Radical carbonylations

Free-Radical Carbonylation of Alkyl Halides in scC02... 

The utility of SCFs is not limited to organotransi-tion metal chemistry. scC02 is a promising medium for free-radical carbonylation of organic halides to ketones or aldehydes. As shown in Figure 15A, the... 

A new free-radical carbonylation strategy, employing S -phenyl chlorothioformates and alkyl halides, has been developed. Reaction with (Eu3Sn)2 furnishes the corresponding S -phenyl esters in moderate yields (Scheme 30). 

The same research group has further performed radical carbonylation reactions on the same microreactor system [36]. First, alkyl halides were initiated and effectively reacted with pressurized carbon monoxide to form carbonyl compounds. The principle was subsequently successfully extrapolated to the multicomponent coupling reactions. 1-Iodooctane, carbon monoxide and methyl vinyl ketone were reacted in the presence of 2,2 -azobis(2,4-dimethylvaleronitrile) (V-65) as an initiator and tributyltin hydride or tris(trimethylsilyl)silane (TTMSS) as catalyst (Scheme 15). 

Scheme 15 A three-component condensation including a radical carbonylation [36]...

Fukuyama T, Rahman T, Kamata N et al (2009) Radical carbonylations using a continuous microflow system. Beilstein J Org Chem 5 No. 34... 

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... 

Free-radical-mediated four-component coupling reactions are rare. However, when an allyltin-mediated radical carbonylation is conducted in the presence of electron-deficient alkenes, four-component coupling reactions take place efficiently to give good yields of p-functionalized <5,fi-unsaturated ketones [40]. The wide scope of this four-component coupling reaction is noteworthy Primary, secondary, and tertiary alkyl bromides and iodides can be used as well as aromatic and vinylic halides. A variety of electron-deficient alkenes, such as methyl vinyl ketone, ethyl acrylate, acrolein, acrylonitrile, and vinyl sulfone, can be used as the acyl radical trap (Scheme 6.23). Fluorous allyltin compounds can also be used in four-component coupling reactions [41]. 

Radical carbonylation can also be conducted in a zinc-induced reduction system. A similar three-component transformation reaction to that illustrated in the second equation of Scheme 6.14 can be attained using zinc and protic solvents (Scheme 6.38) [59]. The observed stereochemical outcome is identical to that for the tin hydride-mediated reaction, providing a additional evidence for free-radical generation, radical carbonylation, and acyl radical cyclization taking place simultaneously, even in the zinc-induced system. In this system, however, the final step is reduction to form a carbanion and protonation. 

Radical carbonylative ring-closure of 6-iodohexyl acrylate (153) with (Me3Si)3 SiH/AIBN in supercritical C02 as reaction media affords the 11-membered macrolide (154) (eq. 4.55). 

Very recently Ryu and coworkers disclosed radical carbonylation/Sonogashira coupling sequences (Fig. 44) [218]. The reaction is applicable to primary, secondary, and tertiary alkyl iodides 177, and terminal aryl or alkyl alkynes 185. Alkynyl... 

Cyclization of alkyl radicals derived from acryl enamides gives piperidin-2-ones (Equation (10)).51 Radical carbonyla-tions have become a promising tool for the introduction of carbon monoxide into organic molecules. Macrocyclic compounds are prepared by intramolecular cyclization via radical carbonylation (Equation (1l)).53... 

As discussed in section 4, reaction of the peroxy radicals with N02 gives thermally unstable peroxy nitrates. Reaction with H02 gives hydroperoxides and possibly carbonyl compounds. Reaction with other peroxy radicals (R 02) gives alkoxy radicals, carbonyls, and alcohols. The alkoxy radicals will then either isomerize, react with 02, or decompose (see Sect. 3). Thus, the NO3 radical-initiated atmospheric degradation of alkenes leads to oxiranes (generally in small yield), nitrooxy hydroperoxides, nitrooxy carbonyls, and nitrooxyalcohols. For a detailed listing of products from individual alkenes the reader should consult Calvert et al. [55]. 

It is noteworthy that l-(2-iodoethyl)-17/-pyrrole, under the usual radical carbonylation conditions, gave 3-(17/-pyrrol-l-yl)propanal 990 in 60% yield (Equation 235), and no 2,3-dihydro-17/-pyrrolizin-l-one 981 (R = H) (Equation 232) <2000TL3035>. 

Scheme 43 Formation of thioesters through radical carbonylations...

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

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