The first general asymmetric synthesis of γ,γ‐disubstituted γ‐amino acids by copper‐catalyzed ring opening of nonstrained lactones with amines is reported. This approach features ample scope, ...operational simplicity, and wide functional‐group diversity. The catalytic process allows access to a series of highly functionalized enantioenriched γ‐amino acids featuring quaternary stereocenters with excellent enantiomeric ratios of up to 98:2 and excellent yields of up to 98 %.
Open sesame: The first general asymmetric synthesis of γ,γ‐disubstituted γ‐amino acids by copper‐catalyzed ring opening of nonstrained lactones with amines is reported. This catalytic system allows the synthesis of a series of highly functionalized γ‐amino acids, featuring quaternary stereocenters, with excellent enantiomeric ratios of up to 98:2 and yields of up to 98 %.
Axial chirality widely exists in natural products, pharmaceutical compounds, and other functional molecules; these axially chiral compounds also find wide utility as catalysts or ligands in organic ...synthetic chemistry. Nevertheless, whereas significant progress has been made toward the synthesis of enantioenriched axially chiral molecules over the past two decades, the strategies involving organocatalysis have only started to emerge recently. N-heterocyclic carbene (NHC) organocatalysts have been recognized to be powerful tools for the rapid construction of complex molecular architectures. However, previous works have mainly focused on the assembly of point chirality and only recently has it been realized that the asymmetric synthesis of axial chirality could be achieved by using NHCs as organocatalysts. This Perspective highlights the developments and advances in the synthesis of axially chiral scaffolds catalyzed by NHCs. The aim of this Perspective is to provide an overview of this area and serve as a stepping stone for future investigations.
Atropisomeric molecules have found proven applications and have shown promising potential in chemistry and medicine. The design of N‐heterocyclic carbene (NHC) catalyzed reactions to construct ...atropisomerically enriched molecules has emerged as an important research topic in recent years. These reactions include kinetic resolutions, asymmetric desymmetrizations, central‐to‐axial chirality conversions, and cycloadditions. This Minireview evaluates and summarizes the progress in NHC‐based organic catalysis for access to atropisomers, and briefly states our personal perspectives on the future advancement of this topic. NHC catalysis has provided rich and unique reaction modes that have led to success in the asymmetric synthesis of central‐chiral molecules. It is expected that similar success could also be achieved in developing NHC catalysis to prepare atropisomeric molecules, including those not easily accessible by other methods.
The design of N‐heterocyclic carbene (NHC) catalyzed reactions to construct atropisomerically enriched molecules has emerged as an important research topic in recent years. This Minireview summarizes progress made so far, and briefly states perspectives for the future advancement of this topic.
The catalytic dearomatization of naphthols offers a unique platform to rapidly access structurally complex and densely functionalized molecular architectures. Thermodynamically more favorable, with ...respect to the analogous phenol‐variant, the transformation of the phenolic ring into the corresponding naphthalenone (cited here as naphthyl dearomatization) has faced a considerable amount of attention over the past decade with constant improvements towards stereocontrol. A collection of the most representative and recent catalytic variants involving carbon–carbon as well as carbon–heteroatom bond forming events are presented in this Minireview article.
Bringing the 2D‐naphthyl core into a 3D‐dimension. The dearomatization of α‐ and β‐naphthols is currently considered a synthetic shortcut to rapidly access densely functionalized naphthalenone cores also in stereochemically defined manner. The latest developments in the area based on metal‐, organo‐, and visible‐light photoredox catalysis have been described.
Display omitted
•The enantioselective Michael addition of malonates with unsaturated ketones.•Catalyzed by samarium amide SmN(SiMe3)23 together with the chiral phenoxy-functionalized amino alcohol ...proligands.•The products with good group tolerance, mostly in high to excellent yields (85–98%) and good to excellent ee values (50– >99%).•A possible mechanism was proposed.
A combination of rare-earth metal amides REN(SiMe3)23 and chiral phenoxy-functionalized amino alcohol proligands was developed to realize the enantioselective Michael addition of malonates with unsaturated ketones. The reactions catalyzed by samarium amide SmN(SiMe3)23 were performed best together with the chiral proligand H3L1 (H3L1 = 2,4-di-tert-butyl-6-(((1S,2R)-2-hydroxy-1,2-diphenylethyl) amino)methyl)phenol) in DCE with good group tolerance, mostly in high to excellent yields (85–98 %) and good to excellent ee values (50− >99 %). The possible mechanism was also proposed.
