Enantiomeric silanes

Biological Recognition of Enantiomeric Silanes and Germanes Syntheses and Antimuscarinic Properties of the Enantiomers of the Si/Ge Analogues Cyclohexyl(hydroxymethyl)phenyl(2-piperidinoethyl)silane and -Germane and Their Methiodides... 

Trimethyl(l-phenyl-2-propenyl)silane of high enantiomeric excess has also been prepared by asymmetric cross coupling, and reacts with aldehydes to give optically active products in the presence of titanium(IV) chloride. The stereoselectivity of these reactions is consistent with the antiperiplanar process previously outlined75. 

Complete control of stereochemistry was also obtained in a total synthesis of ptilocaulin. As the key step, addition of trimethyl(2-propenyI)silane to an enantiomerically pure 5,6-di-aikylcyclohexenone in the presence of titanium(IV) chloride was used to establish a new stereocenter at C-5 with appropriate configuration31. 

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with moderate enantioselectivity.104 The homoallylic alcohol can be liberated by oxidation followed by base-catalyzed (3-elimination. The alcohols obtained in this way are formed in 70 5% e.e. 

Intramolecular hydrosilylation of the fe-alkenyl silane yields the chiral spirosilane with high diastereoselectivity (Scheme 30). With 0.3-0.5 mol.% of catalyst consisting of [Rh(hexadiene)Cl]2 and a range of chelating phosphines P-P (P-P = (R)-BINAP (6), (R,R)-DIOP (5)), a maximum chemical yield of spirosilane of 82% was found with 83% enantiomeric excess. These values were improved considerably by the use of the new ligand... 

A chiral bis(oxazolinyl)phenylrhodium complex was found to catalyze the asymmetric hydrosilylation of styrenes with hydro(alkoxy)silanes such as HSiMe(OEt)2 (Scheme 7).47 Although the regioselectivity in forming branched product 27 is modest, the enantiomeric purity of the branched product 27 is excellent for styrene and its derivatives substituted on the phenyl group. The hydrosilylation products were readily converted into the corresponding benzylic alcohols 29 (up to 95% ee) by the Tamao oxidation. 

Recently, Schaumann et al. 153,154 an(j Bienz et tf/.155,156 have developed dependable routes for the resolution of racemic functionalized organosilanes with Si-centered chirality using chiral auxiliaries, such as binaphthol (BINOL), 2-aminobutanol, and phenylethane-l,2-diol (Scheme 2). For instance, the successive reaction of BINOL with butyllithium and the chiral triorganochlorosilanes RPhMeSiCl (R = /-Pr, -Bu, /-Bu) affords the BINOL monosilyl ethers 9-11, which can be resolved into the pure enantiomers (A)-9-ll and (7 )-9-11, respectively. Reduction with LiAlFF produces the enantiomerically pure triorgano-H-silanes (A)- and (R)-RPhMeSiH (12, R = /-Pr 13, -Bu 14, /-Bu), respectively (Scheme 2). Tamao et al. have used chiral amines to prepare optically active organosilanes.157... 

Kawakami et al. have prepared optically active bifunctional l,3-dimethyl-l,3-diphenyldisiloxanes.158,159 Strohmann et al. have prepared enantiomerically enriched Si-centered silyllithium compounds, which react stereo-specifically with triorganochlorosilanes.160-162 In solution, slow racemization of the silyllithium compounds takes place, which, however, can be circumvented by transmetallation with MgBr2. Oestreich et al. prepared new Si-centered cyclic silanes adopting the strategies developed by Corriu and Sommer.163 Bienz et al. have developed enantioselective routes for the preparation of C-centered chiral allenylsilanes.156,164-166... 

A catalytic amount of ketone 26 was used to investigate the substrate scope of the asymmetric epoxidation. High enantioselectivities can be obtained for a wide variety of trans- and trisubstituted olefins (Table 3, entries 1 ) [54]. Simple trans-olefins, such as franx-7-tetradecene, can be epoxidized in high yield and enantiomeric excess, indicating that this asymmetric epoxidation is generally suitable for frani-olefms. 2,2-Disubstituted vinyl silanes are epoxidized in high ees (Table 3, entries 5, 6) and enantiomerically enriched 1,1-disubstituted epoxides can be... 

Attempts to make C2-symmetric ferrocenes by double lithiation of a bis-acetal met with only limited success . A second lithiation of the ferrocenylacetal 298 leads to functionalization of the lower ring of the ferrocene, in contrast with the second adjacent lithiation of the oxazolines described below. This can be used to advantage if, for example, the first-formed aldehyde 301 is protected in situ by addition of the lithiopiperazine 53 °, directing f-BuLi to the lower ring (Scheme 139) °. The same strategy can be used to introduce further functionalization to products related to 302. For example, silane 303, produced in enantiomerically pure form by the method of Scheme 138, may be converted to the ferrocenophane 304 by lithiopiperazine protection, lithiation and functionalization (Scheme 140) . 

