[organic] angelw reports a new strategy for the synthesis of silanized saturated carbon (heterocyclic) ring

Aromatics hydrogenation can directly transform aromatic rings with two-dimensional planar structure into cyclohexane compounds with three-dimensional space, so it has important strategic value in pharmaceutical chemistry and other fields However, some functional groups on the aromatic ring may inhibit the activity of the reaction or de functionalize during the reaction, which to some extent limits the wide application of the method (Figure 1a) For example, silylated aromatics may be unstable to electrophilic and nucleophilic reagents, alkoxy and halosilane groups are prone to nucleophilic cleavage of si-x bond, and the large steric hindrance of silicon substituents may hinder the effective coordination of aromatics and catalysts In addition, it is difficult to control the regioselectivity and enantioselectivity of 1,2-disubstituted alkenes, which makes hydrosilylation of alkenes very challenging Therefore, it is of great significance to develop new synthesis methods (source: angelw Chem Int.ed.) recently, Dr Christoph schlephorst and Professor Frank glorius of the University of Minster in Germany jointly developed a scheme 1B (angelw Chem Int ed., 2018, 57, 8297) for the conversion of silylated aromatic hydrocarbons into saturated silylated carbon and heterocyclic compounds by aromatics hydrogenation The author is based on the recently reported hydrogenation of PFA (Science, 2017, 357, 908) Through further optimization of the conditions, it is found that the hydrogenation of trimethylsilylaromatic hydrocarbons can be carried out smoothly and efficiently with RH CAAC (1, scheme 2) as catalyst and SiO 2 as additive The product has excellent D.R (37:1) Next, the applicability of the substrate was studied (Figure 2) The change of Si based partial steric hindrance has no obvious effect on the reaction The reaction of ortho substituted substrate can produce a product with a single non enantiomer Alkoxysilyl group and halosilyl group have good tolerance Other functional groups on the aromatic ring, such as boron group, BOC protected amino group and ester group, also have good tolerance Other electron absorbing groups (such as trifluoromethyl, fluorine) or electron donating groups (such as methoxy) can also be tolerated It should be noted that the reaction is also suitable for condensed aromatics and heterocyclic aromatics (source: angelw Chem Int.ed.) then, the author synthesized the muscle relaxant esperisone analogue 4 from the product 3af and 4-ethyl-phenylacetone by acid mediated Mannich reaction, which provided a new method for the structural modification of the lead compound (Figure 3B) In addition, the author combined with the idea of carbon silicon exchange, and synthesized the silicon iridium ester 3aG with fruit odor by this reaction, which further proved the practical application value of this reaction (Figure 3B) (source: angelw Chem Int.ed.) finally, the author found that the method can be used to transform PFB into CIS PFC efficiently, and the reaction can achieve gram scale preparation Compared with the previously reported method, the silica effect in the reaction can significantly improve the yield of the reaction, with obvious advantages (source: angelw Chem Int.ed.) conclusion: Dr Christoph schlepphorst, University of Minster, Germany, and Professor Frank glorius jointly developed a RH CAAC catalyzed hydrogenation of silylated aromatics The reaction can be used to prepare three-dimensional structure of silylated saturated carbon ring and heterocyclic compounds, and can be used to synthesize analogues of esperisone and aromatic silylated irises.