Decarboxylative, diastereoselective and exo-selective 1,3-dipolar cycloaddition for diversity-oriented construction of structurally spiro-[butyrolactone-pyrrolidine-chromanone] hybrids

Synlett ◽  
2021 ◽  
Author(s):  
Dong-Gui Guo ◽  
Zheng Li ◽  
Xiao-Xue Han ◽  
Lei Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Transition State ◽  
Medicinal Chemistry ◽  
Homoserine Lactone ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
Mild Conditions ◽  
Good Substrate ◽  
Substrate Tolerance

Inspired by the chemistry and biology of butyrolactones, pyrrolidines and chromanones, herein we successfully developed a simple domino 1,3-dipolar cycloaddition of homoserine lactone-derived azomethine ylides for construction of biologically important spiro-[butyrolactone-pyrrolidine-chromanone] hybrids in the presence of the catalyst Et3N under mild conditions. It is based on the application of carboxylic acid activated chromones as dienophiles followed by a decarboxylation process. This reaction displayed good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities via an exo-transition state (up to 85% yield and >20:1 diastereomeric ratio). In particular, this is the first example of introduction of chromanone moiety into spiro [butyrolactone-pyrrolidine] frameworks, which might be valuable in medicinal chemistry.

Decarboxylative-Mediated Regioselective 1,3-Dipolar Cycloaddition for Diversity-Oriented Synthesis of Structurally exo′-Selective Spiro[oxindole-pyrrolidine-dihydrocoumarin] Hybrids

Synthesis ◽  
2020 ◽  
Author(s):  
Ying Zhou ◽  
Xiong-Wei Liu ◽  
Shun-Qin Chang ◽  
Qi-Lin Wang ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Transition State ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
Diversity Oriented Synthesis ◽  
Biologically Relevant ◽  
Good Substrate ◽  
Quaternary Center ◽  
Substrate Tolerance ◽  
High Yields

A general and practical three-component regioselective 1,3-dipolar cycloaddition of 3-amino-oxindole-based azomethine ylides and coumarins has been developed. This reaction displayed good substrate tolerance and gave a diverse array of biologically relevant spiro[ox-­i­ndole-pyrrolidine-dihydrocoumarin] derivatives bearing four contiguous stereocenters including one spiro quaternary center in moderate to high yields (up to 90%) with high diastereoselectivities (up to 15:1 dr). It is based on the application of carboxylic acid activated coumarins as dienophiles followed by a decarboxylation process. The possible mechanism of the 1,3-dipolar cycloaddition is proposed via an exo′-transition state. Furthermore, this is the first example of decarboxylative-mediated regioselective 1,3-dipolar cycloaddition of 3-amino-oxindole-based azomethine ylides and coumarins.

Energizing Listless Pyrimidines by Pre-Distortion for the General Synthesis of 7-Aza-Indazoles from 2-Hydrazonylpyrimidines via Intramolecular Diels-Alder Reactions

2019 ◽  
Author(s):  
Vincent Le Fouler ◽  
yu Chen ◽  
Vincent Gandon ◽  
Vincent Bizet ◽  
Christophe Salomé ◽  
...  
Keyword(s):  
Transition State ◽  
Medicinal Chemistry ◽  
Functional Group ◽  
Diels Alder ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Mild Conditions ◽  
General Synthesis

<p>Pyrimidines are almost unreactive partners in Diels-Alder cycloadditions with alkenes and alkynes, and usually only reactions under drastic conditions were historically reported. We describe how 2-hydrazonylpyrimidines, easily obtained in two steps from commercially available 2-halopyrimidines can be exceptionally activated by trifluoro acetylation. This allows a Diels-Alder cycloaddition under very mild conditions, leading to a large diversity of <i>aza</i>-indazoles, a ubiquitous scaffold in medicinal chemistry. This reaction is general, scalable and has an excellent functional group tolerance. Quantum mechanical calculations show how the simple <i>N</i>-trifluoromethylation of 2-hydrazonylpyrimidines distorts the substrate into a transition state-like geometry that readily undergoes the intramolecular Diels-Alder cycloaddition. </p>

scholarly journals An efficient and facile access to highly functionalized pyrrole derivatives

