Radical carbonylations, examples

Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp2TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

The free-radical carbonylation of iodoalkanes in SCCO2 initiated by AIBN (0.2-0.3 equiv.) with (TMS)3SiH (1.5 equiv.) was studied for both intermolecular reactions and intramolecular reactions (Scheme 42). For example, the carbonylative addition of 1-iodooctane 304 to acrylonitrile was carried out at 80°C and 50 atm of CO in SCCO2 under a total pressure of 310 atm to give 4-oxododecanenitrile 305 in 90% yield. Also, the intramolecular carbonylation of 6-iodohexyl acrylate 306 under similar conditions afforded 11-membered macro-lide 307 in 68% yield. 

Radical carbonylation reaction serves as a powerful tool for the synthesis of a range of carbonyl compounds. Radical carbonylation has been successfully applied to the synthesis of functionalized ketones from alkyl, aryl, and alkenyl halides.The radical aminocarbonylation reaction of alkynes and azaenynes provided efficient routes to 2-substituted acrylamides, lactams, and pyrrolidinones. For example, the aminocarbonylation of 4-pentyn-l-yl acetate 318 initiated by tributyltin hydride (Bu"3SnH) (30mol%) with AIBN (20mol%) gave acrylamide 325 in 92% yield (Scheme 43).A proposed mechanism starts from the addition of tributyltin radical 319 to alkyne... 

It is important to note that even certain phase-transfer catalysts can be carbonylated to carboxylic acids, not by cobalt tetracarbonyl anion catalysis, but by acetylcobalt tetracarbonyl. This is a slow but high-yield reaction that occurs for quaternary ammonium salts that are capable of forming reasonably stable free radicals. For example, phenylacetic acid is formed in 95% yield from benzyltriethylammonium chloride (benzyl radi-... 

Scheme 5. Radical carbonylations to give cyclopentanes. E is, for example, -COOR.

For example, the following example of tandem radical carbonylation, which was reported by Curran, Ryu, and their co-workers, suggests that the E/Z configurations of a,yff-unsaturated acyl radicals are not directly associated with the subsequent radical cyclization (Scheme 4-10) [23]. The fact that the reaction was clean... 

Radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers provides a new type of multi-component coupling reaction, and a typical example is given in Scheme 4-38 [65]. In this method, plural radical Cl synthons are consecutively combined. 

A variety of methods are available for the synthesis of heterocyclic carbonyl compounds by radical cyclization. For example, the cyclization of alkoxycarbonyl radicals is particularly useful for the synthesis of five- and six-membered ring lactones [80]. Recent applications of this cyclization method include Zard s photoly-tical transformation of an alkoxycarbonyl dithiocarbonate having a double bond which can serve as a key step in the synthesis of ( )-cinnamolide and RA. Evans s enantioselective synthesis of 4-hydroxy butenolide terminus, which is applicable to the synthesis of mucocin [81J. Amidyl radical cyclizations are frequently utilized for the synthesis of five- and six-membered ring lactams [82]. However, this section only focuses on recent methods for heterocyclic carbonyl compounds by an n-i-1 type strategy based on radical carbonylations. 

It has also been speculated that the concomitantly generated perfluoroalkyl radicals play a minor role in ozone depletion but, in contrast with chlorine, the trifluor-omethyl radical, for example, is cleared from the atmosphere relatively quickly via its irreversible conversion to carbonyl difluoride (GF2O) [28]. Whereas bromine... 

Unlike the 4-alkenyl/CO system, the following two cyclization systems, based on C-N double bonds, are completely selective and favor a five-membered ring (Scheme 8). Fallis and Brinza who used a diphenylhydrazone derivative as an acyl radical trap [32] reported the first example in this series. As shown in the first two examples in Table 3, radical carbonylation gave 2-hydrazinocyclopentanones in good yields. Ryu, Komatsu and coworkers reported acyl radical cyclization onto N C double bond, which proceeds exclusively in a 5-exo manner to give pyrrolidi-nones in good yield (runs 3-5) [33]. For an aromatic substrate, it is necessary to use a ketimine rather than an aldimine, since aromatic radical abstracts an imine hy-... 

The next four examples shown in Table 3 demonstrate that tin hydride-mediated radical carbonylation can be efficiently combined with intramolecular Sh2 type reaction of acyl radicals at sulfur, providing good yields of y-thiolactones [37]. The ability of the ert-butyl radical as an Sh2 type leaving group is inferior to that of the benzyl radical [38]. Nevertheless, the fer/-butyl radical in this case has an advantage over the benzyl radical, since the starting benzylthiobutyl radical suffers an unde-... 

