does the concentration of an acid affect its ability to catalyse a reversible reaction? eg. if you increase/decrease conc. of the already strong HCL acid - does it mean a higher concentration would release H3O at a faster rate or has more released in a fixed time or sm? Or not cos catalysts regenerate.
I am a beginner in Lewis acid and base. In this photo, the opening of epoxide by a nucleophile e.g. alkyne anion is catalyzed by BF3.
https://preview.redd.it/rm9u6prj7ao71.png?width=1005&format=png&auto=webp&s=c689b800e21a22988ad8a8987b23641d6ec5ba1a
- According to Wikipedia, BF3-Et2O serves as a source of BF3. What are the factors to select a molecule that coordinates with the Lewis acid BF3? For example, the same Wikipedia page also describes methanol and even propanol can be used (seems the same principle as the lone pair electron on O donates into empty p orbital in B) Can I say any Lewis bases can coordinate with BF3 for this Lewis acid catalysis?
- And, according to Wikipedia, the mechanism of lewis acid catalysis is:
> Lewis acid catalysis often involves binding of the catalyst to Lewis basic heteroatoms and withdrawing electron density.
- so, just to confirm my understanding: The electronegativity of boron and fluorine differs greatly. When BF3 forms an adduct to the oxygen atom in epoxide, the electron density of oxygen is drawn to the 3 fluorine atoms in BF3, hence increasing the electrophilicity of oxygen atom. Therefore, rate of the attack by the nucleophile (alkyne anion) to open the epoxide is enhanced.
Please explain to me if I have made any mistakes, thanks a lot.
https://preview.redd.it/khjcmm2cbtn71.png?width=1005&format=png&auto=webp&s=130a0f2d9bdafc93cc160430f847d0e23f3237d2
I am a beginner in Lewis acid and base. In this photo, the opening of epoxide by a nucleophile e.g. alkyne anion is catalyzed by BF3.
- BF3-Et2O is a source of BF3 (from Wiki). If I understand correctly, this is because it is impossible for a use 'naked' BF3 since it is a gas in room temperature. Then, can I say I can use any other kinds of Lewis Base to bond with BF3, as long as
- It is liquid and does not react with any reactants here, so that it can be a solvent?
- to confirm why it is called catalysis: when BF3 is bonded to to the oxygen in epoxide, the electron density of oxygen are pulled away, this in turn pull away the electrons from carbon, making it much more nucleophilic.
- BF3 is good here since 3 B-F bonds are highly polar to the F, so the ability to pull electrons is very high (from the photo)
Please explain to me if I have made any mistakes, thanks a lot.
I read a book which explains that enzymes reduce the (ΔG‡) by many mechanisms. The book mentions that one of those mechanisms is to decrease ΔH‡ using the acid/base catalysis.
How can this be possible? What's the relationship between the acid/base catalysis and the ΔH‡??
Carbodicarbene (CDC), unique carbenic entities bearing two lone pairs of electrons are well-known for their strong Lewis basicity. We demonstrate herein, upon introducing a weak Brønsted acid benzyl alcohol (BnOH) as a co-modulator, CDC is remoulded into a Frustrated Lewis Pair (FLP)-like reactivity. DFT calculation and experimental evidence show BnOH loosely interacting with the binding pocket of CDC via H-bonding and p-p stacking. Four distinct reactions in nature were deployed to demonstrate the viability of proof-of-concept as synergistic FLP/Modulator (CDC/BnOH), demonstrating enhanced catalytic reactivity in cyclotrimerization of isocyanate, polymerization process for L -lactide (LA), methyl methacrylate (MMA) and dehydrosilylation of alcohols. Importantly, the catalytic reactivity of carbodicarbene is uniquely distinct from conventional NHC which relies on only single chemical feature of nucleophilicity. This finding also provides a new spin in diversifying FLP reactivity with co-modulator or co-catalyst.
https://ift.tt/35nAyMY
Using the Eschweiler–Clarke reaction, a series of flexible amine‐linked COFs was synthesized by catalysis and reduction of formic acid. The unique bifunctional properties of formic acid can not only catalyze the formation of rigid C=N bond like acetic acid, the most common catalyst in COF synthesis, but also reduce and transform it to flexible C−N bond simultaneously, giving COFs the accommodative adaptability to guest molecules.
