Chirality base effect

Concept A variety of metal-based chiral catalysts effect enantioselective chemical transformations that allow for concise and efficient synthesis of optically pure organic molecules. These transformations,... 

The desymmetrization of the A -phenylcyclopropylsuccinimide (185) has been effected by its reaction at low temperature with a chiral base (186) and an in situ electrophile, trimethylsilyl chloride. The silylated product (187) was obtained in 80% yield and 95% ee (Scheme 18). ... 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

The cage-type peptide cyclophanes (7 and 8) exhibit discrimination toward steroid hormones, as effected by hydrophobic and n-n interactions. In addition, the chirality-based discrimination between a- and -estradiol as well as between D- and L-amino acids bearing an aromatic moiety is performed on the basis of their capacity of forming efficient hydrogen bonding with the host molecules in aqueous media [41, 43]. 

Besides BINAP or p-TolBINAP, optically active peraryldiphosphines with axial chirality based on the biphenyl groups (6,6 -dimethylbiphenyl-2,2 -diyl)bis(diphenylphosphine) and its analog are also effective ligands for the asymmetric isomerization as expected [21],... 

The resolution of 3-phenylFischer s base itself would make available the chiral base for the preparation of not only indolinospiropyrans, but also for cyanine, merocyanine, and styryl dyes. Several attempts to effect this resolution using the camphorsulfonic, bromocamphorsulfonic, and dibenzoyltartaric acids in lower alcohols, 1,2,-dimethoxyethane and tetrahydrofuran, were unsuccessful in giving a clean resolution. Perseverance and luck are of prime importance. 

The obvious question is whether the achiral stereodirecting base effect observed with DAG is a particular case of this alcohol or general behavior of secondary chiral carbinols. In order to answer this question and to get a better insight into the mechanism of the reaction, the reactivity of different chiral carbinols with methane-sulfinyl chloride was tested using the optimal conditions previously determined for DAG (1) in the presence of i-Pr2NEt in toluene at -78 °C, and (2) with pyridine in THF at -78 °C.116... 

Koga and coworkers have investigated the steric effect of the 4-substituent in the deprotonation of cyclic ketones. Small substituents (e.g. R = Me) gave silylenol ether in 46% ee using (R)-25 as chiral base and the ee increased up to 78% with larger aryl substituents (R = Ph, i-Pr, f-Bu)50. 

A Pd-catalyzed oxidative cyclization of phenols with oxygen as stoichiometric oxidant in the noncoordinating solvent toluene has been developed for the synthesis of dihydrobenzo[ ]furans (Equation 136). Asymmetric variants of this Wacker-type cyclization have been reported by Hayashi and co-workers employing cationic palladium/2,2 -bis(oxazolin-2-yl)-l,l -binaphthyl (boxax) complexes <1998JOC5071>. Stoltz and co-workers have reported ee s of up to 90% when (—)-sparteine is used as a chiral base instead of pyridine <2003AGE2892, 2005JA17778>. Attempts to effect such a heteroatom cyclization with primary alcohols as substrates, on the other hand, led to product mixtures contaminated with aldehydes and alkene isomers, which is in contrast to the reactions with the Pd(ii)/02 system in DMSO <1995TL7749>. 

In certain cases, seemingly simple enolates can have a chiral memory effect . For example, treatment of a-imino lactam (5)-88 with f-BuOK in CD3OD for 6-13 days at 25°C gave the corresponding enantiomerically deuteriated a-imino lactam l-d-(S)-89 in quantitative yield with 98% D incorporation and ee 97% (equation 15) , via a conformationally chiral enolate. This methodology has been extended towards enan-tioselective alkylation of enolates. Excellent levels of enantioselectivity (ee 88%) were achieved for a-imino lactam (S)-SS using KHMDS as Brpnsted base and benzyl iodide as the electrophile . Interestingly, to prevent unwanted racemization of the intermediate enolate, the reaction time for deprotonation was lowered to 10 seconds, and to ensure rapid alkylation, 20 equivalents of Bnl were used . 

A similar scheme was reported by Pino, based on the stereoregulating effect of electron donors and on the stereoelectivity obtained in the polymerization of racemic a-olefins in the presence of chiral bases 109). 

Several studies on the hydrogenation of carbonyl compounds using cobalt complexes have been reported, including the hydrogenation of benzil in the presence of bis(dimethylglyoximato)co-balt(II)-chiral amine complexes. The highest ee (78%) was obtained when quinine was used as the chiral base (equation 17). Cyano cobalt complexes have also been reported to be effective for the hydrogenations of ketones. ... 

Chiral secondary alcohols are one of the most valuable key intermediates for the synthesis of pharmaceuticals and advanced materials. The well-organized molecular catalyst 43, consisting of BINAP-Ru" and the chiral diamine, effects highly enantioselective hydrogenation of simple, unfuctionalized ketones to give secondary alcohols with over 99% ee in 100% yield (Scheme 12) [43]. In the presence of base, an alkali, the reaction proceeds in 2-propanol at room temperature under... 

Shortly later, Brunner demonstrated the uselessness of copper [34]. The reaction of hemimalonate 45a carried out at room temperature in THF with 10mol% of cinchonine 43 without copper afforded 46a with 34% ee (Scheme 7.26), comparable to that obtained with copper but with a higher reaction rate. Beside its chiral inducting effect, the alkaloid also has a catalytic role in the decarboxylation process since the substrate is perfectly stable at room temperature in the absence of base. 

The vast majority of strategies aimed at effecting enantioselective Diels-Alder reactions rely on complexation of an unsaturated carbonyl compound to a chiral Lewis acid, but this is not the only catalytic method for achieving enantiofacial bias. A unique approach outlined in Scheme 52 takes advantage of a diene (or precursor) possessing an acidic proton [138] treatment with a catalytic amount of a chiral base results in transient formation of an oxidodiene which undergoes oxyanion-accelerated cycloaddition with a maleimide [139]. 

While several stoichiometric chiral lithium amide bases effect the rearrangement of raeso-epoxides to allylic alcohols [1], few examples using catalytic amounts of base have been reported. Asami applied a pro line-derived ligand to the enantioselective deprotonation of cyclohexene oxide to afford 2-cyclohexen-... 

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