Radical enol acetates

The reaction of A -bromosuccinimide with 5a-cholestan-3-one enol acetate in aprotic conditions, described by Green and Long, is probably free radical in character cf. ref. 69). 

Intramolecular coupling reactions between nucleophilic olefins have also proven to hold potential as synthetically useful reactions. The first example of this type of reaction was reported by Shono and coworkers who examined the intramolecular coupling reaction of an enol acetate and a monosubstituted olefin (Scheme 41) [50]. This reaction was conducted in an effort to probe the nature of the radical cation intermediate generated from the anodic oxidation of... 

Electrochemical oxidation of enol acetates in an undivided cell gives monomeric products in parallel with the reactions of simple alkenes [47, 48]. Thus, in the reaction of menthol enol acetate 23, the a-acetoxyketone product arises from nucleophilic attack of acetate ion on the radical-cation while the enone product... 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

The oxidation of enol acetates in acetic acid containing tetraethylammonium p-toluenesulfonate gives four types of compounds (equation 23) conjugated enones (A), a-acetoxycarbonyl compounds (B), geminal diacetoxy compounds (C) and triacetoxy compounds (D). Similar to enol ethers, the Erst reactive intermediates are cation radicals generated from enol acetates by one-electron oxidation. The yields and the distribution of products A, B, C and D depend on the structure of the starting enol acetates and the reaction conditions. ... 

The reactions of enol ester radical cations formed in anodic oxidations were pioneered by Shono [220-225] almost two decades ago. A reaction mode was identified that formally corresponds to that of enol cation radicals. Depending on the electrolysis conditions enol acetates were either converted to a-acetoxy ketones (high concentration of acetate) or to enone products (absence of acetate). Similarly, a-methoxy ketones were obtained through electrolysis in methanol-Et4NOTs. Yields for additional reactions not listed here varied between 29% and 90% [222,223]. 

Mechanistically, it was argued that the products are derived from enol acetate radical cations that are either attacked by nucleophiles (A) or by a base (B) (Scheme 9). 

Since no evidence was provided in support of the above mechanistic proposals there is a priori no reason to exclude mechanism C as an alternative route to the observed products (see also Scheme 5). Interestingly, route C would also readily explain the observed regioselectivity in the oxidative cyclization reaction of enol acetates [221]. Some years later, however, Laurent and coworkers [226,227] demonstrated that in the presence of fluoride (CHjCN/EtsN, 3HF) enol acetate radical cations partially afforded rearrangement products (e.g. 141) not compatible with mechanism C. Rather, the products found suggest that fluoride adds directly to enol acetate radical cations providing the most stable radical intermediate (e.g. 140). 

These results, however, do not imply that mechanism C is impossible in general [228]. Recently, sterically hindered enol acetates, where nucleophilic attack (mech. A) and deprotonation (mech. B) on the radical cation stage are suppressed, were synthesized and studied by cyclic voltammetry as well as by product analysis [229]. Accordingly, enol acetates 146-149 undergo loss of CH3CO upon one-electron oxidation and open up a novel route to a-carbonyl cation chemistry. 150-153 rearrange subsequently to the benzofurans 19-21,23. The C-O bond cleavage reaction in 147 is rather slow (k < 10 s as derived from fast-scan cyclic voltammetry studies. 

This method could be successfully applied for a straightforward synthetic approach to 2,5,7,10-tetraoxabicyclo[4.4.0]decanes [256]. Some direct [257] and indirect [258] evidence has been found supporting attack of water as a nucleophile at the a-carbon, a reaction mode already identified for enol acetate radical cations [226,227], although this may not be general. 

N-Iodosuccinimide reacts with enol acetates derived from ketones to give a-iodoketones, and the reaction has found application in the steroid field/ The iodination of the enol acetates seems to proceed by an ionic mechanism, and preliminary work indicates that N-iodosuccinimide is not capable of at least some of the radical-chain iodinations analogous to radical-chain brominations brought about by N-bromosuccinimide. ... 

