Copper‐Catalyzed Oxidative Dimerizations of 3‐N‐Hydroxy‐aminoprop‐1‐enes to form 1,4‐Dihydroxy‐2,3‐diaminocyclohexanes with C₂ Symmetry

Abstract

This work describes the one-step construction of complex and important molecular frameworks through copper-catalyzed oxidations of cheap tertiary amines. Copper-catalyzed aerobic oxidations of N-hydroxyaminopropenes to form C2 -symmetric N- and O-functionalized cyclohexanes are described. Such catalytic oxidations proceed with remarkable stereocontrol and high efficiency. Reductive cleavage of the two NO bonds of these products delivers 1,4-dihydroxy-2,3-diaminocyclohexanes, which are important skeletons of several bioactive molecules.

Cu‐Catalyzed Aerobic Oxidative Cyclizations of 3‐N‐Hydroxyamino‐1,2‐propadienes with Alcohols, Thiols, and Amines To Form α‐O‐, S‐, and N‐Substituted 4‐Methylquinoline Derivatives

“…The data in Equation (9) suggests that a radical pathway is operative in this system. As some N ‐hydroxyamines are reported to undergo metal‐free aerobic oxidations to generate N ‐amidoxyl radicals,18, 19 we speculate that substrate 1 a undergoes a Cu/O 2 oxidation to generate amidoxy radical G to induce a radical/allene cyclization,20 yielding allylic radical H . This radical subsequently yields a five‐membered heterocycle I after hydrogen abstraction from species 1 a .…”

Copper‐Catalyzed Three‐Component Annulations of Alkenes, Nitrosoarenes, and N‐Hydroxyallylamines To Form Fused Oxazinane/Isoxazolidine Heterocycles

“…Other N-hydoxyaminoallyl esters 1h and 1i were also applicable substrates to afford desired 8h and 8i (R = benzyl and tert-butyl) in 62-65 % yields (entries [8][9]. We also prepared unsaturated ketones 1j-1lto deliver our targets 8j-8l(R = Ph, Me, n-hexyl) in 31-65 %yields (entries [10][11][12]. Other nitrosobenzenes 3b and 3c were applicable to these annulations to produce compounds 8m-8n in 54-59 %yields (entries [13][14].…”

Copper‐Mediated [3+2] Annulation of 3‐N‐Hydroxyallylamines with Nitrosoarenes

“…The dimerization of I′ yielded no common 1,5‐hexadiene derivatives, but afforded 1,4‐dihydroxy‐2,3‐diaminocyclohexanes I′ 2 efficiently [Eq. ()] . Herein, we report Cu‐mediated [3+2] annulation reactions of 3‐ N ‐hydroxyallylamines with nitrosoarenes to form isoxazolidin‐5‐yl products 3 [Eq.…”

“…(1)]. [9] Herein, we report Cu-mediated [3+ +2] annulation reactions of 3-N-hydroxyallylamines with nitrosoarenes to form isoxazolidin-5-yl products 3 [Eq.…”