A highly diastereoselective synthesis of 3-carbethoxy-2,5-disubstituted-3-pyrrolines by phosphine catalysis

Zhu, Xue‐Feng; Henry, Christopher E.; Kwon, Ohyun

doi:10.1016/j.tet.2005.03.104

Cited by 125 publications

(46 citation statements)

References 17 publications

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“…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: 55%

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.

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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.

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Section: Resultsmentioning

confidence: 55%

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.

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“…A similar behaviour was also previously observed where more nucleophilic phosphines such as tributylphosphine instead of triphenylphosphine were required to carry out the reaction of N-sulfonylimines with sterically demanding γ-(t-butyl)-allenoates. 19 In contrast with this observation, the reaction of γ-methylallenoate 12c 18a,14 with Nbenzylidenebenzenesulfonamide 13 can be carried out in the presence of triphenylphosphine affording the cis-3-pyrroline 14c. Under conventional reaction conditions this heterocycle was obtained in 38% yield, whereas the microwave-assisted reaction led to the same product in 43% yield in a short reaction time.…”

Section: Resultsmentioning

confidence: 99%

Microwave-assisted reactions of allenic esters: [3+2] annulations and allenoate-Claisen rearrangement

Lopes¹,

Santos²,

Palácios³

et al. 2009

Arkivoc

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The reactivity of allenic esters towards an activated N-sulfonylimine and electron-deficient alkenes with a phosphine under microwave irradiation is explored. The methodology is shown to be efficient for the one-step synthesis of 3-pyrrolines and cyclopentenes in a regio-and diastereoselective manner. This formal [3+2] cycloaddition is complete within five minutes. It was also demonstrated that microwave irradiation is the best energy source to carry out the Lewis acid catalyzed allenoate-Claisen rearrangement leading to 3-(pyrrolidin-1-yl)hepta-2,6-dienoates.

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“…12 Of particular importance to this discussion is the synthesis of 2,5-disubstituted pyrroline-3-carboxylates through the reactions of γ-substituted allenoates and imines. 13 2,5-Disubstituted pyrroline-3-carboxylates are important scaffolds that are commonly used as intermediates en route to other important nitrogen atom-containing heterocycles. 14 Aside from their use as synthetic intermediates, some 2,5-disubstituted-3-pyrrolines themselves exhibit significant biological activity.…”

Section: Discussionmentioning

confidence: 99%

“…1 H NMR (400 MHz, CDCl 3 ) δ: 1.12 (s, 9 H); 1.27 (t, J = 7.1 Hz, 3 H), 4.11-4.25 (m, 2 H), 5.59-5.63 (m, 2 H). 13 17 Differential scanning calorimetry of (1) was completed (DSC, 30 °C to 300 °C, ramp 10 °C/min). Exothermic decomposition was observed with an onset temperature of 90 °C.…”

Section: Notesmentioning

confidence: 99%

PHOSPHINE-CATALYZED [3 + 2] ANNULATION: SYNTHESIS OF ETHYL 5-(tert-BUTYL)-2-PHENYL-1-TOSYL-3-PYRROLINE-3-CARBOXYLATE

2011

Org. Synth.

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A highly diastereoselective synthesis of 3-carbethoxy-2,5-disubstituted-3-pyrrolines by phosphine catalysis

Cited by 125 publications

References 17 publications

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

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

Microwave-assisted reactions of allenic esters: [3+2] annulations and allenoate-Claisen rearrangement

PHOSPHINE-CATALYZED [3 + 2] ANNULATION: SYNTHESIS OF ETHYL 5-(tert-BUTYL)-2-PHENYL-1-TOSYL-3-PYRROLINE-3-CARBOXYLATE

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