Conclusions
2.4. Experimental section
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The structure of the compound 47a was confirmed by the 1H, 13C, COSY, DEPT and X-ray analysis.
Figure 2.3.1 : ORTEP diagram is drawn with 30% probability elipsoid.
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procedure was used to prepare compounds 42b-g, 42i and 42j.10,14,25 N-tethered compounds 46a- 46g were prepared as per the literature procedures.10,14,26
2.4.3. General Procedure for preparation of O-tethered compounds 42a-j:
In an oven dried round bottom flask NaH (1.5 equiv.) was taken and dry tetrahydrofuran (THF) (20 mL) was added to it. To this a solution of propargyl alcohol (1 equiv.) or its derivatives were added slowly. The reaction mixture was stirred for 0.5 h at 0 C. Allyl bromide (1 equiv.) was added to the reaction mixture drop wise. The reaction was monitored by thin layer chromatography and after completion of the reaction, THF was removed by evaporation. The residue was extracted with ethyl acetate (30 ml), washed with water and brine solution (20 ml x 2). Organic layer was dried over anhydrous Na2SO4 and solvent was evaporated using rotary evaporator to give crude product. The crude product was purified on silica gel column chromatography using ethyl acetate and hexane as eluents. The ether (1.0 equiv.) thus obtained was treated with meta-chloroperbenzoic acid (m-CPBA) (1.5 equiv.) in dichloromethane (15 mL) at 0 oC. The reaction mixture was brought to room temperature and stirred for specific time.
After completion of the reaction which was found by TLC, a saturated aqueous solution of Na2SO3 was added to quench excess m-CPBA. Dichloromethane was added to the reaction mixture, washed with saturated sodium bicarbonate and brine solution, and dried over anhydrous Na2SO4. Evaporation of the solvent gave the crude product which was purified by neutral alumina using ethyl acetate and hexane as eluents.
Synthesis of 2-Phenyl-3-(((3-(p-tolyl)prop-2-yn-1-yl)oxy)methyl)oxirane (42b):
In an oven dried round bottom flask NaH ( 36 mg, 1.5 mmol ) was taken and dry THF (3 mL/mmol) was added to it. To this a solution 3-p-tolylprop-2-yn-1-ol (146 mg, 1mmol) were added slowly. After stirring for 0.5 h at 0 C, 3-Bromo-1-phenyl-1-propene (148 mg, 1 mmol) was added to the reaction mixture drop wise. The reaction was monitored by TLC and after completion of the reaction THF was removed by evaporation. The residue was extracted with ethyl acetate (10 ml), washed with water and brine solution (5 ml x 2). Organic layer was dried over anhydrous Na2SO4 and solvent was evaporated using rotary evaporator to give crude product. The crude product was purified on silica gel column chromatography using ethyl acetate and hexane as eluents. The 1-((E)-3-(3-p-tolylprop-2-ynyloxy)prop-1-enyl)benzene ( 262 mg, 1mmol) thus obtained was treated with meta-chloroperbenzoic acid (258 mg, 1.5 mmol) in dichloromethane (5 mL) at 0 oC. The reaction mixture was brought to room temperature and stirred for specific time. After completion of the reaction which was found by TLC, a saturated TH-1580_11612224
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aqueous solution of Na2SO3 was added to quench excess m-CPBA. Dichloromethane was added to the reaction mixture, washed with saturated sodium bicarbonate and brine solution, and dried over anhydrous Na2SO4. Evaporation of the solvent gave the crude product which was purified by neutral alumina using ethyl acetate and hexane as eluents over silica gel to give 2-Phenyl-3- (((3-(p-tolyl)prop-2-yn-1-yl)oxy)methyl)oxirane 42b (242 mg, 87%) as a colourless oil.
2.4.4. General Procedure for the Synthesis of N-tethered compounds 46a-g:
To an oven dried round bottom flask with magnetic stir bar was added allyl bromide (1.1 equiv.), 4-methylbenzenesulfonamide (1 equiv.), K2CO3 (2 equiv.) and acetone (5 mL/mmol). The round bottom flask was heated at 60 oC. Upon completion of the reaction (16 h), the solution was cooled to room temperature, filtered through a short plug of celite and washed with EtOAc, and solvent was removed in vacuo to afford a crude product. Purification of the resulting crude residue via silica gel flash column chromatography afforded the desired N-toysl allylic amine. In an oven dried round bottom flask NaH (1.5 equiv.) was taken and dry THF (20 mL) was added to it. To this a solution of N-tosyl allylic amine (1 equiv.) or its derivatives were added slowly. The reaction mixture was stirred for 0.5 h at 0 C. Propargyl bromide (1 equiv.) was added to the reaction mixture drop wise. The reaction was monitored by thin layer chromatography and after completion of the reaction THF was removed by evaporation. The residue was extracted with ethyl acetate (30 ml) and washed with water and brine solution (20 ml x 2). Organic layer was dried over anhydrous Na2SO4 and solvent was evaporated using rotary evaporator to obtain crude product. The crude product was purified on silica gel column chromatography using ethyl acetate and hexane as eluents to give the N-tethered product. The product (1.0 equiv.) thus obtained was treated with meta chloroperbenzoic acid (1.5 equiv.) in dichloromethane at 0 oC. The reaction mixture was brought to room temperature and stirred for specific time. After completion of the reaction which was found by TLC, a saturated aqueous solution of Na2SO3 was added to quench excess m-CPBA. Dichloromethane (30 mL) was added to the reaction mixture, washed with saturated sodium bicarbonate and brine solution, and dried over anhydrous Na2SO4. Evaporation of the solvent gave the crude product which was purified by neutral alumina using ethyl acetate and hexane as eluents.
