Uncatalyzed Diboron Activation by a Strained Hydrocarbon: Experimental and Theoretical Study of [1.1.1]Propellane Diborylation.

The synthesis of strained carbocyclic building blocks is relevant for Medicinal Chemistry, and methylenecyclobutanes are particularly challenging with current synthetic technology. Careful inspection of the reactivity of [1.1.

Modular Synthesis of (Borylmethyl)silanes through Orthogonal Functionalization of a Carbon Atom.

(Borylmethyl)trimethylsilanes are important building blocks in organic synthesis displaying a unique reactivity. Yet, the synthesis of more advanced derivatives is limited by the advanced silicon intermediates required for their preparation. Herein, a one-pot synthesis of (borylmethyl)silanes is developed, sourced on available alkyl-, aryl-, alkoxy-, aryloxy-, and silyl-hydrosilane materials.

An application of interactive fuzzy optimization model for redesigning supply chain for resilience.

Supply chain disruptions compel professionals all over the world to consider alternate strategies for addressing these issues and remaining profitable in the future. In this study, we considered a four-stage global supply chain and designed the network with the objectives of maximizing profit and minimizing disruption risk. We quantified and modeled disruption risk as a function of the geographic diversification of facilities called supply density (evaluated based on the interstage distance between nodes) to mitigate the risk caused by disruptions.

Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

Invited for the cover of this issue is the group of Abraham Mendoza at Stockholm University. The image depicts a Grignard reagent "turbo-charged" with a magnesium anilide additive. Read the full text of the article at 10.

Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline-derived turbo-Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.

Modular Enantioselective Synthesis of -Cyclopropanes through Self-Sensitized Stereoselective Photodecarboxylation with Benzothiazolines.

Chiral -cyclopropanes are strained rigid analogues of alkyl chains, whose study and application are limited by their difficult synthesis. A modular approach from olefin materials is enabled by the discovery of the electron donor-acceptor (EDA) interaction between 2-substituted benzothiazolines and -hydroxyphthalimide esters. These complexes are activated by visible light without photocatalysts, and the benzothiazoline reagent plays a triple role as a photoreductant, a stereoselective hydrogen-atom donor, and a Brønsted acid.

Combined Experimental and Computational Study of Ruthenium -Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions.

A combined experimental-computational approach has been used to study the cyclopropanation reaction of -hydroxyphthalimide diazoacetate (NHPI-DA) with various olefins, catalyzed by a ruthenium-phenyloxazoline (Ru-Pheox) complex. Kinetic studies show that the better selectivity of the employed redox-active NHPI diazoacetate is a result of a much slower dimerization reaction compared to aliphatic diazoacetates. Density functional theory calculations reveal that several reactions can take place with similar energy barriers, namely, dimerization of the NHPI diazoacetate, cyclopropanation (inner-sphere and outer-sphere), and a previously unrecognized migratory insertion of the carbene into the phenyloxazoline ligand.

-Hydroxyphthalimidyl diazoacetate (NHPI-DA): a modular methylene linchpin for the C-H alkylation of indoles.

Despite the extensive studies on the reactions between conventional diazocompounds and indoles, these are still limited by the independent synthesis of the carbene precursors, the specific catalysts, and the required multi-step manipulation of the products. In this work, we explore redox-active carbenes in the expedited and divergent synthesis of functionalized indoles. NHPI-DA displays unusual efficiency and selectivity to yield insertion products that can be swiftly elaborated into boron and carbon substituents that are particularly problematic in carbene-mediated reactions.

Comparative Analysis of the Bibliographic Data Sources Dimensions and Scopus: An Approach at the Country and Institutional Levels.

This paper presents a large-scale document-level comparison of two major bibliographic data sources: Scopus and Dimensions. The focus is on the differences in their coverage of documents at two levels of aggregation: by country and by institution. The main goal is to analyze whether Dimensions offers as good new opportunities for bibliometric analysis at the country and institutional levels as it does at the global level.

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light.

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

Computational and Experimental Study of Turbo-Organomagnesium Amide Reagents: Cubane Aggregates as Reactive Intermediates in Pummerer Coupling.

The dynamic equilibria of organomagnesium reagents are known to be very complex, and the relative reactivity of their components is poorly understood. Herein, a combination of DFT calculations and kinetic experiments is employed to investigate the detailed reaction mechanism of the Pummerer coupling between sulfoxides and turbo-organomagnesium amides. Among the various aggregates studied, unprecedented heterometallic open cubane structures are demonstrated to yield favorable barriers through a concerted anion-anion coupling/ S-O cleavage step.

Scalable Synthesis of Esp and Rhodium(II) Carboxylates from Acetylacetone and RhCl·HO.

Rhodium(II) carboxylates are privileged catalysts for the most challenging carbene-, nitrene-, and oxo-transfer reactions. In this work, we address the strategic challenges of current organic and inorganic synthesis methods to access these rhodium(II) complexes through an oxidative rearrangement strategy and a reductive ligation reaction. These studies illustrate the multiple benefits of oxidative rearrangement in the process-scale synthesis of congested carboxylates over nitrile anion alkylation reactions, and the impressive effect of inorganic additives in the reductive ligation of rhodium(III) salts.

