(3S)-3-[tert-butyl(dimethyl)silyl]oxyoxolan-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.92 g (38.4 mmol) of (S)-3-hydroxybutyrolactone with 5.23 g (2 equivalents, 76.8 mmol) of imidazole are introduced at 0° C. into 50 ml of absolute DMF. 7.53 g (1.3 equivalents, 49.92 mmol) of TBSCl is now slowly added and stirred for 2.5 hours.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b, 6 g, 27.8 mmol) in methanol (40 mL) was added potassium carbonate (500 mg, 3.6 mmol). The reaction was refluxed overnight. The methanol was removed in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to yield (S)-methyl 2-(tert-butyldimethylsilyloxy)-4-hydroxybutanoate (91c, 3.9 g, 15.7 mmol) as a clear oil. [M+H] calc'd for C11H24O4Si, 249. found, 249. The reaction was refluxed overnight The methanol was removed in vacuo the residue partitioned between ethyl acetate and water The organic phase was washed with H2O×2 dried over anhydrous sodium sulfate The solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b, 6 g, 27.8 mmol) in methanol (40 mL) was added potassium carbonate (500 mg, 3.6 mmol). The reaction was refluxed overnight. The methanol was removed in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to yield (S)-methyl 2-(tert-butyldimethylsilyloxy)-4-hydroxybutanoate (91c, 3.9 g, 15.7 mmol) as a clear oil. [M+H] calc'd for C11H24O4Si, 249. found, 249. The reaction was refluxed overnight The methanol was removed in vacuo the residue partitioned between ethyl acetate and water The organic phase was washed with H2O×2 dried over anhydrous sodium sulfate The solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-hydroxydihydrofuran-2(3H)-one (91a, 5 g, 49 mmol) in anhydrous DMF (40 mL) was added imidazole (6.7 g, 98 mmol) and TBDMS-chloride (8.1 g, 54 mmol) and the reaction is stirred for 3 h. The reaction was diluted with diethyl ether and washed with 1N HCl×3. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed in vacuo to yield (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b) as a clear oil (10.6 g, 49 mmol). 1H NMR (400 MHz, CHLOROFORM-d) δ 0.15 (s, 3H), 0.18 (s, 3H), 0.86-0.99 (m, 9H), 2.23 (dq, J=12.63, 8.67 Hz, 1H), 2.46 (dddd, J=12.63, 7.58, 6.57, 3.28 Hz, 1H), 2.84-3.01 (m, 1H), 4.20 (td, J=9.16, 6.44 Hz, 1H), 4.33-4.47 (m, 2H). washed with 1N HCl×3 The organic phase was dried over anhydrous sodium sulfate the solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.92 g (38.4 mmol) of (S)-3-hydroxybutyrolactone with 5.23 g (2 equivalents, 76.8 mmol) of imidazole are introduced at 0° C. into 50 ml of absolute DMF. 7.53 g (1.3 equivalents, 49.92 mmol) of TBSCl is now slowly added and stirred for 2.5 hours.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b, 6 g, 27.8 mmol) in methanol (40 mL) was added potassium carbonate (500 mg, 3.6 mmol). The reaction was refluxed overnight. The methanol was removed in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to yield (S)-methyl 2-(tert-butyldimethylsilyloxy)-4-hydroxybutanoate (91c, 3.9 g, 15.7 mmol) as a clear oil. [M+H] calc'd for C11H24O4Si, 249; found, 249. The reaction was refluxed overnight The methanol was removed in vacuo the residue partitioned between ethyl acetate and water The organic phase was washed with H2O×2 dried over anhydrous sodium sulfate The solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-hydroxydihydrofuran-2(3H)-one (91a, 5 g, 49 mmol) in anhydrous DMF (40 mL) was added imidazole (6.7 g, 98 mmol) and TBDMS-chloride (8.1 g, 54 mmol) and the reaction is stirred for 3 h. The reaction was diluted with diethyl ether and washed with 1N HCl×3. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed in vacuo to yield (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b) as a clear oil (10.6 g, 49 mmol). 