A-Aminophosphonic acids and esters

Compounds which have been studied in the phosphonic group included an a-aminophosphonic acid and ester, a thiamin betaine, a cyclopropane-phosphonate, a cyclic ester (82), and two phosphazenes. ... 

Wieczorek, J.S. and Gancarz, R., a-Aminophosphonic Acid Esters, Polish Patent 105,252, 1980. 

Fig. 14.45. Transformation of an a-phosphonylcarboxylic acid ester (B) via the related carboxylic acid azide F and its Curtius degradation in ethanol to furnish an ethoxycarbonyl-protected a-aminophosphonic acid ester E. The N- and 0-bound protective groups of the latter compounds are cleaved off under acidic conditions. In this manner a-aminophosphonic acids are synthesized. They are interesting analogs of the biologically important a-amino carboxylic acids.

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

One of the very first methods for the preparation of a-aminophosphonic acids appears to be the one described by Kabachnik and Medved [8]. The Kabachnik-Fields reaction is still very useful, especially for the preparation of dialkyl 1-aminoalkanephosphonates. According to this method, a-aminophosphonates were obtained reacting ammonia, carbonyl compounds (aldehydes and ketones), and dialkyl H-phosphonate. A little later. Fields [9] presented a method of synthesis of 1-aminoalkylphosphonic acids by replacing ammonia with amine—reacting both (aldehydes and ketones) with ammonia, or amine and dialkyl H-phosphonate to give dialkyl esters of 1-aminoalkylphosphonic acid (see Appendix). Hydrolysis of the esters produced free aminoalkylphosphonic acids. Yields of aminophosphonates vary from 40 to 47%. 

Startg. iminoester salt in benzene added with stirring to a soln. of Na-diethyl phosphite in the same solvent at 10° product. Y 72%. F.e. inch pyrrole and azepine derivs., and cyclic a-aminophosphonic acid esters, s. V.Y. Mavrin et al., Zh. Obshch. Khim. 58, 1668-9 (1988). 

Hydrogen chloride a-Aminophosphonic acid esters from dialkyl phosphites and azomethines... 

Without additional reagents a-Aminophosphonic acid esters from aldehydes and amines... 

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

Di- and oligo-peptides with a terminalo-aminophosphonous acid residue have been prepared by coupling with N-hydroxy succinimide esters of N-benzyloxycarbonylamino acids or peptides. 

Derivatives of camphanic acid, such as esters or amides, are usually prepared by the reaction of camphanoyl chloride with suitable nucleophiles. Thus, the enol ester with 2-oxopropaneni-trile 72 was used as a chiral dienophile71. As chiral dienes for inverse Diels-Alder reactions, esters with the enolates of 1,3-diketones, e.g., 73, have been prepared72. Amides, such as 74 and 75, have been used for the synthesis of chiral aminophosphonic acids (Section D.8.) and for acyliminium reactions (Section D.1.4.5.). 

Mention might also be included here of the nature and potential importance of the choice of amino-protection and ester groupings in work on the aminophosphonic acids. The choice of groups for protection at nitrogen is obviously based on experience in conventional amino acid chemistry, and both r rr-butyloxycarbonyl (boc) and benzyloxy-carbonyl (cbz) groups are extensively employed. Most recorded syntheses of aminoalkyl-phosphonic and -phosphinic acids have relied on diethyl or dimethyl esters, largely as a consequence of the ready availability of the simple trialkyl phosphites and dialkyl hydro-genphosphonates the same esters are also preparable under mild conditions from the free acids by the action of ortho esters RC(OR )3 (R = H or Me, R = Me or Until... 

Peptides containing a P-terminal aminophosphonic acid have been prepared by coupling protected amino acids with dialkyl or diaryl esters of aminoalkanephosphonic acids or free acids. Protection of the amino phosphonic acid groups is an important step in the phospho-nopeptide synthesis. Aminophosphonates based on the H-phosphonate diesters are used directly for the preparation of phosphonopeptides. Diphenyl aminoalkanephosphonates are attractive starting materials for phosphonopeptide synthesis because they are readily available, and efficient coupling is easily achieved by most methods used in peptide chemistry. 

Some new amidophosphoric acid esters containing substituted pyridine moieties have been synthesized and characterized by H, P H) NMR, IR, and mass spectrometry. The study, synthesis, and spectroscopic characterization of phosphonates has been well documented during 2008 and several papers are worthy of mention. Starting with a-aminophosphonates and on a green chemistry theme, three types of D,D-diethyl V-dehy-droabietic a-aminoaryhnethylphosphonates have been synthesized from natural product derivatives following a two-step, solvent-free reaction... 

Selke, R., Holz, J. and Riepe, A., Impressive enhancement of the enantioselectivity for a hydroxy-containing rhodium(I) bisphosphine catalyst in aqueous solution by micelle-forming amphiphiles, Chem. Eur. J., 1998, 4, 769, and references cited therein. For a recent application, see Grassert, I., Schmidt, U., Ziegler, S., Fischer, C. and Oehme, G., Use of rhodium complexes with amphiphilic and nonamphiphilic Ugands for the preparation of chiral of-aminophosphonic acid esters by hydrogenation in micellar media. Tetrahedron Asymmetry, 1998, 9, 4193. 

There are only a few examples for the transformations of phosphorus-containing compounds witii baker s yeast [475, 476]. Thus baker s yeast has been used for the synthesis of a-aminophosphonates in a one-pot reaction from aldehyde, diethyl phosphite, and an amine [477]. The reduction of (3-chloro-2-oxo-propyl)-phosphonic acid diethyl ester by baker s yeast gave (2R)-3-chloro-2-hydrox5qjropyl-phosphoric acid diethyl ester, which could be used for the synthesis of (R)-camitine [478-480]. The... 

---