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In the Mitsunobu reaction of 4a, the yield of 5a was improved by using toluene instead of THF as a solvent with a decrease in the amount of elimination product, a diene.
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The 2,4-anti/syn stereochemistry of the pyrrolidine ring was determined by a NOESY experiment on 2-(4-bromophenyl)-1-(4-methylbenzenesulfonyl)-4- (trifluoromethyl)pyrrolidine (7d) as a representative example. A cross peak between the 2- and 4-protons was not observed in the major product, but in the minor product. As for the 4-proton of the pyrrolidine ring, the signal of the anti-isomer was observed at lower field (δ 2.92) than that of the syn-isomer (δ 2.64), with this spectral criterion confirming similar stereochemistry for 7a-c.
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Attempted TEMPO-catalyzed oxidation of 10 with trichloroisocyanuric acid was not successful due to affecting the difluromethylene moiety.
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The 2,4-anti/syn stereochemistry of the pyrrolidine ring was determined by a NOESY experiment on TBS protected prolinol 14 as a representative example. Cross peaks between the 2-proton and the 5α-proton and between the 5β-proton and the difluoromethyl proton were observed as shown below.
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