LongLarf

Nature Chemistry, Published online: 30 December 2020; doi:10.1038/s41557-020-00576-z

Methods for producing organic molecules rich in sp3-hybridized carbon centres can be particularly useful for drug development. Now, it has been shown that the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates enables the synthesis of chiral alkyl boronates. The reaction proceeds via nickel hydride insertion into an internal alkene followed by nickel-catalysed alkyl–alkyl cross-coupling.

The art of Borrowers: Borrowing hydrogen is one of the most powerful acceptorless dehydrogenative transformations with sustainable feedstocks because of its atomic economy, use of sustainable resources, avoidance of toxic reagents, and no formation of waste byproducts. Traditional catalysts are mainly based on noble metals. Herein, the first example of a tungsten‐catalyzed N‐alkylation of amines with alcohols via borrowing hydrogen. This phosphine‐free approach is simple and tolerate a large number of functional groups.

Abstract

The implementation of non‐noble metals mediated chemistry is a major goal in homogeneous catalysis. Borrowing hydrogen/hydrogen autotransfer (BH/HA) reaction, as a straightforward and sustainable synthetic method, has attracted considerable attention in the development of non‐noble metal catalysts. Herein, we report a tungsten‐catalyzed N‐alkylation reaction of anilines with primary alcohols via BH/HA. This phosphine‐free W(phen)(CO)₄ (phen=1,10‐phenthroline) system was demonstrated as a practical and easily accessible in‐situ catalysis for a broad range of amines and alcohols (up to 49 examples, including 16 previously undisclosed products). Notably, this tungsten system can tolerate numerous functional groups, especially the challenging substrates with sterically hindered substituents, or heteroatoms. Mechanistic insights based on experimental and computational studies are also provided.

Ionic fifteenth: The diverse synthetic pathways to π‐conjugated systems with quaternary phosphorus, its unique connectivity and tunable electron deficient character, along with the non‐covalent cation‐anion interactions, introduce new photophysical and electrochemical features to ionic chromophores.

Abstract

Tunable electron‐accepting properties of the cationic phosphorus center, its geometry and unique preparative chemistry that allows combining this unit with diversity of π‐conjugated motifs, define the appealing photophysical and electrochemical characteristics of organophosphorus ionic chromophores. This Minireview summarizes the achievements in the synthesis of the π‐extended molecules functionalized with P‐cationic fragments, modulation of their properties by means of structural modification, and emphasizes the important effect of cation‐anion interactions, which can drastically change physical behavior of these two‐component systems.

An unprecedented methylation of various iminoamido heterocycles by using Corey—Chaykovsky reagents is described. The use of aqueous solvent in the coupling reaction and the selective methylation and alkylation of azauracil nucleosides are highlighted.

Abstract

The direct methylation of N‐heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp²)‐H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional‐group tolerance were attained. Moreover, this method can be readily applied to the site‐selective methylation of azauracil nucleosides. The feasibility of gram‐scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium‐labeling experiments aided the elucidation of a plausible reaction mechanism.

Biocatalysis has developed into a mature technology for chemical and pharmaceutical synthesis as well as other areas where high selectivity and mild reaction conditions are required. This Review highlights recent achievements with a special focus on industrialized applications including the introduction of key performance indicators (KPIs) to judge the efficiency of enzymes.

Abstract

Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.

Dehydroamino‐acid‐containing natural peptides and proteins were rapidly and selectively borylated at the β‐position using copper(II) catalysis. The introduced boronic‐acid functionalities are valuable handles for chemical mutagenesis and, in a reversible click reaction with triols, for the pH‐controlled labeling of ribosomally synthesized and post‐translationally modified peptides (RiPPs).

Abstract

We report the fast and selective chemical editing of ribosomally synthesized and post‐translationally modified peptides (RiPPs) by β‐borylation of dehydroalanine (Dha) residues. The thiopeptide thiostrepton was modified efficiently using Cu^II‐catalysis under mild conditions and 1D/2D NMR of the purified product showed site‐selective borylation of the terminal Dha residues. Using similar conditions, the thiopeptide nosiheptide, lanthipeptide nisin Z, and protein SUMO_G98Dha were also modified efficiently. Borylated thiostrepton showed an up to 84‐fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity was maintained in thiostrepton and nosiheptide. The introduced boronic‐acid functionalities were shown to be valuable handles for chemical mutagenesis and in a reversible click reaction with triols for the pH‐controlled labeling of RiPPs.

Carbamates from CO₂ : Transition metal‐free approaches for the generation of carbamates using CO₂ as a C1 synthon are summarized. This Minireview focuses on the benefits of the recent advances of transition metal‐free methodologies and mechanistic insights in the pursuit of carbamate generation for the synthesis of fine chemicals and pharmaceuticals as a CO₂‐fixation strategy.

Abstract

Utilization of carbon dioxide as a C1 synthon is highly attractive for the synthesis of valuable chemicals. However, activation of CO₂ is highly challenging, owing to its thermodynamic stability and kinetic inertness. With this in mind, several strategies have been developed for the generation of carbon–heteroatom bonds. Among these, formation of C−N bonds is highly attractive, especially, when carbamates can be synthesized directly from CO₂. This Minireview focuses on transition metal‐free approaches for the fixation of CO₂ to generate carbamates for the production of fine chemicals and pharmaceuticals. Within the past decade, transition metal‐free approaches have gained increasing attention, but traditional reviews have rarely focused on these approaches. Direct comparisons between such methods have been even more scarce. This Minireview seeks to address this discrepancy.

