Palladium-Catalyzed Siloxycyclopropanation of Alkenes Using Acylsilanes

We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.

Download Full-text

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

10.26434/chemrxiv.12034743 ◽

2020 ◽

Author(s):

Aleksandra Balliu ◽

Aaltje Roelofje Femmigje Strijker ◽

Michael Oschmann ◽

Monireh Pourghasemi Lati ◽

Oscar Verho

Keyword(s):

Carboxylic Acid ◽

Building Blocks ◽

Wide Range ◽

Palladium Catalyzed ◽

Directing Group ◽

High Yields ◽

Vinyl Iodides ◽

Initial Results

In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both cis- and trans-configured carboxylic acid building blocks from the C–H alkenylation products.

Download Full-text

Suzuki–Miyaura cross-coupling for chemoproteomic applications

10.26434/chemrxiv.12055218.v1 ◽

2020 ◽

Author(s):

Jian Cao ◽

Ernest Armenta ◽

Lisa Boatner ◽

Heta Desai ◽

Neil Chan ◽

...

Keyword(s):

Mass Spectrometry ◽

Cross Coupling ◽

Protein Profiling ◽

Protein Labeling ◽

Caspase 8 ◽

Complex Cell ◽

Bioorthogonal Chemistry ◽

Reaction Conditions ◽

Target Deconvolution ◽

Palladium Catalyzed

Bioorthogonal chemistry is a mainstay of chemoproteomic sample preparation workflows. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper-catalyzed azide –alkyne cycloaddition (CuAAC) or 'click' chemistry. Here we demonstrate that gel-based activity-based protein profiling (ABPP) and mass-spectrometry-based chemoproteomic profiling can be conducted using Suzuki–Miyaura cross-coupling. We identify reaction conditions that proceed in complex cell lysates and find that Suzuki –Miyaura cross-coupling and CuAAC yield comparable chemoproteomic coverage. Importantly, Suzuki–Miyaura is also compatible with chemoproteomic target deconvolution, as demonstrated using structurally matched probes tailored to react with the cysteine protease caspase-8. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual protein labeling.

Download Full-text