Lewis acid–catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides to access chiral azabicycles

Abstract

[2,3]-Sigmatropic rearrangement of ammonium ylides represents a fundamental reaction for stereoselective synthesis of nitrogenous compounds. However, its applicability is limited by the scarcity of efficient, catalytic, and mild methods for generating ammonium ylides. Here, we report silver-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides, furnishing chiral azabicycles with bridgehead quaternary stereogenic centers in high enantiomeric purity (up to 99% ee). A combination of density functional theory calculations and experimental studies revealed that residual water in the reaction system is crucial for the mild reaction conditions by functioning as a proton shuttle to assist carbon-silver bond protonation and C2─H deprotonation to generate the ammonium ylide. This reaction has a broad application scope. Besides the diverse substituents, N-fused azabicycles of various ring sizes are also easily accessed. In addition to silver salts, this strategy has also been successfully implemented by using a stoichiometric amount of nonmetallic I2.

Recent Applications of Ammonium Ylide Based [2,3]-Sigmatropic and [1,2]-Stevens Rearrangements To Transform Amines into Natural Products

“…81 The team also extended this reaction to access chiral indolizidines bearing allenyl groups (Scheme 23c ). 81 82 Here, the proposed overall transformation is depicted beginning with N -propargyl derivatives 163 . Treatment with magnesium iodide generated alkyl iodide intermediates 164 that cyclized to bicyclic ammoniums 165 .…”

Rhodium-Catalyzed Asymmetric (3 + 2 + 2) Annulation via N–H/C–H Dual Activation and Internal Alkyne Insertion toward N-Fused 5/7 Bicycles

“…The traditional routes to access such enantioenriched compounds need multiple steps with chiral starting materials. Transition metal-catalyzed strategies, including Heck cyclization, , olefin ring-closing metathesis, nucleophilic cyclization of in situ generating iminium ion, and rearrangement of ammonium ylide, can also be applied to synthesize these compounds [Scheme A­(a–d)] . Nevertheless, they only provide racemic products and always need to use prefunctionalized heterocycle substrates to introduce the second core ring.…”

Water-Induced Chiral Separation on a Au(111) Surface

“…Chirality is a universal phenomenon from single molecules to living organisms. Since the first example on the chiral separation of enantiomorphous crystals of sodium ammonium tartrate, chirality has been recognized widely with great scientific interest in many fields such as biochemistry, − molecular biology, , pharmacology, − and material sciences. − It is well known that biomolecules in life such as sugars and amino acids are chiral and exist in only one enantiomer. − Water is one of the most important molecules in vivo , which is demonstrated to play a crucial role in driving biological self-assembly processes, while it is still unclear if the water molecule is related to the origin of chirality in life. Previously, water has been demonstrated to play a significant role in vitro in chiral generation, chiral amplification, chiral inversion, etc.…”