Formation of macrocyclic ring systems by carbonylation of trifunctional P/B/B frustrated Lewis pairs.

The trifunctional P/B/B frustrated Lewis pairs featuring bulky aryl groups at phosphorus [Dmesp (), Tipp (), Mes* ()] react with H by heterolytic hydrogen splitting followed by cleavage of HB(CF) to give the zwitterionic six-membered heterocyclic PH phosphonium/borate products . Compounds react with carbon monoxide by means of a Lewis acid induced CO insertion/rearrangement sequence that eventually results in the formation of the macrocyclic dimers . The respective carbonylation reaction of the Mes*P/B/B FLP gives the macrocyclic trimer .

Formation and reactions of active five-membered phosphane/borane frustrated Lewis pair ring systems.

The reactive five-membered frustrated P/B Lewis pair 6a was generated from Tipp-P(vinyl)2 (Tipp: 2,4,6-triisopropylphenyl) by a series of anti-Markovnikov and Markovnikov hydroboration reactions. The in situ generated compound dimerized to give 7a under kinetic control and the dimer pair 8a/9a under thermodynamic control. The Mes*-P(vinyl)2 analogue (Mes*: 2,4,6-tri-tert-butylphenyl) reacts in a similar way, but in this case the thermodynamic dimers are observed at r.

Synthesis of 3-aza[4.4.3]propellanes with high σ receptor affinity.

In order to obtain rigid σ receptor ligands with defined orientation of pharmacophoric elements, the azapropellane scaffold was chosen. Schmidt rearrangement of propellan-8-ones 6 and 10 provided 3-azapropellan-4-ones 7 and 11. Benzylation of the secondary lactams 7 and 11 followed by LiAlH reduction furnished the azapropellanes 4a and 4c, respectively.

Highly Enantioselective [5 + 2] Annulations through Cooperative N-Heterocyclic Carbene (NHC) Organocatalysis and Palladium Catalysis.

The highly enantioselective [5 + 2] annulation of enals with vinylethylene carbonates through a cooperative N-heterocyclic carbene (NHC)/Pd catalytic system is reported. The use of a bidentate phosphine ligand was crucial to prevent coordination of the NHC organocatalyst to the active Pd catalyst. The complementary and matched combination of the chiral NHC catalyst and chiral phosphine ligand promotes high levels of both reactivity and enantioselectivity (mostly ≥99% ee).

Unprecedented Dearomatized Spirocyclopropane in a Sequential Rhodium(III)-Catalyzed C-H Activation and Rearrangement Reaction.

An unprecedented dearomatized spirocyclopropane intermediate was discovered in a sequential Cp*Rh -catalyzed C-H activation and Wagner-Meerwein-type rearrangement reaction. How the oxidative O-N bond is cleaved and the role of HOAc were uncovered in this study. Furthermore, a Cp*Rh -catalyzed dearomatization reaction of N-(naphthalen-1-yloxy)acetamide with strained olefins was developed, affording a variety of spirocyclopropanes.

Lewis Acid Catalyzed Stereoselective Dearomative Coupling of Indolylboron Ate Complexes with Donor-Acceptor Cyclopropanes and Alkyl Halides.

Indolylboron ate complexes readily generated from 2-lithioindoles and boronic esters underwent multicomponent dearomative coupling with D-A cyclopropanes and alkyl halides in the presence of Sc(OTf) as a catalyst. The reactions proceeded with complete diastereoselectivity and excellent stereospecificity to provide indolines containing three contiguous stereocenters. The valuable boronic ester moiety remains in the product and allows for subsequent functionalization.

Palladium-Catalyzed Decarboxylative Heck-Type Coupling of Activated Aliphatic Carboxylic Acids Enabled by Visible Light.

The palladium-catalyzed coupling reaction of N-hydroxyphthalimide esters and styrenes to deliver exclusively (E)-substituted olefins under irradiation with visible light is reported. This method tolerates N-hydroxyphthalimide esters derived from primary, secondary, tertiary as well as benzylic carboxylic acids. Notably, Pd(PPh ) is employed as an inexpensive palladium source and no addition of base or classical photocatalyst is required.

Formation of Reactive π-Conjugated Frustrated N/B Pairs by Borane-Induced Propargyl Amine Rearrangement.

