[79547-82-3] · C21H16O2 · (MW 300.36)
(reagent used as chiral proton source or chiral ligand in several enantioselective reactions)
Physical Data: mp 89-91 °C; [a]D27 +38.9 [c 0.68, THF, 99.3% ee (R)], [a]D28 -44.8 (c 1.4, CHCl3, 99.3% ee (R)]; HPLC [CHIRALCEL OD, 5% i-PrOH-hexane, retention time for the (R)-enantiomer, 25.12 min; for the (S)-enantiomer, 35.47 min]; IR (Nujol) 3478 cm-1; 1H NMR (300 MHz, CDCl3) d3.81 (s, 3H), 4.91 (s, 1H, exchangeable with D2O), 7.04 (br d, 1H, J = 7.7 Hz), 7.14-7.40 (m, 6H), 7.49 (d, 1H, J = 9.3 Hz), 7.86 (br d, 1H, J = 8.0 Hz), 7.90 (d, 2H, J = 8.5 Hz), 8.06 (d, 1H, J = 9.1 Hz); MS m/z = 300 (M+, 100%).
Solubility: soluble in alcohol, diethyl ether, toluene, and most organic solvents.
Form Supplied in: white solid.
Preparative Methods: (R)-2-hydroxy-2´-methoxy-1,1´-binaphthyl [(R)-BINOL-Me] can be prepared from commercially available (R)-1,1´-bi-2-naphthol [(R)-BINOL] by the use of 1 mol equiv of methyl iodide and sodium hydride in N,N-dimethylformamide (DMF)1a or by the use of Mitsunobu reaction.1b
Purification: recrystallization from toluene-hexane or purification by silica gel column chromatography from a hexane- AcOEt (8:1) eluent.
Handling, Storage, and Precautions: very stable in air.
Enantioselective protonation of silyl enol ethers is a very simple and attractive route for preparing optically active carbonyl compounds.2 However, it is difficult to achieve high enantioselectivity using simple chiral Brønsted acids because of the conformational flexibility in the neighborhood of the proton. In 1994, the authors found that the
Taniguchi and Ogasawara have applied the enantioselective protonation using LBA to the asymmetrization of a meso-1,2-enediol bis(trimethylsilyl) ether having an endo-tricyclic [4.2.1.02.5]nonene framework (up to 90% ee) (
The authors have succeeded in the enantioselective protonation using a stoichiometric amount of an achiral proton source and a catalytic amount of (R)-BINOL-Me in place of (R)-BINOL (
The mechanism of the catalytic cycle has been investigated by 1H NMR analysis of the 1 to 1 reaction mixtures of the silyl enol ether and chiral LBAs, (R)-BINOL-SnCl4 and (R)-BINOL-Me-SnCl4, at -78 °C. In the former case, two singlets for the TMS groups of Me3SiCl and the mono trimethylsilyl ether of (R)-BINOL have been observed at a molar ratio of 15 to 85. In the latter case, only one singlet for TMSCl has been observed. The presence of Me3SiCl suggests the generation of tin(IV) aryloxide intermediates. The catalytic cycle can be reasonably explained by assuming that the tin(IV) aryloxide intermediate is reconverted to the chiral LBA by receiving a proton and a chloride from 2,6-dimethylphenol and Me3SiCl or SnCl4, respectively (
The LBAs, BINOL-SnCl4 and BINOL-Me-SnCl4, are highly effective proton donors for the enantioselective protonation of allyltrimethyltins to give optically active olefins.3d In the presence of 1.5 equiv of (R)-BINOL-Me-SnCl4 in toluene, the protonation of (E)-3-phenyl-2-butenyltrimethyltin proceeds rapidly at -78 °C to form (S)-3-phenylbut-1-ene with good enantioselectivity and complete g-regioselectivity (
The E/Z substrate-dependent absolute stereochemistry and the steric influence of tin-substituents on the enantioselectivity observed in these reactions suggest that the mechanism is essentially different from that of silyl enol ethers. Although the detailed stereochemical course is not ascertained, it is possible that the protonation may occur via a two chlorine-bridged intermediate involving allyltrimethyltin and LBA.
