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This article discusses the synthesis of ¿-aryl carbonyl compounds using palladium catalysis. The authors focus on the deprotonative ¿-arylation of Meyers's chiral bicyclic lactams (MCBLs) as a potential method for synthesizing these compounds. They explore different bases and catalytic systems to optimize the reaction conditions and achieve high yields. The authors also investigate the reaction scope by testing various aryl and heteroaryl bromides. They propose a mechanism for the formation of the arylated lactam products based on their experimental findings. Overall, this study provides valuable insights into the synthesis of ¿-aryl carbonyl compounds and highlights the potential of MCBLs as versatile substrates. [Extracted from the article]

This article discusses the development of sustainable catalytic chemical methods for O-glycosylation using iron-based salts as catalysts. The authors experiment with different reaction conditions and optimize the yield of the glycosylation reaction. The study demonstrates the potential of iron-based salts as a sustainable and affordable alternative for large-scale synthesis. The article provides detailed information about the synthesis and characterization of various compounds, including their yields, physical properties, and spectroscopic data. This information can be useful for researchers studying organic chemistry or interested in the synthesis and characterization of specific compounds. [Extracted from the article]

This article explores the use of ionic ligand-substrate interactions in enantioselective palladium-catalyzed Suzuki-Miyaura reactions. Traditionally, stereochemical control in asymmetric catalysis has relied on steric repulsion, but recent research has investigated the use of noncovalent interactions, such as ionic interactions, to enhance stereoselectivity. The article focuses on the challenges and advancements in utilizing ionic interactions in transition-metal catalysis and presents recent work on developing chiral dialkyl biarylphosphine ligands with nonligating ionic groups for long-range stereocontrol in Suzuki-Miyaura reactions. The authors demonstrate the successful creation of chirality at remote quaternary stereocenters through the use of ionic substrate-catalyst interactions. Further research is needed to fully understand the complex networks of ionic interactions and explore the potential of ionic chiral catalysts. [Extracted from the article]

[32] Palladium-catalyzed Suzuki-Miyaura cross-coupling of B 3l b with bromobenzene or iodomethane provided ( I E i )-allyl fluorides B 7 b or B 8 b in good yields without any degradation of the I E i / I Z i ratios. [39] The reaction shows a broad substrate scope of -silyl-substituted allylboronate esters, affording various ( I E i )-boryl-substituted allyl fluorides in good yields with high selectivities. Keywords: allyl fluorides; chemoselectivity; fluorodesilylation; regio-selectivity; stereoselectivity EN allyl fluorides chemoselectivity fluorodesilylation regio-selectivity stereoselectivity 2165 2168 4 10/31/23 20231127 NES 231127 Graph The selective introduction of fluorine atoms into organic molecules has emerged as a prominent research field in organic synthesis, owing to the specific physicochemical properties of organofluorines, such as improved metabolic stability and high lipophilicity. Upon treatment of B 1a b with Selectfluor ( B 2a b ) in acetonitrile at room temperature, the corresponding 1-boryl-substituted allyl fluoride B 3a b was obtained in a moderate SP 1 sp H NMR yield of 35% with an I E i / I Z i ratio of 9:1 (entry 1). [Extracted from the article]

In this paper, we report an alternative approach to the targeted -oxyallylboronate: a copper-catalyzed 1,4-acylboration of , -unsaturated esters with B SB 2 sb pin SB 2 sb and pivalic anhydride is described (Scheme 1c). H SB 2 sb O SB 2 sb under acetate buffer conditions [11] furnished the corresponding allylic alcohol B 4 b with maintenance of the ketene acetal moiety, which can be a good synthetic handle for further manipulations. The ligand gave a large impact on the yield and I E/Z i selectivity, with the electron-withdrawing monodentate P(3,5-(CF SB 3 sb ) SB 2 sb C SB 6 sb H SB 3 sb ) SB 3 sb proving to be best (entries 1-5). Keywords: allylboronate; borylation; conjugate addition; copper; stereoselectivity EN allylboronate borylation conjugate addition copper stereoselectivity 2205 2209 5 10/31/23 20231127 NES 231127 Graph Allylborons constitute an important class of organoboron compounds in modern synthetic organic chemistry because they enable the chemo- and stereoselective allylation of organic molecules, after which the resulting allyl moiety can be transformable with high diversity. [Extracted from the article]

