Cyclizations of Alkoxyallenes: Mechanisms, Intermediates, ­Products – A Personal Account on Solved and Unsolved Problems with Unique Allene Building Blocks

Synthesis ◽  
2017 ◽  
Vol 49 (15) ◽  
pp. 3291-3302 ◽  
Author(s):  
Hans-Ulrich Reissig ◽  
Reinhold Zimmer
Keyword(s):  
Natural Products ◽  
Carboxylic Acids ◽  
Carbonyl Compounds ◽  
Building Blocks ◽  
Ring Closure ◽  
Pyridine Derivatives ◽  
Personal Account ◽  
Three Component Reaction ◽  
Hydroxylamine Derivatives ◽  
Oxazine Derivatives

The additions of lithiated alkoxyallenes to electrophiles, such as carbonyl compounds, thioketones, imines, and nitrones, provide the expected primary addition products. These alkoxyallene intermediates undergo ring-closure reactions under quite different conditions. Whereas allenyl hydroxylamine derivatives spontaneously cyclize to 1,2-oxazine derivatives, the related allenyl amines, thiols, and alcohols require, with distinct exceptions, promotion by acids, base, silver(I), or gold(I). The different mechanisms of these processes are discussed in this account. The serendipitous discovery of a novel three-component reaction of lithiated alkoxyallenes, nitriles, and carboxylic acids followed by a cyclization to pyridine derivatives is also reported and the mechanism involved is illustrated. This account also compiles exemplary examples of natural products and other compounds prepared by subsequent reactions of alkoxyallene-based cyclization products, but the fascinating ring-closing event of the allenyl intermediates is the main focus of this report.1 Introduction2 Cyclizations of Allenyl Hydroxylamines to 1,2-Oxazine Derivatives3 Cyclizations of Allenyl Amines to Dihydropyrrole Derivatives4 Cyclizations of Allenyl Imines to Pyrroles – Discovery of a New Three-Component Synthesis of Pyridines5 Cyclizations of Allenyl Thiols to Vinylthiiranes and Dihydrothiophene Derivatives6 Cyclizations of Allenyl Alcohols to Dihydrofuran Derivatives7 Conclusions

A stereolibrary of conformationally restricted amino acids based on pyrrolidinyl/piperidinyloxazole motifs

2015 ◽  
Vol 21 (6) ◽  
pp. 391-395 ◽  
Author(s):  
Oleksiy S. Artamonov ◽  
Taras Bulda ◽  
Tkhe Kyong Fam ◽  
Evgeniy Y. Slobodyanyuk ◽  
Dmitry M. Volochnyuk ◽  
...  
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Drug Discovery ◽  
Carboxylic Acids ◽  
Building Blocks ◽  
Conformationally Restricted ◽  
Lead Compounds ◽  
Restricted Amino Acids

AbstractA stereolibrary of conformationally restricted oxazole-containing amino acids, namely all isomers of 5–pyrrolydinyl- and 5-piperidinyloxazole-4-carboxylic acids, were designed and synthesized in three steps by the reaction of the corresponding N-Boc-protected amino acids and ethyl isocyanoacetate. These natural products-inspired amino acids are valuable building blocks for the synthesis of peptidomimetics and potential lead compounds for drug discovery.

Alkoxyallenes as Starting Materials for the Syntheses of Natural Products

2020 ◽  
Vol 23 (27) ◽  
pp. 2976-3003 ◽  
Author(s):  
Volker Martin Schmiedel ◽  
Hans-Ulrich Reissig
Keyword(s):  
Natural Products ◽  
Carbonyl Compounds ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Natural Product Synthesis ◽  
Subsequent Reaction ◽  
Enol Ethers ◽  
Carbocyclic Compounds ◽  
Nazarov Cyclizations ◽  
High Stereoselectivity

