Gold-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. 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

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 Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

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. 

B1.2. GOLD-CATALYZED ASYMMETRIC ALDOL REACTION OF cc-ISOCYANOCARBOXYLATES... 

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... 

TABLE 8B1.1. Gold-Catalyzed Asymmetric Aldol Reaction of Isocyanoacetate 3a with Aldehydes (Scheme 8B1.1)"... 

Figure 8B1.1. Proposed transition-state model of the gold-catalyzed asymmetric aldol reaction.

The usefulness of the gold-catalyzed aldol reaction was demonstrated by application of the method to the asymmetric synthesis of the important membrane components D-erythro and ffereo-sphingosines, and their stereoisomers (Scheme 8B1.2) [13], and MeBmt, an unusual amino acid in the immunosuppressive undecapeptide cyclosporine (Scheme 8B1.3) [14]. 

As pointed out by Togni and Pastor, enantioselectivities in the gold-catalyzed aldol reaction of aldehydes containing an a-heteroatom are significantly different from those of simple aldehydes (Table 8B1.3) [15,16]. Low enantioselectivities for rrani-oxazolines are observed in the aldol reactions of 2-thiophene-, 2-furan-, and 2-pyridinecarboxaldehyde (entries 2, 4,7). In the reactions of the 2-furan- and 2-pyridinecarboxaldehyde, cA-oxazolines with fairly high enantiomeric purities are formed as the minor product but in a rather low trans/cis ratio. A similar a-heteroatom effect is also observed in the aldol reaction of 2,3-Oisopropylidene-D-glyceraldehyde. 

TABLE 8B1.3. Asymmetric Aldol Reaction of Isocyanoacetate 3b with Functionalized Aldehydes in the Presence of Gold(I) Catalyst Containing Ligand 2a (Scheme 8B1.1) 1... 

It is interesting that aldol-type condensation of tosylmethyl isocyanide (16) with aldehydes is catalyzed by the silver catalyst more stereoselectively than that catalyzed by the gold catalyst under the standard reaction conditions (Scheme 8B1.9) [26], Elucidation of the mechanistic differences between the gold and silver catalysts in the asymmetric aldol reaction of 16 needs further study. Oxazoline 17 can be converted to optically active a-alkyl-p-(A-methyl-amino)ethanols. 

Cobb, A.J.A., Shaw, D.M., Longbottom, D.A., Gold, J.B. and Ley, S.V. (2005) Organocatalysis with proline derivatives improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem., 3, 84. 

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. 

The gold(I)-catalyzed asymmetric aldol reaction with the chiral ligand R)- S)-(1) has been applied in the synthesis of o-erythro-and /lireo-sphingosines (eq 11). The D-eo lIiw-sphingosine can be prepared from the three isomer by inversion of the C-3 hydroxyl group. 

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