A Sustainable Multicomponent Pyrimidine Synthesis

Abstract

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.

Manganese‐Catalyzed Multicomponent Synthesis of Pyrimidines from Alcohols and Amidines

“…Notably,both Ir [7] and Mn complexes catalyze the two distinct reactions (BH/HA and ADC) efficiently under similar reaction conditions.C oc omplexes stabilized by such ligands are nearly inactive in the ADC step.T he (double) diagonal relationship Mn-Ru-Ir could be an explanation for the analogous catalytic reactivity between Mn and Ir observed here.C onsidering the many applications of Ir catalysts in (de)hydrogenation reactions,w ef eel that manganese has ag reat potential to partially replace Ir in such reactions. In combination with the b-alkylation of secondary alcohols by primary alcohols,ar eaction that has not yet been described for Mn catalysts,aconsecutive 4component process was developed to give fully substituted pyrimidines in ao ne-pot procedure.B oth multicomponent methods are strong regarding the synthesis of selectively alkylated and arylated products.P recatalysts stabilized by PN 5 Pligands (triazine backbone) are about twice as efficient as those stabilized by PN 3 Pl igands (pyridine backbone).…”

“…[1] Alcohols can be obtained from indigestible and abundantly available lignocellulose biomass, [2,3] and thus the development of alcohol re-functionalization reactions can contribute to the conservation of our fossil carbon resources and the reduction of CO 2 emissions.A variety of reactions have been developed recently to catalytically synthesize aromatic N-heterocyclic compounds,s uch as pyrroles, [4,5] pyridines, [6] pyrimidines, [7] and others, [8] from alcohols. [1] Alcohols can be obtained from indigestible and abundantly available lignocellulose biomass, [2,3] and thus the development of alcohol re-functionalization reactions can contribute to the conservation of our fossil carbon resources and the reduction of CO 2 emissions.A variety of reactions have been developed recently to catalytically synthesize aromatic N-heterocyclic compounds,s uch as pyrroles, [4,5] pyridines, [6] pyrimidines, [7] and others, [8] from alcohols.…”

“…Amore sustainable approach would be the use of catalysts based on abundantly available 3d metals,s uch as Co,F e, and Mn (nonprecious or base metals), to additionally conserve our rare noble metal resources.M ilstein and co-workers recently introduced ac obalt-catalyzed synthesis of pyrroles from diols and amines [10] (Scheme 1, top). [11] We recently introduced av ariety of nonprecious metal catalysts for reactions involving (de)hydrogenation steps [11d, 12-15] and report here on am anganese-catalyzed version of the multicomponent reaction of alcohols and amidines to form pyrimidines [7] (Scheme 1, bottom). [5a] Thenonprecious metal manganese,the third most abundant metal in the earthscrust, has been overlooked in recent years with regard to catalysis involving a( de)hydrogenation step.…”

Manganese‐Catalyzed Sustainable Synthesis of Pyrroles from Alcohols and Amino Alcohols

“…It would be highly desirable to combine both sustainability concepts and develop catalysts based on abundantly available transition metals,s uch as Mn, Fe,a nd Co (base or nonprecious metals), for the conversion of alcohols into N-heterocycles. [15] Efficient hydrogenation and dehydrogenation catalysis with Mn has only been reported very recently. [12] Kirchner and co-workers [13] and our group [14] described aM n-complex-catalyzed multicomponent synthesis of pyrimidines from up to three different alcohols and amidines, ar eaction originally developed by our group with Ir catalysts.…”

Single-catalyst high-weight% hydrogen storage in an N-heterocycle synthesized from lignin hydrogenolysis products and ammonia

“…of H 2 (ref. 20). Based on this concept of alcohol-to-heterocycle conversion, it seems feasible to develop a reaction that converts key building blocks of the overabundant and indigestible biomass lignin to N -heterocycles suitable for reversible high-wt% hydrogen storage.…”