The resulting solution was evaporated under reduced pressure to give the crude product, which was further purified by column chromatography on silica gel (20% EtOAc/hexane) to furnish B 30 b (49.5 mg, 0.19 mmol, 58%) as a white solid; mp 107.4-107.7 °C. The resulting solution was evaporated under reduced pressure to give the crude product B 29 b , which was further purified by column chromatography on silica gel (20% EtOAc/hexane) to furnish B 29 b (10.5 mg, 0.04 mmol, 75%) as a clear sticky oil. Keywords: epoxidation; cyclization; carbocation; fused-ring systems; stereoselectivity EN epoxidation cyclization carbocation fused-ring systems stereoselectivity 2757 2772 16 08/17/23 20230901 NES 230901 Graph Various oxacycles are privileged scaffolds in pharmaceutical industries, cosmetics, natural products, and drug discovery, among others. TOF-HRMS: I m i / I z i [M + Na] SP + sp calcd for C SB 19 sb H SB 20 sb O SB 4 sb Na: 335.1254; found: 335.1247. tert -Butyldimethyl((3-phenyl-1,3-dihydroisobenzofuran-1-yl)methoxy)silane (26b') By following the General Procedure G, and purification by column chromatography on silica gel (20% EtOAc/hexane), the product (24.0 mg, 0.71 mmol, 44%) was obtained as a yellow sticky gum. [Extracted from the article]

Stereoselective construction of conjugated dienes and polyenes has remained an enduring synthetic problem owing to the central roles these compounds play in natural product synthesis, methodology, and medicine. This review focuses on recent developments in dienylation as an emerging strategy for the direct installation of unsaturated four-carbon units of conjugated π-systems, outlining the regio- and stereoselectivity, as well as the synthetic scope of reactions with various dienylating reagents and the mechanistic implications of the catalytic cross-coupling processes that are used to enable dienylation. 1 Introduction 2 Sulfolenes 3 1,3-Dienes 4 Small-Ring Dienylation Reagents 5 Pyrones, Alkynes, and Homoallenylboronates 6 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

The application of bifunctional organocatalysts in organic chemistry has advanced remarkably owing to their high stability to moisture and air, relatively low toxicity, ease of handling, and recoverability. Among chiral bifunctional organocatalysts, squaramides have emerged as a privileged catalyst in recent years. This review article presents a comprehensive report on fine-tunable bifunctional chiral squaramide-catalyzed sulfa-Michael addition, which is based upon synchronous interplay of synergistic 'electrophilic–nucleophilic' dual activation strategies via multiple H-bonding interactions for the construction of both common and complex molecular entities bearing multiple stereocenters. Mechanistic discussions are kept brief, but significant understandings have been recorded. The contribution of squaramide catalyst to the construction of C–S bonds via sulfa-Michael addition has been applied in medicinal, natural, and industrial chemistry. Attention is focused on summarizing the progress made in chiral squaramide-catalyzed asymmetric sulfa-Michael addition and subsequent cascade/domino reaction sequences between 2011 and 2022. 1 Introduction 2 Quinine-Squaramide Organocatalysis 3 Iminophosphorane-Squaramide Organocatalysis 4 Chinchona-Squaramide Organocatalysis 5 trans -1,2-Diaminocyclohexane-Squaramide Organocatalysis 6 Conclusion [ABSTRACT FROM AUTHOR]

The strained/frustrated electrostatic interactions between the ion pair of TTBPy+ X– increases the reactivity in both the ions, resulting in the activation of a third molecule like sulfonamides (aromatic/-aliphatic) via hydrogen bonding. This intriguing weak-interactions-based reactivity has been utilized to develop an organocatalytic synthesis of 2-deoxy-sulfonamido-glycosides from glycals. The sulfonamidoglycosylation of glycals using a catalytic amount of 2,4,6-tri- tert -butylpyridinium salts proceeded stereoselectively to provide N -glycosides in good to high yields. This process was demonstrated with l -rhamnal and d -galactal. Besides, IR spectroscopic studies explain that the hindered protonated pyridine cannot behave as a cationic Brønsted acid as is generally perceived. [ABSTRACT FROM AUTHOR]

Morpholine is a heterocyclic moiety that is widely used in medicinal chemistry as a building block. It has unique physicochemical properties, as it can improve both pharmacokinetic and pharmacodynamic properties of active pharmaceutical ingredients. However, the efficient synthesis of enantiomerically pure morpholine building blocks remains challenging. Herein, we report the synthesis of optically pure 3-hydroxymethylmorpholine building blocks, as well as their sulfamidates, exploiting a stereospecific strategy from chiral pool material. [ABSTRACT FROM AUTHOR]

Bimolecular nucleophilic substitution (SN 2) is one of the most well-known fundamental reactions in organic chemistry to generate new molecules from two molecules. In principle, a nucleophile attacks from the back side of an alkylating agent having a suitable leaving group, most commonly a halide. However, alkyl halides are expensive, very harmful, toxic and not so stable, which makes them problematic for laboratory use. In contrast, trialkyl phosphates are inexpensive, readily accessible and stable at room temperature, under air, and are easy to handle, but rarely used as alkylating agents in organic synthesis. Here, we describe a mild, straightforward and powerful method for nucleophilic alkylation of various N -, O -, C - and S -nucleophiles using readily available trialkyl phosphates. The reaction proceeds smoothly in excellent yield, and quantitative yield in many cases, and covers a wide range of substrates. Further, the rare stereoselective transfer of secondary alkyl groups has been achieved with inversion of configuration of chiral centers (up to 98% ee). [ABSTRACT FROM AUTHOR]

