Chiral Allylsilane Additions to Chiral alpha-Substituted Aldehydes

Journal of the Brazilian Chemical Society

Universidade Estadual de Campinas, Campinas, Brazil¹  Giacomini, Rosana¹  Dias, Luiz C.¹ 

关键词: chiral allylsilane;    transmetallation;    1;    4-asymmetric induction;    polyacetate derived natural products;   

DOI  :  10.1590/S0103-50531998000400008

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

The Lewis acid-mediated reaction of allylsilanes with aldehydes is a well-known procedure for the preparation of homoallylic alcohols1. The stereochemical outcome of this reaction has been occasionally explained by considering Lewis acid-carbonyl complexation. This type of complexation mainly occurs through two discrete pathways, chelation and non-chelation controlled, depending on the nature of the Lewis acid and on the steric requirements of the carbonyl ligand. Condensation of allylic metals (e.g. M: Si, Ti, Sn, B, Cr) with various carbonyl compounds can be used to achieve acyclic stereoselection, and has been applied to the synthesis of natural products1. Chiral allylmetal reagents may be thought of as acetate-enolate equivalents for diastereoselective construction of stereochemically well-defined homoallylic alcohols. Because these reactions complement the aldol reactions, they are among the most important groups of organometallic reagents available for the control of acyclic stereochemistry. Many methods can be used to control the configurations of stereogenic centers that are close to each other2,3. However relatively few methods are available for control of the stereochemistry of more remote stereogenic centers4,5. We describe herein a divergently stereocontrolled reaction between chiral aldehydes and a chiral allylic silane bearing an ethereal functionality, whose coordination to the Lewis acid was found to play a very important role6. These allylsilanes offer an attractive site for metal ligation with a benzyloxyl substituent and undergo Lewis acid promoted reactions with chiral aldehydes with efficient 1,4-asymmetric induction6. The preparation of chiral allylsilane 3 from methyl ester 1 is detailed in Scheme 1. Allylsilanes can be obtained by the reaction of esters with a-silyl substituted Grignard reagents, but yields in this reaction are typically low due to kinetically-preferred enolization of the intermediate a-silylketone rather than addition of a second equivalent of Grignard reagent7. In 1987 Bunnelle and Narayanan reported that this complication can be circumvented in cases of simple esters by premixing the a-silyl Grignard reagent with anhydrous cerium (III) chloride8. The yields in this reaction are greatly increased presumably due to suppression of the enolization process9. The cerium reagent generated from cerium (III) chloride and trimethylsilylmethyl-magnesium chloride reacts with ester 1 to give bis-(silylmethyl)-carbinol 210, which after treatment with silica gel in CH2Cl2 affords allylsilane 3 in 70% isolated yield after flash chromatography (Scheme 1)11.    It seems unlikely that the above reaction proceeds via the intermediacy of an alkylcerium species, but it is clear that the presence of cerium (III) chloride is essential. It may be that cerium is involved in a direct interaction with the intermediate ketone species which enhances nucleophilic attack at the carbonyl and limits competitive enolization. Control experiments established that the Grignard reagent alone reacts very sluggishly at low reaction temperatures (starting ester along with small amounts of a-silylketone are obtained). Chiral aldehydes 9, 10 and 13 and their enantiomers were prepared from methyl 3-hydroxy-2-methylpropionate 4, both enantiomers of which are commercially available10,12. Standard literature methods were employed. The final step in each

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