Application Of 2-hydroxymethylphenyl Silane

Transition metal-catalyzed coupling has become an efficient method to construct carbon-carbon bonds in modern organic synthesis.The advantages of low toxicity and stability of organosilicon compounds make the coupling reaction involving organosilicon reagents widely used.Researchers have developed a range of organosilicone coupling reagents,but these require expensive fluoride activators that are corrosive to glass containers.The o-hydroxymethyl phenyl silane developed by Hiyama’s group has many advantages,such as the need for no fluoride activator;easy to prepare;stable in nature and can be stored for a long time.In this paper,we develop new applications of o-hydroxymethyl phenyl silane as a coupling reagent and for the synthesis of natural products and silica-containing molecules with potential physiological activity.The main contents are as follows:(1)Natural product(+)-Herbertine-1,14-diol has unique physiological activity.Its structure contains two continuous chiral centers,and one of them is an all-carbon quaternary stereocenter,so it is difficult to complete synthesis.In this paper,we developed a palladium-catalyzed ring-opening tandem reaction of alkenyl 2-hydroxymethylphenyl silane with o-bromo-phenyl-substituted cyclobutanone to construct a vinyl-substituted 1-indanone skeleton with an all-carbon quaternary stereocenter(up to 92% yield,up to 93% ee)in one step.The synthesis of natural product(+)-Herbertine-1,14-diol was completed by using this tandem reaction as a key step.(2)1,3-Dihydroisobenzofuran skeleton exists widely in drugs.The synthesis of sila-dihydroisobenzofuran skeleton by silasubstitution strategy can provide an idea for the search of new drug lead compounds.We designed an intramolecular asymmetric cyclization of o-hydroxymethylphenylsilane catalyzed by copper,and constructed a sila-dihydroisobenzofuran skeleton with high stereoselectivity in one step(up to 91%yield,up to 90% ee).In summary,we developed the application of o-hydroxymethylphenylsilane in the synthesis of natural products and molecular scaffolds with potential drug activity,and constructed 1-indanones containing all-carbon quaternary stereocenters and siladihydroisobenzofuran scaffolds containing silicon chiral centers,respectively.