Amines chiral zirconium catalysts

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). 

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)... 

Ishitani, H., Komiyama, S., Hasegawa, Y., Kobayashi, S. Catalytic Asymmetric Strecker Synthesis. Preparation of Enantiomerically Pure a-Amino Acid Derivatives from Aidimines and Tributyitin Cyanide or Achirai Aidehydes, Amines, and Hydrogen Cyanide Using a Chiral Zirconium Catalyst. J. Am. Chem. Soc. 2000,122, 762-766. 

In the presence of a chiral zirconium " " or aluminum " catalyst, Bu3SnCN react with imines to give a-cyanoamines enantioselectively. The reaction of an imine and TMSCN gives the cyano amine with good enantioselectivity using a chiral scandium catalyst.Titanium catalysts have been used in the presence of a chiral Schiff base. Treatment of an imine with a chiral 1,4,6- triazabicy-clo[3.3.0]oct-4-ene and then HCN give the a-cyano amine with good enantioselectivity. 

A variety of chiral, non-racemic zirconium complexes were explored in attempts to develop an enantioselective variant of this reaction (Scheme 3) [7-9]. Eor example, when allyUc amines lla,b were treated with EtMgCl and 10% of C2-symmetric BINOL-zirconium bis(tetrahydroindenyl)ethane (12, Brintzinger s catalyst [10], BINOL is l,l -binaphthalene 2,2 -dioate), chiral ethylated products 13a,b were obtained in 34-39% yield with enantiomeric excesses (ee) of ca. 26% [8]. Use of a (neomenthylindene)ZrCpCl2 catalyst 14, designed to improve the steric differentiation of the diastereomeric transition states, improved the chemical yields of amines at lower catalyst loadings (2-4%) and increased the ees of the reactions by a factor of three in the case of 11a [8,9]. Similar reactivity is observed in zirconocene dichloride-catalyzed cyclization of 1,6- and 1,7-enynes with 12.5% Cp2ZrCl2 using EtsAl as the stoichiometric reductant. For these substrates, the alkyne coordinates... 

Given the importance of chiral amines to synthetic chemistry as well as other fields asymmetric hydrogenation of imines has attracted wide interest but limited success compared to C=C and C=0 bond reduction. The first asymmetric hydrogenation of imines was carried out in the seventies with mthenium- and rhodium-based catalysts, followed later by titanium and zirconium systems [82]. Buchwald found that... 

Addition of organometallic reagents to imines is not limited to allylmetal derivatives. Hoveyda and Snapper have demonstrated that dialkylzinc reagents can add to imines in a one-pot procedure. Using a zirconium complex as metal catalyst and a chiral peptide, diverse enantioenriched aryl, aliphatic and alkynyl amines 142 have been obtained with high levels of enantioselectivity (Scheme 8.60) [136],... 

---