Isolation and Reactivity of Arylnickel(II) Complexes in Nickel-Catalyzed Borylation of Aryl Fluorosulfates.

Aryl fluorosulfates have emerged as versatile SuFExable substrates, harnessing the reactivity of the S-F bond. In this study, we unveil their alternative synthetic utility in nickel-catalyzed borylation via C-O bond activation. This method highlights mild reaction conditions, a broad substrate scope, and moderate functional group tolerance, rendering it a practical and appealing approach for synthesizing a diverse array of aryl boronate esters. Furthermore, computational analysis sheds light on the reaction pathways, uncovering the participation of LNi(0) and LNi(II)ArX species. This insight is supported by the 31P NMR reaction monitoring along with isolation and single-crystal X-ray structural elucidation of well-defined arylnickel(II) intermediates obtained from the oxidative addition of aryl fluorosulfates. A comprehensive investigation, merging experimental and computational approaches, deepens our understanding of the alternative reactivity of SuFExable substrates.

Cu-Catalyzed Synthesis of 2-Silyl-1,3-butadienes from Allenols and Applications to One-Pot Synthesis of Tetrasubstituted Arylsilanes.

A copper-catalyzed chemo- and stereoselective method for the synthesis of (E)-2-silyl-1,3-butadienes from a broad range of allenols using mild Si-B reagents is reported in this study. Our protocol required a short reaction time at ambient temperature to produce the desired dienes in high yields. Synthetic applications are highlighted by the one-pot synthesis of tetrasubstituted arylsilanes from allenols as well as the further functionalization of C-Si bonds.

Unlocking High Porosity: Post-Synthetic Solvothermal Treatment of Cu-Paddlewheel Based Metal-Organic Cages.

Metal-organic cages (MOCs) have garnered significant attention due to their unique discrete structures, intrinsic porosity, designability, and tailorability. However, weak inter-cage interactions, such as van der Waals forces and hydrogen bonding can cause solid-state MOCs to lose structural integrity during desolvation, leading to the loss of porosity. In this work, a novel strategy to retain the permanent porosity of Cu-paddlewheel-based MOCs, enabling their use as heterogeneous catalysts is presented. Post-synthetic solvothermal treatments in non-coordinating solvents, mesitylene, and p-xylene, effectively preserve the packing structures of solvent-evacuated MOCs while preventing cage agglomeration. The resulting MOCs exhibit an exceptional N2 sorption capacity, with a high surface area (SBET  = 1934 m2  g-1 for MOP-23), which is among the highest reported for porous MOCs. Intriguingly, while the solvothermal treatment reduced Cu(II) to Cu(I) in the Cu-paddlewheel clusters, the MOCs with mixed-valenced Cu(I)/Cu(II) maintained their crystallinity and permanent porosity. The catalytic activities of these MOCs are successfully examined in copper(I)-catalyzed hydrative amide synthesis, highlighting the prospect of MOCs as versatile reaction platforms.

Synthesis of alkynamides through reaction of alkyl- or aryl-substituted alkynylaluminums with isocyanates.

An efficient and facile method for the preparation of alkynamides through Et3N-catalyzed alumination of alkyl- or aryl-substituted terminal alkynes with AlMe3 and sequential nucleophilic addition of in situ generated alkynylaluminums to isocyanates is described. This method has the merits of using readily available isocyanates and monosubstituted alkynes, easy access to organoaluminums, short reaction times, and high efficiency. A gram-scale synthesis of the desired alkynamide and its application to the formation of α-methylene-ß-lactams demonstrates the synthetic utility of this method.

Stereoselective Formal Hydroamidation of Si-Substituted Arylacetylenes with DIBAL-H and Isocyanates: Synthesis of (E)- and (Z)-α-Silyl-α,ß-unsaturated Amides.

An efficient and stereoselective method for the synthesis of (E)- and (Z)-α-silyl-α,ß-unsaturated amides and its synthetic applications are presented herein. The solvent-controlled hydroaluminations of Si-substituted alkynes with DIBAL-H generate diastereomerically enriched alkenylaluminum reagents that are directly reacted with isocyanates at ambient temperature to afford α-silyl-α,ß-unsaturated amides in high yields with retained stereoselectivity. In particular, this process enables the synthesis of a broad range of (E)-α-silyl-α,ß-unsaturated amides, which are the less studied isomers. The synthetic utility of this method is highlighted by its short reaction time, ease of purification, easily accessible substrates and reagents, gram-scale synthesis, and the further transformations of C-Si bonds into C-H, C-X, and C-C bonds.

