The borrowing hydrogen or hydrogen autotransfer methodology is an elegant and sustainable or green concept to construct carbon-carbon bonds. In this concept, alcohols, which can be obtained from barely used and indigestible biomass, such as lignocellulose, are employed as alkylating reagents. An especially challenging alkylation is that of unactivated esters and amides. Only noble metal catalysts based on iridium and ruthenium have been used to accomplish these reactions. Herein, we report on the first base metal-catalyzed α-alkylation of unactivated amides and esters by alcohols. Cobalt complexes stabilized with pincer ligands, recently developed in our laboratory, catalyze these reactions very efficiently. The precatalysts can be synthesized easily from commercially available starting materials on a multigram scale and are self-activating under the basic reaction conditions. This Co catalyst class is also able to mediate alkylation reactions of both esters and amides. In addition, we apply the methodology to synthesize ketones and to convert alcohols into aldehydes elongated by two carbon atoms.

The development of catalytic reactions for synthesizing different compounds from alcohols to save fossil carbon feedstock and reduce CO emissions is of high importance. Replacing rare noble metals with abundantly available 3d metals is equally important. We report a manganese-complex-catalyzed multicomponent synthesis of pyrimidines from amidines and up to three alcohols. Our reaction proceeds through condensation and dehydrogenation steps, permitting selective C-C and C-N bond formations. β-Alkylation reactions are used to multiply alkylate secondary alcohols with two different primary alcohols to synthesize fully substituted pyrimidines in a one-pot process. Our PN P-Mn-pincer complexes efficiently catalyze this multicomponent process. A comparison of our manganese catalysts with related cobalt catalysts indicates that manganese shows a reactivity similar to that of iridium but not cobalt. This analogy could be used to develop further (de)hydrogenation reactions with manganese complexes.

Since alcohols are accessible from indigestible biomass (lignocellulose), the development of novel preferentially catalytic reactions in which alcohols are converted into important classes of fine chemicals is a central topic of sustainable synthesis. Multicomponent reactions are especially attractive in organic chemistry as they allow the synthesis of large libraries of diversely functionalized products in a short time when run in a combinatorial fashion. Herein, we report a novel, regioselective, iridium-catalyzed multicomponent synthesis of pyrimidines from amidines and up to three (different) alcohols. This reaction proceeds via a sequence of condensation and dehydrogenation steps which give rise to selective C-C and C-N bond formations. While the condensation steps deoxygenate the alcohol components, the dehydrogenations lead to aromatization. Two equiv of hydrogen and water are liberated in the course of the reactions. PN5P-Ir-pincer complexes, recently developed in our laboratory, catalyze this sustainable multicomponent process most efficiently. A total of 38 different pyrimidines were synthesized in isolated yields of up to 93%. Strong points of the new protocol are its regioselectivity and thus the immediate access to pyrimidines that are highly and unsymmetrically decorated with alkyl or aryl substituents. The combination of this novel protocol with established methods for converting alcohols to nitriles now allows to selectively assemble pyrimidines from four alcohol building blocks and 2 equiv of ammonia.

Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an α,N-fused 2-pyridone, an endo- or exo-α,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular "inside-out" approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C -symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the α,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es.

