Crossed Aldol Reactions Using Silicon Enolates

To a 0.2-0.5 m solution of chiral imide 26 in CH2CI2 under argon (0 °C) was added 1.1 equiv. dibutylboryl triflate followed by 1.2 equiv. diisopropylethyl-amine. After 30 min the reaction mixture was cooled (—78 °C) and 1.1 equiv. isobutyraldehyde was added and stirred for 0.5 h at —78 °C and then for 1.5 h at room temperature. The reaction was quenched with pH 7 phosphate buffer and the boron aldolate complex was oxidized with 30% hydrogen peroxide-methanol (0 °C, 1 h). The aldol product 34 was then isolated by ether extraction (syn/anti = 497 1). 

Typical Procedure for onti-Selective Asymmetric Boron Aldol Reaction (Eq. (18)) [15c] 

Crossed Aldol Reactions Using Silicon Enolates 

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Crossed Aldol Reactions Using Silicon Enolates 137... 

It is reported that enol ethers react with acetals or ketals, promoted by Lewis acids, to give aldol-type adducts these reactions of alkyl enol ethers are, however, often accompanied by undesired side reactions [21]. Further, is difficult to perform crossed-aldol reactions selectively because conventional aldol reactions are conducted under equilibrium conditions using a basic or acidic catalyst in protic solvents [22]. Detailed studies of this new aldol reaction of silicon enolates, however, reveal a number of advantages over conventional methods. 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

The aldol reaction has long been recognized as one of the most useful synthetic tools. Under classical aldol reaction conditions, in vhich basic media are usually employed, dimers, polymers, self-condensation products, or a,j5-unsaturated carbonyl compounds are invariably formed as byproducts. The lithium enolate-mediated aldol reaction is regarded as one useful synthetic means of solving these problems. Besides the vell-studied aldol reaction based on lithium enolates, very versatile regio- and stereoselective carbon-carbon bond forming aldol-type reactions have been established in our laboratory by use of boron enolates (1971), silicon enolates-Le vis acids (1973), and tin(II) enolates (1982). Here we describe the first t vo topics, boron and silicon enolate-mediated crossed aldol reactions, in sequence. 

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