1H NMR (400 MHz, CHLOROFORM-d) δ 0.15 (s, 3H), 0.18 (s, 3H), 0.86-0.99 (m, 9H), 2.23 (dq, J=12.63, 8.67 Hz, 1H), 2.46 (dddd, J=12.63, 7.58, 6.57, 3.28 Hz, 1H), 2.84-3.01 (m, 1H), 4.20 (td, J=9.16, 6.44 Hz, 1H), 4.33-4.47 (m, 2H). washed with 1N HCl×3 The organic phase was dried over anhydrous sodium sulfate the solvent was removed in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl lithium (670 μl [1.11 mmol, 1.1 equiv] of a 1.65 M solution in diethyl ether) is added dropwise to a stirred solution of (S)-2-(tertbutyidimethylsilyloxy)-γ-butyrolactone 12 (218 mg, 1.01 mmol) in THF (4.0 ml) cooled to −78° C. is added dropwise. After stirring at −78° C. for 3 h, the reaction is quenched by the addition of glacial acetic acid (72 μl, 1.26 mmol, 1.25 equiv). Diethyl ether (20 ml) and saturated aqueous sodium bicarbonate solution (10 ml) are added. After stirring for 5 min the organic layer is separated and the aqueous layer is extracted with diethyl ether (2×20 ml). The combined organic extracts are dried over magnesium sulfate and concentrated in vacua. Crude (3S)-3-(tertbutyidimethylsilyloxy)-2-hydroxy-2-methyl-tetrahydrofurane 13 (235 mg, 93%) is obtained as a colourless crystalline solid (mixture of diastereomers) which is used for the synthesis of (S)-3,5-di-(tert-butyldimethylsilyloxy)-pentan-2-one 14 without further purification. is added dropwise After stirring for 5 min the organic layer is separated the aqueous layer is extracted with diethyl ether (2×20 ml) The combined organic extracts are dried over magnesium sulfate concentrated in vacua

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Imidazole (241 mg, 3.54 mmol, 2.2 equiv) and tert-butyl-dimethylsilyl chloride (267 mg, 1.77 mmol, 1.1 equiv) are added to a solution of (3S)-dihydro-3-hydroxy-2(3H)-furanone 11 (164 mg, 1.61 mmol) in dimethyl formamide (1.5 ml). The mixture is stirred for 24 h at r.t. Purification of the reaction mixture by flash column chromatography (pentane/diethyl ether 10:1) affords (S)-2-(tert-butyidimethylsilyloxy)-γ-butyrolactone 12 (321 mg, 93%) as a colourless oil. [α]D20=−31.7; [α]54620=−37.4 (c=0.86, CHCl3); 13C-NMR (100 MHz, CDCL3): δ(ppm)=175.8; 68.2; 64.7; 32.3; 25.6; 18.2; −4.8; −5.3 Purification of the reaction mixture by flash column chromatography (pentane/diethyl ether 10:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b, 6 g, 27.8 mmol) in methanol (40 mL) was added potassium carbonate (500 mg, 3.6 mmol). The reaction was refluxed overnight. The methanol was removed in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was washed with H2O×2 and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to yield (S)-methyl 2-(tert-butyldimethylsilyloxy)-4-hydroxybutanoate (91c, 3.9 g, 15.7 mmol) as a clear oil. [M+H] calc'd for C11H24O4Si, 249. found, 249. The reaction was refluxed overnight The methanol was removed in vacuo the residue partitioned between ethyl acetate and water The organic phase was washed with H2O×2 dried over anhydrous sodium sulfate The solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-3-hydroxydihydrofuran-2(3H)-one (91a, 5 g, 49 mmol) in anhydrous DMF (40 mL) was added imidazole (6.7 g, 98 mmol) and TBDMS-chloride (8.1 g, 54 mmol) and the reaction is stirred for 3 h. The reaction was diluted with diethyl ether and washed with 1N HCl×3. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed in vacuo to yield (S)-3-(tert-butyldimethylsilyloxy)dihydrofuran-2(3H)-one (91b) as a clear oil (10.6 g, 49 mmol). 1H NMR (400 MHz, CHLOROFORM-d) δ 0.15 (s, 3H), 0.18 (s, 3H), 0.86-0.99 (m, 9H), 2.23 (dq, J=12.63, 8.67 Hz, 1H), 2.46 (dddd, J=12.63, 7.58, 6.57, 3.28 Hz, 1H), 2.84-3.01 (m, 1H), 4.20 (td, J=9.16, 6.44 Hz, 1H), 4.33-4.47 (m, 2H). washed with 1N HCl×3 The organic phase was dried over anhydrous sodium sulfate the solvent was removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.92 g (38.4 mmol) of (S)-3-hydroxybutyrolactone with 5.23 g (2 equivalents, 76.8 mmol) of imidazole are introduced at 0° C. into 50 ml of absolute DMF. 7.53 g (1.3 equivalents, 49.92 mmol) of TBSCl is now slowly added and stirred for 2.5 hours.