rather than on the triple bond. Evidence is provided that alkyl radical cyclizations onto azides are not feasible in the presence of thiol, in contrast with the reported utility of these cyclization reactions in the presence of Bu3SnH and TMSS.

Thiol radical addition to alkynes. Sulfanyl radical addition and hydrogen atom abstraction relative reaction rates

Abstract 2-(Toluenesulfanyl)- 1 and 2-(benzenesulfanyl)-phenylacetylene 10 reacted with benzenethiol and toluenethiol, respectively, in the presence of AIBN at 84 and 154 °C to give products deriving from vinyl radicals 2 which undergo hydrogen abstraction reaction and 5- ortho and 5- exo cyclization onto both the adjacent phenyl rings in competition with the β-fragmentation. Definitive evidence has been obtained that alkanesulfanyl radical addition to the alkyne triple bond is a non-reversible process, whereas arenesulfanyl radicals add in a reversible mode. Competing experiments involving several alkynes towards benzenethiol and benzeneethanethiol radical addition have been performed in order to determine the relative rate constants of the sulfanyl radical addition to the alkyne triple bond (k 1 ) and the hydrogen abstraction reaction by the resulting vinyl radicals (k H ). The k 1 values are mainly determined by the vinyl radical stabilization provided by the C-(α) vinyl radical substituent, whereas the k H values seem to be mainly determined by polarity factors. An unexpected different behavior between α-propyl and α-long-chain substituents is discussed in terms of different hybridization of the vinyl radical.

Synthesis of 5-Acetoxy-2(5H)-Furanones through Manganese(III)-Promoted Functionalization of Arylacetylenes

Abstract Reaction of phenylacetylenes 1a – e with manganese(III) triacetate in acetic acid/acetic anhydride at reflux gave the corresponding 5-acetoxy-5-phenyl-2(5 H )-furanones 2a – e in good yield (40–86%). Furanones 2 were derived from further oxidation of the initially formed 5-phenyl-2(3 H )-furanones 4 which were in turn obtained through regioselective addition of carboxymethyl radicals to the alkyne 1 triple bond and subsequent oxidative cyclization of the resulting α-phenylvinyl radical 3 . In contrast, the (trimethylsilyl)alkylacetylene 1f gave the corresponding furanone 2f in only 25% yield, whereas alkylacetylenes 1g – h totally failed to give the corresponding furanones 2f – h , probably due to the incapability of the α-alkyl vinyl radical intermediates 3g – h of undergoing oxidative cyclization.

Attempts at vinyl radical carbonylation through cyclization onto carbonyl and cyano groups

Abstract Sulfanylvinyl radicals 4–6, 16, produced from toluenesulfanyl radical addition to alkynes 1–3, 15, gave only products arising from cyclization onto the thiophenyl ring and H-abstraction. No products were obtained deriving from possible 5-membered cyclization onto the esteric or thioesteric carbonyl group. Similar results were obtained from toluenesulfanyl radical addition to alkynyl nitriles 20 and 24, which did not provided any evidence for 5- or 6-membered vinyl radical cyclization onto the aliphatic cyano group. In contrast, both toluenesulfanyl- and benzenesulfanyl- vinyl radicals 32 and 37a smoothly cyclize onto the aromatic cyano group leading to ketones 35 and 39. This protocol represents a novel indirect radical carbonylation and provides a useful synthetic approach to indenones.

REARRANGEMENTS AND CYCLIZATIONS IN VINYL RADICALS. UNUSUAL EXAMPLE OF 1,4-RADICAL TRANSLOCATION

Vinyl radical 5 undergoes 5-exo cyclization onto the CC double bond in competition with the 5-exo cyclization onto the aryl ring. In addition, radical 5 exhibits an unusual 1,4-radical translocation/β-fragmentation process. In contrast, radical 4 exclusively undergoes 5-exo cyclization onto the benzene ring. This latter reaction leads to spiro radical intermediates which can either give the 1,4-aryl migration products or can be trapped by 2-cyano-iso-propyl radicals.

Sulfanyl radical mediated cyclization of aminyl radicals

Abstract 1-(2-Aminopheny)pent-1-yne 1 reacted with benzenethiol at 150 °C under radical conditions to give the thiol alkyne adduct 2 , the benzothiophene 4 and the indole 5 . Reaction of 1 with benzenesulfanyl radicals produced from diphenyl disulfine in the absence of hydrogen donors gave only the indole 5 in high yields. Formation of indole 5 was explained in terms of sulfanyl radical mediated aminyl radical cyclization onto the alkyne triple bond.

Sulfanyl radical addition to alkynyl azides: an insight into vinyl radical cyclization onto the azido function

Abstract 5- Exo -Cyclization of 2-sulfanylvinyl radicals 16 and 21 is a fast process which prevents intramolecular addition to the sulfanyl aromatic ring and hydrogen abstraction. In contrast, the 2-sulfanylvinyl radicals 3 and 9 are reluctant to add to their aliphatic azido substituent either in a π -( endo ) or in a π -( exo ) mode. These radicals exclusively undergo cyclization onto the adjacent aromatic ring and H-transfer from the thiol present.

Excess electron transfer in G-quadruplex

The excess electron transfer in a G-quadruplex is successfully probed by using the reaction of hydrated electrons with quadruplex complex of pentamers and the 8-bromoguanine moieties as the detection system.

2-Cyano-iso-propyl radical addition to alkynes

Abstract The thermolysis of azobis iso butyronitrile (AIBN) in benzene in the presence of various mono- and di-substituted acetylenes has been investigated in order to ascertain the chemical reactivity of transient 2-cyano- iso propyl radical (CPR) towards carbon-carbon triple bonds. Results show that this rather sluggish and bulky carbon centered radical successfully adds in a regioselective fashion to alkynes bearing an electron acceptor phenyl, methoxycarbonyl and trimethylsilyl substituent, but fails with alkylacetylenes and those sterically hindered. The produced vinyl radicals undergo H-abstraction reaction, alkyne addition, aromatic addition and intramolecular cyclization in a relative proportion strongly dependent upon the nature of both 1- and 2-substituent. Two unprecedented examples of 4- exo and 6- exo vinyl radical cyclization onto the cyano triple bond are reported.

THIOL MEDIATED 5-(π-ENDO)ORTHO VINYL RADICAL CYCLIZATIONS

Abstract The radical reaction of benzenethiol with alkynes 1a-o carried out at 154 °C affords a mixture of thiol/alkyne adduct 3 and benzothiophene 5, deriving from vinyl radical intermediates 2 through hydrogen abstraction and 5-(π-endo)orthocyclization onto the adjacent thiophenyl ring, respectively. This latter reaction occurs through the reversible formation of cyclohexadienyl radical intermediates 4 which can evolve to 5 to an extent largely depending on the reaction conditions employed. The 5-ortho cyclization is governed both by stereoelectronic factors, which favor the cyclization of p-centered, linear α-arylvinyl radicals 2a-f, and polar factors, which favor the cyclization of α-EWG substituted vinyl radicals 2c,n,o.