RESEARCH
| REPORT
Fig. 4. Experiments to probe reaction mechanism. (A) Aminoarylation with (Z)-anethole (28). (B) Tracking reaction progress for aminoarylation with
Z)-anethole (28) [triangles, 2; red squares, (Z)-anethole; diamonds, 9; purple squares, (E)-anethole]. (C) Determination of the photostationary state for
anethole isomers catalyzed by 3. (D) Favored and disfavored conformations for intermediate III.
(
diastereomer as a result of bond rotation out-
competing cyclization of intermediate III. Nota-
bly, performing the title aminoarylation with
arylation. Given the current availability of sulfon-
amide building blocks along with the ubiquity of
alkenes as feedstock substrates, we view the method
to be a highly enabling platform for research efforts
synthesizing the arylethylamine pharmacophore
diastereoselectively in a single operation.
20. G. J. Choi, R. R. Knowles, J. Am. Chem. Soc. 137, 9226–9229
2015).
(
21. D. C. Miller, G. J. Choi, H. S. Orbe, R. R. Knowles, J. Am. Chem.
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(Z)-anethole afforded a nearly identical yield of 9
22. K. A. Margrey, D. A. Nicewicz, Acc. Chem. Res. 49, 1997–2006
(2016).
(72%), in comparison to (E)-anethole (82%), whereas
diastereomer 9′ was not observed (Fig. 4A). Re-
23. T. M. Nguyen, N. Manohar, D. A. Nicewicz, Angew. Chem. Int.
Ed. 53, 6198–6201 (2014).
1
action progress analysis by H nuclear magnetic
24. N. J. Gesmundo, J.-M. M. Grandjean, D. A. Nicewicz, Org. Lett.
17, 1316–1319 (2015).
resonance spectroscopy of (Z)-anethole amino-
arylation revealed that (E)-anethole is generated
during the reaction (Fig. 4B). On the basis of this
observation, we examined the rates of isomeriza-
tion for each anethole isomer to the photostationary
state (Fig. 4C). This revealed a photostationary
state of 1.4:1 (Z:E), with the initial rate of (Z)-
anethole isomerization being much faster than
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Overall, these mechanistic details describe
how the combination of a Smiles-Truce aryl trans-
fer and radical cation chemistry can be combined
into a highly diastereoconvergent alkene amino-
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