Inventory replenishment decision model for the supplier selection problem using metaheuristic algorithms.

In supply chain management, fast and accurate decisions in supplier selection and order quantity allocation have a strong influence on the company's profitability and the total cost of finished products. In this paper, a novel and non-linear model is proposed for solving the supplier selection and order quantity allocation problem. The model is introduced for minimizing the total cost per time unit, considering ordering, purchasing, inventory, and transportation cost with freight rate discounts.

-PrNMgCl·LiCl Enables the Synthesis of Ketones by Direct Addition of Grignard Reagents to Carboxylate Anions.

The direct preparation of ketones from carboxylate anions is greatly limited by the required use of organolithium reagents or activated acyl sources that need to be independently prepared. Herein, a specific magnesium amide additive is used to activate and control the addition of more tolerant Grignard reagents to carboxylate anions. This strategy enables the modular synthesis of ketones from CO and the preparation of isotopically labeled pharmaceutical building blocks in a single operation.

Mechanism and regioselectivity of the anionic oxidative rearrangement of 1,3-diketones towards all-carbon quaternary carboxylates.

The oxidative rearrangement of 1,3-diketones is an underexplored alternative to enolate chemistry in the synthesis of all-carbon quaternary carboxylates. The mechanistic investigation of this reaction has resulted in a mild base mediated protocol, whose regioselectivity has been studied in challenging acyclic substrates.

General Cyclopropane Assembly by Enantioselective Transfer of a Redox-Active Carbene to Aliphatic Olefins.

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes.

Mechanistic Insight into Enantioselective Palladium-Catalyzed Oxidative Carbocyclization-Borylation of Enallenes.

The asymmetric palladium-catalyzed oxidative carbocyclization-borylation of enallenes, employing a chiral phosphoric acid as co-catalyst, constitutes an efficient and convenient entry into functionalized building blocks with cyclopentene scaffolds in high enantiopurity. Up till now there has been a lack of knowledge concerning the origin of enantioselectivity of this reaction as well as the absolute configuration of the product. Herein, we report the crystal structure of one of the compounds generated via this carbocyclization, providing the link between the configuration of the products and the configuration of the chiral phosphoric acid used in the reaction.

Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic Media.

A new Pummerer-type C-C coupling protocol is introduced based on turbo-organomagnesium amides, which unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of C(sp )-, C(sp )-, and C(sp)-nucleophiles, and seamlessly integrates with C-H and C-X magnesiation. Given the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides, and boronic esters through a single strategy.

Direct and Stereospecific [3+2] Synthesis of Pyrrolidines from Simple Unactivated Alkenes.

Pyrrolidines are important heterocyclic compounds with endless applications in organic synthesis, metal catalysis, and organocatalysis. Their potential as ligands for first-row transition-metal catalysts inspired a new method to access complex poly-heterocyclic pyrrolidines in one step from available materials. This fundamental step forward is based on the discovery of an essential organoaluminum promoter that engages unactivated and electron-rich olefins in intermolecular [3+2] cycloadditions.

Scalable Synthesis of Piperazines Enabled by Visible-Light Irradiation and Aluminum Organometallics.

The development of more active C-H oxidation catalysts has inspired a rapid, scalable, and stereoselective assembly of multifunctional piperazines through a [3+3] coupling of azomethine ylides. A combination of visible-light irradiation and aluminum organometallics is essential to promote this transformation, which introduces visible-light photochemistry of main-group organometallics and sets the basis for new and promising catalysts.

Two-phase synthesis of (-)-taxuyunnanine D.

The first successful effort to replicate the beginning of the Taxol oxidase phase in the laboratory is reported, culminating in the total synthesis of taxuyunnanine D, itself a natural product. Through a combination of computational modeling, reagent screening, and oxidation sequence analysis, the first three of eight C-H oxidations (at the allylic sites corresponding to C-5, C-10, and C-13) required to reach Taxol from taxadiene were accomplished. This work lays a foundation for an eventual total synthesis of Taxol capable of delivering not only the natural product but also analogs inaccessible via bioengineering.

Total synthesis of taxane terpenes: cyclase phase.

A full account of synthetic efforts toward a lowly oxidized taxane framework is presented. A non-natural taxane, dubbed "taxadienone", was synthesized as our first entry into the taxane family of diterpenes. The final synthetic sequence illustrates a seven-step, gram-scale and enantioselective route to this tricyclic compound in 18% overall yield.

A catalytic multicomponent coupling reaction for the enantioselective synthesis of spiroacetals.

The first multicomponent catalytic asymmetric synthesis of spiroacetals has been described. Hybrid molecules comprising a spiroacetal scaffold (a natural-product inspired scaffold) and an α-amino acid motif (a privileged fragment) are easily available through a gold phosphate-catalysed one-pot three component coupling reaction of alkynols, anilines and glyoxylic acid.

Guided desaturation of unactivated aliphatics.

The excision of hydrogen from an aliphatic carbon chain to produce an isolated olefin (desaturation) without overoxidation is one of the most impressive and powerful biosynthetic transformations for which there are no simple and mild laboratory substitutes. The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space. Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis.