Chiral silicon species

Before reviewing the different routes to optically active silanes and discussing some relevant points, namely, the determination of enantiomeric purity and configuration, we shall give a brief overview of the stereochemical stability of chiral silicon species. 

Since the stereochemical behavior of chiral silicon species differs from that of corresponding carbon species, it seems of interest to summarize briefly the current status of the field, making comparison also with related germanium and tin compounds. 

II. SYNTHESIS AND CHEMICAL BEHAVIOUR OF CHIRAL SILICON SPECIES... 

A complete stereocontrol is achieved by addition of the bulky silyl radical (Me3Si)3Si to a chiral and conformationally flexible electron-deficient olefin 163, as shown in equation 68213. Replacement of (Me3Si)3Si with a less sterically hindered (n-Bu)3Sn gives a mixture of syn and anti diastereomeric adducts 164 and 165 in a ratio of 7 3. The A values (kcalmol-1) of the tin, carbon and silicon species follow the order (n-Bu Sn (1.1) < Me (1.7) < Me3Si (2.5), and the bond length for C—Sn (2.2 A) is longer than that for C-Si (1.85 A)214 215. 

But also by the hydrogenation of other silanes the formation of certain partially hydrogenated species is preferred (see Eq. 7, catalyst used PhsMePI, Si = chiral silicon atom). 

The observed activation of allyltrihalosilanes with fluoride ion and DMF and the proposition that these agents are bound to the silicon in the stereochemistry-determining transition structures clearly suggested the use of chiral Lewis bases for asymmetric catalysis. The use of chiral Lewis bases as promoters for the asymmetric allylation and 2-butenylation of aldehydes was first demonstrated by Denmark in 1994 (Scheme 10-31) [55]. In these reactions, the use of a chiral phos-phoramide promoter 74 provides the homoallylic alcohols in high yield, albeit modest enantioselectivity. For example, the ( )-71 and benzaldehyde affords the anti homoallylic alcohol 75 (98/2 antUsyn) in 66% ee. The sense of relative stereoinduction clearly supports the intermediacy of a hexacoordinate silicon species. The stereochemical outcome at the hydroxy center is also consistent with a cyclic transition structure. 

ClCH2SiMe2 and compounds with chiral silicon centres, stabilisation of reactive phosphorus species through protection by large groups such as (Me SDjC (Tsi), the jc-ray structures of silatranes, the chemistry of organochlorosilanes, and silyl, germyl and stannyl... 

The concept of Lewis base activation of Lewis acids was developed by Denmark, and it takes advantage of the fact that the Lewis acidity of silicon is increased when the coordination sphere is enlarged. If chiral Lewis bases are provided, here chiral phosphoramides and bisphosphoramide, SiCl can be efficiently employed in asymmetric Mukaiyama aldol reactions. The Lewis base activation can be performed on trichlorosilyl enolates (24), which can be generated in situ by mercury-mediated trans-silylalion of a TMS silyl enol ether (18) in the presence of SiCl. Generation of the hypervalent silicon species produces a more Lewis acidic silicon moiety, which acts to coordinate and activate the aldehyde that has to be brought to reaction (Scheme 2.128) [48]. 

A similar approach, even though initiated by a Brpnsted acid, is the organocatalytic approach put forward by List et al. [50]. They used their chiral disulfonimide 36 to induce VMARs stereoselectively. With aromatic aldehydes as the substrates, selectivities up to 98 2 er can be obtained. Additionally, they were able to perform bis-VMARs with triene 40. As mentioned earlier, even though a chiral Brpnsted acid is used, the transition state also includes a hypervalent silicon species (42), which contains the disulfonimide anion and the coordinated aldehyde in a pentavalent, trigonal bipyiamidal geometry (Scheme 2.130). 

It is important to note that a stoichiometric use of the achiral proton source is crucial to obtain high enantioselectivity for this catalytic system to scavenge a cationic silicon species. The authors proposed two plausible transition states for each BBA form (Scheme 1.35). As in the case of TADDOL, BBA formation should lead to high enantioselectivity by virtue of their well-organized chiral cavities. 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

Asymmetric reduction of alkyl aryl ketones with trialkoxysilanes is promoted by a catalytic amount of chiral nucleophiles [39]. The reactive species is a transiently prepared hypervalent silicon hydride. 2, 4, 6 -Trimethylacetophenone was reduced with equimolecular amounts of trimethoxysilane in the presence of the monolithio salt of (R)-BINAPHTHOL (substrate Li=20 l) in a 30 1 ether-TMEDA mixed solvent at 0 °C to afford the R product in 90% ee (Scheme 21) [40]. The presence of TMEDA was crucial to achieve high yield and enantiose-lectivity. Reduction of less hindered ketonic substrates preferentially gave the... 

