Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Conformational Flexibility as a Tool for Enabling Site-Selective Functionalization of Unactivated sp³ C-O Bonds in Cyclic Acetals.

ABSTRACT: A dual catalytic manifold that enables site-selective functionalization of unactivated sp³ C-O bonds in cyclic acetals with aryl and alkyl halides is reported. The reaction is triggered by an appropriate σ*-p orbital overlap prior to sp³ C-O cleavage, thus highlighting the importance of conformational flexibility in both reactivity and site selectivity. The protocol is characterized by its excellent chemoselectivity profile, thus offering new vistas for activating strong σ sp³ C-O linkages.

SUBMITTER: Romano C

PROVIDER: S-EPMC9264358 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds.

Project description:A general efficient regioselective cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was demonstrated using atmospheric (1-2 atm) carbon monoxide as a C1 source. This straightforward approach provides access to α-spiral succinimide regioselectively in a good yield. Cobalt catalyzed sp3 C-H bond carbonylation is reported for the first time including the functionalization of (β)-C-H bonds of α-1°, 2°, 3° carbons and even internal (β)-C-H bonds. Our initial mechanistic investigation reveals that the C-H activation step is irreversible and will possibly be the rate determining step.

| S-EPMC5369400 | biostudies-literature

Anaerobic functionalization of unactivated C-H bonds.

Project description:The functionalization of alkanes was once thought to lie strictly within the domain of enzymes that activate dioxygen in order to generate an oxidant with suitable potency to cleave inert C-H bonds. The emergence of the radical SAM superfamily of enzymes-those which use S-adenosyl-l-methionine as a precursor to a 5'-deoxyadenosyl 5'-radical-has kindled a renaissance in the study of radical-dependent enzymatic reactions, and is ushering in a wealth of new and intriguing chemistry that remains to be elucidated. This review will focus on a special subclass of radical SAM enzymes that functionalize inert C-H bonds, highlighting the functional groups and the chemistry that leads to their insertion. Within this class are first, enzymes that catalyze sulfur insertion, the prototype of which is biotin synthase; second, enzymes that catalyze P-methylation or C-methylation, such as P-methylase or Fom3; third, enzymes that catalyze oxygen insertion, such as the anaerobic magnesium protoporphyrin-IX oxidative cyclase (BchE); and fourth, enzymes that functionalize n-hexane or other alkanes as the first step in the metabolism of these inert compounds by certain bacteria. In addition to surveying reactions that have been studied at various levels of detail, this review will speculate on the mechanisms of other types of reactions that this chemistry lends itself to.

| S-EPMC2762545 | biostudies-literature

Peracid Oxidation of Unactivated sp3 C-H Bonds: An Important Solvent Effect.

Project description:The peracid oxidation of hydrocarbons in chlorinated solvents is a low yielding and poorly selective process. Through a combination of DFT calculations, spectroscopic studies, and kinetic measurement it is shown that the origin of this is electronic in nature and can be influenced through the addition of hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA). Performing the reaction of a cycloalkane with mCPBA in a fluorinated alcohol solvent such as nonafluoro-tert-butanol (NFTB) or hexafluoroisopropanol (HFIP), which act as strong HBD and poor HBA, leads to significantly higher yields and selectivities being observed for the alcohol product. Application of the optimised reaction conditions allows for the selective oxidation of both cyclic and linear alkane substrates delivering the corresponding alcohol in up to 86 % yield. The transformation shows selectivity for tertiary centres over secondary centres and the oxidation of secondary centres is strongly influenced by stereoelectronic effects. Primary centres are not oxidised by this method. A simple computational model developed to understand this transformation provides a powerful tool to reliably predict the influence of substitution and functionality on reaction outcome.

| S-EPMC10946557 | biostudies-literature

Dithiane-directed Rh(iii)-catalyzed amidation of unactivated C(sp3)-H bonds.

