Enantioselective Construction of Vicinal Sulfur‐functionalized Quaternary and Tertiary Stereocenters via Organocatalytic Michael Addition of 5H‐Thiazol‐4‐ones to 1‐Azadienes

Abstract

An organocatalytic enantioselective Michael addition of 5H‐thiazol‐4‐ones to 1‐azadienes has been developed. In the presence of chiral phosphoric acid, a series of optically active benzofuran derivatives featured by vicinal sulfur‐containing quaternary and tertiary stereocenters were obtained in high yields (71‐99%) with high stereoselectivities (70–96% ee and 8 : 1–20 : 1 d.r.).

Asymmetric 1,4-Michael Addition Reaction of Azadienes with α-Thiocyanoindanones Catalyzed by Bifunctional Chiral Squaramide

“…1 H NMR spectra were measured with Bruker Ascend 400 MHz spectrometer; chemical shifts were reported in δ (ppm) units relative to tetramethylsilane (TMS) as internal standard. 13 C NMR spectra were measured at 100 MHz with 400 MHz spectrometer; chemical shifts were reported in ppm relative to tetramethylsilane and referenced to solvent peak (CDCl 3 , δ C = 77.00). High-resolution mass spectra (Electron spray ionization) were measured with an Agilent 6520 Accurate-Mass Q-TOF MS system equipped with an electrospray ionization (ESI) source.…”

“…Enantiomeric excesses were determined by chiral HPLC analysis using an Agilent 1200 LC instrument with a Daicel Chiralpak IA, IC, or ADH column. 1 H and 13 C NMR spectra for newly synthesized compounds, X-ray single crystal data for product 3ja and copies of the HPLC chromatograms can be found in the Supplementary Materials.…”

“…The development of efficient and convenient ways to obtain compounds containing benzofuran structural motifs is the common goal pursued by many organic chemists. As far as we know, azadienes derived from benzofurans can undergo 1,4-Michael addition reactions with suitable nucleophiles due to their high reactivity to quickly construct multisubstituted benzofuran derivatives, and a variety of benzofuran derivatives have been successfully obtained by using azadienes [9][10][11][12][13][14]. In addition, thiocyanate compounds have various biological activities such as being anticancer, antimicrobial, and insecticidal; they have a wide range of applications in the fields of medicine, pesticides, and materials (Figure 2).…”

“…[α] D25 = +84.7 • (c 0.78, CH 2 Cl 2 ). 1 H NMR (400 MHz, CDCl 3 ): δ 7.77 (d, J = 7.6 Hz, 1H, ArH), 7.71 (d, J = 7.2 Hz, 1H, ArH), 7.58−7.54 (m, 2H, ArH), 7.47 (d, J = 8.0 Hz, 2H, ArH), 7.40-7.29 (m, 4H, ArH), 6.91-6.82 (m, 6H, ArH), 6.68 (s, 1H, NH), 5.00 (s, 1H, CH), 4.00 (d, J = 18.8 Hz, 1H, CH 2 ), 3.22 (d, J = 18.8 Hz, 1H, CH 2 ), 2.21 (s, 3H, CH 3 ), 2.19 (s, 3H, CH 3 ) ppm 13. C NMR (100 MHz, CDCl 3 ): δ 198.4, 153.7, 151.7, 149.8, 143.5, 137.3, 136.2, 136.0, 133.0, 131.4, 129.3, 129.2, 129.1, 128.5, 127.1, 126.1, 126.0, 125.5, 125.4, 123.8, 121.0, 116.9, 111.3, 110.2, 61.7, 44.0, 35.8, 21.5, 21.0 ppm.…”

“…2 Hz, 1H, CH 2 ), 1.68 (s, 3H, CH 3 ) ppm 13. C NMR (100 MHz, CDCl 3 ): δ 198.3, 153.9, 151.2, 149.5, 143.5, 136.3, 135.6, 132.9, 132.8, 132.3, 132.0, 129.1, 129.0, 128.6, 128.2, 128.1, 127.4, 126.9, 126.54, 126.51, 126.4, 126.1, 126.0, 125.6, 125.5, 123.9, 121.4, 117.3, 111.4, 110.3, 61.7, 44.1, 35.7, 20.8 ppm.…”