摘要:

Optically active secondary alcohols are important intermediatesfor the construction of optically active natural products and biologicallyactive compounds. Among various methods for the construction of opticallyactive secondary alcohols, addition of diorganozinc reagents to aldehydesin the presence of a catalytic amount of a chiral β-aminoalcohol hasbeen extensively studied.1Extremely highenantioselectivity has been reported in the reactions employing a varietyof aminoalcohol ligands. However, in order for these reactions to besuccessfully exploited in large-scale applications, the chiral ligand hasto be readily available or easily recycled. Toward this goal,immobilization of chiral ligands onto heterogeneous supports has beeninvestigated and a number of support materials such as inorganic solids andpolymers have been developed.2Recently,various mesoporous silicas with pore sizes ranging from 2 to 10 nm havebeen synthesized using self-assemblies of surfactants and block copolymersas templates.3These mesoporous silicas havebeen successfully employed as supports for various chiral catalysts.4Herein, we report on new heterogeneous catalystsystems that utilize proline derivatives anchored on the mesoporous silicassuch as MCM-41 and SBA-15.Although the reactions of diethylzinc with benzaldehyde using ephedrineimmobilized onto amorphous silica gel5andmesoporous silica6have been investigated,the degree of enantioselection under these heterogeneous catalyticconditions has been less than satisfactory. In connection with the lowenantioselectivty, several issues need to be addressed: (1) employment of amore selective ligand, (2) suppressing undesired catalytic activity on thesilica surface, (3) changing silica pore sizes, and (4) addition of extrametal reagent. In terms of a more selective ligand system, a prolinol-basedligand developed by Soaiet al.7was selected in our study. Since the free SiOH moieties of the silicasurface could catalyze the reaction,6thuslowering the reaction enantioselectivity, mesoporous silicas containing thechiral ligand having its surface capped with trimethylsilyl groups8have been prepared. To investigate the effect ofthe pore size on the enantioselectivity, we have used two differentmesoporous silicas, MCM-41 and SBA-15, which have similar hexagonal porearrays but with different pore dimensions. We have also investigatedreaction enantioselectivity when the catalyst system was treated withBunLi before addition of the aldehyde.The synthetic procedure including preparation of the ligand,immobilization onto silicas and capping with trimethylsilyl moieties isshown inScheme 1. The new chiralaminoalcohol3was synthesized as follows. The amine group of4-hydroxyproline (Aldrich Chemicals™) was protected using ethylchloroformate and the acid was converted to a methyl ester to give thecarbamate ester2. Treatment of compound2usingphenylmagnesium chloride furnished a tertiary alcohol, and the carbamategroup was converted to the corresponding methylamine through treatment withlithium aluminium hydride (LAH) yielding compound3in an overallyield of 72% from1. MCM-41 and SBA-15 were synthesized accordingto the previously reported procedures.3Chloropropyl linkers were grafted on the walls of mesoporous silicas bytreating with(CH3CH2O)3Si–CH2CH2CH2Cl in refluxing toluene. Reaction of the resultingchloropropyl-derivatized mesoporous silicas (5band5c)with the chiral pyrrolidinemethanol3yielded silicas6band6c, respectively. In order to cap remaining free SiOH groupson the walls of mesoporous silicas,5band5cweretreated in refluxing hexamethyldisiloxane (HMDS) for 12 h. To the best ofour knowledge, this is the first anchoring of SBA-15 silica with a chiralligand and the X-ray diffraction (XRD) patterns of SBA-15 derivatizedsamples have been taken during various stages of the preparation. The XRDresults clearly demonstrated that the mesoporous structure of SBA-15 waspreserved during the preparation of