N-Propargyltetramethylpiperidine reacts with a series of trans-alkenyl-B(CF) compounds to give the substituted alkenyl-bridged frustrated N/B Lewis pairs 5. Their structures and spectroscopic features indicate a pronounced participation of the mesomeric s-trans-iminium/borata-alkene resonance form. The compounds are thought to be formed in a stepwise addition/rearrangement process which is initiated by a trans-1,2-amine/borane FLP addition to the carbon-carbon triple bond to generate a reactive zwitterionic aziridinium/alkenylborate intermediate.

Large-scale total synthesis of C-labeled citrinin and its metabolite dihydrocitrinone.

The analysis of the nephrotoxic mycotoxin citrinin in food, feed, and physiological samples is still challenging. Nowadays, liquid chromatography coupled with mass spectrometry is the method of choice for achieving low limits of detection. But matrix effects can present impairments for this method.

Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis.

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E-oximino α-diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral Rh complex and a subsequent intermolecular 1,3-dipolar cycloaddition catalyzed by a chiral N,N'-dioxide Nd Lewis acid complex.

Contra-Thermodynamic, Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two-Dimensional Chemical Space.

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z-α-substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp )-B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E-α-substituted styrenyl BPins to generate the corresponding Z-isomers with high fidelity.

Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2'-Bipyridine.

The synthesis, structural characterization, cytotoxicity, and antimicrobial properties of four new complexes formed by employing acrylate anion and 2,2'-bipyridine are reported herein. X-ray crystallography revealed the trinuclear nature of [Mn₃(2,2'-bipy)₂(C₃H₃O₂)₆] (), meanwhile complexes with general formula [M(2,2'-bipy)(C₃H₃O₂)₂(H₂O)]∙H₂O (() M: Ni, = 1, = 0; () M: Cu, = 1, = 0; () M: Zn, = 0, = 1; 2,2'-bipy: 2,2'-bipyridine; C₃H₃O₂: acrylate anion) were shown to be mononuclear. The lowest minimum inhibitory concentration (MIC) of 128 μg mL was recorded for all four tested complexes against , for complex () against , and for complex () against .

A highly fluorescent water soluble spirobifluorene dye with a large Stokes shift: synthesis, characterization and bio-applications.

The first water-soluble spirobifluorene derivative has been synthesized, which exhibits high fluorescence quantum yield and a large Stokes shift (>100 nm). Proteins induce changes in the emission color, allowing to reach the nanomolar detection limit. Cellular uptake and cytotoxicity studies in living cells revealed its biocompatibility, indicating potential application for live cell imaging.

Efficient Synthesis of Arylated Furans by a Sequential Rh-Catalyzed Arylation and Cycloisomerization of Cyclopropenes.

A novel and efficient strategy for the synthesis of arylated furans was successfully developed by a Rh -catalyzed coupling of N-phenoxyacetamides and cyclopropenyl esters. Mechanistic investigation reveals that the arylated furans are formed via arylation of the cyclopropenyl esters followed by cycloisomerization.

Manganese(I)-Catalyzed C-H (2-Indolyl)methylation: Expedient Access to Diheteroarylmethanes.

An unprecedented Mn -catalyzed (2-indolyl)methylation of heteroarenes is reported. This method makes use of an aromatizing cascade strategy to install a (2-indolyl)methyl group into target molecules, thereby leading to the expedient synthesis of previously challenging and important unsymmetrical diheteroarylmethanes, in particular bis(2-indolyl)methanes. The proposed cascade process comprises the reorganization of multiple bonds with controlled regioselectivity and high atom economy and can be performed on a gram-scale.

Reduction of Dioxygen by Radical/B(p-C F X) Pairs to Give Isolable Bis(borane)superoxide Compounds.

Triplet dioxygen was reduced by TEMPO or trityl radicals in the presence of two molar equivalents of the strong B(p-C F X) (X: F or H) boron Lewis acids under mild conditions to give the bis(borane)superoxide systems 2. The sensitive radical anion species were isolated and characterized by methods including X-ray crystal structure analysis and EPR spectroscopy.

C -Symmetric Tricyclo[2.2.1.0 ]heptane-3,5,7-triol.

A straightforward access to a hitherto unknown C -symmetric tricyclic triol both in racemic and enantiopure forms has been developed. Treatment of 7-tert-butoxynorbornadiene with peroxycarboxylic acids provided mixtures of C - and C -symmetric 3,5,7-triacyloxynortricyclenes via transannular π-cyclization and replacement of the tert-butoxy group. By refluxing in formic acid, the C -symmetric esters were converted to the C -symmetric formate.

