Cheng Jinpei, Li Xin group, Nankai University: asymmetric allyl alkylation to prepare chiral phosphorus compounds

As an important bioactive molecule, chiral phosphorus compounds are also the backbone of many chiral ligands, which are widely used in biology, medicine and organic synthesis Chiral phosphorus compounds are mainly prepared by resolution, chiral cofactor induction, asymmetric cross coupling and asymmetric addition, but most of the reactions involve metal catalysis and the conditions are relatively harsh (Fig 1) So far, there are only two reports on the preparation of chiral phosphorus compounds by organic catalysis Therefore, it is still significant and challenging to develop organic catalytic synthesis methods of chiral phosphorus compounds Fig 1 (source: chem SCI.) asymmetric allylic alkylation (AAA) based on MBH adduct catalyzed by organic Lewis base is a very simple and efficient method for the synthesis of chiral compounds, but it is mainly used for the construction of carbon centered chiral compounds Based on the previous development of asymmetric allylic alkylation strategy (AAA) based on MBH adducts to synthesize chiral aniline compounds (j.am.chem.soc 2018, 140, 12836-12843), further tap the potential of AAA reaction in the synthesis of non carbon center chiral compounds, and realize the synthesis of chiral phosphorus compounds by AAA reaction based on the desymmetry strategy (Fig 2) The reaction has a wide range of substrates and good stereoselectivity The enantioselectivity of a large number of experimental products can be well maintained Further conversion of the product can lead to the synthesis of new catalysts, and the preliminary exploration in asymmetric catalysis has been completed Fig 2 (source: chem SCI.) by analyzing the linear free energy relationship between the basic parameters of the substrate and the stereoselectivity, the researchers found that the selectivity of the product was affected by the electronic and steric resistance of the R2 substituent group on the aromatic ring In addition, the size of the R1 group connected to the phosphorus center also contributes a lot to the stereoselectivity control Through theoretical calculation, a reasonable transition state model is proposed, and the enantioselectivity which is consistent with the experiment is obtained, and the relevant information obtained in the linear self use relationship analysis is reasonably explained (Fig 3, FIG 4) Figure 3 (source: chem SCI.) Figure 4 (source: chem SCI.) this achievement was recently published in Chem SCI (DOI: 10.1039 / c8sc05439h) Yang Guohui, the second year doctoral student of the research group, is the first author of this paper The work was supported by NSFC, Nankai University and the State Key Laboratory of elemental organic chemistry