Radicals, anti-Markovnikov alkenes

This radical anti-Markovnikov addition of HX to alkenes is restricted to HBr both HI and HCl add in a Markovnikov fashion by an ionic... 

C is correct. Anti-Markovnikov alkene free radical addition is demonstrated by reaction mechanisms 1 and 2, both of which rely on peroxides as reagents. Based on tine experimental results provided by the question stem, anti-Markovnikov addition only succeeds using HBr. 

Free radical anti-Markovnikov addition of coordinated phosphine to non-coor-dinated alkene, a still relatively rarely explored reaction providing the effective formation of a C-P bond, remains a promising strategy for macrocycle formation. 

Se-phenyl areneselenosulfonates (24) undergo facile free-radical addition to alkenes to produce / -phenylseleno sulfones (25) in excellent yield86,87 (see Scheme 7). The addition occurs regiospecifically and affords anti-Markovnikov products contrary to the analogous boron trifluoride catalyzed reaction which produces exclusively Markovnikov and highly stereospecific products86 (equation 37). Reaction 36 has been shown to have the radical... 

Thus the observed orientation in both kinds of HBr addition (Markovnikov electrophilic and anti-Markovnikov free radical) is caused by formation of the secondary intermediate. In the electrophilic case, it forms because it is more stable than the primary in the free-radical case because it is sterically preferred. The stability order of the free-radical intermediates is also usually in the same direction 3°>2°>1° (p. 241), but this factor is apparently less important than the steric factor. Internal alkenes with no groups present to stabilize the radical usually give an approximately 1 1 mixture. 

The addition of hydrogen halides to simple alkenes, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule. " When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 985). It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCl only rarely. In the rare cases where free-radieal addition of HCl was noted, the orientation was still Markovnikov, presumably beeause the more stable product was formed. Free-radical addition of HF, HI, and HCl is energetically unfavorable (see the discussions on pp. 900, 910). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides... 

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]. 

Electron transfer sensitization allows either the radical cation or the radical anion of an aromatic alkene to form as desired, which finally results in nucleophile addition with Markovnikov and anti-Markovnikov regiochemistry. In an apolar solvent, the tight radical ion pair undergoes a stereoselective reaction when the electron-accepting sensitizer is chiral (Figure 3.10). ... 

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. 

Anti-Markovnikov free-radical-induced addition of HBr to alkenes can be prevented by carrying out the reaction in the presence of small amounts of antioxidants that inhibit the reaction of oxygen with the alkene to form peroxides. 

Although HI addition to alkenes and alkynes is faster than that of the other hydrohalides and free radical anti-Maikovnikov additions are not a problem, this reaction has received less attention than the others.173 The hydroiodination of alkenes is most commonly run using concentrated HI in water or acetic acid at or below room temperature. While the early literature suggests that simple terminal alkenes afford small amounts of anti-Markovnikov products, only Markovnikov products have been reported in the more recent literature (equations 125-129).67 176-179... 

A well-known example of the application of mechanistic understanding to help to control product yields is also of commercial significance - the addition of HBr to alkenes which may occur via cationic or radical mechanisms, Scheme 2.1 [2a]. Very pure alk-l-enes (1), in the absence of peroxides, react to give the 2-bromo-products (2) by Markovnikov addition. In the presence of peroxides or other radical sources, anti-Markovnikov addition gives the 1-bromo-products (3). 

Radical addition to alkenes is strongly influenced by polar effects, and reductive radical additions are nearly always anti-Markovnikov. Resonance stabilisation of the unpaired electron in R can decrease the rate of addition, while the stabilisation of the adduct radical... 

The photoaddition of secondary phosphines onto alkenes is one of the straightforward approaches for the synthesis of organophosphorus compounds. An anti-Markovnikov phosphorus-centered free radical addition onto the olefin has been... 

In 1933, M. S. Kharasch and F. W. Mayo found that some additions of HBr (but not HC1 or HI) to alkenes gave products that were opposite to those expected from Markovnikov s rule. These anti-Markovnikov reactions were most likely when the reagents or solvents came from old supplies that had accumulated peroxides from exposure to the air. Peroxides give rise to free radicals that initiate the addition, causing it to occur by a radical mechanism. The oxygen-oxygen bond in peroxides is rather weak, so it can break to give two alkoxy radicals. 

