Aluminium amalgam was prepared by dipping 0.5cm wide strips of aluminium foil (4.79g, 177.5mmol) in a solution of mercuric chloride (1.5g) in water (150ml) for 15sec, then washing sequentially with ethanol and diethyl ether. The freshly prepared aluminium amalgam strips were then quickly transferred into a solution of the (2'S, 3S/R)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)-4-oxo-3-phenylsulfonyl-butnoyl-glycylglycine methyl ester (12) (2.64g, 5.47mmol) in methanol (400ml) under reflux. The mixture was stirred at reflux for 24h, then cooled to room temperature and filtered. The resulting solution was concentrated to ca. 20ml under reduced pressure, then mixed with ethyl acetate (300ml), washed with saturated sodium chloride (300ml), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 1:1) to give (2'S)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)-4-oxo-butanoylglycylglycin methyl ester (15) (1.25g, 66%) as a colourless oil, [alpha]D -42deg (c 1.0, dichloromethane).

Proton Nmr (ca. 1:1 mixture of rotamers) deltaH (300MHz, CDCl3) 1.36(4.5H, s, OC(CH3)3 rotamer), 1.41(4.5H, s, OC(CH3)3 rotamer), 2.16-1.81(4H, m, 2xCH2), 2.56-2.49(2H, m, CH2CO), 2.84-2.73(2H, m, CH2CO), 3.51-3.37(2H, m, CH2NBoc), 3.70(1.5H, s, OCH3 rotamer), 3.72(1.5H, s, OCH3 rotamer), 3.98(2H, m, CH2CO2Me), 4.23(0.5H, dd, J=5.0, 9.0Hz, CHNBoc rotamer), 4.31(0.5H, dd, J=5.0, 9.0Hz, CHNBoc rotamer), 6.19(0.5H, br. s, NH rotamer), 6.28(0.5H, br. s, NH rotamer); Vmax: 3333, 1756, 1694, 1625cm^-1; m/z (NH3, CI) 360(M+NH4⁺, 100%), 343(M+H⁺, 40%), 345(42%). Found [M+NH4]⁺ 360.2125, C16H30N3O6 requires 360.2134.

Preparation of (2'S)-4-(N-tert-Butoxycarbonylpyrrolidin-2-yl)-4-oxo-butanoylglycyl-L-alaine Methyl Ester (16)

Aluminium amalgam was prepared by dipping 0.5cm wide strips of aluminium foil (9.90g, 366.94mmol) in a solution of mercuric chloride (2.24g) in water (150ml) for 15sec., then washing sequentially with ethanol and diethyl ether. The freshly prepared aluminium amalgam strips were then quickly transferred into a solution of the (2'S, 3S/R)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)-4-oxo-3-phenylsulfonyl-butnoyl-glycyl-L-alanine methyl ester (13) (6.05g, 12.18mmol) in methanol (500ml) under reflux. The mixture was stirred at reflux for 24h, then cooled to room temperature and filtered. The resulting solution was concentrated to ca. 50ml under reduced pressure, then mixed with ethyl acetate (300ml), washed with saturated sodium chloride (200ml), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 1:1) to give (2'S)-4-(N-tert-butoxycarbonylpyrrolidin-2-yl)-4-oxo-butanoylglycyl-L-alaine methyl ester (16) (2.72g, 64%) as a colourless oil, [alpha]D -45deg (c 1.0, dichloromethane).

Proton Nmr (ca. 1:1 mixture of rotamers) deltaH (300MHz, CDCl3) 1.37(4.5H, s, OC(CH3)3 rotamer), 1.42(4.5H, s, OC(CH3)3 rotamer), 1.42(3H, m, CH3), 1.52-2.17(4H, m, 2xCH2), 2.38-2.54(2H, m, CH2CO), 2.64-2.90(2H, m, CH2CO), 3.37-3.52(2H, m, CH2NBoc), 3.71(1.5H, s, OCH3 rotamer), 3.72(1.5H, s, OCH3 rotamer), 4.23(0.5H, dd, J=5.5, 8.5Hz, CHNBoc rotamer), 4.33(0.5H, dd, J=4.5, 8.5Hz, CHNBoc rotamer), 4.49-4.57(m, 1H, CHMe), 6.18(0.5H, br. d, J=8.5Hz, NH rotamer), 6.23(0.5H, br. d, J=8.5Hz, NH rotamer); Vmax: 3334, 1747, 1691cm^-1; m/z(NH3, CI) 374(M+NH4⁺, 100%), 357(M+H⁺, 64%), 359(33%). Found [M+H]⁺ 357.2023, C17H29N2O6 requires 357.2025.