Dehydrative Cross-coupling Reactions Of P(O)-H Species And Alcohols To Construct Phosphorylated Heterocycles

Recently,the dehydrative coupling reactions of alcohols(C-OH)with P(O)-H compounds have emerged as one of the most efficient strategies to construct C-P bonds as it is an atom-economical approach with water as the only by-product.On the other hand,phosphorus-substituted heterocycles have wide applications in numerous fields including medicinal chemistry and organic synthesis.Therefore,this thesis focuses on the dehydrative reactions of P(O)-H compounds with rarely studied benzylic alcohols for the construction of phosphorus-substituted heterocycles containing C(sp~3)-P bonds and C(sp~2)-P bonds,such as C2-phosphorylated indoles,C3-phosphorylated hydrobenzofurans and C3-phosphorylated benzofurans,which are listed below:Firstly,a(±)-CSA(camphorsulfonic acid)catalyzed direct 1,2-phosphorylation of 3-indolylmethanols with P(O)-H species have established for the first time.It not only provided an efficient and practical new method for the synthesis of C2-phosphorylated indoles,but also enriched the reaction mode of 3-indolylmethanols.This alternative protocol features broad substrate scope with respect to both 3-indolylmethanols derived from isatins,acyclicα-keto amide,α-keto ester,1,2-diketone and simple ketones and H-phosphine oxides or H-phosphonates and mild reaction conditions.Mechanistic studies indicate that the existence of an electron-withdrawing group(such as amide,carbonyl,ester,trifluoromethyl)adjacent to the hydroxyl group of 3-indolylmethanols plays a decisive role to undergo 1,2-addition reaction and obtain C2-phosphorylated indoles.Secondly,a regioselective C3-phosphorylation of 2-benzofuryl-ols with P(O)-H species has been established for the first time to synthesize C3-phosphorylated hydrobenzofurans in generally moderate to good yields.The key to achieve the high C3-regioselectivity is the use of an“OMe”group at the C6-position to enable the 1,6-conjugate addition of P(O)-H compounds to para-quinone methides(p-QMs)-like ion pair generated in situ from 2-benzofuran-ols.Moreover,an“one-pot”tandem C3-phosphorylation/aromatization to C3-phosphorylated benzofurans is developed.This protocol not only provides an alternative method for synthesis of C3-phosphorylated hydrobenzofurans and benzofurans but also represents a new strategy for the dearomatization of benzofurans.