Asymmetric Electrophilic α-Amination of Silyl Enol Ether Derivatives via the Nitrosocarbonyl Hetero-ene Reaction

Abstract

The first example of a general asymmetric nitrosocarbonyl hetero-ene reaction is described. The procedure uses a copper-catalyzed aerobic oxidation of a commercially available chiral nitrosocarbonyl precursor (EleNOr) and is operationally simple. The transformation is both high yielding and highly diastereoselective for a range of silyl enol ether derivatives. A variety of synthetically useful postfunctionalization reactions are presented along with a mechanistic rationale that can be used as a predictive model for future asymmetric reactions with nitrosocarbonyl intermediates.

Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups

“…Herein, we report a novel class of nitrosocarbonyl donors that upon deprotonation and loss of the leaving group (Scheme 1, HX = pyrazolone) generate nitrosocarbonyl intermediates that can hydrolyze to release HNO under physiological conditions. As has been demonstrated in recent reports, 33,35,36,[40][41][42]45 nitrosocarbonyls can react with nucleophiles through an N-selective nitrosocarbonyl aldol reaction to produce Nsubstituted hydroxamic acid adducts. We have recently found that pyrazolones are efficient traps for nitrosocarbonyl intermediates to generate N-substituted hydroxamic acid derivatives with pyrazolone leaving groups (NHPY) in a reversible manner.…”

“…[26][27][28] Recently, the aerobic oxidation of hydroxamic acids by metal catalysts under mild conditions has been developed as an efficient strategy for nitrosocarbonyl generation. [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] In general, however, the above methods are not suitable for HNO generation under physiological conditions. Herein, we report a novel class of nitrosocarbonyl donors that upon deprotonation and loss of the leaving group (Scheme 1, HX = pyrazolone) generate nitrosocarbonyl intermediates that can hydrolyze to release HNO under physiological conditions.…”

Copper‐Catalyzed Amination of Congested and Functionalized α‐Bromocarboxamides with either Amines or Ammonia at Room Temperature

“…Common drawbacks include 1) overalkylation, 2) elimination of alkyl halides by either E2 or E1 pathways as a side reaction, 3) functional‐group compatibilities, and 4) lack of efficient methods for congested C(sp 3 )−N bond formation . Recent related progress in this area includes the use of α‐aminations of carbonyl compounds, photoinduced N‐alkylation with unactivated alkyl halides, and aminations with nitroso compounds . These reported methodologies might solve some problems related to C(sp 3 )−N bond formation, but the amination of hindered and functionalized alkyl groups with either amines or ammonia is still challenging.…”

Copper‐Catalyzed Amination of Congested and Functionalized α‐Bromocarboxamides with either Amines or Ammonia at Room Temperature

“…Common drawbacks include 1) overalkylation, 2) elimination of alkyl halides by either E2 or E1 pathways as a side reaction, 3) functional‐group compatibilities, and 4) lack of efficient methods for congested C(sp 3 )−N bond formation . Recent related progress in this area includes the use of α‐aminations of carbonyl compounds, photoinduced N‐alkylation with unactivated alkyl halides, and aminations with nitroso compounds . These reported methodologies might solve some problems related to C(sp 3 )−N bond formation, but the amination of hindered and functionalized alkyl groups with either amines or ammonia is still challenging.…”