Radical initiators, addition substrates

Michael addition of pentM-yn-1-thiol to an activated alkyne produces co-yne vinylsulfides 424 as a separable mixture of the E and Z isomers. On treatment with -Uu (SnI I and a radical initiator, these substrates undergo a double radical cyclization accompanied by [(-fragmentation of the stannyl radical. The process is regio-, chemo-, and stereo-selective and produces the -isomer of the 5-substituted 3,4-dihydm-2//-thiopyran (Scheme 134) <1997JOC8630>. 

The first relevant report of a selective cyclization toward the (Cy 5) radical from a diallylic substrate was made in 1964 by Brace in the free radical chain reaction of 1,6-heptadiene (Scheme 25, X = CHj) with 1-iodoperfluoropropane initiated by AIBN. Further work, mainly by this author, confirmed (Scheme 25) the high selectivity toward formation of the (Cy 5) radical, in complete agreement with the results obtained with the 5-hexenyl radical (Sections II. 1 and III.1). Thus all reports, particularly in the polymerization area, that assumed formation of (Cy6) compounds must be regarded as suspect For instance, Cadogan and Hey reported the formation of a Cy5/Cy6 mixture by radical-initiated addition of various addenda to ethyl diallylacetate (X = CHCOjEt) but had to recognize later that the two compounds were in fact the two stereoisomeric (Cy5) compounds. 

Several cyditol derivatives of varying ring size, for example, (69)/(70), have been prepared based on an enzymatic aldolization as the initial step. Substrates carrying suitably installed C,H-acidic functional groups such as nitro, ester, phosphonate (or halogen) functionalities made use of facile intramolecular nucleophilic (or radical) cyclization reactions ensuing, or subsequent to, the enzyme-catalyzed aldol addition (Figure 10.27) [134—137]. 

The HX compounds are electrophilic reagents, and many polyhalo and polycyano alkenes, (e.g., Cl2C=CHCl) do not react with them at all in the absence of free-radical conditions. When such reactions do occur, however, they take place by a nucleophilic addition mechanism, (i.e., initial attack is by X ). This type of mechanism also occurs with Michael-type substrates C=C—Z, where the orientation is always such that the halogen goes to the carbon that does not bear the Z, so the product is of the form X—C—CH—Z, even in the presence of free-radical initiators. Hydrogen iodide adds 1,4 to conjugated dienes in the gas phase by a pericyclic mechanism ... 

Oxidations initiated by thermally induced electron transfer in an oxygen-CT complex represent the thermal analog of the Frei photo-oxidation and are properly classified as hybrid type IlAOi-type IIaRH oxidations (Fig, 2), Such reactions require either zeolites with high electrostatic fields or substrates with low oxidation potentials. In addition, elevated temperatures are known to promote the thermally initiated electron-transfer step, although the possible intrusion of a classical free-radical initiation chain oxidation at higher temperatures must be considered. 

Free-radical additions can occur with any type of substrate. The determining factor is the presence of a free-radical attacking species. Some reagents, e.g., HBr. RSH, attack by ionic mechanisms if no initiator is present, but in the presence of a free-radical initiator, the mechanism changes and the addition is of the free-radical type. Nucleophilic radicals... 

The addition of HX to double bonds in the dark and in the absence of free-radical initiators is closely related to hydration The orientation of the elements of HX in the adduct always rnrrrsponds to Markownikoff addition 16 no deuterium exchange wish solvent is found in unreacted olefins recovered after partial reaction, nor is recovered starting material isomerized after partial reaction.17 However. the addition of HX apparently can proceed by a number of different mechanisms depending on the nature Ol the substrate and on the reaction conditions. Thus when HC1 is added to f-butylethylene in acetic acid, the rate is first-order in each reactant and the products are those shown in Equation 7.5.le Since 4 and 6 were demonstrated to be stable to the reaction conditions, the rearranged product (5) can be formed only if a carbocationic intermediate is formed during reaction. However, the carbocation exists almost solely in an intimate ion pair, and the rate of collapse of the ion pair to products must be faster than, or comparable to, the rate of diffusion of Cl- away from the carbocation. This must be so because the ratio of chloride to acetate products is unaffected by... 

We will now consider successively the different reactions (4) and (5) of this reaction scheme in order to examine what is their relative importance for obtaining block or graft copolymers. Initially it was admitted that the graft copolymers were produced only by reaction (4b), considering that in the competition between monomer and substrate for primary initiator radicals the addition of vinyl monomers [reaction (2)] is much easier than the abstraction of an atom of another molecule [reaction (4 a)]. This assumption is based on the higher value of the activation energy for a chain transfer reaction than for a monomer addition, at least in the case of saturated molecules (88). 

