Radical initiators, addition alkenes

Although scheme (138) is the standard mechanism for the radical-catalyzed isomerization of isomeric alkenes, kinetic data for both substitution and isomerization are sparse. Using cis- or frcms-diiodo-ethene and labeled iodine atoms, Noyes et al. (1945) demonstrated that iodine atoms exchanged with predominant retention isomerization was the slower process, the barrier being <4 kcal/mole. Corresponding studies with dibromoethene and bromine atoms indicate a barrier of ca. 3 kcal/mole (Steinmetz and Noyes, 1952) in which bromine-atom departure from and isomerization of the intermediate were competitive. Qualitative selective or stereospecific radical-initiated additions to alkenes have since indicated that radical intermediates probably have stereostability, but the studies cited are definitive. The kinetic analysis provided the essential model for SS in mechanistic schemes such as (138), whether for SE, SH or SN processes. 

The polar addition of HBr to alkenes leads to the more substituted bromide, whereas the radical-initiated addition of HBr gives the less substituted bromide. Thus, you have the ability to make either regioisomer when the alkene is imsym-metrically substituted. The addition of HCl and HI always gives the more substituted halide. 

Arylthiols (but not alkylthiols) add to terminal alkynes regioselectively to afford a Markovnikov-type adduct 212 in good yield using Pd(OAc)2 as a catalyst[120]. This result is clearly different from the an/i-Markovnikov addition induced by a radical initiator. The hydroselenation of terminal alkynes with benzeneselenol catalyzed by Pd(OAc)2 affords the terminal alkene 213, which undergoes partial isomerization to the internal alkene 214[121]. 

Free-Radical-Initiated Synthesis. Free-radical-initiated reactions of hydrogen sulfide to alkenes are commonly utilized to prepare primary thiols. These reactions, where uv light is used to initiate the formation of hydrosulfuryl (HS) radicals, are utilized to prepare thousands of metric tons of thiols per year. The same reaction can be performed using a radical initiator, but is not as readily controlled as the uv-initiated reaction. These types of reactions are considered to be anti-Markownikoff addition reactions. 

The regioselectivity of addition of Itydrogen bromide to alkenes can be complicated if a free-radical chain addition occurs in competition with the ionic addition. The free-radical reaction is readily initiated by peroxidic impurities or by light and leads to the anti-Markownikoff addition product. The mechanism of this reaction will be considered more fully in Chapter 12. Conditions that minimize the competing radical addition include use of high-purity alkene and solvent, exclusion of light, and addition of free-radical inhibitors. ... 

The free radical additions of sulfonyl halides to alkenes, catalyzed by light or typical chemical radical initiators (In), were first investigated in the 1950s69. The products which are / -halo sulfones (22) were obtained via a chain reaction in which RSO j acts as the chain carrier, namely61-62,70,71... 

The (TMS)3Si radical addition to terminal alkenes or alkynes, followed by radical cyclization to oxime ethers, were also studied (Reaction 50). The radical reactions proceeded effectively by the use of triethylborane as a radical initiator to provide the functionalized pyrrolidines via a carbon-carbon bond-forming process. Yields of 79 and 63% are obtained for oxime ethers connected with an olefin or propargyl group, respectively. 

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 ... 

Similar additions have been successfully carried out with carboxylic acids, anhydrides, acyl halides, carboxylic esters, nitriles, and other types of compounds. These reactions are not successful when the alkene contains electron-withdrawing groups such as halo or carbonyl groups. A free-radical initiator is required, usually peroxides or UV light. The mechanism is illustrated for aldehydes but is similar for the other compounds ... 

The mechanism is usually electrophilic (see p. 972), but when free-radical initiators (or UV light) are present, addition can occur by a free-radical mechanism. Once Br-or Cl- radicals are formed, however, substitution may compete (14-1 and 14-2). This is espiecially important when the alkene has allylic hydrogens. Under free-radical conditions (UV light) bromine or chlorine adds to the benzene ring to give, respectively, hexabromo- and hexachlorocyclohexane. These are mixtures of stereoisomers (see p. 161). ... 

The addition of carbon-based radicals to alkenes has been shown to be successful in water. Thus, radical addition of 2-iodoalkanamide or 2-iodoalkanoic acid to alkenols using a water-soluble radical initiator in water generated y-lactones (Eq. 3.29).118... 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Carbon-carbon bond formation is a fundamental reaction in organic synthesis [1, 2,3,4], One way to form such a bond and, thus, extend a carbon chain is by the addition of a polyhalogenated alkane to an alkene to form a 1 1 adduct, as shown in Scheme 1. This reaction was first reported in the 1940s and today is known as the Kharasch addition or atom transfer radical addition (ATRA) [5,6], Historically, Kharasch addition reactions were conducted in the presence of radical initiators or... 

Radical [3 + 2 cycloaddition. Cyclopentanes can be prepared by addition of alkenes across vinylcyclopropanes catalyzed by phenylthio radicals formed from (C6H5S)2 and AIBN. A Lewis acid such as A1(CH3)3 can increase the rate and the stereoselectivity of this radical initiated cycloaddition. Thus the combination of the vinylcyclopropyl ester 1 with f-butyl acrylate (2) provides the four possible cyclo-... 

