Addition of Other Carbon Radicals

Other functional groups provide sufficient stabilization of radicals to permit successful chain additions to alkenes. Acyl radicals are formed by abstraction of the formyl hydrogen from aldehydes. As indicated in Table 3.17 (p. 315), the acyl radicals are somewhat stabilized. The C—H BDE for acetaldehyde, which is 88.3 kcal/mol, decreases slightly with additional substitution but increases for The chain 

Acyl radicals are strongly bent with a nearly trigonal angle, according to MP2/ 

6-31G computations. The C=0 bond length is just under 1.200A, somewhat shorter than a normal carbonyl bond. The SOMO orbital is in the plane of the molecule and 

The efficiency of aldehyde additions can be improved by adding an alternative hydrogen atom donor, such as methyl thioglycolate or A-hydroxysuccinimide.  

Acyl radicals can also be generated from acyl selenides and fn-n-butylstannane.  

The chain addition of formamide to alkenes is a closely related reaction. It results in the formation of primary amides. The reaction is carried out with irradiation in acetone. The photoexcited acetone initiates the chain reaction by abstracting hydrogen from formamide  

CH3COCH3 CH3COCH3 + HCONH2 -CONH2 + RCH=CH2 RCHCH2CONH2 + HCONH2 

Although the case of polyhalomethyl radicals is the most general reaction studied to date, other functional groups provide sufficient stabilization of potential radical centers to permit successful chain reactions. Although none of these reactions has been widely applied in synthesis, some would seem to be efficient enough to merit consideration as synthetic processes. 

Acyl radicals are formed by abstraction of the formyl hydrogen from aldehydes. Both the hydrogen abstraction and addition step are favorable, and a chain reaction can occur  

Closely related is the chain addition of formamide to alkenes, a reaction that provides primary amides. The initiating radicals are generated photolytically. Excited-state acetone abstracts a hydrogen atom from formamide, and the addition is a chain process  

3-Dioxolane, the cyclic ethylene glycol acetal of formaldehyde, is also alkylated by alkenes under free-radical conditions. Here, it is the CH2 group between the two oxygen atoms that is the preferred site of hydrogen abstraction. 

Although the case of polyhalomethyl radicals is the most favorable situation studied to date, other functional groups provide sufficient stabilization of potential 

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Absolute rate constants for the attack of aryl radicals on a variety of substrates have been reported by Scaiano and Stewart (Ph ) 7 and Citterio at al. (/j-CIPh-).379,384 The reactions are extremely facile in comparison with additions of other carbon-centered radicals [e.g. jfc(S) = 1.1x10s M"1 s"1 at 25 °C].3,7 Relative reactivities are available for a wider range of monomers and other substrates (Tabic 3.b). Phenyl radicals do not show clear cut electrophilic or... 

A plausible nucleation mechanism could be the gradual formation of carbon structures For instance by formation of linear carbon chains which via the addition of other linear chains and the addition of small carbon radicals can grow to bear graphite-like polycyclic networks. 

Carotenoid radicals — Many of the important oxidations are free-radical reactions, so a consideration of the generation and properties of carotenoid radicals and of carbon-centered radicals derived from carotenoids by addition of other species is relevant. The carotenoid radicals are very short-lived species. Some information has been obtained about them by the application of radiation techniques, particularly pulse radiolysis. Carotenoid radicals can be generated in different ways. "... 

Addition of the dicyanomethyl radical to propadiene (la) occurs exclusively at Q (not shown in Scheme 11.8) [60]. On the other hand, methyl-substituted allenes, e.g. Id, undergo /3-selective reactions with 2-bromomalodinitrile (15). The significant /3-selectivity has been associated with the steric demand of the incoming radical 16, which favors addition to the sterically least hindered site at the diene Id to provide allylic radical 17. However, it seems likely that a stabilization of an intermediate allylic radical, e.g. 17, by methyl substituents contributes significantly to the observed regioselectivity of product formation. Trapping of intermediate 17 with bromine atom donor 15 proceeds at the least substituted carbon to afford allylic bromide 18. 

In addition to the above two commonly found impurities, there are a number of other acid radical impurities which exist in pharmaceutical substances, namely arsenate, carbonate, cyanide, nitrate, oxalate, phosphate and silicate. 

One of the mildest general techniques to extend a carbon chain entails the addition of a carbon-centered radical to an alkene or alkyne. The method for conducting these addition reactions often determines the types of precursors and acceptors that can be used and the types of products that are formed. In the following section, synthetically useful radical additions are grouped into chain and non-chain reactions and then further subdivided by the method of reaction. Short, independent sections that follow treat the addition of carbon-centered radicals to other multiple bonds and aromatic rings and the additions of hete-roatom-centered radicals. 

Addition to n bonds is a second very common reaction of free radicals. Interaction of die free radical widi die 7r -electron pah causes one of die n electrons to pair up widi die unpaired electron of the free radical to produce a new bond to one of die r-bonded atoms. The remaining n electron is now unpaired and dius forms a new free-radical species. The process is often very favorable since the new a bond (70-90 kcal/mol) formed in die addition process is normally much stronger than die jt bond (60 kcal/mol) which is broken in the reaction. In the above example a new carbon-carbon a bond is formed by free-radical addition to produce a new carbon-centered free radical however, a wide variety of other free-radical species add readily to olefins. 

The addition of (TMS SiH across carbon-carbon multiple bonds under free-radical conditions is well documented82. Although no recent reports of such hydrosilylation processes are reported, the addition of (TMS Si radical to multiple bonds, followed by other radical reactions, were investigated (vide infra). The hydrosilylation of ketones and aldehydes is also well known83. In this respect Brook and coworkers have recently shown that the (TMS)3Si group can be used for the protection of primary and secondary alcohols84. 

In 1967, Heiba and Dessau reported perhaps one of the earliest examples of a radical cychzation cascade that is initiated by intermolecular addition of C-centered radicals to alkynes. Reaction of carbon tetrachloride with 1-heptynes 1 in the presence of benzoyl peroxide (BPO) as radical initiator resulted, among other products, in the formation of 1,1-dichlorovinylcyclopentane derivatives 2 in moderate yields (Scheme 2.1). °... 

A conventional free-radical initiator is added (contrary to some other controlled free-radical polymerization techniques) that generates radicals, which can add either to the monomer or the S=C moiety of the RAFT agent (step 1). In most cases the addition of small carbon-centered radicals to the RAFT agent is rapid and is not rate determining. Therefore, step (1) involves polymeric radical addition to 1 to form an intermediate radical species 2 that will fragment back to the original polymeric radical species or fragment to a dormant species 3... 

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