Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Catalytic Access to 4-(sec-Alkyl)Anilines via 1,6-Conjugate Addition of Grignard Reagents to in Situ Generated aza-p-Quinone Methides.

ABSTRACT: The synthesis of aniline derivatives, common building blocks in many pharmaceuticals, agrochemicals, dyes or polymers, has been limited to reactions based on benzene-toluene-xylene derivatives (BTX) due to their ample availability. Despite the large number of existing methodologies, the synthesis of chiral 4-(sec-alkyl)anilines has not been accomplished so far. In this work, a tandem strategy based on the generation of a reactive aza-p-quinone methide (aza-p-QM) intermediate followed by Cu(I)-catalyzed addition of Grignard reagents has been developed.

SUBMITTER: Zurro M

PROVIDER: S-EPMC9486948 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Catalytic Access to 4-(sec-Alkyl)Anilines via 1,6-Conjugate Addition of Grignard Reagents to in Situ Generated aza-p-Quinone Methides.

Zurro Mercedes M Ge Luo L Harutyunyan Syuzanna R SR

Organic letters 20220902 36

The synthesis of aniline derivatives, common building blocks in many pharmaceuticals, agrochemicals, dyes or polymers, has been limited to reactions based on benzene-toluene-xylene derivatives (BTX) due to their ample availability. Despite the large number of existing methodologies, the synthesis of chiral 4-(sec-alkyl)anilines has not been accomplished so far. In this work, a tandem strategy based on the generation of a reactive aza-p-quinone methide (aza-p-QM) intermediate follow ...[more]

PMID: 36053069

Similar Datasets

Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides.

Project description:The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).

| S-EPMC8588318 | biostudies-literature

Base-Catalyzed 1,6-Conjugate Addition of Nitroalkanes to p-Quinone Methides under Continuous Flow.

Project description:A mild base-catalyzed protocol for the synthesis of substituted nitroalkane derivatives has been developed under continuous flow using a microreaction technique. This transformation basically involves the 1,6-conjugate addition of nitroalkanes to p-quinone methides, leading to the substituted nitroalkanes in good to excellent yields.

| S-EPMC6644449 | biostudies-literature

Catalyst-Free 1,6-Conjugate Addition/Aromatization/Sulfonylation of para-Quinone Methides: Facile Access to Diarylmethyl Sulfones.

Project description:An efficient, catalyst-free strategy to construct diarylmethyl sulfones via 1,6-conjugate addition/aromatization/sulfonylation reaction of para-quinone methides with sulfonyl hydrazides under mild and environmentally benign conditions has been developed. The established protocol provided a highly chemo- and regioselectivity synthesis of a diverse array of novel diarylmethyl sulfones with excellent yields, and the reaction could be scaled up.

| S-EPMC6641250 | biostudies-literature

3-Nitroindoles Serving as N-Centered Nucleophiles for Aza-1,6-Michael Addition to para-Quinone Methides.

Project description:An unprecedented N-alkylation of 3-nitroindoles with para-quinone methides was developed for the first time. Using potassium carbonate as the base, a wide range of structurally diverse N-diarylmethylindole derivatives were obtained with moderated to good yields via the protection group migration/aza-1,6-Michael addition sequences. The reaction process was also demonstrated by control experiments. Different from the previous advances where 3-nitrodoles served as electrophiles trapping by various nucleophiles, the reaction herein is featured that 3-nitrodoles is defined with latent N-centered nucleophiles to react with ortho-hydrophenyl p-QMs for construction of various N-diarylmethylindoles.

| S-EPMC10384903 | biostudies-literature

Halogenation Reactions of Alkyl Alcohols Employing Methyl Grignard Reagents.

Project description:Grignard reagents are commonly used as carbanion equivalents. Herein, we report an example of Grignard reagents acting as halide nucleophiles to form alkyl iodides and bromides. We establish that Grignard reagents can convert alkyl mesylates into alkyl halides, as well as be employed in a one-pot halogenation reaction starting from alcohols, which proceed through mesylate intermediates. The halogenation reaction is confirmed to occur by an SN2 pathway with inversion of configuration and is demonstrated to be efficient on multi-gram scale.

| S-EPMC9486953 | biostudies-literature

Synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of p-quinone methides with organosulfur reagents† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3ra01815f

Project description:A rapid and simple method was developed for the synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of para-quinone methides (p-QMs) with organosulfur reagents. A series of diarylmethyl thioethers were synthesized at 13–85% yields by this method. After that, the antibacterial activities of synthesized diarylmethyl thioethers and their derivatives were evaluated. The MIC range (μg mL−1) against Staphylococcus aureus ATCC 25923 and clinically isolated methicillin-resistant S. aureus was 8–128 and 64–128, respectively. A rapid and simple method was developed for the synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of para-quinone methides (p-QMs) with organosulfur reagents.

| S-EPMC10132255 | biostudies-literature

TBAB-Catalyzed 1,6-Conjugate Sulfonylation of para-Quinone Methides: A Highly Efficient Approach to Unsymmetrical gem-Diarylmethyl Sulfones in Water.

Project description:A highly efficient sulfonylation of para-quinone methides with sulfonyl hydrazines in water has been developed on the basis of the mode involving a tetrabutyl ammonium bromide (TBAB)-promoted sulfa-1,6-conjugated addition pathway. This reaction provides a green and sustainable method to synthesize various unsymmetrical diarylmethyl sulfones, showing good functional group tolerance, scalability, and regioselectivity. Further transformation of the resulting diarylmethyl sulfones provides an efficient route to some functionalized molecules.

| S-EPMC7038064 | biostudies-literature

Genetically Encoded Quinone Methides Enabling Rapid, Site-Specific, and Photocontrolled Protein Modification with Amine Reagents.

Project description:Site-specific modification of proteins with functional molecules provides powerful tools for researching and engineering proteins. Here we report a new chemical conjugation method which photocages highly reactive but chemically selective moieties, enabling the use of protein-inert amines for selective protein modification. New amino acids FnbY and FmnbY, bearing photocaged quinone methides (QMs), were genetically incorporated into proteins. Upon light activation, they generated highly reactive QM, which rapidly reacted with amine derivatives. This method features a rare combination of desired properties including fast kinetics, small and stable linkage, compatibility with low temperature, photocontrollability, and widely available reagents. Moreover, labeling via FnbY occurs on the β-carbon, affording the shortest linkage to protein backbone which is essential for advanced studies involving orientation and distance. We installed various functionalities onto proteins and attached a spin label as close as possible to the protein backbone, achieving high resolution in double electron-electron paramagnetic resonance distance measurements.

| S-EPMC7581489 | biostudies-literature

Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents.

Project description:A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp2-hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp2-hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C-C bonds.

| S-EPMC8163237 | biostudies-literature

Fe-Catalyzed dicarbofunctionalization of electron-rich alkenes with Grignard reagents and (fluoro)alkyl halides.

Project description:An iron-catalyzed regioselective dicarbofunctionalization of electron-rich alkenes is described. In particular, aryl- and alkyl vinyl ethers are used as effective linchpins to couple alkyl or (fluoro)alkyl halides and sp2-hybridized Grignard nucleophiles. Preliminary results demonstrate the ability to engage thioethers as linchpins and control enantioselectivity in these transformations, an area which is largely unexplored in iron-catalyzed three-component cross-coupling reactions.

| S-EPMC8722523 | biostudies-literature