The radical chain mechanism involving allytin belongs to the fragmentation method family and can be schematically presented as in equation 38, which involves five steps (i) initiation step, (ii) reaction with the substrate, forming the carbon-centred radical, (iii) a possible evolution of this radical, (iv) addition of the newly formed radical to the allylic double bond and (v) /3-scission, regenerating the chain-carrying tin radical. 

To achieve low radical concentrations, most radical reactions are traditionally performed as chain reactions. Atom or group transfer reactions are one of the two basic chain modes. In this process the atom or group X is the chain carrier. A metal complex can promote such chain reactions in two ways. On one hand, the catalyst acts only to initiate the chain process by generating the initial radical 29A from substrate 29 (Fig. 10). This intermediate undergoes the typical radical reactions, such as additions or cyclizations leading to radical 29B, which stabilizes to product 30 by abstracting the group X from 29. A typical example is the use of catalytic amounts of cobalt(II) salts in oxidative radical reactions catalyzed by /V-hydroxyphthalimide (NHPI), which is the chain carrier [102]. 

Anodic cyanation has been shown to be a direct process by electrochemical methods in conjunction with the analysis of products from cpe experiments (nos. 11 and 34, Table 8). In addition, cyano radicals can be generated in homogeneous solution, and a comparison of processes initiated by radical cation and cyano radical initiated processes reveals the indiscriminate nature of the latter towards aromatic substrates (cf. also Williams, 1960). This is in contrast to the electrophilic nature of the radical cation process. 

The initiation step (i) producing the tributyltin radical can be performed by thermolysis of radical initiators such as AIBN. Complementarily, the use of a Et3B/02 system or of photochemical irradiation allows the reactions to proceed at low temperature. The reaction (ii) with the substrate forming the carbon radical applies the same substrates as those used in tin hydride chemistry, such as iodides, bromides, selenides xanthates and even thiocarbonates. Furthermore, the possible competitive addition of tributyltin radicals to the allyltin reagent is of no consequence due to the rapid /3-fragmentation of the resulting carbon-centred radical, which renders this reaction a degenerate one. It is noteworthy that less reactive radical precursors such as chlorides or phenyl thioethers can be used efficiently. The evolution of the radical (iii) via several intra- or intermolecular elementary... 

The term hydrosilation (or hydrosilylation) refers to the addition of a molecule containing a Si-H bond across the multiple bond of a substrate, usually an alkene, alkyne, or carbonyl compound (equation 1). The reaction can be promoted by UV-light, radiation (y- and X rays), radical initiators, Lewis acids, nucleophiles, or, most importantly, transition metal catalysts. Hydrosilation is related to the important processes of hydrogenation (see Hydrogenation) and hydroboration (see Hydroboration), all of which belong to the general reaction class of hydroelementation. 

One of the earliest examples of the synthetic promise of radical reactions for preparing polycyclic products was provided by Corey s y-lactone synthesis. This approach was actually based on a well-known reaction of a-carbonyl radicals, generated by manganese(iii) oxidation of carboxylic acids, with unsaturated substrates. The mechanism of the basic steps shown for the preparation of lactone 418 (Scheme 2.140) involves initial addition of the a-carbonyl radical 419 to the double bond of styrene, followed by oxidation of the radical intermediate 419a to carbocation 419b, and subsequent intramolecular reaction with the carboxyl nucleophile to yield the lactone product. 

In this paperthe relative stabilities of various small-ring propellanes are discussed in terms of enthalpies of hydrogenolysis of the conjoining bond and dissociation energies of this bond in the various substrates. This is perhaps the place to state that the mechanism of addition of bromine, in the dark, to the conjoining bond of several [m.n.l]propellanes, has been discussed in generaF. It is concluded that thermally initiated low temperature radical chain addition to the cyclopropane rings is involved. 

The research team of J. Tadanier prepared a series of C8-modified 3-deoxy-P-D-manno-2-octulosonic acid analogues as potential inhibitors of CMP-Kdo synthetase. One of the derivatives was prepared from a functionalized olefinic carbohydrate substrate by means of the Wohl-Ziegler bromination. The stereochemistry of the double bond was (Z), however, under the reaction conditions a cis-trans isomerization took place in addition to the bromination at the allylic position (no yield was reported for this step). It is worth noting that the authors did not use a radical initiator for this transformation, the reaction mixture was simply irradiated with a 150W flood lamp. Subsequently the allylic bromide was converted to an allylic azide, which was then subjected to the Staudinger reaction to obtain the corresponding allylic amine. 

---