(3aR,7aS)-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: There were weighed out 1,2-bis(hydroxymethyl)cyclohexane (7, meso compound) (144 mg, 1.00 mmol) and (S)-(−)-3,3,5,5-tetramethyl-4H-dinaphtho[2,1-c:1′,2′-e]-azepin-N-oxyl (3.0 mg, 1.00 mmol). Then, 2 ml of acetone was added to obtain a uniform solution. Two platinum electrodes (1.5×1.0 cm) were applied to the solution which was then subjected to an electrolytic oxidation reaction for 4 hours while being vigorously stirred at 0° C. and maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol). After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was effected with 5 ml of acetone and acetone was distilled off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1), giving (1R, 6S)-8-oxabicyclo[4.3.0]nonan-7-one (8) (cis lactone) (122 mg, yield 92%, optical purity 85%). to obtain a uniform solution was then subjected to an electrolytic oxidation reaction for 4 hours maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol) After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was distilled off The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: There were weighed out 1,2-bis(hydroxymethyl)cyclohexane (7, meso compound) (144 mg, 1.00 mmol) and (S)-(−)-3,3,5,5-tetramethyl-4H-dinaphtho[2,1-c:1′,2′-e]-azepin-N-oxyl (3.0 mg, 1.00 mmol). Then, 2 ml of acetone was added to obtain a uniform solution. Two platinum electrodes (1.5×1.0 cm ) were applied to the solution which was then subjected to an electrolytic oxidation reaction for 4 hours while being vigorously stirred at 0° C. and maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol). After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was effected with 5 ml of acetone and acetone was distilled off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane-7/1), giving (1R,6S)-8-oxabicyclo[4.3.0]nonan-7-one (8) (cis lactone) (122 mg, yield 92%, optical purity 85%). to obtain a uniform solution was then subjected to an electrolytic oxidation reaction for 4 hours maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol) After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was distilled off The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane-7/1)

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

Procedure: Under argon, a solution of diisopropylamine (3.85 ml, 27.5 mmol) in 20 ml of dry THF is cooled to 0° C. and slowly admixed with butyllithium (11 ml, 27.5 mmol, 2.5M in hexane). With ice-cooling. This solution is stirred for 15 min and then cooled to −78° C. and a solution of cis-8-oxabicyclo[4.3.0]nonan-9-one (3.5 g, 25 mmol) in 10 ml of THF is added dropwise. The mixture is stirred at −78° C. for another 30 min and then mixed with benzyl bromide (3.27 ml, 27 mmol). The mixture is then slowly warmed to room temperature and stirred for another 16 h. The solvent is removed and the residue is taken up in 20 ml of dichloromethane and washed 2× with in each case 20 ml of 2 M HCl. The organic phase is dried over magnesium sulphate, filtered and concentrated. The residue is purified by column chromatography (mobile phase: cyclohexane:ethyl acetate 10:1). With ice-cooling The mixture is stirred at −78° C. for another 30 min The mixture is then slowly warmed to room temperature stirred for another 16 h The solvent is removed washed 2× with in each case 20 ml of 2 M HCl The organic phase is dried over magnesium sulphate filtered concentrated The residue is purified by column chromatography (mobile phase: cyclohexane:ethyl acetate 10:1)

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

Procedure: Under argon, a solution of diisopropylamine (3.85 ml, 27.5 mmol) in 20 ml of dry THF is cooled to 0° C. and slowly admixed with butyllithium (11 ml, 27.5 mmol, 2.5M in hexane). With ice-cooling. This solution is stirred for 15 min and then cooled to −78° C. and a solution of cis-8-oxabicyclo[4.3.0]nonan-9-one (3.5 g, 25 mmol) in 10 ml of THF is added dropwise. The mixture is stirred at −78° C. for another 30 min and then mixed with benzyl bromide (3.27 ml, 27 mmol). The mixture is then slowly warmed to room temperature and stirred for another 16 h. The solvent is removed and the residue is taken up in 20 ml of dichloromethane and washed 2× with in each case 20 ml of 2 M HCl. The organic phase is dried over magnesium sulphate, filtered and concentrated. The residue is purified by column chromatography (mobile phase: cyclohexane:ethyl acetate 10:1). With ice-cooling The mixture is stirred at −78° C. for another 30 min The mixture is then slowly warmed to room temperature stirred for another 16 h The solvent is removed washed 2× with in each case 20 ml of 2 M HCl The organic phase is dried over magnesium sulphate filtered concentrated The residue is purified by column chromatography (mobile phase: cyclohexane:ethyl acetate 10:1)

