Substituted Vinyl Radicals

Total synthesis of (-l-)-lycoricidine, (—)-lycoricidine and (-l-)-narciclasine via 6-exo cyclization of substituted vinyl radicals with oxime ethers has been reported . Thus, interaction of oxime ether 321 with thiophenol and then with Sml2 and TFA afforded (-l-)-lycoricidine 322 in good overall yield (equation 139). 

Sequences in which addition precedes cyclization are not as straightforward to conduct as the reverse however, they are very important because a net annulation results (that is, a new ring is formed by the union of two acyclic precursors in one experimental step). The intermediate radical is differentiated from the other radicals provided that the cyclization reaction is rapid, but it can be difficult to differentiate the initial radical from the final radical. As illustrated in Scheme 57, this is particularly true in the tin hydride method because many different types of radicals react with tin hydride at similar rates. Reaction of (69) under standard radical addition conditions produces (70), which results from a sequence of addition/cy-clization/addition.233 That the last C—C bond is formed actually results from a lack of selectivity the initial and final radicals are not differentiated and they must undergo the same reaction. Of course, this lack of selectivity is of no consequence if the product contains the desired skeleton and the needed functionality for subsequent transformations. Such sequences are very useful for forming three carbon-carbon bonds, and they can also be conducted by Barton s thiohydroxamate method.234 Structural modifications are required to differentiate the initial and final radicals, and, as illustrated by the conversion of (71) to (72), phenyl groups can provide the needed differentiation (probably by retarding the rate of addition more than they retard the rate of hydrogen abstraction). Clive has demonstrated that phenyl-substituted vinyl radicals also provide the needed selectivity, as illustrated by the second example in Scheme 57.233... 

An intramolecular 1,5-hydrogen abstraction in a substituted vinyl radical has been postulated by Heiba and Dessau (1967) to account for the products formed from the peroxide-initiated addition of carbon tetrachloride to hept-l-yne in the liquid phase. Such a 1,5-abstraction involves the participation of a six-membered cyclic transition state. 

Using the rotating cryostat we have obtained direct evidence for the occuri ence of such an intramolecular hydrogen abstraction in a series of substituted vinyl radicals. The vinyl radical, RCH=CH, has been prepared in an inert matrix (water or benzene) by the reaction of sodium with the appropriate vinyl halide. 

Tin hydrides readily form radicals. Typically Bu3SnH reacts with AIBN to give tin radicals that add to alkynes at the unsubstituted end to give the more substituted vinyl radical. The vinyl radical captures a hydrogen atom 74 from another molecule of Bu3SnH to produce another tin radical and complete the chain. The other product is a vinyl stannane Z-75. Here is the complete scheme ... 

A second 7r-type structure (2), in which the unpaired electron resides in a p orbital, has often been invoked for vinyls having R groups capable of delocalizing the unpaired electron, e.g. R=Ph, C(0)0R, CN. However, EPR data indicate that vinyl radicals with a-C(0)0R substituents are bent and that the linear structure is highly probable for a-phenyl substituted vinyl radicals . It is worth pointing out that the linear structure has been identified with certainty for the sterically crowded vinyl 3. Structural information obtained by the muon spin rotation (//SR) technique is consistent with this overall picture. A qualitative explanation of the configurational instability of vinyl radicals (when R = H), compared with that of vinyl anions, is given in a recent paper ... 

In the cases of aromatic aUcynes, the radical addition of PhSeH induced by oxygen (or air) is a very fast process (the addition is finished immediately after mixing the alkynes and PhSeH), giving a n-Markovnikov adduct regioselectively. The key species, PhSe-, adds to alkynes to generate vinyl radicals, a-Aryl-substituted vinyl radicals (formed by the addition of PhSe- to aromatic alkynes) are among 7t-radicals and more stable than a-alkyl-substituted vinyl radicals as a-radicals (formed by the addition of PhSe- to aliphatic alkynes) [86]. Therefore, it is relatively difficult, compared with the hydrothiolation, to control the selectivity in transition-metal-catalyzed hydroselenation of aromatic alkynes. 