Abstract
Compared to the current mainstream rigid covalent organic frameworks (COFs) linked by imine bonds, flexible COFs have certain advantages of elasticity and self‐adaptability, but their construction and application are greatly limited by the complexity in synthesis and difficulty in obtaining regular structure. Herein, we reported for the first time a series of flexible amine‐linked COFs with high crystallinity synthesized by formic acid with unique catalytic and reductive bifunctional properties, rather than acetic acid, the most common catalyst for COF synthesis. The reaction mechanism was demonstrated to be a synchronous in situ reduction during the formation of imine bond. The flexibilities of the products endow them with accommodative adaptability to guest molecules, thus increasing the adsorption capacities for nitrogen and iodine by 27 % and 22 %, respectively. Impressively, a novel concept of flexibilization degree was proposed firstly, which provides an effective approach to rationally measure the flexibility of COFs.
https://ift.tt/2PoHLIh
Combining organo‐, bio‐, and metal‐catalyst for up to six synthetic steps allowed the one‐pot production line towards (enantiopure) key building blocks for natural product synthesis as well as polymer science in gram‐scale. The basis was set by an in‐depth investigation of the initial steps of the sequence and investigating the central role of the organocatalyst {Org: 1,4‐diazabicyclo[2.2.2]octane (DABCO)} as well as benzoic acid.
Abstract
Establishing one‐pot, multi‐step protocols combining different types of catalysts is one important goal for increasing efficiency in modern organic synthesis. In particular, the high potential of biocatalysts still needs to be harvested. Based on an in‐depth mechanistic investigation of a new organocatalytic protocol employing two catalysts {1,4‐diazabicyclo[2.2.2]octane (DABCO); benzoic acid (BzOH)}, a sequence was established providing starting materials for enzymatic refinement (ene reductase; alcohol dehydrogenase): A gram‐scale access to a variety of enantiopure key building blocks for natural product syntheses was enabled utilizing up to six catalytic steps within the same reaction vessel.
https://ift.tt/3e6iZVz
We report the discovery that simple carboxylic acids, such as benzoic acid, boost the activity of N-heterocyclic carbene (NHC) catalysts in the oxidative esterification of aldehydes. A simple and efficient protocol for the transformation of a wide range of sterically hindered alpha- and beta-substituted aliphatic aldehydes/enals, catalyzed by a novel and readily accessible N-Mes-/N-2,4,6-trichlorophenyl 1,2,4-triazolium salt, and benzoic acid as co-catalyst, was developed. A whole series of a/b-substituted aliphatic aldehydes/enals hitherto not amenable to NHC-catalyzed esterification could be reacted at typical catalyst loadings of 0.02 - 1.0 mol %. For benzaldehyde, even 0.005 mol % of NHC catalyst proved sufficient - the lowest value ever achieved in NHC catalysis. Preliminary studies point to carboxylic acid-induced acceleration of acyl transfer from azolium enolate intermediates as the mechanistic basis of the observed effect.
https://ift.tt/3eZeCNU
Bimetallic cooperative catalysis is reported for the direct decarbonylative heteroarylation of carboxylic acids via acyl C‐O/C‐H coupling. The cooperative action of copper and palladium catalysts is exploited for chemoselective synthesis of heterobiaryl motifs. A broad substrate scope (>70 examples) is accessible, including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents.
Abstract
Cooperative bimetallic catalysis is a fundamental approach in modern synthetic chemistry. We report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C‐O/C‐H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst in decarbonylation, which enables highly chemoselective synthesis of important heterobiaryl motifs through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative method uses common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the reaction. The key step involves intersection of the two catalytic cycles via transmetallation of the copper–aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation.
https://ift.tt/39KFTAs
Playfully easy! The targeted combination of organo- and biocatalysts enables the scalable conversion of inexpensive commercial substrates into a library of highly valuable enantiomerically pure synthetic building blocks for natural product synthesis. The approach included newly designed monomers for radical polymerization, as described by Jörg Pietruszka et al. in their Research Article (DOI: 10.1002/anie.202103406). Graphic design: Irene Küberl.
https://ift.tt/3yRgss6
We report the first crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl‐CoA (AcCoA), serotonin, and 5‐MT which exhibit a unique enzymatically active dimeric fold. MD simulations indicated a novel acid/base‐assisted catalysis. The pH and temperature‐depended activity were also shown. This is the first comprehensive study in plant N‐acetyltransferase combining biochemical, structural, and theoretical analysis.