Project description:An oxidant-free Rh(iii)-catalyzed direct amidation of alkyl dithianes via C(sp3)-H bond activation utilizing diverse and robust dioxazolone reagents is reported. The reaction hinges on use of a Cp*Rh(iii) complex in combination with an essential amino-carboxylate additive to generate usefully protected 1,3-aminoaldehyde derivatives. The scalability of the reaction was demonstrated as was a series of downstream product functionalizations, including dithiane deprotection, anion alkylation and reductive desulfurization, highlighting the general applicability of this transformation in the synthesis of novel scaffolds and building blocks.

| S-EPMC6457195 | biostudies-literature

Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds.

Project description:Selective deuteration of unactivated C(sp3)-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp3)-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D2O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp3)-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp3)-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp3)-H bonds.

| S-EPMC9307835 | biostudies-literature

Remote Allylation of Unactivated C(sp3)-H Bonds Triggered by Photogenerated Amidyl Radicals.

Project description:The allylation reaction is a highly versatile transformation in chemical synthesis. While many elegant direct C(sp2)-H allylation reactions have been developed, the direct allylation of unactivated C(sp3)-H bonds is underdeveloped. By applying photoredox catalysis and a [1,5]-HAT process, herein we report a direct allylation of unactivated C(sp3)‒H bonds. This photocatalyzed transformation is tolerant of several functional groups in the amide and allylic chloride substrates. Various allyl-substituted amide products were obtained with good yields and high δ-selectivity.

| S-EPMC8186322 | biostudies-literature

Photo-induced copper-catalyzed alkynylation and amination of remote unactivated C(sp3)-H bonds.

Project description:A method for remote radical C-H alkynylation and amination of diverse aliphatic alcohols has been developed. The reaction features a copper nucleophile complex formed in situ as a photocatalyst, which reduces the silicon-tethered aliphatic iodide to an alkyl radical to initiate 1,n-hydrogen atom transfer. Unactivated secondary and tertiary C-H bonds at β, γ, and δ positions can be functionalized in a predictable manner.

| S-EPMC8179574 | biostudies-literature

Palladium-catalyzed ligand-promoted site-selective cyanomethylation of unactivated C(sp3)-H bonds with acetonitrile.

Project description:The direct cyanomethylation of unactivated sp3 C-H bonds of aliphatic amides was achieved via palladium catalysis assisted by a bidentate directing group with good functional group compatibility. This process represents the first example of the direct cross-coupling of sp3 C-H bonds with acetonitrile. Considering the importance of the cyano group in medicinal and synthetic organic chemistry, this reaction will find broad application in chemical research.

| S-EPMC5477045 | biostudies-literature

Iodine(III) promotes cross-dehydrogenative coupling of N-hydroxyphthalimide and unactivated C(sp3)-H bonds.

Project description:Cross-dehydrogenative coupling reactions provide a method to construct new chemical bonds by direct C-H activation without any pre-functionalization. Compared to functionalization of a C-H bond α- to ether oxygen, α- to carbonyl, or at a benzylic position, functionalization of unactivated hydrocarbons is difficult and often requires high temperatures, a transition-metal catalyst, or a superstoichiometric quantity of volatile, toxic, and explosive tert-butylhydroperoxide. Here, a cross-dehydrogenative C-O coupling reaction of N-hydroxyphthalimide with unactivated alkanes, nitriles, ethers, and thioethers has been realized by using iodobenzene diacetate as the radical initiator. The current protocol enables efficient functionalization of unactivated hydrocarbons and nitriles through inert C(sp3)-H bond activation under mild reaction conditions. O-substituted NHPI derivatives are generated in good yields under metal-free conditions.

| S-EPMC9814821 | biostudies-literature

Site Selective Chlorination of C(sp3 )-H Bonds Suitable for Late-Stage Functionalization.

Project description:C(sp3 )-Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp3 )-H bond. However, most current methods for the chlorination of C(sp3 )-H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late-stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp3 )-H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H-atom abstractor under mild conditions, and a readily-accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late-stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients.

| S-EPMC8594412 | biostudies-literature