Who's in control? Substrate‐assisted nonreductive carbon dioxide conversion is a recently emerged concept that has significantly pushed the existing boundaries of catalytic formation of CO₂‐based heterocycles. The key mechanistic principles together with the new synthetic opportunities that have arisen from this approach are delineated, and areas with new potential and future developments are identified.

Abstract

The unparalleled potential of substrate‐induced reactivity modes in the catalytic conversion of carbon dioxide and alcohol or amine functionalized epoxides is discussed in relation to more conventional epoxide/CO₂ coupling strategies. This conceptually new approach allows for a substantial extension of the substitution degree and functionality of cyclic carbonate/carbamate products, which are predominant products in the area of nonreductive CO₂ transformations. Apart from the creation of an advanced library of CO₂‐based heterocyclic products and intermediates, also the underlying mechanistic reasons for this novel reactivity profile are debated with a prominent role for the design and structure of the involved catalysts.

Zinc(II) catalysis: This review reports the state of the art in the growing sector of esterification and transesterification of fatty acids and their esters catalyzed by Zn(II) species. The result is a framework in which this ion stands out thanks to its suited Lewis acidity, which is accompanied by a whole series of technical and ecological benefits in line with current sustainability requirements.

Abstract

The growing concern about global warming and the consumption of fossil fuels has driven in recent decades the use of biomass as a renewable feedstock. In this context, vegetable oils, the corresponding fatty acids (FAs) and esters (FAEs) have primary importance: their esterification and transesterification lead to innovative products, that find application in several sectors, from biofuels to solvents, from surfactants to cosmetic ingredients and plasticizers. Lewis acid catalysis represents the most accredited methodology for developing processes of esterification and transesterification in line with sustainability requirements. The results available so far reveal the prevalent catalytic role of Zn(II) salts and coordination compounds, due to their beneficial eco‐toxicological profile, combined with an appropriate acidity, finely tunable through selective functionalization. This review provides a picture of the state of the art in this important sector of biomass valorization.

This minireview covers the know literature on [3+2]‐cycloaddition of activated methylene isocyanides published since 2015. The review is divided into the three major parts that refer to the three heterocycles which can be prepared by reactions of isocyanides with C=C, C≡C, C=O, and C=N bonds.

This review is devoted to the recent advances in the chemistry of methylene isocyanides with C=C, C≡C, C=O, and C=N bonds. In this paper, we show a variety of [3+2] cycloaddition reactions for isocyanides, carried out both under catalytic and non‐catalytic conditions. In addition, we also focused on diastereo‐ and enantioselectivity data.

Transition‐metal‐catalyzed dehydrogenation of fluorinated alcohols is a highly energy‐demanding process and largely under explored. This work reports an acceptorless dehydrogenative method for the synthesis of bio‐active polyfluoroalkylated bis‐indoles by using a cheap nickel catalyst and fluorinated alcohols. Detailed theoretical and experimental studies propose a unique secondary effect of indole molecules during the dehydrogenation process.

Abstract

An acceptorless dehydrogenative strategy for the synthesis of polyfluoroalkylated bis‐indoles is described by employing an earth‐abundant nickel‐based catalytic system under air. The notable feature of the present transformation is the use of bench stable and easily affordable polyfluorinated alcohols without any pre‐functionalization for the introduction of precious polyfluoroalkyl groups. The developed straightforward protocol accomplished biologically relevant fluoroalkyl bis‐indoles in a sustainable fashion. Extensive DFT study predicts the unique role of indole molecules which stabilizes the transition states during the dehydrogenation process of polyfluorinated alcohols, presumably through non‐covalent π⋅⋅⋅π and H‐bonding interactions.

The enantioselective functionalization of nonactivated enantiotopic secondary C–H bonds is one of the greatest challenges in transition‐metal‐catalyzed C–H activation proceeding via an inner‐sphere mechanism. Notably, such reactions have remained elusive within the realm of palladium(0)‐catalysis. Here we report that  N ‐heterocyclic carbene ligands from the IBiox family display a unique reactivity profile in the Pd 0 ‐catalyzed intramolecular arylation of such nonactivated secondary C–H bonds. Chiral C 2 ‐symmetric IBiox ligands allowed to achieve high enantioselectivities for a broad range of valuable indane products containig a tertiary stereocenter. Similar reaction conditions were applicable to the arylation of secondary C–H bonds adjacent to amides. Depending on the amide substituents and upon control of reaction time, indanes containing a labile tertiary stereocenters were also obtained with high enantioselectivities. Analysis of the steric maps of the IBiox ligands indicated that the level of enantioselectivity correlates with the difference between the two most occupied and the two less occupied space quadrants, and provided a blueprint for the design of even more efficient ligands.

Publication date: 29 January 2021

Source: Tetrahedron, Volume 80

Author(s): Mei Sun, Yan-Ling Yu, Long Zhao, Ming-Wu Ding