Elimination reactions, radical-mediated

In broad terms, the following types of reactions are mediated by the homolytic fission products of water (formally, hydrogen, and hydroxyl radicals), and by molecular oxygen including its excited states—hydrolysis, elimination, oxidation, reduction, and cyclization. 

By far the most generally useful synthetic application of allyltributyltin is in the complementary set of transition metal- and radical-mediated substitution reactions. When the halide substrates are benzylic, allylic, aromatic or acyl, transition metal catalysis is usually the method of choice for allyl transfer from tin to carbon. When the halide (or halide equivalent) substrate is aliphatic or alicyclic, radical chain conditions are appropriate, as g-hydrogen elimination is generally not a problem in these cases. 

To avoid the formation of ketenes by alkoxide elimination, ester enolates are often prepared at low temperatures. If unreactive alkyl halides are used, the addition of BU4NI to the reaction mixture can be beneficial [134]. Examples of the radical-mediated a-alkylation of support-bound a-haloesters are given in Table 5.4. Further methods for C-alkylating esters on insoluble supports include the Ireland-Claisen rearrangement of O-allyl ketene acetals (Entry 6, Table 13.16). Malonic esters and similar strongly C,H-acidic compounds have been C-alkylated with Merrifield resin [237,238]. 

The synthesis of gm-diallyl derivatives can be achieved by double alkylation of active methylene groups. We realized that installation of gem-diallyl functionality on a carbon atom, not activated by any electron-withdrawing group, is a difficult proposition. The problem becomes insurmountable on carbohydrate precursors because base-catalyzed reactions lead to tandem elimination of water molecules, resulting in the formation of complex mixtures, We observed interesting reactions with carbohydrate cyclopropyl precursors. For example, the radical-mediated cyclopropyl scission of the spirocyclopropyl bromide (86) with n-BusSnH gave the C-aUyl derivative (87) in a stereo-controlled fashion. On the other hand, hydrogenation of the cyclopropylaldehyde derivative (88) over Pd/C provided 89 with a quaternary chiral center (Scheme 30.14). 

As exemplified in the following cases, this addition reaction has often been used as the first step in the preparation of vinyl sulfones. The adduct must therefore undergo a subsequent elimination reaction. A base is needed to perform dehydrohalogenation. The selenides resulting from the addition of selenosul-fonates can be eliminated very smoothly through oxidation. Thus, Yus and co-workers [104] have based a very simple method for the preparation of j9-sulfonyl-a,j9-unsaturated compounds on the addition of tosyl iodide to Michael acceptors (equation (50)) whereas Barton et al. [105] have shown that the addition of phenylseienotosylate to electron-rich olefins, catalyzed by Ru(II) complexes, is efficient (equation (51)). An alternative approach is the Ce(IV)-mediated addition of arylsulfinates to electron-rich olefins which proceeded directly to the olefinic product resulting from oxidative elimination of the intermediate alkyl radical (equation (52)) [106]. 

One advantage of a CRP, such as ATRP, is the ability to control the MW and MWD of copolymers containing functional monomers. Control over MW requires efficient initiation and preservation of activity in the majority of the polymeric chains. However, termination and other side reaaions are also present in ATRP, and they become more prominent as higher MW polymers are targeted. For example, in the copper-mediated ATRP of styrene, a slow termination process was observed, mainly arising from the interaction of the Cu species with both the growing radical and the maaomolecular alkyl halide. The catalytic species can participate in the OSET reactions by either oxidation of polystyryl radicals to carbocations or reduction of radicals to carbanions via reactions with Cu(II) and Cu(l) species. Studies with model compounds and maao-molecular PS species demonstrated that the elimination reaction was accelerated in the presence of the Cu(II) complex. This process was faster for bromine-mediated ATRP than for chlorine-based systems and was more noticeable in polar... 

Baldwin et al. used a radical-mediated ring expansion of 3-stannylcyclohexanones to provide efficient routes to cis-and trans-cyclononenones. Thus, bromo ketone 109 underwent a radical reaction to generate cyclopentyl aUcoxy radical 110. Fragmentation and elimination of a stannyl radical led to cyclononenone 111, which was further elaborated to rac-phoracantholide I (Scheme 25.52), originally isolated from the metastemal secretion of the eucalypt lon-gicom Phoracantha synonyma. 

The mechanism for the transformation of 5 to 4 was not addressed. However, it seems plausible that samarium diiodide accomplishes a reduction of the carbon-chlorine bond to give a transient, resonance-stabilized carbon radical which then adds to a Smni-activated ketone carbonyl or combines with a ketyl radical. Although some intramolecular samarium(n)-promoted Barbier reactions do appear to proceed through the intermediacy of an organo-samarium intermediate (i.e. a Smm carbanion),10 ibis probable that a -elimination pathway would lead to a rapid destruction of intermediate 5 if such a species were formed in this reaction. Nevertheless, the facile transformation of intermediate 5 to 4, attended by the formation of the strained four-membered ring of paeoniflorigenin, constitutes a very elegant example of an intramolecular samarium-mediated Barbier reaction. 

Barrero, Oltra and coworkers reported on the use of epoxygeranyl acetate in titanocene-mediated cyclizations and found that the termination of the reaction took place via a /i-hydride elimination after trapping of the radical by the second equivalent of Cp2TiCr [94,95]. This finding together with Takahashi s tandem cyclization [96] (see below) marks the first example of extremely interesting developments in epoxypolyene cyclizations via radicals that are discussed separately in the following section. 

The trimethylsilyl ethers 212 of four-membered 1-alkenyl-1-cyclobutanols rearrange to the ring-expanded 0-mercuriocyclopentanones 213. These can be converted into the a-methylenecyclopentanones 214 through elimination or further expanded by one-carbon atom into cyclohexanones 215 via the Bu3SnH-mediated free radical chain reactions [116]. A similar radical intermediate is suggested to be involved in the ring expansion of a-bromomethyl-fi-keto esters [117]. (Scheme 84)... 

TMC ATRA reactions can also be conducted intramolecularly when alkyl halide and alkene functionalities are part of the same molecule. Intramolecular TMC ATRA or atom transfer radical cyclization (ATRC) is a very attractive synthetic tool because it enables the synthesis of functionalized ring systems that can be used as starting materials for the preparation of complex organic molecules [10,11], Furthermore, halide functionality in the resulting product can be very beneficial because it can be easily reduced, eliminated, displaced, converted to a Grignard reagent, or if desired serve as a further radical precursor. The use of copper-mediated ATRC in organic synthesis has been reviewed recently and some illustrative examples are shown in Scheme 3 [10,11,31,32,33],... 

It is also essential that competing radical pathways are excluded. The radical intermediates should therefore be relatively persistent. This is the case here, because tertiary radicals are relatively slowly trapped by hydrogen atom donors, e.g., THF, which is usually applied as solvent in titanocene-mediated or -catalyzed reactions, or a second equivalent of Cp2TiCl. Flowever, in the absence of other pathways this reduction, which was followed by a -hydride elimination, was observed [75,76]. Our results with 10 are summarized in Table 5. 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

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