Hydrophosphonylation ketones

In addition to aldehydes, the hydrophosphonylation reaction was also attempted on ketones. Thus, Xu and Wang have studied the reaction of diphenyl phosphite with N-allq lated isatins catalysed by quinine that gave superior results in comparison to thiourea catalysts (Scheme 15.2). 

HYDROPHOSPHONYLATION OF ALDEHYDES AND NONACTIVATED KETONES BY CHARGE-NEUTRAL HOMOLEPTIC AND HETEROLEPTIC COMPLEXES OF LARGE ALKALINE EARTHS... 

Ternary and quaternary a-hydroxy-phosphonates, an important class of biologically active compounds, are commonly obtained by addition of dialkylphosphites onto aldehydes or ketones [30]. Well-defined mono- or bimetallic complexes of rare-earth metals, titanium, or aluminum have emerged over the past two decades as effective catalysts for this so-called hydrophosphonylation of aldehydes [31] and, with more difficulty, that of ketones [31c,d, 32], which are far less reactive because of their lower electrophilicity. In some cases, good enantioselectivities could be achieved thanks to the use of chiral metal-based precatalysts [31, 32], Despite their several similarities with rare-earth elements, we were surprised to see that discrete complexes of the large Ae metals had never been utilized to catalyze hydrophosphonylation reactions. 

In fact, we found that hydrophosphonylation of aldehydes and nonactivated ketones could be achieved selectively and rapidly at room temperature using very low catalytic loadings (as low as 0.02 mol%) of the simple Ae[N(SiMe3)2l2(THF)2 complexes (Ae = Ca, Sr, Ba) (Scheme 28.11, Table 28.7) [33]. Indeed these homoleptic Ae precatalysts turned out as... 

Scheme 28.11 Ae heteroleptic and homoleptic complexes screened for the hydrophosphonylation of aldehydes and ketones [33].

Hence, the readily prepared Ae[N(SiMe3)2]2(THF)2 provided efficient and easy access to catalyzed hydrophosphonylation reactions not only with benzaldehydes but also for less reactive, nonactivated ketones, for which turnover fi equencies as high as 1200-1500 min were achieved these values outclass those reported to date by a considerable margin. 

Asymmetric hydrophosphonylation reactions were extended to trifluoromethyl ketones (Scheme 4.148) [238], This approach was interesting since ketones often displayed sluggish reactivity in hydrophosphonylation reactions. While only a few examples were screened, several electron-donating and withdrawing gronps were compatible with the catalyst system, and moderate to excellent yields of the hydroxyphosphonates were obtained. As mentioned in other sections of this text, the retention of the aryl bromide... 

Zhou X, Zhang Q, Hui YH (2010) Catalytic asymmetric synthesis of quatranary a-hydroxy trifluoromethyl phosphonate via chiral aluminum (ID) catalyzed hydrophosphonylation of trilluoromethyl ketones. Org Lett 12 4296-4299... 

The rare earth metal amido complexes (230) have been found to be an excellent catalysts for the Pudovik hydrophosphonylation of wide range of aldehydes and unactivated ketones. The catalysed reactions between diethyl phosphite and aldehydes in the presence of the eomplexes (230) afforded the a-hydrmy aryl phosphonates (229) (R = H) in high yields (up to 99%) at room temperature in short reaction times of 5 to 10 min. The reaction of ketones with diethyl phosphite has been also realised providing corresponding a-hydrojy phosphonates (229) (R H) in moderate to high yields (50-99%) (Scheme 77).Moreover, Carpentier and coworkers have shown for the first time that the selective Pudovik addition of diethylphosphite to aldehydes or ketones to yield a-hydroxy phosphonates (229) could be also effectively promoted by complexes of the large alkaline earth metals (231), Ca, Sr, and Ba. ° ... 

Feng et al. have reported highly enantioselective hydrophosphorylation of aldehydes catalyzed by aluminum complexes with tridentate Schifif base (Scheme 8.74) [188]. Excellent yields (up to 96%) and enantiomeric excess (up to 97%) were found in the addition reaction. Same authors have also studied asymmetric hydrophosphorylation of aldehydes catalyzed by bifunctional chiral aluminum complexes [189] and Lewis acid-catalyzed hydrophosphonylation of ketones [190]. 

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