Cyclic phosphinic acids amidation

Direct Esterification and Amidation of Cyclic Phosphinic Acids... 

After the esterifications and thioesterifications, the direct amidation of cyclic phosphinic acids was also attempted. The interaction of l-hydroxy-3-phospholene oxide (7) and 1-hydroxy-phospholane oxides (11 and 13) with primary amines under MW conditions took place in conversions of ca. 33% (Scheme 5). The amides (18-20) were isolated with 23-29% yields [37,39]. 

The only comprehensive and readily-available surveys of thio- and seleno-phosphonic and -phosphinic acids appear to be those in the compilation by Kosolapoff and Maier which appeared during the 1970s, and those in the Houben-Weyl volumes. Some further information relevant to heterocyclic systems which possess endo- or exo-cyclic phosphorus-sulphur bonds has been surveyed by Mann Gefter has also provided a useful compilation of syntheses and data for unsaturated thiophosphonates and related compounds. As in the preceding chapters concerned with the synthesis of the various classes of phosphonic and phosphinic acids, literature surveys have been presented for individual compounds and the field, as a whole, is surveyed annually". In addition. Hall and Inch reviewed the mechanistic implications of changes in stereochemistry following displacement reactions at phosphorus in cyclic phosphorus(V) esters and amides, and in so doing discussed the reaction s of many such thiophosphoryl compounds. 

Cyclic and secondary amides, such as 2-pyrrolidinone, can be amidocarbony-lated only with formaldehyde (12). Lin and Knifton reported on the catalytic performance of various cobalt/ligand systems in the synthesis of iV-acetylglycine. Basic phosphines, such as PBus, allowed low pressure conditions (55 bar). The addition of Ph2SO or succinonitrile resulted in improved selectivity and facilitated the catalyst recovery (13-15). The addition of acid cocatalysts (plfa < 3 e.g., trifluoroacetic acid) allowed for low temperature conditions and the absence of hydrogen (16) (Scheme 3). 

Another example using palladium as the metal center involves the use of a carboxylic phosphine, which was effective in the intra- and intermolecular Heck reaction of a dimethyliodo derivative and of iodobenzene, respectively, with ethyl acrylate [23], For the intramolecular reaction, the cyclic amide was produced in nearly quantitative yields using mild reaction conditions (Eq. 9). A comparison with the TPPTS system reveals the m-TPPTC (m-triphenylphosphine tricarboxylic acid [ Li salt]) analog to be a more efficient system. After one hour of reaction, a 60% conversion was observed compared to approximately 45% with the TPPTS system. 

Amides. Despite many investigations in the 1970s and 1980s on Pd-catalyzed a-arylation of carboxylic acid derivatives, that of amides had not been studied until recently. In 1998, the reaction of potassium enolates of 7V,7V-dimethylacetamide (DMA) and other amides with aryl bromides in the presence of catalytic amounts of Pd(dba)2 and bidentate phosphines, such as BINAP and dppf, was shown to provide the desired a-arylated products in up to roughly 70% yields, as shown in Table Diarylation competed with monoaryladon to the extent of up to 18%. Under the conditions used, the intermolecular reactions of amides other than acetamides were rather disappointing, as indicated by the last two entries in Table 5. Clearly, additional development is desirable. Its intramolecular cyclic version, however, is considerably more favorable, as discussed in the following subsection. 

---