Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes [component]

S7 Ligand Preparation a. Preparation of (4S,4'S)-4,4'-diheptan-4-yl)-4,4',5,5'-tetrahydro-2,2'-bioxazole (L1, (S,S)- 4-HeptylBiOX) NH 2 HO n Pr n Pr N H HO n Pr n Pr 2. KOH (2.5 equiv) MeOH, 75 °C 2 equiv (S,S)-4-HeptylBiOX (L1): The synthesis of this ligand was adapted from procedures described by Denmark and coworkers. 5 (S)-2-amino-3-propylhexan-1-ol (2 equiv, 2.80 g, 17.6 mmol) and dimethyloxalate (1 equiv, 1.04 g, 8.80 mmol) were dissolved in PhMe (200 mL) and heated to 80 °C. The reaction
more » ... 80 °C. The reaction was allowed to stir overnight with the diamide precipitating out of solution as a white solid. Reaction was cooled to room temperature and concentrated in vacuo to afford the crude diol as a sticky white solid (3.3 g, 8.86 mmol). The crude diol was dissolved in PhMe (60 mL) and heated to 70 °C whereupon thionyl chloride (1.4 mL, 19.2 mmol) was added. Reaction was stirred at 70 °C for 30 minutes then heated to 90 °C for 90 minutes. The reaction was cooled to room temperature and poured into 20% KOH solution cooled to 0 °C. The aqueous layer was separated and extracted (3x) with DCM and the combined organic layers were washed with 20% KOH solution, NaHCO 3 and brine. The organic layer was dried with Na 2 SO 4 , filtered through a pad of Celite, and concentrated under reduced pressure to afford the dichloride as a sticky brown solid. The crude dichloride (3.6 g, 8.8 mmol) was immediately dissolved in MeOH (90 mL) and KOH (1.23 g, 21.9 mmol) was added. The reaction was heated to reflux for 14 hours. The reaction was cooled to room temperature and concentrated to remove MeOH. The crude mixture was loaded directly onto a silica gel column and eluted with 10-40% EtOAc/Hex. The pure ligand was obtained as an off-white solid (1.55 g, 53% over 3 steps, >99% ee). R f = 0.15 (silica gel, 20% EtOAc/Hex, UV). [α] D 25 = +119° (c = 1.0, CHCl 3 ). 1 H NMR (500 MHz, CDCl 3 ): δ 4.47 -4.33 (m, 2H), 4.18 -4.11 (m, 1H), 1.65 (q, J = 6.2, 5.6 Hz, 1H), 1.48 -1.12 (m, 7H), 0.95 -0.86 (m, 5H).
doi:10.1021/jacs.7b01705.s003 fatcat:2qrnwkkmgraq3ewvb3tiq5n5bq