Photochemical Deracemization of Lactams with Deuteration Enabled by Dual Hydrogen Atom Transfer.

Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such as energy transfer, single electron transfer, and ligand-to-metal charge transfer have been leveraged to promote stereoablation, approaches relying on hydrogen atom transfer, which circumvent the limitations imposed by the triplet energy and redox potential of racemic substrates, remain underexplored. Conceptually, the most attractive method for tertiary stereocenter deracemization might be hydrogen atom abstraction followed by hydrogen atom donation.

Design and optimization of a novel solenoid with high magnetic uniformity.

Currently, solenoids are extensively utilized in various research fields due to their flexibility of fabrication and high magnetic field strength. However, the internal magnetic field of the solenoid itself exhibits some non-uniformity defects, which limits its application in some domains. This article proposes a novel single winding tightly wound solenoid structure with an improved magnetic field uniformity.

Enantioselective Synthesis of Axially and Centrally Chiral Styrenes via Nickel-Catalyzed Desymmetric Hydrocyanation of Biaryl Dienes.

Herein, a highly regio-, enantio-, and diastereoselective nickel-catalyzed desymmetric hydrocyanation of biaryl dienes for the simultaneous construction of axial and central chiralities is presented, which offers a convenient approach to a variety of tirenes containing the union of an axially chiral biaryl and a centrally α-chiral nitrile under mild conditions using a commercially available catalyst. The synthetic utility is highlighted by the development of a novel axially chiral phosphine ligand and biphenyl-based chiral diene ligand and their potential applications in the field of asymmetric catalytic reactions.

Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis.

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated the great potential of non-natural photoenzymes, all of the transformations are initiated by single-electron reduction of the substrate, with only one notable exception. Herein, we report an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins using a novel mutant of gluconobacter ene-reductase (GluER-W100F-W342F).

Nickel-Catalyzed Enantioselective Hydrothiocarbonylation of Cyclopropenes.

Hydrothiocarbonylation of olefins using carbon monoxide and thiols is a powerful method to synthesize thioesters from simple building blocks. Owing to the intrinsic challenges of catalyst poisoning, transition-metal-catalyzed asymmetric thiocarbonylation, particularly when utilizing earth abundant metals, remains rare in the literature. Herein, we report a nickel-catalyzed enantioselective hydrothiocarbonylation of cyclopropenes for the synthesis of a diverse collection of functionalized thioesters in good to excellent yields with high stereoselectivity.

Divergent Photosensitizer Controlled Reactions of 4-Hydroxycoumarins and Unactivated Olefins: Hydroarylation and Subsequent [2+2] Cycloaddition.

Herein, we report a photoinduced approach for hydroarylation of unactivated olefins using 4-hydroxycoumarins as the arylating reagent. Key to the success of this reaction is the conversion of nucleophilic 4-hydroxycoumarins into electrophilic carbon radicals via photocatalytic arene oxidation, which not only circumvents the polarity-mismatch issue encountered under ionic conditions but also accommodates a broad substrate scope and inhibits side reactions that were previously observed. Moreover, divergent reactivity was achieved by changing the photocatalyst, enabling a subsequent [2+2] cycloaddition to deliver cyclobutane-fused pentacyclic products that are otherwise challenging to access in high yields and with high diastereoselectivity.

Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions.

Site- and enantioselective incorporation of deuterium into organic compounds is of broad interest in organic synthesis, especially within the pharmaceutical industry. While catalytic approaches relying on two-electron reaction manifolds have allowed for stereoselective delivery of a formal deuteride (D) or deuteron (D) at benzylic positions, complementary strategies that make use of one-electron deuterium atom transfer and target non-benzylic positions remain elusive. Here we report a photochemical approach for asymmetric radical deuteration by utilizing readily available peptide- or sugar-derived thiols as the catalyst and inexpensive deuterium oxide as the deuterium source.

Hydroalkylation of Unactivated Olefins via Visible-Light-Driven Dual Hydrogen Atom Transfer Catalysis.

