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

Abstract

One-pot cascade annulations among nitrosoarenes, alkenes, and N-hydroxyallylamines have been achieved with CuCl/O catalysts, forming fused oxazinane/isoxazolidine heterocycles with excellent diastereoselectivity (d.r. >20:1). To enhance the synthetic utility, we developed a successive cleavage of the two N-O bonds of the resulting heterocycles. A mechanism involving dipolar [3+2] cycloadditions of nitrone intermediates with their tethered alkenes is postulated for formation of these heterocycles.

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].…”

“…Notably,i nt he absence of ac atalyst, the reaction still afforded heterocycles 4a and 5a in 7-8 %y ields,t ogether with unreacted 1a in a6 3% recovery.T his observation is helpful to the reaction mechanism (entry 9). Them olecular structures of two bicyclic heterocycles 4aand 5aare inferred from X-ray diffractions of their relatives 4fand 5d; [11] only one diastereomeric product was formed for each product (d.r. > 20:1).…”

“…Ther eaction is applicable to 2-pyridinylethene 2i to afford desired 4i in 41 %yield together with side product 5i in 21 % yield (entry 9). Other nitrosobenzenes 3b-3c (X = Me,C l) were also suitable for these annulations to afford compounds 4j and 4k in 60 %a nd 52 %y ields,r espectively (entries [10][11].…”

“…> 20:1), despite there being four stereogenic centers.The structures were elucidated by X-ray diffraction of one representative 8f. [11] In the reaction of unsaturated ester 1d with styrene derivatives (X = Me (2b), Cl (2c), and F( 2d))…”

Gold‐catalyzed [4+2] Annulations of Dienes with Nitrosoarenes as 4 π Donors: Nitroso‐Povarov Reactions

“…[5] Forn itrosoarenes,t heir reactions with styrenes were reported to generate two nitrone species by ar adical process. [6] To continue our interest in new nitroso reactions, [4,7] this workr eports novel [4+ +2] annulations between cyclopentadienes and nitrosoarenes,a sdepicted in [Scheme 1,Eq. (2)].…”