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Functionalization of Si‐bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon‐stereogenic architectures by functionalization of Si‐bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5‐palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5‐palladium migration reaction. The key to the success is the discovery and fine‐tuning of the different substituents of α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐based phosphoramidites, which ensure the enantioselectivity and desired reactivity. [ABSTRACT FROM AUTHOR]

Ribonucleic acids (RNAs) play a vital role in living organisms. Many of their cellular functions depend critically on chemical modification. Methods to modify RNA in a controlled manner—both in vitro and in vivo—are thus essential to evaluate and understand RNA biology at the molecular and mechanistic levels. The diversity of modifications, combined with the size and uniformity of RNA (made up of only 4 nucleotides) makes its site‐specific modification a challenging task that needs to be addressed by complementary approaches. One such approach is solid‐phase RNA synthesis. We discuss recent developments in this field, starting with new protection concepts in the ongoing effort to overcome current size limitations. We continue with selected modifications that have posed significant challenges for their incorporation into RNA. These include deazapurine bases required for atomic mutagenesis to elucidate mechanistic aspects of catalytic RNAs, and RNA containing xanthosine, N4‐acetylcytidine, 5‐hydroxymethylcytidine, 3‐methylcytidine, 2′‐OCF3, and 2′‐N3 ribose modifications. We also discuss the all‐chemical synthesis of 5′‐capped mRNAs and the enzymatic ligation of chemically synthesized oligoribonucleotides to obtain long RNA with multiple distinct modifications, such as those needed for single‐molecule FRET studies. Finally, we highlight promising developments in RNA‐catalyzed RNA modification using cofactors that transfer bioorthogonal functionalities. [ABSTRACT FROM AUTHOR]

P‐stereogenic compounds are widely used as ligands in asymmetric catalysis and are present in a myriad of bioactive compounds and pharmaceuticals. Yet, their stereocontrolled preparation remains challenging. Herein, we report a novel strategy towards versatile chiral‐at‐P alkenylphosphonamidates through a one‐pot Ni‐catalyzed C−P coupling/diastereoselective hydrolysis of readily available phosphoramidites and alkenyl halides. Remarkably, a chemo‐ and diastereodivergent behavior was observed upon subtle changes in the reaction conditions. Additionally, selective derivatizations of chiral alkenylphosphonamidates demonstrate their versatility as building blocks for the synthesis of structurally diverse P‐stereogenic compounds. [ABSTRACT FROM AUTHOR]

Oligonucleotides containing cleavable linkers have emerged as versatile tools to achieve stimulus‐responsive and site‐specific cleavage of DNA. However, the limitations of previously reported cleavable linkers including photolabile and disulfide linkers have restricted their applications in vivo. Inspired by the cathepsin B‐sensitive dipeptide linkers in antibody–drug conjugates (ADCs) such as Adcetris, we have developed Val‐Ala‐02 and Val‐Ala‐Chalcone phosphoramidites for the automated synthesis of enzyme‐cleavable oligonucleotides. Cathepsin B digests Val‐Ala‐02 and Val‐Ala‐Chalcone linkers efficiently, enabling cleavage of oligonucleotides into two components or release of small‐molecule payloads. Based on the prior success of dipeptide linkers in ADCs, we believe that these dipeptide linker phosphoramidites will promote new clinical applications of therapeutic oligonucleotides. [ABSTRACT FROM AUTHOR]

The weak noncovalent interactions and flexibility of ligands play a key role in enantioselective metal‐catalyzed reactions. In transition metal complexes and their catalytic applications, the experimental assessment and the design of key interactions is as difficult as the prediction of the enantioselectivities, especially for flexible, privileged ligands such as chiral phosphoramidites. Therefore, the interligand interactions in cis‐PdIIL2Cl2 phosphoramidite complexes were investigated by NMR spectroscopy and computations. We were able to induce a strong conformational preference by breaking the symmetry of the C2‐symmetric side chain of one of the ligands, and shift the equilibrium between hetero‐ and homocomplexes towards heterocomplexes because of interligand interactions in the cis‐complexes. The modulation of aryl substituents was exploited, along with the solvent effect. The combined CH–π and π–π interactions reveal design patterns for binding and folding of chiral ligands and catalysts. [ABSTRACT FROM AUTHOR]

