Protection‐Group‐Free Synthesis of Sequence‐Defined Macromolecules via Precision λ‐Orthogonal Photochemistry

An advanced light‐induced avenue to monodisperse sequence‐defined linear macromolecules via a unique photochemical protocol is presented that does not require any protection‐group chemistry. Starting from a symmetrical core unit, precision macromolecules with molecular weights up to 6257.10 g mol^?1 are obtained via a two‐monomer system: a monomer unit carrying a pyrene functionalized visible light responsive tetrazole and a photo‐caged UV responsive diene, enabling an iterative approach for chain growth; and a monomer unit equipped with a carboxylic acid and a fumarate. Both light‐induced chain growth reactions are carried out in a λ‐orthogonal fashion, exciting the respective photosensitive group selectively and thus avoiding protecting chemistry. Characterization of each sequence‐defined chain (size‐exclusion chromatography (SEC), high‐resolution electrospray ionization mass spectrometry (ESI‐MS), and NMR spectroscopy), confirms the precision nature of the macromolecules.     

“Living” free radical copolymerization of styrene and N-vinylcarbazole

Poly[styrene-co-(N-vinylcarbazole)] copolymers with controlled molecular weights and narrow polydispersities were synthesized by nitroxide-mediated “living” free radical copolymerization using an initiator/capping agent system consisting of benzoyl peroxide (BPO) and the stable nitroxyl radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The copolymerization behaves in a “living” fashion and allows the synthesis of poly[styrene-co-(N-vinylcarbazole)]/polystyrene block copolymers via a controlled chain-extension reaction of the prepared copolymers with styrene.     

Stereocontrolled Total Synthesis of (+)‐trans‐Dihydronarciclasine

A highly stereoselective and efficient total synthesis of trans‐dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester–enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six‐ring vinylogous ester intermediate, which is generated from the γ,δ‐unsaturated ester functional group of the Claisen rearrangement product in an efficient three‐step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel–Crafts‐type cyclization to form the B ring via an isocyanate intermediate derived from an N‐Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N‐Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence.     

Intermolecular C−H Amidation of (Hetero)arenes to Produce Amides through Rhodium‐Catalyzed Carbonylation of Nitrene Intermediates

Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium‐catalyzed three‐component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene‐intermediates and direct C?H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N₂ as the only by‐product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh‐nitrene intermediate.     

An Efficient One‐pot Synthesis of Aryl‐substituted 1‐(Thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates via a Hantzsch Synthesis‐Knorr Reaction Sequence

The treatment of α‐bromoalkyl aryl ketones and 2‐(propan‐2‐ylidene)hydrazine carbothioamide afforded 4‐aryl‐2‐(2‐(propan‐2‐ylidene)hydrazinyl)thiazoles via a Hantzsch‐thiazole synthesis, which reacted with 4‐aryl‐2,4‐diketoesters via a sequential Knorr‐pyrazole reaction to deliver a variety of aryl‐substituted ethyl 1‐(thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates in a one‐pot fashion with moderate to high yields. The key intermediates 4‐aryl‐2,4‐diketoesters, existing as its enolic lithium salt, were synthesized in situ by a high‐yield tert‐BuOLi‐mediated Claisen condensation of alkylphenones and diethyl oxalate. This class of elegant molecule comprises aryl groups on the two different heterocyclic cores, and the configurations of two representative molecules were determined by single crystal X‐ray crystallography.     

Rhodium‐Catalyzed PIII‐Directed ortho‐C−H Borylation of Arylphosphines

Transition‐metal‐mediated metalation of an aromatic C?H bond that is adjacent to a tertiary phosphine group in arylphosphines via a four‐membered chelate ring was first discovered in 1968. Herein, we overcome a long‐standing problem with the ortho‐C?H activation of arylphosphines in a catalytic fashion. In particular, we developed a rhodium‐catalyzed ortho‐selective C?H borylation of various commercially available arylphosphines with B₂pin₂ through P^III‐chelation‐assisted C?H activation. This discovery is suggestive of a generic platform that could enable the late‐stage modification of readily accessible arylphosphines.     

