Synthesis of N,N′‐Disulfonylamidines from Sulfonamides and Alkynes by a Two‐Step, One‐Pot Reaction with Nonafluorobutanesulfonyl Azide

Abstract

Nonafluorobutanesulfonyl azide is an advantageous alternative to triflyl azide for the efficient synthesis of sulfonyl azides from sulfonamides in terms of its higher reactivity, lower cost, and non‐hazardous nature. The reagent has proven its utility in a novel synthesis of N,N′‐disulfonylamidines from available sulfonamides by a copper‐catalyzed two‐step, one‐pot sequential process with added terminal alkynes.

Nonafluorobutanesulfonyl Azide as a Shelf-Stable Highly Reactive Oxidant for the Copper-Catalyzed Synthesis of 1,3-Diynes from Terminal Alkynes

“…The growing number of applications of NfN 3 in synthetic organic chemistry (as a diazo-transfer reagent, 1,3-dipole in cycloaddition-started multicomponent reactions, or as a nitrenenoid precursor in CH amination reactions), , out-performing its more costly and hazardous lower homologue triflyl azide (TfN 3 ), calls for a rational assessment of its safety of use and shelf stability. To this end, the sensitivity of neat NfN 3 toward heat, impact, and electrostatic discharge (ESD) has been quantified (Table and the Supporting Information).…”

“…In our recent work on the copper-catalyzed synthesis of N , N ′-disulfonyl­amidines from sulfonamides and terminal alkynes using the shelf-stable nonafluoro­butane­sulfonyl azide (NfN 3 ), we observed the formation of varying amounts of 1,3-diynes when attempting to perform the reaction in a one-pot fashion by mixing all the reagents together with the copper catalyst. This formal oxidative homocoupling of the starting terminal alkyne was the dominant process under some of the conditions tested in those studies.…”

Amidines: their synthesis, reactivity, and applications in heterocyclic synthesis

“…Sulfonyl amidines 74 were synthesized from sulfonylamides 73 by one-pot diazo-transfer and intermolecular copper (I)-catalyzed reaction with alkynes (Scheme 37). 63,64 Scheme 37. Synthesis of N-sulfonyl amidines 74.…”

“…Under similar conditions, the reaction of α-bromostyrene (93) with tert-butylisocyanide and pyrrolidine or piperidine produced the isomeric methylidine amidines 94a,b (Scheme 43). 63 Scheme 43. Synthesis of α,β-unsaturated amidines 94a,b.…”

Synthesis of N-Sulfonyl Amidines and Acyl Sulfonyl Ureas from Sulfonyl Azides, Carbon Monoxide, and Amides

“…Notably, they serve as a highly conserved motif seen in both substrates and inhibitors of trypsin-like serine proteases due to their strong ionic interactions with the acidic S1 pockets. − In addition to being key intermediates in the synthesis of heterocyclic compounds, amidines are also chelators of transition metals (e.g., Zn II ) and have been successfully exploited as inhibitors of anthrax lethal factor, a zinc metalloenzyme. , The emergence of sulfonyl amidines as bioactive pharmacophores (Figure ) with antiresorptive, antitumor, and antiproliferative properties has led to numerous new synthetic developments to access this highly polar, structurally rigid, and hydrogen-bond-rich moiety (Scheme ). These include (a) direct condensation of sulfonamide and formamide, (b) three-component aerobic oxidative coupling of sulfonamides, terminal alkynes, and amines catalyzed by Cu­(OTf) 2 , (c) the coupling of primary, secondary, or tertiary amines and sulfonyl azides with terminal alkynes, (d) coupling of thioamides and sulfonyl azides, and (e) dehydrogenation of tertiary amines coupled with a tandem reaction with sulfonyl azides (Scheme ).…”