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

Abstract

Fort he first time a-diazocarbonyls have been used as highly active N-terminal electrophiles in the presence of bicyclic amidine catalysts.The CÀNbond-forming reactions of active methylene compounds as Cnucleophiles with a-diazocarbonyls as N-terminal electrophiles proceed quickly under ambient conditions,i nt he presence of 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU), because of the formation of the reactive N-terminal electrophilic intermediates.DBU activates both the active methylene and a-diazocarbonyl. 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. 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.[1] These compounds have been extensively studied as metal carbene precursors, [2] 1,3-dipoles, [3] and Cnucleophiles.[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. Recently,F eng and co-workers developed an efficient CÀNb ond-forming reaction, namely,t he a-functionalization of ketones,c atalyzed by a N,N'-dioxide scandium complex, but the reaction is limited to a-alkyl-a-diazoesters.[7] Theoretical calculations at the B3LYP/6-31G* level of theory indicate that the carbonyl oxygen atom of ethyl a-alkyl-a-diazoester coordinates to the strong Lewis acid, Sc(OTf) 3 ,a nd enables the positive charge on the terminal nitrogen atom to increase greatly (Scheme 1a).[7] Herein, we report the first C À Nb ond-forming reaction of active methylenes,a st he Cnucleophiles,w ith various a-diazocarbonyls as N-terminal electrophiles by using DBU as ac atalyst (Scheme 1b). [8,9] In the presence of either DBU or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), the terminal nitrogen atom of an a-diazocarbonyl turns out to be highly electrophilic,a nd the C À Nb ond-forming reactions can proceed quickly under ambient conditions. As part of our research on carbon-carbon and carbonheteroatom bond-forming reactions, [9,10] we recently developed an efficient a-CÀHf unctionalization reaction of aamino carbonyls for C À Cb ond formation through ab asepromoted intramolecular cross-dehydrogenative coupling (CDC).[11] These results and our interests in the synthetic applications of diazo compounds [12] prompted us to investigate the reactions of ...

Visible Light‐Induced [3+2] Cyclization Reactions of Hydrazones with Hypervalent Iodine Diazo Reagents for the Synthesis of 1‐Amino‐1,2,3‐Triazoles

“…The diazomethyl radical can act as carbyne equivalent to construct a chiral carbon center via an assembly point functionalization. Inspired by these results, and as part of our ongoing research on hydrazones [7] and diazo compounds, [5b–d, 8] we proposed that 1‐amino‐1,2,3‐triazoles could be constructed by reacting hydrazones with hypervalent iodine diazo reagents using an aminyl radical‐polar crossover strategy [9]…”