A simple synthetic approach to unsymmetrically substituted (γ-oxoalkyl)phosphine oxides

Abstract

SHORT COMMUNICATIONSPhosphine oxides and phosphines having a chiral phosphorus atom, including optically active compounds, are successfully used as ligands for metalcomplex catalysts in organic and asymmetric synthesis [1][2][3]; some derivatives are known as pesticides and biologically active substances [4]. However, more extensive application of these compounds is seriously limited due to complexity of methods for the preparation of phosphine oxides and phosphines with three different substituents, especially with those containing additional functional groups. Taking into account continuously growing demands for such compounds, development of accessible procedures for their synthesis remains to be important (see, e.g., [3][4][5][6][7]). Most known procedures require the use of expensive reagents and are complex and laborious; isolation of intermediate and final products is often difficult. Either racemates are obtained with subsequent optical resolution or stereoselective syntheses are necessary.We proposed a new and simple synthetic approach to unsymmetrically substituted phosphine oxides containing an oxo group as additional functional substituent in the γ-position with respect to the phosphorus atom. This approach is based on the reaction of accessible phosphorus-containing heterocycles having two P-C bonds, in particular 2-alkyl(aryl)-3,3,5-trimethyl-2,3-dihydro-1,2λ 5 -oxaphosphole 2-oxides like I [8][9][10][11], with Grignard compounds. Hydrolysis of the reaction mixture gives targeted (1-methyl-4-oxopent-2-yl)phosphine oxides II in more than 95% yield. Due to specific structure of the initial dihydrophosphole oxides (they possess one exo-and one endocyclic P-C bond and reactive endocyclic P-O bond), the third P-C bond is formed with high chemoselectivity with no any side process. As a result, the products are formed in high yields and with high purity. The structure of phosphine oxides II thus obtained was confirmed by IR, 1 H, 31 P, and 13 C NMR, and mass spectra. 4-[Ethyl(methyl)phosphoryl]-4-methylpentan-2-one (IIa).Compound Ia, 5.7 g (35.6 mmol), was added dropwise to the Grignard compound prepared according to standard procedure from 1.3 g (54.2 mmol) of magnesium and 4.1 ml (5.9 g, 54.2 mmol) of ethyl bromide in 100 ml of diethyl ether. When the addition was complete, the mixture was heated to the boiling point under vigorous stirring over a period of 1 h, cooled to 20°C, and neutralized under vigorous stirring at the boiling point by adding in succession 30 ml of water and 5 ml of hydrochloric acid. The organic phase was separated, the aqueous phase was extracted with methylene chloride (2 × 100 ml), the extracts were combined with the organic phase, the solvent was distilled off, and the residue was dried under reduced pressure (12 mm) at 100°C. Yield 6.6 g (98%), light brown oily substance. IR spectrum, cm -1 : I, R 1 = Me (a), Ph (b); II, R 1 = Me, R 2 = Et (a), Pr (b); R 1 = Ph, R 2 = PhCH 2 (c).