Free‐Radical Carbonylations: Then and Now

Abstract

Although known since the 1950s, free‐radical carbonylation has not received much attention until only recently. In the last few years the application of modern free‐radical techniques has revealed the high synthetic potential of this reaction as a tool for introducing CO into organic molecules. Clearly now is the time for a renaissance of this chemistry. Under standard conditions (tributyltin hydride/CO) primary, secondary, as well as tertiary alkyl bromides and iodides can be efficiently converted into the corresponding aldehydes. Aromatic and α,β‐unsaturated aldehydes can also be prepared from the parent aromatic and vinylic iodides. If the reaction is carried out in the presence of alkenes containing an electron‐withdrawing substituent, the initially formed acyl radical subsequently adds to the alkene, leading to a general method for the synthesis of unsymmetrical ketones. This three‐component coupling reaction can be extended successfully to allyltin‐mediated reactions. Thus, β,γ‐enones can be prepared from organic halides, CO, and allyltributylstannanes. In a remarkable one‐pot procedure alkyl halides can be treated with a mixture of alkene, allyltributylstannane, and carbon monoxide in a four‐component coupling reaction that provides β‐functionalized δ,ϵ‐unsaturated ketones by the formation of three new CC bonds. The reaction of 4‐pentenyl radicals with CO leads to acyl radical cyclization, which provides a useful method for the synthesis of cyclopentanones. Certain useful one‐electron oxidations can be combined efficiently with free‐radical carbonylations. These findings and others discussed in this article clearly demonstrate that free‐radical carbonylation can now be considered a practical alternative to transition metal mediated carbonylation.

Transition Metal Catalyzed Coupling Reactions under C−H Activation

“…[50] Corresponding carbonylations of aliphatic hydrocarbons with carbon monoxide under nonoxidizing conditions are of particular industrial interest since such processes might be able to compete with hydroformylation. Since the early work of Tanaka et al, radical reactions, [51] which in addition to the transition metal catalysis require photochemical activation, have been favored for this. Whereas Tanaka et al…”

Atom‐Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed CH Activation of Alkanes and Coupling with CO and Electrophilic Alkenes

“…[3] We recently reported a related transformation that can be achieved by using tetrabutylammonium cyanoborohydride as an alternative for toxic tin hydride.…”

Tin‐Free Radical Carbonylation: Synthesis of Acylated Oxime Ethers Using Alkyl Allyl Sulfone Precursors, Carbon Monoxide, and Phenylsulfonyl Oxime Ether

“…[1] Many cases of previously reported radical carbonylation utilize highly toxic organotin reagents as mediators. [2,3] In connection with our interest on tin-free radical reactions, [4] we have reported that alkyl allyl sulfone precursors are very effective for radical carbon-carbon bond formation under tin-free conditions.…”

“…[5] Furthermore, we also reported the synthesis of thiol esters and acyl cyanides based on tinfree radical carbonylations using alkyl allyl sulfone precursors [Eq. (1)]. [6,7] In our continued efforts to develop tin-free radical carbonylation reactions, we have studied the radical reactions of sulfonyl oxime ether 2 [8] with alkyl allyl sulfone precursors under CO pressure to achieve consecutive radical acylations in an indirect manner under tin-free conditions [Eq.…”