Charakteristischf ürB ischinolizidin-Alkaloidei st ein chirales .1]nonan), an das Kombinationen aus einem a,N-anellierten 2-Pyridon, endo-oder exo-a,N-anellierten Piperidin(on)en und einem exo-Allylsubstituenten angebrachts ind. Wire ntwickelten eine modulare "Inside-Out"-Strategie,die einen Zugang zu den meisten Vertretern dieser Naturstoffklasse erlaubt. Ihr Anwendungspotential wurde anhand der asymmetrischen Synthese von 21 Bischinolizidin-Naturstoffen demonstriert, darunter mehr als zehne nantioselektive Erstsynthesen. Schlüsselschritte sind die erste erfolgreicheH erstellung beider Enantiomere von C 2 -symmetrischem 2,6-Dioxobispidin durch Desymmetrisierung einer 2,4,6,8-Tetraoxo-Vorstufe,d er Aufbau des a,N-anellierten 2-Pyridons über eine Enamin-Bromacrylsäure-Strategie und die Einführung von endo-oder, wahlweise,exo-anellierten Piperidin(on)en. 2018W iley-VCH Verlag GmbH &C o. KGaA, Weinheim Angew.C hem. 2018, 130,2 456 -2460Schema 1. Retrosynthese der Bischinolizidin-Naturstoffe. Nur eines der beiden enantiomeren Bispidin-Kerngerüste ist abgebildet.Schema 2. Synthese des chiralen Schlüsselintermediats 8 und die Rçntgenkristallstrukturenvon 11 und 12.[13] DEAD = Diethylazodiacarboxylat, ADDP = 1,1'-(Azodicarbonyl)dipiperidin, TFA = Trifluoressigsäure, Boc = tert-Butoxycarbonyl.Schema 3. Anellierungvon 8 zum tricyclischen Schlüsselintermediat 7. Piv = Pivaloyl.Schema 4. Tricyclische Bischinolizidin-Naturstoffe 18-23 aus 7.

Die Entwicklung von neuartigen, vorzugsweise katalytischen Reaktionen, um Verbindungsklassen ausgehend von Alkoholen herzustellen, ist von hoher Bedeutung,d as ie zur Erhaltung der fossilen Kohlenstoffressourcen und zur Reduktion von CO 2 -Emissionen beiträgt. Um die extrem seltenen Edelmetallressourcen zu schonen, ist der Ersatz von seltenen Metallen wie Ir,Rhoder Pt durchbreit verfügbare 3d-Metalle in Schlüsseltechnologien wie der Katalyse ebenso wichtig.W ir berichten hier über eine durch einen Mangankomplex katalysierte Version der Mehrkomponentensynthese von Pyrimidinen aus Amidinen und drei (unterschiedlichen) Alkoholen. Die Reaktion verläuft über Kondensations-und Dehydrierungsschritte,w as selektive C-C-und C-N-Bindungsknüpfungen erlaubt. Wir nutzen selektive b-Alkylierungen, um sekundäre Alkohole mehrfach mit unterschiedlichen primären Alkoholen zu alkylieren, um vollständig substituierte Pyrimidine in einem Eintopfprozess zu synthetisieren. PN 5 P-Mn-Pincer-Komplexe, die in unserem Labor entwickelt wurden, katalysieren diesen nachhaltigen Mehrkomponentenprozess am effizientesten. Ein Vergleichunserer Mangankomplexemit verwandten Cobaltkomplexen zeigt, dass Mangan der katalytischen Reaktivitätv on Iridium nahekommt, Cobalt jedoch nicht. Wire rwarten, dass diese Analogie dazu genutzt werden kann, weitere katalytischeA nwendungen von Mangankomplexen zu entwickeln, bei denen Hydrierungs-oder Dehydrierungsschritte involviert sind. Hintergrundinformationen zu diesem Beitrag sind unter: http://dx.

A Sustainable Multicomponent Pyrimidine Synthesis. -An Ir-catalyzed three--component coupling of a secondary alcohol, a primary alcohol, and an amidine is established to give a variety of tri-and tetrasubstituted pyrimidines. A stepwise four--component protocol applying two different primary alcohols offers a similar entry to tetrasubstituted pyrimidines as well. -(DEIBL, N.; AMENT, K.; KEMPE*, R.; J. Am. Chem. Soc. 137 (2015) 40, 12804-12807, http://dx.doi.org/10.1021/jacs.5b09510 ; Anorg. Chem. II, Univ. Bayreuth, D-95440 Bayreuth, Germany; Eng.) -Mais

A modular “inside‐out” approach to 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses, is reported by M. Breuning et al. in their Communication on page 2432 ff. Key was the successful preparation of both enantiomers of C2‐symmetric 2,6‐dioxobispidine by desymmetrization and the successive α,N‐annulation of a 2‐pyridone and endo‐ or exo‐fused piperidines to the chiral core building block.