Abstract
Serotonin N‐acetyltransferase (SNAT) is the key rate‐limiting enzyme in melatonin biosynthesis. It mediates melatonin biosynthesis in plants by using serotonin and 5‐methoxytryptamine (5‐MT), but little is known of its underlying mechanisms. Herein, we present a detailed reaction mechanism of a SNAT from Oryza sativa through combined structural and molecular dynamics (MD) analysis. We report the crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl‐CoA (AcCoA), serotonin, and 5‐MT. OsSNAT exhibits a unique enzymatically active dimeric fold not found in the known structures of arylalkylamine N‐acetyltransferase (AANAT) family. The key residues W188, D189, D226, N220, and Y233 located around the active pocket are important in catalysis, confirmed by site‐directed mutagenesis. Combined with MD simulations, we hypothesize a novel plausible catalytic mechanism in which D226 and Y233 function as catalytic base and acid during the acetyl‐transfer reaction.
https://ift.tt/3o7N3oy
Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c01811
Teng Yuan, Qi Tang, Chuan Shan, Xiaohan Ye, Jin Wang, Pengyi Zhao, Lukasz Wojtas, Nicholas Hadler, Hao Chen, and Xiaodong Shi
https://ift.tt/3uQOhHT
Enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β‐unsaturated carboxylic acids is demonstrated via CoII catalysis. Broad substrate scope is achieved, yielding chiral carboxylic acids in good yields with excellent enantiocontrol. A CoII catalytic cycle involving migratory insertion and σ‐bond metathesis processes is posited whereby steric substrate ligand effects promote enantiocontrol.
Abstract
Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α,β‐unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di‐ and trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted α,β‐unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β‐unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 % yield and 99 % ee). Combined experimental and computational mechanistic studies support a CoII catalytic cycle involving migratory insertion and σ‐bond metathesis processes. DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate.
https://ift.tt/39NJ0Yw
A radical addition reaction between glycine esters and racemic α‐bromoketones catalyzed by synergistic Brønsted acid/photoredox catalysis is presented. This dual catalysis controls the reactive radical intermediate and iminium ion to facilitate the bond‐forming event in a highly stereochemical manner. An array of valuable enantioenriched unnatural α‐AAs bearing two contiguous stereocenters are accessible.
Abstract
An unprecedented radical cross‐coupling reaction was achieved between glycine esters and racemic α‐bromoketones catalyzed by synergistic Brønsted acid/photoredox catalysis, thus serving as an efficient platform for the synthesis of highly valuable enantioenriched unnatural α‐amino acid derivatives. This dual catalysis provides a powerful capability to control the reactive radical intermediate and iminium ion, thereby enabling enantioconvergent bond‐formation in a highly stereochemical manner. An array of valuable enantioenriched unnatural α‐amino acid derivatives bearing two contiguous stereogenic centers are readily accessible with high diastereoselectivity and excellent enantioselectivity, which include α‐amino acids with a unique β‐fluorinated quaternary stereocenter or its β‐all‐carbon counterpart. A strong chiral amplification effect was observed in this dual catalytic system.
https://ift.tt/3lUEb3F
A simple strategy comprising of the grafting of amino acids onto porous MOFs followed by metalation with earth‐abundant metals, such as iron, affords heterogeneous single‐site chiral catalysts by site isolation. The iron catalysts displayed high activity and excellent enantioselectivity in hydrosilylation and hydroboration of carbonyls.
Abstract
We report a strategy to develop heterogeneous single‐site enantioselective catalysts based on naturally occurring amino acids and earth‐abundant metals for eco‐friendly asymmetric catalysis. The grafting of amino acids within the pores of a metal‐organic framework (MOF), followed by post‐synthetic metalation with iron precursor, affords highly active and enantioselective (>99 % ee for 10 examples) catalysts for hydrosilylation and hydroboration of carbonyl compounds. Impressively, the MOF‐Fe catalyst displayed high turnover numbers of up to 10 000 and was recycled and reused more than 15 times without diminishing the enantioselectivity. MOF‐Fe displayed much higher activity and enantioselectivity than its homogeneous control catalyst, likely due to the formation of robust single‐site catalyst in the MOF through site‐isolation.
