Dienamine Activation of Diazoenals: Application to the Direct Synthesis of Functionalized 1,4‐Oxazines

Abstract

A novel rhodium-catalyzed dienamine activation of diazoenals resulted in a new class of γ-functionalized donor-acceptor dienamines. The synthetic utility of these dienamines has been demonstrated in a cooperative rhodium(II)/Brønsted acid and gold(I)-catalyzed direct [3+3] annulation of enaldiazo ketones with N-propargyl anilines, thus leading to highly substituted enal-functionalized 1,4-oxazines. The reaction is proposed to involve dienamine activation through the diacceptor rhodium enalcarbenoid NH-insertion and a gold-catalyzed intramolecular site-selective 6-exo-dig heterocyclization. The methodology was applied to the efficient synthesis of structurally complex [1,4]oxazino[4,3-a]quinolone, which is present in the antibacterial agent PNU-286607.

A One-Pot Reaction toward the Diastereoselective Synthesis of Substituted Morpholines

“…Activation of 2-buten-1,4-diyl diacetate with Pd(0) in the presence of an amino-alcohol led to the formation of the 2-vinyl morpholine with an excellent yield through the sequential formation of a C–N and C–O bond (Scheme , eq 4). It is worth mentioning that the use of a chiral ligand can give access to enantioenriched morpholines. ,, …”

Metal‐Catalyzed Cyclization: Synthesis of (Benzo)morpholines and (Benzo)[1,4]dihydrooxazines

“…A different approach was studied by Kalepu and Katukojvala involving a bis‐metallic catalysis (Scheme ) . The authors described the formation of dihydroxazines by means of a Rh(II)‐catalyzed activation of diazo‐enals 117 in the presence of propargylic aniline 116 to yield bis‐enamines 120 .…”

Metal-Catalyzed Cyclizations to Pyran and Oxazine Derivatives

“…19 Similarly, 2-methylene-3,4-dihydro-1,4-oxazines can be accessed by a cooperative Rh(II)/Brønsted acid and Au(I)catalyzed 'formal' [3+3] annulation of enal diazo ketones with N-propargylanilines (Scheme 17). 23 The reaction probably takes place through the 6-exo heterocyclization of a gold-activated N-tethered alkynone generated in situ by the Rh-catalyzed reaction of enal diazo ketones with Npropargylanilines (Scheme 17). Cp*RuCl(cod) (10 mol%)…”