Gold complexes aldol reaction

The gold complex, generated in situ from bis(4-isocyanocyclohexyl)gold(I) tetrafluoroborate and (A)-A-methyl-,V-[2-(dialkylamino)ethyl]-l-[(5)-r,2-bis(diphenylphosphino)ferrocenyl]eth-ylamine, is an effective catalyst for the aldol reaction of various aldehydes with methyl iso-cyanoacetate to give the trans- and cw-4,5-dihydro-l,3-oxazoles. Depending on the aldehyde, the transjeis product ratio ranges from 84 16 to 100 0, and the ee of the main diastereomer is between 72 and 97%26. 

The gold(I) complex of a chiral ferrocenylphosphine complex promotes asymmetric aldol reactions of a-isocyanocarboxylates to form chiral oxazolines in high diastereo- and enantio-selectivities (Scheme 52).225,226 In these reactions, the analogous silver(I) ferrocenylphosphine complex also works well. 

Asymmetric Aldol Reactions with a Chiral Ferrocenylphosphine-Gold( I) Complex... 

Scheme 3-30. Gold(I) complex-catalyzed asymmetric aldol reactions.

Asymmetric aldol reaction. In the presence of a gold(I) complex (1) and a chiral ferrocenylphosphine (2), various aldehydes react with methyl isocyanoacetate... 

The gold catalyst has provided some very important achievements in chemistry in general, such as the asymmetric aldol reaction of aldehydes with isocyanoacetates reported by Ito, Sawamura and Hayashi [12,176]. The use of chiral ferrocenylpho-sphine gold (I) complexes allowed them to obtain enantiomerically-pure oxazo-lines. 

In 1986 Ito, Sawamura, and Hayashi [4] reported that gold(I) complexes prepared from cationic gold complex 1 and chiral ferrocenylphosphine ligands (2) bearing a tertiary amino group at the terminal position of a pendant chain are effective catalysts for asymmetric aldol reaction of... 

Worth mentioning are chiral gold complexes [20d, e] as well as chiral quaternary ammonium fluorides [21], which are used successfully as catalysts in the asymmetric aldol reaction. 

Gold(I)-Catalyzed Aldol Reaction. In 1986 an elegant enantioselective and diastereoselective synthesis of dihydrooxazolines was reported, using the aldol reaction of an aldehyde with an a-isocyanoacetate ester (formally a Knoevenagel reaction) using a cationic gold(I) complex of (1) (eq 1). ... 

The gold(I) complex is prepared in situ by the reaction of (1) with bis(cyclohexyl isocyanide)gold(I) tetrafluoroborate (2), typically in anhydrous dichloromethane. The dihydrooxazolines obtained provide a ready access to enantiomerically pure p-hydroxy-a-amino acid derivatives. High diastereo- and enantios-electivity are generally maintained with a wide variety of substituted aldehydes, and a-isocyanoacetate esters. N,N-Dimethyl-a-isocyanoacetamides and a-keto esters have been substituted for the a-isocyanoacetate ester and aldehyde component, respectively, sometimes with improved stereoselectivity. The effect of both the central and planar chirality of (1) on the diastereo- and enantioselectivity of the gold(I)-catalyzed aldol reaction has been studied. The modification of the terminal di-alkylamino group of (1) can lead to improvements in the stereos-... 

Table 3. Diastereo- and enantioselective aldol reaction of methyl isocyanoacetate (27) with tildehydes catalyzed by chiral ferrocenylphosphine 86c gold(I) complex.

Ito and coworkers found that chiral ferrocenylphosphine-silver(I) complexes also catalyze the asymmetric aldol reaction of isocyanoacetate with aldehydes (Sch. 26) [51]. It is essential to keep the isocyanoacetate at a low concentration to obtain a product with high optical purity. They performed IR studies on the structures of gold(I) and silver(I) complexes with chiral ferrocenylphosphine 86a in the presence of methyl isocyanoacetate (27) and found significant differences between the iso-cyanoacetate-to-metal coordination numbers of these metal complexes (Sch. 27). The gold(I) complex has the tricoordinated structure 100, which results in high ee, whereas for the silver(I) complex there is an equilibrium between the tricoordinated structure 101 and the tetracoordinated structure 102, which results in low enantioselectivity. Slow addition of isocyanoacetate 27 to a solution of the silver(I) catalyst and aldehyde is effective in reducing the undesirable tetracoordinated species and results in high enantioselectivity. 

Silver(i) complex coordinated with the ferrocenylbisphosphine ligand 8g is also effective as a catalyst for the asymmetric aldol reaction of isocyanoacetate when the isocyanoacetate is kept in low concentration in the reaction system (Scheme 2-58) [82], Thus, by the slow addition of isocyanoacetate over a period of 1 h to a solution of aldehyde and the silver catalyst, iranj-oxazolines are formed in 80—90% ee, the enantioselectivity being only a little lower than that observed in the gold(i)-catalyzed... 

The ferrocenylphosphine-silver complex catalyzes the aldol-type reaction of tosylmethyl isocyanide 71 with aldehydes with higher stereoselectivity than the gold complex (Scheme 2-59) [84]. The reaction with several aldehydes produces trans-4-tosyloxazolines 72 in up to 86% ee, which can be converted into optically active l-alkyl-2-aminoethanols by reduction with LiAlH4. 

Gold(I)/ferrocenylphosphine 2a-d complexes are applicable to asymmetric aldol reactions of a-alkyl substituted a-isocyanoacetates 12. Although the dependency of stereoselectivity on the structures of the substrates is fairly large, some combinations of 12 and aldehydes show high enantio- and diastereoselec-tivity (Scheme 3). The reaction with paraformaldehyde yields (S)-4-alkyl-2-ox-azoHne-4-carboxylates in 64 to 81% ee, which can be readily transformed to the... 

Ferrocenyldiphosphines 3.41 (R = Me2NCH2CH2) are used as ligands in gold-catalyzed asymmetric aldol reactions of a-isocyanoesters or -amides [408, 752, 858, 950], Silver complexes can also be used with the modified phosphine 3.41 (R = (CH2)5 or (CH g) [951, 952]. 

Table 11 Enantioselectivity and Diastereoselectivity in the Aldol Reactions of Methyl Isocyanoacetate Under Catalysis by Chiral Ferrocenylphosphine-Gold Complexes (equation 22)...

Asymmetric aldolization of a-isocyanoacetamide and fluorinated benzaldehydes has been realized with a gold(I) salt and a ferrocenyl amine-phosphine ligand. (Salen)-Ti complexes serve well in catalyzing the condensation of diketene with aldehydes. " A camphor lactam is an adequate chiral auxiliary as its derived imide undergoes asymmetric aldol reactions. 

It has been reported that a chiral ferrocenylphosphine-gold(I) complex catalyses the asymmetric aldol reaction of an isocyanoacetate... 

Hayashi-Ito asymmetric Aldol reaction with chiral ferrocenylphosphine-gold complex. 

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