2018 ◽  
Vol 14 ◽  
pp. 884-890 ◽  
Author(s):  
Meng Gao ◽  
Wenting Zhao ◽  
Hongyi Zhao ◽  
Ziyun Lin ◽  
Dongfeng Zhang ◽  
...  
Keyword(s):  
Medicinal Chemistry ◽  
Alcohol Solution ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
Complete Oxidation ◽  
One Pot ◽  
Pyrrole Derivatives ◽  
Chemistry Research ◽  
Efficient Construction ◽  
Sodium Alkoxide

A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily complete oxidation with DDQ, has been successfully developed. Further transformation with alkylamine/sodium alkoxide alcohol solution conveniently afforded novel polysubstituted pyrroles in good to excellent yields. This methodology for highly functionalized pyrroles performed well over a broad scope of substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research.

4-(N,N-Dimethylamino)pyridine (DMAP)-Catalyzed 1,3-Dipolar Cycloaddition of 3-Aminooxindole-Based Azomethine Ylides with α,β-Unsaturated Acyl Phosphonates for the Construction of Spiropyrrolidinyl-2,3′-oxindoles

Synthesis ◽  
2018 ◽  
Vol 51 (06) ◽  
pp. 1353-1364 ◽  
Author(s):  
Zhuo Chen ◽  
Lin Chen ◽  
Jin He ◽  
Rong-Guo Sun ◽  
Li Fan ◽  
...  
Keyword(s):  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
One Pot ◽  
Mild Conditions ◽  
Unsaturated Acyl ◽  
Brønsted Base

A novel, one-pot 1,3-dipolar cycloaddition of 3-amimooxindole-based azomethine ylides with α,β-unsaturated acyl phosphonates and subsequent derivatization of the intermediates is described. Employing 4-(N,N-dimethylamino)pyridine (DMAP), an organic Brønsted base, as a robust catalyst leads to an architecturally diverse set of spiropyrrolidinyl-2,3′-oxindoles bearing four contiguous stereocenters and an ester or an amide at the γ-position of the pyrrolidine motif. The products are obtained in moderate to excellent yields and with good diastereoselectivities under mild conditions. The potential of this methodology is demonstrated through a gram-scale reaction and a further transformation of one of the products.

Synthesis, Semiempirical, Stereoselectivity and Pharmacological Activity of a New Class of Spiro Pyrrolidine and Isoquinoline Derivatives

2006 ◽  
Vol 61 (2) ◽  
pp. 213-220 ◽  
Author(s):  
A.V. Londhe ◽  
B. Gupta ◽  
S. Kohli ◽  
P. Pardasani ◽  
R. T. Pardasani
Keyword(s):  
Carboxylic Acid ◽  
Pharmacological Activity ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
New Class ◽  
Chiral Centers ◽  
Toxicological Activity ◽  
Isoquinoline Derivatives

Abstract1,3-Dipolar cycloaddition of azomethine ylides derived from acenaphthylene-1,2-dione and 5- methyl-benzo[b]-thiophene-2,3-dione with L-proline, thiazolidine-4-carboxylic acid and 1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid with various electron deficient dipolarophiles leads to the formation of novel spiroheterocycles having two or more chiral centers. Semiempirical studies have been performed to understand the stereochemical course of the reaction. The synthesized cycloadducts have been screened for antimicrobial and toxicological activity.

scholarly journals Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

2014 ◽  
Vol 10 ◽  
pp. 692-700 ◽  
Author(s):  
Rupankar Paira ◽  
Tarique Anwar ◽  
Maitreyee Banerjee ◽  
Yogesh P Bharitkar ◽  
Shyamal Mondal ◽  
...  
Keyword(s):  
Catalytic System ◽  
Cycloaddition Reaction ◽  
Regioselective Synthesis ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
General Applicability ◽  
Mild Conditions ◽  
Stabilized Azomethine Ylides ◽  
High Yields

