A novel four-component reaction for the synthesis of functionalised dihydropyrimidines

In a multi-component reaction (MCR) of a phosphonate, nitriles, aldehydes and isocyanates, N3-functionalised dihydropyrimidines can be synthesised efficiently via a Horner-Emmons/aza Diels-Alder pathway.     

Sustainable Three‐Component Synthesis of Isothioureas from Isocyanides,Thiosulfonates, and Amines

Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable. We report a novel general approach towards S‐alkyl and S‐aryl isothioureas through a copper(I)‐catalyzed three‐component reaction between amines, isocyanides, and thiosulfonates. The formal synthesis of a superpotent sweetener further illustrates the applicability of our method.     

Base Metal Catalyzed Isocyanide Insertions

Isocyanides are diverse C₁ building blocks considering their potential to react with nucleophiles, electrophiles, and radicals. Therefore, perhaps not surprisingly, isocyanides are highly valuable as inputs for multicomponent reactions (MCRs) and other one‐pot cascade processes. In the field of organometallic chemistry, isocyanides typically serve as ligands for transition metals. The coordination of isocyanides to metal centers alters the electronic distribution of the isocyano moiety, and reaction pathways can therefore be accessed that are not possible in the absence of the metal. The tunable reactivity of the isocyanide functional group by transition metals has evolved into numerous useful applications. Especially palladium‐catalyzed isocyanide insertion processes have emerged as powerful reactions in the past decade. However, reports on the use of earth‐abundant and cheap base metals in these types of transformations are scarce and have received far less attention. In this Minireview, we focus on these emerging base metal catalyzed reactions and highlight their potential in synthetic organic chemistry. Although mechanistic studies are still scarce, we discuss distinct proposed catalytic cycles and categorize the literature according to 1) the (hetero)atom bound to and 2) the type of bonding with the transition metal in which the (formal) insertion occurs.     

In situ formation of allyl ketones via Hiyama-Nozaki reactions followed by a chromium-mediated Oppenauer oxidation

In Hiyama-Nozaki reactions of allylchromium with aldehydes the expected products are homoallylalcohols. However, oxidation products derived from these, predominantly allyl ketones, can be common side products. This can be explained by an Oppenauer-(Meerwein-Ponndorf-Verley)-type mechanism (OMPV-reaction). The amount of oxidation is strongly dependent on the substitution pattern of the reaction partners and the reaction conditions. An appropriate choice of these can lead to preferential formation of ketones instead of the alcohols. In addition to its synthetic usefulness, the oxidation-reduction equilibrium is of the utmost importance for the design of enantioselective Hiyama-Nozaki reactions because it is also a potential racemization pathway.     

An atom efficient and solvent-free synthesis of structurally diverse amides using microwaves

An array of structurally diverse amides was synthesized efficiently by combining (primary and secondary) amines and carboxylic acids in one-pot under solvent-free microwave (MW) conditions. In most cases, no racemization was observed with optically active inputs and chiral amides were obtained in high ee or de.     

The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin–West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal–organic frameworks.     

Fruit Wastes as a Valuable Source of Value-Added Compounds: A Collaborative Perspective

The by-products/wastes from agro-food and in particular the fruit industry represents from one side an issue since they cannot be disposed as such for their impact on the environment but they need to be treated as a waste. However, on the other side, they are a source of bioactive healthy useful compounds which can be recovered and be the starting material for other products in the view of sustainability and a circular economy addressing the global goal of “zero waste” in the environment. An updated view of the state of art of the research on fruit wastes is here given under this perspective. The topic is defined as follows: (i) literature quantitative analysis of fruit waste/by-products, with particular regards to linkage with health; (ii) an updated view of conventional and innovative extraction procedures; (iii) high-value added compounds obtained from fruit waste and associated biological properties; (iv) fruit wastes presence and relevance in updated databases. Nowadays, the investigation of the main components and related bioactivities of fruit wastes is being continuously explored throughout integrated and multidisciplinary approaches towards the exploitation of emerging fields of application which may allow to create economic, environmental, and social value in the design of an eco-friendly approach of the fruit wastes.     

Force constants of BN,SiC, AlN and GaN sheets through discrete homogenization

The force constants related to the bond stretching and angular variation of boron nitride, silicon carbide, aluminium nitride and gallium nitride nanosheets are directly evaluated from ab-initio reference solutions of the Young’s modulus and the Poisson’s ratio. To this end, the analytical expressions of the elastic constants of a generic monolayer hexagonal diatomic sheet are derived, starting from its sticks-and-springs molecular mechanics model, through proper tools of the homogenization of periodic discrete media. Numerical benchmark assessments are given.     

Multicomponent synthesis of dihydropyrimidines and thiazines

A broad range of differently substituted dihydropyrimidines and thiazines can be efficiently prepared by using a four-component reaction between phosphonates, nitriles, aldehydes, and iso(thio)cyanates. The scope and limitations of this multicomponent reaction are fully described. Variation of all four components has been investigated. The nitrile and aldehyde inputs can be varied extensively, but variation of the phosphonate input remains limited. An interesting rearrangement leading to phosphoramidates has been observed. Furthermore, the multicomponent reaction seems to be restricted to the use of isocyanates with strongly electron-withdrawing substituents, but an interesting additional exchange reaction under microwave conditions leads to dihydropyrimidines with less electron-withdrawing substituents at N3. In addition, a diastereoselective formation of dihydropyrimidines has been observed when using a chiral aldehyde as the input. Finally, by changing the isocyanate component to an isothiocyanate, thiazines are efficiently formed instead of the corresponding thio-dihydropyrimidines.