(R)- & (S)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl1

[76189-55-4]  · C44H32P2  · 2,2-Bis(diphenylphosphino)-1,1-binaphthyl  · (MW 622.70)

(chiral diphosphine ligand for transition metals;2 the complexes show high enantioselectivity and reactivity in a variety of organic reactions)

Alternate Name: BINAP.

Physical Data: mp 241-242 °C; [a]25D -229° (c = 0.312, benzene) for (S)-BINAP.3

Solubility: sol THF, benzene, dichloromethane; modestly sol ether, methanol, ethanol; insol water.

Form Supplied in: colorless solid.

Analysis of Reagent Purity: GLC analysis (OV-101, capillary column, 5 m, 200-280 °C) and TLC analysis (E. Merck Kieselgel 60 PF254, 1:19 methanol-chloroform); Rf 0.42 (BINAPO, dioxide of BINAP), 0.67 (monoxide of BINAP), and 0.83 (BINAP). The optical purity of BINAP is analyzed after oxidizing to BINAPO by HPLC using a Pirkle column (Baker bond II) and a hexane/ethanol mixture as eluent.3

Preparative Methods: enantiomerically pure BINAP is obtained by resolution of the racemic dioxide, BINAPO, with camphorsulfonic acid or 2,3-di-O-benzoyltartaric acid followed by deoxygenation with Trichlorosilane in the presence of Triethylamine.3

Handling, Storage, and Precautions: solid BINAP is substantially stable to air, but bottles of BINAP should be flushed with N2 or Ar and kept tightly closed for prolonged storage. BINAP is slowly air oxidized to the monoxide in solution.

BINAP-RuII Catalyzed Asymmetric Reactions.

Halogen-containing BINAP-Ru complexes are most simply prepared by reaction of [RuCl2(cod)]n or [RuX2(arene)]2 (X = Cl, Br, or I) with BINAP.4 Sequential treatment of [RuCl2(benzene)]2 with BINAP and sodium carboxylates affords Ru(carboxylate)2(BINAP) complexes. The dicarboxylate complexes, upon treatment with strong acid HX,5 can be converted to a series of Ru complexes empirically formulated as RuX2(BINAP). These RuII complexes act as catalysts for asymmetric hydrogenation of various achiral and chiral unsaturated compounds.

a,b-Unsaturated carboxylic acids are hydrogenated in the presence of a small amount of Ru(OAc)2(BINAP) to give the corresponding optically active saturated products in quantitative yields.6 The reaction is carried out in methanol at ambient temperature with a substrate:catalyst (S:C) ratio of 100-600:1. The sense and degree of the enantioface differentiation are profoundly affected by hydrogen pressure and the substitution pattern of the substrates. Tiglic acid is hydrogenated quantitatively with a high enantioselectivity under a low hydrogen pressure (eq 1), whereas naproxen, a commercial anti-inflammatory agent, is obtained in 97% ee under high pressure (eq 2).6a

Enantioselective hydrogenation of certain a- and b-(acylamino)acrylic acids or esters in alcohols under 1-4 atm H2 affords the protected a- and b-amino acids, respectively (eqs 3 and 4).2a,7 Reaction of N-acylated 1-alkylidene-1,2,3,4-tetrahydroisoquinolines provides the 1R- or 1S-alkylated products. This method allows a general asymmetric synthesis of isoquinoline alkaloids (eq 5).8

Geraniol or nerol can be converted to citronellol in 96-99% ee in quantitative yield without saturation of the C(6)-C(7) double bond (eq 6).9 The S:C ratio approaches 50 000. The use of alcoholic solvents such as methanol or ethanol and initial H2 pressure greater than 30 atm is required to obtain high enantioselectivity. Diastereoselective hydrogenation of the enantiomerically pure allylic alcohol with an azetidinone skeleton proceeds at atmospheric pressure in the presence of an (R)-BINAP-Ru complex to afford the b-methyl product, a precursor of 1b-methylcarbapenem antibiotics (eq 7).10 Racemic allylic alcohols such as 3-methyl-2-cyclohexenol and 4-hydroxy-2-cyclopentenone can be effectively resolved by the BINAP-Ru-catalyzed hydrogenation (eq 8).11

Diketene is quantitatively hydrogenated to 3-methyl-3-propanolide in 92% ee (eq 9). Certain 4-methylene- and 2-alkylidene-4-butanolides as well as 2-alkylidenecyclopentanone are also hydrogenated with high enantioselectivity.12

Hydrogenation with halogen-containing BINAP-Ru complexes can convert a wide range of functionalized prochiral ketones to stereo-defined secondary alcohols with high enantiomeric purity (eq 10).13 3-Oxocarboxylates are among the most appropriate substrates.13a,4d For example, the enantioselective hydrogenation of methyl 3-oxobutanoate proceeds quantitatively in methanol with an S:C ratio of 1000-10 000 to give the hydroxy ester product in nearly 100% ee (eq 11). Halogen-containing complexes RuX2(BINAP) (X = Cl, Br, or I; polymeric form) or [RuCl2(BINAP)]2NEt3 are used as the catalysts. Alcohols are the solvents of choice, but aprotic solvents such as dichloromethane can also be used. At room temperature the reaction requires an initial H2 pressure of 20-100 atm, but at 80-100 °C the reaction proceeds smoothly at 4 atm H2.4c,4d

3-Oxocarboxylates possessing an additional functional group can also be hydrogenated with high enantioselectivity by choosing appropriate reaction conditions or by suitable functional group modification (eq 12).13b,13c

The pre-existing stereogenic center in the chiral substrates profoundly affects the stereoselectivity. The (R)-BINAP-Ru-catalyzed reaction of (S)-4-(alkoxycarbonylamino)-3-oxocarboxylates give the statine series with (3S,4S) configuration almost exclusively (eq 13).14

