Synthesis of 1,3-Diols via Controlled, Radical-Mediated C-H ..

The invention of a method for the synthesis of 1,3-diols from the corresponding alcohols is described, via controlled, radical-mediated C−H functionalization. The sequence described herein entails near quantitative conversion to the corresponding trifluoroethyl carbamate, followed by a variant of the Hofmann−Löffler−Freytag reaction, cyclization, and hydrolysis to provide the 1,3-diols. In addition to the 10 examples presented herein, the syntheses of four natural products are facilitated by this directed oxyfunctionalization. This methodology is demonstrated to be orthogonal to other known C−H oxidations. Finally, this sequence is efficient, practical, inexpensive, and scalable.

with oxygen- and nitrogen-radicals: ..

1,3-Diol synthesis via controlled, radical-mediated C-H functionalization ..
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C-radicals generated via a 1,5-H radical ..

Pyridines are among the most prevalent heterocyclic structural units in pharmaceutical and agrochemical targets, as well as in materials science. Pyridines also provide convenient synthetic precursors to chiral dihydro- and tetrahydropyridines, as well as piperidines, which continue to be of interest as intermediates in alkaloid synthesis, in NADH models, and as important biologically active structures. Dihydropyridines in turn may also be converted to substituted pyridines through oxidation. Similarly, pyridines, dihydropyridines, and tetrahydropyridines are important building blocks in thepreparation of piperidine scaffolds via reduction or nucleophilic additions. The chemistry to directly functionalize pyridine remains a significant challenge due to poor chemoselectivity and the lower energy of the π-system relative to benzene. As a result, electrophilic aromatic substitution is not effective without the inclusion of substituents to activate the pyridine ring. This review examines the functionalization of -activated pyridinium species by the addition of nucleophiles and electrophiles, as well as by transition metal-mediated functionalization. The issues of regioselectivity, stereoselectivity, and the mechanisms of the additions will be addressed. Sections 2-4 are concerned with nucleophilic additions to pyridinium species forming dihydropyridines, which may be progressed to substituted pyridines or piperidines. The following two sections are concerned with the synthesis of substituted pyridines without the disruption of the aromaticity, via pyridinyl metal species. Section 5 examines electrophilic addition to -heteroatom pyridinium species following deprotonation adjacent to the nitrogen to afford substituted pyridines. The last section is concerned with transition metal-mediated C-H functionalization of pyridinium species. This review covers a substantial time period of the literature, from the 1940s to the current day, and state-of-the-art methodologies, and as such reflects some of the changing approaches and challenges in organic chemistry. The chemistry of benzopyridine derivatives (such as quinolines), intramolecular rearrangement, cycloaddition reactions, reductions (including addition of hydride), electrophilic aromatic substitution, and radical reactions, though important, will not be considered in this review.

Carboxylate-Directed C H Functionalization - [PDF …

Pyridines are among the most prevalent heterocyclic structural units in pharmaceutical and agrochemical targets, as well as in materials science. Pyridines also provide convenient synthetic precursors to chiral dihydro- and tetrahydropyridines, as well as piperidines, which continue to be of interest as intermediates in alkaloid synthesis, in NADH models, and as important biologically active structures. Dihydropyridines in turn may also be converted to substituted pyridines through oxidation. Similarly, pyridines, dihydropyridines, and tetrahydropyridines are important building blocks in thepreparation of piperidine scaffolds via reduction or nucleophilic additions. The chemistry to directly functionalize pyridine remains a significant challenge due to poor chemoselectivity and the lower energy of the π-system relative to benzene. As a result, electrophilic aromatic substitution is not effective without the inclusion of substituents to activate the pyridine ring. This review examines the functionalization of -activated pyridinium species by the addition of nucleophiles and electrophiles, as well as by transition metal-mediated functionalization. The issues of regioselectivity, stereoselectivity, and the mechanisms of the additions will be addressed. Sections 2-4 are concerned with nucleophilic additions to pyridinium species forming dihydropyridines, which may be progressed to substituted pyridines or piperidines. The following two sections are concerned with the synthesis of substituted pyridines without the disruption of the aromaticity, via pyridinyl metal species. Section 5 examines electrophilic addition to -heteroatom pyridinium species following deprotonation adjacent to the nitrogen to afford substituted pyridines. The last section is concerned with transition metal-mediated C-H functionalization of pyridinium species. This review covers a substantial time period of the literature, from the 1940s to the current day, and state-of-the-art methodologies, and as such reflects some of the changing approaches and challenges in organic chemistry. The chemistry of benzopyridine derivatives (such as quinolines), intramolecular rearrangement, cycloaddition reactions, reductions (including addition of hydride), electrophilic aromatic substitution, and radical reactions, though important, will not be considered in this review.

The conversion of an alcohol into a 1,3- diol via controlled, radical-mediated C-H functionalization has been demonstrated
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