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 a-ami...

Copper(II)‐catalyzed Domino Reaction of the Acyclic Ketene‐(S,S)‐Acetals with Diazo Compounds: Convenient Synthesis of Poly‐substituted Thiophenes

“…Based on the above results and previously reported studies, [10,17,20] a plausible mechanism is proposed for this reaction (Scheme 1). First, decomposition of nucleophilic diazo compounds in the presence of Cu (OTf) 2 affords electrophilic copper carbenoid A with the elimination of N 2 .…”

“…[11,12] In addition, the situ-generation of sulfur ylides from diazo compounds and sulfide has been well documented for the construction of CÀ S and CÀ C bond [13,14] via the Doyle-Kirmse [15] or Stevens [16] rearrangement reaction. As part of our ongoing research on ketene dithioacetal [18,19] and diazo compounds, [20] we report herein a new strategy for the direct and convenient synthesis of poly-substituted thiophenes via a Cu(II)-catalyzed domino reaction between the acyclic ketene-(S,S)acetals and diazo compounds. As part of our ongoing research on ketene dithioacetal [18,19] and diazo compounds, [20] we report herein a new strategy for the direct and convenient synthesis of poly-substituted thiophenes via a Cu(II)-catalyzed domino reaction between the acyclic ketene-(S,S)acetals and diazo compounds.…”

“…In stark contrast, little attention has been paid to cleavage CÀ S bond [17] via sulfur ylide to produce thiophenes. As part of our ongoing research on ketene dithioacetal [18,19] and diazo compounds, [20] we report herein a new strategy for the direct and convenient synthesis of poly-substituted thiophenes via a Cu(II)-catalyzed domino reaction between the acyclic ketene-(S,S)acetals and diazo compounds.…”

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

“…[11] These results and our interests in the synthetic applications of diazo compounds [12] prompted us to investigate the reactions of a-amino ketones with a-diazocarbonyls.Unexpectedly,the model reaction of the N-aryl a'-aminoa,b-unsaturated ketone 1a [11] with EDA( 2a), catalyzed by DBU (50 mol %), proceeded very rapidly at room temperature to give ethyl 2-{(Z)-2-[(E)-4-(4-chlorophenyl)-2-oxo-1-(p-tolylamino)but-3-en-1-ylidene]hydrazinyl}acetate (3a)i n high yield, thus leaving the cinnamoyl moiety of 1a intact ( Table 1, entry 3). [13] Further increase in the amount of DBU did not improve the yield of 3a(entries 4and 5). 1,5-DBN was also an efficient catalyst, but afforded 3a in al ower yield (entry 6), and other bases,s uch as 1,4-diazabicyclo-[2.2.2]octane (DABCO), triethylamine,N aOH, and Cs 2 CO 3 were entirely ineffective (entries 7-10).…”

Synthesis of ortho‐Azophenols by Formal Dehydrogenative Coupling of Phenols and Hydrazines or Hydrazides

“…[30c, 32] In the current context,w ee xplored the reactivity of 12 towards Grignard reagents, with the hope of accessing less-polarized azophenols by nucleophilic addition to the terminal nitrogen. [33] Gratifyingly,t his provides at wo-step alternative for the synthesis of azophenolsp ossessing aromatic rings (entries 1-3), or even an alkyl substituent (entry 4), that cannot be incorporated using our standardp henol/hydrazine coupling conditions. We anticipate an umber of opportunities to exploit ortho-azobenzoquinones,w hich, unlike their para-isomers or naphthalene/phenanthreneanalogues, have not been previously synthesized.…”