A concise stereoselective synthesis of (Z)-1,2-bis(arylsulfanyl)ethenes by the reaction of arylsulfonyl chlorides with calcium carbide in the presence of cuprous iodide as a catalyst is described. The salient features of this protocol are its use of an inexpensive and easily handled solid alkyne source as a surrogate for flammable and explosive gaseous acetylene, its commercially available starting materials, its high stereoselectivity, and its simple workup procedures. The stereochemical structure of a selected product was determined by single-crystal X-ray diffraction. This method can be extended to a gram scale. [ABSTRACT FROM AUTHOR]

The asymmetric ring opening of azlactones via dynamic kinetic resolution (DKR) is investigated by contrasting thioureas incorporating 1-arylethyl substituents against their more acidic trifluoromethylated analogs. All the catalysts under study outperform Takemoto's thiourea because of the inclusion of an additional chiral center. However, the difference in yield and selectivity between the fluorinated and non-fluorinated catalysts is minimal. We explain this observation by analysis of calculated transition states. Our findings show that the hydrogen bond (HB) between the NH linked to the 1-arylethyl and the negatively charged oxygen in the benzyloxy ion is the longest in the HB network, whereas the HB between the ammonium group and the same oxygen atom is the shortest. Thus, the substituents and the HB donor ability of this chiral fragment attached to the thiourea are not important in the reaction. [ABSTRACT FROM AUTHOR]

N -Sulfinyl metalloenamines, generated by deprotonating α-linear N - tert -butanesulfinyl ketimines, reacted with nitroalkenes via stereoselective conjugate addition to give Michael adducts with opposite stereochemistry to that obtained using α-branched sulfinylketimines. In the presence of excess base (2.5 equiv t -BuOK), the adducts derived from α-linear ketimines were further stereoselectively deprotonated to afford the corresponding kinetically favorable N -sulfinyl (Z)-enamine derivatives in good yields with good stereoselectivities. A reaction model was proposed to rationalize the observed stereochemistry. [ABSTRACT FROM AUTHOR]

Modifications of glycosidic linkers are valuable in medicinal chemistry and natural-product synthesis. Whereas considerable attention has been paid to the development of methods for monoglycosylation, the corresponding geminal diglycosylation has almost been ignored. Little work has focused on exploring new routes for stereoselective gem -diglycosylation, presumably due to challenges in controlling selectivity and activity on a confined quaternary carbon center. Highlighted herein is a recent advance in stereoselective C,B-glycosylation through an unprecedented PPh3-promoted 1,2-boronate-migration process. [ABSTRACT FROM AUTHOR]

The path-selectivity and stereoselectivity of gridization pathways into fluorene-based drawing hand grids (DHGs-F) are precisely modulated through tuning acid conditions and side-chain effects. BF3 ·OEt2 supports the realization of the gridization path (rac -DHG1-F, yield: 82%, meso -DHG1-F, yield: 11%). On the contrary, CF3 SO3 H will lead to the enhancements in polymerization pathways (about 85% yield). When the side chain is a methoxyl group, rac -DHG1-F and meso -DHG1-F will be obtained. However, when the side chain is a group without an oxygen atom, only rac -DHGs-F can be obtained (de = 100%). Moreover, through excitonic physical properties, rac -DHGs-F exhibits a more π-electronic delocalization, potentially serving as the intriguing tactic strategy to modulate the optoelectronic properties. [ABSTRACT FROM AUTHOR]

A tandem intramolecular conjugate addition reaction was conducted with α,β-bisenones as selected Michael acceptors which were converted into 1,2,3-trisubstituted six-membered rings in the presence of activated sulfur nucleophiles. The products were obtained in good to excellent yields (maximum yield: 99%). Various substituted α,β-bisenones and sulfur nucleophiles were examined to understand the substrate scope of the reaction. Only one diastereomer was isolated, as lithium iodide mediated enolate trapping reactions improve the stereoselectivity of reactions involving 1,2,3-trisubstituted cyclohexanes. [ABSTRACT FROM AUTHOR]

