Silver‐Catalyzed Cascade Reaction of N‐Isocyaniminotriphenylphosphorane with Aldehydes: Synthesis of Unsymmetrical Azines

Abstract

A direct synthesis of azines from the silver catalyzed domino interaction of N-isocyaniminotriphenylphosphorane and aldehydes is reported. The reaction proceeds through a tandem aza-Wittig, insertion, intramolecular cyclization and [a] Typical Synthetic Procedure (with 3a as an example): To a dried Schlenk flask N-Isocyanoiminotriphenylphosphorane 1 (604 mg, 2.0 mmol), 4-chlorobenzaldehyde 2a (70.3 mg, 0.5 mmol) and Ag 2 CO 3 (27.5 mg, 0.10 mmol) were added under air atmosphere. After evacuated and refilled with nitrogen 3 times, 1,4-dioxane (4 mL), DIPEA (41.3 μL, 0.25 mmol) and BF 3 ·Et 2 O (18.5 μL, 0.15 mmol) was added in one portion to the mixture by syringe. The mixture was stirred at 100°C for 12 h until substrate 2a disappeared. After completion, the resulting mixture was concentrated and extract with diethyl ether (3 × 15 mL), washed with brine (3 × Eur.7239 40 mL). Then combined organic layer was dried with MgSO 4 and concentrated. Finally, the crude product was further purified by flash column chromatography and recrystallization with diethyl ether to give pure product 3a as a yellow solid in 77 % yield.

One Reacts as Two: Applications of N-Isocyaniminotriphenylphosphorane in Diversity-Oriented Synthesis

“…The mechanism (not shown here) likely encompasses an initial aza-Wittig interaction of NIITP with an aldehyde, then complexation of the resultant Nisocyano-imine with Ag(I), followed by insertion, intramolecular cyclization, and final ring-opening to render the unsymmetrical azines. 143 As shown before, the Michael addition of NIITP to activated alkynes followed by trapping by a suitable nucleophile is known, 134,138 but this reaction depends on the presence of electron-withdrawing groups conjugated to the triple bond. Activation of nonconjugated alkynes toward nucleophiles can be achieved with Bronsted and Lewis acid catalysts, especially those based on Cu, Pd, Ag, and Au.…”

“…Metal catalysis is a powerful tool to enable chemical transformations that would be otherwise unviable. Recently, silver catalysis has proven especially useful for enabling the reaction of NIITP with aldehydes and inactivated alkynes via reaction pathways not previously described. − Scheme depicts the direct synthesis of azines by a silver catalyzed tandem process comprising the reaction of substituted benzaldehydes with NIITP 1 in the presence of a silver­(I) salt. The reaction proceeded smoothly at 100 °C in 1,4-dioxane for aliphatic, vinylic, aromatic and heterocyclic aldehydes, furnishing unsymmetrical azines 84 in moderate to good yields.…”

“…The authors found that using DIPEA as base and BF 3 as additive was beneficial for the reaction yield. The mechanism (not shown here) likely encompasses an initial aza -Wittig interaction of NIITP with an aldehyde, then complexation of the resultant N -isocyano-imine with Ag­(I), followed by insertion, intramolecular cyclization, and final ring-opening to render the unsymmetrical azines …”

Progress in Reactions of N‐Isocyanoiminotriphenylphosphorane

“…Our group has developed a silver‐catalyzed cascade reaction of NIITP 1 with aldehydes 16 for constructing unsymmetrical azines 17 bearing CH=N‐N=C(CN)‐N=PPh 3 skeletal structure recently . In this reaction, NIITP played as both “phosphonium ylide” and “CN” roles.…”

DEAD-Mediated Oxidative Ugi/Aza-Wittig Reaction for the Synthesis of 5-(1,2,3,4-Tetrahydroisoquinolin-1-yl)-1,3,4-oxadi­­azoles Starting from (N-Isocyanimine)triphenylphosphorane

“…18 Recently, (N-isocyanimine)triphenylphosphorane (1) has been found to be a versatile and odorless reagent in some multicomponent reactions to construct substituted 1,3,4-oxadiazoles via tandem Ugi or isocyanide-Nef and intramolecular aza-Wittig condensation. 19 It has also been used in the preparation of other heterocycles or organic molecules, such as pyrazoles, 20 unsymmetrical azines, 21 1,3,4-oxadiazepines, 22 pyrrolidine-2,5-diones, 23 and 1,2,4-triazolo [4,3-c]quinazolines. 24 It was reported even as a safe cyano source in the cyanation of some alkynes.…”