(1R,6R)-6-methylcyclohex-3-ene-1-carboxylic acid

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

Procedure: Test compounds: Liquid trimedlure (UOP Chemicals, East Rutherford, N.J.) (98% pure; density 1.02 g/ml) and ceralure (Agrisense/Biosys, Palo Alto, Calif.) (98% pure; density 1.43 g.ml) were purchased from commercial sources. The 2 g polymeric plug (Agrisense/Biosys, Palo Alto, Calif.) was the same product used by action agencies such as USDA-APHIS and California Department of Food and Agriculture (CDFA) in their surveillance and detection programs against medfly. The enantiomers of ceralure B1 (ethyl-cis-5-iodo-trans-2-methylcyclohexane-1-carboxylate) (henceforth referred to as the 1R,2R,5R and 1S,2S,5S enantiomers respectively) were synthesized using the 9 step process (described above) which yielded both enantiomers with high purity (97% ) and an overall yield of 15%. The racemic mixture of the two enantiomers was produced starting from racemic (5), which is (1RS, 6RS)-6-methyl-3-cyclohexene-1-carboxylic acid, using the above described process used to produce ethyl (1R,2R,5R)-5-iodo-2-methylcyclohexane-1-carboxylate (4a). were synthesized yielded both enantiomers with high purity (97% ) The racemic mixture of the two enantiomers was produced

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

Procedure: Test compounds: Liquid trimedlure (UOP Chemicals, East Rutherford, N.J.) (98% pure; density 1.02 g/ml) and ceralure (Agrisense/Biosys, Palo Alto, Calif.) (98% pure; density 1.43 g.ml) were purchased from commercial sources. The 2 g polymeric plug (Agrisense/Biosys, Palo Alto, Calif.) was the same product used by action agencies such as USDA-APHIS and California Department of Food and Agriculture (CDFA) in their surveillance and detection programs against medfly. The enantiomers of ceralure B1 (ethyl-cis-5-iodo-trans-2-methylcyclohexane-1-carboxylate) (henceforth referred to as the 1R,2R,5R and 1S,2S,5S enantiomers respectively) were synthesized using the 9 step process (described above) which yielded both enantiomers with high purity (97% ) and an overall yield of 15%. The racemic mixture of the two enantiomers was produced starting from racemic (5), which is (1RS, 6RS)-6-methyl-3-cyclohexene-1-carboxylic acid, using the above described process used to produce ethyl (1R,2R,5R)-5-iodo-2-methylcyclohexane-1-carboxylate (4a). were synthesized yielded both enantiomers with high purity (97% ) The racemic mixture of the two enantiomers was produced

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

Procedure: To a solution of optically active 5 (16.8 g, 120 mmol), in methylene chloride (200 mL) and water (400 mL), was added NaHCO3 (20.1 g, 240 mmol), KI (120 g, 0.720 mmol) and iodine (91.0 g, 0.360 mmol). The resulting mixture was protected from light and stirred for 24 h. The solution was cooled (0° C.) and sodium thiosulfate was carefully added until the dark iodine color disappeared. This was extracted with diethyl ether (4×300 mL). The combined organics were dried (MgSO4) and the volatiles were removed in vacuo to give a yellowish solid (27.8 g, 87% yield). This was carried onto the next step without further purification. Rf 0.33 (ethyl acetate/hexane 1:9); m.p. 99-100° C.; 1H NMR (300 MHz, CDCl3) δ 4.86 (dd, J=3.6, 5.9, 1H), 4.35-4.38 (m, 1H), 2.90 (m, 1H), 2.63-2.73 (m, 1H), 2.49-2.52 (m, 1H), 2.20-2.36 (m, 2H), 1.95-2.00 (m, 1H). 1.38 (d, J=7.2, 3H); 13C NMR (75 MHz, CDCl3) δ 178.2, 81.6, 43.8, 34.3, 29.3, 27.8, 19.5, 19.1; MS (EI) m/z 266 (M+, 4), 139 ([M-I]+, 80), 95 (100), 79 (16), 67 (26), 55 (29); [α]D−3.60° (c=2.22, CHCl3). This was extracted with diethyl ether (4×300 mL) The combined organics were dried (MgSO4) the volatiles were removed in vacuo

