Ring-expansion approaches for the total synthesis of salimabromide

We describe the evolution of a synthetic strategy for the construction of the marine polyketide salimabromide. Combining a bicyclo[3.1.0]hexan-2-one ring-expansion to build up a functionalized naphthalene and an unprecedented rearrangement/cyclization cascade, enabled synthesis of a dearomatized tricyclic subunit of the target compound. Alternatively, an intramolecular keteniminium [2 + 2]-cycloaddition and subsequent Baeyer–Villiger ring-expansion gave access to the sterically encumbered architecture of salimabromide. Sequential oxidation of the carbon framework finally enabled the total synthesis of this unusual natural product.     

Reduction vs. Addition: The Reaction of an Aluminyl Anion with 1,3,5,7‐Cyclooctatetraene

The potassium aluminyl complex K[Al(NON^Ar)] (NON=NON^Ar=[O(SiMe₂NAr)₂]^2?, Ar=2,6‐iPr₂C₆H₃) reacts with 1,3,5,7‐cyclooctatetraene (COT) to give K[Al(NON^Ar)(COT)]. The COT‐ligand is present in the asymmetric unit as a planar μ₂‐η²:η⁸‐bridge between Al and K, with additional K???π‐aryl interactions to neighboring molecules that generate a helical chain. DFT calculations indicate significant aromatic character, consistent with reduction to [COT]^2?. Addition of 18‐crown‐6 causes a rearrangement of the C₈‐carbocycle to form the isomeric 9‐aluminabicyclo[4.2.1]nona‐2,4,7‐triene anion.     

Pd‐Catalyzed Selective Carbonylation of gem‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters

The first catalyst for the alkoxycarbonylation of gem‐difluoroalkenes is described. This novel catalytic transformation proceeds in the presence of Pd(acac)₂/1,2‐bis((di‐tert‐butylphosphan‐yl)methyl)benzene (btbpx) ( L4 ) and allows for an efficient and straightforward access to a range of difluoromethylated esters in high yields and regioselectivities. The synthetic utility of the protocol is showcased in the practical synthesis of a Cyclandelate analogue using this methodology as the key step.     

Introducing Perylene as a New Member to the Azaborine Family

Substitutional doping of perylene with two boron atoms at the 6b/12b positions and two oxygen or nitrogen atoms at the 1/7 positions has been achieved. The modular synthesis route developed for these bis‐BO‐ ( 3 ) and bis‐BN‐perylenes ( 5 ) starts from the readily accessible borinic acid derivative of the doubly brominated 9,10‐dihydro‐9,10‐diboraanthracene (DBA), 1,5‐Br₂DBA(OH)₂. A Stille‐type reaction first furnishes the alkynyl‐substituted species 1,5‐(RCC)₂DBA(OH)₂ ( 2 ), which undergo double ring closure to afford 3 via the gold‐catalyzed addition of the O?H bonds to the C≡C bonds. Treatment of 2 with MeN(SiMe₃)₂ leads to aminoborane intermediates 1,5‐(RCC)₂DBA(N(H)Me)₂, which can be ring‐closed to give 5 in a similar manner as in the case of 3 . Different substituents R (such as Me, tBuPh) can be introduced at the 2/8 positions of the perylene core. The products obtained undergo reversible reduction and are efficient blue/turquoise emitters.     

Steigerung der Wasseroxidation durch In‐situ‐Elektrokonversion eines Mangangallids: Ein intermetallischer Vorläuferansatz

Erstmals wurden, in einen intermetallischen Vorläuferansatz, durch In‐situ‐Elektrokonversion von Mangangallid (MnGa₄) hochleistungsfähige und langzeitstabile MnO_x‐basierte Elektrokatalysatoren für die Wasseroxidation in alkalischem Medium hergestellt. Überraschend führt seine Elektrokorrosion, unter gleichzeitigem Verlust von Ga, gleichzeitig zu drei kristallinen Typen von MnO_x‐Mineralien mit verschiedenen Strukturen und induzierten Defekten: Birnessit δ‐MnO₂, Feitknechtit β‐MnOOH und Hausmannit α‐Mn₃O₄. Das Vorkommen und die intrinsische Stabilität von aktiven Mn^III/Mn^IV‐Zentren in den drei gebildeten MnO_x‐Phasen erklärt die hervorragende Effizienz und Stabilität des Systems für die elektrokatalytische Wasseroxidation. Nach der elektrophoretischen Abscheidung des MnGa₄‐Vorläufers auf elektrisch leitfähigem Nickelschaum wurde ein niedriges Überpotential von 291 mV bei der Stromdichte von 10 mA cm^?2 erreicht, das praktisch den Überpotentialen von edelmetallbasierten Katalysatoren entspricht und für mehr als fünf Tage beständig ist.     

