Phosphine‐Catalyzed [4+2] Annulation: Synthesis of Ethyl 6‐Phenyl‐1‐Tosyl‐1,2,5,6‐Tetrahydropyridine‐3‐Carboxylate

Lu, Kui; Kwon, Ohyun

doi:10.1002/0471264229.os086.21

Cited by 11 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the allene–imine [4 + 2] annulation is a robust process, with the large-scale preparation of tetrahydropyridines having been reported. 373…”

Section: Nucleophilic Phosphine Catalysis Of Allenesmentioning

confidence: 99%

Phosphine Organocatalysis

et al. 2018

Self Cite

View full text Add to dashboard Cite

The hallmark of nucleophilic phosphine catalysis is the initial nucleophilic addition of a phosphine to an electrophilic starting material, producing a reactive zwitterionic intermediate, generally under mild conditions. In this Review, we classify nucleophilic phosphine catalysis reactions in terms of their electrophilic components. In the majority of cases, these electrophiles possess carbon–carbon multiple bonds: alkenes (section 2), allenes (section 3), alkynes (section 4), and Morita–Baylis–Hillman (MBH) alcohol derivatives (MBHADs; section 5). Within each of these sections, the reactions are compiled based on the nature of the second starting material—nucleophiles, dinucleophiles, electrophiles, and electrophile–nucleophiles. Nucleophilic phosphine catalysis reactions that occur via the initial addition to starting materials that do not possess carbon–carbon multiple bonds are collated in section 6. Although not catalytic in the phosphine, the formation of ylides through the nucleophilic addition of phosphines to carbon–carbon multiple bond–containing compounds is intimately related to the catalysis and is discussed in section 7. Finally, section 8 compiles miscellaneous topics, including annulations of the Hüisgen zwitterion, phosphine-mediated reductions, iminophosphorane organocatalysis, and catalytic variants of classical phosphine oxide–generating reactions.

show abstract

“…Nevertheless, the allene–imine [4 + 2] annulation is a robust process, with the large-scale preparation of tetrahydropyridines having been reported. 373…”

Section: Nucleophilic Phosphine Catalysis Of Allenesmentioning

confidence: 99%

Phosphine Organocatalysis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…S3) possess the scaffolds derived from the sequence of phosphine-catalyzed annulation, Tebbe methylenation, Diels-Alder reaction, and sometimes hydrolysis (scaffolds s24-s27, s31, s32, and s36 in Scheme 1). As reported earlier (24), tetrahydropyridine s1 and pyrrolidine s2 were formed through the phopshinecatalyzed [4 þ 2] and [3 þ 2] annulation reaction between allenoates and imines (11)(12)(13)(14) and converted into the corresponding ethoxy dienes via Tebbe reaction. The subsequent Diels-Alder reaction of the dienes with maleimides, N-phenyl triazolinedione, and N-sulfonamido arylimines provided multicyclic enol ethers s24, s25/s26, s27, s31, s32, each of which provided 9, 5, 5, 3, and 8 hits out of 10, 12, 5, 9, and 10 compounds, respectively, in confirmatory experiments (Fig.…”

Section: Resultsmentioning

confidence: 56%

“…The goal in developing previously undescribed reactions was to provide previously unexampled heterocyclic frameworks that deviate from the relatively limited pool of molecular motifs used by pharmaceutical companies. For allenes, one-step ring-forming reactions were carried out using either commercially available or otherwise readily available imines, maleimides, aldehydes, aziridines, and electron-deficient olefins, resulting in scaffolds s1-s8 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). For electron-deficient acetylenes, a one-step double-Michael reaction with readily available dinucleophiles was effected by a diphenylphosphinopropane catalyst, providing heterocyclic frameworks s9-s20 (21,22).…”

mentioning

confidence: 99%

Diversity through phosphine catalysis identifies octahydro-1,6-naphthyridin-4-ones as activators of endothelium-driven immunity

Cruz

Wang²,

Kibbie

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The endothelium plays a critical role in promoting inflammation in cardiovascular disease and other chronic inflammatory conditions, and many small-molecule screens have sought to identify agents that prevent endothelial cell activation. Conversely, an augmented immune response can be protective against microbial pathogens and in cancer immunotherapy. Yet, small-molecule screens to identify agents that induce endothelial cell activation have not been reported. In this regard, a bioassay was developed that identifies activated endothelium by its capacity to trigger macrophage inflammatory protein 1 beta from primary monocytes. Subsequently, a 642-compound library of 39 distinctive scaffolds generated by a diversity-oriented synthesis based on the nucleophilic phosphine catalysis was screened for small molecules that activated the endothelium. Among the active compounds identified, the major classes were synthesized through the sequence of phosphine-catalyzed annulation, Tebbe reaction, Diels–Alder reaction, and in some cases, hydrolysis. Ninety-six analogs of one particular class of compounds, octahydro-1,6-naphthyridin-4-ones, were efficiently prepared by a solid-phase split-and-pool technique and by solution phase analog synthesis. Structure-function analysis combined with transcriptional profiling of active and inactive octahydro-1,6-naphthyridin-4-one analogs identified inflammatory gene networks induced exclusively by the active compound. The identification of a family of chemical probes that augment innate immunity through endothelial cell activation provides a framework for understanding gene networks involved in endothelial inflammation as well as the development of novel endothelium-driven immunotherapeutic agents.

show abstract

“…Enaminones were generated via a novel synthesis method employing sonication or Ru(II) catalysis . Compounds 18 and 19 were prepared according to literature procedures . Compound 5 was prepared by the allylation of compound 19 , followed by olefin metathesis of the resulting allylamine, which was then converted into 5 by the catalytic hydrogenation .…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel Proteasome Inhibitors from an Enaminone Library

et al. 2015

View full text Add to dashboard Cite

A library of structurally distinct enaminones was synthesized using sonication or Ru(II) catalysis to couple primary, secondary, and tertiary thioamides with α-halocarbonyls or α-diazocarbonyls. Screening the library for proteasome inhibition using a luciferase-based assay identified seven structurally diverse compounds. Two of these molecules targeted luciferase, while the remaining five exhibited varying potency and specificity for the trypsin-like, chymotrypsin-like, or caspase-like protease activities of the proteasome. Physiological relevance was confirmed by showing these molecules inhibited proteasomal degradation of the full-length protein substrate p21cip1 expressed in tissue culture cells. A cell viability analysis revealed that the proteasome inhibitors differentially affected cell survival. Results indicate a subset of enaminones and precursor molecules identified in this study are good candidates for further development into novel proteasome inhibitors with potential therapeutic value.

show abstract

Phosphine‐Catalyzed [4+2] Annulation: Synthesis of Ethyl 6‐Phenyl‐1‐Tosyl‐1,2,5,6‐Tetrahydropyridine‐3‐Carboxylate

Abstract: Ethyl 2‐(triphenylphosphoranylidne)propionate Ethyl 2‐methylbuta‐2,3‐dienoate ( E)‐N‐ Benzylidene‐4‐methylbenzenesulfonamide p‐ Tolunesulfonamide Benzaldehyde … Show more

Cited by 11 publications

References 36 publications

Phosphine Organocatalysis

Phosphine Organocatalysis

Diversity through phosphine catalysis identifies octahydro-1,6-naphthyridin-4-ones as activators of endothelium-driven immunity

Identification of Novel Proteasome Inhibitors from an Enaminone Library

Contact Info

Product

Resources

About