Radical hydroalkylation of olefins enabled by hydrogen atom transfer (HAT) catalysis represents a straightforward means to access C()-rich molecules from abundant feedstock chemicals without the need for prefunctionalization. While Giese-type hydroalkylation of activated olefins initiated by HAT of hydridic carbon-hydrogen bonds is well-precedented, hydroalkylation of unactivated olefins in a similar fashion remains elusive, primarily owing to a lack of general methods to overcome the inherent polarity-mismatch in this scenario. Here, we report the use of visible-light-driven dual HAT catalysis to achieve this goal, where catalytic amounts of an amine-borane and an in situ generated thiol were utilized as the hydrogen atom abstractor and donor, respectively.

Deracemization Enabled by Visible-Light Photocatalysis.

Deracemization is an ideal but challenging strategy for the conversion of a racemic mixture into a single enantiomer. Recent studies have demonstrated that visible-light photocatalysis could be utilized to promote selective deracemization of axially chiral allenes as well as cyclopropylquinolones and cyclic ureas with central chirality either through energy transfer or through a sequence of electron, proton, and hydrogen-atom transfer.

A Semi-Explicit Surface Tracking Mechanism for Multi-Phase Immiscible Liquids.

We introduce a new method to efficiently track complex interfaces among multi-phase immiscible fluids. Unlike existing techniques, we use a mesh-based representation for global liquid surfaces while selectively modeling some local surficial regions with regional level sets (RLS) to handle complex geometries that are difficult to resolve with explicit topology operations. Such a semi-explicit surface mechanism can preserve volume, fine features and foam-like thin films under a relatively low computational expenditure.

Direct α-alkylation of primary aliphatic amines enabled by CO and electrostatics.

Primary aliphatic amines are important building blocks in organic synthesis due to the presence of a synthetically versatile NH group. N-functionalization of primary amines is well established, but selective C-functionalization of unprotected primary amines remains challenging. Here, we report the use of CO as an activator for the direct transformation of abundant primary aliphatic amines into valuable γ-lactams under photoredox and hydrogen atom transfer (HAT) catalysis.

Remote C-H alkylation and C-C bond cleavage enabled by an in situ generated palladacycle.

The direct and selective functionalization of C-H bonds of arenes is one of the most challenging yet valuable aims in organic synthesis. Despite notable recent achievements, a pre-installed directing group proved to be essential in most of the methodologies reported so far. In this context, the use of a transient directing group that can be generated in situ has attracted attention and demonstrated the great potential of this strategy.

Palladium-Catalyzed Hydrohalogenation of 1,6-Enynes: Hydrogen Halide Salts and Alkyl Halides as Convenient HX Surrogates.

Difficulties associated with handling H and CO in metal-catalyzed processes have led to the development of chemical surrogates to these species. Despite many successful examples using this strategy, the application of convenient hydrogen halide (HX) surrogates in catalysis has lagged behind considerably. We now report the use of ammonium halides as HX surrogates to accomplish a Pd-catalyzed hydrohalogenation of enynes.

Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor.

FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.

Modern Transition-Metal-Catalyzed Carbon-Halogen Bond Formation.

The high utility of halogenated organic compounds has prompted the development of a vast number of transformations which install the carbon-halogen motif. Traditional routes to these building blocks have commonly involved multiple steps, harsh reaction conditions, and the use of stoichiometric and/or toxic reagents. In this regard, using transition metals to catalyze the synthesis of organohalides has become a mature field in itself, and applying these technologies has allowed for a decrease in the production of waste, higher levels of regio- and stereoselectivity, and the ability to produce enantioenriched target compounds.

Palladium-catalysed norbornene-mediated C-H functionalization of arenes.

The Catellani reaction--a palladium-catalysed C-H functionalization reaction mediated by norbornene--was first reported in 1997. The capacity to functionalize both the ortho and ipso positions of aryl halides in a single transformation held great appeal. We reported an annulative Catellani reaction in 2000.

Harmony of CdI2 with CuBr for the one-pot synthesis of optically active α-allenols.