Covalent‐Allosteric Inhibitors to Achieve Akt Isoform‐Selectivity

Isoforms of protein kinase Akt are involved in essential processes including cell proliferation, survival, and metabolism. However, their individual roles in health and disease have not been thoroughly evaluated. Thus, there is an urgent need for perturbation studies, preferably mediated by highly selective bioactive small molecules. Herein, we present a structure‐guided approach for the design of structurally diverse and pharmacologically beneficial covalent‐allosteric modifiers, which enabled an investigation of the isoform‐specific preferences and the important residues within the allosteric site of the different isoforms. The biochemical, cellular, and structural evaluations revealed interactions responsible for the selective binding profiles. The isoform‐selective covalent‐allosteric Akt inhibitors that emerged from this approach showed a conclusive structure–activity relationship and broke ground in the development of selective probes to delineate the isoform‐specific functions of Akt kinases.     

Dimerisation of Dipiperidinoacetylene: Convenient Access to Tetraamino-1,3-Cyclobutadiene and Tetraamino-1,2-Cyclobutadiene Metal Complexes

The reaction of 1,2-dipiperidinoacetylene ( 1 ) with 0.5 equivalents of SnCl₂ or GeCl₂⋅dioxane afforded the 1,2,3,4-tetrapiperidino-1,3-cyclobutadiene tin and germanium dichloride complexes 2 a and 2 b , respectively. A competing redox reaction was observed with excess amounts of SnCl₂, which produced a tetrapiperidinocyclobutadiene dication with two trichlorostannate(II) counterions. Heating neat 1 to 110 °C for 16 h cleanly produced the dimer 1,3,4,4-tetrapiperidino-3-buten-1-yne ( 3 ); its reaction with stoichiometric amounts of SnCl₂ or GeCl₂⋅dioxane furnished the 1,3,4,4-tetrapiperidino-1,2-cyclobutadiene tin and germanium dichloride complexes 4 a and 4 b , respectively. Transition-metal complexes containing this novel four-membered cyclic bent allene (CBA) ligand were prepared by reaction of 3 with [(tht)AuCl], [RhCl(CO)₂]₂, and [(Me₃N)W(CO)₅] to form [(CBA)AuCl] ( 5 ), [(CBA)RhCl(CO)₂] ( 6 ), and [(CBA)W(CO)₅] ( 7 ). The molecular structures of all compounds 2 – 7 were determined by X-ray diffraction analyses, and density functional theory (DFT) calculations were carried out to rationalise the formation of 3 and 4 a .     

Structure–Solubility Relationship of 1,4-Dioxane Complexes of Di(hydrocarbyl)magnesium

Systematic variation of the 1,4-dioxane (dx) concentration during the precipitation of sparingly soluble [MgBr₂(dx)₂] from ethereal Grignard solutions of RMgBr has allowed the structural investigation of crystallized [R₂Mg(dx)_n] (n=1, 1.5, 2, and 3), which form during this dioxane method, depending on the bulkiness of R. The numbering of the complexes explored in this study is based on the number n of dioxane molecules per magnesium atom, followed by the substituent R; an apostrophe denotes coordination polymers. The following derivatives were studied by X-ray crystal-structure determination and NMR spectroscopy: n=1: [Me₂Mg(μ-dx)]_∞ ( 1′-Me ) and [nPr₂Mg(μ-dx)]_∞ ( 1′-nPr ); n=1.5: [{iPr₂Mg(dx)}₂(μ-dx)] ( 1.5-iPr ), [{oTol₂Mg(dx)}₂(μ-dx)] ( 1.5-oTol ), and [(Me₃Si-C≡C)₂Mg(dx)_1.5]_∞ ( 1.5′-C₂SiMe₃ ); n=2: [tBu₂Mg(dx)₂] ( 2-tBu ) and [oTol₂Mg(dx)₂] ( 2-oTol ); n=3: [Ph₂Mg(dx)₃] ( 3-Ph ). In the structure types 1′ , 1.5 , and 2 , the magnesium atom exhibits the coordination number 4, whereas pentacoordinate metal atoms are observed in types 3 and 1.5′ . The structure type 2′ is realized for [(Ph-C≡C)₂Mg(dx)₂]_∞ ( 2′-C₂Ph ), [MgCl₂(dx)₂]_∞ ( 2′-Cl ), and [MgBr₂(dx)₂]_∞ ( 2′-Br ) with hexacoordinate metal atoms. The solubility of the dioxane adducts in common organic solvents strongly depends on the degree of aggregation with the solubility decreasing from molecular to strand to layer structures.     

Chemoselectivity of Tertiary Azides in Strain-Promoted Alkyne-Azide Cycloadditions

The strain-promoted alkyne-azide cycloaddition (SPAAC) is the most commonly employed bioorthogonal reaction with applications in a broad range of fields. Over the years, several different cyclooctyne derivatives have been developed and investigated in regard to their reactivity in SPAAC reactions with azides. However, only a few studies examined the influence of structurally diverse azides on reaction kinetics. Herein, we report our investigations of the reactivity of primary, secondary, and tertiary azides with the cyclooctynes BCN and ADIBO applying experimental and computational methods. All azides show similar reaction rates with the sterically non-demanding cyclooctyne BCN. However, due to the increased steric demand of the dibenzocyclooctyne ADIBO, the reactivity of tertiary azides drops by several orders of magnitude in comparison to primary and secondary azides. We show that this chemoselective behavior of tertiary azides can be exploited to achieve semiorthogonal dual-labeling without the need for any catalyst using SPAAC exclusively.