Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

Abstract

The ruthenium(II)-catalyzed C À Hfunctionalization of (hetero)aryl azomethine imines with allylic acetals is described.The initial formation of allylidene-(methyl)oxoniums from allylic acetals could trigger C(sp 2 )À Ha llylation, and subsequent endo-type [3+ +2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones.T he utility of this method is showcased by the late-stage functionalization of bioactive molecules such as estrone and celecoxib.C ombined experimental and computational investigations elucidate ap lausible mechanism of this new tandem reaction. Notably,the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.Inrecent decades,g reat advances in transition-metal-catalyzed CÀHf unctionalization have been achieved due to its remarkable advantage in atom economy and environmental sustainability. [1] Thec ombination of C À Hf unctionalization and annulation with various p-unsaturated reactants has been recognized as avaluable strategy for the efficient construction of carbocyclic and heterocyclicc ompounds. [2] Significant progress in this direction has been realized by av ariety of transition-metal catalysts.I np articular, ruthenium catalysts have been employed due to their low cost, high efficiency, broad substrate scope,a nd good functional group tolerance under relatively mild conditions. [3] Azomethine imines have been widely employed in cycloaddition reactions with various coupling partners such as alkenes,a lkynes,a nd allenoates. [4] Recently,L ie tal. has reported the C(sp 2 ) À Hf unctionalization of azomethine imines under Rh III catalysis to provide 1,2-dihydrophthalazi-nes [5a] and bridged benzoxazepines. [5b] Alkenes have been intensively studied for the formation of heterocyclic compounds in CÀHf unctionalization event involving the nucleophilic addition of directing groups to olefinic moieties or the electrophilic addition of directing groups to M À Ci ntermediates.V ery recently,our group disclosed the Rh III -catalyzed C À Hf unctionalization and in situ annulation reaction using Morita-Baylis-Hillman adducts to afford 2-benzazepines, [6a] bridged benzoxazepines, [6b] and 2-naphthols. [6c] In these transformations,weobserved that the ester functionality on MBH adducts can lower the energy barrier of the migratory insertion step,h ence enhancing the catalytic cycle.O nt he other hand, allyl acetate was inactive under the identical reaction condition, which was supported by DFT calculations. [6a] These results indicate that the electron density on olefin moiety is crucial for the success of the reaction. In this regard, we envisioned that we might overcome this issue if ah igher inductive effect at the allylic position can be produced. Owing to their equilibrium under metal catalysis, [7] allylic acetals might serve as highly activated acrolein oxonium precursors for cross-coupling reactions (Scheme 1A). Interestingly,w ed iscovered in the...

Site-selective and metal-free C–H nitration of biologically relevant N-heterocycles

“…With great advance on C-H functionalization reactions (Mishra et al 2017(Mishra et al , 2018Pandey et al 2018;Sambiagio et al 2018;Lee et al 2019), direct C-H nitration of Abstract The site-selective and metal-free C-H nitration reaction of quinoxalinones and pyrazinones as biologically important N-heterocycles with t-butyl nitrite is described. A wide range of quinoxalinones were efficiently applied in this transformation, providing C7-nitrated quinoxalinones without undergoing C3-nitration.…”

“…With great advance on C–H functionalization reactions (Mishra et al 2017 , 2018 ; Pandey et al 2018 ; Sambiagio et al 2018 ; Lee et al 2019 ), direct C–H nitration of (hetero)arenes has been recently developed. The metal-free oxidative C–H nitration of phenols or amines has been explored, as shown in Fig.…”

Ruthenium-Catalyzed C(sp2)–H Bond Bisallylation with Imidazopyridines as Directing Groups

“…13 C{ 1 H} NMR (151 MHz, CDCl 3 ) major isomer: δ 170.0, 144. 9,143.4,140.1,133.3,132.9,131.9,128.2,126.8,126.2,125.74,124.8,124.24,117.47,112.1,111.6,61.2,52.29,52.1,51.9,36.8,31.69,27.3,26.47,14.01. Minor isomer: δ 168.9,145.0,143.5,140.5,133.4,133.0,132.0,128.4,126.6,126.1,125.72,124.9,124.21,117.50,61.3,52.31,52.0,51.7,36.9,31.73,26.52,13.99 [1,2-α]pyridin-2-yl)-5-methoxy-1,3-phenylene)bis(but-2-ene-4,1-diyl))dimalonate (3ba).…”

“…13 C{ 1 H} NMR (101 MHz, CDCl 3 ) major isomer: δ 202.8, 168. 9,145.0,143.6,140.1,132.7,131.7,128.4,126.9,126.4,125.7,125.0,124.3,117.6,112.2,111.5,68.9,60.0,36.87,31.8,31.0,28.9,25.8,21.6. Minor isomer: δ 202.7,168.8,144.9,143.5,140.5,133.4,128.3,125.1,124.2,117.5,112.1,111.6,69.0,59.7,36.90,21.5 4E,4′E)-bis(2-acetylhex-4-enoate) (3ah).…”

“…13 C{ 1 H} NMR (101 MHz, CDCl 3 ) major isomer: δ 204. 9,169.4,145.0,143.6,140.1,133.41,132.7,131.7,128.4,126.5,125.7,125.1,124.23,117.6,112.2,111.5,61.2,59.0,43.9,36.9,31.7,31.1,25.9,16.81,14.07,13.53. Minor isomer: δ 204.8,169.3,144.9,143.5,140.2,133.37,128.3,126.8,126.6,125.2,124.2,112.1,61.3,58.7,44.0,16.76,13.52.…”