https://ift.tt/38XCQVd
Nature Chemistry, Published online: 01 February 2021; doi:10.1038/s41557-020-00628-4
A de novo designed zinc-binding protein has been converted into a highly active, stereoselective catalyst for a hetero-Diels–Alder reaction. Design and directed evolution were used to effectively harness Lewis acid catalysis and create an enzyme more proficient than other reported Diels–Alderases.
https://ift.tt/3cx3mHI
The synthesis of α‐aryl‐β 2 ‐amino esters through enantioselective aminomethylation of an arylacetic acid ester in high yields and enantioselectivity via cooperative isothiourea and Brønsted acid catalysis is demonstrated. The scope and limitations of this process are explored (25 examples, up to 94% yield and 96:4 er), with applications to the synthesis of ( S )‐Venlafaxine·HCl and ( S )‐Nakinadine B. Mechanistic studies are consistent with a C(1)‐ammonium enolate pathway being followed rather than an alternative dynamic kinetic resolution process. Control studies indicate that (i) a linear effect between catalyst and product er is observed; (ii) an acyl ammonium ion can be used as a precatalyst; (iii) reversible isothiourea addition to an in situ generated iminium ion leads to an off‐cycle intermediate that can be used as a productive precatalyst.
https://ift.tt/2NMU14K
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c12819
Duanyang Kong, Maxime Munch, Qiqige Qiqige, Christopher J. C. Cooze, Benjamin H. Rotstein, and Rylan J. Lundgren
https://ift.tt/3t2BGAi
Nickel‐catalyzed linear‐selective hydroarylation of unactivated alkenes with arylboronic acids is demonstrated by a redox‐neutral NiII/NiII catalytic cycle for the first time. This novel catalytic cycle, enabled by the use of an electron‐rich diimine ligand, features broad substrate scope, and excellent functional‐group and heterocycle compatibility under mild reaction conditions in the absence of additional oxidants and reductants.
Abstract
Reported here is the discovery of a redox‐neutral NiII/NiII catalytic cycle which is capable of the linear‐selective hydroarylation of unactivated alkenes with arylboronic acids for the first time. This novel catalytic cycle, enabled by the use of an electron‐rich diimine ligand, features broad substrate scope, and excellent functional‐group and heterocycle compatibility under mild reaction conditions in the absence of additional oxidants and reductants. Mechanistic investigations using kinetic analysis and deuterium‐labelling experiments revealed the protonation to be the rate‐determining step in this redox‐neutral catalysis, and the reversible chain‐walking nature of the newly developed diimine‐Ni catalyst.
https://ift.tt/2EEMX51
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c09974
Xingchen Yan, Luo Ge, Marta Castiñeira Reis, and Syuzanna R. Harutyunyan
https://ift.tt/38wMkY4
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c04107
Shang Gao, Meng Duan, Qianzhen Shao, K. N. Houk, and Ming Chen
https://ift.tt/3nSnE1p
The reaction between α,β‐unsaturated lactones and 1,3‐dienes looks like a Diels–Alder reaction, but it is a vinylogous Michael addition as indicated by experimental results and DFT calculations. A short sequence was established accessing (natural) mellein and angelicoin derivatives.
Abstract
The reactions of α,β‐unsaturated δ‐lactones with activated dienes such as 1,3‐dimethoxy‐1‐[(trimethylsilyl)oxy]‐1,3‐butadiene (Brassard's diene) are barely known in literature and show high potential for the synthesis of isocoumarin moieties. An in‐depth investigation of this reaction proved a stepwise mechanism via the vinylogous Michael‐products. Subsequent cyclisation and oxidation by LHMDS and DDQ, respectively, provided six mellein derivatives (30–84 %) and four angelicoin derivatives (40–78 %) over three steps. DFT‐calculations provide insights into the reaction mechanism and support the theory of a stepwise reaction.
https://ift.tt/3dt2As5
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c07257
https://ift.tt/3hjn4GE
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c08599
https://ift.tt/32kf4zQ
The potential of a dicationic strontium ansa ‐arene complex for Lewis‐acid catalysis has been explored. The key to its synthesis was a simple salt metathesis from SrI 2 and 2 Ag[Al(OR F ) 4 ] giving the base‐free strontium‐perfluoroalkoxyaluminate Sr[Al(OR F ) 4 ] 2 (OR F = OC(CF 3 ) 3 ). Addition of the ansa ‐arene yielded the highly Lewis‐acidic, dicationic strontium ansa ‐arene complex. In preliminary experiments, it was successfully applied as catalyst in a CO 2 ‐reduction to CH 4 and a surprisingly controlled isobutylene polymerization.
https://ift.tt/3gSM47q
In an efficient approach to catalytic asymmetric [4+2] cycloaddition, acidic prodienes were deprotonated by a betaine species to form a copper dienolate, and the dienophile was activated by hydrogen‐bond formation (see scheme). The polyfunctional catalyst promoted the transformation with high enantioselectivity as well as high turnover numbers.