Molecules with restricted rotation around a single bond or atropisomers are found in a wide number of natural products and bioactive molecules as well as in chiral ligands for asymmetric catalysis ...and smart materials. Although most of these compounds are biaryls and heterobiaryls displaying a C−C stereogenic axis, there is a growing interest in less common and more challenging axially chiral C−N atropisomers. This review offers an overview of the various methodologies available for their asymmetric synthesis. A brief introduction is initially given to contextualize these axially chiral skeletons, including a historical background and examples of natural products containing axially chiral C−N axes. The preparation of different families of C−N based atropisomers is then presented from anilides to chiral five‐ and six‐membered ring heterocycles. Special emphasis has been given to modern catalytic asymmetric strategies over the past decade for the synthesis of these chiral scaffolds. Applications of these methods to the preparation of natural products and biologically active molecules will be highlighted along the text.
The synthesis of axially chiral compounds featuring a N−C stereogenic axis are presented and discussed, with an emphasis in catalytic asymmetric approaches. Diverse strategies and methodologies, based either on metal‐catalyzed transformation or in organocatalytic activation, comprise not only the direct generation of the N−C axis but also desymmetrization, kinetic resolution, dynamic kinetic resolution and different types of chirality transfer.
The increasing synthetic utility of allenes in organic synthesis combined with their incorporation into a growing list of natural products and active pharmaceutical ingredients has stimulated an ...intense effort recently to identify efficient catalytic methods for their synthesis. In addition, as the only common functional group in organic chemistry that possesses axial chirality, efforts to discover new asymmetric catalysts for the enantioselective synthesis of axially chiral allenes has intensified as these substrates become more ubiquitous as chiral building blocks for downstream asymmetric methodologies. Nonetheless, despite this intensive effort, the ability to access racemic or chiral allenes from readily available starting materials using catalytic processes has yet to meet the demand of their expanding applications. The focus of this Perspective is to provide a critical assessment on the most recent developments in the field of catalytic syntheses of allenes (2011–2013) highlighting both the advantages and limitations associated with current approaches with a future outlook on the unmet synthetic need that still persists.
•Construction of CC bond using Pd catalyzed cross coupling reactions.•Recent advances made in Pd catalyzed reaction using NS ligands.•The review focused on literature based on NS ligands.
Phosphine ...ligands have been widely used in catalytic reactions, but they have several limitations such as low air, moisture, and thermal stability. Consequently, in recent decades, researchers have been challenged to develop phosphine-free conditions for Pd-catalyzed cross-coupling reactions. This review focuses on the use of different N-S-based ligands in Pd-catalyzed cross-coupling reactions. The advantage of these ligands is that S acts as a soft ligand for soft Pd metals. In addition, S has a high coordination ability with Pd. In the last twenty years, ligands containing S in combination with N atoms have been developed and used in many enantioselective reactions. This review surveys the research in this area and discusses the prospects for future developments.
Display omitted
Glucose dehydrogenase (GDH) generally functions as an expensive cofactor NAD(P)H regenerator in an enzyme-coupled cofactor regeneration system, as in the production of fine chemicals. However, ...whether GDH can accept substrates other than glucose remains to be explored. Based on a known mutant of GDH with high thermostability, DN46 (E170K–K252L), we employed semirational design-based directed evolution to expand its substrate scope and promote its application in the asymmetric synthesis of methyl 2-hydroxyl carboxylates. After one round of saturation mutagenesis and two rounds of iterative saturation mutagenesis, an enantioselectivity-enhanced mutant DN46-E96Q-H147V (>99% ee, R-preference) and enantioselectivity-reversed mutant DN46-E96Q-I150A-W152L with high enantioselectivity (>97% ee, S-preference) evolved. With glucose as a cosubstrate, we developed a dual-function GDH-based substrate-coupled cofactor regeneration system for asymmetric synthesis. Furthermore, in light of a deeper understanding of the catalytic mechanism, a rational design was successfully performed to create a mutant DN46-W152G for the upscaled synthesis of (R)-2-chloromandelic acid methyl ester, the precursor of the medicine (S)-clopidogrel. This work expands the utilization of GDH, provides a design method for rational design of this enzyme, and will support future work regarding its application toward achieving even broader substrate scope.
PDF