Similarly, at a carbon anode in 1 1 MeOH-THF, anodic cyclization of allylsilane enol ether (XCIX) proceeded stereoselectively to give (C) [Eq. (63)]. The use of allyl silanes as the unsaturated nucleophilic component in such radical-cation cyclizations proved to be beneficial, though the exact mechanistic details remain somewhat speculative [147]. The method represents an improvement over earlier methods involving anodic cyclization of alkenyl-substituted enol acetates [148]. 

An extension of this methodology has been developed for epoxides containing an adjacent enol acetate and reaetion sequenees similar to the one described in Scheme 11 are reported [21]. An attractive feature of the overall transformation is the retention of the enol acetate moiety in the product that allows for further synthetic elaboration. It has been demonstrated that epoxide opening ean also be initiated by the intramolecular addition of ketyl radicals formed by electron transfer from Sml2. For an example proeeeding with excellent diastereoselectivity see Seheme 14 [25]. 

When acetylenes are irradiated in aqueous solution [27], in acetic acid [28], or in alcohols [29,30], photoaddition reactions take place to give a ketone, an enol acetate, or an enol ether, respectively. In the photohydration reaction, a hydrated proton attacks the singlet excited state of the acetylene directly [31], On the other hand, alcohols give addition products by attack on the excited states of acetylenes in a radical-like mechanism. Radical photoaddition to acetylenes occurs also with saturated hydrocarbons such as cyclohexane [29], and with cyclic ethers such as tetrahydrofiiran [32], Simple acetylenes are photoreduced on irradiation in hydrocarbon solvents for example photolysis of dec-l-yne or dec-5-yne in pentane gives the corresponding alk-ene (dec-l-ene or trans- and ds-dec-5-enes) [32]. 

Unsaturation and Aromatization Reactions. Unsaturated aldehydes, esters, and lactones can be accessed via strategies involving radical bromination and subsequent elimination. The allylic bromination of unsaturated lactones may be followed by elimination with base to obtain dienoic and trienoic lactones (eqs 11 and 12) Conversion of an aldehyde to the enol acetate allows the radical bromination at the C position to proceed smoothly and, upon ester hydrolysis, the a,/3-unsaturated aldehyde is obtained (eq 13) ... 

The gas-phase pyrolysis of chrysanthanyl acetate affords a mixture of acyclic unsaturated aldehydes and enol acetates, all of which are probably derived from the 1,4-biradical (625). ° Results are also discussed of the pyrolyses of chrysanthanyl alcohol and other emio-pinen-7-ols. The photochemical free radical reaction between P-pinene and t-butyl hypochlorite has been studied, and the oxidative addition of cyclopentanone to p-pinene in the presence of cupric salts has been observed. Photoaddition of iV-nitrosopiperidine to P-pinene at — 40 gave the a-piperidinium... 

In 2014, an intramolecular atom transfer radical cyclisation (ATRC) between a trichloroacetamide and an anisole or enol acetate moiety was applied to the synthesis of highly functionalized 2-azaspiro[4.5]decanes or morphan compounds, respectively, using the second-generation Grubbs catalyst 20. The procedure was further employed to construct the azatricyclic framework of the immunosuppressant FR901483 by the elaboration of its azatricyclic core [eqn (7.15)]. 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

Resolution (enantiomers), 307-309 Resonance, 43-47 acetate ion and, 43 acetone anion and. 45 acyl cations and, 558 allylic carbocations and, 488-489 allylic radical and, 341 arylamines and, 924 benzene and, 44. 521 benzylic carbocation and, 377 benzylic radical and, 578 carbonate ion and. 47 carboxylate ions and, 756-757 enolate ions and, 850 naphthalene and, 532 pentadienyl radical and. 48 phenoxide ions and, 605-606 Resonance effect, 562 Resonance forms, 43... 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

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