Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Cao Z

PROVIDER: S-EPMC8179574 | 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

Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)-H bonds with alkynes.

Project description:Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)-C(sp) coupling of unactivated C(sp3)-H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)-H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P-ligand catalyst for asymmetric oxidative cross-coupling of unactivated C(sp3)-H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N-fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C(sp3)-H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C(sp3)-C(sp), C(sp3)-C(sp2), and C(sp3)-C(sp3) bonds when allied with follow-up transformations.

| S-EPMC6908613 | biostudies-literature

"Sandwich" Diimine-Copper Catalyzed Trifluoroethylation and Pentafluoropropylation of Unactivated C(sp3 )-H Bonds by Carbene Insertion.

Project description:We report here "sandwich"-diimine copper complex-catalyzed trifluoroethylation and pentafluoropropylation of unactivated C(sp3 )-H bonds in alkyl esters, halides, and protected amines by employing CF3 CHN2 and CF3 CF2 CHN2 reagents. Reactions proceed in dichloromethane solvent at room temperature. Identical C-H functionalization conditions and stoichiometries are employed for generality and convenience. Selectivities for C-H insertions are higher for compounds possessing stronger electron-withdrawing substituents. Preliminary mechanistic studies point to a mechanism involving a pre-equilibrium forming a "sandwich"-diimine copper-CF3 CHN2 complex followed by rate-determining loss of nitrogen affording the reactive copper carbene. It reacts with trifluoromethyldiazomethane about 6.5 times faster than with 1-fluoroadamantane explaining the need for slow addition of the diazo compound.

| S-EPMC10642771 | 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

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

Visible-light promoted regioselective amination and alkylation of remote C(sp3)-H bonds.

Project description:The C-N cross coupling reaction has always been a fundamental task in organic synthesis. However, the direct use of N-H group of aryl amines to generate N-centered radicals which would couple with alkyl radicals to construct C-N bonds is still rare. Here we report a visible light-promoted C-N radical cross coupling for regioselective amination of remote C(sp3)-H bonds. Under visible light irradiation, the N-H groups of aryl amines are converted to N-centered radicals, and are then trapped by alkyl radicals, which are generated from Hofmann-Löffler-Freytag (HLF) type 1,5-hydrogen atom transfer (1,5-HAT). With the same strategy, the regioselective C(sp3)-C(sp3) cross coupling is also realized by using alkyl Hantzsch esters (or nitrile) as radical alkylation reagents. Notably, the α-C(sp3)-H of tertiary amines can be directly alkylated to form the C(sp3)-C(sp3) bonds via C(sp3)-H - C(sp3)-H cross coupling through the same photoredox pathway.

| S-EPMC7081228 | biostudies-literature

Intermolecular CDC amination of remote and proximal unactivated Csp3 -H bonds through intrinsic substrate reactivity - expanding towards a traceless directing group.

Project description:An intermolecular radical based distal selectivity in appended alkyl chains has been developed. The selectivity is maximum when the distal carbon is γ to the appended group and decreases by moving from γ → δ → ε positions. In -COO- linked alkyl chains, the same distal γ-selectivity is observed irrespective of its origin, either from the alkyl carboxy acid or alkyl alcohol. The appended groups include esters, N-H protected amines, phthaloyl, sulfone, sulfinimide, nitrile, phosphite, phosphate and borate esters. In borate esters, boron serves as a traceless directing group, which is hitherto unprecedented for any remote Csp3 -H functionalization. The selectivity order follows the trend: 3° benzylic > 2° benzylic > 3° tertiary > α to keto > distal methylene (γ > δ > ε). Computations predicted the radical stability (thermodynamic factors) and the kinetic barriers as the factors responsible for such trends. Remarkably, this strategy eludes any designer catalysts, and the selectivity is due to the intrinsic substrate reactivity.

| S-EPMC8635183 | 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

Hydroxy-directed fluorination of remote unactivated C(sp3)-H bonds: a new age of diastereoselective radical fluorination.

Project description:We report a photochemically induced, hydroxy-directed fluorination that addresses the prevailing challenge of high diastereoselectivity in this burgeoning field. Numerous simple and complex motifs showcase a spectrum of regio- and stereochemical outcomes based on the configuration of the hydroxy group. Notable examples include a long-sought switch in the selectivity of the refractory sclareolide core, an override of benzylic fluorination, and a rare case of 3,3'-difluorination. Furthermore, calculations illuminate a low barrier transition state for fluorination, supporting our notion that alcohols are engaged in coordinated reagent direction. A hydrogen bonding interaction between the innate hydroxy directing group and fluorine is also highlighted for several substrates with 19F-1H HOESY experiments, calculations, and more.

| S-EPMC9200124 | biostudies-literature

Copper-catalyzed remote C(sp3)-H azidation and oxidative trifluoromethylation of benzohydrazides.

Project description:The Hofmann-Löffler-Freytag (HLF) reaction is a prototypical example of radical-based remote functionalization of unactivated C(sp3)-H bond. While 1,5-hydrogen atom transfer (1,5-HAT) of the amidyl radical is thermodynamically favorable and is well-established, the method for the subsequent functionalization of the translocated carbon radical is still limited. We report herein two catalytic remote C(sp3)-H functionalization protocols. Cu(MeCN)4PF6-catalyzed reaction of 2-alkyl benzohydrazides 3 with TMSN3 in the presence of MeCO2OtBu affords the ?-azido amides 4, while CuCl-catalyzed reaction of 3 with Togni's reagent provides 2-(?-trifluoromethylvinyl)benzamides 5 via an oxidative ?-trifluoromethylation of the alkyl group. Mechanistic studies suggest that the ?-azidation of benzohydrazides 3 goes through 1,5-HAT followed by a Cu-mediated azido transfer cascade, while the oxidative ?-trifluoromethylation of 3 proceeds via, after 1,5-HAT process, a radical-polar crossover mechanism.

| S-EPMC6377619 | biostudies-literature