Autoinduction, enantioselective

Zinc-containing compounds have also been used as catalyst. Recently, Trost et al. reported asymmetric aldol reactions of methyl ynones 331 with pyruvaldehyde ketals 330 in the presence of a dinuclear zinc catalyst 329 generated from ZnEt2 and a pentadentate 0,N,0,N,0-ligand (328, Scheme 168).428 This reaction is a unique case of enantioselective autoinduction with product incorporation into the catalyst and a reversal of the absolute configuration. 

The non-equivalence of enantiomers through the spontaneous breaking of mirror-symmetry in nature is amplified by asymmetric autocatalytic reaction [34], e.g. Frank s spontaneous asymmetric synthesis [35, 36] (Fig. 7-8). Alberts and Wyn-berg have reported in enantioselective autoinduction that chiral lithium alkoxide products may be involved in the reaction to increase the enantioselectivity (Eq. (7.9)) [37]. The product % ee however does not exceed the level of catalyst % ee. In asymmetric hydrocyanation catalyzed by cyclic dipeptides, the (Si-cyanohydrin product complexes with the cyclic peptide to increase the enantioselectivity in the (S)-cyanohydrin product, the reaction going up to 95.8% ee (Eq. (7.10)) [38]. In the presence of achiral amine, (/ )-l-phenylpropan-l-ol catalyzed carbonyl-addition reaction of diethylzinc has been reported to show lower % ee than that of the catalyst employed [39]. 

It is remarkable that Danda reported enantioselective autoinduction in asymmetric cyanation. When a small amount of the optically pure cyanohydrin was added to the reaction mixture, highly enantioselective cyanation occurred even by using almost racemic catalyst 5, Fig. 1 (2% ee) [32]. 

The result of their exploratory effort was the determination that an enantioselective autoinductive mechanism is operative. Only one other example of such a mechanism exists in the context of the Diels-Alder reaction [53]. In a series of clever experiments, the authors found that achiral additives achieve the same end, facihtating uniformly high asymmetric induction throughout the course of... 

Alberts and Wynberg studied the addition of ethyllithium to PhCHO, mediated by the lithiated product (k)-l-phenyl-l-propanol-dj [40]. The (i )-l-phenyl- 1 -propanol enantiomer was formed in 17% enantiomeric excess in the reaction. For this asymmetric induction rendered by the product, the authors coined the expression enantioselective autoinduction . It was suggested that the formation of mixed aggregates consisting of the labeled chiral mediator and the or-ganoHthium reagent influences the stereochemistry of subsequent C-C bond formation [41]. 

Jackman s group performed enantioselective additions of RLi (R=Me, n-Bu) to PhCHO, mediated by a series of chiral Hthium alkoxides [42]. The highest enantioselectivities were achieved with the Hthiated ephedrine derivative lR,2S)-9 with n-BuLi and PhCHO in a ratio of 0.3 0.15 0.1 with 75% ee (GC) of (S)-l-phenyl-l-pentanol in THF at -78°C. An analysis during the course of addition showed that no enantioselective autoinduction [40] by the chiral prod-... 

Enantioselective autoinduction was also investigated (Fig. 8.27). [117] The reaction of an aldehyde with hydrogen cyanide in presence of the chiral diketopiper-azine, the enantiomeric purity ofwhich varies from 12 to 100%, gives the cyanohydrin in the same optical purity as that of the catalyst (hlue curve). However, if to the mixture of the aldehyde and the diketopiperazine with varying optical purity, 9 mole % of (S)-cyanohydrin in an optical purity of 92 % ee is added prior to the addition of hydrogen cyanide, the enantiomeric excess in the product is almost independent of the optical purity of the catalyst itself (red curve). 

Albert, A. H. and Wynberg, H. (1990) Enantioselective autoinduction in the aldol condensation of ethyl acetate and benzaldehyde selective precipitation of an optically inactive Li-O aggregate, J. Chem. Soc. Chem. Commun, 453-454. 

Catalyst 329, prepared from trimethylaluminum and 3,3/-bis(triphenylsily 1)-1,1 /-bi-2-naphthol, allowed the preparation of the endo cycloadduct (2S )-327 with 67% ee. The use of non-polar solvents raised the ee, but lowered the chemical yield213. Recently, it was reported that the reaction to form 327 exhibited autoinduction when mediated by catalyst 326214. This was attributed to a co-operative interaction of the cycloadduct with the catalyst, generating a more selective catalytic species. A wide variety of carbonyl ligands were tested for their co-operative effect on enantioselectivity. Sterically crowded aldehydes such as pivaldehyde provided the best results. Surprisingly, 1,3-dicarbonyl compounds were even more effective than monocarbonyl compounds. The asymmetric induction increased from 82 to 92% ee when di(l-adamantyl)-2,2-dimethylmalonate was added while at the same time the reaction temperature was allowed to increase by 80 °C, from -80 °C to 0°C. 

An impressive example of autoinduction (28) has been observed in the enantioselective hydrocyanation of 3-phenoxybenzaldehyde catalyzed by cyclo[( )-phenylalanyl-(ff)-hystidyl] (Scheme 8) (29). The ee... 

The situation is further complicated by chiral autoinduction, first reported by Danda et al. for the hydrocyanation of 3-phenoxybenzaldehyde [39]. It was found that the enantiomeric excess of the product increases with reaction time, and that addition of small amounts of optically pure cyanohydrin at the beginning of the reaction led to high ee of the bulk product, irrespective of catalyst ee. It was concluded that the active catalyst is not the diketopiperazine alone but a 1 1 aggregate with the product cyanohydrin of the opposite configuration (e.g. (R,R)-1 plus S-mandelonitrile) [39]. Lipton et al. later developed a mathematical model for this effect and exploited it to improve the enantioselectivity of the hydrocyanation of... 

Szlosek M, Figadere B (2000) Highly Enantioselective Aldol Reaction with 2-Trimethylsi-lyloxyfuran The First Catalytic Asymmetric Autoinductive Aldol Reaction. Angew Chem Int Ed 39 1799... 

In the aldol reaction of 2-trimethylsilyloxyfuran with aldehydes catalyzed by (BINOL)2Ti complex, a significant impact of the product on the enantioselectivity of the catalysis was observed [124]. As shown in Scheme 14.44, the addition of 5 mol% of the product (82% ee) in the catalyst can enhance the enantiomeric excess of the product from 70% to 96%. Therefore, an asymmetric autoinduction might be involved in the catalytic system. On the basis of this observation. 

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