Silyl Aldol-type reaction catalyzed

Scheme 120 illustrates aldol-type reaction of aldehydes and silyl ene-thiolates catalyzed by 20 mol % of Sn(II) triflate-chiral diamine combined system in propionitrile or dichloromethane (291). A variety of aldehydes such as aliphatic, ,/3-unsaturated, and aromatic aldehydes are usable. The reaction is facilitated by high affinity of the Sn atom to sulfur atoms and the weak Si—S bond. A binaphthol-containing Ti oxo... 

SCHEME 120. Lewis acid-catalyzed asymmetric aldol-type reaction of enol silyl ethers. 

Aldol-type reactions. Trityl perchlorate catalyzes an aldol-type reaction between silyl enol ethers and acetals or ketals to give p-alkoxy ketones. The yields are comparable to those obtained with TiCU (6, 594). The iyn-aldol is formed predominantly ( 4 1). 

Asymmetric Aldol-Type Reaction. CAB complex (2) is an excellent catalyst for the Mukaiyama condensation of simple achiral enol silyl ethers of ketones with various aldehydes. The CAB-catalyzed aldol process allows the formation of adducts in a highly diastereo- and enantioselective manner (up to 96% ee) under mild reaction conditions (eqs 4 and 5). The reactions are catalytic 20 mol % of catalyst is sufficient for efficient conversion, and the chiral auxiliary can be recovered and reused. 

CAB 2, R = H, derived from monoacyloxytartaric acid and diborane is also an excellent catalyst (20 mol %) for the Mukaiyama condensation of simple enol silyl ethers of achiral ketones with various aldehydes. The reactivity of aldol-type reactions can, furthermore, be improved, without reducing the enantioselectivity, by use of 10-20 mol % of 2, R = 3,5-(CF3)2C6H3, prepared from 3,5-bis(trifluoromethyl)phenyl-boronic acid and a chiral tartaric acid derivative. The enantioselectivity could also be improved, without reducing the chemical yield, by using 20 mol % 2, R = o-PhOCgH4, prepared from o-phenoxyphenylboronic acid and chiral tartaric acid derivative. The CAB 2-catalyzed aldol process enables the formation of adducts in a highly diastereo- and enantioselective manner (up to 99 % ee) under mild reaction conditions [47a,c]. These reactions are catalytic, and the chiral source is recoverable and re-usable (Eq. 62). 

Trimethylsilyloxy)furan can also be used as a functionalized silyl enol ether for the asymmetric catalytic aldol-type reaction. Figadere has reported that the reaction of aliphatic aldehydes with the siloxyfuran catalyzed by BINOL-derived titanium complex provides the diastereomeric mixtures with high enantioselectivity (Sch. 42) [107], The addition reaction proceeds at the y position of the siloxyfuran to give butenolides of biological and synthetic importance. 

Several examples of Sc(OTf)3-catalyzed aldol reactions of silyl enolates with aldehydes were been examined. Silyl enolates derived from ketones, thioesters, and esters reacted smoothly with different types of aldehyde in the presence of 5 mol % Sc(OTf)3 to afford the aldol adducts in high yields. Sc(OTf)3 was also found to be an effective catalyst in aldol-type reactions of silyl enolates with acetals. The reactions proceeded smoothly at -78 °C or room temperature to give the corresponding aldol-typc adducts in high )delds without side-reaction products. It should be noted that aldehydes were more reactive than acetals. For example, while 3-phenylpropionalde-hyde reacted with the ketene silyl acetal of methyl isobutyrate at -78 °C to give the aldol adduct in 80 % yield, no aldol-type adduct was obtained at -78 °C in the reaction of the same ketene silyl acetal with 3-phenylpropionaldehyde dimethyl acetal. The acetal reacted with the ketene silyl acetal at 0 °C to room temperature to give the... 

A second, less used, strategy encompasses the Lewis acid catalyzed intramolecular reaction of a silyl enol ether with a propargyl cation. The latter can be conveniently generated by a cobalt complexed propargyl ether. This complexation strongly helps the carbocation formation. By using cobalt complexation, intramolecular aldol type reactions (for R = OR ) have been accomplished. ... 

SbF6)2 [61], and an oxovanadium(IV) complex [62] are effective catalysts. Matsuda et al. recenfly reported that a cationic Ir complex generated in situ from [Ir(COD) (PPh3)2]OTf and H2 catalyzes aldol and aldol-type reactions of aldehydes and acetals with silyl enolates in CH2CI2 [63]. 

Chiral auxiliary-bound substrates have also been used for the asymmetric process. The aldol reaction of chiral pyruvates such as 46 is a reliable method for highly enantioselective synthesis of functionalized tertiary alcohols (Scheme 10.38) [112]. The Lewis acid-catalyzed aldol-type reactions of chiral acetals with silyl enolates are valuable for the asymmetric synthesis of -alkoxy carbonyl compounds ]113, 114]. 

