- Unified synthesis of quinone sesquiterpenes based on a radical decarboxylation and quinone addition reaction
-
A unified synthesis of several quinone sesquiterpenes is described herein. Essential to this strategy is a novel radical addition reaction that permits the attachment of a fully substituted bicyclic core 16 to a variably substituted quinone 10. The addition product 15 can be further functionalized, giving access to natural products with a high degree of oxygenation at the quinone unit. The quinone addition reaction is characterized by excellent chemoselectivity, taking place only at conjugated and unsubstituted double bonds, and regioselectivity, being strongly influenced by the resonance effect of heteroatoms located on the quinone ring. These features were successfully applied to the synthesis of avarol (1), avarone (2), methoxyavarones (4, 5), ilimaquinone (6), and smenospongidine (7), thereby demonstating the synthetic value of this new method.
- Ling, Taotao,Poupon, Erwan,Rueden, Erik J.,Kim, Sun H.,Theodorakis, Emmanuel A.
-
p. 12261 - 12267
(2007/10/03)
-
- Synthesis of (-)-ilimaquinone via a radical decarboxylation and quinone addition reaction.
-
[reaction: see text] A stereoselective synthesis of (-)-ilimaquinone (4) is presented. The synthetic strategy is based on a novel radical decarboxylation and quinone addition methodology that produces quinone 7 from reaction of thiohydroxamic acid derivat
- Ling, Taotao,Poupon, Erwan,Rueden, Erik J,Theodorakis, Emmanuel A
-
p. 819 - 822
(2007/10/03)
-
- The invention of radical reactions. Part 39. The reaction of white phosphorus with carbon-centered radicals. An improved procedure for the synthesis of phosphonic acids and further mechanistic insights
-
White phosphorus in tetrahydrofuran under argon reacts in a long radical chain reaction with carbon radicals derived from Barton PTOC esters. The reaction is initiated by traces of oxygen and strongly inhibited by TEMPO. From the duration of the induction period the chain length can be measured as approximately one million. Each P4 molecule can add up to two carbon radicals. Oxidation of the adducts provides a convenient synthesis of phosphonic acids in high yield. With H2O2 at 0°C oxidation to the appropriate phosphinic acids is fast. For sensitive natural products the further transformation to phosphonic acids is best carried out at room temperature with an excess of SO2. In this way even linoleic acid can be convened to the corresponding phosphonic acid in good yield without any attack on the skipped diene unit. TEMPO is also remarkable for its stabilization of white phosphorus in solution when exposed to oxygen. Likewise an ordinary phosphine, like tributyl phosphine, is also stabilized by small amounts of TEMPO.
- Barton, Derek H. R.,Vonder Embse, Richard A.
-
p. 12475 - 12496
(2007/10/03)
-
- N-hydroxypyridine-2(1H)-thione derivatives of carboxylic acids as activated esters. Part II. Applications in peptide synthesis
-
The N-hydroxypyridine-2(1H)-thione derivatives of two urethane-protected α-amino acids readily reacted with the α-amino acid esters or the corresponding benzenesulfenamides to give simple dipeptides in reasonable yields. The benzenesulfenamides are the re
- Barton, Derek H. R.,Ferreira, J. Albert
-
p. 9367 - 9386
(2007/10/03)
-
- The invention of radical reactions. Part XXXVII. A convenient radical synthesis of dialkyl diselenides from carboxylic acids
-
A new and convenient synthesis of dialkyl diselenides from carboxylic acids by Barton PTOC ester based radical chemistry is described. This method was especially successful when O-cholestan-3β-yl-2,2,2-trichloroselenoacetate and O-neopentyl selenobenzoate
- Barton, Derek H. R.,Fontana, Giovanni
-
p. 11163 - 11176
(2007/10/03)
-
- N-hydroxypyridine-2(1H)-thione derivatives of carboxylic acids as activated esters. Part I. The synthesis of carboxamides
-
The reaction between an acyl derivative of N-hydroxypyridine-2(1H)- thione (a Barton PTOC ester) and either an amine (primary or secondary), or the corresponding sulfenamide, led to the formation of a carboxamide in a clean transformation requiring minimal work-up and purification. The reaction with a sulfenamide is particularly useful since the only by-product, an unsymmetrical disulfide, is of both synthetic and biological value. In sterically demanding cases, Barton PTOC esters were more reactive towards benzenesulfenamides than to the corresponding free amines.