Synthetic Strategies for (-)-Cannabidiol and Its Structural Analogs.

(-)-Cannabidiol ((-)-CBD), a non-psychoactive phytocannabinoid from Cannabis, and its structural analogs have received growing attention in recent years because of their potential therapeutic benefits, including neuroprotective, anti-epileptic, anti-inflammatory, anxiolytic, and anti-cancer properties. (-)-CBD and its analogs have been obtained mainly based on extraction from the natural source; however, the conventional extraction-based methods have some drawbacks, such as poor quality control along with purification difficulty. Chemical-synthetic strategies for (-)-CBD could tackle these issues, and, additionally, generate novel (-)-CBD analogs that exhibit advanced biological activities. This review concisely summarizes the historic and recent milestones in the synthetic strategies for (-)-CBD and its analogs.

Single-Molecule Rotation for EGFR Conformational Dynamics in Live Cells.

Monitoring the dynamics of proteins in live cells on appropriate spatiotemporal scales may provide key information regarding long-standing questions in molecular and cellular regulatory mechanisms. However, tools capable of imaging the conformational changes over time have been elusive. Here, we present a single-molecule stroboscopic imaging probes by developing gyroscopic plasmonic nanoparticles, allowing for replication of protein-protein interactions and the conformational dynamics based on rotational and lateral velocities. This study fundamentally monitors the rotational motion of a membrane protein, epidermal growth factor receptor (EGFR), to decipher undiscovered structural dynamics in live cells without any molecular perturbations. This method offers a strategy to visualize assemblies and conformational changes, and provides unique insights into the mechanism underlying the molecular dynamics for receptors.

Defect Engineering into Metal-Organic Frameworks for the Rapid and Sequential Installation of Functionalities.

Postsynthetic treatments are well-known and important functionalization tools of metal-organic frameworks (MOFs). Herein, we have developed a practical and rapid postsynthetic ligand exchange (PSE) strategy using a defect-controlled MOF. An increase in the number of defects amounts to MOFs with enhanced rates of ligand exchange in a shorter time frame. An almost quantitative exchange was achieved by using the most defective MOFs. This PSE strategy is a straightforward method to introduce a functionality into MOFs including bulky or catalytically relevant moieties. Furthermore, some mechanistic insights into PSE were revealed, allowing for a sequential ligand exchange and the development of multifunctional MOFs with controlled ligand ratios.

Total synthesis of laidlomycin.

The synthesis of laidlomycin is described. With an established stereocontrolled synthetic route to the aldehyde 5, the known ß-keto phosphonate 4 was coupled with 5 and the resulting enone was subjected to a sequential hydrogenolysis/hydrogenation and equilibration process to effect the correct spiroketalization for the natural product. The stereogenic carbons were elaborated by desymmetrization for C12, allylation for C13, vanadyl-induced epoxidation for C16, Zn(BH4)2 reduction for C17, a chiral building block for C18 and C24, Shi epoxidation for C20 and C21, Myers' alkylation for C22, and thermodynamic control for C25.

The Total Synthesis of Inostamycin†A.

The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency.

N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.

Catalytic enantioselective protoboration of disubstituted allenes. Access to alkenylboron compounds in high enantiomeric purity.

Proto-boryl additions to 1,1-disubstituted allenes in the presence of 1.0-5.0 mol % of chiral NHC-Cu complexes, B2(pin)2, and t-BuOH proceed to afford alkenyl-B(pin) products in up to 98% yield, >98:2 site selectivity, and 98:2 er. The enantiomerically enriched alkenylboron products can be converted to otherwise difficult-to-access alkenyl bromides, methyl ketones or carboxylic acids. What's more, the corresponding boronic acids may be used in highly stereoselective NHC-Cu-catalyzed allylic substitution reactions.

NHC-Cu-catalyzed protoboration of monosubstituted allenes. Ligand-controlled site selectivity, application to synthesis and mechanism.

Two types of NHC-Cu complexes catalyze protoborations of terminal allenes to afford valuable 1,1- or trisubstituted vinylboron species with high site selectivity and stereoselectivity. The scope of the method, application to natural product synthesis, and mechanistic basis for the observed selectivity trends are presented.

Site- and enantioselective formation of allene-bearing tertiary or quaternary carbon stereogenic centers through NHC-Cu-catalyzed allylic substitution.

