The reaction of aromatic and aliphatic aldehydes with hypophosphorus acid under microwave irradiation was examined. The reaction gave a mixture of a racemic pair of bis(alpha-hydroxyalkyl)phosphinic acids and acetal derivatives from the corresponding bis(alpha-hydroxyalkyl)phosphinic acids of meso-stereochemistry in good yield. The difference in solubility in organic solvents due to polarity allowed us to readily separate these compounds. This method constitutes an easy, rapid, and good-yielding preparation and separation of bis(alpha-hydroxyalkyl) phosphinic acid diastereoisomers from simple starting materials using microwave irradiation.
A novel class of phosphinic acid derivatives, four-membered cyclic oxaphosphetanes, was synthesized by the reaction of bis(hydroxymethyl)phosphinic acids with a mixture of triphenylphosphine and diisopropyl azodicarboxylate in toluene-dichloromethane at room temperature via an intramolecular Mitsunobu reaction.Organophosphorus compounds occupy an important place among the various types of organoelemental compounds in which chemists are now interested. 1 Among the organophosphorus compounds, phosphinic acids are an important class of compounds that exhibit a variety of interesting and useful properties. Phosphinic acids have attracted growing attention because of their novel applications in the areas of industrial, agricultural, medicinal, and synthetic intermediates. [2][3][4][5] In addition, the structure of the phosphinic functional group mimics the transition state of peptide hydrolysis and the symmetric nature of the phosphinic acid derivatives are expected to benefit in their binding to the homodimer of HIV-protease having C 2 -axis symmetry. 6 The presence of the phosphorus atom in the heterocycle could regulate important biological functions and also increase the biological activity of this type of compound, in a similar way to that reported for enzymatic inhibitors and for other pharmaceuticals. 7 In contrast to extensive studies on the synthesis of heterocyclic compounds 8 and phosphinic derivatives, 9,10 relatively few papers have been reported on the synthesis of heterocyclic phosphinic compounds. 11 Since heterocycles have shown a variety of biological activity, and since phosphinic acids can be used in industry, agriculture, and medicine, and in organic synthesis, we set out to expand the range of compounds accessible from simple building blocks.The Mitsunobu reaction, a dehydration-condensation reaction between alcohols and various nucleophiles, has gained wide application in organic synthesis due to its effectiveness and versatility. 12 This mild reaction converts a hydroxy group into a potent leaving group that can be displaced by a wide variety of nucleophiles. The Mitsunobu reaction allows the conversion of primary and secondary alcohols into esters, phenyl ethers, thioethers, and various other compounds; it is a stereospecific reaction. The nucleophile employed should be acidic, since dialkyl azodicarboxylate must be protonated during the course of the reaction to prevent side reactions. As a part of our effort to explore the utility of novel reactions for the synthesis of organophosphorus compounds, 13 we recently described a new method for the synthesis and separation of bis(a-hydroxyalkyl)phosphinic acids from the reaction of hypophosphorus acid with aldehydes. 14 Herein, we report the synthesis of a new class of cyclic four-membered phosphinic acids via the reaction of bis(a-hydroxyalkyl)phosphinic acids with a mixture of triphenylphosphine and diisopropyl azodicarboxylate via intramolecular Mitsunobu reaction.We first carried out the reaction of benzaldehyde with hypophosphorus acid (1a)...
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