Total Synthesis and Characterization of 7-Hypoquinuclidonium Tetrafluoroborate and 7-Hypoquinuclidone BF_3 Complex

Derivatives of the fully twisted bicyclic amide 7-hypoquinuclidone are synthesized using a Schmidt–Aubé reaction. Their structures were unambiguously confirmed by X-ray diffraction analysis and extensive spectroscopic characterization. Furthermore, the stability and chemical reactivity of these anti-Bredt amides are investigated. 7-Hypoquinuclidonium tetrafluoroborate is shown to decompose to a unique nitrogen bound amide–BF_3 complex of 7-hypoquinuclidone under anhydrous conditions and to react instantaneously with water making it one of the most reactive amides known to date

An Efficient Protocol for the Palladium-Catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst

Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2-allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and piperazinones has been previously reported by our laboratory. The efficient construction of chiral all-carbon quaternary centers by allylic alkylation was previously achieved with a catalyst derived in situ from zero-valent palladium sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved reaction protocol with broad applicability among different substrate classes in industry-compatible reaction media using loadings of palladium(II) acetate as low as 0.075 mol% and the readily available chiral PHOX ligands. The novel and highly efficient procedure enables facile scale-up of the reaction in an economical and sustainable fashion

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge

Climate scenarios for Switzerland CH2018 - approach and implications

To make sound decisions in the face of climate change, government agencies, policymakers and private stakeholders require suitable climate information on local to regional scales. In Switzerland, the development of climate change scenarios is strongly linked to the climate adaptation strategy of the Confederation. The current climate scenarios for Switzerland CH2018 - released in form of six user-oriented products - were the result of an intensive collaboration between academia and administration under the umbrella of the National Centre for Climate Services (NCCS), accounting for user needs and stakeholder dialogues from the beginning. A rigorous scientific concept ensured consistency throughout the various analysis steps of the EURO-CORDEX projections and a common procedure on how to extract robust results and deal with associated uncertainties. The main results show that Switzerland?s climate will face dry summers, heavy precipitation, more hot days and snow-scarce winters. Approximately half of these changes could be alleviated by mid-century through strong global mitigation efforts. A comprehensive communication concept ensured that the results were rolled out and distilled in specific user-oriented communication measures to increase their uptake and to make them actionable. A narrative approach with four fictitious persons was used to communicate the key messages to the general public. Three years after the release, the climate scenarios have proven to be an indispensable information basis for users in climate adaptation and for downstream applications. Potential for extensions and updates has been identified since then and will shape the concept and planning of the next scenario generation in Switzerland

Ring-Closing Metathesis Approaches towards the Total Synthesis of Rhizoxins

Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ring-closure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) E double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.ISSN:1420-304

Sequential Ruthenium Catalysis for Olefin Isomerization and Oxidation: Application to the Synthesis of Unusual Amino Acids

How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by <i>in situ</i> transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α-tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam

Unprecedented Reactivity of Iridium(I) Secondary Phosphine Oxide Complexes: Formation of P-Coordinated Phosphinate Complexes by P−Aryl Bond Cleavage

Aryl−iridium(III) hydride complexes with a P-coordinated phosphinate were formed from [Ir(cod)Cl]2 and secondary phosphine oxide−oxazoline ligands under basic conditions. The structure of these complexes, whose formation involved C−P cleavage, was assigned by X-ray analysis and NMR spectroscopy

Sequential Ruthenium Catalysis for Olefin Isomerization and Oxidation: Application to the Synthesis of Unusual Amino Acids

How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by <i>in situ</i> transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α-tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam

Total Synthesis of Hygrolines and Pseudohygrolines

A concise two-step synthesis of all four diastereoisomeric hygrolines ((−)-hygroline (<b>1</b>), (+)-hygroline (<b>2</b>), (−)-pseudohygroline (<b>3</b>), (+)-pseudohygroline (<b>4</b>)) has been developed based on the (−)-sparteine (<b>5</b>)- or (+)-sparteine surrogate <b>11</b>-mediated enantioselective lithiation of <i>N</i>-Boc pyrrolidine (<b>6</b>), followed by reaction of the chiral anion with (<i>S</i>)- or (<i>R</i>)-propylene oxide. Reduction of the resulting <i>N</i>-Boc amino alcohols furnished hygrolines and pseudohygrolines in 30% to 56% overall yields with <i>dr</i>’s > 95:5