Catalytic enantioselective allylic substitutions that result in addition of an allenyl group (<2% propargyl addition) and formation of tertiary or quaternary C-C bonds are described. Commercially available allenylboronic acid pinacol ester is used. Reactions are promoted by a 5.0-10 mol % loading of sulfonate-bearing chiral bidentate N-heterocyclic carbene (NHC) complexes of copper, which exhibit the unique ability to furnish chiral products arising from the S(N)2' mode of addition. Allenyl-containing products are generated in up to 95% yield, >98% S(N)2' selectivity, and 99:1 enantiomeric ratio (er). Site-selective NHC-Cu-catalyzed hydroboration of enantiomerically enriched allenes and conversion to the corresponding ß-vinyl ketones demonstrates the method's utility.

Enantioselective formation of tert-alkylamines by desymmetrization of 2-substituted serinols.

Novel enantioselective desymmetrization of 2-substituted 2-amino-1,3-propanediols has been established to generate asymmetric quaternary carbon centers comprising an amino group. Enantioselective as well as chemical conversion proved to be greatly dependent on the protecting group of the amino group in the substrate, desymmetrizing reagent, base, solvent, and naturally, catalyst. The highly effective desymmetrization has been implemented by using N-benzoylated substrates with benzoyl chloride and triethylamine in the presence of tetraphenylbisoxazoline (24)-CuCl(2) complex in THF at ambient temperature. An extensive survey of catalysts revealed that dimethylmalonate-bridged bisoxazoline-CuCl(2) complexes were superior. Among them, the tetraphenylbisoxazoline (24)-CuCl(2) complex turned out to work most efficiently with a wide array of the substrates. All the examined substrates, with the exception of 2-phenylserinol 36, were desymmetrized in the presence of 24-CuCl(2) complex to give high enantioselectivities ranging from 85 to 95 % ee. Complementary use of the diisopropylbisoxazoline (22)-CuCl(2) complex has remedied the mediocre desymmetrization of 36 to give a significantly improved enantioselectivity from 63 to 83 % ee.

PIL5, a phytochrome-interacting bHLH protein, regulates gibberellin responsiveness by binding directly to the GAI and RGA promoters in Arabidopsis seeds.

Previous work showed that PHYTOCHROME-INTERACTING FACTOR3-LIKE5 (PIL5), a light-labile basic helix-loop-helix protein, inhibits seed germination by repressing GIBBERELLIN 3beta-HYDROXYLASE1 (GA3ox1) and GA3ox2 and activating a gibberellic acid (GA) catabolic gene (GA2ox2). However, we show persistent light-dependent and PIL5-inhibited germination behavior in the absence of both de novo GA biosynthesis and deactivation by GA2ox2, suggesting that PIL5 regulates not only GA metabolism but also GA responsiveness. PIL5 increases the expression of two GA repressor (DELLA) genes, GA-INSENSITIVE (GAI) and REPRESSOR OF GA1-3 (RGA/RGA1), in darkness. The hypersensitivity of gai-t6 rga-28 to red light and the suppression of germination defects of a rga-28 PIL5 overexpression line show the significant role of this transcriptional regulation in seed germination. PIL5 also increases abscisic acid (ABA) levels by activating ABA biosynthetic genes and repressing an ABA catabolic gene. PIL5 binds directly to GAI and RGA promoters but not to GA and ABA metabolic gene promoters. Together, our results show that light signals perceived by phytochromes cause a reduction in the PIL5 protein level, which in turn regulates the transcription of two DELLA genes directly and that of GA and ABA metabolic genes indirectly.

Chiral imine copper chloride-catalyzed enantioselective desymmetrization of 2-substituted 1,2,3-propanetriols.

Catalytic enantioselective desymmetrization of meso-2-substituted glycerols has been developed to secure a novel synthetic route to chiral tertiary alcohols. The transformation has been realized by monobenzoylation using benzoyl chloride and triethylamine in the presence of the imine ligand (25)-CuCl2 complex in THF at ambient temperature. The desymmetrization turned out to be greatly dependent on acylating reagent, base, solvent, and needless to say, catalyst. Extensive screening of chiral ligands led us to combine bromopyridinecarboxaldehyde 1 and phenyloxazoline amine 12 derived from tert-leucine, the bromo and phenyl substituents of which proved to be indispensable. All of the substrates have been desymmetrized to the corresponding monobenzoates with high enantioselectivity up to 96% enantiomeric excess. The catalytic system allows broad structural diversity of substrates and its synthetic versatility has been demonstrated by an efficient synthetic route to a known key precursor 68 of triazole antifungals.