| Asymmetric hydroformylation (AHF) is an atom-economic method to convert olefins into enantiomerically pure aldehydes. This aldehydes are versatile building blocks for many pharmaceuticals and agrochemicals. Despite its importance, asymmetric hydroformylation is still seldom utilized by industry. This is due to several technical challenges. Among the most significant are difficulty in controlling regio-and enantioselectivities concurrently, and limited substrate scope for any single ligand. Chiral ligands, can be used to provide an enantioselective product. Since the introduction of the Binaphos, the development of chiral phosphorus ligands has significantly facilitated enhanced regio-and enantioselectivity in rhodium-catalyzed AHF. Although new ligands that are able to provide chiral aldehydes at reasonably high temperatures without sacrificing their selectivities are highly desirable, only a few successful examples were documented in the past two decades.Recent reports have shown that mixed phosphorus ligands bearing two different phosphorus groups are effective in asymmetric hydroformylation. Although good regio-and enantioselectivities have been achieved for AHF reaction of many substrates, such as monosubstituted and 1,2-disubstituted olefins, only very limited examples are involved in Rh-catalyzed desymmetrizing hydroformylation. And as we know few studies have been made on the asymmetric hydroformylation of vinyl heteroarenes, which provide access to important building blocks for synthesizing biologically active compounds.Herein, we have been developed an efficient synthesis of (S,R)-Bn-Yanphos from readily available chiral BINOL in gram scale. They have high regio-and enantioselectivities (up to 96% ee) in Rh-catalyzed asymmetric hydroformylations of Cyclopentene and vinyl heteroarenes. The research contents are as follows:1. We have developed a highly efficient route to make (S,R)-Bn-Yanphos in gram scale from readily available chiral BINOL with only 6 steps.2. We developed an efficient approach to synthesize chiral cyclopentanalcarboxaldehydes by catalytic desymmetrizing hydroformylation of cyclopropenes. This transformation exhibited excellent enantioselectivities and high diastereoselectivities under mild conditions with low catalyst loading. More importantly, this method provides a concise route to the synthesis of chiral carbocyclic nucleosides and has potential applications in synthesis of bioactivities molecules.3. We have demonstrated the asymmetric hydroformylation of vinylheteroarenes with Bn-Yanphos/Rh(Ⅰ) catalyst, and synthesized the corresponding aldehydes in good yields and with high enantioselectivity. In addition, The subsequent reduction of a-heteroarylpropanal to a-heteroarylpropanol without loss of enantiomeric excess. |