A Novel Coordination Polymer, [Ag4^1 （bpdc）（H2bpdc）（Hbpdc）2]n （bpdc = 2,2＇-bipyridyl-3,3＇-dicarboxylate）： Coordination Models of bpdc Ligands

A novel coordination polymer, [Ag₄ppdc)(H₂bpdc)(Hbpdc)₂] (bpdc = 2,2′‐bipyridyl‐3,3′‐dicarboxylate), was hydrothermally synthesized at 403 K and structurally characterized by single crystal X‐ray diffraction analysis. The compound crystalizes in the monoclinic space group C2/c with a=1.9516(4) nm, b=1.9503(4) nm. c=1.2566(3) nm, and β=112.48(3)°. In the two‐dimensional crystal structure, Ag^I center is coordinated, in a scarce coordination environment, double‐capped tetrahedron, by one bpdc ligand to form N‐Ag‐N chelate bond via two pyridyl N atoms, and other two bpdc ligands to form two O‐Ag‐O chelate bonds, respectively, via two carboxyl O atoms. The bpdc ligands are present in one non‐protonated form, bpdc, and two protonated forms, Hbpdc and H2bpdc, which all act as μ3‐ligand in a hexadentate fashion (N, N′; O, O′; O, O′) to coordinate with three Ag centers, respectively, through the three chelate bonds. This coordinated fashion of bpdc ligand is first found in the title compound. W‐Us‐NIR reflectance spectroscopy study revealed insulator nature for the crystal with an optical energy gap of 3.1 eV.     

Facile Synthesis of Polycyclic Pentalenes with Enhanced Hückel Antiaromaticity

Pentalenes represent highly reactive Hückel antiaromatics with 8π electrons. Usually, pentalenes are stabilized by incorporation of two benzene rings in a fused fashion. In dibenzo[a ,e ]pentalenes, however, the high aromaticity of the fused benzene rings compromises the inherent antiaromaticity of the pentalene core. Herein, we disclose that this forfeited antiaromaticity can be restored by fusing four additional aromatic rings onto the peripheral positions of dibenzo[a,e]pentalenes. Such polycyclic pentalenes were prepared by successive transannular cyclizations via in situ‐generated tetrakisdehydro[16]annulenes. The thus obtained compounds showed intriguing properties, for example, characteristic absorptions in the visible‐to‐near‐infrared (NIR) region and low reduction potentials. These results hence afford a design principle to produce highly antiaromatic yet stable pentalenes. The antiaromaticity of the pentalene core can be widely tuned via the degree of aromaticity of the peripherally fused rings.     

Pyrrolidine and α-methylene-α-lactam from the cyclization of α-(alkylaminoethyl)acrylate: Synthesis of aza-sarkomycins

Diene readily adds primary amines to give which can cyclize either in a Michael addition fashion or via a displacement reaction to give, respectively, pyrrolidine or methylene lactam which further isomerizes to under the employed reaction conditions. Compound can be obtained as the sole product from the reaction of diene precursor with amines followed by vacuum pyrolysis.     

Intramolecular Aza‐Diels–Alder Reactions of ortho‐Quinone Methide Imines: Rapid,Catalytic, and Enantioselective Assembly of Benzannulated Quinolizidines

Aza‐Diels–Alder reactions (ADARs) are powerful processes that furnish N‐heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi‐ and polycyclic systems with high stereoselectivity. We report herein a novel Brønsted acid catalyzed process in which ortho‐quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one‐step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo‐ and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho‐quinone methide imine formation, and ADAR.     

[4 + 2] Heterocyclization for Efficient Formation of Substituted Quinoxalines through Carbon–Oxygen Bonds Cleavage

A new domino strategy for efficient synthesis of highly functionalized quinoxaline derivatives via [4 + 2] heterocyclization involving ring‐opening of oxirane process has been developed. The reaction promoted by Cs₂CO₃ was easy to perform in a simple operation from common and inexpensive starting materials. The bisfunctionalization of quinoxaline framework including C2 benzylation and C3 arylation was readily achieved in domino fashion that involved the cleavage of three C–O bonds of 1,3‐diaryl‐2,3‐epoxypropan‐1‐one.     