A new series of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and pyrrolo[1,2-a]phenanthrolines were efficiently built up from an 8-hydroxyquinoline derivative or phenanthroline via 1,3-dipolar cycloaddition reaction involving non-stabilized azomethine ylides, generated in situ from the parent furo[3,2-h]quinoliniums/phenanthroliums, in presence of a copper(II) chloride–phenanthroline catalytic system. The methodology combines general applicability with high yields.

Energizing Listless Pyrimidines by Pre-Distortion for the General Synthesis of 7-Aza-Indazoles from 2-Hydrazonylpyrimidines via Intramolecular Diels-Alder Reactions

2019 ◽  
Author(s):  
Vincent Le Fouler ◽  
yu Chen ◽  
Vincent Gandon ◽  
Vincent Bizet ◽  
Christophe Salomé ◽  
...  
Keyword(s):  
Transition State ◽  
Medicinal Chemistry ◽  
Functional Group ◽  
Diels Alder ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Mild Conditions ◽  
General Synthesis

<p>Pyrimidines are almost unreactive partners in Diels-Alder cycloadditions with alkenes and alkynes, and usually only reactions under drastic conditions were historically reported. We describe how 2-hydrazonylpyrimidines, easily obtained in two steps from commercially available 2-halopyrimidines can be exceptionally activated by trifluoro acetylation. This allows a Diels-Alder cycloaddition under very mild conditions, leading to a large diversity of <i>aza</i>-indazoles, a ubiquitous scaffold in medicinal chemistry. This reaction is general, scalable and has an excellent functional group tolerance. Quantum mechanical calculations show how the simple <i>N</i>-trifluoromethylation of 2-hydrazonylpyrimidines distorts the substrate into a transition state-like geometry that readily undergoes the intramolecular Diels-Alder cycloaddition. </p>

scholarly journals A Photocatalyst-Free, SET-Mediated Photochemical Approach for the Synthesis of Dumbbell-Like Amine-Functionalized Bis-C60 Fullerene through C–C Bond Formation

Synlett ◽  
2019 ◽  
Vol 30 (12) ◽  
pp. 1462-1468
Author(s):  
Amol Balu Atar
Keyword(s):  
Bond Formation ◽  
Azomethine Ylides ◽  
C60 Fullerene ◽  
Dipolar Cycloaddition ◽  
Cycloaddition Reactions ◽  
Mild Conditions ◽  
Amine Functionalized ◽  
Novel Method ◽  
Free Set

A novel method for the synthesis of dumbbell-like amine-functionalized bis-C60 fullerene from simple bis-α-silyl tertiary benzyl amines and C60 fullerene is described. The photoreactions between bis-α-silyl tertiary benzyl amines and C60 furnished single-bonded bis-aminomethyl-1,2-dihyrofullerenes and double-bonded 1,2,5-trisubstituted bis-fulleropyrrolidines through 1,3-dipolar cycloaddition reactions of azomethine ylides under mild conditions.

SuFEx Activation with Ca(NTf2)2: A Unified Strategy to Access Sulfamides, Sulfamates and Sulfonamides from S(VI) Fluorides

2020 ◽  
Author(s):  
Subham Mahapatra ◽  
Cristian P. Woroch ◽  
Todd W. Butler ◽  
Sabrina N. Carneiro ◽  
Sabrina C. Kwan ◽  
...  
Keyword(s):  
Room Temperature ◽  
Medicinal Chemistry ◽  
Mild Conditions ◽  
Broad Array

<p><br></p> <p>A method to activate sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides with calcium triflimide, and DABCO for SuFEx with amines is described. The reaction was applied to a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions. Additionally, we highlight the application of this transformation to parallel medicinal chemistry to generate a broad array of nitrogen-based S(VI) compounds. </p>

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