In 1893, P. Biginelli reported the synthesis of functionalized 3, 4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea, and ethyl acetoacetate. In the past decade, this long-neglected multicomponent reaction has experienced a remarkable revival, mainly due to the interesting pharmacological properties associated with this dihydropyrimidine scaffold. In this Account, we highlight recent developments in the Biginelli reaction in areas such as solid-phase synthesis, combinatorial chemistry, and natural product synthesis.

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Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog.

Utilisation of 1,3‐Dicarbonyl Derivatives in Multicomponent Reactions

Recent developments in the chemistry of enaminones

Multicomponent reactions have gained significant importance as a tool for the synthesis of a wide variety of useful compounds, including pharmaceuticals. In this context, the multiple component approach is especially appealing in view of the fact that products are formed in a single step, and the diversity can be readily achieved simply by varying the reacting components. The eco-friendly, solvent-free multicomponent approach opens up numerous possibilities for conducting rapid organic synthesis and functional group transformations more efficiently. Additionally, there are distinct advantages of these solvent-free protocols since they provide reduction or elimination of solvents thereby preventing pollution in organic synthesis “at source”. The chemo-, regio- or stereoselective synthesis of high-value chemical entities and parallel synthesis to generate a library of small molecules will add to the growth of multicomponent solvent-free reactions in the near future. In this review we summarized the results reported mainly within the last 10 years. It is quite clear from the growing number of emerging publications in this field that the possibility to utilize multicomponent technology allows reaction conditions to be accessed that are very valuable for organic synthesis. Therefore, diversity oriented synthesis (DOS) is rapidly becoming one of the paradigms in the process of modern drug discovery. This has spurred research in those fields of chemical investigation that lead to the rapid assembly of not only molecular diversity, but also molecular complexity. As a consequence multi-component as well as domino or related reactions are witnessing a new spring.

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Recent developments in solvent-free multicomponent reactions: a perfect synergy for eco-compatible organic synthesis

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: 
wherein M is N or CR 4 ; Q 1 and Q 2 are each independently selected from the group consisting of CO, SO, SO 2 , and C═NR 9 ; and each L, X, R 1 , R 2 , and R 3 are as defined herein.

Dipeptidyl peptidase inhibitors

A synthetic entry into fused pyran derivatives through carbon transfer reactions of 1,3-oxazinanes and oxazolidines with carbon nucleophiles

An expedient protocol of the Biginelli dihydropyrimidine synthesis using carbonyl equivalents

Carbon transfer reactions of functionalized oxazolidines and their open chain enamine tautomers to enamine nucleophiles. A facile synthesis of substituted pyridines and ring annulated derivatives

A novel synthesis of functionalized aldehyde equivalents through addition of carbanions on Δ2-oxazolinium cations☆

Acid catalysed condensations of various 2 substituted 1,3-oxazinanes 3 and 1,3-oxazolidines 4 with cyclic carbon nucleophiles viz. 5,5-dimethyl-1,3-cyclohexanedione and 1,3-cyclohexanedione furnish xanthene derivatives, whereas a Knoevenagel reaction proceeds with acyclic nucleophiles. In case of 4b and 4c, a unique synthesis of functionalised α-tetralones has emerged. Reactions of mixtures of cyclic and acyclic carbon nucleophiles with 3 provide some functionalised and partially reduced benzopyran derivatives.

Jasbir Singh

Papers

A synthetic entry into fused pyran derivatives through carbon transfer reactions of 1,3-oxazinanes and oxazolidines with carbon nucleophiles

An expedient protocol of the Biginelli dihydropyrimidine synthesis using carbonyl equivalents

Carbon transfer reactions of functionalized oxazolidines and their open chain enamine tautomers to enamine nucleophiles. A facile synthesis of substituted pyridines and ring annulated derivatives

A novel synthesis of functionalized aldehyde equivalents through addition of carbanions on Δ2-oxazolinium cations☆

A Synthetic Entry into Fused Pyran Derivatives Through Carbon Transfer Reactions of 1,3‐Oxazinanes and Oxazolidines with Carbon Nucleophiles.