1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

Abstract

An effective synthesis of the hitherto unknown 1-imidoalkylphosphonium salts has been developed in the reported study. The crucial step in the method included the decarboxylative α-methoxylation of N-phthaloyl- or N-succinylamino acids to the corresponding N-(1-methoxyalkyl)imides, followed by the displacement of the methoxy group by the triarylphosphonium group through melting of the imide derivative with triarylphosphonium tetrafluoroborate. The imidoalkylating properties of the obtained 1-imidoalkylphosphonium salts were tested using the Tscherniac–Einhorn-type reaction with aromatic hydrocarbons as a model reaction. It was found that the Cα–P+ bond strength can be considerably reduced and the imidoalkylation of arenes can be markedly facilitated using 1-imidoalkylphosphonium salts derived from triarylphosphines with electron-withdrawing substituents such as tris(m-chorophenyl)phosphine, tris(p-chlorophenyl)phosphine and tris[p-(trifluoromethyl)phenyl]phosphine. Microwave irradiation also considerably facilitates the cleavage of the highly polar Cα–P+ bond.

Michaelis-Arbuzov-Type Reaction of 1-Imidoalkyltriarylphosphonium Salts with Selected Phosphorus Nucleophiles

“…In 2017, we described a three-step protocol for the synthesis of 1-imidoalkyltriarylphosphonium salts from α-amino acids and demonstrated their reactivity as imidoalkylating agents on the example of reaction with aromatic compounds [32,33]. In this study, we present the results of our research on the synthetic utility of 1-imidoalkyltriarylphosphonium salts in the Michaelis-Arbuzov-type reaction with phosphorus nucleophiles (III, Scheme 1).…”

1-(N-Acylamino)alkyltriarylphosphonium Salts with Weakened Cα-P+ Bond Strength—Synthetic Applications

“…The presence of a positively charged nucleofugal phosphonium moiety in the close surroundings of the N -acyl group determines its unique chemical properties such as high reactivity in α-amidoalkylations [1,2,3,4,5,6,7,8,9,10]. This type of reactions has enjoyed unflagging interest for years as a synthetic method with great potential, especially valuable for C-C and C-heteroatom bond formation [1,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37].…”

“…Of course, the reactivity of N -acyliminium cation 2 or N -acylimine 3 toward a nucleophile is also significant [1,2,3]. To produce the proper α-amidoalkylating agents, for instance N -acyliminium cation 2 or N -acylimine 3 from the most popular precursors such as α-amido sulfones (Z = SO 2 Ar), N -(1-benzotriazolil)alkylamides (Z = Bt), and N -(1-alkoxyalkyl)amides (Z = OR), it is necessary to use catalysts, mainly Lewis acids (route a , Scheme 1 (I)) [18,19,20,21,22,23,24,25,29,30,31,32,33,34,35,36,37].…”

“…Recently, we have proven that the use of 1-( N -acylamino)alkyltriarylphosphonium salts 4 derived from the EWG-substituted triarylphosphines facilitates the cleavage of C α -P + bond and thereby the generation of N -acyliminium cation (Scheme 1 (II)) [2,3]. This phenomenon significantly increases the reactivity of 1-( N -acylamino)alkyltriarylphosphonium salts with weakened C α -P + bond strength and allows us to conduct α-amidoalkylation without the need for any catalyst.…”

Facile Efficient Synthesis of New Alkoxymethylphosphonium Tetrafluoroborates; Valuable Alternative to Their Halide Analogues

“…Among functionalized phosphonium salts, α-alkoxyphosphonium salts illustrate many applications, though methods for their synthesis have certain limitations [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Alkoxymethyltriphenylphosphonium tetrafluoroborates are less studied and only few methodologies have been reported such as the reaction of triphenylphosphine with α-alkoxy ethers in the presence of fluoroboric acid or tertafluoroboric acid [35,36]. Tuckmantel et al utilized ethereal boron trifluoride (BF 3 .OEt 2 ) for the preparation of methoxyalkylphosphonium tetrafluoroborates, majorly having electron withdrawing group (EWG) group at α-carbon to generate more electrophilic center [37].…”