Aryl transfer reactions, enantioselective

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. 

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]. 

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]. 

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]. 

The asymmetric reduction of aryl ketone can be achieved with ruthenium catalysts (Scheme 24), prepared separately or in situ by formation of [RuCl2(arene)]2 and ligand, in z-PrOH [81]. The high enantioselectivities and rate are very dependent upon the functionality of the substrate, T -arene and A -substitution of the diamino or amino alcohol ligands on ruthenium [81]. The hydrogen transfer reaction in z-PrOH is reversible, necessitating low concentrations, while extensive... 

Due to their widespread application in the Suzuki-Miyaura reaction, arylboronic acids are attractive aryl transfer precursors. However, in the zinc-promoted reaction, an excess of Et2Zn (up to 7equiv.) must be added in order for efficient transmetallation to occur. The application of a reactive aryl metal species necessitating only a catalytic amount of metal would thus be advantageous. In recent years, several rhodium-catalyzed enantioselective protocols have been described, as well as processes involving palladium and nickel. 

In addition, in 2007, Jprgensen and co-workers [117] developed asymmetric a-arylation of aldehydes by reaction with quinones. The a-arylation proceeded in high yields, and the corresponding optically active a-arylated aldehydes were obtained with excellent enantioselectivities (up to 99% ee). Based on the proposed mechanism, this transformation proceeds via an addition/proton-transfer reaction sequence resulting in formal a-arylation. 

The group of Miyaura [78, 89] applied arylbismuth compounds [88] in these metal-catalyzed reactions. The application of this compound type in such met2il-catalyzed reactions is stiU rare. In fact, as has already been mentioned, Miyaura s group reported the use of chiral phosphane/dicationic palladium(II) complexes (based on (S,S)-Chiraphos and (S,S)-Dipamp) in the 1,4-addition of triaryl-bismuth reagents to cyclic and acyclic enones in aqueous methanol at low temperature (Scheme 5.32). Enantioselectivities of up to 95% ee were achieved for cyclic enones. The use of Cu(BF4)2 to help the reoxidation of Pd(0) to the catalyticaUy active Pd(II) species was an advantage, as well as the efficiency of the aryl transfer, allowing utilization of 2-2.8 of the three phenyl groups on the bismuth atom. Several years ago, Yamamoto, Nishikata, and Miyaura [68c] published a personal account of... 

An enantioselective imino-ene reaction was developed by Lectka to provide ct-amino acid derivatives.27 Aryl alkenes (cr-methyl styrene, tetralene), aliphatic alkenes (methylene cyclohexane), and heteroatom-containing enes, all gave high yields and high ee s of the homoallylic amides (Equation (17)). The mechanism of this reaction has been proposed to proceed through a concerted pathway. This mechanism is evidenced by a large kinetic isotope effect observed in the transfer of H(D). 

In these Heck reactions some degree of enantioselectivity (up to 83% ee) is achieved in the presence of (/ )-BINAP, although the yields of Heck products are often very low in the highest degree of enantioselectivity (e.g., 19% isolated yield at 83% ee) [93]. An example of a tandem Heck reaction is shown below involving the arylation of dihydropyrrole 132 with 1-naphthyl triflate (133) [92]. Complete chirality transfer is observed for the arylation of 134 to 135. 

The Br0nsted acid catalyzed enantioselective reduction of several methyl-aryl ketimines affords the corresponding amines in good yields and enantioselectivities (Table 4.1). The mild reaction conditions and generally good chemoselectivity of this transfer hydrogenation render this transformation an attractive and metal-free approach to optically active amines. 

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