Rapid Synthesis of Bicyclic N‐Heterocyclic Cores from N‐Terminal α,β‐Unsaturated Diazoketones

Abstract

A method for the synthesis of bicyclic N‐heterocyclic cores from N‐terminal α,β‐unsaturated diazoketones has been developed. The transformation involves three sequential steps that include N‐deprotection, an intramolecular aza‐Michael, and a photochemical Wolff rearrangement as a one‐pot protocol. By using this strategy, a series of substituted bicyclic N‐heterocycles, particularly, indolizidines and pyrrolizidines, were synthesize in good yields.

Catalytic Friedel–Crafts Alkylation of Electron Rich Aromatic Derivatives with α-Aryl Diazoacetates Mediated by Brønsted Acids

“…Diazocarbonyl compounds are important molecules that can undergo a variety of transformations in a highly selective fashion . Their adaptability is exemplified through applications toward the construction of complex molecular architectures . There have been a plethora of reports of metal-catalyzed transformations within the field of diazocarbonyl chemistry over the years, and some recent examples are highlighted in Scheme , with gold, rhodium, and even main group element boron employed.…”

Organocatalytic Enantioselective Sulfa-Michael Additions to α,β-Unsaturated Diazoketones

“…Considering that Michael acceptors (MAs) are well known to participate in many enantioselective reactions, the use of α,β-unsaturated diazoketones could be an interesting alternative to achieve enantiopure diazo compounds. Known as multifunctional reagents given they contain a diazo group, a ketone functionality, and a double bond in a single molecule, α,β-unsaturated diazoketones are powerful intermediates to a multitude of applications in the field of organic synthesis, including conjugate additions . For example, bicyclic N -heterocyclic cores such as indolizidines and pyrrolizidines were synthesized from N -terminal α,β-unsaturated diazoketones in an intramolecular aza-Michael reaction, followed by a photochemical Wolff rearrangement in a one-pot protocol .…”

“…Known as multifunctional reagents given they contain a diazo group, a ketone functionality, and a double bond in a single molecule, α,β-unsaturated diazoketones are powerful intermediates to a multitude of applications in the field of organic synthesis, including conjugate additions . For example, bicyclic N -heterocyclic cores such as indolizidines and pyrrolizidines were synthesized from N -terminal α,β-unsaturated diazoketones in an intramolecular aza-Michael reaction, followed by a photochemical Wolff rearrangement in a one-pot protocol . Moreover, aza-Michael additions to α,β-unsaturated diazoketones have been shown to shorten the synthesis of the natural products preussin and barmumycin …”

α-Imino Iridium Carbenes from Imidoyl Sulfoxonium Ylides: Application in the One-Step Synthesis of Indoles

“…Diazo compounds are one of the best precursors to generate carbenes in organic synthesis . However, it is noteworthy that there are important limitations related to large-scale applications using these compounds due to safety issues resulting from rapid exothermic reactions and gas release .…”