Titanium BINOLates

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. 

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-... 

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. 

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. 

Titanium complexes are often encountered in Lewis acid-catalysed reactions. This is certainly true for catalysed aldol reactions. Mikami and Matsukawa demonstrated that titanium/BINOL complexes e.g. complex (7.20) afforded high yield and enantioselectivity in the aldol reactions of thioester ketene silylacetals with a variety of aldehydes. In contrast to some of the aldol reactions described above, the stereochemistry of the adducts is dependant on the geometry of the enol ether. Thus, reaction of the (B)-enol ether (7.21) with aldehyde (7.22) yields the sy -aldol adduct (7.23) predominantly while the (Z)-e.no ether (7.24) results in isolation of the anti-adduct (7.25) as the major product. The authors invoke a closed silatropic ene transition state (structure (7.26) for syn-transition state), substantiated by suitable crossover experiments, to explain the diastereoselectivities... 

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 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... 

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... 

Scheme 7.10 Preparation of titanium-BINOL complex supported on SBA-15.

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. ° ... 

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... 

Scheme 5.62 Enantioselective Mukaiyama aldol additions mediated by titanium-BINOL complexes 196 according to Mikami and Keck. Proposed Zimmerman-Traxler-type transition state model.

Scheme 5.63 Vinylogous aldol addition of silyl dienolate 203a mediated by titanium-BINOL complex enantioselective synthesis of phorbaside A building block 205.

Recently, Maruoka and coworkers have also developed an asymmetric inverse electron demand 1,3-dipolar cycloaddition of C,A -cyclic azomethine imines with fort-butyl vinyl ether catalyzed by a newly developed axially chiral dicarboxylic acid having diarylmethyl groups at the 3,3 -positions (Scheme 7.7) [18]. Based on this finding, the concept of the inverse electron demand umpolung 1,3-dipolar cycloaddition was introduced as a strategy for switching the regioselectivity of the cycloaddition from that of the titanium BINOLate-catalyzed normal electron demand 1,3-dipolar cycloaddition with enals (Table 7.3) by... 

For the diazoacetates, Mamoka and coworkers reported on the chiral titanium BINOLate-catalyzed highly enantioselective 1,3-dipolar cycloaddition reactions between diazoacetates and monodentate a-substituted acroleins, which give 2-pyrazolines with an asymmetric tetrasubstituted carbon center in 2006 (Table 7.6) [23], The titanium BINOLates, such as (5)-BlNOL/Ti(OPr )4 (2 1 molar ratio) complex (TB-b) and bis (5)-binaphthoxy)(isopropoxy)titanium oxide (TB-c), showed good results in terms of yields and enantiose-lectivities compared with simple (5)-BINOL/Ti(OPr )4 (1 1 molar ratio) complex (TB-a). The synthetic utility of the present reaction was further demonstrated by the total synthesis of a bromopyrrole alkaloid manzacidin A (Scheme 7.13), which was isolated firom the Okinawan sponge Hymeniacidon sp. [24],... 

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