Recently, Miranda and coworkers reported that tin hydride-mediated radical carbonylation can be applied to include the synthesis of ketones fused with heterocyclic rings, such as pyrroles and indoles. In the example given in run 10, an acyl radical attack at aromatic carbon and in situ oxidation leads to an indole-fused cyclopentanone in good yield [39]. On the other hand, an example shown in run 11 makes use of a methanesulfonyl group as a leaving radical [40]. When a related substrate which does not contain a sulfonyl substituent was used, a simple radical formylation took place. 

Ryu, Sonoda and coworkers reported that tris(trimethylsilyl)silane is a useful mediator for a three-component coupling reaction [45]. Table 4 summarizes examples of radical carbonylations mediated by (TMS)3SiH. The first example shows a three-component coupling reaction in which hexyl iodide, CO, and acrylonitrile combine to form a P-cymo ketone. The CO addition step is in competition with the addition to the alkene and the hydrogen abstraction from radical mediator. Thus, it is anticipated that a set of less efficient hydrogen donors, such as (TMS)3SiH, and the use of a smaller excess amount of an alkene is most favorable. Indeed, the reaction can be carried out at only 20 30 atm of CO pressure, substantially below the 80-90 atm which is used for carbonylative acyl radical reactions which are mediated by tin hydride, and a nearly stoichiometric amount (1.2 equiv) of acrylonitrile is sufficient. Some other examples, which include vinyl radical carbonylation, are also shown in Table 4. 

The final example shown in Table 5 shows that allyltin-mediated radical carbonylation can be successfully applied to macrocyclization, as in the case of tris(trimethylsilyl)silane [46b]. 

The radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers [58, 59, 60] provides a new type of multicomponent coupling reaction where plural radical Cl synthons are consecutively combined [61]. In the transformation, allyltin was used to serve as a trap of benzenesulfonyl radical which converts sulfonyl radical to a tin radical, thus creating a chain. Scheme 14 illustrates such an example, where the product was easily dehydroxylated to give the corresponding tricarbonyl compound on treatment with zinc/AcOH. The radical acylation reaction by Kim s sulfonyl oxime ethers can be conducted under irradiation with the addition of hexamethylditin. This is an alternative path for achieving a similar transformation without the use of photolysis equipment. Scheme 15 illustrates several examples where carbon monoxide and Kim s sulfonyl oxime ethers are successfully combined to create new tandem radical reaction sequences [61],... 

Maricq et al. [180] have studied the self-reaction of FCO radicals. Although the self-reaction will be of minor importance for upper atmospheric chemistry, this reaction is critical in laboratory studies involving FCO radicals. For example, in the measurement of quantum yields from CFjO, CFCIO, and HFCO photodissociation, the self reaction could lead to a gross underestimation of the quantum yields. The rate coefficient of 1.9 0.2 X 10 cm s suggests that the self-reaction is quite rapid. In the self-reaction, the FCO radicals recombine to form oxylfluoride, which is produced with excess energy above the barrier for molecular dissociation to carbonyl fluoride and carbon monoxide [192]. 

The mechanism Is considered to Involve the charge-transfer state (MInorganic radical—for example, I, N3, and so on. Similarly, the rate constants of quenching of triplet eosln by anions In aqueous... 

In the case of the methyl peroxy radical, for example, the presence of an F atom, Cl atom (s), or OH group, increases the rate constant by more than a factor of 10. The effect of bromine, on the contrary seems smaller. The enhancement is even larger with the presence of a carbonyl group e.g. acetonylperoxy) or an aromatic ring e.g, benzylperoxy). 

When another group having higher priority for citation as principal group is also present, the ketonic oxygen may be expressed by the prefix 0x0-, or one can use the name of the carbonyl-containing radical, as, for example, acyl radicals and oxo-substituted radicals. Examples are... 

It might be noted that most (not all) alkenes are polymerizable by the chain mechanism involving free-radical intermediates, whereas the carbonyl group is generally not polymerized by the free-radical mechanism. Carbonyl groups and some carbon-carbon double bonds are polymerized by ionic mechanisms. Monomers display far more specificity where the ionic mechanism is involved than with the free-radical mechanism. For example, acrylamide will polymerize through an anionic intermediate but not a cationic one, A -vinyl pyrrolidones by cationic but not anionic intermediates, and halogenated olefins by neither ionic species. In all of these cases free-radical polymerization is possible. 

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