Phosphonates amino

The reactions proceeded smoothly under solvent-free conditions. Both aromatic and aliphatic aldehydes provided excellent yields of products (80-92%) in a short reaction time, whereas ketones gave phosphonates in good yields (65-80%) after slightly longer irradiation (6-8 min). Several aromatic, a,(3-unsaturated, heterocyclic and aliphatic aldehydes also worked well to afford the phosphonates in high yields. 

When the substrates were irradiated for just 8-12 min, the reaction in all cases resulted in the formation of stable, hydrated intermediates, Fig. 5.3, which were isolated and characterised. If the intermediate was continuously irradiated (an additional 6-10 min) further, dehydration occuredyielding5-aryl-6-cyano-7-phenyl-5,8-dihydropyrido [2,3-d ] pyrimidin-4(3//)-one as the principal product. 

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Furazanic amino phosphonates 187 are accessible by the Kabachnik-Filds reaction in the presence of dibenzo-24-crawn-8 in 80-85% yields (Scheme 119) (92ZOB2708, 93ZOB1776). 

Fee et al. have investigated the Fewis acid-catalyzed three-component synthesis of a-amino phosphonates [73]. This was carried out in the ionic liquids [BMIM][PFg],... 

The substrate scope is limited, as electron-withdrawing groups (X = p-N02 or p-CF3) on the aromatic substituent are not tolerated. However, this route does provide valuable intermediates to unnatural a-amino phosphonic acid analogues and the sulfimine can readily be oxidized to the corresponding sulfonamide, thereby providing an activated aziridine for further manipulation, or it can easily be removed by treatment with a Grignard reagent. 

Methodology for the cyclization of a-hydroxy-P-amino phosphonates has also been developed and employed in synthesis of aziridine-2-phosphonates [79, 80]. Mesyla-tion of a-hydroxy-P-amino phosphonates 89 (Scheme 3.29), for example, gave a-mesyloxy-P-amino phosphonates 90. Treatment of 90 with K2CO3 afforded azir-idine-2-phosphonates 91 in 93-95% yield [79]. 

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure N-sulfinimines, has also been developed by Davis and others for the asymmetric synthesis of aziridine-2-phosphonates [81-84], As an example, treatment of the lithium anion generated from dimethyl chloromethylphos-phonate (93 Scheme 3.30) with N-sulfmimine (Ss)-92 gave the a-chloro-P-amino phosphonate 94, which could be isolated in 51% yield. Cyclization of 94 with n-BuLi gave cis-N-sulfmylaziridine-2-phosphonate 95 in 82% yield [81],... 

The discussion of the activation of bonds containing a group 15 element is continued in chapter five. D.K. Wicht and D.S. Glueck discuss the addition of phosphines, R2P-H, phosphites, (R0)2P(=0)H, and phosphine oxides R2P(=0)H to unsaturated substrates. Although the addition of P-H bonds can be sometimes achieved directly, the transition metal-catalyzed reaction is usually faster and may proceed with a different stereochemistry. As in hydrosilylations, palladium and platinum complexes are frequently employed as catalyst precursors for P-H additions to unsaturated hydrocarbons, but (chiral) lanthanide complexes were used with great success for the (enantioselective) addition to heteropolar double bond systems, such as aldehydes and imines whereby pharmaceutically valuable a-hydroxy or a-amino phosphonates were obtained efficiently. 

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

Huber, J.W. and Gilmore, W.R, Optically active a-amino-phosphonic acids from ureidophosphonates, Tetrahedron Lett., 3049, 1979. 

Redmore, D., N-Benzyl-a-amino phosphonic acids, J. Org. Chem., 43,996,1978. 

Sasai, H., Arae, S., Tahara, Y., and Shibasaki, M., Catalytic asymmetric synthesis of alpha-amino phosphonates using lanthanoid-potassium-BINOL complexes, /. Org. Chem., 60, 6656, 1995. 

To complement the above information, a highly enantioselective synthesis of a-amino phosphonate diesters should be mentioned.164 Addition of lithium diethyl phosphite to a variety of chiral imines gives a-amino phosphonate with good to excellent diastereoselectivity (de ranges from 76% to over 98%). The stereoselective addition of the nucleophile can be governed by the preexisting chirality of the chiral auxiliaries (Scheme 2-63). 

The preparation of resolved species which are chiral at the germanium metal center have been reported (Equation (37), Table 2)44 47 as have species containing biologically important ligands48-52 including derivatives of a-amino-phosphonic acid.48-50... 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

Based on prior results where Ricci used Cinchona alkaloids as phase-transfer-catalysts, the group proceeded to look at hydrophosphonylation of imines [48], Employing the chiral tertiary amine as a Brpnsted base, a-amino phosphonates products were synthesized in high yields and good selectivities. 

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

Three years later. List and coworkers extended their phosphoric acid-catalyzed dynamic kinetic resolution of enoUzable aldehydes (Schemes 18 and 19) to the Kabachnik-Fields reaction (Scheme 33) [56]. This transformation combines the differentiation of the enantiomers of a racemate (50) (control of the absolute configuration at the P-position of 88) with an enantiotopic face differentiation (creation of the stereogenic center at the a-position of 88). The introduction of a new steri-cally congested phosphoric acid led to success. BINOL phosphate (R)-3p (10 mol%, R = 2,6- Prj-4-(9-anthryl)-C H3) with anthryl-substituted diisopropylphenyl groups promoted the three-component reaction of a-branched aldehydes 50 with p-anisidine (89) and di-(3-pentyl) phosphite (85b). P-Branched a-amino phosphonates 88 were obtained in high yields (61-89%) and diastereoselectivities (7 1-28 1) along with good enantioselectivities (76-94% ee) and could be converted into... 

Fields EK (1952) The synthesis of esters of substituted amino phosphonic acids. J Am Chem Soc 74(6) 1528-1531... 

Pudovik AN (1952) Addition of dialkyl phosphites to imines. New method of synthesis of esters of amino phosphonic acids. Dokl Akad Nauk SSSR 83 865-868... 

Nowack, B., and A. T. Stone, Degradation of nitrilotris(methylene-phosphoric acid) and related amino(phosphonate) chelating agents in the presence of manganese and molecular oxygen , Environ. Sci. Technol., 34,4759-4765 (2000). 

Protected-amino phosphonic acid monoesters 51 are usually activated by conversion to the phosphonochloridates 52, then coupled with appropriate amine components such as C-protected amino adds or peptides to give phosphonoamidates 53 (Scheme 17). This procedure is in contrast to typical peptide coupling conditions, in which carboxylic acid chlorides are avoided because of their susceptibility to epimerization at the a-carbon. Since enolate-... 

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