The enantioselective azo-based α-amination of an aldehyde followed by a Horner–Wadsworth–Emmons-based vinyl sulfone formation is reported. The thus obtained optically active N , N ′-diprotected trans -(phenylsulfonyl)vinyl hydrazine products were then converted into the corresponding N-functionalised trans -(phenylsulfonyl)vinyl amines. Specifically, reaction of 4-phenylbutanal with di- tert -butyl azodicarboxylate (DBAD) in the presence of l - or d -proline, followed by addition of diethyl [(phenylsulfonyl)methyl]phosphonate, gave either enantiomer of di- tert -butyl trans -1-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]hydrazine-1,2-dicarboxylate. The enantiomeric excesses of the (+)- and (–)-enantiomers prepared in this manner were in the range 86–89%. The conversion of these γ-hydrazino vinyl sulfones into the corresponding γ-amino-substituted compounds was achieved following a Boc deprotection, Zn reduction, N-functionalisation sequence. This three-step sequence was reasonably efficient (approx. 50%) and no erosion of enantiopurity was found to have taken place. The compounds accessed via this process include both enantiomers of tert -butyl trans -[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]carbamate and epimeric dipeptide mimetics including 4-methyl- N -{(S)-1-oxo-3-phenyl-1-[((S , E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino]propan-2-yl}piperazine-1-carboxamide (also known as K777). [ABSTRACT FROM AUTHOR]

We have developed a regio- and stereoselective thermal [3+2]-cycloaddition protocol involving acetoxy allenoates as 1,2-dipoles under metal-free conditions for the synthesis of 1,4,5-tri/1,5-disubstituted 1,2,3-triazoles. δ-Acetoxy allenoates act as α- and β-carbon donors and lead to trisubstituted 1,2,3-triazoles with an alkenyl functionality at the 5-position. In sharp contrast to this, β- and γ-carbons participate in the case of β′-acetoxy allenoates to afford 1,5-disubstituted triazole cores. This [3+2] cycloaddition shows a broad substrate scope concerning acetoxy allenoate as well as azide and offers essentially E-stereoisomers in good to high yields. Divergently, the reaction of δ-acetoxy allenoate with trimethylsilyl azide gives an acyclic, nitrogen-inserted product with the cleavage of C–C bonds. [ABSTRACT FROM AUTHOR]

This paper describes a stereoselective synthesis of (–)-heliannuol E through intramolecular cyclization of a phenol mesylate. The introduction of the aromatic group was achieved by α-selective propargyl substitution of a propargylic phosphate. [ABSTRACT FROM AUTHOR]

Zhipeng Zhang (left) received his B.S. degree from Shandong University (China) in 2004, and his Ph.D. degree from the Shanghai Institute of Organic Chemistry (SIOC) in 2010 under the supervision of Professor Kuiling Ding. In 2011, he began his postdoctoral studies with Professor Benjamin List at the Max Planck Institute for Coal Research in Mülheim an der Ruhr, Germany. After three years of research on asymmetric organocatalysis, he joined the group of Professor Jin-Quan Yu at The Scripps Research Institute in La Jolla, California as a postdoctoral research associate in 2014. He subsequently worked at the Genomics Institute of the Novartis Research Foundation (GNF) from 2016, before he began his independent career as a professor at the East China University of Science and Technology (ECUST) in 2017. His current research interests include asymmetric catalysis and synthetic methodology, focusing on the design and development of novel chiral ligands and catalysts. Baoguo Zhao (right) received his B.S. degree from Wuhan University in 1996, his M.S. degree from Nanjing University under the supervision of Professor Jianhua Xu in 2002, and his Ph.D. degree from the Shanghai Institute of Organic Chemistry (SIOC) under the supervision of Professor Kuiling Ding in 2006. He subsequently worked with Professor Yian Shi for five years as a postdoctoral fellow at the Department of Chemistry of Colorado State University. In 2011, he joined Shanghai Normal University at the Department of Chemistry as a full professor. His current research interests are in the area of biomimetic asymmetric catalysis, including the development of bioinspired chiral catalysts and synthetic methodologies. [ABSTRACT FROM AUTHOR]

Asymmetric crotylation has firmly earned a place among the set of valuable synthetic tools for stereoselective construction of carbon skeletons. For a long time the field was heavily dominated by reagents bearing stoichiometric chiral auxiliaries, but now catalytic methods are gradually taking center stage, and the area continues to develop rapidly. This account focuses primarily on preformed organometallic reagents based on silicon and, to some extent, boron. It narrates our endeavors to design new and efficient chiral Lewis base catalysts for the asymmetric addition of crotyl(trichloro)silanes to aldehydes. It also covers the development of a novel protocol for kinetic resolution of racemic secondary allylboronates to give enantio- and diastereomerically enriched linear homoallylic alcohols. As a separate topic, cross-crotylation of aldehydes by using enantiopure branched homoallylic alcohols as a source of crotyl groups is discussed. Finally, the synthetic credentials of the developed methodology are illustrated by total syntheses of marine natural products, in which crotylation plays a key role in setting up stereogenic centers. 1 Introduction 2 Pyridine N -Oxides as Lewis Base Catalysts 3 Bipyridine N , N ′-Dioxides as Lewis Base Catalysts 4 Chiral Allylating Reagents 5 Synthetic Applications 6 Concluding Remarks [ABSTRACT FROM AUTHOR]