Synthesis of 4-Methyl-N-((2-methyloxiran-2-yl)methyl)-N-(undec-2-yn-1- yl)benzenesulfonamide (46a):
To an oven dried round bottom flask with magnetic stir bar was added 3-Bromo-2- methylpropene (0.11 ml, 1.1 mmol), 4-Toluenesulfonamide (171mg, 1 mmol), K2CO3 (276 mg, 2mmol) and acetone (10 mL). The round bottom flask was heated at 60 0C. Upon completion of TH-1580_11612224
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the reaction (6 h), the solution was cooled to room temperature, filtered through a short plug of celite and washed with EtOAc, and solvent was removed in vacuo to afford a crude product.
Purification of the resulting crude residue via silica gel flash column chromatography afforded 2- methyl-N-tosylprop-2-en-1-amine. In an oven dried round bottom flask NaH ( 36 mg, 1.5 mmol) was taken and dry THF (10 mL) was added to it. To this a solution of 2-methyl-N-tosylprop-2- en-1-amine (225 mg, 1 mmol) was added slowly. After stirring for 0.5 h at 0 C, 1-bromopent-2- yne (230 mg,1 mmol) was added to the reaction mixture drop wise. The reaction was monitored by TLC and after completion of the reaction THF was removed by evaporation. The residue was extracted with ethyl acetate (20 ml) and washed with water and brine solution (10 ml x 2).
Organic layer was dried over anhydrous Na2SO4 and solvent was evaporated using rotary evaporator to obtain crude product. The crude product was purified on silica gel column chromatography using ethyl acetate and hexane as eluents to give N-(2-methylallyl)-N- tosylundec-2-yn-1-amine. The product (375 mg, 1.0 mmol) thus obtained was treated with meta- chloroperbenzoic acid (258 mg, 1.5 mmol) in dichloromethane at 0 oC. The reaction mixture was brought to room temperature and stirred for specific time. After completion of the reaction which was found by TLC, a saturated aqueous solution of Na2SO3 was added to quench excess mCPBA. Dichloromethane (30 mL) was added to the reaction mixture, washed with saturated sodium bicarbonate and brine solution, and dried over anhydrous Na2SO4. Evaporation of the solvent gave the crude product which was purified by neutral alumina using ethyl acetate and hexane as eluents to afford 4-Methyl-N-((2-methyloxiran-2-yl)methyl)-N-(undec-2-yn-1- yl)benzenesulfonamide 46a (352 mg, 90%) as a colourless oil.
2.4.5. General Procedure for Lewis Acid Catalyzed Intramolecular C−C Bond Formation of Alkyne-Epoxide 47a-j and 48a-g:
To a corresponding alkyne-epoxide substrates (1.0 equiv) in dichloromethane (5 ml) at 0 oC, BF3.Et2O (0.2 equiv.) was added drop wise and the reaction mixture was brought to room temperature. The reaction was continued for specified time and monitored by TLC. After completion of the reaction, the reaction mixture was treated with saturated sodium bicarbonate solution (5 ml). The product was extracted with CH2Cl2 (2 x 10 ml) and washed with brine.
Organic layer was separated and dried over anhydrous Na2SO4 and evaporated using rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography using ethyl acetate and hexane as eluents to afford the cyclic compounds 2.
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Synthesis of Phenyl(4-phenyl-3,6-dihydro-2H-pyran-3-yl)methanone (47a):
To 1-((Z)-3-(3-phenylprop-2-ynyloxy)prop-1-enyl)benzene 41a (248 mg, 1.0 mmol) in CH2Cl2
(5 mL/mmol) at 0 oC, BF3.Et2O (0.025 ml, 0.2 mmol) was added drop wise and the reaction mixture was brought to room temperature. The reaction was continued for specified time and monitored by TLC. After completion of the reaction, the reaction mixture was treated with saturated sodium bicarbonate solution (5 ml). The product was extracted with CH2Cl2 (2 x 10 ml) and washed with brine. Organic layer was separated and dried over anhydrous Na2SO4 and evaporated using rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography using ethyl acetate and hexane as eluents to afford Phenyl(4-phenyl-3,6-dihydro-2H-pyran-3-yl)methanone 47a, (179 mg, 68%) as a colourless solid.