Formaldehyde in multicomponent reactions

Multicomponent reactions (MCRs) have undoubtedly emerged as the most indispensable tool for organic chemists worldwide, finding extensive utility in the synthesis of intricate natural products, heterocyclic molecules with significant bioactivity, and pharmaceutical agents. The multicomponent one-pot 1,3-dipolar cycloaddition reactions, which were initially conceptualized by Rolf Huisgen in 1960, find extensive application in contemporary heterocyclic chemistry. In terms of green synthesis, the multicomponent 1,3-dipolar cycloaddition is highly favored owing to its numerous advantages, including high step- and atom-economies, remarkable product diversity, as well as excellent efficiency and diastereoselectivity. Among the numerous pieces of research, the most fascinating reaction involves the utilization of azomethine ylides generated from isatins and amino acids that can be captured by various dipolarophiles. This approach offers a highly efficient and convenient method for constructing spiro-pyrrolidine oxindole scaffolds, which are crucial building blocks in biologically active molecules. Consequently, this review delves deeper into the dipolarophiles utilized in the 1,3-dipolar cycloaddition of isatins and amino acids over the past six years.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAllenamides: A Powerful and Versatile Building Block in Organic SynthesisTing Lu†, Zhenjie Lu†, Zhi-Xiong Ma†, Yu Zhang*‡, and Richard P. Hsung*†View Author Information† Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, United States‡ Discovery Research, Dow AgroSciences LLC, Indianapolis, Indiana 46268, United States*E-mail: [email protected] (Y.Z.); [email protected] (R.P.H.).Cite this: Chem. Rev. 2013, 113, 7, 4862–4904Publication Date (Web):April 4, 2013Publication History Received14 January 2013Published online4 April 2013Published inissue 10 July 2013https://pubs.acs.org/doi/10.1021/cr400015dhttps://doi.org/10.1021/cr400015dreview-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views12321Altmetric-Citations308LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Amides,Cyclization,Isomerization,Propargyls Get e-Alerts

Efficient multicomponent processes for synthesis of novel poly-nuclear hetero aryl substituted terpyridine scaffolds: Single crystal XRD study

Vinyl MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

We introduce a novel versatile phosphoramidite building block for the modification of oligonucleotides (ONs) with acyl hydrazides on the 5′- or 3′-terminus, or both. The reaction of these hydrazide functionalized ONs with 4-methoxyphenylaldehyde is demonstrated for solution derivatization. Hydrazides are considered nowadays as promising reactants, which show enhanced reactivity at neutral and slightly acidic conditions and higher stability of yielding products as compared to the aliphatic amines, which are broadly used for ONs derivatization. Our method to introduce hydrazides into ONs employs a phosphoramidite modifier designed to split, during ammonia or lithium hydroxide treatment, into two hydrazides via β-elimination of a central bis-2-carbonylethoxysulfone unit. It allows the creation of ONs derivatized with a hydrazide moiety at the 5′-, 3′- and both 5′- and 3′-termini, as well as two different hydrazide containing ONs at the same time, viz. in one sequence on the same solid support. In latter case one can, for example, synthesize two hydrazide containing ONs, where one is 5′-modified and second one is 3′-modified. This work was supported by German Research Council (DFG) and the Federal Ministry of Education and Research (BMBF, Germany). S.I. Antsypovich gratefully acknowledges a stipend and his fellowship from German Academic Exchange Service (DAAD) and Alexander von Humboldt Foundation (AvH-Stiftung, Germany), respectively.

Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent reactions or other chemistries, aiding in the creation of a variety of complex, drug-like molecules. These innovative tetrazole building blocks are efficiently and directly synthesized using a Passerini three-component reaction (PT-3CR), employing cost-effective and readily available materials. We further showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes. It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods.

A new multidentate bifunctional organic ligand – di-N,N′-(2-cyano-2-oximinoacetyl)piperazine – was synthesized in high yield using a two-step procedure carried out under ambient conditions. At first, the reaction of piperazine and neat methylcyanoacetate led to the di-N,N′-(cyanoacetyl)piperazine (1), which then was converted into bis-cyanoxime, di-N,N′-(2-cyano-2-oximinoacetyl)piperazine (HL, 2) using a room temperature nitrosation reaction with gaseous methylnitrite. Synthesized bis-cyanoxime was characterized by 1H, 13C NMR, UV-visible, IR spectroscopy and the X-ray analysis. The ligand 2 exists as a mixture of three diastereomers arising from the syn- and anti-geometry of the cyanoxime group. The prolonged crystallization of 2 from an ethanol–water mixture leads to the formation of: (a) colorless crystals that according to the X-ray analysis contain a 51.2:48.8% co-crystallized mixture of both isomers that have the same H-bonding motif (minority), and (b) a white amorphous material that represents an almost pure anti-isomer (majority). The deprotonation of 2 leads to the formation of a yellow dianion that demonstrated pronounced solvatochromism of its n → π* transition in the nitroso-chromophore. The disodium salt Na2L·4H2O (3) was obtained from 2 using NaOC2H5 in ethanol. The new bis-cyanoxime 2 reacts with Tl2CO3 and AgNO3 in aqueous solutions with the formation of light-stable, sparingly soluble yellow precipitates of M′2L·xH2O composition (M′ = Tl, Ag; Tl = 4, x = 0; Ag = 5, x = 2). The reaction of 3 with Ni2+ or K2M′′Cl4 (M′′ = Pd, Pt) in aqueous solutions leads to NiL·4H2O (6), PdL·4H2O (7) and PtL·5H2O (8). The crystal structure of 4 was determined and revealed the formation of a 3D-coordination polymeric complex in which the bis-cyanoxime acts as a dianionic, bridging, formally decadentate ligand. Each Tl(I) center has two bonds (2.655, 2.769 Å), shorter than the sum of ionic radii Tl–O (oxime group), and three longer, >2.89 Å, mostly electrostatic Tl···O contacts, involving oxygen atoms of the amide-group and the oxime-group of neighboring units. Among several possible binding modes, the coordination of the bis-cyanoxime dianion of 2 adopted in complex 4 is unusual, and evidenced its great potential as a versatile building block for coordination and supramolecular chemistry.

