Enolates carbon-centered radicals

In the reduction of radicals by ET, simple carbanions are practically never formed, and one-electron reduction of a carbon-centered radicals is only effective if the electron can be accommodated by the substituent, e.g., a carbonyl group [reaction (24), whereby upon electron transfer the enolate is formed (Akhlaq et al. 1987)]. Thus, in their reduction reactions these radicals react like heteroatom-centered radicals despite the fact that major spin density is at carbon. 

Not only alkenes and arenes but also other types of electron-rich compound can be oxidized by oxygen. Most organometallic reagents react with air, whereby either alkanes are formed by dimerization of the metal-bound alkyl groups (cuprates often react this way [80]) or peroxides or alcohols are formed [81, 82]. The alcohols result from disproportionation or reduction of the peroxides. Similarly, enolates, metalated nitriles, phenolates, enamines, and related compounds with nucleophilic carbon can react with oxygen by intermediate formation of carbon-centered radicals to yield dimers (Section 5.4.6 [83, 84]), peroxides, or alcohols. The oxidation of many organic compounds by air will, therefore, often proceed faster in the presence of bases (Scheme 3.21). 

Treatment of a-iodo ketone and aldehyde with an equimolar amount of Et3B yielded the Reformatsky type adduct in the absence of PhaSnH (Scheme 21), unlike ot-bromo ketone as shown in Scheme 15 [22], Ethyl radical abstracts iodine to pro-duee carbonylmethyl radical, which would be trapped by EtsB to give the corresponding boron enolate and regenerate an ethyl radical. The boron enolate reacts with aldehyde to afford the adduct. The three-component coupling reaction of tert-butyl iodide, methyl vinyl ketone and benzaldehyde proceeded to give the corresponding adduct 38, with contamination by the ethyl radical addition product 39. The order of stability of carbon-centered radical is carbonylmethyl radical > Bu > Pr > Ef > Me . 

Magnus reported the direct a- and )9-azido functionalization of triisopropylsilyl enol ethers using trimethylsilylazide and iodosylbenzene. In this mechanistically complex reaction sequence, it is believed that azidation of a carbon centered radical is occurring [78],... 

In connection with this search, the chemical behavior of the carbon-centered radical was also examined [118]. The similar hydroxycyclobutenone 140 bearing Barton s ester at C-4 was photolyzed (W-lamp) to again give a 5-endo-cyclized product, 4-cyclopentene-l,3-dione 145, prior to enol-keto tautomerization (Scheme 27). 

The hydrohydrazination represented a general solution for the amination of alkenes, but the protected hydrazines obtained are sometimes difficult to transform to the free amines. At this point, we turned to sulfonyl azides as nitrogen sources, based on then-capacity to react both with enolates and carbon-centered radicals. Mechanistic investigations of the hydrohydrazination reaction had suggested a radical character for the formed organocobalt intermediate. " We were pleased to see that the Cobalt-catalyst 4 was able to promote the hydroazidation of 4-phenylbut-l-ene (3) with ethanesulfonyl azide (7), giving the product derived from the formal Markovnikov addition of hydrazoic acid onto the C-C double bond exclusively, albeit in moderate yields (50%). 

The preparation of a-selenoketones, esters, nitriles and related compounds can easily be performed via alkylation of the corresponding enolates or stabilized carbanions [21]. These compounds have found many synthetic applications in radical chemistry. In Eq. (9), a typical example involving a ketone is depicted [22]. The stability of a-selenoketones such as 41 is remarkable. Similar reactions with lactones have been performed. For instance, this approach has been applied to the stereoselective synthesis of oxygen-containing rings to either faces of a bicyclic structure [23]. The approach based on a-selenenylation/radical allyla-tion compares favorably with classical enolate allylation procedures, which usually leads to mixture of mono- and diallylated compounds. Furthermore, this strategy is excellent for the preparation of quaternary carbon centers [24] as shown by the conversion of 43 to 45, a key intermediate for the synthesis of fredericamycin A, [Eq. (10)] [25]. Similar reactions with sulfoxides [26] and phosphonates [27] have also been reported. 

Pulse radiolysis studies using optical detection suggested the main species in equilibrium to be the ot-aminoalkyl radical (31) and the A -protonated ot-aminoalkyl radical (32) whereas results from ESR studies were indicative of protonation at the a-carbon site to form the iV-centered radical cation (30). A subsequent study showed that these results could be attributed to kinetic and thermodynamic factors [84]. Thus iV-protonation resulting in the formation of 32 is kinetically favored and is hence observed in the short time-scales involved in pulse-radiolysis systems. In the longer times involved in ESR measurements the thermodynamically more stable N-centered radical cation will be observed. The pA a of 30 and 32 were estimated as 8.0 and 3.6 by use of pulse radiolysis [84]. Using the equation for similar keto enol tautomerism of barbituric acid [97], the ratio of 30/32 was estimated to be 10 /10 = 10", indicating the N-centered radical (30) to be the predominant protonated species. 

The structure of the products is determined by the site of protonation of the radical anion intermediate formed after the first electron transfer step. In general, ERG substituents favor protonation at the ortho position, whereas EWGs favor protonation at the para position.215 Addition of a second electron gives a pentadienyl anion, which is protonated at the center carbon. As a result, 2,5-dihydro products are formed with alkyl or alkoxy substituents and 1,4-products are formed from EWG substituents. The preference for protonation of the central carbon of the pentadienyl anion is believed to be the result of the greater 1,2 and 4,5 bond order and a higher concentration of negative charge at C(3).216 The reduction of methoxybenzenes is of importance in the synthesis of cyclohexenones via hydrolysis of the intermediate enol ethers. 

Cyclobutadiene iron tricarbonyl complexes also stabilized carbocations on an adjacent carbon. The cation reacts with silyl enol ethers to afford alkylated complexes such as (127) (Scheme 187). A samarimn diiodide -mediated intermolecular radical cychzation of iron tricarbonyl complex (128) is depicted in Scheme 188. An excellent stereocontrol at three contiguous centers is observed. 

Any reaction that creates a new bond to an achiral carbon has the potential to create a new chiral center if that carbon has a tetrahedral geometry in the product. Examples in which the starting carbon was also tetrahedral include free-radical halogenation (replace H- with X-) and a-alkylation of an enolate... 

For lead references see Yamamoto, Y. Maruyama, K. The Opposite Diastereoselectivity in Alkylation and Protonation of Enolates J. Chem. Soc., Chem. Commun. 1984, 904-905. Fleming, I. Lewis, J. J. A Paradigm for Diastereoselectivity in Electrophilic Attack on Trigonal Carbon Adjacent to a Chiral Center The Methylation and Protonation of Some Open-Chain Enolates J. Chem. Soc., Chem. Commun. 1985, 149-151. McGarvey, G. J. Williams, J. M. Stereoelectronic Controlling Features of Allylic Asymmetry. Application to Ester Enolate Alkylations J. Am. Chem. Soc. 1985, 107, 1435-1437. Hart, D. J. Krishnamurthy, R. Investigation of a Model for 1,2-Asymmetric Induction in Reactions of a-Carbalkoxy Radicals A Stereochemical Comparison of Reactions of a-Carbalkoxy Radicals and Ester Enolates J. Ors. Chem. 1993, 57, 4457-4470. 

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