Keck allylation reaction asymmetric catalysts

Keck reported an asymmetric allylation with a catalytic amount of chiral titanium catalyst [24]. The enantioselective addition of methallylstannane to aldehydes is promoted by a chiral catalyst 13 prepared from chiral BINOL and Ti(0-i-Pr)4 (Scheme 9.10). An example of asymmetric amplification was reported by using (R)-BINOL of 50% ee, and the degree of asymmetric amplification was dependent on the reaction temperature. Tagliavini also observed an asymmetric amplification in the enantioselective allylation with a BIN0L-Zr(0-i-Pr)2 catalyst [25]. 

Keck [89a-c], Tagliavini [89d,e], and Yu [89f] have extensively studied the BINOL-Ti- or binol-Zr promoted reactions of achiral aldehydes with allylstan-nanes. The initial studies employed BINOL and either Ti(Oi-Pr)4 or TiCl2(0/-Pr)2 as the Lewis acid promoter in the reaction of achiral aldehydes with allyltributyl-stannane. The reaction affords good yields of the desired homoallylic alcohol with a high degree of enantioselectivity even with as little as 10 mol% of the chiral catalyst (Scheme 10-49) [89a]. The rate and turnover of the catalytic, asymmetric allylation reaction have also been optimized. It was found that when /-PrSSiMe3 is added to the reaction, a rate acceleration occurs, allowing as little as 1-2% of the catalyst to be used [89 fj. 

Keck almost simultaneously reported two procedures using chiral titanium catalysts 6A and 6B for the enantioselective addition of allyltributyltin to aldehydes [11]. In the first procedure, the catalyst 6A is prepared from a 1 1 mixture of (R)-binaphthol and titanium tetraisopropoxide. The second procedure for the preparation of 6B, in contrast, requires a 2 1 mixture of BINOL, Ti(0 Pr)4, and a catalytic amount of CF3SO3H or CF3CO2H. Using 10 mol % of the catalyst 6A or 6B, a variety of aromatic, aliphatic, and a,P-unsaturated aldehydes are efficiently transformed into the corresponding optically active homoallylic alcohols with high enantioselectivity. An improved procedure was later published for the catalytic asymmetric allylation reactions using the 2 1 BINOL/Ti catalytic system [12]. 

A. Furstner and co-workers devised an efficient synthesis of (-)-gloeosporone, a fungal germination inhibitor. They utilized the Keck asymmetric allylation method to create the 7(R>homoallylic alcohol subunit. The reaction of the substrate aldehyde in the presence of the in situ generated catalyst provided the product with high yield and as the only diastereomer. It is important to note that it was essential to use freshly distilled Ti(/-OPr)4 for the preparation of the catalyst in order to get high enantioselectivity and reproducible results. 

Keck asymmetric allylation The reaction of aldehydes with allyltributylstannane in the presence of Lewis acid catalysts to form homoallylic alcohols. 236... 

Keck and Tagliavani reported within months of each other the asymmetric ally-lation reactions with allyltri-n-butylstannane and various aldehydes with BINOL-Ti(IV) catalysts 451 and 452, respectively [289, 2901. Although the two catalysts give similar yields and enantioselectivities with a range of aldehydes, the diiso-propoxide catalyst 451 has been used more extensively. Keck and co-workers have shown that a variety of aldehydes react with allyl and methallyltri-n-butyl-stannane in modest to excellent yield and with good to excellent enantioselection using (/ )-451 as the catalyst (Table 11-25) [289, 296, 2971. 

The use of titanium catalysts formed from (S)- or (/ )-binaphthol 1.44 and H(Oi-Pr)4 or Ti(0/-Pr)2Cl2 has been proposed by Keck, Umani-Ronchi and their cowoikers [1218-1221] for the asymmetric allylation of aldehydes with CH2=C(R)CH2SnBu3 (R = H,Me). These reactions occur near room temperature in the presence of molecular sieves, and excellent yields and enantiomeric excesses are obtained (Figure 6.53). 

Since Keck s original disclosure in 1993 many groups have been interested in expanding the scope of the reaction with a variety of chiral catalysts. These catalytic systems have, in general, moderated the reaction conditions and increased enantioselectivity. This section attempts to present the scope and limitations of many of those systems in an effort to assist in choosing the best system for asymmetric allylation of a specific substrate. 

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