Lewis aldol reactions, asymmetric version

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

Besides the silyl enolate-mediated aldol reactions, organotin(IY) enolates are also versatile nucleophiles toward various aldehydes in the absence or presence of Lewis acid.60 However, this reaction requires a stoichiometric amount of the toxic trialkyl tin compound, which may limit its application. Yanagisawa et al.61 found that in the presence of one equivalent of methanol, the aldol reaction of an aldehyde with a cyclohexenol trichloroacetate proceeds readily at 20°C, providing the aldol product with more than 70% yield. They thus carried out the asymmetric version of this reaction using a BINAP silver(I) complex as chiral catalyst (Scheme 3-34). As shown in Table 3-8, the Sn(IY)-mediated aldol reaction results in a good diastereoselectivity (,anti/syn ratio) and also high enantioselectivity for the major component. 

The activation of the carbonyl group by Lewis acids was another leap made in the 1960s as typified by Mukaiyama-aldol reaction. In sharp contrast to the conventional carbonyl addition reactions that had been run under basic conditions, this new method allowed the addition of various nucleophiles under acidic conditions with high chemo- and stereocontrol and, consequently, the scope of the carbonyl addition reaction was extensively expanded. The Lewis acid-promoted ally-lation with allylmetals and ene reaction also received as much attention as the aldol-type reaction. It should be further pointed out that the catalytic versions of asymmetric reactions, which represent one of the most exciting topics in recent synthetic chemistry, owe their development strongly to the Lewis acid activation protocol. The design of a variety of chiral ligands for metals has produced luxuriant fruits in this field. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Recent developments include an asymmetric version of the aldol reaction in the y-position. The silyl enol ether 82 from ethyl crotonate reacts with aldehydes in the presence of the Lewis acid SiCI4 and an asymmetric catalyst (see the paper if you are interested in the structure of this complex catalyst) to give a high yield of the aldol product 83. The y a ratio is >99 1 and the product 83 is virtually enantiomerically pure.23... 

Asymmetric aldol reaction of silyl enol ethers. (16,221-222). The use of TiCI4 as promoter of aldol condensation of silyl enol ethers with aldehydes, first reported in 1973 (6,590-591), has seen wide use, but has the drawbacks that 1 cquiv. of the Lewis acid is required and that an asymmetric version requires use of chiral aldehydes or chiral silyl enol ethers. More recently, the combination of a salt and a weak Lewis acid, neither effective catalysts themselves, was found to be effective in catalytic (5-10 mol %) amounts. Further research showed that tin(ll) triflatc when coordinated with a chiral diamine can effect catalytic asymmetric allylation of aldehydes (13,302) and Michael reactions (15,313-314), even though this complex cannot promote aldol condensation. Eventually the combination of tin(Il) triflatc, a chiral diamine,... 

Reports of the use of chiral aluminum Lewis acids in the asymmetric aldol reaction are quite limited. The first enantioselective aluminum-catalyzed Mukaiyama aldol reaction was reported about 10 years ago (158). In this asymmetric version, /5-hydroxy ester was formed in high enantiomeric excess by the ketene silyl acetal with aldehyde in the presence of a chiral Lewis acid prepared from diethylaluminum chloride (Et2AlCl) and chiral diol derived from... 

Recent efforts in this area are focused mainly on the improvement of the catalytic asymmetric version of the aldol reaction A wide variety of chiral Lewis acid catalysts derived from Ti, Sn,t lanthanides,and... 

With the current emphasis on enantioselective synthesis, it is not surprising that numerous, highly successful asymmetric versions of aldol reaction have been developed. Noncatalytic methods involve the use of stoichiometric amounts of a chiral auxiliary in diastereoselective aldol reactions. Small-molecule-catalyzed aldol reactions typically would involve the use of a chiral Lewis acid for aldehyde activation or a chiral Lewis base for donor... 

The Lewis-acid-catalyzed carbonyl-ene reaction represents an important alternative method for the addition of an allyl group to a carbonyl group (Equation 23). The resulting secondary homoallylic alcohols are amenable to a number of structural modifications and constitute useful synthetic building blocks. Because the olefin of the products can be a surrogate for a carbonyl functionality, these homoallylic alcohol are formally the synthetic equivalent of aldol addition products. Powerful asymmetric versions of the carbonyl-ene reaction [196, 197] provide an important alternative to the more traditional allylation methods, which primarily employ silanes, boranes, or stannanes (see Chapter 5). 

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