Total Synthesis of Putative Chagosensine

Abstract

IR spectra were recorded on Alpha Platinum ATR (Bruker) at room temperature, wavenumbers (ṽ) are given in cm -1 .Mass spectrometric samples were measured using the following instruments: MS (EI): Finnigan MAT 8200 (70 eV), ESI-MS: Bruker ESQ3000, accurate mass determinations: Bruker APEX III FT-MS (7 T magnet) or MAT 95 (Finnigan).Optical rotations were measured with an A-Krüss Otronic Model P8000-t polarimeter at a wavelength of 589 nm. The values are given as specific optical rotation with exact temperature, concentration (c/(10 mg/mL)) and solvent.LC-MS analyses were conducted on a Shimadzu LC-MS 2020 instrument (pumps LC-20AD, autosampler SIL-20AC, column oven CTO-20AC, diode array detector SPD-M20A, controller CBM-20A, ESI detector and software Labsolutions) with a ZORBAX Eclipse Plus column (C18 1.8 μm, 4.6 mm ID × 50 mm (Agilent)) or a YMC-ODS-A C18 column (S-5 μm, 120 Å, 4.6 mm ID × 150 mm). A binary gradient of MeCN or MeOH in water was used as eluent at a flow rate of 0.8 or 1.0 mL/min. The oven temperature was kept at 35 °C and the detection wave length at 250 nm. Conditions for each compound are specified below. Preparative LC was performed with a Shimadzu LC-20A prominence system (pumps LC-20AP, column oven CTO-20AC, diode array detector SPD-M20A, fraction collector FRC-10A, controller CBM-20A and LC-solutionsoftware); conditions for each compound are specified below.GC-MS was measured on a Shimadzu GCMS-QP2010 Ultra instrument. Chiral GC was measured on an Agilent 7890B GC instrument with the procedure specified conditions. Model StudiesBis-boronate 7. A pressure Schlenk flask charged with Pt(PPh 3 ) 4 (31 mg, 25 µmol) and B 2 pin 2 (0.21 g, 0.83 mmol) was evacuated and backfilled with Argon. A solution of compound 6a (R = TBS, 0.20 g, 0.83 mmol) in degassed DMF (1 mL) was added and the resulting mixture was stirred at 80 °C for 16 hours. The mixture was allowed to cool to room temperature, diluted with t-butyl methyl ether (20 mL) and washed with brine (3 × 5 mL). The combined organic phases were dried over MgSO 4 , filtered through a small pad of Celite and concentrated. The residue was used in the next step without further purification. 1 H NMR (400 MHz, CDCl 3 ) δ = 5.95 (d, J = 1.5 Hz, 1H), 4.19 (ddd, J = 6.6, 5.0, 1.5 Hz, 1H), 1.56-1.41 (m, 2H), 1.39-1.16 (m, 30H), 0.89-0.83 (m, 12H), 0.02 (s, 3H), 0.00 (s, 3H) ppm. 13 cm -1 . MS (ESIpos) m/z (%): 517.4 (100 (M+Na)). HRMS (ESIpos): m/z calcd. for C 26 H 52 O 5 B 2 SiNa: 517.3662, found: 517.3664.Dienylboronate 9. PdCl 2 (dppf) (3.6 mg, 4.9 µmol), K 3 PO 4 (0.1 g, 0.5 mmol), and ethyl 3-cisiodoacrylate (8) (21 µL, 0.16 mmol) were added to a solution of teh crude bis-boronate 7 (80 mg, 0.16 mmol) in THF (1 mL) and H 2 O (43 µL, 2.4 mmol).The mixture was stirred at 60 °C for 16 hours before it was allowed to cool to room temperature. The mixture was dried over MgSO 4 , filtered and concentrated. The residue was purified by flash chromatography (hexane/EtOAc 9:1) to afford the title compound as a colorless oil (52 mg, 69%). 1 H NMR (400 MHz, CDCl ...

trans‐Hydroboration of Propargyl Alcohol Derivatives and Related Substrates

“…The enabling profile of the reaction is perhaps best appreciated by the formation of products 23 and 24 . The polyfunctionalized alkyne precursors were key intermediates of our approaches to the structurally demanding marine macrolide chagosensine and the antibiotic 5,6‐dihydrocineromycin B, respectively.…”

Porous Ligand Creates New Reaction Route: Bifunctional Single-Atom Palladium Catalyst for Selective Distannylation of Terminal Alkynes

“…1.2-Ditin-substituted olefins can be easily converted into poly-functionally diverse olefins via the Migita-Kosugi-Stille cross-coupling reaction, 28 which are often used as important synthetic blocks in organic synthesis. 29 The distannylation of alkyne is the only route for this special compound. Most of the existing distannylation of alkynes uses alkylditin as substrates; these reactions suffer from inevitable shortcoming, such as high metal loading, low yields, poor stereo-and chemoselectivity, narrow substrate scope, and requirement of stoichiometric amount of base (Scheme 1, path c).…”

Multi‐Gram Scale Synthesis of Chiral 3‐Methyl‐2,5‐trans‐tetrahydrofurans

“…3-Methyl-2,5-trans-tetrahydrofurans are critical structural elements for various natural products, biologically active compounds, and pharmaceuticals. [1][2][3][4][5][6][7] For instance, natural products chagosensine, [8,9] cationomycin, [10,11] amphidinolides C, C2, C3, and F [12 -15] possess such trans-tetrahydrofuran substructures ( Figure 1). As a consequence, many methodologies have been developed for the construction of this type of heterocycle.…”