Hydrogenation of certain racemic 2-substituted 3-oxocarboxylates occurs with high diastereo- and enantioselectivity via dynamic kinetic resolution involving in situ racemization of the substrates.15 The (R)-BINAP-Ru-catalyzed reaction of 2-acylamino-3-oxocarboxylates in dichloromethane allows preparation of threonine and DOPS (anti-Parkinsonian agent) (eq 14).16 In addition, a common intermediate for the synthesis of carbapenem antibiotics is prepared stereoselectively on an industrial scale from a 3-oxobutyric ester (1) with an acylaminomethyl substituent at the C(2) position.16a The second-order stereoselective hydrogenation of 2-ethoxycarbonylcycloalkanones gives predominantly the trans hydroxy esters (2) in high ee, whereas 2-acetyl-4-butanolide is hydrogenated to give the syn diastereomer (3).17

Certain 1,2- and 1,3-diketones are doubly hydrogenated to give stereoisomeric diols. 2,4-Pentanedione, for instance, affords (R,R)- or (S,S)-2,4-pentanediol in nearly 100% ee accompanied by 1% of the meso diol.13b

A BINAP-Ru complex can hydrogenate a C=N double bond in a special cyclic sulfonimide to the sultam with >99% ee.18

The asymmetric transfer hydrogenation of the unsaturated carboxylic acids using formic acid or alcohols as the hydrogen source is catalyzed by Ru(acac-F6)(h3-C3H5)(BINAP) or [RuH(BINAP)2]PF6 to produce the saturated acids in up to 97% ee (eq 15).19

BINAP-Ru complexes promote addition of arenesulfonyl chlorides to alkenes in 25-40% optical yield.20

BINAP-RhI Catalyzed Asymmetric Reactions.

The rhodium(I) complexes [Rh(BINAP)(cod)]ClO4, [Rh(BINAP)(nbd)]ClO4, and [Rh(BINAP)2]ClO4, are prepared from [RhCl(cod)]2 or Bis(bicyclo[2.2.1]hepta-2,5-diene)dichlorodirhodium and BINAP in the presence of AgClO4.21 [Rh(BINAP)S2]ClO4 is prepared by reaction of [Rh(BINAP)(cod or nbd)]ClO4 with atmospheric pressure of hydrogen in an appropriate solvent, S.21a BINAP-Rh complexes catalyze a variety of asymmetric reactions.2

Prochiral a-(acylamino)acrylic acids or esters are hydrogenated under an initial hydrogen pressure of 3-4 atm to give the protected amino acids in up to 100% ee (eq 16).21a The BINAP-Rh catalyst was used for highly diastereoselective hydrogenation of a chiral homoallylic alcohol to give a fragment of the ionophore ionomycin.22

The cationic BINAP-Rh complexes catalyze asymmetric 1,3-hydrogen shifts of certain alkenes. Diethylgeranylamine can be quantitatively isomerized in THF or acetone to citronellal diethylenamine in 96-99% ee (eq 17).23 This process is the key step in the industrial production of (-)-menthol. In the presence of a cationic (R)-BINAP-Rh complex, (S)-4-hydroxy-2-cyclopentenone is isomerized five times faster than the (R) enantiomer, giving a chiral intermediate of prostaglandin synthesis.24

Enantioselective cyclization of 4-substituted 4-pentenals to 3-substituted cyclopentanones in >99% ee is achieved with a cationic BINAP-Rh complex (eq 18).25

Reaction of styrene and catecholborane in the presence of a BINAP-Rh complex at low temperature forms, after oxidative workup, 1-phenylethyl alcohol in 96% ee (eq 19).26

Neutral BINAP-Rh complexes catalyze intramolecular hydrosilylation of alkenes. Subsequent Hydrogen Peroxide oxidation produces the optically active 1,3-diol in up to 97% ee (eq 20).27

BINAP-Pd Catalyzed Asymmetric Reactions.

BINAP-Pd0 complexes are prepared in situ from Bis(dibenzylideneacetone)palladium(0) or Pd2(dba)3.CHCl3 and BINAP.28 BINAP-PdII complexes are formed from Bis(allyl)di-m-chlorodipalladium, Palladium(II) Acetate, or PdCl2(MeCN)2 and BINAP.29-31

A BINAP-Pd complex brings about enantioselective 1,4-disilylation of a,b-unsaturated ketones with chlorinated disilanes, giving enol silyl ethers in 74-92% ee (eq 21).29

A BINAP-PdII complex catalyzes a highly enantioselective C-C bond formation between an aryl triflate and 2,3-dihydrofuran (eq 22).30 The intramolecular version of the reaction using an alkenyl iodide in the presence of PdCl2[(R)-BINAP] and Silver(I) Phosphate allows enantioselective formation of a bicyclic ring system (eq 23).31

Enantioselective electrophilic allylation of 2-acetamidomalonate esters is effected by a BINAP-Pd0 complex (eq 24).32

A BINAP-Pd0 complex catalyzes hydrocyanation of norbornene to the exo nitrile with up to 40% ee.28

BINAP-IrI Catalyzed Asymmetric Reactions.

[Ir(BINAP)(cod)]BF4 is prepared from [Ir(cod)(MeCN)2]BF4 and BINAP in THF.33

A combined system of the BINAP-Ir complex and bis(o-dimethylaminophenyl)phenylphosphine or (o-dimethylaminophenyl)diphenylphosphine catalyzes hydrogenation of benzylideneacetone33a and cyclic aromatic ketones33b with modest to high enantioselectivities (eq 25).


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Masato Kitamura & Ryoji Noyori

Nagoya University, Japan



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