Diverse Functionalization of Ruthenium-Chelated 2-Picolylamines: Oxygenation, Dehydrogenation, Cyclization, and N-Dealkylation

Abstract

Chemical noninnocence" of metal-coordinated 2-picolylamine (PA) derivatives has been introduced upon its reaction with the metal precursor [Ru II (Cl)-(H)(CO)(PPh 3 ) 3 ] under basic conditions. This in effect leads to the facile formation of metalated amide, imine, ring-cyclized pyrrole, and an N-dealkylated congener based on the fine-tuning of an amine nitrogen (N amine ) and a methylene center (C α ) at the PA backbone. It develops oxygenated L1′ in 1 and cyclized L4′ in 4 upon switching of the N amine substituent of PA from aryl to an electrophilic pent-3-en-2-one moiety. On the other hand, imposing the substituent at the C α position of PA modifies its reactivity profile, leading to a dehydrogenation (2/3) or N-dealkylation (6) process. The divergent reactivity profile of metalated PA is considered to proceed through a common dianionic intermediate. Further, a competitive scenario of C−H bond functionalization of coordinated PA versus the ligand-exchange process has been exemplified in the presence of external electrophile such as benzyl bromide or methylene iodide. Authentication of the product formation as well as elucidation of the reaction pathway has been addressed by their crystal structures and spectroscopic features in conjunction with the transition-state (TS) theory.

Redox Induced Tunable Functionalization of Picolylamines on Selective Ru‐Platform

“…Interestingly, the structure of 1 also showed that β‐ketoiminate moiety allied to the picolinoyl fragment of coordinated L1′ dangling outward from the chelate ring formed by L1′, which might have extended the preferred orientation for the facile oxygenation at its C α instead of its cyclization as reported earlier (Scheme 1). [4a] Structural parameters involving {Ru(acac) 2 } fragment in both 1 and 3 are in agreement with the reported analogous systems [4a,5] …”

“…Ortho ‐proton of the pyridine ring of coordinated L2′ appeared as a doublet ( J =4.7 Hz) in the isolated utmost downfield region of 8.7–8.8 ppm. Disappearance of NH (11.17 ppm) and C α −H (4.48 ppm) resonances of free HL2 [4a] in the 1 H NMR of 2 (Figure S3a–c, Supporting Information) established the conversion of amine to imine functionality in the reaction sequence (Scheme 2). However, C=O group of the free β‐ketoiminate fragment of L2′ in 2 exhibited its unperturbed identity at around 200 ppm in 13 C NMR (Figure S3b, Supporting Information).…”

“…The outline of the oxygenation process in 1 was derived primarily based on the earlier reports for the analogous systems [2a,4a–c] . A common dianionic intermediate ( DA − ) generated via the activation of acidic methylene group of PA on coordination to {Ru(acac) 2 } was therefore considered for the correlation of reactivity pattern.…”

“…In this context, the recent article elucidated that β‐ketominate incorporated PA (HL) could undergo cyclization or N ‐dealkylation based on the substituent present at the methylene (C α ) position selectively on coordination with electron poor metal precursor [Ru II (Cl)(H)(CO)(PPh 3 ) 3 ] (Scheme 1). [4a] …”

“…To our delight, switching the metal precursor from electron poor [Ru II (Cl)(H)(CO)(PPh 3 ) 3 ] (earlier work [4a] ) to electron rich [Ru II (acac) 2 (CH 3 CN) 2 ] (present work) has drastically altered the reactivity profile of coordinated L − depending on the substituent at C α : cyclization/N‐dealkylation in the former versus oxygenation ( 1 : CH 2 →C=O when R=H)/dehydrogenation ( 2 : −CH−NH→−C=N when R=Ph) in the latter (Scheme 1 and Scheme 2). Further, a C−N bond scission of the oxygenated product 1 has been perceived in the reaction sequence to yield {Ru(acac) 2 } coordinated picolinate unit in 3 (Scheme 2).…”