Asymmetric synthesis, at silicon

According to Scheme 11, asymmetric synthesis at silicon will be observed if (i) substitution by Y is selective in the sense of leading to monosubstitution products, and (ii) substitution by Y is stereoselective. We have also suggested that higher optical yields will be obtained for substitutions occurring with inversion rather than retention of configuration (68). 

From a synthetic point of view, asymmetric synthesis at silicon in dihydrosilanes has proved to be useful. It provided the basis for a one-pot synthesis of Sommer s compound, R-(+)- or S-(-)-l-NpPhMeSiH, in 96% e.e. with a 51% chemical yield starting from 1 -NpPhSiH2 (83). The synthesis of a new optically active oxasilacycloalkane has also been realized in this way (84). Moreover, the stereochemistry of a cleavage reaction of a silicon-carbon bond has been determined using asymmetric synthesis (85). The configurations of the pertinent compounds could not be correlated in any other way. 

An asymmetric synthesis at silicon was developed starting from tetragonal silicon compounds. Prochiral compounds of type R1R2SiX2 having two enantiotopic functional groups X are of particular interest. Owing to the many stereospecific substitution reactions that can be performed at a functional silicon atom, the preparation of optically... 

Asymmetric synthesis at silicon using hydrosilylation catalyzed by chiral rhodium complexes... 

Asymmetric synthesis at a prochiral silicon center in catalytic asymmetric reactions has been effected in the hydrosiiyiation of ketones with dihydrosilanes using rhodium complexes as catalysts . ... 

Catalytic alcoholysis of silanes by a variety of transition metal based catalysts is a useful method to form silyl ethers under mild conditions (Scheme 19). The process is atom-economical hydrogen gas is the only byproduct. This mild method has not been fully exploited for the preparation of unsymmetrical bis-alkoxysilanes. A catalytic synthesis using silicon alcoholysis would circumvent the need of bases (and the attendant formation of protic byproducts), and eliminate the need for excess silicon dichlorides in the first silyl ether formation. We sought catalytic methods that would ultimately allow formation of chiral tethers that are asymmetric at the silicon center (Scheme 20). Our method, once developed, should be easily transferable for use with high-value synthetic intermediates in a complex target-oriented synthesis therefore, it will be necessary to evaluate the scope and limitation of our new method. 

The stereochemistry of the elimination of the p-hydroxysilane at silicon has been investigated. In studies by Larson and coworkers, the 3-hydroxyalkyl(l-iuq)hthyl)phenylmethylsilanes (307) and (309) were isolated and subjected to elimination conditions to ascertain the stereochemistry of the elimination on the silyl groip (Scheme 44). The acid-catalyzed eliminations proceed with inversion of stereochemistry at silicon, while the base-catalyzed elimination occurred with retention. These results are in agreement with the mechanism proposed of anti elimination under acidic conditions and syn elimination under basic. While the optically pure silicon was useful for determining the course of the elimination, it could not be utilized in asymmetric synthesis. Addition of the anion to various carbonyls afforded virtually no diastereoselectivity, and it was not possible to separate the diastereomers formed either by crystallization or by chromatography. 

General features of chirality at silicon and the routes to optically active compounds. It is now timely to cover this area, since various methods of wide applicability, including asymmetric synthesis, have become available. 

Numerous tetrahedral optically active organosilicon compounds have now been obtained, and various resolution procedures have been successfully employed. They include resolution through separation of diastereomers as well as kinetic resolution and asymmetric synthesis. Moreover, the stereospecificity of substitution reaction at silicon makes possible the synthesis of various optically active compounds starting from resolved organosilicon compounds. 

The general features of chirality at silicon and the routes to optically active compounds, including asymmetric synthesis. 

Formaldehyde is one of the most important Cl electrophiles in organic synthesis. Whereas hydroxymethylation of enolate components with formaldehyde provides an efficient method to introduce a Cl functional group at the a-position of carbonyl groups, few successful examples of catalytic asymmetric hydroxymethylation have been reported (for other examples of asymmetric hydroxymethylation, see [30-33] for examples of catalytic asymmetric hydroxymethylation without using silicon enolates, see [32, 34, 35]). 

We sought catalytic methods that would allow formation of chiral tethers that are asymmetric at the silicon center. Synthesis of the chiral tether by our method would be advantageous for the reasons we described in the Introduction. Chiral information could be transferred during an intramolecular reaction. This would be an example of substrate-controlled transformation. 

Almost all fimctional silicone fluids of today s industrial production are either of a cyclic nature, containing the appropriate residues, or are linear oils bearing reactive functionalities at both ends or in the chain. The chemical nature of silicone synthesis done by equilibration and condensation is prohibitive for formation of asymmetrical silicones, in contrast to organic molecules like oleic acid or even ethanol. Currently there is only one way of preparing monofunctional silicone fluids, which is through kinetic anionic ring opening polymerization of the cyclic silicone monomer hexamethyl-cyclotrisiloxane (D3). 

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