In the presence of Na2 CO3 , conjugate addition of α-halo hydrazones to nitroso compounds proceeded readily to give polyfunctionalized nitrones in reasonable chemical yields and excellent stereoselectivities. The chemical structure and the stereochemical configuration of the products were unambiguously identified by an X-ray single-crystal structural analysis. [ABSTRACT FROM AUTHOR]

Allylic alcohols form perrhenate esters upon reaction with Re2 O7 or HOReO3. These species undergo nonstereospecific and nonregiospecific alcohol-transposition reactions through cationic intermediates. Sequencing these nonselective processes with reversible trapping by electrophiles results in cyclization reactions where regio- and stereocontrol are dictated by thermodynamics. The cationic intermediates can also be utilized as electrophiles in intra- or intermolecular dehydrative reactions with nucleophiles. These processes serve as the basis for applications in catalytic syntheses of a wide range of heterocyclic and carbocyclic structures that often show considerable increases in molecular complexity. This Account describes a sequence of events that started from a need to solve a problem for the completion of a natural product synthesis and evolved into a central element in the design of numerous new transformations that proceed under mild conditions from readily accessible substrates. 1 Introduction 2 Exploratory Studies 3 Application to Spiroketal Synthesis 4 Reactions with Epoxides as Trapping Agents 5 Development of Dehydrative Cyclizations 6 Bimolecular Reactions 7 Spirocyclic Ether Formation 8 Conclusions [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of substituted morpholine derivatives has been achieved through a two-step process involving diastereoselective addition of a Grignard reagent to a sulfinyl imine, followed by cyclization. [ABSTRACT FROM AUTHOR]

Chiral o-aminobenzylamines are synthons for many chiral ligands and catalysts that have been widely used in asymmetric synthesis. Here, we report a highly efficient and stereoselective addition of Grignard reagents to N -[(o -aminophenyl)methylene]sulfinamides to give a range of o -aminosulfinylimines in good yields with good to excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

The multi-component 1,3-dipolar cycloaddition of ninhydrin, α-amino acids (or peptides), and cyclopropenes for the synthesis of spirocyclic heterocycles containing both 3-azabicyclo[3.1.0]hexane and 2 H -indene-1,3-dione motifs has been developed. This method provides easy access to 3-azabicyclo[3.1.0]hexane-2,2′-indenes with complete stereoselectivity and a high degree of atom economy under mild reaction conditions. A broad range of cyclopropenes and α-amino acids have been found to be compatible with the present protocol, which offers an opportunity to create a new library of biologically significant scaffold (3-azabicyclo[3.1.0]hexane). In addition, the сomprehensive study of mechanism of azomethine ylide formation from ninhydrin and sarcosine was performed by means of M11 density functional theory (DFT) calculations. It has been revealed that experimentally observed 1-methylspiro[aziridine-2,2′-indene]-1′,3′-dione is a kinetically controlled product of this reaction and appears to act as a 1,3-dipole precursor. This theoretical study also shed light on the main transformations of the azomethine ylide derived from ninhydrin and sarcosine such as a 1,3-dipolar cycloaddition to cyclopropene dipolarophiles, a dimerization reaction and a (1+5) electrocyclization reaction. The antitumor activity of some synthesized compounds against cervical carcinoma (HeLa-) cell line was evaluated in vitro by MTS-assay. [ABSTRACT FROM AUTHOR]

Generally, glycosylation reactions activate an anomeric substituent in a glycosyl donor to generate an oxocarbenium ion intermediate. Here we report a novel glycosylation reaction triggered by the activation of a 2-O-substituted propargyl group in a 3,6- O -1,1′-[(ethane-1,2-diyl)bibenzene-2,2′-bis(methylene)]-β-thioglucoside. This reaction proceeds through a cationic Au(I)-mediated intramolecular migration of the anomeric substituent onto the alkyne moiety of the propargyl group, followed by α-attack by the hydroxy group in the glycosyl acceptor on the oxocarbenium ion. The migration of the anomeric group occurs selectively through a 6- exo - dig pathway. The 2-(phenylsulfanyl)prop-2-en-1-yl group produced during the glycosylation is removable under conditions similar to those used for removing an allyl group. This reaction will be developed for further applications in orthogonal oligosaccharide synthesis. [ABSTRACT FROM AUTHOR]

The emergence of cyclic peptides as pharmaceuticals has led to an eruption of new methodologies for macrocyclization. However, the cyclization of peptides at high concentrations presents a challenge due to the production of side products like dimers and oligomers. This factor is more pronounced with the cyclization of peptides composed of fewer than seven amino acids, thus has created a need for a new synthetic strategy. Herein, we will elucidate a new chemoselective method termed 'CyClick' that works in an exclusively intramolecular fashion preventing the formation of commonly occurring side products such as dimers and oligomers, even at relatively high concentration. 1 Introduction 2 Known Methodologies 3 Novel CyClick Chemistry 4 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