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

Procedure: With stirring and ice-cooling, 80 ml of a solution of cis-cyclohexane-1,2-dicarboxylic anhydride (15.4 g, 100 mmol) in THF are added over a period of 10 min to a mixture of sodium borohydride (3.8 g, 100 mmol) in 20 ml of THF. The ice-bath is removed and the mixture is stirred for 2 h. 40 ml of 6 N hydrochloric acid are added carefully and the mixture is concentrated. 200 ml of water are added and the aqueous phase is extracted with ether. The organic phase is dried, filtered, concentrated and distilled under reduced pressure (123° C., 13 mm; 75° C., 0.5 mm). ice-cooling The ice-bath is removed the mixture is stirred for 2 h 40 ml of 6 N hydrochloric acid are added carefully the mixture is concentrated 200 ml of water are added the aqueous phase is extracted with ether The organic phase is dried filtered concentrated distilled under reduced pressure (123° C., 13 mm; 75° C., 0.5 mm)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: There were weighed out 1,2-bis(hydroxymethyl)cyclohexane (7, meso compound) (144 mg, 1.00 mmol) and (S)-(−)-3,3,5,5-tetramethyl-4H-dinaphtho[2,1-c:1′,2′-e]-azepin-N-oxyl (3.0 mg, 1.00 mmol). Then, 2 ml of acetone was added to obtain a uniform solution. Two platinum electrodes (1.5×1.0 cm) were applied to the solution which was then subjected to an electrolytic oxidation reaction for 4 hours while being vigorously stirred at 0° C. and maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol). After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was effected with 5 ml of acetone and acetone was distilled off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1), giving (1R, 6S)-8-oxabicyclo[4.3.0]nonan-7-one (8) (cis lactone) (122 mg, yield 92%, optical purity 85%). to obtain a uniform solution was then subjected to an electrolytic oxidation reaction for 4 hours maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol) After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was distilled off The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: There were weighed out 1,2-bis(hydroxymethyl)cyclohexane (7, meso compound) (144 mg, 1.00 mmol) and (S)-(−)-3,3,5,5-tetramethyl-4H-dinaphtho[2,1-c:1′,2′-e]-azepin-N-oxyl (3.0 mg, 1.00 mmol). Then, 2 ml of acetone was added to obtain a uniform solution. Two platinum electrodes (1.5×1.0 cm) were applied to the solution which was then subjected to an electrolytic oxidation reaction for 4 hours while being vigorously stirred at 0° C. and maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol). After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was effected with 5 ml of acetone and acetone was distilled off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1), giving (1R, 6S)-8-oxabicyclo[4.3.0]nonan-7-one (8) (cis lactone) (122 mg, yield 92%, optical purity 85%). to obtain a uniform solution was then subjected to an electrolytic oxidation reaction for 4 hours maintaining the current at 30 mA (quantity of electricity being 4.5 F/mol) After completion of reaction, silica gel was filtered off from the reaction mixture, extraction was distilled off The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=7/1)