Alkoxyallenes are easily available and versatile building blocks for the preparation of a variety of natural products (terpenes, polyketides, alkaloids, amino acids, carbohydrates etc.) originating from different classes. The synthetic use of the three allene carbon atoms frequently follows the “normal” reactivity pattern showing that alkoxyallenes can be regarded as special enol ethers. Additions of alcohols or amines to alkoxyallenes form vinyl-substituted O,O- or N,O-acetals that are frequently used in ring-closing metathesis reactions. This methodology delivers crucial heterocyclic units of the target compounds. Enantioselective additions provide products with high enantiopurity. Alternatively, an “Umpolung” of reactivity of alkoxyallenes is achieved by lithiation at C-1 and subsequent reaction with electrophiles, such as alkyl halides, carbonyl compounds, imines or nitrones. High stereoselectivity of the addition step can be achieved by substrate control or auxiliary control. The high diastereo- or enantioselectivity is transferred to the subsequent acyclic or cyclic products. The cyclization of primary addition products occurs efficiently under mild conditions and provides functionalized dihydrofuran, dihydropyrrole or 1,2-oxazine derivatives. These are valuable intermediates for the synthesis of a variety of heterocyclic natural products. Nazarov cyclizations or gold catalyzed rearrangements allow the synthesis of five- and six-membered carbocyclic compounds that are also used for natural product synthesis. Dedicated to Dr. Reinhold Zimmer, a pioneer of alkoxyallene chemistry, on the occasion of his 60th birthday.

1,2,3-Thiadiazole mit ungesättigten Seitenketten - Monomerbausteine für Photoresist-Materialien / 1,2,3-Thiadiazoles with Unsaturated Side Chains - Monomeric Building Blocks for Photoresists

1995 ◽  
Vol 50 (7) ◽  
pp. 1121-1126 ◽  
Author(s):  
Norbert Hanold ◽  
Helga Kalbitz ◽  
Mousa Al-Smadi ◽  
Herbert Meier
Keyword(s):  
Carboxylic Acids ◽  
Building Blocks ◽  
Thermal Polymerization ◽  
Ring Closure ◽  
Side Chains ◽  
Phosphonium Salts ◽  
High Tendency ◽  
Wittig Reactions

The phosphonium salts 4 are versatile reagents for the synthesis of 1,2,3-thiadiazoles 6 with unsaturated side chains. The preparation starts with the α-chloroketones 1 which are transformed in a stepwise process to the phosphonium salts 2 and 3. The reaction with SOCl2 leads to a regioselective ring closure 3 → 4 . Subsequent Wittig reactions yield the monomers 6, which exhibit with the exception of 6ac a high tendency for a thermal polymerization. Cleavage of the ester groups in 6ca and 6 cd generates the carboxylic acids 7ca and 7 cd which possess a higher stability.

Catalytic asymmetric allylation of carbonyl compounds and imines with allylic boronates

2014 ◽  
Vol 1 (3) ◽  
pp. 303-320 ◽  
Author(s):  
Hua-Xing Huo ◽  
Jeremy R. Duvall ◽  
Meng-Yuan Huang ◽  
Ran Hong
Keyword(s):  
Natural Products ◽  
Carbonyl Compounds ◽  
Building Blocks ◽  
Asymmetric Allylation ◽  
Organic Reaction ◽  
Homoallylic Alcohols ◽  
Catalytic Asymmetric

Enantioselective allylation is a highly used organic reaction to prepare chiral homoallylic alcohols and amines, which serve as important building blocks in the synthesis of a variety of natural products and pharmaceuticals.

A FACILE SYNTHESIS AND REACTIONS OF AMINO SELENOLO[2,3-b]PYRIDINE CARBOXYLATE

2015 ◽  
Vol 12 (1) ◽  
pp. 3910-3918 ◽  
Author(s):  
Dr Remon M Zaki ◽  
Prof Adel M. Kamal El-Dean ◽  
Dr Nermin A Marzouk ◽  
Prof Jehan A Micky ◽  
Mrs Rasha H Ahmed
Keyword(s):  
Biological Activity ◽  
Carbonyl Compounds ◽  
Mass Spectra ◽  
The Other ◽  
Pyridine Derivatives ◽  
Facile Synthesis ◽  
High Biological Activity ◽  
Basic Hydrolysis ◽  
Pyridine Carboxylate ◽  
Hydrolysis Of

 Incorporating selenium metal bonded to the pyridine nucleus was achieved by the reaction of selenium metal with 2-chloropyridine carbonitrile 1 in the presence of sodium borohydride as reducing agent. The resulting non isolated selanyl sodium salt was subjected to react with various α-halogenated carbonyl compounds to afford the selenyl pyridine derivatives 3a-f  which compounds 3a-d underwent Thorpe-Ziegler cyclization to give 1-amino-2-substitutedselenolo[2,3-b]pyridine compounds 4a-d, while the other compounds 3e,f failed to be cyclized. Basic hydrolysis of amino selenolo[2,3-b]pyridine carboxylate 4a followed by decarboxylation furnished the corresponding amino selenolopyridine compound 6 which was used as a versatile precursor for synthesis of other heterocyclic compound 7-16. All the newly synthesized compounds were established by elemental and spectral analysis (IR, 1H NMR) in addition to mass spectra for some of them hoping these compounds afforded high biological activity.

