The Total Synthesis of (‐)‐Lemonomycin.

Abstract

Material and Methods. Unless otherwise stated, reactions were performed at ambient temperature (typically 20 °C) in flame-dried glassware under a nitrogen or argon atmosphere using dry, deoxygenated solvents. Solvents were dried by passage through an activated alumina column under argon. Acrolein was distilled under nitrogen immediately prior to use. All other commercially obtained reagents were used as received. Reaction temperatures were controlled by an IKAmag temperature modulator. Thin-layer chromatography (TLC) was performed using E. Merck silica gel 60 F254 precoated plates (0.25 mm) and visualized by UV, anisaldehyde, permanganate, or CAM staining. ICN Silica gel (particle size 0.032-0.063 mm) was used for flash chromatography. Preparatory reversed-phase HPLC was performed on a Waters HPLC with a Waters Delta-Pak 25 x 100 mm, 15 mm C 1 8 column equipped with a guard, utilizing a flow rate of 10 mL/min and a ramp of 1% B/min (A eluent = 95:5:0.05 water:acetonitrile:trifluoroacetic acid, B eluent = 5:95:0.01 water:acetonitrile:trifluoroacetic acid) with visualization at 270 nm. Analytical chiral HPLC was performed with an Agilent 1100 Series HPLC utilizing a chiralcel AD column (4.6 mm x 25 cm) obtained from Daicel Chemical Industries, Ltd with visualization at 254 nm. Optical rotations were measured with a Jasco P-1010 polarimeter.1 H and 1 3 C NMR spectra were recorded on either a Varian Mercury 300 (at 300 MHz and 75 MHz respectively), Varian Mercury 500 (at 500 MHz and 125 MHz respectively), or on a Varian Mercury 600 (600 MHz for proton only) spectrometer and are reported relative to Me 4 Si (d 0.0). Data for 1 H NMR spectra are reported as follows: chemical shift (d ppm), multiplicity, coupling constant (Hz) and integration. Data for 1 3 C NMR spectra are reported in terms of chemical shift. IR spectra were recorded on a Perkin Elmer Paragon 1000 spectrometer and are reported in frequency of absorption (cm -1 ). UV spectra were measured on a Beckman-Coulter DU 7400 spectrophotometer. High resolution mass spectra were obtained from the Caltech Mass Spectral Facility. Crystallographic data have been deposited at the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK and copies can be obtained on request, free of charge, by quoting the publication citation and the deposition number (see individual structures for deposition number). Am. Chem. Soc. 2002, 124, 7284-7285.