Scandium-Catalyzed Propargylation of 1,3-Diketones with Propargyl Alcohols Bearing Sulfur or Selenium Functional Groups: Useful Transformation to Furans and Pyrans

Abstract

Alkynyl and allenyl ketones have been widely used to form substituted furans and pyrans by methods such as acidmediated [1][2][3][4][5][6][7][8][9][10][11] and metal-catalyzed [12][13][14][15][16][17][18][19][20] cyclizations. Because of the wide utility of these furans and pyrans as building blocks for natural products and pharmaceuticals, 21,22) extending the list of ketones starting materials known to be suitable for their creation is important. Useful examples of the synthesis of propargylated ketones exist, [23][24][25][26] but it is questionable whether the ketones obtained are indeed practical for the synthesis of furans and pyrans. [27][28][29] Recently, we developed a method for highly regioselective C-C bond formation using propargyl alcohols with nucleophiles catalyzed by scandium triflate in MeNO 2 . 30,31) This unique reaction is achieved via the two-phase condition, and is effectively stabilized by a-sulfanyl and a-selanyl functional groups. During our on going study of catalytic reactions, we investigated in the formation of C-C bonds in propargyl alcohols with 1,3-diketones and their base-promoted transformations to heterocycles. In this article, we describe the formation of propargylated 1,3-diketones by Lewis-acid catalytic reactions, which easily yield furans and benzofurans under basic conditions. Results and DiscussionFirst, we prepared the propargylated 1,3-diketones via our original method that uses sulfur-substituted propargyl alcohol 1a with 1,3-diphenylpropanedione under the optimized conditions of 5 mol% scandium triflate, 10 mol% Bu 4 NHSO 4 , MeNO 2 -H 2 O (10 : 1). The reaction was completed within 10 min and the product was obtained as 2-benzoyl-3-(pmethoxyphenyl)-1-phenyl-5-(phenylsulfanyl)pent-4-yn-1-one (2a) in 77% yield. The structure of 2a was determined from its spectral features, which consist of the acetylenic infrared absorption at 2189 cm Ϫ1 and a pair of doublets at 5.16 and 5.86 (Jϭ10 Hz) in the 1 H-NMR spectra, and a molecular ion peak at m/z 476 (C 31 H 24 O 3 S) in the mass spectrum. This result indicates that 1,3-diketone was added to the propargyl cation, not the allenic cation. We next investigated reactions of propargyl alcohols with other 1,3-diketones and similar analogs, and the results are shown in Table 1. The reaction of 1a with 2,4-pentanedione gave the product 2b in 47% yield (entry 2); however, the reaction of 1a with ethyl acetoacetate gave rise to a complex mixture (entry 3). We also explored the reactions of the propargyl alcohols bearing a variety of aromatic groups at the a-position of the hydroxyl group, as shown in entries 4 and 5. In addition, we found that the selenium-substituted propargyl alcohols 1e-j also gave the adducts 2e-j in high yields (entries 6-11 of Table 1). However, the reactions of both 1,3-cyclohexanedione and cyclopentanedione gave 6,7-dihydro-5H-cyclohexa[b]pyran-5-one 3k, l and the cyclopentane derivative 3n, respectively, not the propanediones (entries 12, 13, 15 of Table 1). 32,33) The reaction of 2-methyl-1,3-hexanedione g...

Lewis Acid-Catalyzed Propargylic Etherification and Sulfanylation from Alcohols in MeNO2-H2O

“…[40][41][42][43] Scandium-catalyzed etherifications in nitromethane resulted in a complex mixture; however, the addition of H 2 O drastically improved the reaction and provided ether 3a in 84% yield (entries 1 and 2). and 5).…”

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

“…A hidden Brønsted acid-catalyzed transformation was proposed, wherein the Sc­(OTf) 3 reacts with water in situ to generate triflic acid, which facilitates the reaction. Scandium has been utilized by other authors toward these types of transformations as well. , Zinc has been employed by Wang in the substitution of allyl alcohols with 1,3-dicarbonyl compounds and (hetero)­arenes using mechanochemical high-speed vibration milling (HSVM) conditions (Scheme b) . Other metals that have been used in the deoxygenative functionalization of alcohols through S N 1-type pathways include bismuth, , cobalt, gallium, zirconium, molybdenum, mercury, hafnium, cerium, aluminum, , lithium, and platinum .…”

Synthesis of Seleno‐Heterocycles via Electrophilic/Radical Cyclization of Alkyne Containing Heteroatoms

“…The propargylated 1,3-diketone 52 underwent intramolecular cyclization in the presence of sodium methoxide as a base and THF-MeOH solvent to give 3-benzoyl-2-phenyl-5-(phenyl sulfanyl/selanyl methyl) furan derivatives 53 (Scheme 18). [46]…”