- Barton, Derek H. R.,Ferreira, J. Albert
-
p. 9347 - 9366
(2007/10/03)
-
- The Invention of Radical Reactions. XXXIII Homologation Reactions of Carboxylic Acids by Radical Chain Chemistry
-
Various carbon radicals can be generated from carboxylic acids via the corresponding Barton esters.These radicals can be used for the synthesis of longer chain homologues of the original acids.
- Barton, Derek H. R.,Chern, Ching-Yuh,Jaszberenyi, Joseph Cs.
-
p. 407 - 426
(2007/10/02)
-
- A facile preparation method for α,α-difluoroalkanecarboxylic acids and esters. A formal difluoromethylene insertion to alkanecarboxylic acids using radical reaction
-
Various alkyl radicals generated by the photoreaction of a series of Barton esters reacted with 1,1-dichloro-2,2-difluoroethene to give radical adducts as the major product accompanied with self-trapping products. Primary, secondary, tertiary, benzyl, and some unsaturated alkyl radicals as well as those with another functional group such as ether, carbonyl, and azide were applicable. Barton esters of diacids also afford 1:2 adducts with a small amount of 1:1 adducts and bis-self-trapping products except for the succinic case. These adducts were hydrolyzed with AgNO3/H2O-THF to α,α-difluoroalkanecarboxylic acids and methanolyzed with AgNO3/MeOH to the corresponding methyl esters. 4-Azido-2,2-difluorobutylic acid and the methyl ester were converted to difluoro-GABA and difluoro-γ-lactams.
- Okano, Takashi,Takakura, Nobuyuki,Nakano, Yuko,Okajima, Asako,Eguchi, Shoji
-
p. 1903 - 1920
(2007/10/02)
-
- Use of 2,3-Bis(phenylsulfonyl)-1-propene as a Multicoupling Reagent
-
2,3-Bis(phenylsulfonyl)-1-propene (1) reacts with various amines to afford products derived from addition across the double bond as well as SN2' displacement.When treated with 2-piperidinemethanol, bissulfone 1 gave the expected SN2'
- Padwa, Albert,Kline, Donald N.,Murphree, S. Shaun,Yeske, Philip E.
-
p. 298 - 306
(2007/10/02)
-
- The invention of radical reactions. Part XXV. A convenient method for the synthesis of the acyl derivatives of N-hydroxypyridine-2-thione
-
Treatment of the readily available di-N-oxide - of 2-thiopyridine disulfide 6 with tributylphosphine in the presence of a carboxylic acid provides a convenient and high yielding synthesis of the acyl derivatives 2 of N-hydroxy-2-thio-pyridone. Application of this procedure to the acids 17 and 18 gave, after irradiation in the presence of t-butylthill, the desired decarboxylated derivatives in high (>90%) yield.
- Barton,Samadi
-
p. 7083 - 7090
(2007/10/02)
-
- Homologation of carboxylic acids by improved methods based on radical chain chemistry of acyl derivatives of N-hydroxy-2-thiopyridone
-
Reaction of substituted terminal olefins with carbon radicals generated carboxylic acids gives adducts that can be transformed to one carbon atom longer homo-acids in high overall yield. With 6b yields are very good and the conditions of hydrolysis exceptionally mild.
- Barton, Derek H. R.,Chern, Ching-Yuh,Jaszberenyi, Joseph Cs.
-
p. 5013 - 5016
(2007/10/02)
-
- Decarboxylative radical addition to vinylsulphones and vinylphosphonium bromide: Some further novel transformations of geminal (pyridine-2-thiyl) phenylsulphones
-
Irradiation of O-acyl derivatives 1 of N-hydroxy-2-thiopyridone with visible light in the presence of phenyl vinyl sulphone or vinyl triphenylphosphonium bromide leads to the corresponding adducts 8 and 9 which can undergo a wide variety of further transformations.
- Barton,Boivin,Crepon nee da Silva,Sarma,Togo,Zard
-
p. 7091 - 7108
(2007/10/02)
-
- THE INVENTION OF RADICAL REACTIONS PART XVIII. A CONVENIENT SOLUTION TO THE 1-CARBON PROBLEM (R-CO2H --> R-13CO2H)
-
Radicals generated by photolysis (W light) of esters derived from N-hydroxy-2-thiopyridone react with electrophilic isocyanides 2a and (in the presence of trifluoroacetic acid) 2b to give adducts of type 3.Convenient reaction procedures have been worked out to hydrolyse the adducts to amides of type 5, from which the original acid can be regenerated under mild conditions.The three important acids oleic, linoleic and arachidonic have all given smooth reactions.In suitable examples, quantitative evolution of carbon dioxide and incorporation of 13C without dilution have been demonstrated.This reaction sequence will be useful for the labelling in the carboxyl group of prostaglandins, leukotrienes, and the side chain carboxyls of peptides.