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

Procedure: (1R,6S)-(+)-8-oxabicyclo[4.3.0]nonan-7-one (1 gram) was dissolved in 5 ml of absolute ethanol, followed by the addition of 0.5 gram of gaseous ammonia. The solution was kept in a stoppered flask, and the progress of the reaction was followed by thin layer chromatography (eluent dichloromethane/methanol 20:1). After the reaction was judged complete, the ethanol was evaporated and the resulting residue redissolved in ethyl acetate. Ammonia was removed by extraction with 1% HCl, and the ethyl acetate solution was dried over MgSO4, filtered, and rotary evaporated to leave 0.7 grams of (1S,2R)-2-hydroxymethyl-1-cyclohexanecarboxamide. The solution was kept in a stoppered flask the ethanol was evaporated the resulting residue redissolved in ethyl acetate Ammonia was removed by extraction with 1% HCl the ethyl acetate solution was dried over MgSO4 filtered rotary evaporated

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

Procedure: Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cyclohexane dimethanol (10.0 grams) is dissolved in 150 ml of acetone added to the glycine solution with stirring, followed by the addition of β-NAD+ (Sigma, 0.5 grams). To the resulting solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,6S)-(+)-8-oxabicyclo[4.3.0]nonan-7-one (8.5 grams) as a yellowish oil. After the enzyme has dissolved the pH the reaction mixture is stirred at 30° C During the reaction heating) extracted 3 times with 250 ml of methylene chloride followed by continuous extraction with 1 liter of ethyl acetate for 24 hours The ethyl acetate extract is dried over anhydrous magnesium sulfate evaporated under reduced pressure

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

Procedure: Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cyclohexane dimethanol (10.0 grams) is added to the glycine solution with stirring until dissolution occurs, followed by the addition of β-NAD+ (Sigma, 2 grams) and flavin mononucleotide (Sigma, 30 grams). To the resulting clear orange solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,6S)-(+)-8-oxabicydo[4.3.0]nonan-7-one (9 grams) as an orange oil. The product may be further purified by distillation at reduced pressure to yield a colorless oil, [∂]D=+46° c=1.1, chloroform. The enantiomeric excess is 98% as determined by chiral gas chromatography (Lipodex D column, column temperature 165=° C., injection temperature 180=° C., detector temperature=260° C.). After the enzyme has dissolved the pH the reaction mixture is stirred at 30° C During the reaction heating) extracted 3 times with 250 ml of methylene chloride followed by continuous extraction with 1 liter of ethyl acetate for 24 hours The ethyl acetate extract is dried over anhydrous magnesium sulfate evaporated under reduced pressure

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

Procedure: (1R,6S)-(+)-8-oxabicylo[4.3.0]nonan-7-one (1 gram) was dissolved in 5 ml of absolute ethanol, followed by the addition of 0.5 gram of gaseous ammonia. The solution was kept in a stoppered flask, and the progress of the reaction was followed by thin layer chromatography (eluent dichloromethane/methanol 20:1). After the reaction was judged complete, the ethanol was evaporated and the resulting residue redissolved in ethyl acetate. Ammonia was removed by extraction with 1% HCl, and the ethyl acetate solution was dried over MgSO4, filtered, and rotary evaporated to leave 0.7 grams of (1S,2R)-2-hydroxymethyl-1-cyclohexanecarboxamide. The solution was kept in a stoppered flask the ethanol was evaporated the resulting residue redissolved in ethyl acetate Ammonia was removed by extraction with 1% HCl the ethyl acetate solution was dried over MgSO4 filtered rotary evaporated

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

Procedure: Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cyclohexane dimethanol (10.0 grams) is dissolved in 150 ml of acetone added to the glycine solution with stirring, followed by the addition of β-NAD+ (Sigma, 0.5 grams). To the resulting solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,6S)-(+)-8-oxabicyclo[4.3.0]nonan-7-one (8.5 grams) as a yellowish oil. After the enzyme has dissolved the pH the reaction mixture is stirred at 30° C During the reaction heating) extracted 3 times with 250 ml of methylene chloride followed by continuous extraction with 1 liter of ethyl acetate for 24 hours The ethyl acetate extract is dried over anhydrous magnesium sulfate evaporated under reduced pressure