Abstract
Diels–Alder reactions have become established as one of the most effective ways to prepare stereochemically complex six‐membered rings. Different catalysis concepts have been reported, including dienophile activation by Lewis acids or H‐bond donors and diene activation by bases. Herein we report a new concept, in which an acidic prodiene is acidified by a Lewis acid to facilitate deprotonation by an imidazolium–aryloxide entity within a polyfunctional catalyst. A metal dienolate is thus formed, while an imidazolium–ArOH moiety probably forms hydrogen bonds with the dienophile. The catalyst type, readily prepared in few steps in high overall yield, was applied to 3‐hydroxy‐2‐pyrone and 3‐hydroxy‐2‐pyridone as well as cyclopentenone prodienes. Maleimide, maleic anhydride, and nitroolefin dienophiles were employed. Kinetic, spectroscopic, and control experiments support a cooperative mode of action. High enantioselectivity was observed even with unprecedented TONs of up to 3680.
https://ift.tt/30AAsis
Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c00727
https://ift.tt/2HNnAwm
A palladium catalyst and a chiral phosphoric acid act synergistically to induce enantiocontrol in intramolecular allylic substitution reactions, and statistical modeling has identified multiple noncovalent interactions. These mechanistic studies led to an expansion of synthetic scope to the formation of challenging tertiary ether stereocenters.
Abstract
The mode of asymmetric induction in an enantioselective intramolecular allylic substitution reaction catalyzed by a combination of palladium and a chiral phosphoric acid was investigated by a combined experimental and statistical modeling approach. Experiments to probe nonlinear effects, the reactivity of deuterium‐labeled substrates, and control experiments revealed that nucleophilic attack to the π‐allylpalladium intermediate is the enantio‐determining step, in which the chiral phosphate anion is involved in stereoinduction. Using multivariable linear regression analysis, we determined that multiple noncovalent interactions with the chiral environment of the phosphate anion are integral to enantiocontrol in the transition state. The synthetic protocol to form chiral pyrrolidines was further applied to the asymmetric construction of C−O bonds at fully substituted carbon centers in the synthesis of chiral 2,2‐disubstituted benzomorpholines.
https://ift.tt/3dihrWQ
Using the Eschweiler–Clarke reaction, a series of flexible amine‐linked COFs was synthesized by catalysis and reduction of formic acid. The unique bifunctional properties of formic acid can not only catalyze the formation of rigid C=N bond like acetic acid, the most common catalyst in COF synthesis, but also reduce and transform it to flexible C−N bond simultaneously, giving COFs the accommodative adaptability to guest molecules.
Abstract
Compared to the current mainstream rigid covalent organic frameworks (COFs) linked by imine bonds, flexible COFs have certain advantages of elasticity and self‐adaptability, but their construction and application are greatly limited by the complexity in synthesis and difficulty in obtaining regular structure. Herein, we reported for the first time a series of flexible amine‐linked COFs with high crystallinity synthesized by formic acid with unique catalytic and reductive bifunctional properties, rather than acetic acid, the most common catalyst for COF synthesis. The reaction mechanism was demonstrated to be a synchronous in situ reduction during the formation of imine bond. The flexibilities of the products endow them with accommodative adaptability to guest molecules, thus increasing the adsorption capacities for nitrogen and iodine by 27 % and 22 %, respectively. Impressively, a novel concept of flexibilization degree was proposed firstly, which provides an effective approach to rationally measure the flexibility of COFs.
https://ift.tt/2PoHLIh
Covalent Organic Frameworks The synthesis of a series of flexible amine‐linked COFs is reported by Lijian Ma et al. in their Research Article on page 12396.
