TADDOL-derived titanium complex

Enantioselective carbonyl addition of dialkylzinc reagents to aldehydes is one of the most important and fundamental asymmetric reactions [2,15]. Several chiral titanium complexes have been developed to accelerate this type of reaction (Sch. 3) [16,18-26] since Ohno and Kobayashi achieved high enantioselectivity in the presence of Ti(OPr )4 and chiral disulfonylamide [16,17]. Seebach has also demonstrated that TADDOL-derived titanium complexes function as efficient asymmetric catalysts [18]. 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Asymmetric [2 + 2] cycloaddition reaction affords a practical means of synthesis of optically active cyclobutanes, which can be used as useful intermediates in organic synthesis [138]. Narasaka reported that asymmetric [2 -i- 2] cycloaddition between acryloyl oxazolidinone derivatives and bis(methylthio)ethylene proceeded with high enantios-electivity when catalyzed by TADDOL-derived titanium complex (Sch. 58) [139]. The cyclobutane product was transformed into carbocyclic oxetanocin analogs or (-n)-grand-isol [140]... 

The tartrate (or TADDOL) derived approach to catalyst design has also been applied to the enantioselective a-hydroxylation of p-ketoesters. In this case, an enantiospecihc titanium(IV) complex combines with a sulfonyloxaziridine as the... 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Asymmetric catalysis of ene reactions was initially explored in the intramolecular cases, since the intramolecular versions are much more facile than their intermolecular counterparts. The first example of an enantioselective 6-(3,4) car-bonyl-ene cyclization was reported using a BINOL-derived zinc reagent [55]. However, this was successful only when using an excess of the zinc reagent (at least 3 equivalents). Recently, an enantioselective 6-(3,4) olefin-ene cyclization has been developed using a stoichiometric amount of a TADDOL-derived chiral titanium complex (Scheme 17) [56]. In this ene reaction, a hetero Diels-Alder product was also obtained, the ratio depending critically on the solvent system... 

Recently Mayoral and coworkers have reported the grafting of a TADDOL derivative onto several types of polystyrene resins. The immobilised TADEXDLs were subsequently transformed into their chiral titanium complexes as shown in Scheme 3.6.10. 

Very recently, Seebach and coworkers reported a different approach for the immobilisation of TADEXDL derivatives. Dendritically substituted TADDOLs (90) were co-polymerised with styrene in a suspension polymerisation procedure and subsequently transformed into their titanium complexes. 

Narasaka and coworkers used the titanium complex of the TADDOL (a,a,a, a tetraaryl-l,3-dioxolane-4,5-dimethanol) ligand (8.50) to catalyse Diels-Alder reactions of acyloxazolidinones. Thus, the crotonyl derivative (8.51) was... 

An enantioselective 6-(3,4) olefin-ene cyclization could be achieved using a stoichiometric amount of a TADDOL-derived chiral titanium complex [127]. In this ene reaction, a HDA product was also obtained, where the periselectivity depends critically on the solvent system employed. In both cases, geminal disubstitution is required for good enantiocontrol (Scheme 14.47). 

Some innovative approaches using chiral Lewis acids to promote catalytic enantioselective [2 + 2]-cycloadditions have been documented [36, 148-150]. The earliest example appears to have been reported by Narasaka (Equation 19) [148]. In these cycloaddition reactions, a titanium complex of TADDOL ligand 239 catalyzes the reactions between ketene dithioacetal 237 and acceptors. With fumarate derivative 238, adduct 240 was obtained in 96% yield and 98% ee. 

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