Synthesis of Cyclic N-Acyl Amidines by [3 + 2] Cycloaddition of N-Silyl Enamines and Activated Acyl Azides

Abstract

In this study, we describe the synthesis of cyclic N-acyl amidines from readily available N-heteroarenes. The synthetic methodology utilized the versatile N-silyl enamine intermediates from the hydrosilylation of N-heteroarenes for the [3 + 2] cycloaddition reaction step. We evaluated various acyl azides and selected an electronically activated acyl azide, thereby achieving a reasonable yield of cyclic N-acyl amidines. We analyzed the relationship between the reactivity of each step and the electronic nature of substrates using in situ nuclear magnetic resonance spectroscopy. In addition, we demonstrated gram-scale synthesis using the proposed methodology.

Metal-free transfer hydrogenation/cycloaddition cascade of activated quinolines and isoquinolines with tosyl azides

“…Based on the previous studies, 4,8,10,15 and our experimental results, a plausible mechanism is proposed (Scheme 4c). The hydride attack at the quinolinium salt's C-2 or C-4 positions generates intermediates A or B , which will be in equilibrium.…”

“…1a). 8 The Wang group 9 a and the Wan group 9 b utilized metal-catalyzed strategies to achieve amidines. Interestingly, the Donohoe group recently disclosed a protocol for trapping electrophiles with in situ generated enamines attained via the dearomatization of quinolinium salts (Fig.…”

Synthesis and utility of N-boryl and N-silyl enamines derived from the hydroboration and hydrosilylation of N-heteroarenes and N-conjugated compounds

“…These derivatives underwent intramolecular electrophilic aromatic substitution reactions to produce 7,8-benzomorphane derivatives upon treatment with acetyl chloride. In contrast, subsequent studies by Joung’s group focused on the [3 + 2] cycloaddition of cyclic N- silyl enamines via the borane-catalyzed hydrosilylation of N- heteroarenes with organic azides 12b, 12c or azomethine imines 12d ( Cao et al, 2020a ; Cao et al, 2020b ; Cao et al, 2022 ; Jo et al, 2022 ). Borane-catalyzed hydrosilylations yield a broad range of cyclic N- silyl enamines from various N- heteroarenes.…”

“…After the [3 + 2] cycloaddition of N- silyl enamines with organic azides, including sulfonyl azide 12b and carbonyl azide 12c , amidines 12b′ , 12b″ and 12c′ , 12c″ were produced in good-to-high yields. The formation of amidines occurs through the reaction of N- silyl enamines and azides, generating a triazoline intermediate that immediately rearranges to a cyclic amidine via hydride shift and nitrogen gas extrusion ( Cao et al, 2020a ; Cao et al, 2020b ; Jo et al, 2022 ). In addition, the authors discovered that these N- silyl enamines also underwent [3 + 2] cycloaddition with azomethine imine 12d , resulting in the formation of tetracyclic pyrazolidinone scaffold structures 12d′ in good yield.…”