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with high enantioselectivity.70 The enantioselectivity is dependent on several reaction variables, including the Lewis acid and the solvent. The observed stereoselectivity appears to reflect differences in the precise structure of the electrophilic species that is generated. Mild Lewis acids tend to react with inversion of configuration at the reaction site, whereas very strong Lewis acids cause loss of enantioselectivity. These trends, and related effects of solvent and other experimental variables, determine the nature of the electrophile. With mild Lewis acids, a tight ion pair favors inversion, whereas stronger... 

The enantiomerically pure l-[(benzyl(dimethyl)silyl)methyl]pyrrolidine, obtained from ben-zyl(chloro)(dimethyl)silane and (5,)-2-(methoxymethyl)pyrrolidine , afforded after deprotonation and subsequent alkylation the diastereomerically pure (by NMR spectroscopy) (a-alkylben-zyl)silanes2. To obtain this high degree of diastereoselectivity, the alkylation had to be performed in the weakly complexing solvent diethyl ether. In THF a diastereomeric ratio of only 3 1 was found with iodomethane as alkylating agent. 

The method is especially useful, since oxidation of the benzylic silanes so obtained gives S-configuratcd 1-arylalkanols of high enantiomeric purity. Since the oxidative cleavage of the C-Si bond is known to occur with retention of configuration3, the S configuration is also assumed for the intermediate silanes. 

Widenhoefer and co-workers have developed an effective protocol for the asymmetric cyclization/hydrosilylation of functionalized 1,6-enynes catalyzed by enantiomerically enriched cationic rhodium bis(phosphine) complexes. For example, treatment of dimethyl allyl(2-butynyl)malonate with triethylsilane (5 equiv.) and a catalytic 1 1 mixture of [Rh(GOD)2] SbF6 and (i )-BIPHEMP (5 mol%) at 70 °G for 90 min gave the silylated alkylidene cyclopentane 12 in 81% yield with 98% de and 92% ee (Table 4, entry 1). A number of tertiary silanes were effective for the rhodium-catalyzed asymmetric cyclization/hydrosilylation of dimethyl allyl(2-butynyl)malonate with yields ranging from 71% to 81% and with 77-92% ee (Table 4, entries 1-5). Although the scope of the protocol was limited, a small number of functionalized 1,6-enynes including A-allyl-A-(2-butynyl)-4-methylbenzenesulfonamide underwent reaction in moderate yield with >80% ee (Table 4, entries 6-8). 

The synthetic plan was to assemble both the dihydropyran 3 and the cyclopentane 4 in enantiomerically-pure form, then to effect Lewis acid-mediated coupling of the ally silane of 4 with the anomeric ether of 3 to form a new stereogenic center on the heterocyclic ring. A critical question was not just the efficiency of this step, but whether or not the desired stereocontrol could be achieved at C-3. 

Amino acids continue to be useful starting materials for the preparation of enantiomerically-pure heterocycles. Henk Hiemstra of the University of Amsterdam and Floris Ruljes of the University of Nijmegen report (J. Am. Chem. Soc. 2004,126,4100) that cyclization of the ally silane 9 followed by ring-closing metathesis leads to the highly-functionalized quinolizidine 11. 

Scott G. Nelson of the University of Pittsburgh has developed (J. Org. Chem. 2005, 70,4375) a highly diastereocontrolled route to substituted cyclohexanones using the intramolecular Sakurai reaction. The requisite ally silane 12 was prepared by Claisen rearrangement of the allylic alcohol 10, followed by homologation. The Ti enolate from the Sakurai addition was trapped with isobutyraldehyde to give 13. Although 32 diastereomers of 13 are possible, the diastereomer illustrated was the dominant product from the cylization. Note that use of the enantiomerically-pure form of the alcohol 10 would have led to enantiomerically-pure 13. 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

BINOL-Ti complexes (1) has been shown to serve as efficient asymmetric catalysts for the carbonyl addition reaction of allylic stannanes and silanes 152,53]. The addition reactions to glyoxylates of ( )-2-butenylsilane and -stannane proceed smoothly to afford the corresponding syn-product with high enantiomeric excess (Scheme 8C.21) [52]. 

A number of acyl trimethyl silanes chiral at the a- or -carbon atom have been prepared in non-racemic form. Chiral a-alkoxy and a-silyloxy acyl silanes have been generated in very high yields by oxidative rearrangement of enantiomerically pure silyl epoxides, induced by dimethyl sulphoxide and silyl triflates (Scheme 32)112. 

Chiral /J-amino acyl silanes have been prepared through the addition of 2-lithio-2-trimethylsilyl-l,3-dithiane to enantiomerically pure A-tosylaziridines followed by mercury-mediated thioacetal hydrolysis113. 

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