α-Diazo oxime ethers for N-heterocycle synthesis

Abstract

This Feature Article introduces the preparation and synthetic utility of α-diazo oxime ethers. α-Oximino carbenes are useful synthons for N-heterocycles, and can be easily prepared from α-diazo oxime ethers as precursors. We begin with the preparation of α-diazo oxime ethers and their application in [3+2] cycloaddition. It turns out that the nature of metals bound to carbenes plays a crucial role in modulating the reactivity of α-oximino carbenes, in which copper carbenes smoothly react with enamines, whereas the less reactive enol ethers and nitriles require gold carbenes. In Section 3.2, a discussion on N-O and C-H bond activation is presented. Carbenes derived from diazo oxime ethers show unique reactivity towards N-O and C-H bond activation, in which the proximity of the two functionalities, carbene and oxime ether, dictates the preferred reaction pathways toward pyridines, pyrroles, and 2H-azirines. In Section 3.3, the development of tandem reactions based on α-diazo oxime ethers is discussed. The nature of carbenes in which whether free carbenes or metal complexes are involved dissects the pathway and forms different types of 2H-azirines. The 2H-azirine formation turned out to be an excellent platform for the tandem synthesis of N-heterocycles including pyrroles and pyridines. In the last section, we describe the electrophilic activation of 2H-azirines with vinyl carbenes and oximino carbenes. The resulting azirinium species undergo rapid ring expansion rearrangements to form pyridines and pyrazines.

Thermal Stability and Explosive Hazard Assessment of Diazo Compounds and Diazo Transfer Reagents

“…Carbene C–H insertion processes are becoming increasingly controlled, with potential to streamline synthetic routes . Similarly, heteroatom X–H insertion reactions (X = O, N, S, and P) − and cycloaddition reactions can install important pharmaceutically relevant functionality and heterocycles. Despite these available transformations, the diazo functional group is essentially avoided for reactions at process scale, due to the potential explosion hazard …”

Diazocarbonyl and Related Compounds in the Synthesis of Azoles

“…One of the highly demanded applications of diazocarbonyl compounds and other stabilized analogs is the construction of carbo- and heterocyclic systems. Recently, a range of new methods have been developed for the synthesis of various heterocycles from diazo compounds, some of which are described in reviews [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Versatility and efficiency of diazo compounds are most clearly manifested in the synthesis of azoles—five-membered heterocycles containing a nitrogen atom and at least one other non-carbon atom of either nitrogen, oxygen, or sulfur.…”

Catalytic Asymmetric Carbene Transfer Reactions of Diazo Oxime Ethers with Olefins and Their Synthetic Applications

“…Despite the widespread research into the synthesis of heterocycles from diazo oxime ethers, cyclopropanation via a carbene transfer reaction has not been reported until now . Since the oxime group can be transformed into various useful organic molecules via Beckmann rearrangement and other reactions, we examined diazo oxime ethers as carbene precursors having an oxime functional group for catalytic asymmetric cyclopropanation.…”

“…Despite the widespread research into the synthesis of heterocycles from diazo oxime cyclopropanation via a carbene transfer reaction has not been reported until now. 11 Since the oxime group can be transformed into various useful organic molecules via Beckmann rearrangement and other reactions, we examined diazo oxime ethers as carbene precursors having an oxime functional group for catalytic asymmetric cyclopropanation. Based on the results of our previous studies on the cyclopropanation of various diazo resources 12 (Scheme 1c), the Ru(II)-Pheox catalyst was examined for the metal-catalyzed decomposition of diazo compounds while controlling the enantioselectivity of the cyclopropyl oxime ether derivatives.…”