Aryl transfer

The development of ferrocene 9 was part of our studies on planar-chiral compounds, which also involved the synthesis of other scaffolds such as chromium-tricarbonyl arenes [15], sulfoximidoyl ferrocenes [16], and [2.2]paracyclophanes [17]. In aryl transfer reactions, however, ferrocene 9 proved to be the best catalyst in this series, and it is still used extensively today. 

The same synthetic strategy as in the synthesis of planar-chiral ferrocenes was applied to the preparation of rheniumtricarbonyl 14, which has also been studied as a catalyst in aryl transfer reactions [21], Subsequently, this chemistry has been extended, and various catalytic applications of cyrhetrenes 15, 16 (AAPhos), and related derivatives have recently been demonstrated [22]. 

Later, the oxazolines 25 were examined to study the effects of matched/mismatched combinations of stereogenic centers on catalyzed aryl transfer reactions to aldehydes. Of these mandelic acid-derived catalysts, 25b gave the best results in terms of enantioselectivity (up to 35% ee), while diastereomer (l ,S)-25b proved to be superior to (S,S)-25b with respect to catalyst activity [29]. With both compounds, the absolute configuration of the product was determined by the oxazo-line moiety. 

The use of hydroxy oxazolines 26 in catalytic aryl transfer reactions was investigated subsequently (specifically, addition of BPhs to p-methoxybenzaldehyde in the presence of dimethyl poly(ethylene glycol) (DiMPEG) for details of this... 

Two strategies for the synthesis of enantiomerically enriched diaryl methanols 27 are apparent first, asymmetric reductions of the corresponding diaryl ketones 36 [33], and, second, enantioselective aryl transfer reactions to the respective benzaldehyde derivatives 37 (Scheme 2.1.2.5) [34, 35]. 

The most significant effect on the aryl transfer was observed when the metallocene backbone was changed [21]. Both ee and catalyst turnover were affected, and even with a reduced catalyst loading excellent enantioselectivities were observed in some cases. Three examples will illustrate details of the effects observed using the most effective catalyst, which was obtained from rheniumtri-carbonyl 14. In the formation of 27a, use of 10 mol% cyrhetrene 14 afforded the product with 98% ee. Compared to the result obtained with ferrocene 9 (97% ee) under identical conditions, the ee value achieved with 14 revealed a slight improvement in the enantioselectivity. Remarkably (and in contrast to a catalysis with ferrocene 9) almost the same ee was obtained in an experiment with only 2 mol% 14 (formation of 27a with 96% ee). In the addition to 2-furylcarbaldehyde neither... 

Another limitation of the protocols described so far related to the aryl moiety itself. Until this stage only phenyl groups had been transferred onto (aromatic) aldehydes, which significantly restricted the substrate scope. In order to expand the applicability of the process, alternative aryl sources had to be found. This problem was solved in 2002, when we discovered that simple boronic acids 40 could also be applied in the transmetallation process [49]. For the first time the catalyzed asymmetric aryl transfer allowed a high degree of flexibility in the substitution pattern of the substrates. A wide variety of aryl boronic acids is commercially available alternatively, specific derivatives can easily be synthesized, selected examples of which (with benzaldehyde 37b as the aryl acceptor) are shown in Scheme 2.1.2.10. 

The success of the asymmetric aryl transfer from boronic acids also relied on another important phenomenon. The presence of catalytic amounts (10 mol%) of DiMPEG (MW = 2000) increased the enantioselectivity of the process significantly [49]. For example, without DiMPEG the reaction between benzaldehyde 37b and 1-naphthylboronic acid 40c gave the corresponding diarylmethanol 27g with 31% ee in 56% yield, whereas in the presence of the polyether, 27g was obtained in 85% ee and 91% yield (Scheme 2.1.2.12) [49]. 

Although the precise reason for the MPEG-effect [50] is still unknown, we assume that catalytically active achiral metal species are inactivated by trapping with the polyether and that the catalyzed asymmetric reaction path thereby becomes more dominant. This phenomenon had already been observed in aryl transfer reactions catalyzed by MPEG-bound ferrocene 39 [44], and it can be used to perform catalyses with lower catalyst loadings [50]. 

This protocol has attracted much attention recently, and several groups (those of Chan, Katsuki, Braga, and Zhao) have applied their catalysts to aryl transfer reactions from boronic acids (or derivatives thereof) [51]. 

With the aim of improving understanding of the mechanism of the ferrocene-catalyzed aryl transfer reactions from organozincs to aldehydes, DPT calculations were performed in close collaboration with Norrby [64]. As a result, the experimentally observed higher reactivity of the phenyl transfer to aldehydes compared... 

After screening several compounds, including ferrocene 9 or cyrhetrene 14, which had previously been applied in the aryl transfer reactions to aldehydes and led to excellent enantioselectivities, we found, in collaboration with Erase, that only [2.2]paracyclophane 48 was capable of forming a catalyst system (Scheme 2.1.2.15). Subsequently, the substrate scope was evaluated, and several diaryl-methylamines 47 were obtained with excellent enantioselectivities (up to 97% ee) [69, 70]. 

So far, attempts to expand the substrate scope further by modifying the aryl transfer agent have remained unsuccessful. Thus, imine addition reactions with arylzinc species other than the one prepared in situ by mixing diphenylzinc and diethylzinc still deserve attention, and will be developed in the near future. 

For a general review of catalyzed asymmetric aryl transfer reactions, see C. Bolm, J. P. Hildebrand, K. Muniz, N. Hermanns, Angew. Chem. 2001, 113, 3382 Angew. Chem. Int. Ed. 2001, 40, 3284. 

Steric bulk at the R group of silanols 13 appeared to increase the ee of the aryl transfer products. Unfortunately, however, all attempts to prepare silanol 13 with two t-butyl groups at the silicon atom failed. 

E. Asymmetric Aryl Transfer Reaction to Carbonyl Compounds. 566... 

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