Enol silanes reaction with aldehydes, stereoselectivity

Additions of enol silanes to p-alkoxy aldehyde (85 equation 25) are reported in Table 17. High selectivity (chelation control) was obtained with TiCU via complex (78 entries 1, 2). The same preference for isomers (86) and (87) was obtained with BF3 via complex (80), which simulates chelation. The influence of chelation on simple stereoselection is also evident in the reactions of achiral aldehydes (90) and (92) with silyl enol ethers (Z)-(91) and ( )-(93), which are usually moderately anti selective in their reactions with aldehydes incapable of chelation high syn selectivity was obtained irrespective of the enol ether geometry (equations 26 and 27). - ... 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Heathcock, C. H., Davidsen, S. K., Hug, K. T., Flippin, L. A. Acyclic stereoselection. 36. Simple diastereoselection in the Lewis acid mediated reactions of enol silanes with aldehydes. J. Org. Chem. 1986, 51,3027-3037. 

The pioneering discovery by Mukaiyama in 1974 of the Lewis acid mediated aldol addition reaction of enol silanes and aldehydes paved the way for subsequent explosive development of this innovative method for C-C bond formation. One of the central features of the Mukaiyama aldol process is that the typical enol silane is un-reactive at ambient temperatures with typical aldehydes. This reactivity profile allows exquisite control of the reaction stereoselectivity by various Lewis acids additionally, it has led to the advances in catalytic, enantioselective aldol methodology. Recent observations involving novel enol silanes, such as enoxy silacyclobutanes and O-si-lyl M(9-ketene acetals have expanded the scope of this process and provided additional insight into the mechanistic manifolds available to this versatile reaction. 

The addition reaction of fert-butyl thioacetate-derived silyl ketene acetal produces the corresponding aldol adducts in 84% yield and up to 96% enantiomeric excess (Eq. 16). The enantioselectivity of the products was observed to be optimal with toluene as solvent the use of the more polar dichloromethane consistently produced adducts with 10-15% lower enantiomeric excess. The bulkier ferf-butylthioacetate-derived enol silane was found to lead to uniformly higher levels of enantioselectivity than the smaller S-ethyl thioketene acetal. This process is impressive in that it tolerates a wide range of aldehyde substrates for instance, the aldol addition reaction has been successfully conducted with aldehydes substituted with polar functionaUty such as N-Boc amides, chlorides, esters, and 0-benzyl ethers. A key feature of this system when compared to previously reported processes was the abiUty to achieve high levels of stereoselectivity at 0 °C, in contrast to other processes that commonly prescribe operating temperatures of -78 °C. 

Aluminium montmorilIonite and rhodium carbonyl have been reported as catalysts for the aldol reaction of enol silanes with aldehydes, but in neither case are the stereoselectives at all high. The reaction has also been found to occur without Lewis acid catalysis in water or in 1 1 water oxolane. Although the yields are not high, the method is of interest in that syn-products were... 

The /3-lactone was formed by the cyclization of a 3-hydroxycarboxylic acid with sulfonyl chloride. An alternative synthesis attempted to control all stereochemical relationships in the molecule using the properties of silyl moieties attached to substrates and reagents <20040BC1051>. Stereoselective reactions of this type included the use of silyl groups in enolate alkylations, hydroboration of allylsilanes, and an anti Se2 reaction of an allenyl silane with an aldehyde and ry -silylcupration of an acetylene. The /3-lactone was again formed by the standard sulfonyl chloride cyclization method. 

---