Chiral silicon compounds

These catalytic reactions of dihydrosilanes make possible the use of asymmetric catalysts to produce chiral silicon compounds. Introduction of a chiral ligand L on the rhodium complex will not change the validity of the kinetic Scheme 12. However, in this case complexes 56 and 57 will be diastereomeric and their equilibrium concentrations will be different. The ratio of the substituted silanes will be close to k, [56] k2 [57]. 

An interesting feature of these reactions is that they permit the synthesis of simple chiral silicon compounds in up to 69% optical purity using readily available reagents. Moreover the method appears to be of wide applicability. 

Substitution reactions at silicon have been shown to proceed with high stereoselectivity. Either inversion or retention of configuration at silicon is commonly observed (see Sect. III.) A large number of chiral silicon compounds have thus been prepared by stereospecific substitution of resolved organosilanes. Most of them are mentioned along the way in this review however, at this point we shall... 

The Separation of Some Chiral Silicon Compounds Courtesy of Supelco Inc. 

Silicon compounds which have an asymmetric arrangement of atoms around a tetrahedral silicon centre can, of course, also be chiral. There has been little work on chiral silicon compounds to date but a comprehensive review of this is available,... 

The pentacoordinate silicon compounds 81, 8,54 82,54 83,54 and 8455 are spirocyclic zwitterionic A5S7-silicates with an Si04C skeleton. The chiral zwitterions contain two diolato(2—) ligands that formally derive from aceto-hydroximic acid and benzohydroximic acid (tautomers of acetohydroxamic acid and benzohydroxamic acid). 

The spirocyclic pentacoordinate silicon compounds 85,56 86,39 and 8739 are zwitterionic A5S7-silicates with an S702N2C skeleton. The chiral zwitterions... 

The spirocyclic pentacoordinate silicon compounds 90,45,58 91 45,58 and 9259 are zwitterionic A5Si-silicates with an Si05 skeleton. The chiral zwitter-ions contain two 2-methyllactato(2-) or two benzilato(2-) ligands. In these molecules, two five-membered SiC>2C2 rings are connected by the silicon spirocenter. Compounds 90 and 91 represent isoelectronic analogs of the zwitterionic A5Sz-silicates 58 and 59 (0/CH2 replacement see Section III,D). 

The pentacoordinate silicon compounds 94,23 95,23 96-98,60 99,60,61100,61,62 101-103,60 104,61,62 105,62 106,62 and 10761,63 are monocyclic zwitterionic A5S7-silicates with an Si02FC2 skeleton. The chiral zwitterions each contain one bidentate diolato(2-) ligand that formally derives from 1,2-dihydroxy-benzene, salicylic acid, glycolic acid, oxalic acid, benzohydroximic acid (tautomer of benzohydroxamic acid), 2-methyllactic acid, or (S)-mande-lic acid. 

Most of the zwitterionic compounds studied so far are chiral, with a chiral A5S/-silicate skeleton. Most of them have been isolated as racemic mixtures and in some cases as enantiomerically pure compounds, some of the optically active compounds being configurationally stable in solution. With these experimental investigations, in combination with computational studies, a new research area concerning the stereochemistry of molecular pentacoordinate silicon compounds has been developed. 

As can be seen from Figure 2, the (/ )-enantiomers (eutomers) of the silanols 3 and 7 show a significantly higher affinity for muscarinic M2 and M3 receptors than the corresponding (S)-antipodes (distomers). To the best of our knowledge, this is the first example of a biological discrimination between enantiomeric silicon compounds, with the silicon atom as the center of chirality. The stereoselectivity indices SI [SI = Kn S)/Kd(R) for sila-procyclidine (3) are 1.8 (M2) and 4.1 (M3), respectively. For sila-tricyclamol iodide... 