Radical Addition of HBr to Unsymmetrical Alkenes Now we must explain the anti-Markovnikov orientation found in the products of the peroxide-catalyzed reaction. With an unsymmetrical alkene like 2-methylbut-2-ene, adding the bromine radical to the secondary end of the double bond forms a tertiary radical. 

As we saw in the protonation of an alkene, the electrophile (in this case, Br -) adds to the less substituted end of the double bond, and the unpaired electron appears on the more substituted carbon to give the more stable free radical. This intermediate reacts with HBr to give the anti-Markovnikov product, in which H has added to the more substituted end of the double bond the end that started with fewer hydrogens. 

In Section 8-3B, we saw the effect of peroxides on the addition of HBr to alkenes. Peroxides catalyze a free-radical chain reaction that adds HBr across the double bond of an alkene in the anti-Markovnikov sense. A similar reaction occurs with alkynes, with HBr adding with anti-Markovnikov orientation. 

Radical chloroaminations are known, using radical, transition metal ion or photochemical initiation. They also occur without overt initiation, thus anti-Markovnikov additions to terminal alkenes occur with N,N-dichlorourethane in benzene at 5-40 C (yields <= 60%)P Similar reactions occur with N,N-dichlo-roarenesulfonamides in CH2CI2 at or below room temperature (yields mostly 53-91% 10% with isobu-tylene). ° The remaining N—Cl bond is reaiUly reduced if desired with sodium sulflte. N-Halosulfoximines also add to alkenes thermally or photolytically. ... 

Selenosulfonates (see also Section 3.6.2.3) add to alkenes when catalyzed by Lewis acids. These adducts are transformed via oxidative elimination to vinyl sulfones in good overall yields. Similar to other methods only trans addition is observed. Mixtures of regioisomers are often produced with unsyminetri-cal unactivated alkenes. All other alkenes (i.e. styrene and acrylonitrile) provide Maikovnikov additions. Radical processes yield anti-Markovnikov adducts. Thus, either regioisomeric vinyl sulfone may be prepared from almost any activated alkene by simply varying the mode of addition. ... 

The best experimental conditions to introduce a phenylseleno and an azido group to the alkene double bond are those which employ diphenyl diselenide, sodium azide and iodobenzene diacetate in methylene chloride. Under these conditions, however, the addition reaction occurs through the radical mechanism illustrated in Scheme 12 [581. The addition therefore occurs with an anti Markovnikov orientation and it is not stereospecific. The reaction is initiated by the oxidation of the azido anion to the azido radical, which adds to the alkene to afford a carbon radical. This is trapped by the PhSeSePh to afford the final product and a PhSe radical, which dimerizes to give the diselenide. 

There is a considerable current interest in synthetic applications of radical cation chemistry. Alkene radical cations have been studied extensively, notable examples include the anti Markovnikov addition of nucleophiles [209], and the photo-NO-CAS reaction [210]. The synthetic utility of radical cation mediated chemistry, and... 

Silanes also add to alkenes under radical conditions (using AIBN) with high anti-Markovnikov selectivity. An alternative route to alkylsilanes reacted an alkene with lithium metal in the presence of 3 equivalents of chlorotrimethylsilane. 

Radical addition to alkenes is usually difficult, except when addition occurs to conjugated carbonyl compounds (15-24). An important exception involves radicals bearing a heteroatom a to the carbon bearing the radical center. These radical are much more stable and can add to alkenes, usually with anti-Markovnikov orienta-... 

The group VB hydrides show trends in reactivity similar to those of group IVB. The N-H bond can be reacted with alkenes only under the influence of catalysts or under forcing conditions. The P-H bond can be added to alkenes (hydrophosphination) in a free radical chain process, or under photolytic conditions. Such reactions proceed in good yield and in an anti-Markovnikov manner. Some typical free radical P-H additions are listed in Table 1 . The addition of phosphinyl radicals is reversible and can lead to... 

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