A new efficient method for the synthesis of a high ratio of E -alkenes from E / Z mixtures of alkenes with B2 pin2 in the presence of a rhodium catalyst is described. This reaction features mild reaction conditions, broad functional group tolerance, and highly great application potential. [ABSTRACT FROM AUTHOR]

Cycloaddition reactions of aziridines with dipolarophiles under traditional thermal or photochemical conditions entail destructive routes to form reactive intermediates such as an azomethine ylide. This article highlights a recent study that demonstrates a cycloaddition reaction of aziridine induced by mechanical force. Experimental results suggest that the force-induced cycloaddition of aziridine with dimethyl acetylenedicarboxylate as a dipolarophile does not seem to involve an ylide, with implications for a possible new reaction route. 1 Rivalry between Aziridine and Epoxide 2 Mechanochemically Responsive Polymers 3 Aziridine Mechanophore 4 Concluding Remarks and Outlook [ABSTRACT FROM AUTHOR]

An efficient glycosylation method to synthesize 2-deoxy- O -galactosides based on a Cu(II)-catalyzed reaction without additional ligand has been developed. The glycosylation was amenable to different protected glycal donors and a wide range of acceptors including alcohols, amino acids, sugars, and phenol, and proceeds with excellent yield and high α-selectivity under mild conditions. The reaction proceeds readily on a gram scale, and its versatility is exemplified in the synthesis of oligosaccharides. [ABSTRACT FROM AUTHOR]

A simple strategy to access a wide range of substituted oxime amino ethers in good to high yields via Lewis acid catalyzed SN 2-type ring opening of activated aziridines with aryl aldehyde oximes is reported. [ABSTRACT FROM AUTHOR]

In the reactions of simple starting materials, precise catalytic control of the stereochemical outcome (enantio- and diastereoselectivity), as well as chemoselectivity and regioselectivity is an efficient approach to increase molecular complexity with minimal use of protecting groups. Here, we introduce our ongoing studies on asymmetric catalytic reactions using α-keto esters as pronucleophiles or formal 1,3-dipolarophiles. Capitalizing on the high tunability of our late transition-metal complexes with a suitable basic counteranion, we have established a range of multiselective catalytic protocols starting from α-keto esters to provide a wide variety of stereochemically complex molecules incorporating adjacent stereocenters. 1 Introduction 2 Catalytic Asymmetric Monofluorination with NSFI 3 Catalytic Asymmetric Michael Reaction with Nitroolefins 4 Catalytic Asymmetric [3+2] Cycloaddition with (E)-Nitrones 5 Catalytic Asymmetric [3+2] Cycloaddition with Nitrile Oxides 6 Summary [ABSTRACT FROM AUTHOR]

Synthetic methods that can readily access saturated heterocycles with different substitution patterns and with control of stereo- and regiochemistry are of huge potential value in the development of new medicinal compounds. Directed C–H functionalization of simple and commercially available precursors offers the potential to prepare diverse collections of such valuable compounds that can probe the different available exit vectors from a ring system. Nonetheless, the presence of the Lewis basic heteroatoms makes this a significant challenge. This review covers recent advances in the catalytic C–H functionalization of saturated heterocycles, with a view to different heterocycles (N, O, S), substitution patterns and transformations. 1 Introduction 2 α-C–H Functionalization with Directing Group on Nitrogen 3 C–H Functionalization at Unactivated C(3), C(4), and C(5) Positions 3.1 C–H Functionalization at C(3) with Directing Groups at C(2) 3.2 C–H Functionalization at C(3), C(4), and C(5): Directing Groups at C(4) and C(3) 4 Transannular C–H Functionalization 5 Conclusion [ABSTRACT FROM AUTHOR]

β-Lactams are highly valuable compounds due to their antibiotic activity. Among the number of well-established methodologies for building this privileged scaffold, our research group has settled on a novel synthetic approach for their preparation. This Account focuses on our latest progress in the synthesis of these compounds through a novel base-promoted intramolecular cyclization of benzylfumaramide-based rotaxanes. The mechanical bond plays a significant role in the process by activating the cyclization inside the macrocycle void, avoiding the formation of byproducts and fully controlling the diastereoselectivity. Further investigations on this transformation led to the formation of -enantioenriched 2-azetidinones. The cyclization of enantiopure interlocked α-methylbenzylfumaramides allows the formation of two new stereogenic centers in the lactamic four-membered ring, one of them a quaternary carbon, keeping the initial configuration of the chiral group of the starting material. 1 Introduction 1.1 Mechanically Interlocked Molecules and Applications 1.2 Chemical Stabilization of the Mechanical Bond 2 Literature Methods for 4- exo - trig Ring Closures of Fumaramides for the Synthesis of β-Lactams 3 Our First Encounter with Interlocked β-Lactams 3.1 An Unexpected Result in Our Laboratory 3.2 Finding the Optimal Reaction Conditions 3.3 Elucidating the Effects of the Mechanical Bond 4 Diastereoselective Synthesis of Interlocked and Non-Interlocked β-Lactams 5 Asymmetric Cyclization of Enantiopure Interlocked Fumaramides 6 Conclusions [ABSTRACT FROM AUTHOR]

