Diastereoselective Spirocyclization of Benzoxazines with Nitroalkenes via Rhodium-Catalyzed C–H Functionalization/Annulation Cascade under Mild Conditions

Abstract

A Rh­(III)-catalyzed [3 + 2] annulation of benzoxazines with nitroolefins that proceeds via redox-neutral C–H functionalization has been demonstrated, leading to the novel class of spirocycles in a single step. The construction of three continuous stereogenic centers has been achieved starting from easily accessible achiral substrates in an atom-efficient manner under mild reaction conditions. A broad range of pharmaceutically relevant nitro substituted spirocyclic 2,3-dihydro-1,4-benzoxazine derivatives has been synthesized in good to excellent yields with high diastereoselectivity.

Remarkable Ligand Effect on Rh-Catalyzed C–H-Active [3 + 2] Annulation of Ketimines and Alkynes

“…C–H activation triggered [3 + 2] annulation reactions have been conceptually established as a new class of annulation reactions by applying this emerging synthetic strategy to substrates having no acidic protons. Several successful protocols − including enantioselective versions , have been reported. Of these, transition-metal-catalyzed [3 + 2] annulations of aromatic ketimines/aldimines with unsaturated hydrocarbon electrophiles have received great interest, and significant advances have been achieved due to the high importance of the indenyl/indanyl amine skeleton that was constructed via these protocols (see eq 1, Scheme ).…”

“…Of these, transition-metal-catalyzed [3 + 2] annulations of aromatic ketimines/aldimines with unsaturated hydrocarbon electrophiles have received great interest, and significant advances have been achieved due to the high importance of the indenyl/indanyl amine skeleton that was constructed via these protocols (see eq 1, Scheme ). − , Owing to the high stability of rhodium catalyst, particularly intense efforts have been spent on the rhodium-catalyzed [3 + 2] annulation reactions. , …”

Transition‐Metal‐Catalyzed Synthesis of Spiro Compounds through Activation and Cleavage of C−H Bonds

“…had extended the scope of such diastereoselectivity using nitro olefins ( 80 ) with 2 H ‐1,4‐benzoxazines ( 79 , Scheme 18). [33] …”

“…Deb et al had extended the scope of such diastereoselectivity using nitro olefins (80) with 2H-1,4-benzoxazines (79, Scheme 18). [33] Scheme 5. Rh(III)-catalyzed cross-dehydrogenative arylation with the assistance of imine as directing group.…”

Substrate‐Controlled Product Divergence in Iron(III)‐Catalyzed Reactions of Propargylic Alcohols: Easy Access to Spiro‐indenyl 1,4‐Benzoxazines and 2‐(2,2‐Diarylvinyl)quinoxalines

“…Scrutiny of the literature reveals that though a plethora of methods exist for the synthesis of 1,4‐benzoxazines, [5] methods for the synthesis of spiro‐benzoxazines [4e,6] have been limited in number. In particular, reports [4e,6a–d] for the synthesis of spiro‐indenyl 1,4‐benzoxazines are few which rely on the use of costly Rh III ‐catalyzed C−H functionalization/annulation cascade reactions on pre‐functionalized 1,4‐benzoxazines (Scheme 1a). Therefore, the development of alternative cost‐economic methods to synthesize them from simple substrates, preferably based on concurrent formations of 1,4‐benzoxazine and fused indene ring in one pot would be worthwhile.…”