Lactonization Thiophenol

Radical cyclization is compatible with the presence of other functional groups. Treatment of XCH2CON(R)-C(R )=CH2 derivatives (X = Cl, Br, 1) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization. " Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam, " and there are other examples of radical cyclization with molecules containing a lactam unit " or an amide unit. Radical cyclization occurs with enamines as well. Photochemical irradiation of A,A-dialIyl acrylamide leads to formation of a lactam ring, and in this case thiophenol was added to generate the phenylthio derivative. Phenylseleno N-allylamines lead to cyclic amines. co-Iodo acrylate esters cyclize to form lactones. " ... 

Accordingly, under different conditions, DMC is used as a methylating reagent for a variety of substrates phenols, thiols, thiophenols, aromatic amines, arylace-tonitriles, arylacetoesters, aroxyacetonitriles, aroxyacetoesters, alkylarylsulfones, benzylarylsulfones, and lactones, either under CF or in batch conditions. 

It is not surprising that in attempted AICI3 catalysis of the reaction between thiophenol and various lactones, considerable amounts of thianthrene were obtained from a side reaction (81JOC5163). A low yield of thianthrene itself was obtained by converting o-bromobenzene thiol into its copper derivative (66JOC4071), but a good yield of thianthrene-2,3,7,8-tetracarboxylic acid 83 was observed from a hot reaction between 84 with cuprous oxide in DMF (82MI5). The saturated o-chlorobenzene thiols, 85... 

Hi) Sulfur, selenium and tellurium nucleophiles Cleavage of spirooxiranes (e.g. 59) by thiophenol is a key step in a new route to trans-fused y-lactones (Scheme 50) (81TL279). 

Thiols and thiophenols generally react readily with 0-lactones at C-4 to give excellent yields of 3-alkylmercapto- or 3-arylmercapto-propionic acid (equation 54). For example,... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Stereoselective anti addition of thiophenol to lV-[p-(n-butyl)methacryloyl]-10,2-camphorsultam [the key step in a synthesis of (+)-trans whiskey lactone] has been explained by a sulfur-induced, stereoelectronically directed protonation following C(P)-re face conjugate addition. ... 

Aminothiophenol is cyclized by reaction with prop-2-ynyltriphenylphos-phonium bromide, but some 2-substituted anilines give the phosphonium salt (a possible intermediate in the thiophenol reaction) which may be cyclized separately (see Chapter 16, Section I.S) [2736]. Reaction of thiophenols with the lactonic 2-oxazolin-S-ones can give any one of three products in acetic acid-sodium acetate, cyclization to the thiazole occurs while in some other solvents, acylamino and acylthio products are formed, and may be cyclized by acetic acid-sodium acetate [3088]. 

Michael addition of lithium thiophenolate to the enaminone 697 followed by treatment with mercuric acetate gives the hydroxy lactone 698. N-Methylation followed by base treatment and phenylselenyl chloride provides the azocinone derivative 699, which has been elaborated on to the alkaloid Otonecine 700, Scheme 194 (83TL5731). 

Ort/io-selectivity is generally observed in the reactions of 2,4-dichloro- and 2,4-difluoro-nitrobenzene with alkoxide and thiophenoxide ions [199]. Also in less activated systems, nucleophiles generated from phenols and thiophenols with potassium fluoride-alumina and 18-crown-6-polyether will react in DMSO with cyano- or nitro-substituted fluoro- or chloro-benzenes [200]. Interestingly, the reaction of difluorobenzenes with two diffoent alcohols can occur sequentially. Introduction of the first etho" function deactivates the ring, and use of more forcing conditions allows substitution of the second fluorine [201]. Consecutive displacements of fluorine and nitro groups have been observed in the reaction of ort/io-fluoronitrobenzene with chiral acyl bicyclic lactones in a highly enantioselective synthesis of spirooxindoles [202]. 

Alkanethiols undergo acid-catalysed anti-Markovnikov additions to diketen to give lactones (53), in contrast to thiophenol which adds in a Markovnikov manner. Lactones (53) are converted to y-alkylthiocrotonates on warming with an alcohol. 

Two alternative routes to (+)-swainsonine (ent-37S) developed by Chen and Tsai, Hke that used in their synthesis of lentiginosine (c Scheme 47 Section 3.3.2), created the bond to C-8a by means of free radical cycUzations onto an acylsilane. The first approach entailed the creation of the C-l/C-8a bond (Scheme 86). Amide formation between the amine 638 and the acid chloride prepared in situ from the chiral lactone-acid 639 yielded (—)-640, which was cyclized with base to the imide (—)-641 in 91% yield. Chemoselective reduction of the C-2 carbonyl group, acid-catalyzed reaction with thiophenol, and protection of the hydroxyl substituent as the benzoate gave 642 as a mixture of isomers. After hydrolysis of the dithiane to the acylsilane 643 with iodobenzene bis(trifluoroacetate), treatment with tri-butyltin hydride and l,lCazobis(cyclohexane-l-carbonitrile) (ACCN) as radical initiator produced the indohzidin-5-one 644 in 86% yield as a... 

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