Short description
(English)
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The transfer of a hydrogen atom to a carbon-centered radical is a key step of many important radical reactions such as dehalogenation, deoxygenation, as well as more complex processes involving single and multiple C-C bond formation. The development of highly efficient and non-toxic hydrogen atom donors is of highest interest for synthetic applications ranging from research lab scale to industrial applications. This project is dedicated to the development of bioinspired methods using simple phenols to deliver hydrogen atoms to carbon centered radicals.
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Abstract
(English)
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Radical reactions represent a unique tool for the formation of carbon–carbon bond under very mild reaction conditions. The development of highly efficient, non-toxic hydrogen atom donors is of highest interest for synthetic applications ranging from small laboratory scale to industrial applications. Inspired by Nature who is using thiols and phenols as hydrogen atom donors to inhibit radical reaction, we decided to investigate the use of such compounds in radical chain processes. Radical reactions represent a unique tool for the formation of carbon–carbon bond under very mild reaction conditions. The development of highly efficient, non-toxic hydrogen atom donors is of highest interest for synthetic applications ranging from small laboratory scale to industrial applications. Inspired by Nature who is using thiols and phenols as hydrogen atom donors to inhibit radical reaction, we decided to investigate the use of such compounds in radical chain processes. 1) In the first part of our research, we have demonstrated that catechol derivatives, when used with trialkylboranes, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors.The system 4-tert-butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications as demonstrated by highly efficient radical cyclizations. Cyclizations leading to the formation of quaternary centers can be performed in an all-at-once process (no slow addition of the hydrogen atom donor) at standard concentrations. Moreover, the H-donor properties of catechol derivatives can be fine-tuned by changing their substitution pattern. For instance, in slow radical cyclization processes an enhanced ratio of cyclized/uncyclized products could be obtained by using 3-methoxycatechol instead of 4-tert-butylcatechol. The moderate price and low toxicity of catechols make them attractive reagents for preparative applications. 2) Based on the deiodination process mentioned above, a procedure to achieve the carbohydrogenation of alkenes by addition of electrophilic radicals to the alkenes using 4-tert-butylcatechol as a source of hydrogen atoms has been developed. This reaction is works exceptionally well with non-terminal alkenes and these results are rationalized by polar effects as well as a biomimetic repair mechanism. 3) By using a thiol catalyst, an efficient method for the radical deuteration of iodides and related compounds has been developed. In this reaction, deuterated water is the source of deuterium atoms making this approach particularly attractive. During this work, the mechanism of the Wood deoxygenation reaction based on the use of triethylborane and water, a reaction that was creating the buzz a few year ago in the community of orgnaic chemists, could be revised. 4) The efficiency of the radical addition-translocation-cyclization reaction developed a few year ago in our group could be enhanced but running it with sulfonyl radicals. A unique effect of memory of chirality effect was observed in this reaction. This work represents also an important contribution to the development of environmentally friendly radical reactions.
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