1,2‐Bisphosphines have been identified as one class of important and powerful chiral ligands in asymmetric catalysis with transition metals. Herein, a copper(I)‐catalyzed asymmetric hydrophosphination of α,β‐unsaturated phosphine sulfides was developed with the assistance of "soft–soft" interaction between copper(I)‐catalyst and the phosphine sulfide moiety, which afforded 1,2‐bisphosphine derivatives with diversified electronic nature and steric hindrance in high to excellent yields with high to excellent enantioselectivity. Moreover, the challenging catalytic asymmetric hydrophosphination/protonation reaction was achieved with excellent enantioselectivity. Strikingly, the dynamic kinetic resolution of racemic diarylphosphines was also successfully carried out with high to excellent diastereo‐ and enantioselectivities. Interestingly, the nucleophilic copper(I)‐diphenylphosphide species was characterized by 31P NMR spectrum and mass spectrum. At last, three products were transformed to chiral 1,2‐bisphosphines, which were employed as ligands in Rh‐catalyzed asymmetric hydrogenation of α‐amino‐α,β‐unsaturated ester. The α‐amino acid derivative was produced in high enantioselectivity, which demonstrated the utility of the present methodology. [ABSTRACT FROM AUTHOR]

A Rh‐catalyzed reaction of silacyclobutanes (SCBs) with unactivated alkynes has been developed to form silacyclohexenes with high chemoselectivity. Good enantioselectivity at the stereogenic silicon center was achieved using a chiral phosphoramidite ligand. The resulting silacyclohexenes are useful scaffolds for synthesizing structurally attractive silacyclic compounds. [ABSTRACT FROM AUTHOR]

An iterative polyphosphorylation approach is described, which is based on a phosphoramidite (P‐amidite) derived reagent (c‐PyPA) obtained from the cyclization of pyrophosphate with a reactive diisopropylaminodichlorophosphine. This type of reagent is unprecedented as it represents a reactive P‐amidite without protecting groups. The reagent proved to be stable in solution over several weeks. Its utility is described in the context of iterative monodirectional and bidirectional polyphosphorylations. The ensuing functionalized cyclotriphosphate can be opened with a variety of nucleophiles providing ready access to diverse functionalized polyphosphate chains of defined length with several tags, including both P‐N and P‐O labels. Their interaction with exo‐ and endopolyphosphatases is described. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of a series of C2‐symmetric 3,3′‐diarylated 1,1′‐spirobiindane‐7,7′‐diols (3,3′‐diaryl‐SPINOLs) was developed by sequential Rh‐catalyzed twofold asymmetric conjugate arylation/BF3‐promoted diastereoselective spirocyclization (>20:1 d.r. and >99 % ee for all examples). Some phosphoramidite ligands were prepared from the 3,3′‐Ph‐SPINOL and applied to several catalytic asymmetric reactions, and the 3,3′‐diarylated ligands showed higher enantioselectivities than the privileged nonsubstituted ligands. [ABSTRACT FROM AUTHOR]

An unusual hybrid palladium catalyst containing an anionic chiral CoIII complex and a chiral phosphoramidite ligand shows a high capacity for catalyzing asymmetric thioamide‐directed C(sp3)−H arylation and delivers excellent yield and enantioselectivity (up to 99 % yield, 99 % ee). Significant synergy between the chiral ligand and the anion in terms of stereochemical control was observed. Mechanistic investigations have revealed both the nature of the C−H activation and the origin of the enantioselectivity. [ABSTRACT FROM AUTHOR]

Abstract: Digital polymers are uniform macromolecules that store monomer‐based binary sequences. Molecularly stored information is usually extracted from the polymer by a tandem mass spectrometry (MS/MS) measurement, in which the coded chains are fragmented to reveal each bit (i.e. basic coded monomer unit) of the sequence. Here, we show that data‐extraction can be greatly simplified by favoring the formation of MS/MS fragments containing two bits instead of one. In order to do so, digital poly(alkoxyamine phosphodiester)s, containing binary dyads in each repeat unit, were prepared by an orthogonal solid‐phase approach involving successive phosphoramidite and radical‐radical coupling steps. Three different sets of monomers were considered to build these polymers. In all cases, four coded building blocks—two hydroxy‐nitroxides and two phosphoramidite monomers—were required to build the dyads. Among the three studied monomer sets, one combination allowed synthesis of uniform sequence‐coded polymers. The resulting polymers led to clear dyad‐containing fragments in MS/MS and could therefore be efficiently decoded. Additionally, an algorithm was created to detect specific dyad fragments, thus enabling automated sequencing. [ABSTRACT FROM AUTHOR]