Protodesilylation and isomerization are able to occur during the reaction of silyl enol ethers with a Brønsted acid. The thermodynamic equilibration of trimethylsilyl enol ethers catalyzed by a Brønsted acid was first reported by Stork and Hudrlik in 1968.5 However, this equilibration was not established as a synthetically useful procedure, since the use of a Brønsted acid was seriously complicated by the concurrent formation of higher-molecular-weight materials and ketones. The greater stability of the Si-O bond in silyl enol ethers and the milder nucleophilicity of the conjugate base to the silicon atom favor the latter process. The authors have found that the regio and stereoselective isomerization of a kinetic silyl enol ether to a thermodynamic one is catalyzed by LBA.6 Kinetic TBDMS enol ethers are isomerized to the thermodynamic ones in the presence of catalytic amounts of the coordinate complexes of tin tetrachloride and the monoalkyl ethers of BINOL or biphenol (BIPOL). On the other hand, use of the coordinate complexes with biphenol and other monoaryl alcohols affords predominantly the corresponding ketones. For the various structurally diverse substrates, the isomerization cleanly proceeds in the presence of 5 mol % of the achiral LBA, BIPOL-i-Pr-SnCl4. The catalyst is effective not only for cyclic silyl enol ethers but also acyclic ones, and Z-isomers are stereoselectively produced (
A one-pot procedure from the racemic silyl enol ether to (S)-2-phenylcyclohexanone has been realized by combination of the isomerization and subsequent enantioselective protonation catalyzed by (R)-BINOL-Me in the presence of 2,6-dimethylphenol, tin tetrachloride, and TMSCl (
Non-enzymatic enantioselective polyene cyclizations are very attractive alternatives to the multistep synthesis from naturally occurring chiral synthons. The authors have succeeded in the first enantioselective biomimetic cyclization of polyprenoids catalyzed by LBA.7 (-)-Ambrox® is the most important commercial substitute for ambergris, due to its unique olfactory and fixative properties. The successful preparation of (-)-ambrox® has been achieved by the enantioselective cyclization of homofarnesol promoted by (R)-BINOL-Me-SnCl4, although the enantioselectivity and diastereoselectivity is moderate (
Cyclization of the more reactive o-geranylphenol with (R)-BINOL-SnCl4 gives the trans-fused tricyclic compound as a major diastereomer (36% ee, 84% ds) in good yield (
The authors have found that the same tricyclic ether is obtained with much better selectivity from geranyl phenyl ether (
(-)-Chromazonarol, a minor constituent of the brown Pacific seaweed, has been synthesized using LBA-promoted enantioselective cyclization. The cyclization of 4-benzyloxyphenyl farnesyl ether with (S)-LBA gives the desired tetracyclic compound as the major diastereomer in 44% ee (
This approach using LBA has been applied to the enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group that serves as a less-nucleophilic terminator than a hydroxy group.8 The reaction of 1-homogeranyl-4-(tert-butyldiphenylsiloxy)benzene with (R)-BINOL-Me-SnCl4 gives the desired tricyclic compound in 13% yield with 72% ee. The other products are monocyclization products. The enantioselectivity of the tricyclic compound is improved to 81% ee when mono(o-fluorobenzyl) ether of (R)-BINOL [(R)-BINOL-o-F-Bn] is used instead of BINOL-Me. The desilylation and subsequent diastereoselective cyclization of a crude mixture, which is obtained in the above enantioselective cyclization, gives the desired tricyclic compound in 78% ee and 94% yield in three steps. This compound can be converted to (+)-ferruginol (
The enantioselective cyclization of 1-homogeranyl-3-(tert- butyldiphenylsiloxy)benzene with use of (R)-BINOL-o-F-Bn gives trans-fused tricyclic compound in 78% ee (trans only), together with the monocyclization products. The subsequent diastereoselective cyclization with BF3·Et2O gives (+)-13-acetoxypodocarpa-8(14)-en-13-one, a versatile intermediate for synthesis of naturally occurring diterpenes.
Tetracyclic terpene from Eocene Messel shale (Germany) can be also synthesized by using the LBA-induced enantioselective cyclization of 3-homofarnesyltoluene as a key step (
Yamada and Shibasaki have found that a direct catalytic enantioselective aldol reaction of an aldehyde and unmodified ketone is promoted by a chiral barium complex (5 mol %) prepared from Ba(O-i-Pr)2 and 2.5 mol equiv of (R)-BINOL-Me.9 The possible structure of the barium catalyst which plays the role of a Lewis acid and a Brønsted base, has been characterized by LDI-TOFMS, 13C-NMR spectroscopy and extensive studies of reaction conditions (
The desymmetric transformation of meso-structures has been recognized as a versatile synthetic method for optically active compounds in organic enzymatic processes. The enantioselective intramolecular cyclization of the bis-phenyllithium species, which is generated by addition of butyllithium to a solution of cis-3,5-di(bromophenoxy)cyclopentene, has been attained by addition of lithium salt (1.2 equiv) of (R)-BINOL-Me to produce a cyclopenta[b]benzofuran with 87% ee (
Nagoya University Furo-cho, Chikusa, Nagoya, Japan