TADDOL-titanium

In contrast to the limited success with vinyl sulfides as components of [2 + 2] cycloadditions, allenyl sulfides show wide applicability. As illustrated in Scheme 8.91, Lewis acid-catalyzed [2 + 2] cycloadditions of l-trimethylsilyl-l-methylthio-1,2-propadiene (333) with a variety of electron-deficient olefins 336 provide cycloadducts 337 with excellent regioselectivity but with moderate stereoselectivity [175c], Nara-saka and co-workers reported the first Lewis acid-catalyzed asymmetric [2 + 2] cycloaddition of C-l-substituted allenyl sulfides 319 with a,/3-unsaturated compounds 338 using a chiral TADDOL-titanium catalyst. The corresponding cycloadducts 339 were obtained with 88-98% ee, but a low level of trans/cis selectivity (Scheme 8.92) [169,175d[. 

Scheme 3 Enantioselective chlorination and bromination through TADDOLate-titanium catalysis...

Despite efforts made to improve enantioselectivities by supporting TADDOL-titanium catalyst, the homogeneous conditions remain the best ones. BINOL was also reported as an efficient ligand, however, to our knowledge supported-BINOL-titanium complexes were not studied in the asymmetric Diels-Alder reactions. In contrast, BINOL was extensively studied in the hetero-Diels-Alder reaction and in particular in the pericyclic rearrangement of several aldehydes and electron-rich and highly regioselective Danishefslqr s diene (84) that provide access to 2-substituted-2,3-dihydro-4/f-pyran-4-ones 85 (Scheme 7.50). 

In addition to their work on DA reaction, Seebach et al. also studied polymeric titanium catalyst 82,83 (see Figure 7.7) in the [3 + 2] cycloaddition of 3-crotonoyloxazolidinone and diphenyl nitrone (Table 7.5). The use of soluble catalysts 81a,b,d (entries 1-3) and supported-titanium catalysts 83a,b,d (entries 4-6) afforded similar performances in terms of yield, dia-stereoselectivity and enantioselectivity in favour of adduct 89a. Interestingly, the enantioselectivity was better in heterogeneous conditions with polymeric TADDOL-titanium complex 83d (entry 6, 56% enantiomeric excess) than using soluble catalysts (entries 1-3). 

Narasaka advanced the use of chiral TADDOL-titanium complexes as catalysts for enantioselective Diels-Alder reactions [75-78], In order to minimize the conformational flexibility of the substrates, dienophiles 136 were employed because of their ability to participate in chelate formation with Lewis acids (Equation 15). In the presence of titanium catalyst 137 [76], isoprene (135) undergoes cycloaddition with 136 to give adduct 138 as one diastereomer in 96 % ee and 93 % yield [77]. 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

I would like to thank Professors E. J. Corey and K. Narasaka for giving me a chance to work with super-reactive chiral catalyst 9 and TADDOL-based chiral titanium catalyst 31, respectively. 

A chiral titanium(IV) complex has also been used by Wada et al. for the intermole-cular cycloaddition of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 45 with enol ethers 46 using the TADDOL-TiX2 (X=C1, Br) complexes 48 as catalysts in an enantioselective reaction giving the dihydropyrans 47 as shown in Scheme 4.32 [47]. The reaction depends on the anion of the catalyst and the best yield and enantioselectivity were found for the TADDOL-TiBr2 up to 97% ee of the dihydropyrans 47 was obtained. 

Several titanium(IV) complexes are efficient and reliable Lewis acid catalysts and they have been applied to numerous reactions, especially in combination with the so-called TADDOL (a, a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) (22) ligands [53-55]. In the first study on normal electron-demand 1,3-dipolar cycloaddition reactions between nitrones and alkenes, which appeared in 1994, the catalytic reaction of a series of chiral TiCl2-TADDOLates on the reaction of nitrones 1 with al-kenoyloxazolidinones 19 was developed (Scheme 6.18) [56]. These substrates have turned out be the model system of choice for most studies on metal-catalyzed normal electron-demand 1,3-dipolar cycloaddition reactions of nitrones as it will appear from this chapter. When 10 mol% of the catalyst 23a was applied in the reaction depicted in Scheme 6.18 the reaction proceeded to give a yield of up to 94% ee after 20 h. The reaction led primarily to exo-21 and in the best case an endo/ exo ratio of 10 90 was obtained. The chiral information of the catalyst was transferred with a fair efficiency to the substrates as up to 60% ee of one of the isomers of exo3 was obtained [56]. 

