(R)-1,1-Bi-2,2-naphthol1

[18531-94-7]  · C20H14O2  · (R)-1,1-Bi-2,2-naphthol  · (MW 286.33)

(chiral ligand and auxiliary1)

Alternate Name: BINOL.

Physical Data: mp 208-210 °C; [a]21 +34° (c = 1, THF).

Solubility: sol toluene, CH2Cl2, EtNO2.

Form Supplied in: white solid; widely available.

Preparative Methods: racemic 1,1-bi-2,2-naphthol (BINOL) is most conveniently prepared by the oxidative coupling reaction of 2-naphthol in the presence of transition metal complexes (eq 1).2 The resolution of racemic BINOL with cinchonine may be performed via the cyclic phosphate (eq 2).3 An alternative procedure to provide directly optically active BINOL is the oxidative coupling of 2-naphthol catalyzed by CuII salt in the presence of chiral amines (eq 3).4 The best procedure uses (+)-amphetamine as the chiral ligand and provides BINOL in 98% yield and 96% ee. Above 25 °C the CuII/(+)-amphetamine/(S)-BINOL complex precipitates while the more soluble CuII/(+)-amphetamine/(R)-BINOL complex is slowly transformed into the former complex. 9,9-Biphenanthrene-10,10-diol has also been prepared in 86% yield and with 98% ee by a similar asymmetric oxidative coupling of 9-phenanthrol in the presence of (R)-1,2-diphenylethylamine.5

Handling, Storage, and Precautions: keep tightly closed, store in a cool dark place; on heating in butanol at 118 °C for 24 h, BINOL lost ~1% of its optical rotation; at 100 °C for 24 h in dioxane-1.2 N HCl, BINOL lost 56% of its rotation; after 24 h at 118 °C in butanol-0.7 N KOH, BINOL lost 20% of its rotation.

Hydrocarboxylation.

The cyclic phosphate resolved according to eq 2 can be used as the chiral ligand in the palladium(II) catalyzed asymmetric hydrocarboxylation of arylethylenes.6 The 1-arylpropanoic acid is obtained regiospecifically with high enantioselectivity (91% ee) (eq 4).

Crown Ethers.

BINOL-derived crown ethers have been reported.7 Crown ethers containing 3,3-disubstituted BINOL derivatives are particularly effective for asymmetric synthesis. Thus complexes of these crown ethers (e.g. 18-Crown-6) with Potassium Amide or Potassium t-Butoxide catalyze asymmetric Michael additions. The reaction of methyl 1-oxo-2-indancarboxylate with methyl vinyl ketone with the 3,3-dimethyl-BINOL-crown ether/KO-t-Bu complex gives the Michael product in 48% yield and with 99% ee (eq 5).8

Polymerization.

Complexes of BINOL-derived crown ethers with KO-t-Bu or BuLi have been used as initiators in the asymmetric polymerization of methacrylates.9 Thus optically active polymers are obtained with 80-90% isotacticity. Complexes of BINOL with Diethylzinc or CdMe2 also initiate the asymmetric polymerization of heterocyclic monomers.10 The chiral initiators selectively polymerize one enantiomer to give an optically active polymer. The unreacted monomer is recovered with 92% ee at 67% conversion in the polymerization of methylthiirane with (S)-BINOL/Et2Zn.

Ullmann Coupling Reaction.

Axially dissymmetric biaryls have been synthesized via an intramolecular Ullmann coupling reaction of BINOL-derived aryl diesters (eq 6).11 In the example shown, the functionalized binaphthyl is obtained with high ee after hydrolysis of the intermediate 12-membered cyclic diester.

Reduction of Prochiral Ketones.

BINOL has been used as the chiral ligand of the reagent BINAL-H (see Lithium Aluminum Hydride-2,2-Dihydroxy-1,1-binaphthyl) for asymmetric reduction.12 The reagent reduces prochiral unsaturated ketones to the corresponding secondary alcohols in up to 90% yield and >90% ee (eq 7); (R)-BINAL-H leads to the (R)-alcohols while (S)-BINAL-H gives the (S)-alcohols.

Addition Reactions of Chiral Titanium Reagents to Aldehydes.

The preparation and use of the BINOL-derived titanium complexes in the enantioselective synthesis of some benzhydrols (>90% ee) have been reported (eq 8).13

Cyanosilylation.

The chiral titanium reagent, prepared from the lithium salt of BINOL with TiCl4, has been used as a catalyst for the asymmetric addition of cyanotrimethylsilane to aldehydes.14 In the example shown, the cyanohydrin is obtained with <=82% ee (eq 9).

Diels-Alder Reactions.

