Aldehydes hydrophosphonylation reactions

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

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. 

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. 

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. 

Because organophosphorus compounds are important in the chemical industry and in biology, many methods have been developed for their synthesis [1]. This chapter reviews the formation of phosphorus-carbon (P-C) bonds by the metal-catalyzed addition of phosphorus-hydrogen (P-H) bonds to unsaturated substrates, such as alkenes, alkynes, aldehydes, and imines. Section 5.2 covers reactions of P(lll) substrates (hydrophosphination), and Section 5.3 describes P(V) chemistry (hydrophosphorylation, hydrophosphinylation, hydrophosphonylation). Scheme 5-1 shows some examples of these catalytic reactions. 

LLB, a so-called heterobimetallic catalyst, is believed to activate both nucleophiles and electrophiles.162 For the hydrophosphonylation of comparatively unreactive aldehydes, the activated phosphite can react with only the molecules precoordinated to lanthanum (route A). The less favored route (B) is a competing reaction between Li-activated phosphite and unactivated aldehyde, and this unfavored reaction can be minimized if aldehydes are introduced slowly to the reaction mixture, thus maximizing the ratio of activated to inactivated aldehyde present in solution. Route A regenerates the catalyst and completes the catalysis cycle (Fig. 2-9). 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

The effects of the slow addition of the aldehydes on enantioselection 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 that are precoordinated to lanthanum. However, in the case of reactive aldehydes such as 54 and 124, 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 thus be reduced. Slow addition of the... 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

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. 

Heterobimetallic catalysis mediated by LnMB complexes (Structures 2 and 22) represents the first highly efficient asymmetric catalytic approach to both a-hydro and c-amino phosphonates [112], The highly enantioselective hydrophosphonylation of aldehydes [170] and acyclic and cyclic imines [171] has been achieved. The proposed catalytic cycle for the hydrophosphonylation of acyclic imines is shown representatively in Scheme 10. Potassium dimethyl phosphite is initially generated by the deprotonation of dimethyl phosphite with LnPB and immediately coordinates to the rare earth metal center via the oxygen. This adduct then produces with the incoming imine an optically active potassium salt of the a-amino phosphonate, which leads via proton-exchange reaction to an a-amino phosphonate and LnPB. 

Other titanium complexes derived from tartaric acid have been used as chiral catalysts. The complexes generated from diol 2.50 and TiCl2(0/-Pr)2 are used as catalysts in asymmetric ene-reactions [778, 816], and in Diels-Alder [778, 780] or [2+2] cycloadditions of ketene thioacetals and unsaturated sulfides [778, 817], The best enantiomeric excesses are observed with 2.50 (R = Me, R = Ph) [778, 817] or 2.50 (R = R = Et, Ar = 3,5-Me2CgH3) [45], These catalysts are also efficient in hydrophosphonylation [818] and in asymmetric hydrocyanation of aldehydes with Me3SiCN [778], These titanium complexes may be used in catalytic amounts provided that the reactions are run in the presence of molecular sieves [559,816],... 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

---