Reactions hydrophosphonylation

Heteroaromatic aldehydes undergo similar enantioselective hydrophosphonylation reactions (Scheme 5-34). 

Meanwhile, chiral (thio)urea catalysts have been employed for a variety of imine addition reactions consisting of Mannich, aza-Henry, Pictet-Spengler, and hydrophosphonylation reactions. ... 

Discussion Catalyst 52 is prepared from Boc-(L)-ter -leucine in five steps, with a 75% overall yield [41]. Details of imine and phosphite preparation are also provided by Jacobsen and co-workers [81]. The hydrophosphonylation reactions as reported by Jacobsen can be carried out without any special precautions, in unpurified commercial diethyl ether (Et20) and under an ambient atmosphere. A reduction in temperature was shown to have a beneficial effect on product enantiopurities, but with a decrease in reaction rates. Unbranched aliphatic aldehydes were incompatible with the reaction conditions as reported, due to their rapid decomposition prior to phosphonylation. Although phosphite ester groups that are more electron-withdrawing than o-nitrobenzyl significantly increase the overall reaction rates, products are obtained with diminished optical purities, possibly due to a retro-addition pathway. 

Other applications of the hydrophosphonylation reaction include the addition of dialkyl phosphite to 2-(alkoxycarbonyl)- or 2-cyanoacrylonitriles. The reaction is carried out in the absence of catalysT - or in the presence of NaNH2, RONa,- - or TFAA. The Michael addition can be combined with an elimination reaction. For example, because of the presence of a methylthio leaving group, dialkyl 2,2-dicyano- or 2-cyan()-2-clhoxyc irbonyl-l-methyl thio-(/ )-vinyl phosphonates are the products of the conjugate addition of dialkyl phosphite to the corresponding ketene dithioacetals in the presence of NaH (2 eq) in THF (Scheme 6.24).--°... 

The hydrophosphonylation reaction of aldimines (173) with phosphites (174) has furnished a-amino phosphonates (175) with high enantioselectivities by means of the chiral phosphoric acid (125) derived from R) BINOL (Scheme 47). ... 

The asymmetric hydrophosphonylation reaction of aldimines (207) with dialkyl phosphites (206) has been reported using catalytical amounts of the phosphoric acid (125), derived from (7 )-BINOL to afford (l )-amino phos-phonates (208) in good to high enantioselectivities (up to 90% cc) (Scheme 58). ... 

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). 

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. 

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. 

The use of salen-based aluminum catalysts for asymmetric hydrophosphonylation reactions has been reported however, the selectivity tended to be low [199, 200]. Katsuki modified the structure of the salen ligand and developed a catalyst system for... 

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... 

The synthesis of phosphorus-containing heterocycles has been reported using a palladium-catalyzed approach (Scheme 4.172) [261]. The overall process involved two phosphorus-carbon(sp ) bond-forming reactions and started with a hydrophosphonylation reaction using a supported palladium catalyst to promote the addition. Conversion of the... 

High diastereoselectvity was achieved in the hydrophosphonylation reaction of chiral a-amino aldehydes using 20 mol% of the Al/Li/BINOL catalyst (ALB) developed by Shibasaki (Scheme 8.63) [172]. The ratio of syn-/anti-isomers was easily controlled by chirality of the ALB catalyst. 

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