TADDOL cycloaddition with

The Ti(IV) TADDOL catalyst D leads to moderate to high enantioselectivity in nitrone cycloaddition with iV-acyloxazolidinones. ... 

Scheme 8. Enantioselective Photoreactions in TADDOL Inclusion Compounds with a Cou-marin, a Methacryl Anilide, and an Oxocyclohexenyl-carboxamide. In the first case, the packing of the coumarin molecules in the mixed crystal is such that the double bonds are predisposed for the (2+2) cycloaddition. In the second example, a photochemical electrocychc reaction is followed by a sigmatropic H shift. The third reaction is an intramolecular (2+2) cycloaddition with dia- and enantioselective formation of three new stereogenic centers. There are several more reactions of this type, described in the literature [54], and the Toda group has determined the crystal structures of a number of inclusion compounds to show the correlation between the crystal packing and the configuration of the photoproducts. EMastereoselective solid-phase reactions of chiral guests in TADDOL-host lattices have also been described by the...

In Scheme 10, examples of eaiantioseleetive cycloadditions with formation of three-, four-, five-, and six-membered carbocyclic or heterocyclic rings are presented, to demonstrate the use of Ti-TADDOLates as Lewis acids. The Diels-Alder reaction has, so far, been studied most extensively, and many protocols have been proposed for the preparation of the Ti catalyst, of which as little as 5 mol-% and as much as several equivalents were employed (more often than not, Lewis acids bind strongly to the products of reactions they have mediated cf. the classical Friedel-Crafts acylation with AICI3 ). 

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(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]. 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

The normal electron-demand principle of activation of 1,3-dipolar cycloaddition reactions of nitrones has also been tested for the 1,3-dipolar cycloaddition reaction of alkenes with diazoalkanes [71]. The reaction of ethyl diazoacetate 33 with 19b in the presence of a TiCl2-TADDOLate catalyst 23a afforded the 1,3-dipolar cycloaddition product 34 in good yield and with 30-40% ee (Scheme 6.26). 

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[. 

Immobilization of TADDOL-derivatives to silica and treatment with various tita-nium(IV) salts furnished a catalytic system (38) which was utilized in [2-1-3] cycloadditions of diphenylnitrone and acylated oxazolidinone to yield oxazolines (Scheme 4.23) [65]. It is noteworthy that the ligand X has an impact on the outcome of this cycloaddition. While the dichloro catalyst affords the exo-adduct in good yield and with a high stereoselectivity, the corresponding tosyloxy catalyst preferentially affords the endo-cycloadduct. The efficiency of the process is comparable to those obtained with the analogous soluble catalysts. The catalyst, however, had to be recycled prior to each experiment. 

Fig. 19 Transition states involved in the cycloaddition (endo-mode) of the model diene with benzaldehyde, both in the absence (TS-endo) and the presence (TS-(Si)-4b, TS-(Si)-4b) of the TADDOL catalyst corresponding activation energies Occal mol ](B3LYP/6-31G(d)//B3LYP/6-31G(d) PM3)...

Several chiral Ti(IV) complexes are efficient catalysts and have been applied to numerous reactions, especially in combination with the TADDOL 244 ligands (350). Chiral TiCl2-TADDOLates were the first asymmetric catalysts to be applied in the normal electron-demand 1,3-dipolar cycloaddition of nitrones 225 with alkenoyl-oxazolidinones 241 (Scheme 12.73) (351). These substrates have turned... 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Taddols can also catalyze the HDA reactions of other electron-rich dienes, as demonstrated by Ding and co-workers, who showed that taddol 119 catalyzed the cycloaddition of Brassard s diene with various aromatic aldehydes to give... 

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]... 

Nitrone cycloaddition reactions promoted by dichlorotitanium TADDOLate can be improved by using A(-(2-alkenyl)succinimides as the dipolarophiles. Regioselective and enantioselective formation of cyclopentenecarboxylic esters is observed using 8 to catalyze the [3+2]cycloaddition of 2,3-butadienoates with electron-deficient alkenes. ... 

Various types of chirally modified Lewis acids have been developed for asymmetric Diels-Alder cycloadditions. Some of these, including Ti-TADDOLates, have been attached to crosslinked polymers [11]. A recent example of this approach involved polymeric monoliths 103 containing TADDOL subunits (Scheme 3.29). The treatment of 103 with 71X4 afforded Ti-TADDOLates, which were used for the asymmetric Diels-Alder reachon of cyclopentadiene 104 and 105. The major product obtained in this reachon was the mdo adduct with 43% ee [58]. The supported Ti-catalysts showed an exhaordinary long-term stabihty, being achve for at least one year. 

The titanium-TADDOL system is notable for its breadth of reacting partners. Fumaroyl [104b] andacryloyl [107] imidedienophiles maybe employed with substituted and unsubstituted butadienes to afford cyclohexenes in high enantiomeric excess (Scheme 37). In the case of 2-thioethylbutadiene, the lower yield is accounted for by the intervention of a competing [2-1-2] cycloaddition pathway. 

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