Hydroselenation of olefins: elucidating the β-selenium effect.

We report a light-promoted hydroselenation of alkenes with high -Markovnikov selectivity. Blue light activates an aryl diselenide to generate a seleno radical with subsequent addition into an alkene to form a β-seleno carbon radical. Hydrogen atom transfer (HAT) from the selenol to the carbon radical generates the linear selenide with high selectivity in preference to the branched isomer.

Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors.

Unlabelled: The BCL2 inhibitor venetoclax promotes apoptosis in blood cancer cells and is approved for treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, multiple myeloma cells are frequently more dependent on MCL-1 for survival, conferring resistance to venetoclax. Here we report that mevalonate pathway inhibition with statins can overcome resistance to venetoclax in multiple myeloma cell lines and primary cells.

Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes.

Chiral -cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N:N regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.

Copper-Phosphido Catalysis: Enantioselective Addition of Phosphines to Cyclopropenes.

We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process.

Enantioselective Hydroalkoxylation of 1,3-Dienes via Ni-Catalysis.

As an advance in hydrofunctionalization, we herein report that alcohols add to 1,3-dienes with high regio- and enantioselectivity. Using Ni-DuPhos, we access enantioenriched allylic ethers. Through the choice of solvent-free conditions, we control the reversibility of C-O bond formation.

Adiabatic Passage through Level Anticrossings in Systems of Chemically Inequivalent Protons Incorporating Parahydrogen: Theory, Experiment, and Prospective Applications.

Level anticrossings (LACs) are ubiquitous in quantum systems and have been exploited for spin-order transfer in hyperpolarized nuclear magnetic resonance spectroscopy. This paper examines the manifestations of adiabatic passage through a specific type of LAC found in homonuclear systems of chemically inequivalent coupled protons incorporating parahydrogen (pH). Adiabatic passage through such a LAC is shown to elicit translation of the pH spin order.

Enantioselective Selenol-ene Using Rh-Hydride Catalysis.

This study showcases the first enantioselective hydroselenation of styrenes. Organoselenium building blocks are accessed with selectivity for the branched isomer. Through a Rh-hydride pathway, C-Se bonds can be forged with excellent regio- and enantiocontrol.

Enantioselective Addition of Pyrazoles to Dienes*.

We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic pyrazoles can be generated with excellent regioselectivity. Mechanistic studies support a pathway distinct from previous hydroaminations: a Pd -catalyzed ligand-to-ligand hydrogen transfer (LLHT).

Reducing Challenges in Organic Synthesis with Stereoselective Hydrogenation and Tandem Catalysis.

Tandem catalysis enables the rapid construction of complex architectures from simple building blocks. This Perspective shares our interest in combining stereoselective hydrogenation with transformations such as isomerization, oxidation, and epimerization to solve diverse challenges. We highlight the use of tandem hydrogenation for preparing complex natural products from simple prochiral building blocks and present tandem catalysis involving transfer hydrogenation and dynamic kinetic resolution.

Enantioselective Hydrothiolation: Diverging Cyclopropenes through Ligand Control.

In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl sulfides or allylic sulfides. The choice of bisphosphine ligand dictates whether the pathway involves ring-retention or ring-opening.

Teaching Aldehydes New Tricks Using Rhodium- and Cobalt-Hydride Catalysis.

By using transition metal catalysts, chemists have altered the "logic of chemical synthesis" by enabling the functionalization of carbon-hydrogen bonds, which have traditionally been considered inert. Within this framework, our laboratory has been fascinated by the potential for aldehyde C-H bond activation. Our approach focused on generating acyl-metal-hydrides by oxidative addition of the formyl C-H bond, which is an elementary step first validated by Tsuji in 1965.

A Diverse View of Science to Catalyse Change.

Valuing diversity leads to scientific excellence, the progress of science and most importantly, it is simply the right thing to do. We can value diversity not only in words, but also in actions.

Enantioselective Addition of α-Nitroesters to Alkynes.

By using Rh-H catalysis, we couple α-nitroesters and alkynes to prepare α-amino-acid precursors. This atom-economical strategy generates two contiguous stereocenters, with high enantio- and diastereocontrol. In this transformation, the alkyne undergoes isomerization to generate a Rh -π-allyl electrophile, which is trapped by an α-nitroester nucleophile.

A regioselectivity switch in Pd-catalyzed hydroallylation of alkynes.

By exploiting the reactivity of a vinyl-Pd species, we control the regioselectivity in hydroallylation of alkynes under Pd-hydride catalysis. A monophosphine ligand and carboxylic acid combination promotes 1,5-dienes through a pathway involving isomerization of alkynes to allenes. In contrast, a bisphosphine ligand and copper cocatalyst favor 1,4-dienes a mechanism that involves transmetalation.

Dynamic Kinetic Resolution of Aldehydes by Hydroacylation.

We report a dynamic kinetic resolution (DKR) of chiral 4-pentenals by olefin hydroacylation. A primary amine racemizes the aldehyde substrate via enamine formation and hydrolysis. Then, a cationic rhodium catalyst promotes hydroacylation to generate α,γ-disubstituted cyclopentanones with high enantio- and diastereoselectivities.

Catalytic Hydrothiolation: Counterion-Controlled Regioselectivity.

In this Article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway in which regioselectivity is dictated by the choice of counterion associated with the Rh center. Non-coordinating counterions, such as SbF, allow for η-diene coordination to Rh complexes and result in allylic sulfides.

Enantioselective Coupling of Dienes and Phosphine Oxides.

We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides couple to generate organophosphorus building blocks with high enantio- and regiocontrol. This method constitutes the first asymmetric hydrophosphinylation of dienes.

Catalytic Hydrothiolation: Regio- and Enantioselective Coupling of Thiols and Dienes.

We report a Rh-catalyzed hydrothiolation of 1,3-dienes, including petroleum feedstocks. Either secondary or tertiary allylic sulfides can be generated from the selective addition of a thiol to the more substituted double bond of a diene. The catalyst tolerates a wide range of functional groups, and the loading can be as low as 0.

Tandem Catalysis: Transforming Alcohols to Alkenes by Oxidative Dehydroxymethylation.

We report a Rh-catalyst for accessing olefins from primary alcohols by a C-C bond cleavage that results in dehomologation. This functional group interconversion proceeds by an oxidation-dehydroformylation enabled by N, N-dimethylacrylamide as a sacrificial acceptor of hydrogen gas. Alcohols with diverse functionality and structure undergo oxidative dehydroxymethylation to access the corresponding olefins.

Catalytic Alkyne Arylation Using Traceless Directing Groups.

By using Pd /Mandyphos, we achieved a three-component aminoarylation of alkynes to generate enamines, which are then hydrolyzed to either α-arylphenones or α,α-diarylketones. This Pd-catalyzed method overcomes established known pathways to enable the use of amines as traceless directing groups for C-C bond formation.

Hydrogenation catalyst generates cyclic peptide stereocentres in sequence.

Molecular recognition plays a key role in enzyme-substrate specificity, the regulation of genes, and the treatment of diseases. Inspired by the power of molecular recognition in enzymatic processes, we sought to exploit its use in organic synthesis. Here we demonstrate how a synthetic rhodium-based catalyst can selectively bind a dehydroamino acid residue to initiate a sequential and stereoselective synthesis of cyclic peptides.