The Silyl-modified Sakurai Reaction

Since the 1980s, chemists have attempted to develop novel Lewis acids and Lewis bases able to catalyze the Sakurai reaction with full diastereo- and enantiocontrol. A review by Denmark and Fu [19] summarizes the most recent advances in this area. Thus, we will not discuss these aspects of the Sakurai reaction but shall focus our attention on the one-pot three-component synthesis of homoallylic alcohols and ethers. 

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At the end of his review [7] dealing with the acetalization of carbonyl compounds, Sakurai reported a previously unpublished observation. In the presence of catalytic amounts of iodotrimethylsilane and one equivalent of tetramethoxysilane 38, allyl-trimethylsilane 1 underwent smooth condensation with benzaldehyde 39, leading to adduct 41 in good yield. The silyl-modified Sakurai reaction was born (Scheme 13.15). 

The silyl-modified Prins reaction and the silyl-modified Sakurai reaction are common methods employed for dihydropyran (and tetrahydropyran) synthesis, and are in fact the same reaction. For the sake of clarity, the term silyl-Prins cyclization is adopted herein. A review of the use of silicon containing compounds in reactions of this type is available <1995CRV1375>. 

Mekhalfia A, Marko IE (1991) The silyl modified Sakurai (SMS) reaction. An efficient and versatile one-pot synthesis of homoallylic ethers. Tetrahedron Lett 32 4779 1782... 

If the alcohol 95 is protected as a trimethylsilyl ether and TMSOTf is employed as the Lewis acid, only catalytic amounts of Lewis acid have to be used (Scheme 13.39) [60]. Such a process is known in the literature under the name intramolecular silyl-modified Sakurai reaction (ISMS) [48],... 

The corresponding allylated ethers are also readily obtainable in one step from parent aldehydes or ketones by the silyl modified Sakurai (SMS) reaction the key step is formation of the heteroacetal by la [37],... 

The intramolecular silyl-modified Sakurai reaction has been used to synthesise a subunit of the antibiotic ambrucitine. The vinylsilane (1) reacts with aldehydes or their acetals in the presence of TMSOTf to give the dihydropyran moiety (94T7141). 

Silyl-Modified Sakurai Reaction Secondary and tertiary homoallylic ethers are impotant building blocks in the synthesis of biologically active compounds. In 1991, Marko et al. developed an efficient method for the synthesis of those... 

In 1991, Marko and Mekhalfia [23] employed the readily available trimethylsilyl-triflate (TMSOTf) as the catalyst and decided to call this reaction SMS for silyl-modified Sakurai condensation. Carbon tetrachloride appeared to be the best solvent and the presence of two chlorine atoms at the ortho,ortho positions of the aromatic ring provided good selectivity (Scheme 13.21). 

The acid-promoted Prins reaction between a homoaUyhc alcohol and an aldehyde is a weU-estabhshed synthesis of tetrahydropyrans (Scheme 4) [ 14,15]. While substituted tetrahydropyrans are often assembled by cyclizations forming a C - O bond, the Prins reaction undergoes cyclization by C - C bond formation. The Prins reaction of the silyl-modified substrates [16], which can be regarded as the intramolecular Hosomi-Sakurai reaction, is effectively activated by the allylsilane unit. The stereochemistry of the 2,6-cfs-form produced in the case of the exo-allylsilane unit is elucidated by the 6-membered transition state model, hi the cyclization of the ewdo-aUylsilane substrates, since the silyl group would be fixed on the axial position of the 6-membered transition states, the tetrahydropyrans with both 2,6-cis and fraws-forms can be synthesized (Panek Sect. 3.3.9). This type of cychzation was also... 

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