Directed, Palladium(II)-Catalyzed Enantioselective anti-Carboboration of Alkenyl Carbonyl Compounds

2019 ◽  
Author(s):  
Zhen Liu ◽  
Xiaohan Li ◽  
Tian Zeng ◽  
Keary Engle
Keyword(s):  
Carbonyl Compounds ◽  
Building Blocks ◽  
New Method ◽  
Carbon Based

A substrate-directed enantioselective <i>anti</i>-carboboration reaction of alkenes has been developed, wherein a carbon based nucleophile and a boron moiety are installed across the C=C bond through a 5- or 6-membered palladacycle intermediate. The reaction is promoted by a palladium(II) catalyst and a mondentate oxzazoline ligand. A range of enantioenriched secondary alkylboronate products were obtained with moderate to high enantioselectivity that could be further upgraded by recrystallization. This work represents a new method to synthesize versatile and valuable alkylboronate building blocks. Building on an earlier mechanistic proposal by Peng, He, and Chen, a revised model is proposed to account for the stereoconvergent nature of this transformation.

Formation of Carbon-Oxygen Bond Mediated by Hypervalent Iodine Reagents Under Metal-free Conditions

2020 ◽  
Vol 17 ◽  
Author(s):  
Ayesha Jalil ◽  
Yaxin O Yang ◽  
Zhendong Chen ◽  
Rongxuan Jia ◽  
Tianhao Bi ◽  
...  
Keyword(s):  
Natural Products ◽  
Bond Formation ◽  
Building Blocks ◽  
Review Article ◽  
Hypervalent Iodine ◽  
Metal Free ◽  
Bioactive Natural Products ◽  
The Past ◽  
Oxygen Bond ◽  
Privileged Scaffolds

: Hypervalent iodine reagents are a class of non-metallic oxidants have been widely used in the construction of several sorts of bond formations. This surging interest in hypervalent iodine reagents is essentially due to their very useful oxidizing properties, combined with their benign environmental character and commercial availability from the past few decades ago. Furthermore, these hypervalent iodine reagents have been used in the construction of many significant building blocks and privileged scaffolds of bioactive natural products. The purpose of writing this review article is to explore all the transformations in which carbon-oxygen bond formation occurred by using hypervalent iodine reagents under metal-free conditions

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents

2019 ◽  
Vol 19 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Faeze Khalili ◽  
Sara Akrami ◽  
Malihe Safavi ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
High Yield ◽  
Breast Cancer Cell Lines ◽  
Pyridine Derivatives ◽  
One Pot ◽  
Standard Drug ◽  
Three Component Reaction ◽  
Anti Cancer

Background: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. Objective: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. Methods: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. Results: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. Conclusion: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

scholarly journals Non-Enzymatic Desymmetrization Reactions in Aqueous Media

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 720
Author(s):  
Satomi Niwayama
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Functional Groups ◽  
Organic Compounds ◽  
Recent Progress ◽  
Aqueous Media ◽  
Building Blocks ◽  
Organic Reactions ◽  
Environmentally Benign ◽  
Enzymatic Desymmetrization

Symmetric organic compounds are generally obtained inexpensively, and therefore they can be attractive building blocks for the total synthesis of various pharmaceuticals and natural products. The drawback is that discriminating the identical functional groups in the symmetric compounds is difficult. Water is the most environmentally benign and inexpensive solvent. However, successful organic reactions in water are rather limited due to the hydrophobicity of organic compounds in general. Therefore, desymmetrization reactions in aqueous media are expected to offer versatile strategies for the synthesis of a variety of significant organic compounds. This review focuses on the recent progress of desymmetrization reactions of symmetric organic compounds in aqueous media without utilizing enzymes.

Sign in / Sign up

Export Citation Format

Share Document