Abstract: Isoxazolinone sind biologisch und synthetisch interessante, dicht funktionalisierte Heterocyclen, die lange Zeit nicht in enantiomerenangereicherter Form über asymmetrische Katalyse zugänglich waren. Neben dem Mangel an enantioselektiven Methoden ist die Funktionalisierung der Isoxazolinone oft durch Regioselektivitätsprobleme aufgrund der Konkurrenz mehrerer nukleophiler Zentren innerhalb der Heterocyclen erschwert. Hier beschreiben wir die erste regio‐ und enantioselektive C‐Allylierung von Isoxazolinonen. Diese verlief mit hoher Regioselektivität zugunsten eines linearen Allylierungsprodukts, obwohl Iridium‐Phosphoramidit‐Katalysatoren üblicherweise verzweigte Isomere bilden. Unsere Studien deuten darauf hin, dass dies eine Folge einer Reaktionskaskade ist. Eine anfängliche regio‐ und enantioselektive N‐Allylierung bildet ein verzweigtes Allylintermediat, und eine nachfolgende spontane [3,3]‐Umlagerung ermöglicht einen Chiralitätstransfer. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed enantioselective dearomative arylalkynylation of N-substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL-based phosphoramidite as the chiral ligand. A wide range of 2,3-disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1). [ABSTRACT FROM AUTHOR]

A new class of phosphanylmethylphosphonate reagents has been developed to enable the controlled synthesis of methylene bisphosphonate mono- and diesters. Condensation of such reagents with an alcohol of choice through azole-mediated phosphoramidite chemistry followed by in situ oxidation provides orthogonally protected methylene bisphosphonate tetraesters. Global deprotection of the tetraester leads to terminal methylene bisphosphonates. Alternatively, selective deprotection at the terminal phosphonate followed by a condensation between the acquired methylene bisphosphonate triester and a second alcohol leads to methylene bisphosphonates diesters. [ABSTRACT FROM AUTHOR]

A highly enantioselective gold(I)-catalyzed intermolecular annulation of 2-(1-alkynyl)-2-alken-1-ones with N-allenamides is presented. The present work represents the first example of a gold-catalyzed annulation with the proximal C=C bond of an N-allenamide, and is distinctly different from the previously observed annulations at the distal C=C bond. Interestingly, both enantiomers of the products could be obtained in good yields with high regio-, diastereo-, and enantioselectivity by using either diastereomer of a binolderived phosphoramidite as a chiral ligand. [ABSTRACT FROM AUTHOR]

A Pd0-catalyzed asymmetric Nazarov-type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL-derived phosphoramidite (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all-carbon-atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents. [ABSTRACT FROM AUTHOR]

An aza-crown ether, modified phosphoramidite ligand, has been designed and synthesized. The ON/OFF reversible switch of catalytic activity for its rhodium catalyst was thoroughly investigated in the asymmetric hydrogenation of dehydroamino acid esters modulated by host-guest interactions. In the OFF state, the catalyst is almost inactive (less than 1 % conversion) because of the formation of an intermolecular sandwich complex by two aza-crown ether moities and the cationic rhodium metal center. In using alkali-metal-cations as the trigger, the catalytic activity was turned ON and consequently resulted in full conversions and excellent enantioselectivities (up to 98 % ee). [ABSTRACT FROM AUTHOR]

Disulfide dithymidines linked 3′-5′ or 3′-6′ were synthesized and incorporated into oligonucleotides through a combined phosphotriester and phosphoramidite solid-phase oligonucleotide synthesis approach. The disulfide links are cleaved and formed reversibly in the presence of thiols and oligonucleotides. This link was shown to be sequence-adaptive in response to given templates in the presence of mercaptoethanol. The artificial 3′-5′ and 3′-6′ disulfide link was tolerated by polymerases in the polymerase chain reaction (PCR). By using sequencing analysis, we show that single mutations frequently occurred randomly in the amplification products of the PCR. [ABSTRACT FROM AUTHOR]

An efficient method for the diastereo- and enantioselective construction of vicinal all-carbon quaternary stereocenters through palladium-catalyzed decarboxylative cycloaddition of vinylethylene carbonates with activated Michael acceptors was developed. By using a palladium complex generated in situ from [Pd2(dab)3]⋅CHCl3 and a phosphoramidite ligand as a catalyst under mild reaction conditions, the process provides multifunctionalized tetrahydrofurans bearing vicinal all-carbon quaternary stereocenters in high yields with a high level of absolute and relative stereocontrol. [ABSTRACT FROM AUTHOR]

β-Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring-opening reactions. Transition-metal-catalyzed CH functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd0-catalyzed CH functionalization for aryl-aryl couplings, related reactions involving the formation of saturated C(sp3)C(sp3) bonds are elusive. Reported here is an asymmetric CH functionalization approach to β-lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp3)C(sp3) and strain-building reductive eliminations to for the four-membered ring. In general, the β-lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst. [ABSTRACT FROM AUTHOR]

