BINOL complexes

The above described reaction has been extended to the application of the AlMe-BINOL catalyst to reactions of acyclic nitrones. A series chiral AlMe-3,3 -diaryl-BINOL complexes llb-f was investigated as catalysts for the 1,3-dipolar cycloaddition reaction between the cyclic nitrone 14a and ethyl vinyl ether 8a [34], Surprisingly, these catalysts were not sufficiently selective for the reactions of cyclic nitrones with ethyl vinyl ether. Use of the tetramethoxy-substituted derivative llg as the catalyst for the reaction significantly improved the results (Scheme 6.14). In the presence of 10 mol% llg the reaction proceeded in a mixture of CH2CI2 and petroleum ether to give the product 15a in 79% isolated yield. The diastereoselectiv-ity was the same as in the acyclic case giving an excellent ratio of exo-15a and endo-15a of >95 <5, and exo-15a was obtained with up to 82% ee. 

The reactions of nitrones constitute the absolute majority of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions. Boron, aluminum, titanium, copper and palladium catalysts have been tested for the inverse electron-demand 1,3-dipolar cycloaddition reaction of nitrones with electron-rich alkenes. Fair enantioselectivities of up to 79% ee were obtained with oxazaborolidinone catalysts. However, the AlMe-3,3 -Ar-BINOL complexes proved to be superior for reactions of both acyclic and cyclic nitrones and more than >99% ee was obtained in some reactions. The Cu(OTf)2-BOX catalyst was efficient for reactions of the glyoxylate-derived nitrones with vinyl ethers and enantioselectivities of up to 93% ee were obtained. 

These heterobimetallic M -M -binol complexes consdnite a new class of v/idely applicable chiral catidysts as shown in Scheme 3.16. The new catidysts consist of a centtidmetid ion fe.g.. La" , AT , Sin , Ga , three alkali inetid ions fe.g., LT, Na , K l, and three chirid tliphenol... 

NOL-based systems for addition of (substituted) anilines to meso epoxides. Hou found that a ytterbium-BI NO L complex catalyzed desymmetrization of cyclohexene oxide in up to 80% ee [15], Shibasaki demonstrated that a praseodymium-BINOL complex could promote addition of p-anisidine to several epoxides in moderate yields with modest enantioselectivities (Scheme 7.7) [16]. 

Since these early reports, several groups have continued to improve these catalytic reactions. The most successful catalysts to date are rare earth/alkali metal/BINOL complexes like LLB, while htanium, aluminum, and zinc catalysts have also been described. 

Shibasaki showed that an aluminum-lithium-BINOL complex (ALB) also catalyzes the asymmetric addition of dialkyl phosphites to aldehydes, with ees ranging from 55 to 90% for aryl or unsaturated aldehydes (Scheme 5-37). 

These heterobimetallic M1-M2-binol complexes constitute a new class of widely applicable chiral catalysts as shown in Scheme 3.16. The new catalysts consist of a central metal ion (e.g., La3+, Al3+, Sm3+, Ga3+), three alkali metal ions (e.g., Li+, Na+, K+), and three chiral diphenol... 

Scheme 3.14. Preparation of the optically active La-BINOL complex...

Scheme 3.15. La-BINOL complex-catalyzed asymmetric nitro-aldol reactions...

Another recent example is the asymmetric Mannich-type reaction of hydroxyketones using a ZnEt2-BINOL complex as a catalyst.429 The complex provided superior enantioselectivity and had a very high turnover number. 

Figure 6.25. Asymmetric allylation of benzaldehyde catalysed by a fluorinated Ti/BINOL complex under...

Preparation of diethyl (S)-a-hydroxybenzylphosphonate — Reaction of an aldehyde with a dialkyl phosphite facilitated by a chiral BINOL complex... 

R)-aluminum-lithium-BINOL complex (0.024 g, 0.04 mmol) was dissolved in toluene (0.4 ml), and to this solution was added dimethyl phosphite (0.044 g, 0.4 mmol) at room temperature the mixture was stirred for 30 min. Benzaldehyde (0.042 g, 0.4 mmol) was then added at -40°C. After having been stirred for 51 h at -40°C, the reaction mixture was treated with 1 N hydrochloric acid (1.0 ml) and extracted with ethyl acetate (3 x 10 ml). The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, 20% acetone/hexane) to give the diethyl (S)-a-hydroxybenzylphosphonate (78 mg, 90%) with 85% enantiomeric excess as a colorless solid of mp 86 to 87°C. 

