Acetylene-Triggered Reductive Incorporation of Phosphine Chalcogenides into a Quinoline Scaffold: Toward S_N^HAr Reaction

Abstract

Quinolines react with acylacetylenes and secondary phosphine chalcogenides at 20–75 °C to afford N-acylvinyl-2­(1)-chalcogenophosphoryldihydroquinolines in good and excellent yields. Unlike the pyridine-derived similar intermediates, which eliminate E-alkenes to give aromatic chalcogenophosphorylpyridines, thereby completing SN HAr reaction, with quinolines, the reaction stops at the formation of the above phosphorylated N-acylvinyl-dihydroquinolines, thus representing a pendant SN HAr process. This reaction opens a one-pot atom-economic single-step access to pharmaceutically targeted phosphorylated functionalized dihydroquinolines and isoquinolines.

Electron-Deficient Acetylenes as Three-Modal Adjuvants in SNH Reaction of Pyridinoids with Phosphorus Nucleophiles

“…The longest duration of the process (17 h) was observed for the bulkiest nucleophile (phosphine oxide 2d). The decisive role of the steric effect in such a reaction was noted for an internal acylacetylene, i.e., benzoylphenylacetylene 3c; the reaction occurred at 70-75 • C for 50 h to give the expected N-benzoylvinyl-2-diphenylphosphoryldihydroquinoline 39 and, unexpectedly, 2,4-bis(diphenylphosphoryl)tetrahydroquinoline 40a (Scheme 32), the latter being obviously formed without acylacetylene 3c [69]. The key steric influence on this tandem vinylation/phosphorylation of isoquinoline was particularly displayed in the reaction with internal acetylenes 3c,d.…”

“…In this case, even at a higher temperature (70-75 • C), the process was about ten times slower and the stereoselectivity was lost; the reaction mixture contained 70-75% of the 45 Z-isomer, which was proved to be a kinetic product (Scheme 35). Common oxidants (chloranil or DDQ) induced [69] the retroaromatization to isoquinolines with the elimination of phosphine oxide 2b, which was fixed by quinones. The same transformation was observed for dihydroisoquinoline 45a under the action of t-BuOK in THF.…”

“…The combination of t-BuOK with DDQ allowed reaching a positive result in the completion of the S N H reaction; the expected aromatic bis(2-phenylethyl)phosphorylisoquinoline 46 was detected among the reaction products along with the initial compound 45a (Scheme 36). It is believed [69] that the above phosphorylation is triggered by acylacetylenes, which form with quinolines (isoquinolines) 1,3(4)-dipolar intermediate A. A further hydrogen transfer from phosphine chalcogenides to the carbanionic site of intermediate A occurs and the carbocationic intermediate B, thus produced, accepts the phosphorus-centered anion onto position two of the quinoline moiety to give the final products (Scheme 37).…”

Recent Advances in the Construction of Phosphorus‐Substituted Heterocycles, 2009–2019

“…More recently, the same group further accomplished the reactions of quinolines with secondary phosphine oxides to afford N ‐acylvinyl‐2‐phosphoryldihydroquinolines 320 in good to excellent yields (Scheme ) . Notably, the current reactions did not eliminate E ‐alkenes to give aromatic phosphorylquinolines to complete the S N H Ar reaction, but stopped at the formation of phosphorylated N ‐acylvinyldihydroquinolines.…”

Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

“…The zwitterion approach allows a series of new quinoline-tailored functionalized heterocyclic systems to be designed. This series includes oxazinoquinolines [ [24] , [25] , [26] ], pyrimidoquinolinones [ 27 ], phosphorylated dihydroquinolines [ 28 ].…”