Electrophilically Activated Nitroalkanes in Synthesis of 3,4-Dihydroquinozalines

Nitroalkanes activated with polyphosphoric acid serve as efficient electrophiles in reactions with various nucleophilic amines. Strategically placed second functionality allows for the design of annulation reactions enabling preparation of various heterocycles. This strategy was employed to develop an innovative synthetic approach towards 3,4-dihydroquinazolines from readily available 2-(aminomethyl)anilines.     

Transition-metal-free synthesis of polysubstituted pyrrole derivatives via [4 + 1] annulation of β-keto acids (C1 synthon) and α,β-unsaturated imines

A novel [4 + 1] annulation protocol for the synthesis of polysubstituted pyrrole derivatives from β-keto acids and α,β-unsaturated imines via a tandem Michael addition, decarboxylation and TBAI-catalyzed oxidative annulation has been developed. This method provides a new and facile application of β-keto acids as 1,1-nucleophilic/electrophilic type C1 synthons.     

Total Synthesis of (−)‐Alstofolinine A through a Furan Oxidation/Rearrangement and Indole Nucleophilic Cyclization Cascade

A reaction cascade of aza‐Achmatowicz rearrangement followed by indole nucleophilic cyclization was developed to generate the common indole‐fused azabicyclo[3.3.1]nonane core of the macroline family alkaloids. The key to the success of the strategy relies on the careful manipulation of protecting groups and judicious selection of chemoselective furan oxidation conditions. The synthetic utility was further demonstrated on the asymmetric total synthesis of (?)‐alstofolinine A.     

Sulfilimines as Versatile Nitrene Transfer Reagents: Facile Access to Diverse Aza‐Heterocycles

We herein report the unprecedented synthesis of diverse biologically important aza‐heterocycles by employing sulfilimines as nitrene transfer reagents. This class of sulfur‐based aza‐ylides had not been successfully used for gold nitrene transfer before. This work contains an efficient generation of α‐imino gold carbenes by N?S cleavage of sulfilimines. These gold carbenes undergo C?H insertion, cyclopropanation, and nucleophilic attack to form indoles (44 examples), 3‐azabicyclo[3.1.0]hexan‐2‐imines (24 examples), and imidazoles (3 examples). Our study represents a unique gold‐catalyzed reaction between alkynes and sulfur ylides, and also includes the first aza‐heterocycle synthesis that proceeds by intermolecular nitrene transfer followed by cyclopropanation of the α‐imino gold carbenes. Moreover, an unexpected synthesis of 4‐acylquinolines (3 examples) from 2‐acylphenyl sulfilimines and propargylic silyl ether derivatives by a 1,2‐hydride shift onto the α‐imino gold carbene and a subsequent Mukaiyama aldol cyclization was discovered.     

Donor‐Acceptor Cyclopropanes in the Synthesis of Carbocycles

Donor‐acceptor cyclopropanes not only participate in a broad range of ring openings with nucleophiles, electrophiles, radical and red‐ox agents, but also are excellent substrates for various (3+n)‐cycloaddition and (3+n)‐annulation processes. Moreover, under treatment with Lewis acid donor‐acceptor cyclopropanes can produce new ring systems via isomerization or cyclodimerization. Authors’ contribution to the synthesis of diverse carbocycles from donor‐acceptor cyclopropanes is summarized in this account.