Helvetica Chimica Acta最新文献

With the unique ability to cleave and form an extensive range of carbon–carbon double and triple bonds, alkene and alkyne metathesis advanced to a preferred strategy for the synthesis of natural products. Furthermore, metathesis is ideally suited for cascade reactions and, if well-defined chiral catalysts are employed, even for enantioselective transformations. However, while alkene and alkyne metathesis are frequently employed in the preparation of naturally occurring structures, the ring-opening metathesis of arenes, which are prevalent in natural compounds, is not yet established as avenue for natural product total synthesis. Herein, we now describe that aromatic ring-opening metathesis (ArROM) allows particularly short and efficient total syntheses of aromatic natural products. Moreover, by atroposelective ArROM, synthetic access to naturally occurring biphenanthrene atropisomers was possible with outstanding stereoselectivity, allowing to corroborate unusual differences in their configurational stability under ambient light.

In addition to being a natural fragrance and EU/WHO-approved food additive, the bicyclic monoterpene trans-pinocarveol (TPC) is a versatile chiral building block for the generation of societally important small molecules. Selective oxidation strategies that leverage α-pinene constitute the most direct and sustainable routes to access this target, where they remain in the vanguard of contemporary approaches to generate molecular complexity from this chiral pool resource. However, the subsequent isomerization of α-pinene oxide (APO) to TPC is complicated by competing 1,2-alkyl shifts leading to inevitable for action of various monocyclic products. Motivated by this challenge, an operationally simple protocol to enable the efficient isomerization of APO to TPC is disclosed that leverages inexpensive pyridinium halides as catalysts. This enabling strategy can be performed on a decagram scale, and catalyst recycling is demonstrated through the deployment of HBr-treated commercial 4-polyvinylpyridine.

Medicinal chemistry requires the exploration of structurally diverse compound families to expand the repertoire of bioactive small molecule drugs. Here we investigated the potential of spirocycles with ring sizes four to eight carrying a primary or secondary amine in each ring as drug scaffolds. We found that 285 of these 391 spirocyclic diamines were not listed in PubChem and therefore possibly new. Their structural diversity was evidenced by the very low Tanimoto similarity between scaffolds and the presence of up to three stereocenters per scaffold, raising numbers to 1381 possible stereoisomers. To exemplify their use, we prepared four novel spirocyclic diamines containing azepane or azocane rings and tested their activities as inhibitors of potassium channels, neurotransmitter transporters, and muscarinic acetylcholine receptors (mAChR). We identified a single enantiomeric unsubstituted spirocyclic diamine as a micromolar inhibitor of the M4 mAChR.

Porphyrin atropisomerism is an outstanding tool for the accessibility of shape-specific molecules, yet over 20 years after the unusual rotational barriers of nonplanar porphyrins were observed, a quantitative relationship remains at large. There is a growing need to control this phenomenon in nonplanar porphyrin systems due to the mounting interest in these systems as enzyme mimics and organocatalysts. Hence, in this work, the influence of steric bulk on the stability of nonplanar 5,10,15,20-tetraaryl-2,3,7,8,12,13,17,18-octaethyl-porphyrin atropisomers was explored. The library of atropisomeric porphyrins synthesized herein emphasizes the delicate balance that must be achieved between steric bulk without inducing an undesired amount of macrocycle flexibility to obtain an atropisomer with a predictable rotational barrier. To overcome this challenge, a stabilization strategy was devised by exploiting metal coordination to the peripheral porphyrin functionalities, leading to an atroposelective superstructure formation.

Precise tuning of pore chemistry in three-dimensional porous organic polymers (3D-POPs) is critical for high-performance gas (CO₂)-separation. Here, we demonstrate the impact of functional groups on the dioxin-linked 3D-tPOPs bearing a tetraphenylene core, synthesized under solvothermal conditions using NaCl as a template, on the low- and high-pressure CO₂ uptake. The post-synthetic amidoxime functionalization of 3D-tPOPs, involving the reaction of pendant nitrile moieties with hydroxylamine hydrochloride, has been shown to precisely tailor pore chemistry without altering the network structure. Whereas the incorporation of the amidoxime moieties, 3D-tPOP-AO, enables higher heteroatom content, a critical factor to enhance CO₂ affinity at low pressures, strong hydrogen bonding interactions between amidoxime units limit framework flexibility, thus leading to a significant decrease in the high-pressure gas uptake. 3D-tPOPs on the other hand showed a high CO₂ uptake capacity of 57.4 wt% at 33 bar and 270 K; after modification, CO₂ uptake capacity decreased to 19.4 wt% at 273 K and 34 bar. Similarly, CH₄ uptake capacity also decreased from 14.0 wt% at 116 bar and 270 K to 3.8 wt% at 75 bar and 273 K. These findings highlight the critical role of the interactions between functional groups and pore chemistry to form robust adsorbents with high CO₂ uptake performance at high pressures.

The C(sp³)─H allylation reaction using allyl phenyl sulfone was affected by persulfate anion (PS) under microwave (MW) irradiation. The MW/PS protocol has been found to be applicable to a wide variety of C(sp³)─H bonds of ethers, alkanes, aldehydes, and ketones, leading to the C(sp³)─H allylated compounds. The origin of the site-selectivity in the allylation of cyclohexanone is discussed in terms of the polarity-governed transition states for the radical cascades involving hydrogen atom transfer (HAT), radical addition, and β-elimination.

Reactions of the Lewis acidic, cationic bismuth compound [BiMe₂(SbF₆)] (1) with the spin trap α-phenyl-N-tertbutyl-nitrone (PBN) yield simple Lewis acid/base adducts [BiMe₂(PBN)(SbF₆)] (2) and [BiMe₂(PBN)₂][SbF₆] (3). Such adducts have, for the first time, been fully characterized for the frequently used spin trap PBN. The ability of 2 and 3 to release PBN-trapped methyl radicals under thermal conditions is investigated. This is compared to the ability of a small series of simple neutral organobismuth compounds BiR₃ (R = Me, nBu, iPr, tBu, CF₃) and one mixed aryl/alkyl-substituted bismuth complex to transfer carbon-based radicals to PBN. Applied analytical techniques include NMR spectroscopy, elemental analysis, mass spectrometry, single-crystal X-ray diffraction analysis, and EPR spectroscopy.