Lithium binaphtholate

An aldol reaction of a trimethoxysilyl enol ether, catalysed by a lithium binaphtholate, shows anti diastereoselectivity and modest ees under dry conditions, but addition of water brings about syn adduct formation, with higher ee.131... 

A particularly attractive version of this reaction relies on the action of a catalytic chiral lithium binaphtholate and an excess of water on trimethoxysilylenol ether119. The tetralone enolate thus generated was directly employed in an aldol reaction, which turned out to be poorly diastereoselective but highly enantioselective for both diastereomers (Scheme 27). 

Fig. 2) [34]. These aluminium systems, the most commonly used example being given the acronym ALB for aluminium-lithium-binaphthol, were found to be equally effective for many phospho-aldol transformations as their lanthanide cousins, a little less reactive overall, but especially useful on electron-withdrawing carbonyl substrates (e.g., compare entries 2 and 3 in Table 1 and Table 3).

Ishihara developed a highly diastereo- and enantioselective direct Man-nich-type reaction of aldimines with 1,3-dicarbonyl compounds using chiral lithium binaphtholate salts as effective Lewis-acid-Bronsted-base catalysts (Scheme 2.5). ° The stereoselectivity of the Mannich products anti-S and syn-7 ) was reversed when the nucleophile was changed from acyclic 1,3-dicarbonyl compound 4 to cyclic compound 6. The molecular flexibility and acidity of the nucleophiles 4 and 6 would be the major factor in differentiating the two reaction pathways. 

Nakajima developed an enantioselective aldol-Tishchenko reaction by using chiral lithium binaphtholate 8, to afford 1,3-diol derivatives with three contiguous chiral centres and high stereoselectivities (Scheme 2.6). Acyclic ketones gave l,2-a ff-l,3-a ff-diols such as 9 via TS-11 and cyclic ketones... 

Nakajima also developed an enantioselective addition of lithium acet-ylides to ketones in the presence of chiral lithium binaphtholate catalyst 8 (Scheme 2.7). This is the first example of the catalytic enantioselective addition of lithium acelylides to carhonyl compounds without the aid of other metal sources, such as titanium(iv) and zinc(n) species. 

Kobayashi et al. have reported the use of a chiral lanthanide(III) catalyst for the Diels-Alder reaction [51] (Scheme 1.63, Table 1.26). Catalyst 33 was prepared from bi-naphthol, lanthanide triflate, and ds-l,2,6-trimethylpiperidine (Scheme 1.62). When the chiral catalyst prepared from ytterbium triflate (Yb(OTf)3) and the lithium or sodium salt of binaphthol was used, less than 10% ee was obtained, so the amine exerts a great effect on the enantioselectivity. After extensive screening of amines, ds-1,2,6-... 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

R) -BINAL-H (R)-2,2 -Dihydroxy-1,1 -binaphthol-lithium aluminum hydride,... 

In this context, a chiral hydride reagent, BINAL-H, prepared by modification of lithium aluminum hydride with equimolar amounts of optically pure binaphthol and a simple alcohol, is extremely useful (9b, 18a, 35) Scheme 15 shows the utility of the three-component coupling synthesis. The < > side-chain unit and the hydroxycyclopentenone can be prepared with very high enantioselectivity by reduction of the corresponding enone precursors (35-38). 

Kagan and Schiffers carefully studied the effect of the lithium salts of BINOL (17) and related axially chiral binaphthols on the reduction of a variety of ketones with trialkoxysilanes [24]. They found that diethyl ether, with TMEDA as an additive, was the best solvent for asymmetric reduction of ketones. In the presence of 5 mol% of the monolithium salt of BINOL (17), acetophenone (1) could be reduced with trimethoxysilane in 80% yield and with 61% ee. Enantiomeric excesses > 90% were achieved under the same conditions with 2, 4, 6 -trimethyl-acetophenone (18) or a-tetralone (19) as substrates. Aliphatic ketones such as... 