The mechanism A very detailed mechanistic study of this phosphoramide-catalyzed asymmetric aldol reaction was conducted by the Denmark group (see also Section 6.2.1.2) [59, 60], Mechanistically, the chiral phosphoramide base seems to coordinate temporarily with the silicon atom of the trichlorosilyl enolates, in contrast with previously used chiral Lewis acids, e.g. oxazaborolidines, which interact with the aldehyde. It has been suggested that the hexacoordinate silicate species of type I is involved in stereoselection (Scheme 6.15). Thus, this cationic, diphosphoramide silyl enolate complex reacts through a chair-like transition structure. 

Crystallization is an excellent technique for the purification of chemical species by solidification from liquid mixtures. Many materials are marketed and sold in crystalline form, and a large amount of a product may be obtained from impure solutions even in a single step. Crystallization is widely applied in the electronic industry for manufacturing semiconductor silicon, GaAs, InP, GaP, CdTe, and its alloys, and scintillation optical crystals (Scheel and Fukuda 2003). In the pharmaceutical industry, crystallization is extensively applied to chiral discrimination and polymorphism (CoUins et al. 1997). In biochemistry, crystallization is used for detailed description of protein structmes at the atomic level, which is mostly achieved by x-ray diffraction analysis of single biomolecular crystals (McPherson 2003). 

On the basis of the fact that (R)-BMPP coordinated to the metal center can induce asymmetric addition of methyldichlorosilane across the carbon-carbon double bond of 2-substituted propenes to afford an enantiomeric excess of (R)-2-substituted propylmethyldichlorosilanes, the following processes should be involved in these reactions (a) insertion of the metal center into the silicon-hydrogen bond (oxidative addition of the hydrosilane) (b) addition of the resulting hydridometal moiety to the coordinated olefin preferentially from its re face (in a cis manner) to convert the olefin into an alkyl-metal species and (c) transfer of the silyl group from the metal center to the alkyl carbon to form the product. Since process (b) most likely involves diastereomeric transition states or intermediates, the overall asymmetric bias onto the R configuration at the chiral carbon would have already been determined prior to process (c). A schematic view of such a process is given in Scheme 1. 

The low ionic character of the aluminium-silicon bond has been cleverly utilized to develop a very mild, general and effective synthesis of acyl silanes, successful for aliphatic, aromatic, heteroaromatic, a-aUcoxy, a-amino and even a-chiral and a-cyclopropyl acyl sUanes. Acyl chlorides are treated with lithium tetrakis(trimethylsilyl)aluminium or lithium methyl tris(trimethylsilyl) aluminium in the presence of copper(I) cyanide as catalyst to give the acyl silanes in excellent yields after work-up. Later improvements include the use of 2-pyridinethiolesters in place of acyl halides, allowing preparation of acyl silanes in just a few minutes in very high yields indeed (Scheme 9) °, and the use of bis(dimethylphenylsilyl) copper lithium and a dimethylphenylsilyl zinc cuprate species as nucleophiles. 

The aldol reaction is one of the most useful carbon-carbon bond forming reactions in which one or two stereogenic centers are constructed simultaneously. Diastereo-and enantioselective aldol reactions have been performed with excellent chemical yield and stereoselectivity using chiral catalysts [142]. Most cases, however, required the preconversion of donor substrates into more reactive species, such as enol silyl ethers or ketene silyl acetals (Scheme 13.45, Mukaiyama-type aldol addition reaction), using no less than stoichiometric amounts of silicon atoms and bases (Scheme 13.45a). From an atom-economic point of view [143], such stoichiometric amounts of reagents, which afford wastes such as salts, should be excluded from the process. Thus, direct catalytic asymmetric aldol reaction is desirable, which utilizes unmodified ketone or ester as a nucleophile (Scheme 13.45b). Many researchers have directed considerable attention to this field, which is reflected in the increasing... 

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