It was our delight that the reactions catalyzed were activated even at -40 °C in the presence of a catalytic amount of achiral titanium catalysts (10 mol%) to afford the desilylacetylated 2-pyrazoline cycloadduct Na, l-acetyl-4-methyl-5-(2-oxo-3-oxazolidinylcarbonyl)-2-pyrazoline, in high yields as the far major product (Scheme 7.35). Although some chiral titanium TADDOlate catalysts were successfully applied to activate these reactions leading to the moderate enantioselectivities (up to 55% ee), the chemical yields were not satisfactory. 

An X-ray structure of the complex formed between 3-cinnamoyl-l,3-oxazohdin-2-one and a chiral TADDOL-Ti(IV) complex (see Chapters 1 and 6 by Hayashi and Gothelf, respectively) has been characterized [16]. The structure of this complex has the chiral TADDOLate and cinnamoyloxazohdinone ligands coordinated to titanium in the equatorial plane and the two chloride ligands in the axial plane and is similar to A in Fig. 8.8. The chiral discrimination was proposed to be due to... 

Lewis acid-catalyzed additions can be carried out in the presence of other chiral ligands that induce enantioselectivity.156 Titanium TADDOL induces enantioselectivity in alkylzinc additions to aldehydes. A variety of aromatic, alkyl, and a, (3-unsaturated aldehydes give good results with primary alkylzinc reagents.157... 

Seebach and coworkers have developed enantioselective conjugate additions of primary dialkylzinc reagents to 2-aryl- and 2-heteroaryl-nitroalkenes mediated by titanium-TADDO-Lates (Eq. 4.90). x a TADDOLs and their derivatives are excellent chiral auxiliaries.9611... 

TADDOL 104 and 126 afford 95-99% ee in the asymmetric addition of organozinc reagents to a variety of aldehydes. The best enantioselectivities are observed when a mixture of the chiral titanium TADDOL compound 127 and excess [Ti(OPr1)4] are employed (Scheme 2-49). The mechanism of the alkylzinc addition involves acceleration of the asymmetric catalytic process by the... 

Scheme 2-49. TADDOL and its analogs as titanium ligands in enantioselective addition of diethylzinc reagents to benzaldehyde.

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

In the presence of titanium bis(TADDOLate)s such as 51 and 52 (25 mol%), generated from titanium tetraisopropoxide and the corresponding TADDOL, as well as chlorotri-... 

The phosphino-oxazoline copper(II) complex (55) has also been found to be an effective catalyst[136] as have some titanium complexes, such as the extensively researched titanium-TADDOL system (56)[137]. A modified Ti(IV)-TADDOL compound is the catalyst of choice to promote Diels-Alder cycloaddition reactions between cyclopentadiene and alk-2-enyl phenylsulfonylmethyl ketones[138]. 

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... 

An important catalyst-substrate intermediate that applies to both the TiCl2-TADDOLate catalyzed 1,3-dipolar cycloadditions and Diels-Alder reactions has been isolated and characterized (353). The crystalline compound 248 has been characterized by X-ray analysis, showing that the oxazolidinone is coordinated to the titanium center in a bidentate fashion (Scheme 12.75). The four oxygen atoms. 

Chiral titanium complexes with a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands are versatile auxiliaries in the Lewis acid catalyzed alcoholysis of racemic 4-(arylmethyl)-2-phenyl-5(477)-oxazolones 234, providing the corresponding enantiomerically enriched N-protected amino acid esters 235 (Scheme 7.73). The enantioselectivity of the reaction is dependent on the solvent, temperature, and chiral ligand. Selected examples of the alcoholysis of saturated 5(477)-oxazolones are shown in Table 7.21 (Fig. 7.23). 

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