In the presence of an organic peroxide Initiator, the alkenes and their derivatives undergo addition polymerisation or chain growth polymerisation through a free radical mechanism. Polythene, teflon, orlon, etc. are formed by addition polymerisation of an appropriate alkene or Its derivative. Condensation poiymerisation reactions are... 

We have here a mixture of electrophilic and radical addition reactions to alkenes. Remember the guidelines that radical reactions are characterized by the inclusion of radical initiators, such as light or peroxides. In the absence of such initiators, consider only the alternative electrophilic mechanisms. 

It is the opinion of the present authors that isomerization of a tertiary alkyl radical to a primary radical as in the formation of II from I is improbable. The formation of IV is similarly unlikely. The cycliza-tion of V by intramolecular alkylation seems quite plausible however, equation 9 does not explain either the formation of V or its subsequent cyclization. The following mechanism has the advantages that, like the generally accepted free radical-initiated mechanisms, it postulates a chain reaction and that the intramolecular alkylation step is directly analogous to that proposed for thermal alkylation, namely addition of an alkyl radical to the double bond of the alkene (Frey and Hepp, 12). The method of formation of the chain initiator, R —, again is not critical since R —, merely starts the first cycle of the chain reaction it may be formed by decomposition of the isobutylene. 

Problem 8.36 Write initiation and propagation steps in radical-catalyzed addition of BrCCl, to 1,3-butadiene and show how the structure of the intermediate accounts for a) greater reactivity of conjugated dienes than alkenes, (f>) orientation in addition. 

It is possible to obtain anti-Markovnikov products when HBr is added to alkenes in the presence of free radical initiators, e.g. hydrogen peroxide (HOOH) or alkyl peroxide (ROOR). The free radical initiators change the mechanism of addition from an electrophilic addition to a free radical addition. This change of mechanism gives rise to the anh-Markovnikov regiochemistry. For example, 2-methyl propene reacts with HBr in the presence of peroxide (ROOR) to form 1-bromo-2-methyl propane, which is an anh-Markovnikov product. Radical additions do not proceed with HCl or HI. 

Alkanes can be simultaneously chlorinated and chlorosulfonated. This commercially useful reaction has been applied to polyethylene (201—203). Aromatics can be chlorinated on the ring, and in the presence of a free-radical initiator alkylaromatic compounds can be chlorinated selectively in the side chain Ring chlorination can be selective. A patent shows chlorination of 2,5-di- to 2,4,5-trichlorophenoxyacetic acid free of the toxic tetrachlorodibenzodioxins (204). With alkenes, depending on conditions, the chlorination can be additive or substitutive. The addition of sulfuryl chloride can occur to form a 2-chloroalkanesulfonyl chloride (205). 

Addition to terminal alkenes. - In the presence of a radical initiator, ICH2C1 ddH to terminal alkenes (80°, 6 hours) to give l-chloro-3-iodoalkanes in 80 90% yield (equation 1). Only polymers form from a similar reaction of styrene with lt H2(l addition to internal alkenes is not useful either. 

Here Q denotes an alkyl radical with two unpaired electrons (in QOOH and QO) which may rearrange to form a stable alkene. The compound QO is a cyclic ether3 (which may break down to form an aldehyde4 and a smaller alkene). The sequence of reactions (R64) to (R67) is chain propagating, in that the initial alkyl radical has produced one HO2 or OH radical in addition to one or more stable components. However, it is also possible that a second oxygen molecule may add to QOOH to form a peroxy alkyl hydroperoxy radical,... 

The tin hydride method suffers from one major disadvantage, namely the efficiency of the reagent as a hydrogen atom donor. For successful synthesis, alkenes have to be reactive enough, otherwise direct reduction of the starting precursor becomes a considerable side reaction. In practice, the yields are increased by slow addition of a solution of tin hydride and a radical initiator into the reaction mixture containing an excess of alkene. However, a delicate balance must be maintained. If a large excess of olefin is used, polymerization can compete. 2,2-Azobisisobutyronitrile is the most commonly employed initiator, with a half-life time for unimolecular scission of 1 h at 80°C. 

Clearly, the formation of ROH and a bromine atom is energetically more favorable. The overall process of decomposition of peroxide and attack on hydrogen bromide, which results in the formation of a bromine atom, can initiate a radical-chain addition of hydrogen bromide to an alkene. 

Exercise 10-24 Write two different radical mechanisms for peroxide-initiated addition of hydrogen chloride to alkenes and consider the energetic feasibility for each. 

There are many reagents that add to alkenes only by radical-chain mechanisms. A number of these are listed in Table 10-3. They have in common a relatively weak bond, X—Y, that can be cleaved homolytically either by light or by chemical initiators such as peroxides. In the propagation steps, the radical that attacks the double bond does so to produce the more stable carbon radical. For addition to simple alkenes and alkynes, the more stable carbon radical is the one with the fewest hydrogens or the most alkyl groups at the radical center. 

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