Catalytic Alkyne Allylboration: A Quest for Selectivity.

Catalytic methodologies that enable the synthesis of complex organic molecules from simple and readily available starting materials represent a goal in modern synthetic chemistry. In particular, multicomponent carboboration reactions that provide stereoselective access to densely functionalized building blocks are particularly valuable to achieve molecular diversity. This Perspective covers the developments in the area of catalytic allylboration of alkynes and highlights the key features that have allowed for the control of the regio-, diastereo-, and enantioselectivity in these transformations.

An electroaffinity labelling platform for chemoproteomic-based target identification.

Target identification involves deconvoluting the protein target of a pharmacologically active, small-molecule ligand, a process that is critical for early drug discovery yet technically challenging. Photoaffinity labelling strategies have become the benchmark for small-molecule target deconvolution, but covalent protein capture requires the use of high-energy ultraviolet light, which can complicate downstream target identification. Thus, there is a strong demand for alternative technologies that allow for controlled activation of chemical probes to covalently label their protein target. Here we introduce an electroaffinity labelling platform that leverages the use of a small, redox-active diazetidinone functional group to enable chemoproteomic-based target identification of pharmacophores within live cell environments. The underlying discovery to enable this platform is that the diazetidinone can be electrochemically oxidized to reveal a reactive intermediate useful for covalent modification of proteins. This work demonstrates the electrochemical platform to be a functional tool for drug-target identification.

Catalytic Lewis Base Additive Enables Selective Copper-Catalyzed Borylative α-C-H Allylation of Alicyclic Amines.

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach that enables the transformation of O-benzoyl hydroxylamines into α-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupling with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C-N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O-benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C-C bond formation with the allylcopper species.

Stereoselective Synthesis of Highly Substituted 1,3-Dienes via "à la carte" Multifunctionalization of Borylated Dendralenes.

Despite the high relevance of 1,3-dienes, stereoselective methods to access tetrasubstituted conjugated dienes are still scarce. We here report an efficient and modular approach that provides access to multifunctional tetrasubstituted 1,3-dienes with excellent levels of regio- and stereoselectivity. This methodology is based on a tetracomponent reaction between a borylated dendralene, an organolithium reagent and two different electrophiles. Mechanistic studies reveal that this transformation proceeds through a regio- and stereoselective carbolithiation/electrophilic trapping of an in situ formed dendralenic boron-ate complex, followed by a stereoretentive halodeborylation. The ease in which complex structural dienes can be accessed and their synthetic versatility highlight the importance and utility of this method.

Synthesis and Characterization of Bidentate (P

A new family of cationic, bidentate (P^N)gold(III) fluoride complexes has been prepared and a detailed characterization of the gold-fluoride bond has been carried out. Our results correlate with the observed reactivity of the fluoro ligand, which undergoes facile exchange with both cyano and acetylene nucleophiles. The resulting (P^N)arylgold(III)C(sp) complexes have enabled the first study of reductive elimination on (P^N)gold(III) systems, which demonstrated that C(sp2 )-C(sp) bond formation occurs at higher rates than those reported for analogous phosphine-based monodentate systems.

Copper-catalyzed protoboration of borylated dendralenes: a regio- and stereoselective access to functionalized 1,3-dienes.

A copper-catalyzed protoboration of borylated dendralenes is reported. The method employs an NHC-Cu catalyst and provides access to 1,4-addition products with excellent levels of chemo-, regio- and stereoselectivity. The resulting diene bis(boronates) are oxidized to the corresponding diene diols which are synthetically versatile building blocks.

Copper-Catalyzed Enantioselective Allylboration of Alkynes: Synthesis of Highly Versatile Multifunctional Building Blocks.

The first copper-catalyzed enantioselective allylboration of alkynes is reported. The method employs a multitasking chiral NHC-Cu catalyst and provides access to densely functionalized molecules from simple starting materials with excellent levels of chemo-, regio-, and enantioselectivity. These multifunctional products display highly versatile reactivity as shown by the synthesis of a variety of non-racemic molecular scaffolds. DFT calculations were conducted to gain insight into the high selectivity levels of this catalytic process.

Synthesis of Stereodefined Borylated Dendralenes through Copper-Catalyzed Allylboration of Alkynes.

An efficient method to access diversely substituted borylated dendralenes from simple and readily available materials is reported. This method is based on a multicomponent copper-catalyzed allylboration of alkynes with diboron and a 1,4-dibromo-2-butene which provides bromo- and boron-substituted skipped dienes with a remarkable chemo-, stereo-, and regioselectivity. These products can be easily transformed into dendralenic organoboronates, which display an extremely versatile reactivity as demonstrated by novel selective transformations.