Deoxycyanamidation of Alcohols with N-Cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS)

Abstract

The first one-pot deoxycyanamidation of alcohols has been developed using N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as both a sulfonyl transfer reagent and a cyanamide source, accessing a diverse range of tertiary cyanamides in excellent isolated yields. This approach exploits the underdeveloped desulfonylative (N-S bond cleavage) reactivity pathway of NCTS, which is more commonly employed for electrophilic C- and N-cyanation processes.

N‐Cyanation of Primary and Secondary Amines with Cyanobenzio‐doxolone (CBX) Reagent

“…[10] For example, an operationally simple oxidation-cyanation procedure with the in situ generation of cyanogen halide for electrophilic N-cyanation was reported by Chen [11] and Kuhl, [12] respectively. Other strategies including deoxycyanamidation, [13] elimination, [14] rearrangement, [15] copper-mediated oxidative N-cyanation, [16] and transition-metalcatalyzed conversion of isocyanides to cyanamides [17] are mutually complementary to electrophilic N-cyanation. Despite notable advances achieved in this vein, the aforementioned variations either need multistep manipulations, costly transition metals, complicated starting materials, or require harsh conditions.…”

Lewis Acid‐Mediated Cyanation of Phenols Using N‐Cyano‐N‐phenyl‐p‐toluenesulfonamide

“…[11] Based on these results, a proposed mechanism for this cyanation is demonstrated in Scheme 5. First, we treated the sulfonyl-protected naphthol, 2-methoxynaphthalene, and 2-naphthylamine with the standard reaction conditions, and no cyanation product was observed (eq.…”

“…2). [11] Based on these results, a proposed mechanism for this cyanation is demonstrated in Scheme 5. [12] Initially, the intermediate I generated from SnCl 4 , base and phenol derivative reacts with NCTS via a six-membered transition state II to give the intermediate III, which then undergoes the elimination of PhNSnTs (IV) to give the product V. The subsequent tautomerization leads to the formation of desired cyanation product, which could further react with NCTS in the presence of base to generate product 2.…”

“…Pleasantly, we found that the combination of AlCl 3 and BF 3 · OEt 2 [10] was efficient for the cyanation of 1naphthol, and afforded the 1-hydroxy-2-naphthonitrile in 87% yield. [11] Furthermore, phenol derivatives also reacted smoothly with NCTS to provide the corresponding benzonitriles in moderate to good yields (Scheme 4, 3 w-3 z), although the SnCl 4 can not catalyze the cyanation of these substrates. It is worth noting that the tosylated product 3 u was isolated in 26% when naphthalene-2,7-diol was used as the substrate, which was generated via Ts transfer from the NCTS to the 3 h in the presence of NaOH.…”

“…It is worth noting that the tosylated product 3 u was isolated in 26% when naphthalene-2,7-diol was used as the substrate, which was generated via Ts transfer from the NCTS to the 3 h in the presence of NaOH. [11] Furthermore, phenol derivatives also reacted smoothly with NCTS to provide the corresponding benzonitriles in moderate to good yields (Scheme 4, 3 w-3 z), although the SnCl 4 can not catalyze the cyanation of these substrates.…”