Enantioselective Sakurai-Hosomi Allylation Reactions

Asymmetric allylation is a valuable method for constructing chiral functionalized structures, and many chiral allylmetal reagents directed toward a high level of asymmetric induction have, therefore, been designed and synthesized. Although for some of these good to excellent enantio- and diastereoselectivity are obtained in reactions with achiral aldehydes, we developed the first novel method for a catalytic process in 1991 [49a]. 

The CAB 2 catalyst has powerful activity in the Sakurai-Hosomi allylation of aldehydes and gives homoallylic alcohols in excellent enantiomeric excess (Eq. 66) [49a]. 

Reaction of borane-THF complex with mono(2,6-diisopropyl)benzoyltartaric acid in dry propionitrile at 0 °C affords the catalyst solution. Condensation of achiral aldehydes with allylsilanes is promoted by this catalyst, 2, (20 mol %) at -78 °C to produce homoallylic alcohols with enantio- and diastereoselectivity (Eq. 66). 

Several arylboronic acids have been examined in place of borane-THF to improve the Lewis acidity of 2 and the stereoselectivity [49b]. The boron substituent of 2 has a large effect on the chemical yield and the enantiomeric excess of the allylation adduct, and 3,5-bistrifluoromethylbenzeneboronic acid results in the greatest reactivity— when a complex which is easily prepared from a tartaric acid derivative and 3,5-bistri-fluoromethylbenzeneboronic acid in propionitrile at room temperature is used, the reactivity is improved without reducing the enantioselectivity. For instance, the reaction of l-trimethylsilyl-2-methyl-2-propene with benzaldehyde in the presence of only 10 mol % 2 proceeds to give 99 % yield and 88 % ee (Fig. 19). 

Marshall et al. reported that more reactive allyltin analogs can be used instead of allylsilane nucleophiles in our CAB 1 catalyst system, and found that trifluoroacetic anhydride is an efficient promoter that retains stereoselectivity (Eq. 67) [50aj. 

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Enantioselective Mukaiyama-aldol and Sakurai-Hosomi allylation reactions catalyzed by chiral Lewis acid are currently of great interest because of their utility for the introduction of asymmetric centers and functional groups. 

Most desirable, however, would be chiral catalysts for the addition of the more readily available and less toxic allyl silanes, but so far the efforts towards an enantioselective variant of the Sakurai-Hosomi reaction have been less successful. Some time ago Ketter and Herrmann [3a] obtained 24 % ee for the addition of allyl silane to aldehydes catalyzed by the dichlorotitanate 1. 

We have further found that BINOL-Ti (1) catalyzes the Sakurai-Hosomi reaction of methallylsilanes with glyoxylates (Scheme 28) [73]. Surprisingly, however, the products were obtained in the allylic silane (ene product) form with high enantioselectivity. 

Substituted allylsilanes are subject to ene reaction with aldehydes and a,/3-unsaturated carbonyl compounds in the presence of a Lewis acid. The Et2AlCl-promoted reaction of /3-siloxymethyl-substituted allylsilane 27 with aldehydes gives more functionalized allylsilanes (Equation (37)).148 The use of TiCU instead of Et2AlCl leads to the Hosomi-Sakurai allylation. Catalytic enantioselective carbonyl-ene reactions of methallylsilanes have been achieved by using chiral Ti and A1 complexes.149,150... 

The chiral Bronsted acids (249-250) have been shown to initiate the Hosomi-Sakurai reaction of imines (246) with allyl- and crotyltrimethyl-silane (247) to give products (248) with excellent enantioselectivities (Scheme 64). ... 

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