Synthesis of Benzhydryl-Substituted Amines by Silanolate-Mediated Aldimine Arylation with Functionalized Aryl Nucleophiles Released from Diazene-Based Reagents

Abstract

A transition-metal-free protocol for the arylation of N-phenyl-and N-benzoyl-substituted, benzaldehyde-derived imine derivatives with functionalized aryl pronucleophiles is reported. The aryl nucleophiles are released from siliconprotected aryl-substituted diazenes by desilylation with potassium trimethylsilanolate concomitant with the loss of dinitrogen. A broad range of functional groups is tolerated in the aryl nucleophile but, depending upon their electronic effect, require specific groups at the imine nitrogen atom.

Fluoride-Catalyzed Arylation of α-(Trifluoromethyl)styrene Derivatives with Silicon-Masked, Functionalized Aryl Pronucleophiles

“…However, this led to an increased formation of phenylsilane 4 as side product, as a result of the reaction of the diazene in the absence of sufficient electrophilic reactant. 6 Besides, side product 5 was always detected by GLC analysis, formed by the reaction of the diazene with the solvent dimethylformamide (DMF). However, DMF was the most suitable polar−aprotic solvent for this reaction.…”

“…Recently rediscovered and synthetically versatile N -aryl- N′ -silyldiazenes begin to find useful applications as latent aryl pronucleophiles. − Anionic Lewis bases mediate their desilylation, generating aryl-substituted diazenyl anions that eventually collapse into dinitrogen and aryl nucleophiles that can be decorated with a broad spectrum of functional groups. Accordingly, we have been seeking new reactions for these silicon-masked aryl pronucleophiles.…”

“…Better results were obtained using an excess of 1.5 and 3.0 equiv of 2a affording 3aa in 56% and 46% yields, respectively (entries 9 and 10). However, this led to an increased formation of phenylsilane 4 as side product, as a result of the reaction of the diazene in the absence of sufficient electrophilic reactant . Besides, side product 5 was always detected by GLC analysis, formed by the reaction of the diazene with the solvent dimethylformamide (DMF).…”

“…Accordingly, we have been seeking new reactions for these silicon-masked aryl pronucleophiles. Besides 1,2-addition to C�O 5 and C�N 6 bonds, we reported a fluoride-initiated S N Ar for the arylation of polyfluorinated arenes where an in situ released fluoride anion propagates the catalytic reaction (Scheme 1). 7 Based on this strategy, we envisioned the arylation of more challenging fluoride-containing electrophiles such as α-(trifluoromethyl)styrene derivatives.…”

Bond-Forming Processes Enabled by Silicon-Masked Aryl- and Alkyl-Substituted Diazenes

“…25 For this reason, an excess of the anionic initiator KOSiMe 3 was necessary to afford the valuable benzhydryl-substituted amines (as in 23ga−gg,eg) in good yields (11 + 22 → 23; Scheme 9). 27 A number of substrates such as epoxides and pyridine Noxides were additionally assessed; however, the degradation of the silyldiazene into the cognate arylsilane was the preferential pathway identified (not shown). 23 Nucleophilic Substitutions.…”