A New Reactivity Mode for the Diazo Group: Diastereoselective 1,3‐Aminoalkylation Reaction of β‐Amino‐α‐Diazoesters To Give Triazolines

Abstract

A novel mode of reactivity for the diazo group, the 1,3-addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of b-amino-a-diazoesters to form tetrasubstituted 1,2,3-triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au-catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered.

Activation of α‐Diazocarbonyls by Organic Catalysts: Diazo Group Acting as a Strong N‐Terminal Electrophile

“…Importantly, this reaction is general for both active methylenes and adiazocarbonyls,a nd the activation mode will lead to new synthetic applications of a-diazocarbonyls. [6] In general, the terminal nitrogen atom of a-diazocarbonyls is much less electrophilic than the neighboring nitrogen atom. [1] These compounds have been extensively studied as metal carbene precursors, [2] 1,3-dipoles, [3] and Cnucleophiles.…”

“…a-Diazocarbonyls have been known since 1883 for the synthesis of ethyl diazoacetate (EDA), as reported by Curtius, and have attracted increasing interest because of their versatility. [4][5][6][7] Thus,t he intermolecular nucleophilic attack on the terminal nitrogen atom of a-diazocarbonyls,b ya ctive methylenes such as Cnucleophiles,i su nfavored. [4] However,the utility of the electrophilic capability of their terminal nitrogen atom has rarely been studied, save for af ew reports on the use of highly reactive organolithium, Grignard reagents,o ra cyl anion equivalents as Cnucleophiles, [5] and NaH-mediated 1,3-aminoalkylation of a-aminoa-diazoesters to afford tetrasubstituted 1,2,3-triazolines,thus involving an intramolecular amination as the key step.…”

“…[1] These compounds have been extensively studied as metal carbene precursors, [2] 1,3-dipoles, [3] and Cnucleophiles. [4][5][6][7] Thus,t he intermolecular nucleophilic attack on the terminal nitrogen atom of a-diazocarbonyls,b ya ctive methylenes such as Cnucleophiles,i su nfavored. [6] In general, the terminal nitrogen atom of a-diazocarbonyls is much less electrophilic than the neighboring nitrogen atom.…”

“…Among the solvents tested, DMF seemed to be the best choice.Asimilar result was obtained using DMSO as the solvent (entry 11). [1][2][3][4][5][6][7][8] Under the optimal reaction conditions ( Table 1, entry 3), the scope and generality of the reactions for active methylenes were examined and the results are summarized in Table 2. This above C À Nb ond-forming reaction is highly chemoselective and catalyst dependent (Table 1).…”

Activation of α‐Diazocarbonyls by Organic Catalysts: Diazo Group Acting as a Strong N‐Terminal Electrophile

“…[4] However,the utility of the electrophilic capability of their terminal nitrogen atom has rarely been studied, save for af ew reports on the use of highly reactive organolithium, Grignard reagents,o ra cyl anion equivalents as Cnucleophiles, [5] and NaH-mediated 1,3-aminoalkylation of a-aminoa-diazoesters to afford tetrasubstituted 1,2,3-triazolines,thus involving an intramolecular amination as the key step. [6] In general, the terminal nitrogen atom of a-diazocarbonyls is much less electrophilic than the neighboring nitrogen atom. [4][5][6][7] Thus,t he intermolecular nucleophilic attack on the terminal nitrogen atom of a-diazocarbonyls,b ya ctive methylenes such as Cnucleophiles,i su nfavored.…”