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

Procedure: To a cold (0° C.) solution of 7 (103.86 g, 0.286 mol), in 4:1 THF/water (500 mL), was added 30% hydrogen peroxide (160 mL, 1.40 mol), followed by lithium hydroxide (27.4 g, 0.652 mol). The resulting mixture was slowly allowed to warm to room temperature and after 4 h the reaction was complete. The solution was cooled (0° C.) and sodium sulfite (202 g, 1.6 mole) was added. The bulk of the THF was removed in vacuo and the resulting mixture (pH 12-13) was extracted with methylene chloride (5×200 mL) to remove the chiral auxiliary. The combined methylene chloride organics were dried (MgSO4) and the volatiles were removed in vacuo to yield 44.0 g (87% yield) of the recovered benzyloxazolidinone auxiliary. The aqueous layer was acidified to pH 1-2 with 12 M HCl and extracted with ethyl acetate (5×300 mL). The combined ethyl acetate extracts were dried (Na2SO4) and the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6). The methyl ester of 5 was shown to be at 97% ee on a 30 m Chiraldex column. Rf 0.40 (ethyl acetate/hexane 1:1); m.p. 65-66° C.; 1H NMR (300 MHz, CDCl3) δ 10.2-11.8 (b, 1H), 5.61-5.69 (m, 2H). 2.12-2.33 (m, 4H), 1.89-2.00 (m, 1H), 1.67-1.77 (m, 1H), 1.02 (d, J=6.6, 3H); 13C NMR (75 MHz, CDCl3) δ 182.3, 126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z 140 (M+, 21), 122 ([M-H2O]+, 16), 111 (14), 95 (100), 79 (75), 67 (49); [α]D−99.0° (c=4.89, CHCl3). extracted with ethyl acetate (5×300 mL) The combined ethyl acetate extracts were dried (Na2SO4) the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6)

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

Procedure: To a cold (0° C.) solution of 7 (103.86 g, 0.286 mol), in 4:1 THF/water (500 mL), was added 30% hydrogen peroxide (160 mL, 1.40 mol), followed by lithium hydroxide (27.4 g, 0.652 mol). The resulting mixture was slowly allowed to warm to room temperature and after 4 h the reaction was complete. The solution was cooled (0° C.) and sodium sulfite (202 g, 1.6 mole) was added. The bulk of the THF was removed in vacuo and the resulting mixture (pH 12-13) was extracted with methylene chloride (5×200 mL) to remove the chiral auxiliary. The combined methylene chloride organics were dried (MgSO4) and the volatiles were removed in vacuo to yield 44.0 g (87% yield) of the recovered benzyloxazolidinone auxiliary. The aqueous layer was acidified to pH 1-2 with 12 M HCl and extracted with ethyl acetate (5×300 mL). The combined ethyl acetate extracts were dried (Na2SO4) and the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6). The methyl ester of 5 was shown to be at 97% ee on a 30 m Chiraldex column. Rf 0.40 (ethyl acetate/hexane 1:1); m.p. 65-66° C.; 1H NMR (300 MHz, CDCl3) δ 10.2-11.8 (b, 1H), 5.61-5.69 (m, 2H). 2.12-2.33 (m, 4H), 1.89-2.00 (m, 1H), 1.67-1.77 (m, 1H), 1.02 (d, J=6.6, 3H); 13C NMR (75 MHz, CDCl3) δ 182.3, 126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z 140 (M+, 21), 122 ([M-H2O]+, 16), 111 (14), 95 (100), 79 (75), 67 (49); [α]D−99.0° (c=4.89, CHCl3). extracted with ethyl acetate (5×300 mL) The combined ethyl acetate extracts were dried (Na2SO4) the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6)

