BINOL-TiCl2 complex

The best procedure reported to date for the asymmetric allylation of aldehydes using tributyl(2-propenyl)stannane involves the catalyzed addition with the BINOL-TiCl2 complex as catalyst. Good yields and ee s were obtained for both aromatic and aliphatic aldehydes using 20 mol% of the catalyst127. 

Ziegler et al. have reported the asymmetric desymmetrization approach to the synthesis of tricothecene, anguidine, via an ene cyclization (Scheme 8C.11) [31], The (2,4) ene cyclization (vide infra) of the prochiral aldehyde on silica gel gives a 1 1 diastereomeric mixture. Cyclization with purified Eu(fod)3 as Lewis acid catalyst gives an 8 1 mixture. The major isomer is a potential intermediate for the synthesis of anguidine. However, use of (+)-Eu(hfc)3, (+)-Eu(dppm)3, or (S)-BINOL-TiCl2 complex as chiral Lewis acid affords the major product with only 20-38% ee. 

Table 17. Additions of allylic stannanes to methyl gtyoxylate catalyzed by a (P)-BINOL-TiCl2 complex.

The chiral titanium complexes modified by the perchlorate or trifluoromethanesulfonate ligand such as (R)-l,l -bi-2,2 -naphthotitanium diperchlorate (BIN0L-Ti(C104)2) or (7 )-l,l -bi-2,2 -naphthotitanium ditriflate ((I )-BINOL-Ti(OTf)2) can easily be prepared by the addition of Silver(I) Perchlorate or Silver(I) Trifluoromethanesulfonate (2 equiv) to BINOL-TiCl2 (eq 2). ... 

Mukaiyama Aldol Condensation. As expected, the chiral titanium complex is also effective for a variety of carbon-carbon bond forming processes such as the aldol and the Diels-Alder reactions. The aldol process constitutes one of the most fundamental bond constructions in organic synthesis. Therefore the development of chiral catalysts that promote asymmetic aldol reactions in a highly stereocontrolled and truly catalytic fashion has attracted much attention, for which the silyl enol ethers of ketones or esters have been used as a storable enolate component (Mukaiyama aldol condensation). The BINOL-derived titanium complex BINOL-TiCl2 can be used as an efficient catalyst for the Mukaiyama-ty pe aldol reaction of not only ketone si ly 1 enol ethers but also ester silyl enol ethers with control of absolute and relative stereochemistry (eq 11). ... 

A TiCl2 complex of (P)-BINOL catalyzes the addition of cis- and traws-crotyl and 8-methylcrotyl stannanes to the reactive aldehyde, methyl glyoxylate (Table 17) [31]. The diastereoselectivities of these additions are, however, poor and the ee of the adducts is modest to poor. 

Reetz reported the catalysis by BINOL-TiCl2 of aldol reactions with aliphatic aldehydes [88]. BINOL-TiCli was prepared by treatment of the lithium salt of BINOL with TiCl4 in ether. After removal of the ether the residue was treated with dry benzene and the solid was separated under nitrogen. Removal of the solvent provided the red-brown complex, which was used as the catalyst for the aldol reaction to give 8 % ee. Later, Mukaiyama reported that use of BINOL-Ti oxide prepared from (i-PrO)2-Ti=0 and BINOL resulted in moderate to high enantioselectivity (Sch. 30) [89]. 

When catalytic asymmetric allylation was attempted with a catalytic amount of chiral titanium complexes, BINOL-TiCl2 or BIN0L-Ti(0-/-Pr)2 the reaction was found to be slow. The reaction was performed satisfactorily when BIN0L-Zr(0-/-Pr)2 was employed as catalyst in the presence of molecular sieves (Eq. 18) [19a]. 

A majority of the reported enantioselective Lewis acid-catalyzed allylation processes employ complexes with chiral ligands based on the 1,1-binaphthyl skeleton. In 1993, Umani-Ronchi and Tagliavini [122] and Keck [123] independently reported enantioselective allylation of aldehydes with BINOL-Ti(IV) catalysts 195 (from BINOL/TiCl2(Oi-Pr)2) and 196 (from BINOL/ Ti(Oi-Pr)4), respectively (Equation 13). Excellent enantioselectivity was observed with both catalyst systems ( 90% ee). 

BINOL in conjunction with TiCl2(0-/-Pr)2 gives good enantioselectivity in a D-A reaction with a pyrone as the diene.116 This is a case of an inverse electron demand reaction and the catalysts would be complexed to the diene. 

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... 

Effect of Alkoxy Ligand. Since the modification of the chiral diol in the titanium complex affected the enantioselectivity, we studied the effect of the alkoxide ligand in (/ )-BINOL-Ti(OR)2 and prepared several complexes by treatment of lithium (/ )-binolate with TiCl2(OR)2. Although a primary alkoxide ligand led to minimal asymmetric induction, a secondary alkoxide resulted in reasonable ee s. A tertiary butoxide or binolate ligand decreased the ee considerably. Thus, the bulk of the alkoxide ligand on the titanium complex appears to be extremely important to create an appropriate size of the reaction site. 

The enantioselective aldol addition reactions mediated by BINOL/TiCl (Ot-Pr)4, j complexes as catalysts are highly attractive because of the convenient accessibility of the catalyst components along with the unique substrate scope they display [130-135]. These were developed by Keck and Mikami. Two catalyst preparations, involving BINOL and either TiCl2(Oi-Pr)2 [130] or Ti(Oi-Pr)4 [133], have been dociunented. Both of these furnish aldol adducts with excellent yields and enantioselectivities (Scheme 4.31). The fact that these compounds can mediate aldol additions to a wide range of functionalized aldehydes, such as trifluoroacetaldehyde [132] and chloroacetalde-hyde [131], is impressive, as these are rare substrates in catalytic, enantioselective aldol addition reactions (Scheme 4.32). Additionally, aldehydes such... 

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