Arai, T., Bougauchi, M., Sasai, H., and Shibasaki, M., Catalytic asymmetric synthesis of a-hydroxy phosphonates using the Al-Li-BINOL complex, /. Org. Chem., 61, 2926, 1996. 

Yamagishi, T., Yokonatsu, T., Suemune, K., and Shibuya, S., Enantioselective synthesis of a-hydroxyphosphinic acid derivatives through hydrophosphi-nylation of aldehydes catalyzed by Al-Li-BINOL complex, Tetrahedron, 52, 11725, 1996. 

However, the two methods of choice for the oxidations of a, (B-unsaturated ketones are based on lanthanoid-BINOL complexes or a biomimetic process based on the use of polyamino acids as catalysts for the oxidation 1"1. 

Moreover, these rare earth heterobimetallic complexes can be utilized for a variety of efficient catalytic asymmetric reactions as shown in Scheme 7 Next we began with the development of an amphoteric asymmetric catalyst assembled from aluminum and an alkali metal.1171 The new asymmetric catalyst could be prepared efficiently from LiAlH4 and 2 mol equiv of (R)-BINOL, and the structure was unequivocally determined by X-ray crystallographic analysis (Scheme 8). This aluminum-lithium-BINOL complex (ALB) was highly effective in the Michael reaction of cyclohexenone 75 with dibenzyl malonate 77, giving 82 with 99% ee and 88 % yield at room temperature. Although LLB and... 

Tiible 11. Enantioselective ring opening of various tneso-epoxides with 4-methoxyphenol (105) promoted by Ga-Ii-linked-BINOL complex (116). 

H. Sasai, T. Suzuki, N. Itoh, K. Tanaka, T. Date, K. Oka-mura, M Shibasaki, Catalytic Asymmetric Nitroaldol Reaction Using Optically Active Rare Earth BINOL Complex Investigation of the Catalyst Structure, J. Am Chem Soc 1993,115,10372-10373. 

H. Sasai, T. Tokunaga, S. Watanabe, T. Suzuki, N. Itoh, M. Shibasaki, Efficient Diastereoselective and Enantiose-lective Nitroaldol Reactions from Prochiral Starting MaterialsStUtilization of La-Li-6,6 -Disubstituted BINOL Complexes as Asymmetric CatalystsUtJ. Org Chem 1995, 60, 7388-7389. 

Catalytic Asymmetric Synthesis of Nitroaldols Using a Lanthanum-Lithium-BINOL Complex. 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

Scheme 12.17 shows a representative example of the covalent attachment of a molecular catalyst to an inorganic support material via a hnker ( tether ) [165]. Here the sequential approach was exploited to immobihze catalyticaUy valuable rare-earth metal BINOL complexes [166]. An alkoxysilane funchonalized (R)-BINOL was obtained by a four-step reaction sequence involving brominahon at the 6-position, protechon of the phenohc groups by O-methylahon with CH3I,... 

Scheme 12.17 Synthesis of silica(PMS)-tethered lanthanum (R)-BINOL complexes.

The catalytic activity of a lanthanum (R)-BINOL complex tethered either on silica (62a) or MCM-41 (62b) was evaluated for the enantioselective nitroaldol reaction of cyclohexanecarboxaldehyde (Se), hexanal (Sf), iso-butyraldehyde (Sg) and hydro-cinnamaldehyde (Sh) with nitromethane inTHF (Scheme 12.22) [166]. The silica-anchored lanthanum catalyst 62a gave 55-76% e.e. and yields up to 87%, while the PMS-immobilized catalyst 62b revealed slightly higher e.e.s (57-84%) for the same aldehydes. The homogeneous counterparts showed similar catalytic performance, albeit within a shorter reaction time. The increased enantioselectivity observed for the MCM-41 hybrid catalyst 62b was explained by transformations inside the channels, which is also reflected by lower yields due to hindered diffusion. The recyclability of the immobilized catalysts 62b was checked with hydrocin-namaldehyde (Ph). It was found that the reused catalyst gave nearly the same enantioselectivities after the fourth catalytic run, although the time period for achieving similar conversion increased from initially 30 to 42 h. 

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