Radicophiles

Apparently, the dimerization of 4 is considerably more facile than that of MCP or BCP, resembling those of (dichloromethylene)cyclopropane (455) and radicophilic olefins with a capto-dative substitution pattern [125], some of which are known to cyclodimerize even at room temperature. Indeed, the capto-datively substituted methylenecyclopropane 85 undergoes the homodimerization at 60 °C (Scheme 65) [126]. 

It was discovered that the acetyl derivalive of iV-hydroxy-2-thiopyridone is especially suitable as a source of methyl radicals, being photolysed by irradiation with a simple tungsten lamp. On this basis, and because of the high radicophilicity of tellurides (especially anisyl tellurides), a radical exchange occurs when the reagent is irradiated in the presence of an... 

These reactions of 1-Me resemble that of (dichloromethylene)cyclopropane [31] and radicophilic alkenes with a capto-dative substitution pattern [32]. Thus, it is not surprising that 1-Me reacts with a-ferf-butylthioacrylonitrile (18), yielding the two isomeric cyclobutane derivatives 19a, b (ratio 2.2 1) as a mixture of two diastereomers each [29] (Scheme 5), and this reaction occurs under milder conditions than the [2-1-2] cycloaddition of 18 onto methylenecyclopropane. 

Electron impact mass spectrometry of the cyclobutanedione (24) gives rise to dimethylcarbene radical cation.35 Appearance energy measurements and ab initio calculations indicated that the radical cation lies 84 kJ mol-1 above the propene radical cation and is separated from it by a barrier of 35 k.l mol Diarylcarbene radical cations have been generated by double flash photolysis of diaryldiazomethanes in the presence of a quinolinium salt (by photo-induced electron transfer followed by photo-initiated loss of N2).36 Absolute rate constants for reactions with alkenes showed the radicals to be highly electrophilic. In contrast to many other cation radicals, they also showed significant radicophilic properties. 

Monoalkyl aminium radicals cannot be prepared from PTOC carbamates 29 due to an equilibrium in solution favoring 2-mercaptopyridine-Ar-oxide and an alkyl isocyanate [Eq.(ll)]. With Af-(monoalkyl)thiazole-2-thione carbamates, TTOC carbamates, the equilibrium lies far to the side of the carbamate 84, and these precursors can be prepared from an isocyanate and Ar-hydroxythiazole-2-thione [Eq. (12)]. Under UV photoinitiation in acidic media, TTOC carbamates are efficient precursors for monoalkyl aminium cation radicals (Scheme 26). Monoalkylaminium radical 85 ey-clizes as efficiently as its analogous dialkylaminium radical 66, and the resulting carbon radical 86 can be trapped by a variety of radicophiles (91JOC1309) to prepare substituted pyrrolidines. 

The weak step in this synthesis is the radical addition to the isonitrile. Isonitriles that are sufficiently radicophilic are also easily polymerized. So we decided to develop a better procedure. The sulfonylcyanide function shows some radical behavior.60 This, in principle, can be utilized for constructing a radical chain process. We decided to compare the well-known... 

Many important natural products are (formerly) derived by chain elongation at position 5 of pentoses, or at position 6 of hexoses. Uronic acids, which are easily prepared, can be converted into the 4 radical 90 by chemistry based on the thiohydroxamate 6.77 We postulated that, if the hindrance on the a-side of the molecule was great enough, the carbon-carbon bond formed by reaction of 90 with a suitable radicophilic olefin would be the natural / -bond. In fact, even a dimethyl-ketal as in 90 (B = natural base or protected derivative thereof) was sufficient to direct the bond formation very largely to the desired face.77 The diacetone ketal of glucuronic acid 91 upon conversion to its iV-hydroxy-2-thiopyridone derivative 92 and then photolysis in the usual way in the presence of methyl acrylate gave the expected derivative 93 as a mixture of... 

Xanthates and their relatives may justifiably be considered as major precursors of a wide variety of radicals. The highly radicophilic thiocarbonyl group and the possibility of two distinct modes of fragmentation, summarized in Scheme 1 for the case of a xanthate, allow numerous useful combinations. The foregoing, brief overview of their radical chemistry gives only a glimpse of their vast and exceptional potential for synthesis, a potential that is far from being completely explored and exploited. 

The introduction of 0-acyl thiohydroxamates (mixed anhydrides of carboxylic acids with thiohydroxamic acids) by the Barton group in 1983 [1] has provided one of the mildest and most convenient and versatile sources of carbon-centered radicals which fulfill the above criteria, and can hence, in Sir Derek s own words, be described as disciplined . Since their preparation from carboxylic acids is extremely straightforward, and since they have demonstrated a rapacious radicophilicity in a wide variety of very useful transformations, it is no surprise that these derivatives are commonly named either as Barton esters or by the acronym PTOC (pyridine thiocarbonyl) esters. The ongoing development of this chemistry has been summarized over the years in several useful reviews [2], and some of the tried and tested experimental procedures have also been collated [3]. 

