Asymmetric [3+2] spiroannulation of pyrazolone-derived Morita–Baylis–Hillman carbonates with alkynyl ketones: facile access to spiro[cyclopentadiene-pyrazolone] scaffolds

Wang, Baomin; Huang, Yue; Wang, Wenyao; Wei, Shiqiang; Qü, Jingping

doi:10.1039/d2cc02963d

Cited by 5 publications

(3 citation statements)

References 67 publications

(20 reference statements)

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“…Based on our previous study, we first investigated the reaction of enynamide 1a with Edaravone-derived MBH carbonate 2a as the allylic ylide precursor under the dual catalysis of metal and Lewis base catalyst (Table 1 , see Tables S1 – S3 of the Supplementary Methods for optimization details) 69 , 112 – 117 . We found that PPh 3 and DABCO were ineffective, and no reaction occurred.…”

Section: Resultsmentioning

confidence: 99%

Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

Jiang

Zhang

et al. 2023

Commun Chem

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Significant progress has been made in asymmetric synthesis through the use of transition metal catalysts combined with Lewis bases. However, the use of a dual catalytic system involving 4-aminopyridine and transition metal has received little attention. Here we show a metal/Lewis base relay catalytic system featuring silver acetate and a modified chiral pyrrolidinopyridine (PPY). It was successfully applied in the cycloisomerization/(2 + 3) cycloaddition reaction of enynamides. Bispirocyclopentene pyrazolone products could be efficiently synthesized in a stereoselective and economical manner (up to >19:1 dr, 99.5:0.5 er). Transformations of the product could access stereodivergent diastereoisomers and densely functionalized polycyclic derivatives. Mechanistic studies illustrated the relay catalytic model and the origin of the uncommon chemoselectivity. In subsequent bioassays, the products containing a privileged drug-like scaffold exhibited isoform-selective phosphodiesterase 1 (PDE1) inhibitory activity in vitro. The optimal lead compound displayed a good therapeutic effect for ameliorating pulmonary fibrosis via inhibiting PDE1 in vivo.

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Section: Resultsmentioning

confidence: 99%

Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

Jiang

Zhang

et al. 2023

Commun Chem

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“…The pyrazolone-derived MBH carbonates 1a , 1c – 1n , , and N -( o -chloromethyl)aryl amide 2 , were synthesized according to the literature procedures.…”

Section: Methodsmentioning

confidence: 99%

DMAP-Catalyzed [4+3] Spiroannulation of Pyrazolone-Derived Morita–Baylis–Hillman Carbonates with N-(o-Chloromethyl)aryl Amides to Forge Spiro[pyrazolone-azepine] Scaffolds

et al. 2023

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A novel DMAP-catalyzed [4+3] spiroannulation of pyrazolone-derived Morita–Baylis–Hillman carbonates with N-(o-chloromethyl)aryl amides was developed. This reaction led to the assembly of medicinally relevant pyrazolone and azepine nuclei into a structurally new spirocyclic scaffold, and a diverse array of spiro[pyrazolone-azepine] products were afforded in good to excellent yields (up to 93%) with a wide substrate scope (23 examples) under mild conditions. Moreover, a gram-scale reaction and product transformations were conducted, which further increased the diversity of products.

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“…The Morita–Baylis–Hillman (MBH) carbonates are useful synthons in constructing diverse cyclic compounds. , For example, Chen et al recently introduced the pyrazolone-derived MBH carbonate, which underwent the (2 + 1)/annulation cascade reaction to construct the spiropyrazolone containing a bicyclo[3.1.0]hexane moiety . The (3 + 2) cycloadditions delivering various spiro[4.4] systems were developed by the Guo group, the Wang group, and our group . Based on our previous works and interest in synthesizing medicinally relevant scaffolds through organocatalytic strategies, we propose to control the chemoselectivity of the cycloaddition reaction of MBH carbonate derived from 1,2-diketone using tunable 4-aminopyridine Lewis base catalysts .…”

Section: Introductionmentioning

confidence: 99%

Catalyst-Controlled Switchable (5 + 4)/(3 + 4) Cycloadditions for the Divergent Synthesis of Pyrazole-Fused Seven- and Nine-Membered Heterocycles

Wang,

Qi,

et al. 2023

ACS Catal.

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Developing diversity-oriented synthetic approaches for medium-sized rings is of great interest, and the divergent synthesis of medium-sized rings with different ring sizes poses a challenging task. In this study, we present a catalyst-controlled switchable (5 + 4)/(3 + 4) cycloaddition strategy for the divergent synthesis of seven- and nine-membered heterocycles. Utilizing two different 4-aminopyridine Lewis base catalysts, pyrazole-fused benzazepines or benzoxazonines can be efficiently assembled from the same substrates. These products exhibit good stability without interconversion under the reaction conditions or elevated temperatures. The origin of the catalyst-controlled chemoselectivity was elucidated by means of computational studies involving DFT calculations, distortion/interaction analysis, and noncovalent interaction analysis.

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Asymmetric [3+2] spiroannulation of pyrazolone-derived Morita–Baylis–Hillman carbonates with alkynyl ketones: facile access to spiro[cyclopentadiene-pyrazolone] scaffolds

Abstract: A tertiary amine-catalyzed asymmetric [3 + 2] spiroannulation reaction of pyrazolone-derived Morita–Baylis–Hillman carbonates with alkynyl ketones was achieved under mild conditions. This protocol offers a facile approach to chiral spiro[cyclopentadiene-pyrazolone]...

Cited by 5 publications

References 67 publications

Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

DMAP-Catalyzed [4+3] Spiroannulation of Pyrazolone-Derived Morita–Baylis–Hillman Carbonates with N-(o-Chloromethyl)aryl Amides to Forge Spiro[pyrazolone-azepine] Scaffolds

Catalyst-Controlled Switchable (5 + 4)/(3 + 4) Cycloadditions for the Divergent Synthesis of Pyrazole-Fused Seven- and Nine-Membered Heterocycles

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