Mechanism of Anionic Dearomatizing Reactions of Diphenylphosphinamide Derivatives: A Theoretical and Experimental Study

Abstract

The mechanism of the anionic dearomatisation of phosphinamide derivatives has been investigated both theoretically and experimentally. The potential-energy surface of model reactions was studied at the Becke3LYP/6-31+G* level of theory, and according to this study, a pre-reactive complex is formed between the alkyllithium and the phosphinamide. This complex evolves preferentially through NC(alpha)-metalation of the phosphinamide. The intramolecular nucleophilic addition of the carbanion to the ortho position of the aromatic ring leads to the dearomatised products, in a reaction that has been shown to be under thermodynamic control. Coordinating co-solvents, such as hexamethyl phosphoramide (HMPA) or N,N'-dimethyl-N,N'-propylene urea (DMPU), appear to influence the reaction by favouring the formation of solvent-separated ion pairs. The cyclisation reaction of allylphosphinamide derivatives was also studied. It was found that both the alpha- and gamma-attack of the allyl anion can take place, however the formation of the seven-membered ring products derived from the gamma-attack are clearly favoured.

Carbocycle Synthesis through Facile and Efficient Palladium‐Catalyzed Allylative De‐aromatization of Naphthalene and Phenanthrene Allyl Chlorides

“…[1] Over the past four decades, many methods, including oxidation, [2] reduction, [3] photocycloaddition, [4] [2,3] s-rearrangement, [5] electrophilic addition, [6] nucleophilic addition, [7] and other approaches [8] have been developed for breaking up the conjugated p system. The complexation of aromatic system to transition metals leads to the activation of arenes and thus facilitates the electrophilic addition of [M(h 2 -arene)] (M = Os, Re, Mo, and W) complexes and the nucleophilic addition of [M(h 6 -arene)] (M = Cr, Mn, and Ru) complexes.…”

Synthesis of Inherently Chiral Calix[4]arenes: Stereocontrol through Ligand Choice

“…Oxygen-based ligands were then evaluated: Dimethoxymethane (DMM) returned a moderate conversion (entry 13) with effectively no impact on diastereoselectivity, much like the monodentate ethers . Using N,N′ -dimethylpropylideneurea (DMPU) returned unreacted starting material, but N,N,N′,N′,N′′,N′′ -hexamethylphosphoramide (HMPA, entry 15) resulted in a moderate conversion of product with reversal of the observed diastereoselectivity (a ratio of slightly less than 1:2). , Dimethoxyethane (glyme), a structural analogue of TMEDA, also resulted in partial reversal of the product diastereoselectivity, and the tridentate ligand diethylene glycol dimethyl ether (diglyme) gave both excellent conversions and an appreciable reversal in the diastereoselectivity (almost 1:4).…”

Dearomatizing Anionic Cyclization of Phosphonamides. A Route to Phosphonic Acid Derivatives with Antitumor Properties

“…The Ph 2 P(O) (Pop) group of P -arylphosphinamides fulfills these criteria nicely. Lithiation at either the NC α (Scheme , route a) or ortho position (route b) can be achieved in THF with excellent regiocontrol. The NC α anions are stable in diethyl ether at low temperature, allowing their application in carbon−carbon and carbon−heteroatom bond-forming reactions (route c) .…”

“…The NC α anions are stable in diethyl ether at low temperature, allowing their application in carbon−carbon and carbon−heteroatom bond-forming reactions (route c) . In contrast, in THF and in the presence of HMPA or DMPU, NC α anions undergo dearomatization through anionic cyclization quantitatively. , …”

“…The formation of compounds 8 − 10 implies that s -BuLi deprotonates phosphonamide 5 selectively at the benzylic position and the anion generated, 6 , attacks the ortho position of the P -phenyl ring to give the dearomatized species 7 . Similar to phosphinamides, , quenching the reaction with MeOH introduces a proton at the α carbon with respect to the phosphorus leading to 8a (entry 1), whereas protonation with 2,6-di( tert -butyl)-4-methylphenol (DTBMP) and alkylation with benzyl bromide takes place almost exclusively at the γ position providing 10a and 10b , respectively (entries 3−5). Two aspects of these transformations are worth mentioning.…”