As anticipated, by analogy with the chemistry of Barton esters, the same mixed oxalate esters can be used to prepare tertiary alkyl chlorides, simply by refluxing in carbon tetrachloride [47], and also for the creation of quaternary carbon centers through selection of either a Michael acceptor [46] or 2-(carboethoxy) allyl tert-butyl sulfide [46] as the radicophile. 

Photoelectron, UV and NMR spectroscopy, as well as MNDO calculations all predict a reduced HOMO-LUMO gap for alkenes with captodative substitution, and an enhanced reactivity of the p carbon [43]. This explains their radicophilic behavior and their high reactivity in cycloaddition processes, the diradicaloid transition states of which are stabilized when the mechanism is asynchronous cf. Sec. 3.3.7). 

Nucleophilic radical 79, derived from bromide 78, is expected to add intra-molecularly to the eleetrophilic double bond to yield a-acyl radical 80, but it can also add to the radicophilic alkene group to yield captodative species 81 (Scheme... 

An intramolecular Michael-type 1-endo radical cyclization was reported by Kobayashi and coworkers [35] employing a trifluoromethyl substituted olefin as the internal radicophile. Thus, reaction of the iodide 123 with BuaSnH and AIBN furnished the 1-endo trig cyclized product 124 in 80% yield along with a minor amount of 6-exo trig cyclized product 125. 

Recently, Curran and Liu [63] encountered an interesting 1-exo dig cyclization reaction during their attempts to use cyclopropanes as radicophiles. Reaction of the bromodinitrile 255 with an excess of BusSnH and AIBN resulted in the formation of the eight-membered enaminonitrile 257, whose formation was explained by initial 1-exo dig cyclization of the radical onto one of the nitriles followed by BusSnH-mediated cleavage of the cyclopropyl imine 256. 

A delocalized 0-stannyl radical anion can also be generated from the reaction of an a,/ -unsaturated ketone or aldehyde with tributyltin hydride and radical initiator AIBN [3, 4, 5a, 5b]. Thus, a,/ -unsaturated carbonyl compound 4 (R or R = H or alkyl), can be reacted with wBu SnH under standard free-radical conditions to give allylic O-stannyl ketyl species (5 6), shown in Scheme 2. After hydrogen atom transfer to the -position of 6, a synthetically useful tin(IV) enolate is produced [5b, 5d, 5g. Allylic 0-stannyl ketyls have both one- (radical) and two-electron (anionic) sites for reactivity. These reactions can proceed in a sequential manner - a rapidly-evolving methodology in organic synthesis [2, 5, 8j. If the one-electron reactivity in 6 is used with a radicophile, then the tin enolate or two-electron reactivity can be used in reactions with suitable electrophiles (E ). Note that the carbonyl species. 

C-Glycopyranosides may be obtained from glycopyranosyl halides via intermolecular addition of glycopyranosyl radicals [129]. In a more useful example, the a-aminoacrylate 192 was used as the radical acceptor for preparation of C-glycosyl amino acids 193 and 194 [130] (Scheme 66). In a concise synthesis of showdomycin (197), Barton utilized the trigger reaction of the 7V-hydroxy-2-thiopyridone derivative and the exceptional radicophilicity of tellurides in concocting the conditions for the conversion from the anisyl telluride 195 to the intermediate 196 after oxidative elimination [131] (Scheme 67). In Keck s synthesis of (-t-)-pseudomonic acid C (201), the intermediate 200 was prepared via stereocontrolled intermolecular addition of the radical generated from the iodide 198 to the allylic sulfone 199 [132] (Scheme 68). 

Vinylidenecyclopentanes 45 have been synthesized by a sequential radical reaction. A careful evaluation of the suitable starting materials led to the choice of thiohydroxamic esters like 43 for starting the radical chain shown in Scheme 15. Photolytical decomposition of 43 in the presence of 5-fold molar excess of a radicophilic olefin generated the 5-hexynyl radical 44 which cyclized onto the triple bond. jS-Elimination of a phenylthiyl radical afforded the vinylidenecyclopentane 45 in 60-70% yield. Other insights in the mechanism of these radical chain reactions are given in the paper. 

Baran et al. developed a radical cross-couphng reaction between arylboronic acids and trifluoroborates, in 2011 (Scheme 5.31) [56]. This methodology was applied to achieve a domino cyclization/coupling reaction. When the aryl boronic acid 144 was subjected to Ag+/S20g , a benzofuran radical was generated, which underwent a radical trap with 1,4-benzoquinone as the terminating radicophile. 

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