Aldol condensation asymmetric catalysts

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

It has been reported that the chiral NMR shift reagent Eu(DPPM), represented by structure 19, catalyzes the Mukaiyama-type aldol condensation of a ketene silyl acetal with enantiose-lectivity of up to 48% ee (Scheme 8B1.13) [29-32]. The chiral alkoxyaluminum complex 20 [33] and the rhodium-phosphine complex 21 [34] under hydrogen atmosphere are also used in the asymmetric aldol reaction of ketene silyl acetals (Scheme 8BI. 14), although the catalyst TON is quite low for the former complex. 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

The first example of a C C bond-forming reaction catalysed by gold was the asymmetric aldol condensation developed in 1986.30 The addition of an isocyano acetate to an aldehyde produces the A -oxazole as the major and Z-oxazole as the minor product in excellent enantiomeric excess (ee) in the presence of a cationic gold catalyst, [Au(CyNC)2]BF4, and a chiral diphosphanyl ferrocene ligand (see Scheme 12.5). 

Examples include acetal hydrolysis, base-catalyzed aldol condensation, olefin hydroformylation catalyzed by phosphine-substituted cobalt hydrocarbonyls, phosphate transfer in biological systems, enzymatic transamination, adiponitrile synthesis via hydrocyanation, olefin hydrogenation with Wilkinson s catalyst, and osmium tetroxide-catalyzed asymmetric dihydroxylation of olefins. 

Nitro-Aldol Condensation. A BINOL-derived lanthanide complex has been used as an efficient catalyst for the nitro-aldol reaction (eq 27). Interestingly enough, the presence of water and LiCl in the reaction mixture is essential to obtain the high level of asymmetric induction and chemical yield. 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

Because the aldol reaction is one of the most fundamental bond-construction processes in organic synthesis [86], much attention has been focused on the development of asymmetric catalysts for aldol reactions, using silyl enol ethers of ketones or esters as storable enolate components (the Mukaiyama aldol condensation) [87]. 

Routes by asymmetric organocatalysis are available to account for the occurrence of chiral molecules on earth. L-proline and L-serine yielded relatively high values of ee in aldol condensations (Cordova et al. 2005). An epimer of a distinct amino acid, for instance, proline or serine, can serve as a catalyst in aldol reactions (Cordova et al. 2005). The percentage of the catalyzing amino acid determines the ee of the reaction product. Thus, the preferred formation of D-ribose compared to that of L-ribose can be accounted for by the intrinsic property of the reaction system with an asymmetric molecule acting as biocatalyst. L-proline has exceptional properties due to its structure, Fig. 3.3. 

Asymmetric aldol reaction of silyl enol ethers. (16,221-222). The use of TiCI4 as promoter of aldol condensation of silyl enol ethers with aldehydes, first reported in 1973 (6,590-591), has seen wide use, but has the drawbacks that 1 cquiv. of the Lewis acid is required and that an asymmetric version requires use of chiral aldehydes or chiral silyl enol ethers. More recently, the combination of a salt and a weak Lewis acid, neither effective catalysts themselves, was found to be effective in catalytic (5-10 mol %) amounts. Further research showed that tin(ll) triflatc when coordinated with a chiral diamine can effect catalytic asymmetric allylation of aldehydes (13,302) and Michael reactions (15,313-314), even though this complex cannot promote aldol condensation. Eventually the combination of tin(Il) triflatc, a chiral diamine,... 

Enoxysilacyclobutanes. These compounds can be prepared by Wurtz coupling of 3-chloropropyltrichlorosiIane with Mg in ether. Introduction of one alkyl group is accomplished by reaction with an organolithium reagent, and the silyl chloride can then be used for the formation of silyl enol ethers. Such 0-silyl ketene acetals are extremely reactive in aldol condensations with aldehydes without catalysts. The reaction is syn-selective. An asymmetric version uses silyl ketene acetals bearing a chiral Si-alkoxy (e.g., 8-phenylmenthoxy) group instead of an alkyl substituent. 

Diels-Alder reactions. C2-Symn dienophiles for asymmetric Diels-Ald Lewis acid catalyst(s) the dienophiles Aldol condensation. The reaciK ketene silyl acetals is sy -selectivc m tuted amides and thioamides behave t (i-PrO)3TiCl is used as catalyst. ... 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

In a related study, L-proline catalyzed asymmetric aldol condensation between aldehydes and ketones was examined using SILP asymmetric catalysts [83] (Fig. 5.6-6). In this approach, the catalysts were prepared by impregnation of [BMIM][PF6] ionic liquid containing L-proline direcdy onto a silica gel support, or by treatment of an additional amount of the ionic liquid containing L-proline onto a silica gel support pre-modified with a monolayer of ionic liquid attached to the carrier surface via grafting of the l-(trimethoxysilylpropyl)-3-methylimidazolium cation (as shown earlier in Scheme 5.6-1, middle). 

Chen L, Dumas DP, Wong CH (1992) Deoxytibose 5-phosphate aldolase as a catalyst in asymmetric aldol condensation. J Am Chem Soc 114 741-748... 

Boron-mediated asymmetric aldol condensation methodology developed by Evans [90] served as an inspiration for preparation of daunosamine starting from chiral oxazoUdinones. It appeared that the choice of chiral auxiUary is quite important for the stereochemical outcome of planned reactions [91]. A successful series of reactions started from N -succinoylation of (R)-3-(l-oxo-3-carbomethoxypropyl)-4-diphenylmethyl)oxazolidin-2-one as a novel chiral auxihary. The chain extension was achieved in aldol condensation with protected lactaldehyde and the key intermediate 132 was converted into the target aminosugar 135, via Curtius rearrangement of carboxyhc acid azide, and reduction of lactone to lactol, as depicted in Scheme 24 [58]. Unexpectedly, boron catalysts were rather ineffective in the aldol condensation step and had to be replaced with more reactive lithiiun enolates (which proved to be non-Evans syn selective). 

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