ChemInform Abstract: Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI<sub>2</sub>, the Kagan Reagent

Krief, Alain; Laval, A.‐M.

doi:10.1002/chin.199921280

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“…In particular, reductive ET to organic compounds is a powerful method for the activation of substrates via the formation of radicals, radical anions, anions, and dianions that can be exploited in bond-cleaving and bond-forming reactions. − While alkali metals were used in early synthetic ET procedures, the latter half of the 20th century saw the emergence of a new generation of reductive ET reagents. At the vanguard of this new order was samarium diiodide (SmI 2 ), and the incredible synthetic potential of this reagent was quickly recognized and mapped by the leading synthetic teams of the day. − Indeed, since its introduction to the synthetic community in 1977 by Kagan, , SmI 2 has become one of the most important reducing agents available in the laboratory. − ,− In his seminal paper, Kagan observed that “carboxylic acid and ester were not reduced by SmI 2 ”, and this view became widely accepted in the field . It has taken over 35 years to overturn this dogma and for the reduction of carboxylic acid derivatives using SmI 2 to take its place alongside aldehyde/ketone reduction as a powerful activation mode for synthesis.…”

Section: Introductionmentioning

confidence: 99%

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

2015

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Reductive electron transfer (ET) to organic compounds is a powerful method for the activation of substrates via the formation of radicals, radical anions, anions, and dianions that can be exploited in bond-cleaving and bond-forming processes. Since its introduction to the synthetic community in 1977 by Kagan, SmI2 has become one of the most important reducing agents available in the laboratory. Despite its widespread application in aldehyde and ketone reduction, it was widely accepted that carboxylic acid derivatives could not be reduced by SmI2; only recently has our work led to this dogma being overturned, and the reduction of carboxylic acid derivatives using SmI2 can now take its place alongside aldehyde/ketone reduction as a powerful activation mode for synthesis. In this Account, we set out our studies of the reduction of carboxylic acid derivatives using SmI2, SmI2-H2O, and SmI2-H2O-NR3 and the exploitation of the unusual radical anions that are now accessible in unprecedented carbon-carbon bond-forming processes. The Account begins with our serendipitous discovery that SmI2 mixed with H2O is able to reduce six-membered lactones to diols, a transformation previously thought to be impossible. After the successful development of selective monoreductions of Meldrum's acid and barbituric acid heterocyclic feedstocks, we then identified the SmI2-H2O-NR3 reagent system for the efficient reduction of a range of acyclic carboxylic acid derivatives that typically present a significant challenge for ET reductants. Mechanistic studies have led us to propose a common mechanism for the reduction of carboxylic acid derivatives using Sm(II), with only subtle changes observed as the carboxylic acid derivative and Sm(II) reagent system are varied. At the center of our postulated mechanism is the proposed reversibility of the first ET to the carbonyl of carboxylic acid derivatives, and this led us to devise several strategies that allow the radical anion intermediates to be exploited productively in efficient new processes. First, we have used internal directing groups in substrates to "switch on" productive ET to esters and amides and have exploited such an approach in tag-removal cyclization processes that deliver molecular scaffolds of significance in biology and materials science. Second, we have exploited external ligands to facilitate ET to carboxylic acid derivatives and have applied the strategy in telescoped reaction sequences. Finally, we have employed follow-up cyclizations with alkenes, alkynes, and allenes to intercept radical anion intermediates formed along the reaction path and have employed this strategy in complexity-generating cascade approaches to biologically significant molecular architectures. From our studies, it is now clear that Sm(II)-mediated ET to carboxylic acid derivatives constitutes a general strategy for inverting the polarity of the carbonyl, allowing nucleophilic carbon-centered radicals to be formed and exploited in novel chemical processes.

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Section: Introductionmentioning

confidence: 99%

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

2015

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ChemInform Abstract: Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI₂, the Kagan Reagent

Cited by 1 publication

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Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

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ChemInform Abstract: Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI2, the Kagan Reagent

Cited by 1 publication

References 1 publication

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

Sm(II)-Mediated Electron Transfer to Carboxylic Acid Derivatives: Development of Complexity-Generating Cascades

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ChemInform Abstract: Coupling of Organic Halides with Carbonyl Compounds Promoted by SmI₂, the Kagan Reagent