Allylation Sakurai

Homoallylic alcohol when R =H syn-diastereomer Homoallylic alcohol when R =H anf/-diastereomer 

R = alkyl, aryl R = H, alkyl, aryl R and R = H, alkyl, aryl Lewis acid = TiC, BF3-OE12, SnCl4, EtAICl2 

In the laboratory of B.M. Trost, a modular approach toward the total syntheses of furaquinocins was developed. To introduce the homoallylic side chain in a diastereoselective fashion, they utilized the Sakurai allylation reaction. During their studies they found that the highest diastereoselectivity can be achieved using 1 equivalent of TiCU at room temperature. Application of other Lewis acids such as BF3 OEt2 gave the product with lower selectivity. Attempts to perform the allylation using catalytic amounts of Lewis acids such as FeCIs or Sc(OTf)s led to no conversion. The resulting homoallylic alcohol served as a common intermediate toward the syntheses of both furaquinocin A and B. 

A convergent total synthesis of 15-membered macrolactone, (-)-amphidinolide P was reported by D.R. Williams and coworkers.In their approach, they utilized the Sakurai aiiyiation to introduce the C7 hydroxyl group and the homoallylic side chain. The transformation was effected by BF3-OEt2 at -78 °C to provide the homoallylic alcohol as a 2 1 mixture of diastereomers. The desired alcohol proved to be the major diastereomer, as it resulted from the Felkin-Ahn controlled addition of the allylsilane to the aldehyde. The minor diastereomer was converted into the desired stereoisomer via a Mitsunobu reaction. 

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General Procedure for the Silylformaltion/Sakurai Allylation. Synthesis of Polyol Fragments for Polyketide and Macrolide Synthesis. In a magnetically stirred stainless-steel Parr bomb the substrate (1 eq) is dissolved in benzene. The solution is cooled to - 78 °C until frozen. Rh(acac)(CO)2 (3 mol %) is then added and the Parr bomb is assembled and pressurized with CO (60 bar) and vented. This purge is repeated twice and the Parr bomb is pressurized with CO (60 bar) at - 78 °C. The apparatus is then immersed in an oil bath and heated at 60 °C for 22-24 h. After cooling to 0 °C, the bomb is vented. The solution... 

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

Bismuth Triflate-Catalyzed Sakurai Allylation Reaction. 71... 

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... 

Sakurai allylation Reaction of allylsilanes with a variety of aldehydes and ketones in the presence of a Lewis acid. 392... 

Related reactions Roush asymmetric allylation, Sakurai allylation ... 

Bianchini, C., Glendenning, L. Homogeneous catalysis. Mechanisms of the catalytic Mukaiyama aldol and Sakurai allylation reactions. 

Hollis, T. K., Bosnich, B. Homogeneous Catalysis. Mechanisms of the Catalytic Mukaiyama Aldol and Sakurai Allylation Reactions. J. Am. Chem. Soc. 1995, 117, 4570-4581. 

TiCl4 is used extensively as a Lewis acid in numerous organic transformations, forming adducts that mediate reactivity. Such reactions include Diels Alder, 54,355 hetero Diels Alder,356 cyclization of olefinic aldehydes,357 Flosomi Sakurai allylic coupling reactions,358 cyclopropanations,359 chal-cogen-Baylis Flillman,360 Mukaiyama Aldol reactions,36 363 reductions of ketones to alcohols 364 and stereoselective nucleophilic additions to aldehydes.365... 

The Sakurai allylation works with a variety of Lewis acid catalysts such as TiCU, AICI3, SnCl4, LtAICL, in addition to BF3 OEt. Reviews (a) Denmark, S. E. Almstead, N. G. In Modem Carbonyl Chemistry Otera, J., Ed. Wiley-VCH Weinheim, 2000 Chapter 10 Allylation of Carbonyls Methodology and Stereochemistry, pp. 299-402. (b) Chemler, S. R. Roush, W. R. In Modern Carbonyl Chemistry, Otera, J., Ed. Wiley-VCH Weinheim, 2000 Chapter 11 Recent Applications of the Allylation Reaction to the Synthesis of Natural Products, pp. 403-490. (c) Demnark, S. E. Fu, J. Chem. Rev. 2003,103, 2763-2793. 

Since the discovery of the Hosomi-Sakurai allylation reaction [332] much attention... 

The use of C2-symmetric 1,2- and 1,3-diols as chiral auxiliaries is a reliable method for asymmetric allylation of acetals [382]. Acyclic acetals derived from homochiral 1-phenylethanol undergo the Hosomi-Sakurai allylation with high diastereoselectivity [383]. Tietze et al. have, on the other hand, reported that the TMSOTf-catalyzed successive acetalization-allylation reaction of aliphatic aldehydes with homochiral silyl ethers 123 and allyltrimethylsilane gives the corresponding homoallyl ethers with complete diastereocontrol these ethers can be readily converted into enantiomerically pure homoallyl alcohols without epimerization (Scheme 10.135) [384]. This method is applicable to asymmetric allylation of methyl ketones [385]. 

A good stereocontrol was also exhibited in the Sakurai allylation of the manno analogue of 12, whereby (- -)-6-cp/-castanospermine (2) was synthesized in 42% yield. 

Sakurai allylation reaction (Hosomi-Sakurai reaction)... 

S )-(+)-4-Phenyloxazolidinone (28) was acylated with crotonoyl chloride to give crotonamide 29 (Scheme 5). Diastereoselective Hosomi-Sakurai allylation of 29 with allyltrimethylsilane in the presence of TiCLi afforded compound 30 in a sufficient yield with a diastereomeric ratio of ca. 8 1. Next, the direct conversion of the oxazolidinone 30 into the Weinreb amide 31 was achieved using A,(9-dimethyl-hydroxylamine. 

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