Comparative Studies on the Amidoalkylating Properties of N-(1-Methoxyalkyl)Amides and 1-(N-Acylamino)Alkyltriphenylphosphonium Salts in the Michaelis–Arbuzov-Like Reaction: A New One-Pot Transformation of N-(1-Methoxyalkyl)Amides into Phosphonic or Phosphinic Analogs of N-Acyl-α-Amino Acids

Abstract

It was demonstrated that N-(1-methoxyalkyl)amides do not react with trimethyl phosphite under neutral or

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

“…Applications of 1-( N -acylamino)alkyltriphenylphosphonium salts 4 (Ar = Ph) in the α-amidoalkylation of heteronucleophiles have been reported many times in the literature [5,6,7,8,10]. Usually in these types of reactions, it was necessary to use base catalysts, elevated temperature, and microwave irradiation.…”

“…In 2013, we proposed a plausible reaction mechanism wherein the N -acyliminium cation or N -acylimine, both generated from the 1-( N -acylamino)alkyltriphenylphosphonium salt 4 (Ar = Ph), reacts with phosphorus nucleophile to form alkoxyphosphonium salt 13 —the characteristic intermediate of the Michaelis–Arbuzov reaction. The final step of the reaction is the dealkylation of the alkoxyphosphonium salt 13 and may occur directly with triphenylphosphine (see Scheme 4) [7]. Although we have not yet been able to isolate or even observe the formation of postulated intermediate product, we assume that 1-( N -acylamino)alkyltriarylphosphonium salts with weakened C α -P + bond strength react with phosphorus nucleophiles in an analogous manner.…”

“…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].…”

“…In contrast, 1-( N -acylamino)alkyltriphenylphosphonium salts 1 (Z = Ph 3 P + X − ) do not require the use of acidic catalysts because of the permanent positive charge on the phosphonium group. However, the relatively high stability of C α -P + bond forces the use of a base catalyst (e.g., Hünig’s base, DBU, TBD; route b , Scheme 1 (I)) and sometimes microwave radiation [1,4,5,6,7,8,9,10]. …”

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

“…The nature of the catalytic activity of Hünig’s base and methyltriphenylphosphonium iodide in similar Michaelis–Arbuzov-like reactions of 1-( N -acylamino)alkylphosphonium salts was explained in our previous paper [47]. …”