The chelation-control model is used to predict stereochemical outcomes of many organometallic reactions. Diastereoselectivity arises due to reaction with a chelated intermediate with sterically differentiated faces. Earlier studies with dimethylmagnesium established that the chelated intermediate is a minor component of the reaction mixture, so reaction with the chelated intermediate must be faster than reaction with a non-chelated intermediate. High diastereoselectivity and chelation-induced rate acceleration are correlated with some hydride reducing agents. There are examples in which diastereoselectivity is high, but chelation-induced rate acceleration is not observed, however. In other cases, chelation-induced rate acceleration is observed, but diastereoselectivity remains low. These experiments illustrate that a revision to the chelation-control model is needed. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed three-component intermolecular aryletherification reaction of ferrocene-substituted allenes, aryl iodides and phenols or alcohols is reported. In this three-component reaction, two new C--C and C--O bonds are formed in one step with high regio- and stereoselectivity. The high selectivity obtained in this reaction can be attributed to the steric effect of the bulky ferrocene group. Key words aryletherification, allenes, palladium, stereoselectivity, [ABSTRACT FROM AUTHOR]

The formal (4+1) cyclization between in situ generated achiral carbonyl-stabilized ammonium ylides and vinylogous p-quinone methides can be carried out under operationally simple conditions, leading to two different double bond regioisomers depending on the conditions used. Apart from these racemic approaches, a first proof-of-concept for enantioselective versions of these reactions was also obtained. [ABSTRACT FROM AUTHOR]

A facile synthesis of biologically important trans-functionalized cyclopentenes by a mild Rh(III)-catalyzed alkylation of strained diazabicyclic olefins with aryl ketones in the presence of ammonium acetate has been developed. The reaction proceeds through C–H bond activation of the aryl ketone groups by transforming them in to an autocleavable directing group, such as in situ-formed imine. [ABSTRACT FROM AUTHOR]

Because of their biological relevance, cyclic β-amino acids have generated increasing interest and had significant impact in drug research over the past two decades. Their preparation and further functionalization towards new types of molecular entities have received large interest in synthetic and medicinal chemistry. Various types of metathesis reactions, such as ring-opening (ROM), ring-closing (RCM), or cross metathesis (CM) are used widely for access to either alicyclic β-amino acids or other densely functionalized derivatives of this group of compounds. This account intends to provide an insight into the most relevant synthetic routes to this class of derivatives with the application of metathesis reactions. The review focuses on the presentation of selective and stereocontrolled methodologies in view of versatility, robustness, limitations and efficiency. 1 Introduction 2 Synthesis and Transformation of Cyclic β-Amino Acids through Metathesis Reactions 2.1 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Ring-Closing Metathesis 2.2 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Cross Metathesis 2.3 Synthesis of β-Amino Acids with Larger Ring Systems by Ring- Closing Metathesis 2.4 Synthesis of β-Amino Acids with Condensed Ring Systems by Ring-Rearrangement Metathesis 2.5 Stereocontrolled One-Step Synthesis of Functionalized Cispentacin and Transpentacin Derivatives 2.5.1 Stereocontrolled Synthesis of Functionalized Cispentacin and Transpentacin Derivatives through Ring-Opening Metathesis of Norbornene β-Amino Acid Derivatives 2.5.2 Stereocontrolled Synthesis of Functionalized Azetidinones and β-Amino Acid Derivatives from Condensed Ring β-Lactams by Ring-Opening Metathesis 2.5.3 Carbon–Carbon Double Bond Functionalization of β-Amino Acid Derivatives and β-Lactams with α,β-Unsaturated Carbonyl Compounds through Cross Metathesis 2.5.4 Synthesis of Functionalized β-Amino Acid Derivatives and β-Lactams through Chemoselective Cross Metathesis 3 Conclusions and Outlook. [ABSTRACT FROM AUTHOR]

