Acylphosphonates with alcohols

Studies of Equilibria, Configuration and Conformation. - Alcoholic solutions of acylphosphonates have been shown to contain considerable amounts of hemiketals by examination by P NMR spectroscopy. Because of the great difference between the P chemical shifts of acylphosphonates (831 0) and their hemiketals (63ip= 17-21), P NMR spectroscopy was shown to be a suitable method for studying the rates and equilibrium of hemiketal formation of acylphosphonates with different alcohols. 

The reaction of acylphosphonate diesters with alcohols was reported early to lead to dialkyl hydrogenphosphonates and carboxylate esters In a more recent systematic study, conditions were developed to use acylphosphonates for the acylation of alcohols. It was found that 1,5-diazabicyclo [5.4.0] undec-7-ene (dbu) is a highly effective catalyst for acylation of alcohols by acylphosphonates. Two special aspects deserve mention (1) /er butyl alcohol could be acylated with diethyl benzoylphosphonate, in the presence of dbu and 4-dimethylaminopyridine, to give r r/-butyl benzoate in 57% yield (2) the primary hydroxy group of a diol (e.g. butane 1,3-diol) could be acylated fairly selectively in the presence of a secondary hydroxy group by this methodology (ratio of mono to diacyl product =88 12). 

LTBA can also cleave selectively the P—C bond of acyl phosphonates 2.58, while preserving other functional groups [DSl] (Figure 2.28). Nevertheless, the reduction of similar compounds such as 2.59 by NaBH4 in EtOH buffered by boric acid does preserve the P—C bond and leads to diastereomeric a-phosphorylated alcohols [BS5, DSl] (Figure 2.28). After enolization by NaH, the P—C bond cleavage of acylphosphonates (Et0)2P(0)CH2C0R can be realized with LAH [HS7]. 

Treatment of acylphosphonic acids with NaBH4 in aqueous or alcoholic ammonia solution produces 1-aminoalkylphosphonic acids in good yields... 

Free acylphosphonic acids are easily obtained by treatment of i z.s (trimethylsilyl) (alkoxycar-bonyl)phosphonates with EtOH or by exposure to air for several hours. Diethyl (alkoxycarbo-nyl)phosphonates are prepared by condensation of the corresponding alcohols with the diethyl (chlorocarbonyl)phosphonate in the presence of EtjN or DMAP. ... 

Dialkyl acylphosphonates are used for acylation of alcohols. Kabachnik [236] reported that dimethyl benzoylphosphonate formed crystalline 1 1 addition products with aUphatic alcohols, which can be converted in the presence of dry hydrogen chloride into carboxylic esters and dimethyl H-phosphonate in moderate yields. Sakurai reported that dialkyl acylphosphonates underwent slow acylation with a large excess amount of alcohols to give esters [237]. It was shown that triethylamine catalyzed acylation of alcohols with dialkyl acylphosphonates [238]. It was found that use of l,5-diazabicyclo[5,4,0]undec-5-ene (DBU) increased the rate of the acylation of alcohols with diethyl benzoylphosphonate dramatically [239]. When one equivalent of DBU was used in CHjClj, the acylation was completed within 10 min and the corresponding ester 1 was obtained in 99% yield. The use of 0.1 equivalent of DBU gave 1 in 95% yield. Under this condition, the formation of 3 was suppressed remarkably and only a trace of 3 was formed. 

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