the catalyst.Table 1lists the surface areas, the mean poredimensions, and the amounts of grafted organic groups for the mesoporoussilica based catalysts. The surface area decreased substantially during thechloropropyl-grafting step, especially for SBA-15. Nonetheless, the poredimensions of the SBA-15 based systems did not change significantly duringthese synthetic steps. For comparison, the chiral ligand3wasattached to amorphous silica to provide both non-TMS capped catalyst(6a) and TMS-capped catalyst (8a) using the same reactionconditions applied to the mesoporous silicas.The synthetic routes used in the preparation of various catalysts.Reagents and conditions: a: (i) ethyl chloroformate,NaHCO3, H2O, room temp., 16 h; (ii) SOCl2,MeOH, room temp., 12 h; b: (i) PhMgCl, THF, 0 °C, 5 h; (ii)LiAlH4, THF, reflux, 3 h; c: NaH, BnBr, THF, room temp., 16 h;d: Chloropropyltriethoxysilane, toluene, reflux, 12 h; e:3,xylene, reflux, 12 h; f: HMDS, reflux, 12 hCharacterization of mesoporous silicas during various stages of catalystpreparationMCM-41 basedcatalystsSBA-15 basedcatalystsCatalystSurface area/ m2g−1Mean pore diameter/nmGrafted amount/ mmolg−1CatalystSurface area/ m2g−1Mean pore diameter/nmGrafted amount/ mmolg−1N2adsorption and desorption isotherms were collected at STPon a Micrometrics ASAP2010 gas adsorption analyzer after the materials weredegassed at 250 °C at 30 μTorr for 5 h. The surface areas werecalculated by the BET method and the pore size distributions werecalculated from the adsorption branch of the nitrogen isotherm by the BJHmethod.Silica9193.1Silica8008.95b7503.00.555c4728.51.386b6552.40.406c3208.40.368b6482.30.598c3128.40.37We have investigated asymmetric addition of diethylzinc to benzaldehydeusing these silica-based catalysts and the results are outlined inTable 2. For each silica catalyst, twodifferent sets of reactions were run with 6 mol% of catalyst and either 3equiv. of diethylzinc to benzaldehyde (method A) or 7.2 mol% ofBunLi followed by 3 equiv. of diethylzinc (method B). Toevaluate our catalyst systems against the parent homogeneous catalyst,compound4was prepared from3through etherification ofC(4)–OH with benzyl bromide. Reactions employing the homogeneouscatalyst4provided products with 90 and 93% ee, respectively,viamethods A and B (entries 1 and 2,Table 2). However, when the chiral catalystsanchored on amorphous silica were tested using method A,6aand8agave only 16 and 37% ee, respectively (Table 2entries 4 and 5). When the reactions werecarried out using method B, slight improvements in the enantioselectivitieswere observed (entries 6 and 7). A noticeably higher enantioselectivity wasobserved in the reactions employing MCM-41-based catalyst (entries8–11) and the best results were obtained with the catalysts basedupon SBA-15 (entries 12–15). It is of particular note that catalystsbased upon SBA-15 consistently gave higher enantioselectivity than that ofMCM-41. In both MCM-41 and SBA-15 systems, TMS-capping as well as theemployment of BunLi improved the enantioselectivitysignificantly. Product of the highest ee (75%) was obtained for TMS-cappedSBA-15 based catalyst utilized after treatment with BunLi (entry15). To test the catalytic activity of the silica without a chiral ligand,TMS-capped SBA-15 (7c) was used under otherwise the same reactionconditions, and a 15% yield of the product was observed. It appears that,even with TMS-capping, there remains some residual activity of the silica,resulting in a reduction of the enantioselectivity.Asymmetric diethylzinc addition to benzaldehyde using variouscatalystsIn summary, new mesoporous silica-based catalysts incorporating a chiralpyrrolidinemethanol derivative have been prepared and the asymmetricdiethylzinc addition to benzaldehyde examined. Among various catalyticsystems, the best result (75% ee) was obtained with the TMS-capped SBA-15based catalyst treated with BunLi.

ISSN:1359-7345    

出版商:RSC    

年代:1999

数据来源: RSC