The Lewis acid-promoted aldol-type reaction of thiomethylsilanes with silyl enolates and subsequent fluoride ion-catalyzed cyclization leads, on the other hand, to tetrahydrothiophenes. In these reactions the thiomethylsilanes serve as thiocarbonyl ylide equivalents. 

In contrast to the mechanism discussed in the previous section, catalytic, enantioselective aldol addition processes have been described which proceed through an intermediate aldolate that undergoes subsequent intermolecular silylation. Denmark has discussed this possibility in a study of the triarylmethyl-cation-catalyzed Mukaiyama aldol reaction (Scheme 10) [73]. The results of exploratory experiments suggested that it would be possible to develop a competent catalytic, enantioselective Lewis-acid mediated process even when strongly Lewis acidic silyl species are generated transiently in the reaction mixture. A system of this type is viable only if the rate of silylation of the metal aldolate is faster than the rate of the competing silyl-catalyzed aldol addition reaction (ksj>> ksi-aidoi Scheme 10). A report by Chen on the enantioselective aldol addition reaction catalyzed by optically active triaryl cations provides support for the mechanistic conclusions of the Denmark study [74]. 

Aldol-type reaction. The low-temperature-catalyzed condensation of O-silyl ketene acetals with aldehydes leads to /3-hydroxy esters. The same catalyst also mediates allylation of aldehydes. 

Sc(OTf)3 also catalyzes aldol-type reactions of silyl enolates with acetals. For example, the reaction of 3-phenylpropionaldehyde dimethyl acetal with the ketene silyl acetal of methyl isobutyrate proceeds at 0°C to room temperature to give the desired adduct in 97% yield (eq 2) ... 

The Sc(OTf)3-catalyzed aldol-type reactions of silyl enol ethers with aldehydes can be performed in micellar systems using a catalytic amount of a surfactant such as sodium dodecylsulfate (SDS). In these systems, reactions proceed smoothly in water without using any organic solvent. 

TMSOTf mediates a stereoselective aldol-type condensation of silyl enol ethers and acetals (or orthoesters). The nonbasic reaction conditions are extremely mild. TMSOTf catalyzes many aldol-type reactions in particular, the reaction of relatively non-nucleophilic enol derivatives with carbonyl compounds is facile in the presence of the silyl triflate. The activation of acetals was first reported by Noyori and has since been widely employed (eq 14). ... 

The first use of rare earth metals in the aldol reaction began in the case of cerium enolate (198). Subsequently, Kagan and Kobayashi groups reported systematically the use of rare earth metalscatalyzed for the Mukaiyama aldol-type reaction of silyl enol ethers with aqueous formaldehyde solution (199,200). The efficiency of rare earth metals in a Mukaiyama aldol reaction of 1-trimethylsiloxycyclohexene with benzaldehyde was examined in aqueous THF (Scheme 52). Of the rare earth metal trifiates screened, catalytic efficiency was increased in the order of Yb (91%) > Gd (89%) > Lu (88%) > Nd (83%) > Dy (73%) > Er (52%) > Ho(47%) > Sm (46%) > Eu (34%) > Tm (20%) > La (8%) > Y (trace) (201,202). For different aldol or aldol-type reactions, every rare earth metal occupied its special position in the aldol reaction with distinctive catalytic activity. There were several reviews concerning the rare earth metals catalyzed aldol reactions (203,204). New progress in this context will be discussed herein according to rare earth metals catalysis especially for the past 10 years. 

Mukaiyama aldol reactions of various silyl enol ethers or ketene silyl acetals with aldehydes or other electrophiles like chloromethyl methyl ether and trimethylorthoformate proceed smoothly in the presence of 2 mol% of 1 (eq 1) (3, 5). These reactions can be carried out in aqueous media, so that the reaction of silyl enol ethers with an aqueous solution of formaldehyde does not present any problems. Triphenylboron catalyzes no aldol-type reactions. 

The aldol or aldol-type reaction is well recognized as one of the most important carbon-carbon bond forming reactions in organic synthesis. As shown in Scheme 8.1, two stereogenic centers could be generated in this aldol reaction. The classical aldol condensation between an aldehyde and a ketone is often catalyzed by a base or an acid. Another approach is the acid-catalyzed cross-aldol reaction of silyl enol ethers with carbonyl compounds, the so-called Mukaiyama reaction. 

Loh, T.-P. and Li, X.-R., Clay montmorillonite KIO catalyzed aldol type reaction of aldehydes with silyl enol ethers in water. Tetrahedron, 1999, 55,10789 10802. 

Table 15.5 Aldol-type reaction of aldehydes 1 with silyl ketenes 92a (R = H, = Me), catalyzed by 81 (Scheme 15.18) [83].

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

More recently, asymmetric Mannich-type reactions have been studied in aqueous conditions. Barbas and co-worker reported a direct amino acid catalyzed asymmetric aldol and Mannich-type reactions that can tolerate small amounts of water (<4 vol%).53 Kobayashi found that a diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF2, a chiral diamine ligand, and trifluoromethanesul-fonic acid (Eq. 11.31).54 The diastereoselective Mannich-type reaction... 

---