The extensive use of cyclic compounds in many fields encourages the efficient construction of this class of compounds. Tandem reactions provide easy access to cyclic compounds because of their simple procedures, high efficiency, and superior atom economy. 2-Alkynylbenzaldehyde is a versatile and powerful building block for generating functionalized polycyclic compounds, especially heterocycles, by tandem reactions. This Focus Review discusses recent advances in using 2-alkynylbenzaldehydes as starting materials in the preparation of diverse and complex cyclic compounds. The progress that has been made provides important protocols for the design of more complex compounds and total syntheses of natural products.

1-Azadienes are versatile building blocks for the efficient construction of various N-heterocycles. Depending on the substitution pattern and reaction partner, they may participate in a range of different reactions. An overview of recent methods for the generation of 1-azadienes is presented, as well as their application in cycloaddition, electrocyclization, and multicomponent reactions. Considering the broad range of reactivities and resulting heterocyclic scaffold structures, 1-azadienes are very useful reactive intermediates for the development of modular reaction sequences in diversity-oriented synthesis.

Cyanoacetohydrazide, a versatile building block containing both nucleophilic and electrophilic sites, was exploited to develop new pyridine and chromene derivatives bearing a 4-hydroxy-3-ethoxyphenyl moiety. A series of nitrogen- and oxygen-based heterocycles were generated through multicomponent synthetic approaches using diverse aromatic aldehydes, malononitrile, ethyl cyanoacetate, and salicylaldehyde. Proposed reaction mechanisms involved sequential steps, including Knoevenagel condensation, Michael addition, and intramolecular cyclization. Structural identities of the obtained. IR and NMR spectroscopy, together with elemental analysis, supported the proposed chemical structures of the compounds, all of which verified the expected functional groups and ring frameworks. The incorporation of ethylvanillin as a primary aldehyde source enhanced the pharmacophoric potential of the final molecules. The developed procedures furnished regioselective products in excellent yields under mild conditions. Overall, the findings highlight the applicability of cyanoacetohydrazide in constructing complex heterocyclic frameworks, offering promising scaffolds for future studies in medicinal chemistry, drug design, and functional materials. These findings offer a strong basis for additional biological analysis of the produced substances.

This article describes a design and synthesis of new and versatile chiral building blocks and its application to the biologically active natural product synthesis. The chiral building blocks were prepared using a biocatalysis in an enantiomerically pure state. As an application of the above chiral building blocks to the synthesis of biologically active natural product, we demonstrated the diastereodivergent synthesis of the 3-piperidinol alkaloids cassine, spectaline, prosafrinine, iso-6-cassine, prosophylline, prosopinine, and also established the flexible route to the 5,8-disubstituted indolizidine or 1,4-disubstituted quinolizidine type of Dendrobates alkaloids. As another application to the synthesis of biologically active alkaloids, we accomplished the first enantioselective total synthesis of marine alkaloids clavepictines A, B, and pictamine using a highly stereoselective Michael type quinolizidine ring closure reaction as the crucial step, and the first total synthesis of a marine alkaloid lepadin B was also achieved using aldol cyclization controlled by a A strain.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTaxamycins: a new enediyne family constructed from versatile disilyl-substituted building blocksYee Fung Lu, Curtis W. Harwig, and Alex G. FallisCite this: J. Org. Chem. 1993, 58, 16, 4202–4204Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/jo00068a011RIGHTS & PERMISSIONSArticle Views347Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (299 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Unlike traditional multi-step synthetic approaches, we developed a single-step synthesis of versatile π-conjugated building blocks bearing post-functionalizable C-H and C-Br bonds. Direct C-H arylation of 3-bromothiophene with various iodo(hetero)aryls was successfully carried out with good regio- and chemo-selectivity. Under optimized reaction conditions, 20 new compounds were facilely prepared in yields up to 91 %. One of the obtained compounds was demonstrated to further extend its conjugation length using a succinct synthetic plan to create two symmetrical oligo(hetero)aryls (MLC01 and MLC02) that were fabricated as effective hole-transporting materials (HTM) for perovskite solar cells (PSC). PSC devices utilizing MLC01 as hole-transport layer displayed promising power conversion efficiencies of up to 17.01 %.

2‐Phosphaethynolates, particularly the sodium salts, Na(OCP), are exceedingly versatile nucleophiles, which renders these species important as precursors to phosphorus‐containing π‐conjugated heterocycles. Moreover, the 2‐phosphaethynolate anion serves as a potent phosphide transfer reagent giving rise to the first stable phosphinidine among other products. First studies also make evident that the phosphaethynolate ion serves as a fascinating ligand in coordination chemistry. Sodium salts of the long sought arsenic‐containing analogue, 2‐arsaethynolate, were synthesized only recently allowing the formation of arsenic‐based element organics and coordination compounds.

Efficient synergistic chemical fixation of CO2 by simple metal-free organocatalysts: Mechanistic and kinetic insights