The one-step vinyl migration mechanism makes the same regiochemical prediction. The less substituted vinyl group should migrate, because the substituent(s) will stabilize the residual radical. 

When an unsymmetrically substituted vinyl monomer such as propylene or styrene is polymerized, the radical addition steps can take place at either end of the double bond to yield either a primary radical intermediate (RCH2-) or a secondary radical (R2CH-). Just as in electrophilic addition reactions, however, we find that only the more highly substituted, secondary radical is formed. 

Waters61 have measured relative rates of p-toluenesulfonyl radical addition to substituted styrenes, deducing from the value of p + = — 0.50 in the Hammett plot that the sulfonyl radical has an electrophilic character (equation 21). Further indications that sulfonyl radicals are strongly electrophilic have been obtained by Takahara and coworkers62, who measured relative reactivities for the addition reactions of benzenesulfonyl radicals to various vinyl monomers and plotted rate constants versus Hammett s Alfrey-Price s e values these relative rates are spread over a wide range, for example, acrylonitrile (0.006), methyl methacrylate (0.08), styrene (1.00) and a-methylstyrene (3.21). The relative rates for the addition reaction of p-methylstyrene to styrene towards methane- and p-substituted benzenesulfonyl radicals are almost the same in accord with their type structure discussed earlier in this chapter. 

The main difficulty in obtaining the vinyl radical is that the species easily loses the hydrogen atom and is converted into acetylene. Nevertheless, a very low concentration of the radical H2C=CH has been achieved (Shepherd et al., 1988) by vacuum UV photolysis of ethylene frozen in an argon matrix, and a Fourier transform IR study of this intermediate has been carried out. A variety of and deuterium-substituted ethylene parent molecules were used to form various isotopomers of vinyl radical. On the basis of its isotopic behaviour and by comparison with ab initio... 

Preferential addition to one end or the other of a vinyl (CH2=CHX) or substituted vinyl (CH2=CXY) monomer seems to be the rule to which exceptions are rare. This generalization appears to apply to ionic as well as to free radical polymerizations. The polymers of mono-unsaturated compounds consequently are characterized by a high degree of head-to-tail regularity in the arrangement of successive units. Little is known concerning the sequence of d and I configurations of the asym-... 

Entries 18 to 19 pertain to cyclizations of electrophilic radicals generated by oxidations. Entry 18 is the prototype for cyclization of a number of more highly substituted systems. The reaction outcome is consistent with oxidation of the less-substituted enolic position followed by a 6-endo cyclization. The cyclized radical is then oxidized and deprotonated. In Entry 19, the vinyl radical formed by cyclization is reduced by hydrogen abstraction from the solvent ethanol. 

Figure 2.9 Idealized representation of a linear pol3fmer resulting from radical poUmerization of a mono-O-methacroyl-sucrose (left) and a 1 1 copolymerization product with styrene. Di-O-substituted vinyl-sucroses are deemed to lead to cross-linked pol3miers (right).

The reduction of aryl-substituted vinyl halides by electrochemically generated aromatic anion radicals has also been investigated in DMF (Gatti et al., 1987). Counter-diffusion behaviour at low driving forces (pp. 34, 35) does not appear as clearly as in the case of aryl halides (Fig. 11). However, analysis of the log k vs E° plot according to a quadratic activation-driving force relationship gave standard potential and intrinsic barrier values that... 

Reduction of phenyl vinyl sulphones in dimethylformamide containing phenol as proton donor causes loss of phenylsulphinate ion. The reaction probably involves a series of electron and proton addition steps [74]. In absence of a proton source, phenyl vinyl sulphone radical-anion undergoes a dimerization reaction discussed on p. 57. Reactions of alkyl substituted vinyl sulphones are complicated by alkene migration in the presence of electrogenerated bases. Dimers are formed and further reduction leads to loss of phenylsulphinate ion [81] (Scheme 5.3). 

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