Titanium/BINOL catalysts

Mikami et al. studied the Diels-Alder reaction between a-methylstyrene and n-butyl glyoxylate catalyzed by a titanium binolate catalyst.76-78 Addition of 0.5 equivalents of (Zf)-BINOL to 1 equivalent of the racemic catalyst accelerated the reaction and gave the product with 89.8% ee (Scheme 20). Enantiopure catalyst derived solely from (/ )-BINOL gave the product with 94.5% ee. Here the amplification originates from the creation of a new chiral complex 9 of higher efficiency (rate and enantioselectivity) with respect to each enantiomer of the original racemic catalyst. 

Faller, J. W., Sams, D. W. I., Liu, X. Catalytic Asymmetric Synthesis of Homoallylic Alcohols Chiral Amplification and Chiral Poisoning in a Titanium/BINOL Catalyst System. J. Am. Chem. Soc. 1996,118, 1217-1218. 

In a direct comparison, the CAB catalyst proved to be superior to the titanium binol catalyst in the reaction of branched aldehydes in both reaction times and selectivity. Finally, the CAB-promoted reaction of a chiral aldehyde with ( )-85 was examined (Scheme 10-48). When the aldehyde (7 )-106 reacts with the 2-bute-nylstannane in the presence of the CAB catalyst, a 98/2 mixture of diastereomers is obtained. The CAB-promoted reaction of the aldehyde (S)-106 with the (E)-85 affords a 90/10 mixture of diastereomers. This adduct is the minor isomer from the BF3-promoted addition of ( )-85 to aldehyde (S)-106. Thus, the CAB-promoted additions are strongly reagent controlled, essentially overriding the intrinsic facial preference of the aldehyde substrate. 

This explanation is described as a mnemonic rule [228], which can only be taken as a first approximation of reality. The same rule can be used to rationalize the topicity of other asymmetric Diels-Alder reactions, such as those employing titanium BINOLate catalysts (Figure 6.18i, [230]), or iron bisoxazoline catalysts (Figure 6.18j,k [206,215]). Although the explanation seems reasonable, the picture is not complete, since it does not account for a number of observations, including the fact that the dioxolane substituents exert an extraordinary effect on catalyst efficiency (c/ Table 6.6, entries 2 and 5). Additionally, both titanium TADDOLate [228] and BINOLate [230] complexes show a nonlinear relationship between enantiomeric purity of the catalyst and that of the product, which suggests that some sort of dimerization phenomenon is involved. 

The catalytic asymmetric Michael reaction using silyl enol esters (Mukaiyama-Michael reaction) as the pronucleophiles has been reported using a titanium/BINOL catalyst (in up to 90% ee). Considering furan (11.36) as a silyl enol ether, this has been shown to undergo nucleophilic addition to the Michael acceptor (11.37). The product (11.38) canbe obtained with excellent diastereocon-trol with the scandium complex of hgand (11.39), or with excellent enantiocontrol... 

With environmental consideration in mind, the group has developed a version in concentrated media, i.e. without dichloromethane and only three equivalents of isopropanol. ° For instance, the ketone 64 was converted into the alcohol 65 in 93% yield and 95% enantiomeric excess using only 10 mol% of titanium-BINOL catalyst (Conditions B, Scheme 7.36). A slight decrease of efficiency was observed using 5 mol% of catalyst (Conditions C). The efficiency of the method was illustrated by a tandem asymmetric ally-lation/diastereoselective epoxidation reaction of cyclic enones that is based on the use of the allylation catalyst for a subsequent epoxidation with TBHP, as illustrated in Scheme 7.37. ° ... 

In parallel with the search for catalytic systems, has emerged an impressive amount of results in the field of enantioselective allylation. The pioneering work of Marshall using a chiral (acyloxy)borane (CAB) system [216] was readily followed by titanium/BINOL catalysts [217], leading to homoallylic alcohols with enantiomeric excess up to 98%. An extension of this work in fluorous phase was also developed with 6,6 -perfluoroalkylated BINOLs [218]. Replacing the titanium by zirconium (IV) salts, led to more reactive catalyst for the allylation of aromatic and aliphatic aldehydes [219]. One of the more active catalyst is the zirconium-BINOL system associated with 4-tert-butylcalix [4]arene, which remains active with only 2% of the chiral inductor [220]. The use of activators, such as iPrSSiMe3, iPrSBEt2,... 

A remarkable change in reaction course is notable when changing the metal from aluminum to titanium for cydoaddition reactions using BINOL as the chiral ligand. When the chiral aluminum(III) catalyst is applied the cydoaddition product is the major product, whereas for the chiral titanium(IV) catalyst, the ene product is the major product. The reason for this significant change in reaction course is not fully understood. Maybe the glyoxylate coordinates to the former Le-... 

Two other types of catalysts have been investigated for the enantioselective Strecker-type reactions. Chiral N-oxide catalyst 24 has been utilized in the trimethylsilyl cyanide promoted addition to aldimines to afford the corresponding aminonitriles with enantioselectivities up to 73% ee [14]. Electron-deficient aldimines were the best substrates, but unfortunately an equimolar amount of catalyst 24 was used in these reactions. The asymmetric Strecker addition of trimethylsilyl cyanide to a ketimine with titanium-based BINOL catalyst 25 gave fast conversions to quarternary aminonitriles with enantiomeric excesses to 59%... 