https://ift.tt/3tZSh7i
Cooperative bimetallic catalysis represents a fundamental approach in modern synthetic chemistry that addresses many challenges associated with the evolution of the field. Herein, we report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C–O/C–H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst under decarbonylative regimen, which enables for the highly chemoselective synthesis of important heterobiaryl motifs that enjoy a privileged role in the realm of organic synthesis through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative platform benefits from the direct use of common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the bimetallic decarbonylative platform. The key step involves intersection of the two catalytic cycles via transmetallation of the copper‐aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation. We envision the versatile bimetallic cooperative decarbonylative framework will have an impact on planning synthetic approaches in cooperative catalysis, decarbonylative coupling and synthesis of biaryl motifs .
https://ift.tt/3ugw2LJ
We report the first crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl‐CoA (AcCoA), serotonin, and 5‐MT which exhibit a unique enzymatically active dimeric fold. MD simulations indicated a novel acid/base‐assisted catalysis. The pH and temperature‐depended activity were also shown. This is the first comprehensive study in plant N‐acetyltransferase combining biochemical, structural, and theoretical analysis.
Abstract
Serotonin N‐acetyltransferase (SNAT) is the key rate‐limiting enzyme in melatonin biosynthesis. It mediates melatonin biosynthesis in plants by using serotonin and 5‐methoxytryptamine (5‐MT), but little is known of its underlying mechanisms. Herein, we present a detailed reaction mechanism of a SNAT from Oryza sativa through combined structural and molecular dynamics (MD) analysis. We report the crystal structures of plant SNAT in the apo and binary/ternary complex forms with acetyl‐CoA (AcCoA), serotonin, and 5‐MT. OsSNAT exhibits a unique enzymatically active dimeric fold not found in the known structures of arylalkylamine N‐acetyltransferase (AANAT) family. The key residues W188, D189, D226, N220, and Y233 located around the active pocket are important in catalysis, confirmed by site‐directed mutagenesis. Combined with MD simulations, we hypothesize a novel plausible catalytic mechanism in which D226 and Y233 function as catalytic base and acid during the acetyl‐transfer reaction.
https://ift.tt/3tc2DBr
Establishing one‐pot, multi‐step protocols combining different types of catalysts is one important goal for increasing efficiency in modern organic synthesis. In particular, the high potential of biocatalysts still needs to be harvested. Based on an in‐depth mechanistic investigation of a new organocatalytic protocol employing two catalysts {1,4‐diazabicyclo[2.2.2]octane (DABCO); benzoic acid (BzOH)}, a sequence was established providing starting materials for enzymatic refinement (ene reductase; alcohol dehydrogenase): A gram‐scale access to a variety of enantiopure key‐building blocks for natural product syntheses was enabled utilizing up to six catalytic steps within the same reaction vessel.
https://ift.tt/3e6iZVz
Cooperative bimetallic catalysis represents a fundamental approach in modern synthetic chemistry that addresses many challenges associated with the evolution of the field. Herein, we report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C–O/C–H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst under decarbonylative regimen, which enables for the highly chemoselective synthesis of important heterobiaryl motifs that enjoy a privileged role in the realm of organic synthesis through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative platform benefits from the direct use of common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the bimetallic decarbonylative platform. The key step involves intersection of the two catalytic cycles via transmetallation of the copper‐aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation. We envision the versatile bimetallic cooperative decarbonylative framework will have an impact on planning synthetic approaches in cooperative catalysis, decarbonylative coupling and synthesis of biaryl motifs .
https://ift.tt/3ugw2LJ
We report a strategy to develop heterogeneous single‐site enantioselective catalysts based on naturally occurring amino acids and earth‐abundant metals for eco‐friendly asymmetric catalysis. The grafting of amino acids within the pores of a metal‐organic framework (MOF), followed by post‐synthetic metalation with iron precursor affords highly active and enantioselective (>99% ee for 10 examples) catalysts for hydrosilylation and hydroboration of carbonyl compounds. Impressively, the MOF‐Fe catalyst displayed high turnover numbers of up to 10000 and was recycled and reused more than 15 times without diminishing the enantioselectivity. MOF‐Fe displayed much higher activity and enantioselectivity than its homogeneous control catalyst, likely due to the formation of robust single‐site catalyst in the MOF via site‐isolation.