A highly efficient one-pot synthesis of chiral α-allenols from propargylic alcohols, aldehydes and pyrrolidine induced by CuBr and (R,Ra)-N-PINAP or (R,Sa)-N-PINAP and CdI2 has been developed. Both the yields and enantioselectivities of the allenols of this one-pot procedure are practical. Comparison with ZnI2 control experiments revealed that CdI2 can convert propargylic amine to allene in the presence of CuBr efficiently.

Synthesis of enantioenriched 5,6-dihydrophenanthridine derivatives through retro-carbopalladation of chiral o-bromobenzylamines.

Retro-carbopalladation of aldimines in the presence of a suitable β-hydrogen atom has been observed in the Pd-catalyzed homocoupling reactions of o-bromobenzylamines, providing an expeditious synthetic route to 5,6-dihydrophenanthridine derivatives. Furthermore, a highly enantioselective synthesis of 6-aryl-substituted 5,6-dihydrophenanthridines was achieved in a one-pot manner by taking advantage of Rh and Pd catalysis.

Palladium-catalyzed cyclization reactions of allenes in the presence of unsaturated carbon-carbon bonds.

Modern synthetic chemists have looked for rapid and efficient ways to construct complex molecules while minimizing synthetic manipulation and maximizing atom-economy. Over the last few decades, researchers have made considerable progress toward these goals by taking full advantage of transition metal catalysis and the diverse reactivities of allenes, functional groups which include two cumulative carbon-carbon double bonds. This Account describes our efforts toward the development of Pd-catalyzed cyclization reactions of allenes in the presence of compounds that contain unsaturated carbon-carbon bonds such as alkenyl halides, simple alkenes, allenes, electron-deficient alkynes, or propargylic carbonates.

Gorlos-Phos: addressing the stereoselectivity in palladium-catalyzed exo-mode cyclization of allenes with a nucleophilic functionality.

A novel catalyst system has been indentified for addressing the long-standing issue of Z/E stereoselectivity in palladium-catalyzed exo-mode cyclization reactions of allenes bearing a nucleophilic functionality with organic halides or their equivalents. The readily accessible, sterically hindered monophosphine ligand Gorlos-Phos·HBF4 imparts a remarkable stereocontrolling ability with broad generality under Pd catalysis.

Bimetallic enantioselective approach to axially chiral allenes.

An efficient bimetallic Zn(II)/Cu(I)-mediated asymmetric synthesis of simple axially chiral allenes from terminal alkynes and aldehydes was realized by taking advantage of the chiral amine (S)-α,α-diphenylprolinol 3. This one-pot procedure is compatible with broad scopes of both terminal alkynes and aldehydes, providing axially chiral allenes in practical yields with an excellent enantioselectivity. Control experiments revealed that CuBr is responsible for the efficient formation of propargylic amine while the combination of CuBr and ZnBr2 plays crucial roles in the amine-to-allene transformation.

tert-Butyldimethylsilyl-directed highly enantioselective approach to axially chiral α-allenols.

A highly efficient and enantioselective synthesis of axially chiral α-allenols was realized in practical yields with 96-99% ee or de from TBS-protected propargylic alcohols, aldehydes, and a commercially available, inexpensive, chiral, secondary amine (S)-α,α-diphenylprolinol or its enantiomer followed by desilylation. The easily removable TBS group not only acts as a protecting group, but also as a possible sterically directing group for the excellent enantioselectivity and in situ prevention of possible allene racemization.

Geometric flow approach for region-based image segmentation.

Geometric flows have been successfully used for surface modeling and designing, largely because they are inherently good at controlling geometric shape evolution. Variational image segmentation approaches, on the other hand, detect objects of interest by deforming certain given shapes. This motivates us to revisit the minimal partition problem for segmentation of images, and propose a new geometric flow-based formulation and solution to it.

Palladium-catalyzed cyclization reactions of 2,3-allenyl amines with propargylic carbonates.

A highly efficient and atom-economic route to synthesize 5-(1,3,4-alkatrien-2-yl)oxazolidin-2-ones via palladium-catalyzed cyclization reactions of 2,3-allenyl amines with propargylic carbonates was reported. The CO(2) generated in situ from propargylic carbonates is incorporated into the oxazolidin-2-one unit with high efficiency, affording the products in 70-92% yields.