Among acetylenic natural products, chiral lipidic alkynylcarbinol (LAC) metabolites, mostly extracted from marine sponges, have revealed a broad spectrum of biological activities, in particular, remarkable antitumor cytotoxicity. With reference to one of the simplest natural representatives, [(S)-eicos-(4E)-en-1-yn-3-ol], and a given cancer cell line (HCT116), combined extensive efforts in chemical synthesis (relying on the use of a large chemical toolbox) and biological analysis (in vitro tests), have provided systematic structure–activity relationships (SARs) where the initially selected four structural parameters appear as independent principal components: (i) and (ii) the sp/sp2 content and extent of the terminal and internal unsaturations adjacent to the carbinol center, (iii) the absolute configuration of the latter, (iv) the length of the n-aliphatic backbone. Two key criteria have also been established regarding the functional alkynylcarbinol pharmacophore: the alkynylcarbinol unit must be both secondary and terminal (i.e., substituted by a short ethynyl or ethenyl C2 group). This review is intended to provide a further illustration of the value of a simple rational approach for drug design, and to act as a benchmark for future optimization of LACs as antitumor agents. 1 Introduction 2 2C2-Unsaturated Pharmacophore Candidates 2.1 Alkenylalkynylcarbinols (AACs) 2.2 Dialkynylcarbinols (DACs or DACys) 2.3 Alkynylalkenylcarbinols (iso-AACs) and Dialkenylcarbinols (DACes) 2.4 Oxidation-Protected Dialkynylcarbinols and Dialkynylketones 2.5 Fluorophore-Labeled Lipidic Dialkynylcarbinols 3 C2/C3-Unsaturated Pharmacophore Candidates 3.1 Cyclopropylalkynylcarbinols (CACs) 3.2 Allenylalkynylcarbinols (AllACs) 4 C2/C4- and 3C2-Unsaturated Pharmacophore Candidates 4.1 Butadiynylalkynylcarbinols (BACs) 4.2 Trialkynylcarbinols (TACs) 5 Double-AC-Headed Pharmacophore Candidates 6 Screening on the Lipidic Chain Length 7 Conclusion [ABSTRACT FROM AUTHOR]

Bromoformates and iodoformates are successfully synthesized in high yields with regioselectivity and stereoselectivity by using ZnAl-BrO3- layered double hydroxides (LDHs) and KX (X = Br, I) in the presence of formic acid (HCOOH). The protocol exploits the versatile function of formic acid as solvent, nucleophilic reagent, and acidic medium simultaneously, simplifying the reaction and separation of the products. [ABSTRACT FROM AUTHOR]

β-Dicarbonyl compounds have established themselves as substrates of choice in enantioselective organocatalysis because of their easy activation. Among them, β-diketones, β-diesters, and β-ketoesters lead the dance and there has been only limited work with other β-dicarbonyl compounds as pronucleophiles. In this Synpacts article, we wish to discuss our recent contributions to the introduction of Weinreb β-ketoamides in organocatalyzed transformations, where they can provide an interesting balance between reactivity and selectivity, with also interesting potentialities in terms of postfunctionalization. 1 Introduction 2 Preparation of Weinreb β-Ketoamides 3 Michael Addition to Nitroolefins 4 Multicomponent Synthesis of Tetrahydropyridines 5 Outlook [ABSTRACT FROM AUTHOR]

An efficient synthesis of naturally occurring 1,2- and 1,3-amino alcohol unit containing 2-substituted piperidine alkaloids and their analogues has been developed from L-pipecolinic acid. The protocol describes the regio- and stereoselective oxymercuration--demercuration of 2-alkenyl piperidines based on protecting groups to give piperidine alkaloids as a key step. [ABSTRACT FROM AUTHOR]

A concise, atom-economic, and highly regio/stereoselective synthetic strategy was developed for the construction of phosphorusand nitrogen-fused polycyclic skeleton derivatives. The one-pot, twostep, catalyst-free domino condensation/intramolecular cycloaddition reaction of various substituted 2-(vinylphosphoryloxy)benzaldehydes with pyrazolidin-3-one took place at room temperature. Three new bonds (C-C, 2 × C-N) and two new nitrogen and phosphorus heterocycles were simultaneously constructed. The reaction is particularly attractive due to features such as low cost, mild conditions, atom economy, high stereoselectivity, and potential biological activity of the product. [ABSTRACT FROM AUTHOR]

We have developed a novel protocol for glucosylation by adopting a glucosyl fluoride donor with 2-O-benzoyl-3,4,6-tri-O-benzyl protection. The protocol is useful for the ready assembly of β-linked functional glycoconjugates, and the reaction accommodates a broad range of substrates. Conveniently, water-tolerant and commercially available InI3 is used as a catalyst, and no other additional reagent is required. The method involves an interesting process for glucosyl fluoride activation and, in particular, permits the stereoselective construction of partially benzylated glucopyranosides carrying a selectively removable 2-O-benzoyl group, which hold great potential as glycosyl receptors for building further 1,2-glycosidic linkages. [ABSTRACT FROM AUTHOR]