Enantioselective enzymatic ester hydrolyses have also been used for the preparation of optically active silicon compounds with the silicon atom as the center of chirality. An example of this is the kinetic resolution of the racemic 2-acetoxy-l-silacyclohexane rac-(SiR,CR/SiS,CS)-79 with porcine liver esterase (PLE E.C. 3.1.1.1) (Scheme 16)65. Under preparative conditions, the optically active l-silacyclohexan-2-ol (SiS,CS)-80 was obtained as an almost enantiomerically pure product (enantiomeric purity >96% ee) in ca 60% yield [relative to (SiS,CS )-79 in the racemic substrate]. The biotransformation product could be easily separated from the nonhydrolyzed substrate by column chromatography on silica gel. 

Enantioselective enzymatic amide hydrolyses can also be applied for the preparation of optically active organosilicon compounds. The first example of this is the kinetic resolution of the racemic [l-(phenylacetamido)ethyl] silane rac-84 using immobilized penicillin G acylase (PGA E.C. 3.5.1.11) from Escherichia coli as the biocatalyst (Scheme 18)69. (R)-selective hydrolysis of rac-84 yielded the corresponding (l-aminoethyl)silane (R)-85 which was obtained on a preparative scale in 40% yield (relative to rac-84). The enantiomeric purity of the biotransformation product was 92% ee. This method has not yet been used for the synthesis of optically active silicon compounds with the silicon atom as the center of chirality. 

The synthesis of a number of compounds of the type R R2R3SiM(L)n, with a chiral silicon atom, has made it possible to examine the stereochemistry of reactions of silicon in some detail. Table XXII shows that compounds with silicon linked to Mn, Fe, Co, and Pt have been studied. 

Of course, any tetrahedral atom, not just caibon, that has four different groups bonded to it is a chirality center, and compounds containing such atoms will exist as a pair of enantiomers. Many such compounds have been prepared and resolved, including the following quaternary ammonium salt and the silicon compound ... 

This unusually high barrier for inversion of configuration at the chiral silicon atom in 70g is probably due to (0,0)-exehange via a bicapped tetrahedron intermediate, in analogy to silicon inversion in compounds 30-38.45-48... 

Compound 86 exists in two diastereomeric forms due to the chiral silicon centers, which are evident in the various NMR spectra (Table XXV). The crystal structure of 86 shows a molecular inversion center, and hence belongs to the meso diastereomer. The geometry around silicon in the crystal is a distorted TBP and the chloride is more than 7 A away from silicon, in accord with a pentacoordinate siliconium chloride structure. The dative Si bonds are exceptionally short in 86 (1.802 and 1.807 A) relative to those in other pentacoordinate complexes.2,3,1115... 

Activation parameters at coalescence temperature show that the coordinate interaction in these compounds is not a function of the electronegativity of X but is controlled by the ability of the nitrogen atom to stretch the Si—X bond. The tendency of the silicon atom to increase its valency decreases in the order X = OCOR, Br, Cl > SR F > OR, H This sequence corresponds directly to the rate of racemization of halosilanes and to the substitution of R3SiX with inversion of configuration Although no intramolecular coordination was observed in solutions of acetoxysilanes (CH3) Si(OCOR)4 by the Si NMR method the shape of the H NMR spectra of these compounds with chiral silicon atom points to Si -0 interaction... 

Since the most common cause of chirality is the presence of four different substituents bonded to a tetrahedral atom, tetrahedral atoms other than carbon can also be chirality centers. Silicon, nitrogen, phosphorus, and suit fur are all commonly encountered in organic molecules, and all can be chin rality centers under the proper circumstances. We know, for example, thal trivalent nitrogen is tetrahedral, with its lone pair of electrons acting a4 the fourth substituent (Section 1.11). Is trivalent nitrogen chiral Does compound such as ethylmethylamine exist as a pair of enantiomers j... 

A number of organosilicon compounds with chiral silicon atoms have been obtained as single enantiomers by routes involving ... 

Examples are shown in 24-26. The stereospecificity of substitution reactions at silicon indicates a viable route to other enantiomerically pure silicon compounds. All examples of chiral molecules of the type R R2R3R4Si and R1R2R3SiH have high configurational stability, and in addition halides such as PhSi(Me)(Et)Br do not readily racemize (see Corriu et aid). 

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