Refluxing in benzene with iodine afforded the thermodynamically more stable geometrical isomer
((Z)-1b) in an E/Z ratio of 22/78. Similarly, (E)-1b was obtained in an E/Z ratio of 97/3 in 34% overall
yield, which was relatively unstable to show an E/Z ratio of 82/18 after being stored at –20 °C for 1 week.
In conclusion, we have shown a synthesis of (Z)- and (E)-pulchellalactams (1a) from commercially
available citraconic anhydride. Interestingly, the product ratio in the aldol reaction highly depended on
the reaction time and temperature to give the (E)- and (Z)-isomers, regioselectively.
ACKNOWLEDGEMENTS
We thank Dr. Khisal A. Alvi of AMRI Bothell Research Center for providing the NMR spectra data of
pulchellalactam and for scientific discussions on the stereochemistry of pulchellalactam. This work was
supported in part by a Grant-in-Aid (No.14540491) for Scientific Research from Japan Society for the
Promotion of Science.
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9. The geometrical selectivity was determined by 1H NMR spectrometry before deprotection of the Boc
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10. (Z)-1a: monoclinic (P21/c); a=11.9896(45)Å, b=6.9290(34)Å, c=12.5863(32)Å; β= 115.698(20)°,
Z=4, R1(wR2)=0.0662(0.1679). (E)-1a: monoclinic (P21/c); a=9.6464(158)Å, b=8.4541(63)Å,
c=11.7772(54)Å; β= 107.423(67)°, Z=4, R1(wR2)=0.0591(0.0809).