Compound 23 P1

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Alcohol 22 (60.5 mg, 0.071 mmol, 1 equiv., 1.4:1 d.r.) was dissolved in anhydrous CH₂Cl₂ (3.5 mL). Dess-Martin periodinane (48.2 mg, 0.114 mmol, 1.6 equiv) was added resulting in a white suspension. The reaction was monitored by TLC (95:5 EtOAc/MeOH, CAM, see picture below). After 4 h full conversion was obtained. The mixture was then quenched with with Na₂S₂O₃ (sat., aq.) NaHCO₃ (sat.,aq.) 1:1 ratio (20 mL). The mixture was allowed to stir for 10 min, leaving a clear solution in two phases. The reaction was extracted three times with CH₂Cl₂. The combined organic phases were dried over Na₂SO₄, filtered, and concentrated in vacuo to yield the aldehyde SI-18. ¹H-NMR of the crude mixture show clear formation of aldehyde (9.64 ppm and 9.62 ppm) maintaining the d.r. of 1.4:1.

To a dry flask under argon was added anhydrous THF (58 mL) followed by Et₃N (10 µL, 0.071mmol, 1.0 equiv.), TMEDA (13 µL, 0.086 mmol, 1.2 equiv.) and Zn(OTf)₂ (62 mg, 0.171 mmol, 2.4 equiv.). The crude aldehyde SI-18 (1 equiv.) was dissolved in anhydrous THF (2 mL) and added to the mixture at rt while stirred under argon. After 19 h the reaction was quenched with AcOH (0.5 M) and extracted four time with CH₂Cl₂. The combined organic phases were dried over Na₂SO₂, filtered, and concentrated. FC (2x12 cm) starting with EtOAc/heptane 8:2, going to neat EtOAc and then to EtOAc/MeOH 95:5 yielded the two diastereomeric products 23 P1 (14.7 mg, 0.021 mmol) and 23 P2 (20.6 mg, 0.030 mmol) as white solids in a total yield of 72% over two steps. The P1 elutes before P2 by FC. None of the cis isomers were observed. The stereochemistry was assigned based on which diasteromer that ultimately lead to the natural diasteromer of BE-43547A₁. (P2)

23 P1: R_f 0.63 (EtOAc neat, UV and CAM). Opt. Rot. [α]²⁶_D = -22.8 (c = 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ 7.21 (d, J = 9.1 Hz, 1H), 6.81 (dd, J = 15.1, 3.2 Hz, 1H), 6.70 (brs, 1H), 5.93 (dd, J = 15.1, 2.1 Hz, 1H), 5.01 (ddd, J = 10.3, 7.0, 3.3 Hz, 1H), 4.85 (brs, 1H), 4.52 (d, J = 19.2 Hz, 1H), 4.41 (s, 1H), 4.37 (dd, J = 17.4, 7.3 Hz, 1H), 3.89 (dq, J = 10.6, 6.9 Hz, 1H), 3.81 – 3.67 (m, 3H), 3.64 (d, J = 19.2 Hz, 1H), 2.99 (s, 3H), 1.65 (s, 3H), 1.50 (dh, J = 13.2, 6.7 Hz, 1H), 1.25 (s, 18H), 1.12 (d, J = 6.9 Hz, 2H), 0.91-0 - 86 (m, 9H), 0.86 (d, J = 6.6 Hz, 6H), 0.06 (s, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 215.9, 172.5, 168.1, 167.4, 142.7, 119.7, 80.5, 77.9, 64.8, 52.4, 51.5, 44.2, 41.6, 39.2, 36.0, 32.2, 30.1, 29.8, 29.8, 29.7, 29.7, 29.6, 28.1, 27.6, 26.1, 24.4, 22.8, 21.6, 18.6, 15.8, 14.3, -5.2. HRMS Calc.: C₃₆H₆₆N₃O₈Si⁺ 696.4614; found 696.4616. IR (neat) νmax / cm^-1 3346, 2926, 2855, 1788, 1659, 1541, 1190, 1112, 838.