Palladium‐Catalyzed Dearomative syn‐1,4‐Oxyamination

A palladium‐catalyzed dearomative syn‐1,4‐oxyamination protocol using non‐activated arenes has been developed. This one‐pot procedure utilizes arenophile chemistry, and the corresponding para‐cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn‐1,4‐oxyaminated products. The reaction conditions permit a range of arenes, as well as different O‐nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C?H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.     

配合物(ArO)2Yb(NPh2)2K(THF)4(Ar=C6H2-t-Bu3-2,4,6)的合成、分子结构和催化行为

Reaction of anhydrous YbC13 with 2 equiv, of sodium 2,4,6-tri-tert-butylphenoxide (ArONa, Ar=C6H2-t-Bu3-2,4,6) and 2 equiv, of potassium diphenyl amide in THF afforded the first bis(aryloxo) amido-lanthanide complex of (ArO)2Yb(NPh2)2K(THF)4 (1). In 1, the ytterbium and potassium were bridged via diphenyl amido ligands.The ytterbium metal center was coordinated to two oxygen atoms of aryloxide ligands and two nitrogen atoms of diphenyl amido ligands in a conventional distorted tetrahedral fashion, while the potassium interacted in η^2-fashion with two phenyl rings of the diphenyl amido ligands besides four THF molecules. 1 displayed moderate catalytic activities for the polymerization of methyl methacrylate and acrylonitrile.     

Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio‐ and diastereoselective construction of cyclopropanes through C?H activation of arenes and coupling with readily available cyclopropenes is highly appealing but remains a challenge. A dual directing‐group‐assisted C?H activation strategy was used to realize mild and redox‐neutral Rh^III‐catalyzed C?H activation and cyclopropylation of N‐phenoxylsulfonamides in a highly enantioselective, diastereoselective, and regioselective fashion with cyclopropenyl secondary alcohols as a cyclopropylating reagent. Synthetic applications are demonstrated to highlight the potential of the developed method. Integrated experimental and computational mechanistic studies revealed that the reaction proceeds via a Rh^V nitrenoid intermediate, and Noyori‐type outer sphere concerted proton‐hydride transfer from the secondary alcohol to the Rh=N bond produces the observed trans selectivity.     

Linear tetrablock quaterpolymers via triple click reactions,azide‐alkyne,diels–alder,and nitroxide radical coupling in a one‐pot fashion

Azide‐alkyne and Diels–Alder click reactions together with a click‐like nitroxide radical coupling reaction were used in a one‐pot fashion to generate tetrablock quaterpolymer. The various living polymerization generated linear polymers with orthogonal end‐functionalities, maleimide‐terminated poly(ethylene glycol) (PEG‐MI), anthracene‐ and azide‐terminated polystyrene, alkyne‐ and bromide‐terminated poly(tert‐butyl acrylate) or alkyne‐poly(n‐butyl acrylate), and tetramethylpiperidine‐1‐oxyl (TEMPO)‐terminated poly(ε‐caprolactone) (PCL‐TEMPO) were clicked together in a one‐pot fashion to generate PEG‐b‐PS‐b‐PtBA‐b‐PCL or PEG‐b‐PS‐b‐PnBA‐b‐PCL quaterpolymer using Cu(0), CuBr, and N,N,N′,N″,N″‐pentamethyldiethylenetriamine as catalyst in dimethyl formamide at 80 °C for 36 h. Linear precursors and target quaterpolymers were analyzed via ¹H NMR and gel permeation chromatography. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Automated parallel investigations/optimizations of the reversible addition‐fragmentation chain transfer polymerization of methyl methacrylate

Poly(methyl methacrylate)s were successfully synthesized in a controlled fashion via reversible addition‐fragmentation chain transfer polymerizations utilizing an automated synthesizer. Sixteen polymers were synthesized in a parallel way utilizing the Chemspeed Accelerator? SLT100 to investigate the reproducibility and the control over the polymerizations. The obtained polymers were characterized by gel permeation chromatography (GPC) and automated MALDI TOFMS measurements, thereby proving the reproducibility and controllability of the investigated automated setup. Furthermore, temperature optimization reactions were performed utilizing an individually heatable reactor block. Moreover, to demonstrate the presence of active polymer chains in the reaction mixture, chain extension polymerizations were performed on the automated synthesizer. The results obtained from these chain extension experiments demonstrate the possibility to design well‐defined A‐b‐B block copolymers with different monomers as building units. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5775–5783, 2004     

