Binaphthols aluminum hydrides

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). 

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. 

Enantiomerically pure binaphthol is used as a chiral auxiliary. For example, it has been used to prepare chiral aluminum hydride reducing agents, chiral Lewis acids catalysts,8 and chiral crown ethers.9... 

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. 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

To a solution of (S,S)-552 (0.30 g, 0.506 mmol) in dry diethyl ether (40 ml) was added lithium aluminum hydride (0.20 g, 5.27 mmol, 10 eq.) and the mixture was refluxed with stiring for 4 h. The reaction mixture was quenched with cautious addition of ethyl acetate and then water. The water (20 ml) was added and organic layer was separated. Aqueous layer was extracted with diethyl ether (3 10 ml). Combined organic extracts were washed with water, dried over Na2S04, filtered and evaporated to dryness. Preparative TLC on silica gel with chloroform / ethyl acetate (4 1) afforded 80 mg (50.3 %) of pure (S)-554, [a]54g -61.1° (c = 0.973, acetone), and 127 mg of recovered (5)-binaphthol (4), [a]D " -35.0° (c = 1.06, THF) [14]. 

---