An efficient method for the enantioselective construction of tertiary vinylglycols through a palladium-catalyzed asymmetric decarboxylative cycloaddition of vinylethylene carbonates with formaldehyde was developed. By using a palladium complex generated in situ from [Pd2(dba)3]⋅CHCl3 and a phosphoramidite ligand as a catalyst under mild reaction conditions, the process allows conversion of racemic 4-substituted 4-vinyl-1,3-dioxolan-2-ones into the corresponding 1,3-dioxolanes, as methylene acetal protected tertiary vinylglycols, in high yields with good to excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

Asymmetric intramolecular direct hydroarylation of α-ketoamides gives various types of optically active 3-substituted 3-hydroxy-2-oxindoles in high yields with complete regioselectivity and high enantioselectivities (84-98 % ee). This is realized by the use of the cationic iridium complex [Ir(cod)2](BArF4) and the chiral O-linked bidentate phosphoramidite ( R, R)-Me-BIPAM. [ABSTRACT FROM AUTHOR]

Ein 5 ‐ Formyl ‐ 2′ ‐ desoxycytidin(fdC) ‐ Phosphoramidit ‐ Baustein wurde entwickelt, der die Synthese fdC ‐ haltiger DNA in ausgezeichneter Reinheit und Ausbeute ermöglicht. In Kombination mit Phosphoramiditen für 5 ‐ Methyl ‐ dC, 5 ‐ Hydroxymethyl ‐ dC und 5 ‐ Carboxy ‐ dC gelang die Herstellung eines Segments des OCT4 ‐ Promotors, das alle vier epigenetischen Basen enthält. Aufgrund des großen Interesses an diesen neuen epigenetischen Basen sollte die Fähigkeit, alle vier von ihnen in DNA einzubringen, von besonderer Bedeutung sein. Biologisch relevante Promotorsegmente mit allen vier epigenetischen Nukleosiden sind nun durch Festphasensynthese zugänglich. Mit dem hier vorgestellten fdC ‐ Phosphoramidit werden keine Nebenreaktionen an 5 ‐ Formylcytosin beobachtet. Zusätzlich vermeiden milde Entschützungsbedingungen Oxidationen oder Reduktionen, was mit einer detaillierten massenspektrometrischen Analyse nachgewiesen werden konnte. [ABSTRACT FROM AUTHOR]

Eine chemische Methode für die nachsynthetische Markierung von Prä ‐ MikroRNAs (Prä ‐ miRNAs) auf festem Träger mit einfach zugänglichen Reagentien wird beschrieben. Die Methode wurde genutzt, um eine Bibliothek von 31 Prä ‐ MikroRNAs mit gebräuchlichen Markierungen, einschließlich Cy3, Trioxalen, Biotin und BHQ ‐ 1, herzustellen. [ABSTRACT FROM AUTHOR]

The article discusses the development of a novel approach for unsymmetric diphosphoinositol polyphosphates unified synthesis. It mentions C2-symmetric phosphoramidite application, which allows the desymmetrization of inositol. It states the said application can be adapted for introduction of chemical modifications such as thiophosphates.

Rücktitelbild: Flexible Total Synthesis of 11-Deoxylandomycins and Their Non-Natural Analogues by Way of Asymmetric Metal Catalysis (Angew. Keywords: Asymmetrische Synthesen; Kohlenhydrate; Oligosaccharide; Palladium; Totalsynthesen Asymmetrische Synthesen, Kohlenhydrate, Oligosaccharide, Palladium, Totalsynthesen. [Extracted from the article]

Inspired by biological polymers, sequence-controlled synthetic polymers are highly promising materials that integrate the robustness of synthetic systems with the information-derived activity of biological counterparts. Polymer– biopolymer conjugates are often targeted to achieve this union; however, their synthesis remains challenging. We report a stepwise solid-phase approach for the generation of completely monodisperse and sequence-defined DNA–polymer conjugates using readily available reagents. These polymeric modifications to DNA display self-assembly and encapsulation behavior—as evidenced by HPLC, dynamic light scattering, and fluorescence studies—which is highly dependent on sequence order. The method is general and has the potential to make DNA–polymer conjugates and sequencedefined polymers widely available. [ABSTRACT FROM AUTHOR]

Vollständig regioselektiv, hoch enantioselektiv und in hohen Ausbeuten führt die intramolekulare direkte Hydroarylierung von α ‐ Ketoamiden zu optisch aktiven 3 ‐ substituierten 3 ‐ Hydroxy ‐ 2 ‐ oxindolen. Y. Yamamoto et al. nutzen in ihrer Zuschrift auf S. 2696 ff. zu diesem Zweck einen chiralen kationischen Iridiumkomplex, der in situ gebildet wird und die enantioselektive Addition der stärker gehinderten ortho ‐ C ‐ H ‐ Bindung an eine Carbonylgruppe bewirkt. [ABSTRACT FROM AUTHOR]