A. O. Kolodyazhnaya

An efficient method for the phosphonation of C=X compounds

Reaction of trialkyl phosphites with C=X electrophiles (aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins) in the presence of amines and anilines hydrohalides was studied. We found that pyridine hydrohalides effectively activate the reaction of tralkyl phosphites with various C=X electrophiles: aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins. Particularly high activity showed pyridine hydroiodide. This reaction is a convenient method of synthesis of hydroxyphosphonates, aminophosphonates, carbamoylphosphonates, carbamoylthiophosphonates, and methylenebisphosphonates.

Synthesis of phosphonic analog of (S)-homoproline

N-Boc-Prolinal I was obtained by reduction of NBoc-Proline methyl ester with H-DIBAL [2] and used as a starting compound. The phosphonylation of NBoc-Prolinal I with triethylphosphite in the presence of pyridinium perchlorate as a catalyst [3] led to the formation of hydroxyphosphonate II, which was obtained as a mixture of (S,RP) and (S,SP) diastereoisomers in very high yield. After that the hydroxyphosphonate II was dehydroxylated according to Barton– McCombie method. The treatment of compound II with thiocarbonylbis (imidazole) III in dichloroethane at reflux afforded the compound IV, which was purified by column chromatography and its structure was confirmed by H, C, and P NMR spectra.

Organic catalysis of phospha-aldol condensation

Phospha-aldol reaction of dialkylphosphites with carbonyl compounds is catalyzed by cinchonine alkaloids and thier modified derivatives to give optically active hydroxyphosphonates. The use of diastereomeric pairs of alkaloids allowed obtaining both optical antipodes of hydroxyphosphonates. Cinchonine alkaloids show the highest enantioselectivity as organic catalysts. It was found that ordinary crystallization of some enantiomerically enriched hydroxyphosphonates leads to isolation of the enantiomerically pure stereoisomers. Hydroxyphosphonic acids were obtained by hydrolysis of phosphonates. Fluoroalkylphosphonates were obtained by reaction with diethylaminotrifluorosulfurane (DAST).

A new approach towards synthesis of phosphorylated alkenes

New method of synthesis of trans-vinylphosphonates via reaction of trimethylsilyl(methyl)phosphonites with carbonyl compounds in the presence of carbon tetrachloride has been developed. The reaction involves formation of C-trimethylsilyl substituted ylides and 2-chloro-1,2λ5-oxaphosphetanes as intermediates.

Synthesis of phosphonic analog of glutamic acid

A scheme for the synthesis of phosphonic analog of glutamic acid starting from tert-butyl N-tert-butoxycarbonylaspartate I was developed. The latter was obtained from aspartic acid by the previously described method [1, 2]. The carboxy group of compound I was acylated with ethyl chloroformate and reduced with sodium borohydride in methanol to give tertbutyl-(S)-N-(tert-butoxycarbonyl)homoserine (S)-II [2]. The latter was converted to the bromide (S)-III via the reaction with triphenylphosphine and bromotrichloromethane [3]. Bromide III was introduced into the Arbuzov reaction with trimethylsilyldiethylphosphite to yield phosphonate IV, deprotection of which with diluted hydrochloric acid resulted in the phosphorus analog of glutamic acid V.

Generation of tert-Butyl-λ5-phosphanedione and Its Chemical Properties

Flash vacuum thermolysis of trimethylsilyl tert-butylphosphonohalidates involved elimination of halo(trimethyl)silane with the formation of tert-butyl-λ5-phosphanedione whose structure was confirmed by chemical reactions. tert-Butyl-λ5-phosphanedione readily undergoes trimerization, reacts with 2-phenyloxirane to give cycloaddition product, and takes up alcohols.