RuCl2(cymene) 24mg (Aldrich, 0.04mmol Ru) and (S,S)-TsDPEN 40mg (0.096mmol, Aldrich) in a 250mL (14/20 joint) round flask equipped with a stopcock was flushed with Ar using a long needle. Dichloromethane (4mL, from Aldrich SureSeal) was added and the mixture was stirred under Ar (without reflux condenser) on 40C oil bath for 1 hour. The Ru-salt and the ligand dissolved. After 1 h, the solvent was removed by blowing a stream of Ar into the flask on the 40C bath. De-ionised water 16mL was added into the dry flask (with a film of active catalyst on the wall) and was de-gassed by vac/Ar purge (3-times). A mixture of solid HCO2Na 2.72g (40mmol), CTAB 15mg (0.04mmol) and the starting F-spiroketone 1.110g (4.0 mmol) was added and the flask was flushed with a stream of Ar. Ethyl acetate 2 mL (a good grade, not deoxygenated) was added and the mixture was stirred vigorously under Ar at 40C for 16 hours (the crystals of the starting material gradualy dissolved, the progres was monitored by TLC). The cooled reaction mixture was extracted twice with EtOAc (2x100mL). The combined extracts were dried (with 4A powdered molecular sieves), filtered and evaporated. The residue was purified on a column of silica (80g) in a gradient of methanol in chloroform, 0 to 2.7% of MeOH, then 2.7% isocratic. Y=1.123g (100%) of a light-yellow sticky glass.
The optical purity was assayed using a reverse-phase chiral HPLC column, Chiralpak AD-RH, in water-acetonitrile (no TFA) at 50 or 55C, at 0.8mL/min. The e.r. was 0.5:99.5 by integration. The opposite ligand enantiomer provided 100%Y of the product with e.r. = 99.4:0.6 (with the minor enantiomer peak eluting on the tail of the main one).
The 1H-NMR spectra in DMSO show a 1:1 mixture of rotamers about the amide bond. 1H(d6-DMSO, 400MHz): 7.168(dd, 9.4Hz, 3.1Hz, 1H), 6.977(td, t:8.6Hz, d:3.1Hz, 1H), 6.802(dd, 9.0HZ, 4.8Hz, 1H), 5.509(dd, 6.0Hz, 2.7Hz, 1H), 4.672(m, 1H), 4.039(m, 1H), 3.595(m, 1H), 3.411(m, 0.5H), 3.282(m, 0.5H), 3.049(m, 0.5H), 2.919(m, 0.5H), 2.086(m, 1H), 2.008(s, 1.5H), 1.993(s, 1.5H), 1.805-1.469(m, 5H)