Access to 5,6-Spirocycles Bearing Three Contiguous Stereocenters via Pd-Catalyzed Stereoselective [4 + 2] Cycloaddition of Azadienes

Abstract

We present herein a highly diastereo-and enantioselective Pd-catalyzed [4 + 2] cycloaddition of benzofuran-derived azadienes with vinyl benzoxazinanones, which represents a rare highly stereoselective cycloaddition of this class of fused azadienes as a two-atom synthon. The use of a phosphoramidite ligand bearing a chiral secondary amine with a simple biphenyl backbone proved to be the key to construct the novel spirocyclic tetrahydroquinoline scaffold containing three contiguous stereocenters as a single diastereomer in high enantioselectivity.

Borane-catalyzed cascade Friedel–Crafts alkylation/[1,5]-hydride transfer/Mannich cyclization to afford tetrahydroquinolines

“…Various approaches have been established, including intramolecular cyclization, 2 Povarov reactions, 3 hydrogenation of quinolines 4 and others. 5 Among all the strategies, the oxidative Povarov reaction, a dehydrogenative [4 + 2] annulation reaction between N -alkylanilines and alkenes, represents a promising protocol for the construction of THQs from simple starting materials ( Scheme 1a ). 6 In this reaction, two new C–C bonds were formed via a cascade sp 3 and sp 2 C–H functionalization process.…”

Development of diverse adjustable axially chiral biphenyl ligands and catalysts

“…However, the reaction was incomplete when ( S )- L13 was used as the ligand ( Figures 8 B and 8C). 52 We attempted the cycloaddition of 30 with 31 in the presence of our chiral phosphoramidite ligands ( S )- L14 , L15 or L16 . Inspiringly, ( S )- L16 provided excellent diastereo- and enantioselectivity (>20:1 dr, 97% ee) ( Figure 8 C).…”

“…32 52 : 1 H NMR (400 MHz, Chloroform- d ) δ 8.41 (d, J = 8.1 Hz, 1H), 8.14 – 8.06 (m, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.62 – 7.54 (m, 2H), 7.52 – 7.44 (m, 1H), 7.30 (q, J = 8.3 Hz, 2H), 7.20 – 7.10 (m, 4H), 7.09 – 7.01 (m, 3H), 6.99 – 6.89 (m, 2H), 6.57 (d, J = 8.1 Hz, 2H), 6.44 (d, J = 8.4 Hz, 1H), 5.63 (s, 1H), 5.21 (dt, J = 16.6, 9.7 Hz, 1H), 5.11 (dd, J = 10.0, 2.1 Hz, 1H), 4.54 (d, J = 16.7 Hz, 1H), 2.60 (s, 3H), 2.25 (s, 3H), 2.03 (d, J = 9.5 Hz, 1H) ppm. 13 C NMR (101 MHz, Chloroform- d ) δ 180.1, 170.8, 144.0, 143.6, 139.2, 139.1, 136.3, 135.8, 134.3, 134.3, 130.4, 129.9, 129.3, 129.2, 128.2, 128.2, 127.8, 127.8, 127.4, 127.3, 127.2, 126.4, 122.5, 118.5, 112.0, 96.9, 70.0, 49.2, 21.8, 21.4 ppm.…”

Palladium-catalysed enantio- and regioselective (3 + 2) cycloaddition reactions of sulfamidate imine-derived 1-azadienes towards spirocyclic cyclopentanes

“…2a). [44][45][46][47][48][49][50][51][52][53][54][55] In comparison, their employment as two-atom synthons has been scarcer, 31,34,47,50 among which there are only two examples of (3 + 2) cycloaddition reactions with BDAs known, with chemoselectivity for C]N versus C]C addition being a potential challenge. 31,34 The preference for (4 + n) reactions of BDAs is due to the favoured attack of the intermediate sulfonamide anion on the pendant Pd-Fig.…”