Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Site-Selective Functionalization of Unactivated Allylic C-H Bonds via Direct Deprotonation with KTMP: Application to the Formal Total Synthesis of (+)-Artemisinin from Amorphadiene.

ABSTRACT: The site-selective functionalization of unactivated allylic C-H bonds via direct deprotonation using KTMP is described. The conversion of amorphadiene to artemisinic alcohol via a simple, highly regioselective deprotonation over 4 other possible allylic sites is shown with further extrapolation to the first large-scale telescoped chemical synthesis of artemisinic acid from amorphadiene. Finally, application of the method for the successful site-selective functionalization of unactivated allylic C-H bonds in other terpene-based natural products is also highlighted.

SUBMITTER: Clanton NA

PROVIDER: S-EPMC9841608 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Site-Selective Functionalization of Unactivated Allylic C-H Bonds via Direct Deprotonation with KTMP: Application to the Formal Total Synthesis of (+)-Artemisinin from Amorphadiene.

Clanton Nicholas A NA Wilson Nicolas A NA Ortiz Eliezer E Blumberg Shawn T ST Frantz Doug E DE

Organic letters 20230102 1

The site-selective functionalization of unactivated allylic C-H bonds via direct deprotonation using KTMP is described. The conversion of amorphadiene to artemisinic alcohol via a simple, highly regioselective deprotonation over 4 other possible allylic sites is shown with further extrapolation to the first large-scale telescoped chemical synthesis of artemisinic acid from amorphadiene. Finally, application of the method for the successful site-selective functionalization of unactivated allylic ...[more]

PMID: 36592432

Similar Datasets

Allylic functionalization of unactivated olefins with Grignard reagents.

Project description:New advances in the functionalization of unactivated olefins with carbon nucleophiles have provided more efficient and practical approaches to convert inexpensive starting materials into valuable products. Recent examples have been reported with stabilized carbon nucleophiles, tethered carbon nucleophiles, diazoesters, and trifluoromethane donors. A general method for functionalizing olefins with aromatic, aliphatic, and vinyl Grignard reagents was developed. In a one-pot process, olefins are oxidized by a commercially available reagent to allylic electrophiles, which undergo selective copper-catalyzed allylic alkylation with Grignard reagents. Products are formed in high yield and with high regioselectivity. This was utilized to synthesize a series of skipped dienes, a class of compounds that are prevalent in natural products and are difficult to synthesize by known allylic alkylation methods.

| S-EPMC4038264 | 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

Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification.

Project description:We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.

| S-EPMC3911985 | biostudies-literature

Heteroarylation of unactivated C-H bonds suitable for late-stage functionalization.

Project description:The late-stage introduction of diverse heterocycles onto complex small molecules enables efficient access to new medicinally relevant compounds. An attractive approach to such a transformation would utilize the ubiquitous aliphatic C-H bonds of a complex substrate. Herein, we report a system that enables direct C-H heteroarylation using a stable, commercially available O-alkenylhydroxamate with heterocyclic sulfone partners. The C-H heteroarylation proceeds efficiently with a range of aliphatic substrates and common heterocycles, and is a rare example of heteroarylation of strong C-H bonds. Importantly, the present approach is amenable to late-stage functionalization as the substrate is the limiting reagent in all cases.

| S-EPMC9580477 | biostudies-literature

Metal-free direct alkylation of unfunctionalized allylic/benzylic sp<sup>3</sup> C-H bonds <i>via</i> photoredox induced radical cation deprotonation.

Project description:Despite notable recent efforts, a catalytic and convenient strategy for the direct alkylation of unactivated allylic or benzylic sp3 C-H bonds remains a formidable challenge facing the synthesis community. We herein report an unprecedented allylic/benzylic alkylation using only an organo-photoredox catalyst, which enables coupling of a broad scope of alkenes/arenes and electron-deficient alkenes in an atom- and redox-economic manner. A photoredox induced alkene/arene radical cation deprotonation is proposed to smoothly generate the key allylic and benzylic radical intermediates. It represents the first C-C bond formation via radical cation deprotonation under visible light conditions. The resulting products can be easily scaled up and directly converted to γ,δ-unsaturated or α,β-diaryl-acids, -esters, -amides, -pyrazoles, -isoxazoles, as well as lactones, which enables this mild and selective sp3 C-H alkylation to rapidly access complex bioactive molecules.

| S-EPMC5618257 | biostudies-literature

Catalytic functionalization of unactivated primary C-H bonds directed by an alcohol.

Project description:New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex molecules. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compound containing many such bonds and an array of functional groups. The site-selective functionalization of aliphatic C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-molecule synthesis, and processes catalysed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliphatic C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired molecule. To overcome these limitations, we sought catalysts and reagents that would facilitate aliphatic C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcohols and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodology will be suitable for the site-selective and diastereoselective functionalization of complex natural products.

| S-EPMC11620535 | biostudies-literature

Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C-H Bonds.

Project description:Herein we report the 3,5-bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C-H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C-H insertion and Friedel-Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen-bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C-O bonds. Despite the highly Lewis-acidic nature of these catalysts that enables triflate abstraction from sp2 carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis-basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.

| S-EPMC8448122 | biostudies-literature

C-H bond functionalization via hydride transfer: direct coupling of unactivated alkynes and sp(3) C-H bonds catalyzed by platinum tetraiodide.

Project description:We report a catalytic intramolecular coupling between terminal unactivated alkynes and sp(3) C-H bonds via through-space hydride transfer (HT-cyclization of alkynes). This method enables one-step preparation of complex heterocyclic compounds by alpha-alkenylation of readily available cyclic ethers and amines. We show that PtI(4) is an effective Lewis acid catalyst for the activation of terminal alkynes for hydride attack and subsequent C-C bond formation. In addition, we have shown that the activity of neutral platinum salts (PtX(n)) can be modulated by the halide ligands. This modulation in turn allows for fine-tuning of the platinum center reactivity to match the reactivity and stability of selected substrates and products.

| S-EPMC2971677 | biostudies-literature

Complex allylation by the direct cross-coupling of imines with unactivated allylic alcohols.

Project description:Regioselective, stereoselective: The convergent coupling of allylic alcohols with imines to deliver stereodefined homoallylic amines is described (see scheme). The process proceeds with net allylic transposition without the intermediacy of allylic organometallic reagents. Two stereodefined centers and a geometrically defined di- or trisubstituted alkene are forged with high selectivity.

| S-EPMC3028933 | biostudies-literature

Direct functionalization of C-H bonds by electrophilic anions.

Project description:Alkanes and [B12X12]2- (X = Cl, Br) are both stable compounds which are difficult to functionalize. Here we demonstrate the formation of a boron-carbon bond between these substances in a two-step process. Fragmentation of [B12X12]2- in the gas phase generates highly reactive [B12X11]- ions which spontaneously react with alkanes. The reaction mechanism was investigated using tandem mass spectrometry and gas-phase vibrational spectroscopy combined with electronic structure calculations. [B12X11]- reacts by an electrophilic substitution of a proton in an alkane resulting in a B-C bond formation. The product is a dianionic [B12X11CnH2n+1]2- species, to which H+ is electrostatically bound. High-flux ion soft landing was performed to codeposit [B12X11]- and complex organic molecules (phthalates) in thin layers on surfaces. Molecular structure analysis of the product films revealed that C-H functionalization by [B12X11]- occurred in the presence of other more reactive functional groups. This observation demonstrates the utility of highly reactive fragment ions for selective bond formation processes and may pave the way for the use of gas-phase ion chemistry for the generation of complex molecular structures in the condensed phase.

| S-EPMC7519248 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data