An Efficient One-Pot Synthesis of 1-Aminophosphonates

Abstract

1-Aminophosphonates are valuable compounds with wide range applications in biological and industry. Various reaction conditions and catalysts have been reported for the synthesis of 1-aminophosphonates via three components (dialkylphos-phite+aldehyde+amine) or two component reaction (dialkylphos-phite+imine). We report here a solvent-free synthesis of 1-aminophosphonates under very mild reaction condition. Three component condensation reactions of dialkyl phosphite, carbonyl compound, and an amine gave 1-aminophosphonate in good to excellent yield under solvent- and catalyst-free condition at ambient temperature. Hydrophosphorylation of imines in the presence of dialkylphosphite under same condition gave also 1-aminophosphonates in good to excellent yield. These results showed that the reaction needs no to any catalyst or solvent for activation. It seems a tautomeric form of dialkylphosphite (as one of the components) catalysed the reaction. The reaction yield decreased using any solvent. In addition, a novel method will be reported for the synthesis of N-deprotected 1-aminophosphonates (analogues of 1-amino acids) from N-PMP 1-aminophosphonate in the presence of TCCA. To understand the activity of the dialkylphosphite under solvent free condition, the DFT calculations have provided insight into the basis of this activity.

Catalyst‐ and Solvent‐Free Room Temperature Synthesis of α‐Aminophosphonates: Green Accomplishment of the Kabachnik–Fields Reaction

“…Kaboudin and co-workers also investigated this reaction with 2 eq diisopropyl and diphenyl phosphite (5 c and 5 h) and the appropriate products (6 aj and 6 ao) were obtained in 82 and 85 % yields, respectively, with ChemistrySelect 3 h reaction time. [54] According to our observation, when using 1 eq diisopropyl phosphite (5 c) the reaction was slightly slower, and the product (6 aj) was isolated in almost the same yield (entry 2). When the reaction was carried out with 1 eq diphenyl phosphite (5 h), compound 6 ao was produced in 92 % yield after a short (30 min) reaction time (entry 7).…”

“…An excellent yield was obtained with a short reaction time if a somewhat more expensive reagent, diphenyl phosphite ( 5 h ) was used in the three‐component reaction (entry 7). Kaboudin and co‐workers also investigated this reaction with 2 eq diisopropyl and diphenyl phosphite ( 5 c and 5 h ) and the appropriate products ( 6 aj and 6 ao ) were obtained in 82 and 85 % yields, respectively, with 3 h reaction time [54] . According to our observation, when using 1 eq diisopropyl phosphite ( 5 c ) the reaction was slightly slower, and the product ( 6 aj ) was isolated in almost the same yield (entry 2).…”

New N-acyl- as well as N-phosphonoylmethyl- and N-phosphinoylmethyl-α-amino-benzylphosphonates by acylation and a tandem Kabachnik–Fields protocol

“…17 A wide range of catalysts including metal salts, such as aluminum, ruthenium, zinc, iron, indium, nickel, magnesium and cerium compounds, were described. [18][19][20][21][22][23][24][25] However, most of the Kabachnik-Fields reactions may be performed in a catalyst-free and even solvent-free manner, [26][27][28][29] especially under microwave irradiation. 27,28,30 A special approach is the so-called bis Kabachnik-Fields protocol, in which the primary amine is reacted with two equivalents of the aldehyde (mostly formaldehyde) and with a similar amount of dialkyl phosphite or secondary phosphine oxide to furnish bis( phosphonoylmethyl)-or bis( phosphinoylmethyl)amines, respectively.…”

“…17 A wide range of catalysts including metal salts, such as aluminum, ruthenium, zinc, iron, indium, nickel, magnesium and cerium compounds, were described. 18–25 However, most of the Kabachnik–Fields reactions may be performed in a catalyst-free and even solvent-free manner, 26–29 especially under microwave irradiation. 27,28,30…”

Stereoselective synthesis of vinylphosphonates through aromatic aza-Claisen rearrangement of α-aminophosphonates

“…29 However, this molecular transformation has been applied to only simple substrates because it includes the cleavage of much stronger C–N bonds than the C–O bond in allyl phenyl ethers and thus requires drastic conditions, which may cause a narrow scope of the reaction substrates. 30 As part of our ongoing research to develop the synthesis of phosphonate esters by novel methods, 31–36 we were interested in aromatic aza-Claisen rearrangement of β,γ-unsaturated α-(arylamino)phosphonates. In this Letter, we report that the desired reaction effectively proceeds in trifluoroacetic acid to provide a practical approach to γ-arylated vinylphosphonates.…”