Journal of the American Chemical Society
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(35) Since azadiene 16 has a poor solubility in PhMe, 32 was used for
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(37) The pKa’s of 4-methoxyaniline and 3-methoxyaniline differ by
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(38) The reactions at rt gave no enantioselectivity.
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(40) This observation is consistent with ref 39.
(41) For the determination of absolute configuration, see Supporting
Information.
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(42) Unlike the situation when ZnI2 is used as catalyst in absence of
BOPA (see Table 1), stirring azadiene 16 with 3 equiv of nitro-alkene
17 with 10 mol % Zn(OTf)2 and F-BOPA ligand at rt for 16 h did not
lead to the formation of the 2:1 adduct as judged by MS.
(43) There is no reaction at rt without ZnII, so an uncatalyzed
pathway can be ruled out. The reaction is also irreversible at rt since
no nitro-alkene exchange takes place when the cycloadduct (no
reductive workup) is subject to the reaction conditions with another
nitro-alkene.
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(22) For an elegant catalytic enantioselective synthesis of 3-
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Tan, Y.; Liu, W.-J.; Zhang, Z.-C.; Sun, X.-W.; Lin, G.-Q. Chem.
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(23) For results of the high-throughput screen, please see Supporting
Information.
(24) The 2:1 adduct is observed by 1H NMR of the unpurified
reaction mixture and by MS but has, to date, resisted isolation and
characterization.
(25) For example, other bisoxazoline ligands such as BOX or PYBOX
gives low enantioselectivity. See Supporting Information for details.
(26) BOPA ligands have been used in Zn-catalyzed enantioselective
Michael addition to nitro-alkenes; see: Lu, S. F.; Du, D.-M.; Xu, J. Org.
Lett. 2006, 8, 2115−2118.
(27) Due to the sensitive nature of the tetrahydropyridine, we sought
to adopt a reductive workup procedure to reduce the enamine
functionality and found that the crude tetrahydropyridine can be
reduced to stable 3-nitropiperidine with ZnCl2 and NaBH3CN in
MeOH.
(28) In constrast to the racemic reaction, ZnI2 does not give any
product. Although DME and dioxane are the optimal solvents for the
racemic reaction, their use gives lower ee than PhMe. See Supporting
Information for the results of solvent screen.
(29) Liu, H.; Lu, S.-F.; Xu, J.; Du, D.-M. Chem.Asian J. 2008, 3,
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H
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX