A-Aminophosphonates synthesis

The lanthanide triflate remains in the aqueous phase and can be re-used after concentration. From a green chemistry viewpoint it would be more attractive to perform the reactions in water as the only solvent. This was achieved by adding the surfactant sodium dodecyl sulfate (SDS 20 mol%) to the aqueous solution of e.g. Sc(OTf)3 (10 mol%) [145]. A further extension of this concept resulted in the development of lanthanide salts of dodecyl sulfate, so-called Lewis acid-surfactant combined catalysts (LASC) which combine the Lewis acidity of the cation with the surfactant properties of the anion [148]. These LASCs, e.g. Sc(DS)3, exhibited much higher activities in water than in organic solvents. They were shown to catalyze a variety of reactions, such as Michael additions and a three component a-aminophosphonate synthesis (see Fig. 2.44) in water [145]. 

During the asymmetric synthesis of a-aminophosphonates (14 in Fig. 4.4), numerous attempts to cleave the benzylic C—N bond, involving catalytic or transfer hydrogenolysis, resulted in epimerization at the a-carbon.319... 

Campbell, M.M. and Carruthers, N., Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones, Chem. Commun., 730, 1980. 

Tyka, R., Novel synthesis of a-aminophosphonic acids, Tetrahedron Lett., 677, 1970. 

The beneficial effect of surfactants on enantioselective hydrogenations in water was exploited in the synthesis of a-aminophosphinic and a-aminophosphonic acids. These compounds are stmctural analogues of a-aminocarboxylic acids and their peptides find use as herbicides, bactericides and antibiotics [150,151]. With [Rh(BPPM)(COD)]Bp4 and similar catalysts fast ractions and e.e.-s up to 98% could be obtained in water in the presence of SDS (Scheme 3.12). 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from a-amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the a-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The a-allyl-a-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+)-AV-dicycIohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ee[72]. 

The first three steps show that the reaction sequence in Figure 14.45 actually provides a widely applicable approach to such a-aminophosphonic acids. The step leading to the acyl azide F, i.e., the nitrite oxidation of an acyl hydrazide (Formula C in Figure 14.45), is as commonly used for the preparation of an acyl azide synthesis as that shown in Figure 14.44. 

Addition of the lithium anion of chloromethylphosphonate to sulfinimine 126 gave a-chloro-P-aminophosphonates 195 in a ratio of 59 41 and 98% total yield.104 The diastereomeric products can be separated and each converted to the corresponding aziridine-2-phosphonates 196, new building chiral blocks for the enantioselective synthesis of a-aminophosphonates 197 and azirinyl phosphonates 198.104... 

The most successful asymmetric variants of the Abramov reaction employ chiral substrates, either chiral carbonyl compounds or aldimines, or chiral phosphorus(III) reagents.5,51,86,88 However, the Pudovik reaction using chiral catalysts is a superior route for the asymmetric synthesis of a-hydroxy- and a-aminophosphonates (Section 6). 

Asymmetric addition of phosphorus compounds to C-N double bonds has been widely studied and mainly concerns the synthesis of chiral a-aminophosphonic acids (for reviews on the synthesis of aminophosphonic acids, see refs 36, 37 and 67). For this purpose, the following types of organic nitrogen compounds have been used aldimines and cyclic imines, nitrones, ureidoimino derivatives and imidothioloesters. A separate example is the addition of dialkyl phosphites to hydrazones, which was used for the synthesis of phosphonosugars. 

Chiral P-Hydroxy-a-Aminophosphonic Acids. An enan-tioselective synthesis of substituted dihydrooxazolin-4-yl phos-phonates was reported by the reaction of an aldehyde with a-isocyanomethylphosphonate ester catalyzed by (i )-(5)-(l) (eq 12). The enantiomeric purity of the product was determined by P H NMR spectroscopy using the chiral solvating reagent (.S)-(+)-2,2,2-trifluoro-l-(9-anthryl)ethanol. Independently, an asymmetric synthesis of ot-aminophosphonic acids was reported using the chiral ferrocenylamine catalyst (R)-(S)-(3) (eq 13). ... 

A method for the stereoselective synthesis of a-aminophosphonates and their N-hydroxy derivatives by aminophosphonylation of carbohydrate and amino acid derivatives using nitrone- based chemistry has been reported (an example of reactions of N-monoprotected a-amino nitrones, whose progenitors were alanine, phenylalanine and leucine respectively, affording the corresponding N-hydroxy a-aminophosphonates, is given in Scheme 67). ... 

Laschat, S, Kunz, H, Carbohydrates as chiral templates stereoselective s3mthesis of (R)- and (5)-a-aminophosphonic acid derivatives. Synthesis, 90-95, 1992. 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

Vasella, A., and Voeffray, R., Asymmetric synthesis of a-aminophosphonic acids by cycloaddition of jV-glycosyl-C-dialkoxyphosphonoyInilroncs, Helv. Chim. Acta, 65, 1953, 1982. 

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