Stereoselective synthesis of perylenequinones. Synthesis of the symmetrical perylenequinone phleichrome (4) has been effected by coupling of two identical naphthalene units to provide a binaphthol, which is then oxidized to a perylenequinone. Thus the bromonaphthalene 1 on halo-lithium exchange (f-BuLi) followed by reaction of anhydrous FeCl3 dimerizes to two optically active binaphthyls, (+)-and (— )-2, with 3 1 diastereoselectivity. 

In 1979, Noyori and co-workers invented a new type of chiral aluminum hydride reagent (1), which is prepared in situ from LiAlEE, (S)-l, E-bi-2-naphthol (BINOL), and ethanol. The reagent, called binaphthol-modified lithium aluminum hydride (BINAL-H), affects asymmetric reduction of a variety of phenyl alkyl ketones to produce the alcohols 2 with very high to perfect levels of enantioselectivity when the alkyl groups are methyl or primary1 (Scheme 4.3a). 

The binaphthol-modified lithium aluminum hydride reagents (BINAL-Hs) are also effective in enantioselective reduction of a variety of alkynyl and alkenyl ketones2 (Scheme 4.3b). When the reaction is carried out with 3 equivalents of (S)-BINAL-H at —100 to —78 C, the corresponding propargylic alcohol 3 and allylic alcohol 4 are obtained in high chemical yields with good to excellent levels of enantioselectivity. As is the case with aryl alkyl ketones, the alcohols with (.V)-con figuration are obtained when (S)-BINAL-H is employed. 

Sih (38) has described the reduction of E-l-iodo-l-octen-3-one with Penicillium decumbens to give the desired S-alcohol. Based on optical rotation, the e.e. was about 80%, An asymmetric chemical reduction of this same ketone, using lithium aluminum hydride that had been partially decomposed by one mole each of S-2,2 -dihydroxy-l,T-binaphthol and ethanol (42), gave the desired alcohol in 97% e.e. This reagent also reduced l-octyn-3-one in 84% e.e. to the corresponding alcohol (43). A 92% e.e. could be obtained with B-3-pinanyl-9-borabicyclo[3.3.1]nonane as the reducing agent (44). 

Two asymmetric synthesis approaches to chiral cyclopentenone derivatives can be envisaged. The first, reduced to practice by Noyori (43), involved reduction of cyclopentene-l,4-dione with lithium aluminum hydride chirally modified with binaphthol to give R-4-hydroxycyclopent-2-en-l-one in 94% e.e. Alternatively, manganese dioxide oxidation of allylic alcohol [40] (Fig. 7), in analogy to the cis isomer (54), would be expected to give the same enone. 

Reduction of (S)-(+)- and (R)-(-)-BNP methyl esters or acids by lithium aluminum hydride, or by Red-Al (this volume, p. 13) yields (S)- -)-and (R)-(+)-binaphthol, respectively. This is, at present, the most convenient access to optically active binaphthols, used by Cram and co-workers to prepare macrocyclic polyethers and by Japanese authors in asymmetric synthesis of cyclic binaphthyl-esters. 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

Aspinall et al. employed lithium lanthanide binaphtholates 13 (Scheme 2, THF molecules are omitted) in -BuLi additions to PhCHO (1 2 1 ratio) with 67% ee [(S)-l-phenyl-l-pentanol, diethyl ether, -98°C] [48]. With less equivalents of n-BuLi (1 1 1 ratio) only a 39% ee was observed under the same conditions. 

Scheme 2.4 Enantioselecrtive cyanosilylation of aldehydes with the use of chiral lithium(i) binaphtholates.

Based on acid-base combination chemistry, Shibasaki developed chiral heterobimetallic aluminium(m) lithium(i) bis(binaphtholate) (18), which can catalyse the enantioselective Michael reaction of cyclic enones with... 

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