Tungsten‐Catalyzed Regio‐ and Enantioselective Aminolysis of trans‐2,3‐Epoxy Alcohols: An Entry to Virtually Enantiopure Amino Alcohols

The first catalytic enantioselective aminolysis of trans‐2,3‐epoxy alcohols has been accomplished. This stereospecific ring‐opening process was efficiently promoted by a tungsten/bis(hydroxamic acid) catalytic system, furnishing various anti‐3‐amino‐1,2‐diols with excellent regiocontrol and high enantioselectivities (up to 95 % ee). Moreover, virtually enantiopure 3‐amino‐1,2‐diols could be obtained by the sequential combination of two reactions that both involve the use of a chiral catalyst.     

Synthesis,Structure, and Highly Efficient Copper‐Catalyzed Aziridination with a Tetraaza‐Bispidine Ligand

The distorted trigonal‐bipyramidal Cu^II complex [Cu(L¹)(NCCH₃)]²⁺ of the novel tetradentate bispidine‐derived ligand L¹ with four tertiary amine donors (L¹=1,5‐diphenyl‐3‐methyl‐7‐(1,4,6‐trimethyl‐1,4‐diazacycloheptane‐6‐yl)diazabicyclo[3.3.1]nonane‐9‐one) is a very efficient catalyst for the aziridination of olefins in the presence of a nitrene source. In agreement with the experimental data (in situ spectroscopy, product distribution, and its dependence on the geometry of the substrate and of the nitrene source), a theoretical analysis based on DFT calculations indicates that the active catalyst has the Cu center in its +II oxidation state, that electron transfer is not involved, and that the conversion of the olefin to an aziridine is a stepwise process involving a radical intermediate. The striking change of efficiency and reaction mechanism between classical copper–bispidine complexes and the novel L¹‐based catalyst is primarily attributed to the structural variation, enforced by the ligand architecture.     

Asymmetric Disulfonimide‐Catalyzed Synthesis of δ‐Amino‐β‐Ketoester Derivatives by Vinylogous Mukaiyama–Mannich Reactions

An organocatalytic asymmetric synthesis of δ‐amino‐β‐ketoester derivatives has been developed. A chiral disulfonimide (DSI) serves as a highly efficient precatalyst for a vinylogous Mukaiyama–Mannich reaction of readily available dioxinone‐derived silyloxydienes with N‐Boc‐protected imines, delivering products in excellent yields and enantioselectivities. The synthetic utility of this reaction is illustrated in various transformations, including a new C? C bond‐forming reaction, which provide useful enantioenriched building blocks. The methodology is applied in a formal synthesis of (?)‐lasubin.     

Regio‐ and Stereoselective Reaction of α‐Epoxyketones with AlCl3: An Efficient Approach for the Synthesis of Functionalized β‐Chlorohydrines

A simple and efficient synthesis of functionalized β‐chlorohydrins is described from the regio‐ and stereoselective reaction of α‐epoxyketones with AlCl₃ in acetonitrile at room temperature.     

Gadolinium‐Catalyzed Regio‐ and Enantioselective Aminolysis of Aromatic trans‐2,3‐Epoxy Sulfonamides

The first enantioselective aminolysis of aromatic trans‐2,3‐epoxy sulfonamides has been accomplished, which was efficiently catalyzed by a Gd‐N,N′‐dioxide complex. Under the directing effect of the sulfonamide moiety the ring‐opening reaction proceeded selectively at the C‐3 position in a highly enantioselective manner furnishing various Ts‐ and SES‐protected 3‐amino‐3‐phenylpropan‐2‐olamines as products.     

Silver‐Catalyzed Decarboxylative Allylation of Difluoroarylacetic Acids with Allyl Sulfones in Water

A practical silver‐catalyzed decarboxylative allylation of α,α‐difluoroarylacetic acids with allyl sulfones is described, which provides a variety of β,β‐difluorinated alkenes in good yields. Notably, the reaction proceeds smoothly in water with good functional group tolerance. The practicality and synthetic value of this process was demonstrated by scaled‐up experiment and elaboration of the products via reduction or Heck reaction. Primary mechanism investigations suggest that a radical process might be involved.     

Regio‐ and Stereospecificity in the Oxygenation of Arachidonic Acid Catalyzed by Leu597 Mutants of Rabbit 15‐Lipoxygenase: A QM/MM Study

We combined quantum mechanics/molecular mechanics calculations with molecular dynamics simulations to study the addition of O₂ to the pentadienyl radical of arachidonic acid (AA) catalyzed by the Leu597Val and Leu597Ala mutants of rabbit 15‐lipoxygenase (15‐rLO). In the Leu597Val mutant, the addition of O₂ to C15 of AA is the predominant path, although it reduces the C15/C11 product ratio by almost ten times with respect to the wildtype enzyme. The S stereochemistry is kept. Mutation to Ala causes just the opposite effect: regiospecificity favoring addition to C15 is somewhat sharper than that in the wildtype, but the stereochemistry is R. This is because the extra space created by the mutation to Ala is big enough for AA to move so that it can adopt an alternative binding mode, and this opens new feasible paths for the attack of O₂. So, we showed that the Leu597Ala mutant of 15r‐LO works as an aspirin‐acetylated cyclooxygenase‐2, which makes 15‐(R)‐ hydroperoxyeicosatetraenoic acid.     