Cyclobutyl-Containing Rigid Analogues of Threonine: Synthesis and Physical Chemical Properties.

Hitherto unknown cis- and trans-1-amino-3-hydroxy-3-methylcyclobutanecarboxylic acids were synthesized in multigram scale. The obtained compounds can be considered as achiral conformationally restricted analogues of threonine with fixed spatial orientation of functional groups. pK values are noticeably different for both amino acids.

Transition-Metal-Free Ring-Opening Silylation of Indoles and Benzofurans with (Diphenyl-tert-butylsilyl)lithium.

A practical method is presented for ring opening various indoles and benzofurans with concomitant stereoselective silylation using readily generated (diphenyl-tert-butylsilyl)lithium to afford ortho-β-silylvinylanilines or -phenols. Dearomatization of the heteroarene core proceeds in the absence of any transition-metal catalyst through addition of a silyl anion and a subsequent stereoselective β-elimination. DFT calculations provide insight into the mechanism.

Organocatalytic Asymmetric Synthesis of trans-γ-Lactams.

An N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective formal [3+2] reaction of o-hydroxy aromatic aldimines and cinnamaldehydes for the preparation of enantioenriched trans-γ-lactams was developed. An internal hydrogen bond between the o-hydroxy and the imine function was crucial for the reactivity and chemical selectivity. Trans-γ-lactam 3 d was easily oxidized to multifunctional 1,4-benzoquinone 8, which could further be transformed to biaryl 9 in the presence of a phosphoric acid.

A hydroboration route to geminal P/B frustrated Lewis pairs with a bulky secondary phosphane component and their reaction with carbon dioxide.

The secondary aryl-P(H) phosphanyl substituted tert-butylacetylenes 7a,b (aryl: Mes or Mes*) undergo hydroboration with [HB(CF)] to give the geminal vinylidene-bridged P/B Lewis pairs 8a,b. The treatment of 8a,b with benzonitrile, N-sulfinylaniline, and phenyl isothiocyanate, respectively, gives the addition products 12a,b, 13a,b, and 14 with proton transfer from the phosphorus to the more basic nitrogen site. The reaction of the FLPs 8a,b with carbon dioxide yields a doubly boron bonded addition product.

Redox-Neutral Manganese(I)-Catalyzed C-H Activation: Traceless Directing Group Enabled Regioselective Annulation.

A strategy is reported in which traceless directing groups (TDGs) are used to promote the redox-neutral Mn -catalyzed regioselective synthesis of N-heterocycles. Alkyne coupling partners bearing a traceless directing group, which serves as both the chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, with perfect regioselectivity.

Deconstructing the Catalytic, Vicinal Difluorination of Alkenes: HF-Free Synthesis and Structural Study of p-TolIF.

Recently, contemporaneous strategies to achieve the vicinal difluorination of alkenes via an I(I)/I(III) catalysis manifold were independently reported by this laboratory and by Jacobsen and co-workers. Both strategies proceed through a transient ArI(III)F species generated by oxidation of the ArI catalyst. Herein, an efficient synthesis of p-TolIF from p-TolI and Selectfluor is presented, together with a crystallographic and spectroscopic study.

Stereoselective synthesis of conformationally restricted KOR agonists based on the 2,5-diazabicyclo[2.2.2]octane scaffold.

It has been postulated that the KOR affinity depends on the dihedral angle of the ethylenediamine pharmacophore. Herein, 2,5-diazabicyclooctanes bearing a pyrrolidino moiety in the 7-position were envisaged to study KOR agonists with a conformationally rigid ethylenediamine pharmacophore and thus a defined N(pyrrolidine)-C7-C1-N2 dihedral angle. The first approach with an intramolecular addition at the chiral sulfinylimines 9 failed to give bicyclic products.

Design and reactions of a carbon Lewis base/boron Lewis acid frustrated Lewis pair.

The conjugated dienamine selectively adds Piers' borane [HB(CF)] to give the enamine/borane system , which features a boratirane structure by internal enamine carbon Lewis base to boron Lewis acid interaction. Compound behaves as a C/B frustrated Lewis pair and undergoes typical addition reactions to benzaldehyde, several nitriles and to sulfur dioxide.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.