- Barton, Derek H. R.,Ozbalik, Nubar,Vacher, Bernard
-
p. 3501 - 3512
(2007/10/02)
-
- AN UNUSUAL REACTION BETWEEN THE ESTERS OF N-HYDROXY-2-THIOPYRIDONE AND ACTIVATED AZO COMPOUNDS
-
The esters 1 of N-hydroxy-2-thiopyridone react smoothly at room temperature in a thermal reaction with diethyl azo-dicarboxylic ester to furnish adducts 2 of a novel structure.Photolysis of these adducts affords a convenient route to the little known tetrazanes 8.Azo compounds without electron withdrawing groups do not react.The Cookson reagent, however, is so reactive that it gives diacyl derivatives of type 14.
- Barton, Derek H. R.,Ozbalik, Nubar,Vacher, Bernard
-
p. 7385 - 7392
(2007/10/02)
-
- THE INVENTION OF NEW RADICAL CHAIN REACTIONS. PART XIII. HIGH YIELDING DECARBOXYLATIVE CHALCOGENATION OF ALIPHATIC AND ALICYCLIC ACIDS
-
Irradiation with a tungsten lamp of mixed anhydrides (e.g. 8) derived from aliphatic or alicyclic carboxylic acids and N-hydroxy-2-pyridine thione 3 in the presence of a disulphide, diselenide or ditelluride gives the corresponding chalcogenide (e.g. 9, 10, or 11) in high yield.The process involves a radical decarboxylation followed by SH2 reaction of the intermediate carbon radical on the dichalcogenide.
- Barton, Derek H.R.,Bridon, Dominique,Zard, Samir Z.
-
p. 449 - 462
(2007/10/02)
-
- THE INVENTION OF RADICAL CHAIN REACTIONS. PART XIV. A DECARBOXILATIVE RADICAL ADDITION TO QUINONES
-
Irradiation of esters 3 derived from aliphatic or alicyclic carboxylic acids and N-hydroxy-2-thiopyridone in the presence of various quinones gives high yields of the corresponding adducts (e.g. 9) with net loss of carbon dioxide.
- Barton, Derek H. R.,Bridon, Dominique,Zard, Samir Z.
-
p. 5307 - 5314
(2007/10/02)
-
- The Invention of New Radical Chain Reactions. Part 9. Further Radical Chemistry of Thiohydroxamic Esters; Formation of Carbon-Carbon Bonds
-
Carbon radicals derived from the esters of several types of thiohydroxamic acids have been trapped in a number of different ways.Particular attention has been paid to carbon-carbon bond formation by addition to suitably activated ethylenic linkages.Carboxylic acids can be conveniently converted into homo- and bishomo-acids by free radical chemistry based on thiohydroxamic esters.In a coda the tautomerism of the thiohydroxamic acids have been examined by physical methods.It is confirmed that the esters used are derivatives of the thione tautomer.
- Barton, Derek H.R.,Crich, David,Kretzschmar, Gerhard
-
-
- THE INVENTION OF NEW RADICAL CHAIN REACTIONS. PART X. HIGH YIELD RADICAL ADDITION REACTIONS OF αβ-UNSATURATED NITROOLEFINS. AN EXPEDIENT CONSTRUCTION OF THE 25-HYDROXY-VITAMIN D3 SIDE CHAIN FROM BILE ACIDS.
-
Radicals derived from thiohydroxamic esters 3 readily add to nitroolefins 5 (Z=NO2) to give good yields of α-nitrosulphides.These adducts, where the structure permits, are easily oxidised to carboxylic acids 8 by treatment with alkaline hydrogen peroxide.Reductive cleavage to the corresponding aldehydes or ketones 9 is efficiently carried out by the action of TiCl3.Addition of methyl magnesium iodide to methyl ketone derived from 3α-acetoxy 11-oxo cholanic acid gives steroid 10 possessing the 25-hydroxycholesterol side chain of the vitamin D3 metabolites.Radical additions to 1-phenylthio-2-nitropropene 11 have been briefly studied.
- Barton, Derek H.R.,Togo, Hideo,Zard, Samir Z.
-
p. 5507 - 5516
(2007/10/02)
-