Zirconium catalyst, chiral

Several examples of catalytic aza Diels-Alder reactions using the chiral zirconium catalyst are shown in Table 5.5 [18]. High chemical yields and good to high... 

The first enantioselective aza-Diels-Alder reactions of imino dienophiles on use of a chiral zirconium catalyst [116]... 

A chiral zirconium catalyst generated from Zr(0,-Bu)4 and (R)-3,3 -diiodo-1,1 -binaphthalene-2,2 -diol [(f )-3,3/-l2BINOL] catalyzed... 

Kobayashi et al.51 have reported an asymmetric Mannich-type reaction using chiral zirconium catalysts of type 124 (see Section 3.7). This catalyst is also effective for asymmetric aza Diels-Alder reactions. Kobayashi s study showed that the ligand had a profound influence on the yields and enantiose-lectivities of the reaction, and NMI (1-methylimidazole) proved to be the best ligand.51 With an increase in the amount of catalyst, both the chemical yields and enantioselectivities of the product can be enhanced. Scheme 5-39 depicts such aza Diels-Alder reactions, and its table shows that good to excellent enantioselectivity can be obtained for most reactions. 

Kobayashi and colleagues developed a catalytic enantioselective method for the allylation of imines 24 by substituted allylstannanes 25 with chiral zirconium catalysts 26 and 27 prepared from zirconium alkoxides and l,l -bi-2-naph-thol derivatives (Scheme 10) [19]. The allylation of aromatic imines 24 with 25 afforded the corresponding homoallylic amines 28 in good yields (71-85%) with high stereoselectivities (87-99% ee). 

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

A. H. Hoveyda, Chiral Zirconium Catalysts for Enantioselective Synthesis, in Titanium and Zirconium in Organic Synthesis (Ed. I. Marek, Wiley-VCH, Weinheim, 2002, pp. 180-229). 

Kobayashi S, Ishitani H (2000) Novel binuclear chiral zirconium catalysts used in enantioselective strecker reactions. Chirality 12 540-543 Kobayashi S, Ishitani H, Nagayama S (1995) Synthesis 1995 1195 Kobayashi S, Ishitani H, Ueno M (1998) J Am Chem Soc 120 431 Kobayashi S, Kobayashi J, Ishitani H, Ueno M (2002) Catalytic enantioselective addition of propionate units to imines an efficient synthesis of anti-alpha-methyl-beta-amino acid derivatives. Chem Eur J 8 4185 1190 Krohn K, Kirst HA, Maag H (eds) (1993) Antibiotics and antiviral compounds. VCH, Weinheim... 

Chiral Lewis acids are known. Indeed, an air stable and storable chiral Lewis acid catalyst has been prepared, a chiral zirconium catalyst combined with molecular sieves powder. Association of a bulky silicon group with the bis(trifluoromethanesulfonyl)imide anion leads to enhancement of the electro-phihc character of R3SiNTf2. The presence of a chiral substituent derived from ( )-myrtenal on the silicon atom led to a chiral silicon Lewis acid. ... 

Scheme 7-103 Chiral zirconium catalyst for enantioselective ethylmagnesiation.

Scheme 7-104 Chiral zirconium catalyst for diastereoselective ethylmagnesiation of chiral allylic alcohols.

The use of a chiral zirconium catalyst may extend these reactions to asymmetric synthesis. An example that achieved a chiral transfer at a very high level was reported, but a Grignard reagent was involved in only a transient species, not in the final product [74]. 

Ishitani, H., Ueno, M., Kobayashi, S. Catalytic Enantioselective Mannich-Type Reactions Using a Novel Chiral Zirconium Catalyst. J. Am. Chem. Soc. 1997, 119, 7153-7154. 

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