The hypothesis that the structure of these catalysts is not always in accordance with a monomeric structure has been expressed for both the titanium-BINOL complexes [30] and the corresponding lanthanum species. In the latter case, this hypothesis has been corroborated impres-... 

Reetz et al. reported that a chiral Ti complex prepared from TiCL). and the dilithium salt of (S)-BINOL promoted the aldol reaction of 3-mefhylbutanal with KSA 48 with only poor enantioselectivity (60%, 8% ee) [115 b]. After this pioneering work, the titanium-based catalyst system has been intensively improved to attain an efficient catalytic cycle and high stereoselectivity [147-155]. 

Heterobimetallic binol catalyst based on titanium, aluminum, and scandium have also been reported.40 The results showed that the titanium catalyst was not effective. While the aluminum catalyst was better, it turned out that the scandium derivative was the most efficient. 

Tridentate BINOL catalysts can be derived from titanium tetra(isopropoxide), BINOL ligands, and hindered amine bases. These catalysts have also been shown to provide good yields and ee s for the aldol reactions at low temperatures of 2-methoxypropene with several aldehydes to the P-hydroxyketones, but an acid workup of the products is required. 

Narasaka et al. developed a titanium catalyst generated by complexation with chiral diols.245 xhe dienophile must contain functionality that will coordinate with the metal catalyst to form a chiral complex, and these catalysts are less effective with dienes and dienophiles that do not contain heteroatoms. A related titanium-BINOL complex has been used to catalyze Diels-Alder reactions.246 Kelly prepared a transient... 

Immobilization of chiral ligands to effect asymmetric induction in alkylation of aromatic aldehydes by diorganozinc reagents promoted by PEG-im-mobilized ligands 54-57 can also be promoted by soluble polystyrene-bound species. A recent example of this is work where a polystyrene-bound BINOL was prepared [ 105]. This polymer 69 was used to form titanium-BINOLate and AlLibis(binaphthoxide) catalysts for Et2Zn reaction with benzaldehyde and for asymmetric Michael additions of stabilized carbanions to cyclohexenone. While good stereoselectivities were obtained with these catalysts, the synthetic yields were modest. 

The relatively weaker Lewis acidic titanium complexes require the use of a stronger nucleophile than allylsilanes, and tributylallyltin (6.81) is the most common aUylating agent employed when using titanium-based catalyst systems. In 1993, Umani-Ronchi and Keck published related results using BINOL/titanium derived catalysts. In the Umani-Ronchi system, BINOL is employed, in combination with TiCl2 (0 Pr)2 and shown to work weU with aliphatic... 

The catalysed carbonyl-ene reaction frequently employs reactive aldehydes, especially glyoxalate esters. Mikami s group has studied the titanium/BINOL catalysed carbonyl-ene reaction in considerable detail. Typically, the catalyst is prepared in situ from diisopropoxytitanium dihalide and BINOL in the presence of 4A molecular sieves. Thus, alkenes (7.179) and (7.180) are converted into the homoallylic alcohols (7.181) and (7.182) with high enantioselectivity. Typical examples use up to 10 mol% of catalysts, but variation in the catalyst preparation allows the use of only 0.2 mol%. ... 

The titanium/BINOL catalysed ene reaction is subject to a strong positive nonlinear effect (see Section 6.1). Thus, the use of BINOL of only 33% ee still provides product (7.86) with 91% ee. Higher enantioselectivites (91-99%) in this reaction have been obtained using as little as 0.1 mol% of catalysts prepared from 2 1 molar ratios of BINOLititanium under nearly solvent-free conditions. 

The use of ionic liquids to perform asymmetric sulfoxidation reactions was proposed by Halligudi and coworkers. A chiral titanium-BINOL complex was immobilised onto ionic liquid-modified mesoporous silica (SBA-15) support 14 and the resulting heterogeneous catalyst was successfully employed in asymmetric sulfoxidation of thioanisole using TBHP as... 

Z. Wang and K. Ding Asymmetric ring-opening aminolysis of 4,4-di-methyl-3,5,8-trioxabicyclo[5.1. OJoctane catalyzed by titanium/BINOLate/water system evidence for the Ti(BINOLate)2-bearing active catalyst entities was obtained and the role of water for ihe reaction was examined. [258]... 

Diazoalkanes have also been widely utilized in 1,3-DC reactions with various olefins to construct pyrazolines and pyrazoles, which are easily converted to various types of nitrogen-containing molecules. Maruoka and coworkers developed the unprecedented enantioselective 1,3-DC of diazoacetates 46 and a-substituted acroleins 45 by using certain chiral titanium BINOLate Lewis acids as catalysts (Scheme 2.13) [24], Furthermore, Sibi evaluated a,p-unsaturated pyrazolidinone... 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

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. 

The 4-thiazolidinyl phosphonates 143 (Scheme 44) are known for their therapeutical properties, in particular as anti-inflammatory agents [5,89]. Their asymmetric synthesis by hydrophosphonylation of 3-thiazolines has been described using various chiral auxiliaries chiral phosphites such as (2S,4i )-2H-2-oxo-5,5-dimethyl-4-phenyl-l,3,2-dioxaphosphorinane (de = 2-8%) [90] or BINOL-phos-phite (de = 65-90%) [91] and also chiral catalyst such as titanium or lanthanide chiral complexes (ee = 29-98%) [92]. Hydrophosphonylation of C2-chiral3-thi-azolines has also been performed (de = 32-38%) [93]. 

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