BINOL and its derivatives are used as the chiral ligand of chiral Lewis acid complexes for enantioselective Diels-Alder cycloadditions. BINOL-TiCl2, prepared from the lithium salt of BINOL with Titanium(IV) Chloride, also catalyzes the enantioselective Diels-Alder reaction of cyclopentadiene with methacrolein (eq 10)14,15 The exo adduct is obtained as the major product (56% yield), but with low enantioselectivity (16% ee). More recently, BINOL-TiX2 (X = Br or Cl) have been prepared in situ from diisopropoxytitanium dihalides ((i-PrO)2TiX2, X = Br16 or Cl17) with BINOL in the presence of molecular sieves (MS 4A).16 The Diels-Alder reaction of methacrolein with 1,3-dienol derivatives can be catalyzed by BINOL-TiX2. The endo adducts are obtained in high enantioselectivity (eq 11).18 Asymmetric catalytic Diels-Alder reaction of naphthoquinone derivatives as the dienophile (eq 12)18 can in principle provide an efficient entry to the asymmetric synthesis of anthracyclinone aglycones. The reaction of the 5-hydroxynaphthoquinone with 1-acetoxy-1,3-diene in the presence of MS-free BINOL-TiCl2 (10 mol%) provides the corresponding Diels-Alder product in high chemical yield and with high enantioselectivity (76-96% ee).18b The Diels-Alder product is also obtained by the use of 1 equiv of 3,3-diphenyl-BINOL/borane complex (eq 13); the structure of the intermediate has been proposed.19

3,3-Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3-diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14).20 Endo products are obtained with a high level of asymmetric induction (>90% ee); however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15).21 BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16).22

Hetero Diels-Alder Reaction.

Modified BINOL-derived organoaluminum reagents have been used in the asymmetric hetero Diels-Alder reaction of aldehydes (eq 17). The dihydropyrones are obtained with high cis diastereoselectivity and enantioselectivity.23 The hetero Diels-Alder reaction of glyoxylates proceeds smoothly with methoxydienes using BINOL-TiCl2 as a catalyst to give the cis product in high enantiomeric excess (eq 18).18b,24 The hetero Diels-Alder product thus obtained can be readily converted to the lactone portion of HMG-CoA inhibitors such as mevinolin or compactin.

Carbonyl-Ene Reaction.

BINOL-TiX2 reagent exhibits a remarkable level of asymmetric catalysis in the carbonyl-ene reaction of prochiral glyoxylates, thereby providing practical access to a-hydroxy esters.16,25 These reactions exhibit a remarkable positive nonlinear effect (asymmetric amplification) that is of practical and mechanistic importance (eq 19).26 The desymmetrization of prochiral ene substrates with planar symmetry by the enantiofacial selective carbonyl-ene reaction provides an efficient solution to remote internal asymmetric induction (eq 20).27 The kinetic resolution of a racemic allylic ether by the glyoxylate-ene reaction also provides efficient access to remote but relative asymmetric induction (eq 21).27 Both the dibromide and dichloride catalysts provide the (2R,5S)-syn product with 97% diastereoselectivity and &egt;95% ee.

Ene Cyclization.

An intramolecular (3,4)-ene reaction of unsaturated aldehydes has been accomplished with the BINOL-derived zinc reagent.28 Cyclization of 3-methylcitronellal with at least 3 equiv of BINOL-Zn reagent afforded the trans-cyclohexanol in 86% yield and 88% ee (eq 22). Asymmetric ene cyclizations of type (2,4) are also catalyzed by the BINOL-derived titanium complexes ((R)-BINOL-TiX2, X = ClO4 or OTf), modified by the perchlorate or trifluoromethanesulfonate ligand. The 7-membered cyclization of type 7-(2,4) gives the oxepane in high ee (eq 23).

Cationic Cyclization.

A cationic cyclization of BINOL-derived neryl ether has been accomplished with an organoaluminum triflate catalyst.29 Limonene is obtained in 54% yield and 77% ee (eq 24).

Mukaiyama Aldol Condensation.

The BINOL-derived titanium complex BINOL-TiCl2 is an efficient catalyst for the Mukaiyama-type aldol reaction. Not only ketone silyl enol ether (eq 25),30 but also ketene silyl acetals (eq 26)31 can be used to give the aldol-type products with control of absolute and relative stereochemistry.

Nitro-Aldol Condensation.

A BINOL-derived lanthanide complex has been used as an efficient catalyst for the nitro-aldol reaction (eq 27).32 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.

Carbonyl Addition of Allylic Silanes and Stannanes.

BINOL-TiCl2 reagent also catalyzes the asymmetric carbonyl addition reaction of allylic silanes and stannanes.33 Thus the addition reaction of glyoxylate with (E)-2-butenylsilane and -stannane proceeds smoothly to give the syn product in high enantiomeric excess (eq 28). The reaction of aliphatic and aromatic aldehydes with allylstannane is also catalyzed by BINOL-TiCl2 or BINOL-Ti(O-i-Pr)2 to give remarkably high enantioselectivity.34

Claisen Rearrangements.

A modified BINOL-derived aluminum reagent is an effective chiral catalyst for asymmetric Claisen rearrangement of allylic vinyl ethers (eq 29).35 The use of vinyl ethers with sterically demanding C-3 substituents is necessary for the high level of asymmetric induction.

Alkylation of BINOL-Derived Ester Enolates.

The diastereoselective alkylation of BINOL-derived arylacetates affords the optically active 2-arylalkanoic acids (eq 30).36

Related Reagents.

(R)-1,1-Bi-2,2-naphthotitanium Dichloride; (R)-1,1-Bi-2,2-naphthotitanium Diisopropoxide; (R,R)-[Ethylene-1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)]titanium (R)-1,1-Bi-2,2-naphtholate; (-)-[Ethylene-1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)]zirconium (R)-1,1-Bi-2,2-naphtholate; Lithium Aluminum Hydride-2,2-Dihydroxy-1,1-binaphthyl.


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Koichi Mikami & Yukihiro Motoyama

Tokyo Institute of Technology, Japan



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