Radicals, reduction with alkenes

Radical anions resulting from cathodic reductions of molecules react with electrophilic centers. As an example (Scheme 8), the reduction of compounds in which a double bond is not conjugated with a carbonyl group, involves an intramolecular coupling reaction of radical anion with alkene [12]. 

When double bonds are reduced by lithium in ammonia or amines, the mechanism is similar to that of the Birch reduction (15-14). ° The reduction with trifluoro-acetic acid and EtsSiH has an ionic mechanism, with H coming in from the acid and H from the silane. In accord with this mechanism, the reaction can be applied only to those alkenes that when protonated can form a tertiary carbocation or one stabilized in some other way (e.g., by a OR substitution). It has been shown, by the detection of CIDNP, that reduction of a-methylstyrene by hydridopenta-carbonylmanganese(I) HMn(CO)5 involves free-radical addition. ... 

Iron porphyrins containing vinyl ligands have also been prepared by hydromet-allation of alkynes with Fe(TPP)CI and NaBH4 in toluene/methanol. Reactions with hex-2-yne and hex-3-yne are shown in Scheme 4. with the former giving two isomers. Insertion of an alkyne into an Fe(III) hydride intermediate, Fe(TPP)H, formed from Fe(TPP)Cl with NaBH4, has been proposed for these reactions. " In superficially similar chemistry, Fe(TPP)CI (present in 10 mol%) catalyzes the reduction of alkenes and alkynes with 200 mol% NaBH4 in anaerobic benzene/ethanol. For example, styrene is reduced to 2,3-diphenylbutane and ethylbenzene. Addition of a radical trap decreases the yield of the coupled product, 2,3-diphenylbutane. Both Fe(lll) and Fe(II) alkyls, Fe(TPP)CH(Me)Ph and [Fe(TPP)CH(Me)Ph] , were propo.sed as intermediates, but were not observed directly. ... 

The protic catalytic conditions are also compatible with trapping of the radicals formed after cyclization with acrylates or acrylonitriles prior to their reduction with Cp2TiCl . In this manner highly substituted alkenes for the potential preparation of modified steroids can be accessed (Scheme 19) [97]. 

The above-mentioned important and impressive applications of titanocene mediated and catalyzed epoxide opening have been achieved by using the already classical 5-exo, 6-exo and 6-endo cyclizations with alkenes or alkynes as radical acceptors. Besides these achievements, the high chemoselectiv-ity of radical generation and slow reduction of the intermediate radicals by Cp2TiCl has resulted in some remarkable novel methodology. 

As an example, the propagation steps for the reductive alkylation of alkenes are shown in Scheme 7.1. For an efficient chain process, it is important (i) that the RjSi radical reacts faster with RZ (the precursor of radical R ) than with the alkene, and (ii) that the alkyl radical reacts faster with the alkene (to form the adduct radical) than with the silicon hydride. In other words, the intermediates must be disciplined, a term introduced by D. H. R. Barton to indicate the control of radical reactivity [5]. Therefore, a synthetic plan must include the task of considering kinetic data or substituent influence on the selectivity of radicals. The reader should note that the hydrogen donation step controls the radical sequence and that the concentration of silicon hydride often serves as the variable by which the product distribution can be influenced. 

Among the electron-rich alkenes, vinylsulfides are especially amenable to cation-radical reduction an important feature is the absence of hydrogenolysis of carbon-sulfur bonds. The reduction of [(phenylthio)methylene]cyclohexane is efficient (88%), and the retention of the phenylthio group clearly contrasts with catalytic hydrogenation (Mirafzal et al. 1993). This provides versatile functionality for further synthetic operations. 

Radical additions to alkenes and aromatic systems are well known reactions. The trapping in this manner of radicals obtained by reduction of the aliphatic carbonyl function has proved to be a versatile electrochemical route for the formation of carbon-carbon bonds. Such reactions are most frequently carried out in protic solvents so that the reactive species is a o-radical formed by protonation of the carbonyl radical-anion. Tlie cyclization step must be fast in order to compete with further reduction of the radical to a carbanion at the electrode surface followed by protonation. Cyclization can be favoured and further reduction disfavoured by a... 

The mercurio ketone 4 upon reduction with NaBH4 yields a radical which is trapped in situ by reactive acceptors such as vinyl ketones [37]. Treatment of a 1 3 mixture of mercurio ketone 4 and electron deficient terminal alkenes (or fumarate) in CH2C12 with a concentrated solution of NaBH4 in water gives conjugate adducts, Eq. (36). 

The reductive cleavage of hydroxylamine and its derivatives by electro-generated TP and V forming aminyl radicals and the hydroxide ions has been studied intensively. The aminyl radicals are preferably trapped with alkenes and aromatic compounds. Thus, the reaction of hydroxylamine with electro-generated Tp in the presence of maleic acid yields aspartic acid (Eqs. (66)—(69))... 

The electron transfer to the acetylenic bond forms the frans-sodiovinyl radical 20 that, after protonation, produces tram radical 21. At low temperature (—33°C) in the presence of excess sodium, the conversion of the trans radical to sodiovinyl intermediate 22 is slightly more rapid than the conversion of the tram radical to the cis radical 23 (21 —> 22 > 22 —> 23). As a result, protonation yields predominantly the trans alkene. However, low sodium concentration and increased temperature lead to increasing proportion of the cis alkene. Although other dissolving-metal reductions are less thoroughly studied, a similar mechanism is believed to be operative.34 Another synthetically useful method for conversion of alkynes to trans alkenes in excellent yields is the reduction with CrS04 in aqueous dimethylforma-mide.198... 

The use of the pseudohalogen nitryl iodide, prepared in situ from iodine and silver nitrite, has been found to add to an alkene in what is strictly an anti-Markownikov fashion. The explanation for this lies in that nitryl iodide adds in a radical manner, initially forming the more stable secondary radical after addition of NO2.115 Treatment of 3-0-acetyl-5,6-dideoxy-1,2-0-isopropylidene-a-D-xy/o-hex-5-enofuranose with nitryl iodide was found to afford an unstable adduct, with the nitro group appended to C-6, and iodine attached to the more substituted C-5.116-118 Similarly, treatment of benzyl 2-0-benzyl-3,4-dideoxy-a-D-g/ycero-pent-3-enopyranoside (70, Scheme 19) with nitryl iodide afforded the unstable adduct 71, which, upon exposure to mild base (NaHC03), afforded the eliminated product, namely benzyl 2-0-benzyl-3,4-dideoxy-4-nitro-a-D-g(ycew-pent-3-enopyranoside (72). The eliminated product was then readily converted into benzyl 2-0-benzyl-3,4-dideoxy-(3-L-r/ireo-pentopyranoside (73) by reduction with sodium borohydride. Addition of deuteride using NaBD4 led to axial deuteration atC-3. 

Thus, radical generation, the formation of C-C bonds, and radical reductions are possible in reactions with alkenes and organometallic complexes with M-H bonds. 

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