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

Procedure: Test compounds: Liquid trimedlure (UOP Chemicals, East Rutherford, N.J.) (98% pure; density 1.02 g/ml) and ceralure (Agrisense/Biosys, Palo Alto, Calif.) (98% pure; density 1.43 g.ml) were purchased from commercial sources. The 2 g polymeric plug (Agrisense/Biosys, Palo Alto, Calif.) was the same product used by action agencies such as USDA-APHIS and California Department of Food and Agriculture (CDFA) in their surveillance and detection programs against medfly. The enantiomers of ceralure B1 (ethyl-cis-5-iodo-trans-2-methylcyclohexane-1-carboxylate) (henceforth referred to as the 1R,2R,5R and 1S,2S,5S enantiomers respectively) were synthesized using the 9 step process (described above) which yielded both enantiomers with high purity (97% ) and an overall yield of 15%. The racemic mixture of the two enantiomers was produced starting from racemic (5), which is (1RS, 6RS)-6-methyl-3-cyclohexene-1-carboxylic acid, using the above described process used to produce ethyl (1R,2R,5R)-5-iodo-2-methylcyclohexane-1-carboxylate (4a). were synthesized yielded both enantiomers with high purity (97% ) The racemic mixture of the two enantiomers was produced

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

Procedure: To a solution of optically active 5 (16.8 g, 120 mmol), in methylene chloride (200 mL) and water (400 mL), was added NaHCO3 (20.1 g, 240 mmol), KI (120 g, 0.720 mmol) and iodine (91.0 g, 0.360 mmol). The resulting mixture was protected from light and stirred for 24 h. The solution was cooled (0° C.) and sodium thiosulfate was carefully added until the dark iodine color disappeared. This was extracted with diethyl ether (4×300 mL). The combined organics were dried (MgSO4) and the volatiles were removed in vacuo to give a yellowish solid (27.8 g, 87% yield). This was carried onto the next step without further purification. Rf 0.33 (ethyl acetate/hexane 1:9); m.p. 99-100° C.; 1H NMR (300 MHz, CDCl3) δ 4.86 (dd, J=3.6, 5.9, 1H), 4.35-4.38 (m, 1H), 2.90 (m, 1H), 2.63-2.73 (m, 1H), 2.49-2.52 (m, 1H), 2.20-2.36 (m, 2H), 1.95-2.00 (m, 1H). 1.38 (d, J=7.2, 3H); 13C NMR (75 MHz, CDCl3) δ 178.2, 81.6, 43.8, 34.3, 29.3, 27.8, 19.5, 19.1; MS (EI) m/z 266 (M+, 4), 139 ([M-I]+, 80), 95 (100), 79 (16), 67 (26), 55 (29); [α]D−3.60° (c=2.22, CHCl3). This was extracted with diethyl ether (4×300 mL) The combined organics were dried (MgSO4) the volatiles were removed in vacuo

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

Procedure: To a cold (0° C.) solution of 7 (103.86 g, 0.286 mol), in 4:1 THF/water (500 mL), was added 30% hydrogen peroxide (160 mL, 1.40 mol), followed by lithium hydroxide (27.4 g, 0.652 mol). The resulting mixture was slowly allowed to warm to room temperature and after 4 h the reaction was complete. The solution was cooled (0° C.) and sodium sulfite (202 g, 1.6 mole) was added. The bulk of the THF was removed in vacuo and the resulting mixture (pH 12-13) was extracted with methylene chloride (5×200 mL) to remove the chiral auxiliary. The combined methylene chloride organics were dried (MgSO4) and the volatiles were removed in vacuo to yield 44.0 g (87% yield) of the recovered benzyloxazolidinone auxiliary. The aqueous layer was acidified to pH 1-2 with 12 M HCl and extracted with ethyl acetate (5×300 mL). The combined ethyl acetate extracts were dried (Na2SO4) and the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6). The methyl ester of 5 was shown to be at 97% ee on a 30 m Chiraldex column. Rf 0.40 (ethyl acetate/hexane 1:1); m.p. 65-66° C.; 1H NMR (300 MHz, CDCl3) δ 10.2-11.8 (b, 1H), 5.61-5.69 (m, 2H). 2.12-2.33 (m, 4H), 1.89-2.00 (m, 1H), 1.67-1.77 (m, 1H), 1.02 (d, J=6.6, 3H); 13C NMR (75 MHz, CDCl3) δ 182.3, 126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z 140 (M+, 21), 122 ([M-H2O]+, 16), 111 (14), 95 (100), 79 (75), 67 (49); [α]D−99.0° (c=4.89, CHCl3). extracted with ethyl acetate (5×300 mL) The combined ethyl acetate extracts were dried (Na2SO4) the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6)