Crystal‐to‐Crystal Synthesis of Helically Ordered Polymers of Trehalose by Topochemical Polymerization

The synthesis of crystalline helical polymers of trehalose via topochemical azide–alkyne cycloaddition (TAAC) of a trehalose‐based monomer is presented. An unsymmetrical trehalose derivative having azide and alkyne crystallizes in two different forms having almost similar packing. Upon heating, both the crystals undergo TAAC reaction to form crystalline polymers. Powder X‐ray diffraction (PXRD) studies revealed that the monomers in both the crystals polymerize in a crystal‐to‐crystal fashion; circular dichroism (CD) studies of the product crystals revealed that the formed polymer is helically ordered. This solvent‐free, catalyst‐free polymerization method that eliminates the tedious purification of the polymeric product exemplifies the advantage of topochemical polymerization reaction over traditional solution‐phase polymerization.     

Ultra‐Fast RAFT‐HDA Click Conjugation: An Efficient Route to High Molecular Weight Block Copolymers

The use of the reversible addition fragmentation chain transfer—hetero Diels–Alder (RAFT‐HDA) click reaction for the modular construction of block copolymers is extended to the generation of high molecular weight materials. Cyclopentadienyl end‐functionalized polystyrene (PS‐Cp) prepared via both atom transfer radical polymerization (ATRP) and the RAFT process are conjugated to poly(isobornyl acrylate) (PiBoA) (also prepared via RAFT polymerization) to achieve well‐defined block copolymers with molecular weights ranging from 34 000 to over 100 000 g · mol⁻¹ and with small polydispersities (PDI < 1.2). The conjugation reactions proceeded in a very rapid fashion (less than 10 min in the majority of cases) under ambient conditions of temperature and atmosphere. The present study demonstrates—for the first time—that RAFT‐HDA click chemistry can provide access to high molecular weight block copolymers in a simple and straight‐forward fashion.

     

Discrete macromolecular constructs via the Diels–Alder “Click” reaction

Functional polymeric materials with desired properties can be designed by precise control of macromolecular architectures. Over the recent years, click reactions have enabled efficient synthesis of a variety of polymers with different topologies via efficient polymer–polymer conjugations. While the copper catalyzed Huisgen type (3+2) dipolar cycloaddition between azide and alkyne has been widely used toward this goal, the Diels–Alder (DA) reaction offers an alternative click reaction that allow efficient macromolecular conjugations, oftentimes without the need of any additional reagent or catalyst. This article highlights, with illustrative examples, the power of the DA “click” reaction to efficiently synthesize a variety of different well‐defined macromolecular constructs in a modular fashion. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Highly Efficient Non‐Palladium‐Catalyzed Controlled Synthesis and X‐ray Analysis of Functionalized 1,2‐Diaryl‐, 1,2,3‐Triaryl‐, and 1,2,3,4‐Tetraarylbenzenes

A general, two‐step, highly efficient synthesis of 1,2‐diaryl‐, 1,2,3‐triaryl‐, and 1,2,3,4‐tetraarylbenzenes from simple stitching of α‐oxo‐ketene‐S,S‐acetals and active methylene compounds via a lactone intermediate is described. This procedure offers easy access to highly functionalized arylated benzenes that contain sterically demanding groups in good to excellent yields. The novelty of the procedure lies in the construction of aromatic compounds with the desired conformational flexibility along the molecular axis in a transition‐metal‐free environment through easily accessible precursors. Crystal analysis of these arylated benzene scaffolds showed that the peripheral aryl rings are arranged in a propeller‐like fashion with respect to the central benzene ring. Examination of the crystal packing in the structure of a 1,2,3,4‐tetraarylbenzene revealed an N???π interaction between molecules related by a two‐fold screw axis running in the direction of the a axis. Interestingly, the repeating array of N???π interactions around the axis of this 1,2,3,4‐tetraarylbenzene forces the molecules into a helical pattern.