Benzaldehyde hydrophosphonylation

Scheme 5-42 Zinc-catalyzed asymmetric hydrophosphonylation of benzaldehyde...

A bimetallic catalyst prepared from BINOL and lithium aluminum hydride has been found to result in useful asymmetric induction in the Pudovik reaction [17]. The (f )-ALB catalyst 64 (10 mol %) facilitates the addition of dimethyl phosphite to a variety of electron-rich and electron-poor aryl aldehydes in high yield with induction in the range 71-90 % ee. The nature of the solvent is important in this reaction—the induction for addition to benzaldehyde dropped from 85 % ee to 65 % ee when the solvent was changed from toluene to dichloromethane. Aluminum seems to be a key to the success of this reaction, because reaction with benzaldehyde was not as successful with other bimetallic catalysts. BINOL catalysts with lanthanum and potassium gave only 2 % ee, a catalyst with lanthanum and sodium gave a low 32 % ee, and a catalyst with lanthanum and lithium gave only a 28 % ee [18]. Aliphatic aldehydes were not successfully hydrophosphonylated with dimethyl phosphite by catalyst 64 (Sch. 9). Induction was low (3-24 % ee) for unbranched and branched substrates. a,/3-Unsaturated aldehydes were, however, reported to work nearly as well as aryl aldehydes with four examples in the range 55-89 % ee. The failure of aliphatic aldehydes with this catalyst can be overcome by reduction of the product obtained from reactions with a,)3-unsaturated aldehydes. As illustrated by the reduction of 67 with palladium on carbon, this can be done without epimerization of the a-hydroxy phos-phonate. 

The above-mentioned effects of slow addition of the aldehydes on the enanti-oselection can be best explained as follows. Heterobimetallic catalysts such as LLB are believed to activate both nucleophiles and electrophiles. For the hydrophosphonylation of comparatively unreactive aldehydes the activated phosphite can react only with aldehydes which are pre-coordinated to lanthanum. However, in the case of reactive aldehydes such as benzaldehyde and cinnamaldehyde, the Li-activated phosphite may be able to undergo a competing reaction with the unactivated aldehyde. If such aldehydes are added in one portion, the ee of the product will be reduced. Slow addition of aldehyde,in contrast, has the effect of maximizing the ratio of activated to unactivated aldehyde present in solution, by allowing time for the catalytic cycle to complete and regenerate the catalyst, thereby facilitating aldehyde activation. Reactive aldehydes should, therefore, be added slowly in order to avoid the side reaction which proceeds without activation of the aldehyde by LLB (Scheme 19). 

TABLE 28.7 Hydrophosphonylation of Benzaldehyde, Acetophenone, and Related Derivatives with Diethylphosphite Catalyzed hy Homoleptic and Heteroleptic Ae Complexes [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. 

Kee and coworkers reported that Al(salen) (73a) and Al(salan) (67b) complexes catalyze hydrophosphonylation of benzaldehyde derivatives [70]. Enantioselectivi-ties were modest in the reactions catalyzed by each catalyst. Interestingly, compared to Al(salen) complex (73a), Al(salan) complex (67) results in better enantioselectiv-ity (Scheme 6.55). The structure of (67b) in solution was identified as a dimeric hydroxyl-bridged structure with the twisted ligand geometry. In addition, Jacobsen s Al(salen)Cl (67a), which is well known as an excellent asymmetric catalyst for hydrocyanation of aromatic imines, was not an effective catalyst for this reaction [62]. 

Recent developments in metal-catalysed asymmetric addition of phosphorus nucleophiles, with the formation of P-C bonds, have been reviewed the metals and electrophiles have been discussed widely. DFT study of salicylaldehyde-Al(ni)-catalysed hydrophosphonylation of benzaldehyde by diethylphosphonate (DEPH) reveals that P-H activation by the formation of Al-phosphite species is followed by rate-determining C-P bond formation, which determines the predominant (S) configuration (with 99% ee) of the a-hydroxyl phosphonate ester on regeneration of the salicylaldehyde-Al(III) complexes. Reduction of activated carbonyl groups by alkylphosphanes can proceed either through path a or path b (Scheme 35), as evidenced experimentally and theoretically. ... 

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