https://ift.tt/39Pwd8g
Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α , β ‐unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di ‐ and tri ‐substituted unsaturated acids with noble metals has been well established, asymmetric hydrogenation of challenging tetra ‐substituted α , β ‐unsaturated carboxylic acids is rarely reported. Herein, we demonstrate enantioselective hydrogenation of both cyclic and acyclic tetra ‐substituted α , β ‐unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98% yield and 99% ee). The combined experimental and computational mechanistic studies collectively support a Co(II) catalytic cycle involving migratory insertion and sigma‐bond metathesis processes. In addition, our DFT calculations revealed that the enantioselectivity may origin from the steric effect between the phenyl groups of the ligand and the substrate.
https://ift.tt/37sodZk
Enantioenriched unnatural α‐amino acids are significant building blocks for organic synthesis and play an essential role in pharmaceuticals and biological materials by augmenting the functions of peptides. An unprecedented radical cross‐coupling reaction was achieved between glycine esters and racemic α‐bromoketones catalyzed by synergistic Brønsted acid/photoredox catalysis , thus serving as an efficient platform for the synthesis of highly valuable enantioenriched unnatural α‐amino acid derivatives. This dual catalysis provides a powerful capability to control the reactive radical intermediate and iminium ion, thereby enabling enantioconvergent bond‐formation in a highly stereochemical manner. An array of valuable enantioenriched unnatural α‐amino acid derivatives bearing two contiguous stereogenic centers are readily accessible with high diastereoselectivity and excellent enantioselectivity, which include α‐amino acids with a unique β‐fluorinated quaternary stereocenter or its β‐all‐carbon counterpart. Notably, a strong chiral amplification effect was observed in this dual catalytic system..
https://ift.tt/3lUEb3F
The synthesis of a highly Lewis acidic, dicationic strontium ansa‐arene complex is reported as the salt of a weakly coordinating [Al(ORF)4]− anion (ORF=C(CF3)3). The base‐free strontium perfluoroalkoxyaluminate Sr[Al(ORF)4]2 complex is the source of a naked strontium dication. The strontium ansa‐arene complex was successfully applied as catalyst in CO2 reduction and a highly controlled isobutylene polymerization.
Abstract
The potential of a dicationic strontium ansa‐arene complex for Lewis acid catalysis has been explored. The key to its synthesis was a simple salt metathesis from SrI2 and 2 Ag[Al(ORF)4], giving the base‐free strontium‐perfluoroalkoxyaluminate Sr[Al(ORF)4]2 (ORF=OC(CF3)3). Addition of an ansa‐arene yielded the highly Lewis acidic, dicationic strontium ansa‐arene complex. In preliminary experiments, the complex was successfully applied as a catalyst in CO2‐reduction to CH4 and a surprisingly controlled isobutylene polymerization reaction.
https://ift.tt/3gSM47q
Herein, we reported the discovery of a redox‐neutral Ni(II) catalytic cycle which is capable of the linear‐selective hydroarylation of unactivated alkenes with arylboronic acids for the first time. This novel catalytic cycle, enabled by the use of electron‐rich diimine ligand, features broad substrate scope, excellent functional group and heterocycle compatibility under mild conditions in the absence of additional oxidants or reductants. Mechanistic investigations using kinetic analysis and deuterium‐labelling experiments revealed the protonation is the rate‐determining step in this unprecedent redox‐neutral catalysis, and the reversible chain‐walking nature of the newly developed diimine‐Ni catalyst.
https://ift.tt/2EEMX51
The reaction between α,β‐unsaturated lactones and 1,3‐dienes looks like a Diels–Alder reaction, but it is a vinylogous Michael addition as indicated by experimental results and DFT calculations. A short sequence was established accessing (natural) mellein and angelicoin derivatives.
Abstract
The reactions of α,β‐unsaturated δ‐lactones with activated dienes such as 1,3‐dimethoxy‐1‐[(trimethylsilyl)oxy]‐1,3‐butadiene (Brassard's diene) are barely known in literature and show high potential for the synthesis of isocoumarin moieties. An in‐depth investigation of this reaction proved a stepwise mechanism via the vinylogous Michael‐products. Subsequent cyclisation and oxidation by LHMDS and DDQ, respectively, provided six mellein derivatives (30–84 %) and four angelicoin derivatives (40–78 %) over three steps. DFT‐calculations provide insights into the reaction mechanism and support the theory of a stepwise reaction.
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Journal of the American Chemical SocietyDOI: 10.1021/jacs.0c06412
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