Fluorinated Alcohols As Promoters for the Metal-Free Direct Substitution Reaction of Allylic Alcohols with Nitrogenated, Silylated, and Carbon Nucleophiles

Abstract

The direct allylic substitution reaction using allylic alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) as reaction media is described. The developed procedure is simple, works under mild conditions (rt, 50 and 70 °C), and proves to be very general, since different nitrogenated nucleophiles and carbon nucleophiles can be used achieving high yields, especially when HFIP is employed as solvent and aromatic allylic alcohols are the substrates. Thus, sulfonamides, carbamates, carboxamides, and amines can be successfully employed as nitrogen-based nucleophiles. Likewise, silylated nucleophiles such as trimethylsilylazide, allyltrimethylsilane, trimethylsilane, and trimethylsilylphenylacetylene give the corresponding allylic substitution products in high yields. Good results for the Friedel-Crafts adducts are also achieved with aromatic compounds (phenol, anisole, indole, and anilines) as nucleophiles. Particularly interesting are the results obtained with electron-rich anilines, which can behave as nitrogenated or carbon nucleophiles depending on their electronic properties and the solvent employed. In addition, 1,3-dicarbonyl compounds (acetylacetone and Meldrum's acid) are also successfully employed as soft carbon nucleophiles. Studies for mechanism elucidation are also reported, pointing toward the existence of carbocationic intermediates and two working reaction pathways for the obtention of the allylic substitution product.

Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

“…In the same year, Baeza and Nájera reported the direct substitution reactions of allylic alcohols 5 with nitrogenated, silylated and carbonous nucleophiles 6 using fluorinated alcohols (HFIP and TFE) as promoters (Scheme ) . p ‐Toluenesulfonamide gave rise to the amination product 7 a in almost quantitative yields in both solvents after purification.…”

PhI(OCOCF3)2-catalyzed nucleophilic substitution of aromatic propargyl alcohols

“…Significant progress has also been made using a wide range of metals and Lewis acids, including rhenium, 3 rhenium/gold, 2l gold, 4 Cu, 5 Sc,6 Fe,7 Bi,8 Ca,9 In, 10 B, 11 Zn 12 and I 2 , 13 despite some of them not being broadly applicable to all classes of propargyl alcohols and sometimes requiring an additional cocatalyst to achieve high conversions. In addition, several environmentally friendly processes mediated by cheap and recyclable Brønsted acids, such as p-toluenesulfonic acid, 14 HN(SO 2 CF 3 ) 2 , 15 heteropoly acids, 16 and acidic fluorinated alcohols, 17 have also been developed. However, harsh reaction conditions, and poor yields are typically associated with these processes due to a myriad of competing reactions, including skeletal rearrangement (MeyerSchuster rearrangement), elimination, deprotection, or dimerization of the starting alkynols, particularly with acid-sensitive substrates.…”

Magnetically Separable Nano Fe3O4 Catalyzed Direct Azidation of Allylic and Benzylic Alcohols Followed by Copper-Catalyzed Click Reaction

“…[1][2][3][4][5][6] The direct catalytic substitution of allylic and benzylic alcohols is considered as an atom-economical reaction. [1][2][3][4][5][6] The direct catalytic substitution of allylic and benzylic alcohols is considered as an atom-economical reaction.…”

“…[1][2][3][4] The construction of a C-C bond via the direct catalytic substitution of allylic and benzylic alcohols using the carbon-based nucleophiles is also well explored. [5][6][7][8][9][10][11][12][13] In general, allylated nitrogen compounds including allylic and benzylic amines/azides are considered as important building blocks for the synthesis of heterocycles, natural products, and biologically active molecules. [5][6][7][8][9][10][11][12][13] In general, allylated nitrogen compounds including allylic and benzylic amines/azides are considered as important building blocks for the synthesis of heterocycles, natural products, and biologically active molecules.…”

“…[5][6][7][8][9][10][11][12][13] In general, allylated nitrogen compounds including allylic and benzylic amines/azides are considered as important building blocks for the synthesis of heterocycles, natural products, and biologically active molecules. [6][7][8][9][10][11][12] Recently, Rueping's group reported the direct catalytic azidation of allylic and benzylic alcohols using silver salts under homogeneous catalysis. [6][7][8][9][10][11][12] Recently, Rueping's group reported the direct catalytic azidation of allylic and benzylic alcohols using silver salts under homogeneous catalysis.…”