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The magic of inverted selection: How does metal-catalyzed hydroboration affect product regioselection?
Metal-catalyzed hydroboration reaction in chemistry is an important technique in organic synthesis and is considered one of the many examples of homogeneous catalysis. The development of this technology can be traced back to 1975, when Kono and Ito reported that Wilkinson's catalyst (Rh(PPh3)3Cl) could undergo oxidative addition to the seemingly inactive phenol borane (HBcat), thereby promoting the hydroboration reaction. participate.
Metal-catalyzed hydroboration makes the functionalization of carbon-carbon double bonds more efficient and selective, which is not possible with uncatalyzed hydroboration.
In 1985, Männig and Nöth first demonstrated that Wilkinson's catalyst can indeed catalyze the hydroboration of olefins by HBcat, whereas in the absence of a catalyst, the hydroboration reaction leads to the reduction of the carbon group. With the progress of subsequent research, transition metal-catalyzed hydroboration was found to have unique characteristics of functional group, regio-, stereo- and chemical selectivity.
Reaction mechanism
Rh-catalyzed hydroboration reactions are generally believed to proceed via the dissociation of the Rh(I) center from the triphenylphosphine ligand. Next, the B-H bond of the hydride borate undergoes oxidative addition to form a 16-electron Rh(III) hydride complex. Migrative insertion of the olefin can then afford two regioisomers of the alkyl Rh(III) boride complex.
During the regeneration of the catalyst, the reductive elimination of the borate ester releases the catalyst, a process that allows the catalytic cycle to proceed.
However, there are divergent views in the academic community regarding the coordination mechanism of olefins. The dissociation mechanism supported by Männig and Nöth assumes that the coordination of the olefin is accompanied by the loss of the triphenylphosphine ligand, while the combined mechanism proposed by Burgess et al. assumes that the olefin bonds to the chlorine without losing the ligand. The application of computational methods has helped scholars to explore this area in depth, and the results show that both mechanisms each have their own underlying supporting evidence.
Selectivity
In addition to the early evidence provided by Männig and Nöth, the total synthesis of (+)-ptilocaulin also demonstrated the selective hydroboration of terminal olefins in the presence of ketones. In terms of regioselectivity, the results of catalyzed hydroboration are significantly different from those of uncatalyzed reactions, and Markovnikov or anti-Markovnikov products can be obtained depending on the ligand and olefin. The regioselectivity of the catalytic reaction is particularly outstanding for the hydroboration of Vinylarenes.
Wilkinson's catalyst or Rh(COD)2 (in the presence of PPh3) produces Markovnikov products, while in the absence of a catalyst, anti-Markovnikov products are produced.To explain the high regioselectivity of catalytic hydroboration, Hayashi proposed a mechanism involving η3-phenylRh complexes. Subsequent research has gradually expanded to olefins with different substituents. The most notable achievement was in 1990 when Brown and his team achieved asymmetric hydroboration using an achiral catalyst and a chiral borane derived from ephedrine. The selectivity is generally poor, but the ee value can reach 90%.
The results in this area have been further enhanced with the use of chiral catalysts and achiral borane sources, especially using chiral bisphosphine ligands like BINAP. With the advancement of multiple studies, successful examples for benzene rings with substituents and larger substituents of olefin gradually emerged, which enabled the catalytic hydroboration to be extended to more sterically hindered olefins.
This technology not only has far-reaching significance for academic research, but also provides new perspectives for industrial applications, especially the synthesis of small molecules with complex structures and biological activity.
During catalytic hydroboration, the oxidation products of borate esters are often converted into alcohols, which limits the scope of synthesis, especially when symmetrical and chiral amino groups are required. Through the transformation of cobalt hydride borate compounds, α-substituted phenylethylamines can be synthesized, some of which are commercially valuable compounds. This technology is still being developed and applied in new ways.
Combined with the above research results, how will future research break through the existing synthetic limitations and promote the further development of metal-catalyzed hydroboration technology?
