Asymmetric Oxidative Biaryl Coupling Reactions

The methods for the preparation of enantioenriched axially chiral biaryl compounds include en miatic or chemical resolution of their racemic mixture, atroposelective coupling reactions, transition metal-catalyzed asymmetric 

However, it was proved that the asymmetric induction in these examples was not generated during the oxidative coupling process. According to the investigation executed by Smrcina, Kocovsky, and co-workers, the detailed 

Syntheses of optically active binaphthol-related compounds with chiral cupric-amine complexes. 

A third mechanism was found to be involved in the cross-coupling between 2-naphthol and 3-hydroxy-2-naphthoic acid mediated by the CuCl2-( )-sparteine complex where the purification of the precipitate and the mother liquor both gave rise to the same enantioenriched product (S)-3 

From precipitate (S)-BINOL OH 14% yield. 100% ee OH From solution (S)-BINOL 42% yield, 20% ee 

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Based on their mechanistic investigation on the Cu -mediated oxidative coupling of 2-naphthol derivatives, Smrcina, Kocovsky, and co-workers were able to develop the first catalytic asymmetric oxidative biaryl coupling reaction (Scheme 3.3). AgCl was used as the stoichiometric oxidant to regenerate the Cu species. In order to avoid the formation of detrimental HCl by-product, the corresponding sodium 2-naphthol salts were employed as the coupling partners. The desired product 3 was obtained in 41% yield (8 turnovers) with 32% ee. 

Scheme 3.3 The first catalytic asymmetric oxidative biaryl coupling reaction reported by Smrcina and Kocovsky.

Chiral oxovanadium complexes constitute another family of catalysts that has been successfully utilized in asymmetric oxidative biaryl coupling reactions. A remarkable feature of these catalytic systems is that the tolerated substrates are typically the 2-naphthols that do not bear a coordinating functionality at the C3 position, which can be regarded as a complement to the Cu-based catalytic systems described in Section 3.3. 

Table 3.6 V-catalyzed asymmetric oxidative biaryl coupling reactions reported by Chen.

Uang and co-workers, on the other hand, employed similar chiral oxo-vanadium(iv) complexes to realize asymmetric oxidative biaryl coupling reactions. It was found that the addition of acidic additive was crucial for obtaining superior reactivity, probably due to the disproportionation of V" species to V " and V species under strong acidic conditions. Systematic evaluation of various acid additives revealed that TMSCl was the best choice. The 2-naphthol derivatives eould be converted to the corresponding homo-coupling products at room temperature within 24 hours. The loading of complex 23 and TMSCl could be lowered to only 2 mol% (Scheme 3.9). 

Asymmetric Oxidative Biaryl Coupling Reactions Table 3.7... 

Besides the well-documented Cu- and V-catalyzed asymmetric oxidative biaryl coupling reactions, the reactions catalyzed by chiral complexes based on other transition metals such as Ru and Fe have also appeared in the literature. 

Organocatalysis has also found applications in the area of asymmetric oxidative biaryl coupling reactions. Very recently, the groups of Kurti" and List" independently devised atroposelective [3,3]-rearrangement reactions of N,N -diaryl hydrazines to synthesize enantioenriched BINAM derivatives (Scheme 3.16). 

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