Malonyl radical

Scheme 6.163 Radical carboxaminations with malonyl radicals.

The absolute rate constants for the addition of the cyclic malonyl radical (37) and the di(f-butyl)malonyl radical to over 26 different alkenes have been measured by... 

Radicals can be either reduced (to anions or organometallics) or oxidized to cations by formal single electron transfer (Scheme 11).50 Such redox reactions can be conducted either chemically or electro-chemically51 and the rates of electron transfer are usually analyzed by the Marcus theory and related treatments.50 These rates depend (in part) on the difference in reduction potential between the radical and the reductant (or oxidant). Thus a species such as an a-amino radical with high-lying singly occupied molecular orbital (SOMO) is more readily oxidized, while a species such as the malonyl radical with a low-lying SOMO is more readily reduced. The inherent difference in reduction potential of substituted radicals is an important control element in several kinds of reactions. 

Radical addition to P-alkoxyalkylidenemalonate 347 provides highly electrophilic malonyl radical intermediates 348 that undergo t>-endo cyclization onto tethered unactivated alkenes to afford tetrahydropyrans 349. The diaster-eoselectivity in the product can be improved by using bulky radicals (Scheme 84, Table 17) <2004EJ0372>. 

Addition reaction of electrophilic diethyl malonyl radical to alkenes... 

The addition of alkyl radicals to alkenes is important for C-C bond formation. A tert-butyl radical, a typical nucleophilic radical, reacts with acrylonitrile taking a rate constant of 2.4 X 106 M-1 s-1 (27 °C), through a SOMO-LUMO interaction. However, it reacts with 1-methylcyclohexene, an electron-rich alkene, taking a rate constant of 7.4 X 102M-1 s-1 (21 °C). On the other hand, the diethyl malonyl radical, a typical electrophilic radical, shows the opposite reactivity [66-71]. Similarly, the rate constant for the reaction of nucleophilic C2H5 and cyclohexene is2X 102 M 1 s 1, while that of electrophilic C3F7 with cyclohexene is 6.2 X 105 M-1 s 1. 

Ce4+ and Mn3+ can generate an electrophilic malonyl radical from malonate diester. Thus, the introduction of a malonyl group to an uracil derivative is effective by treatment of the uracil derivatives (15) with CH2(C02R)2 and Mn(OAc)3 in acetic acid under heating conditions as shown in eq. 5.9 [21, 22]. 

Malonyl radicalsThiophenes and furans undergo substitution at C2 when treated with a dialkyl malonate and ceric sulfate at 25°. The reaction is considered to involve oxidative generation of malonyl radicals by the cerium salt. Yields are... 

Photolysis of diethyl bromomalonate in benzene in the presence of compounds with a benzylic hydrogen as possible H-atom source leads to reduction of the ester and bromina-tion of the benzylic compound263. The malonyl radical and not the Br atom turns out to be the H-atom abstracting agent. 

The previous examples rehed on a radical termination. Cationic termination could also be used, after suitable oxidation of the final radical (Scheme 75) [211]. Thus, ester 252 was treated with base and ethylchloro-formate to give anion 253, which was oxidized to malonyl radical 254 by the ferrocenium ion. Cyclization/oxidation gave cation 256, which yielded 93% of malonate 257 by loss of the TMS group. This adduct was further elaborated upon and led to a cyclopentanoid monoterpene, dihydronepetal-actone. 

The review highlights the chemistry described in the past five years with a small emphasis on work from our laboratory. The chemistry of ketyl radicals has been dealt with only in a cursory fashion and readers are advised to consult recent seminal reviews in this area [5]. Due to space limitations, the chemistry of malonyl radicals are also not covered. Readers should consult important contributions from Prof. Snider and a recent review [6]. 

These radicals react like electrophiles, that is, electron-donating substituents on the alkene increase the rate. The malonyl radical, for example, reacts with enamines 23 times faster than with acryl esters. 

Malonyl radicals (130) can be generated from halomalonates using tri-n-butyltin hydride and perhaps not surprisingly turn out to be... 

Oxidation of diethyl a-benzylmalonate (25) by Mn(III) acetate in acetic acid at 70 °C in the presence of mono- or disubstituted alkynes leads to dihydronaphthalene derivatives (26) in moderate to good yields (equation 33). A mechanistic scheme involving the formation of the corresponding malonyl radical, its addition to a triple bond and intramolecular homolytic aromatic substitution of the vinyl radical adducts is discussed. Absolute rate constants, obtained from competitive studies, for the addition of a-benzylmalonyl radicals to a variety of alkynes cover few orders of magnitude e.g. the rate constants at 60 °C are 3x10 and 1 x 10 s for 4-octyne and phenylacetylene respectively. 

Evidence that the transition state of the addition is characterized by a significant charge transfer from the substrate to the radical is also obtained, in agreement with the electrophilic character of malonyl radical. 

Oxidatively generated electrophilic malonyl radicals react regiospecifically with thiophene to form (2-thienyl)malonic ester <88H(27)2627>. Treatment of thiophene with cerium(IV) sulfate and an excess of dimethyl malonate in methanol at room temperature yields 2-thienylmalonic ester in 85% yield. In this case, the initially formed cr-radical is oxidized by the cerium(IV) sulfate. 2-Methylthiophene similarly gives the 5-malonyl-substituted product. Benzo[i]thiophene leads to the 2-malonyl-benzo[Z)]thiophene in 41% yield. Monosubstituted malonates could also be used in this reaction. Thiophene and 2-acetylthiophene react with triethyl methanetricarboxylate in the presence of Mn(III) to form the corresponding thienylmethane tricarboxylic esters. Yields are about 55% <91S567>. 

The rate of ceric oxidation of malonic add and its diethyl ester in acetic acid/sul-furic acid solutions has recently been reported by Vaidya et al. (1987). They find no evidence for precursor complex formation in either system. The reactive Ce(IV) species appear to be Ce(S04)2 ( 2) and CefSO ) " k 2). The second-order rate parameter for the oxidation of malonic add is 40 times greater than that for the ester. Oxidation of the ester is proposed to occur through the enol form yielding a malonyl radical analogous to that identified by Amjad and McAuley. Foersterling et al. (1987) find that the second-order rate constant for malonic acid oxidation by Ce(lV) in sulfuric acid is in excellent agreement with the value of Vaidya et al. They observe that Ce(III) does inhibit the reaction in sulfuric add, which they attribute to a reversible Ce(IV) malonic acid rate-controlling step. 

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