Efficient Synthesis of Oxazolidin‐2‐one via (Chitosan‐Schiff Base)cobalt(II)‐Catalyzed Oxidative Carbonylation of 2‐Aminoalkan‐1‐ols

The (chitosan‐Schiff base)cobalt(II) complex was found to be an efficient catalyst for the oxidative carbonylation (CO/O₂) of 2‐aminoalkan‐1‐ols 1 to give oxazolidin‐2‐ones 2 , in the presence of NaI. The effects of promoters, temperature, solvents, and other reaction conditions were investigated in this study.     

Palladium‐Catalyzed Carbonylative α‐Arylation to β‐Ketonitriles

A carbonylative α‐arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β‐ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient ¹³C‐labelling of the generated carbonyl moiety.     

Synthesis of 1,3‐Amino Alcohols by Hydroxy‐Directed Aziridination and Aziridine Hydrosilylation

We describe an approach to N‐tosyl 1,3‐amino alcohols that consists of a diastereoselective aziridination reaction of acyclic allylic alcohols and an unprecedented regioselective hydrosilylation of α‐hydroxy aziridines. The products contain up to three contiguous stereocenters. Computational studies outline key aspects of the aziridination mechanism, which is different and more intricate than anticipated.     

NaHCO3‐Catalyzed Hihgly Regiospecific Aminobromination of ß,ß‐Dicyanostyrene Derivatives with 1,3‐Dibromo‐5,5‐dimethylhydantoin (DBDMH)

The aminobromination of β,β‐dicyanostyrene derivetives with 1,3‐dibromo‐5,5‐dimethylhydantoin (DBDMH) has been systematic studied. The reaction afforded the vicinal haloamino products in good to excellent yields at room temperature (the highest yield was up to 94 %), and the full regiospecificity of all products were achieved catalyzed by NaHCO₃ in CH₃CN. A possible pathway involving a Michael Addition reaction for this aminobromination was proposed.     

Synthesis of D‐Desosamine and Analogs by Rapid Assembly of 3‐Amino Sugars

D ‐Desosamine is synthesized in 4 steps from methyl vinyl ketone and sodium nitrite. The key step in this chromatography‐free synthesis is the coupling of (R)‐4‐nitro‐2‐butanol and glyoxal (trimeric form) mediated by cesium carbonate, which affords in crystalline form 3‐nitro‐3,4,6‐trideoxy‐α‐D ‐glucose, a nitro sugar stereochemically homologous to D ‐desosamine. This strategy has enabled the syntheses of an array of analogous 3‐nitro sugars. In each case the 3‐nitro sugars are obtained in pure form by crystallization.     

Regio‐ and Enantioselective Rhodium‐Catalyzed Addition of 1,3‐Diketones to Allenes: Construction of Asymmetric Tertiary and Quaternary All Carbon Centers

An unprecedented highly regio‐ and enantioselective rhodium‐catalyzed addition of 1,3‐diketones to terminal and 1,1‐disubstituted allenes furnishing asymmetric tertiary and quaternary all‐carbon centers is reported. By applying a Rh^I/phosphoramidite/TFA catalytic system under mild conditions, the desired chiral branched α‐allylated 1,3‐diketones could be obtained in good to excellent yields, with perfect regioselectivity and in high enantioselectivity. The reaction shows a broad functional‐group tolerance on both reaction partners highlighting its synthetic potential.     

Highly Efficient Synthesis of α‐Halomethylketones via Ce(SO4)2/Acid Co‐Catalyzed Hydration of Alkynes

A general atom‐economical approach for the synthesis of α‐halomethyl ketones is demonstrated through Ce(SO₄)₂/acid co‐catalyzed hydration of a wide range of haloalkynes. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope. This protocol is an alternative to conventional α‐halogenation of ketones.     

Adding a Functional Handle to Nature′s Building Blocks: The Asymmetric Synthesis of β‐Hydroxy‐α‐Amino Acids

β‐Hydroxy‐α‐amino acids are not only used by synthetic chemists but are also found in natural products, many of which show anti‐microbial or anti‐cancer properties. Over the past 30 years, chemists have searched for many asymmetric routes to these useful building blocks. Initial attempts to synthesize these compounds utilized chiral auxiliaries and the reactions of glycine equivalents with aldehydes to form two stereocenters in one step. Other methods with the formation of specific intermediates or that were aimed at a specific amino acid have also been investigated. Asymmetric hydrogenation by dynamic kinetic resolution has emerged as a high‐yielding method for the synthesis of an array of modified amino acids with good stereoselectivity. More recently, amino‐acid functionalization and multicomponent reactions have increased the atom economy and simplified many long and difficult routes. In this Focus Review, many of the elegant syntheses of these compounds are explored. The applications of β‐hydroxy‐α‐amino acids in natural‐product synthesis are also mentioned.