Journal of the American Chemical Society
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(10) For other non-enantioselective intermolecular hydroamina-
ral PHOX ligand, is an efficient and highly enantioselective
catalyst for the intermolecular hydroamination of dienes
with aliphatic amines. Diene and ligand electronics have a
dramatic effect on product distribution, and a more electron
deficient phosphine ligand significantly increases catalyst
reactivity. Current studies are focused on further elucidating
the reaction mechanism and related methods development.
tions with alkyl amines, see: (a) Ickes, A. R.; Ensign, S. C.; Hull, K. L.
J. Am. Chem. Soc. 2014, 136, 11256. (b) Ensign, S. C.; Vanable, E. P.;
Kortman, G. D.; Weir, L. J.; Hull, K. L. J. Am. Chem. Soc. 2015, 137,
13748. (c) Musacchio, A. J.; Lainhart, B. C.; Zhang, X.; Naguib, S. G.;
Sherwood, T. C.; Knowles, R. R. Science 2017, 355, 727.
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(11) For non-enantioselective intermolecular hydroamination of this
class of dienes with anilines and alkyl amines, see: (a) Minami, T.;
Okamoto, H.; Ikeda, S.; Tanaka, R.; Ozawa, F.; Yoshifuji, M. Angew.
Chem., Int. Ed. 2001, 40, 4501. (b) Goldfogel, M. J.; Roberts, C. C.;
Meek, S. J. J. Am. Chem. Soc. 2014, 136, 6227. (c) Banerjee, D.; Junge,
K.; Beller, M. Org. Chem. Front. 2014, 1, 368.
ASSOCIATED CONTENT
Supporting Information
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Experimental procedures and analytical data for new com-
pounds. This material is available free of charge via the In-
(12) For intramolecular enantioselective hydroamination of dienes,
see: (a) Hong, S.; Kawaoka, A. M.; Marks, T. J. J. Am. Chem. Soc.
2003, 125, 15878. (b) Deschamp, J.; Olier, C.; Schulz, E.; Guillot, R.;
Hannedouche, J.; Collin, J. Adv. Synth. Catal. 2010, 352, 2171. (c)
Shapiro, N. D.; Rauniyar, V.; Hamilton, G. L.; Wu, J.; Toste, F. D.
Nature 2011, 470, 245. (d) Kanno, O.; Kuriyama, W.; Wang, Z. J.;
Toste, F. D. Angew. Chem., Int. Ed. 2011, 50, 9919.
AUTHOR INFORMATION
Corresponding Author
(13) For select examples of other catalytic enantioselective intermo-
lecular reactions of acyclic 1,3-dienes, see: (a) Shirakura, M.;
Suginome, M. Angew. Chem., Int. Ed. 2010, 49, 3827. (b) Zbieg, J. R.;
Moran, J.; Krische, M. J. J. Am. Chem. Soc. 2011, 133, 10582. (c) Schus-
ter, C. H.; Li, B.; Morken, J. P. Angew. Chem., Int. Ed. 2011, 50, 7906.
(d) Watkins, A. L.; Landis, C. R. Org. Lett. 2011, 13, 164. (e) Zbieg, J.
R.; Yamaguchi, E.; McIntuff, E. L.; Krische, M. J. Science 2012, 336,
324. (f) Kliman, L. T.; Mlynarski, S. N.; Ferris, G. E.; Morken, J. P.
Angew. Chem., Int. Ed. 2012, 51, 521. (g) McIntuff, E. L.; Yamaguchi,
E.; Krische, M. J. J. Am. Chem. Soc. 2012, 134, 20628. (h) Ebe, Y.;
Nishimura, T. J. Am. Chem. Soc. 2014, 136, 9284. (i) Stokes, B. J.; Liao,
L.; de Andrade, A. M.; Wang, Q.; Sigman, M. S. Org. Lett. 2014, 16,
4666. (j) Timsina, Y. N.; Sharma, R. K.; RajanBabu, T. V. Chem. Sci.
2015, 6, 3994. (k) Wu, X.; Lin, H-C.; Li, M-L.; Li, L-L.; Han, Z-Y.;
Gong, L-Z. J. Am. Chem. Soc. 2015, 137, 13476. (l) Liu, Y.; Xie, Y.;
Wang, H.; Huang, H. J. Am. Chem. Soc. 2016, 138, 4314.
*steven.malcolmson@duke.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to Duke University for sponsoring this re-
search. N. J. A. was supported by NIGMS (T32GM007105–42).
We thank Katherine Wilbur for experimental assistance.
REFERENCES
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(14) For Pd-catalyzed hydroamination with achiral P,N-ligands, see:
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J. Am. Chem. Soc. 2015, 137, 8392. For intermolecular enantioselective
hydroamination of allenes to generate allylic amines, see: (b) Butler,
K. L.; Tragni, M.; Widenhoefer, R. A. Angew. Chem., Int. Ed. 2012, 51,
5175. (c) Kim, H.; Lim, W.; Im, D.; Kim, D-g.; Rhee, Y. H. Angew.
Chem., Int. Ed. 2012, 51, 12055. For a review concerning other exam-
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(3) Löber, O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2001,
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(4) For enantioselective Pd-catalyzed aniline additions to styrenes,
see: (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122,
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(16) Amine attack upon the original η3-allyl Pd salt generates an
ammonium salt that oxidatively protonates Pd, initiating catalysis.
(5) For mechanistic studies of Pd-catalyzed styrene and diene hy-
droamination with anilines, see: (a) Nettekoven, U.; Hartwig, J. F. J.
Am. Chem. Soc. 2002, 124, 1166. (b) Johns, A. M.; Utsunomiya, M.;
Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 1828. For a
study with a Ni catalyst and alkyl amines, see: (c) Pawlas, J.; Nakao,
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(17) See the Supporting Information for details.
(18) For reviews, see: (a) Helmchen, G.; Pfaltz, A. Acc. Chem. Res.
2000, 33, 336. (b) Bausch, C. C.; Pfaltz, A.; PHOX Ligands. In Privi-
leged Chiral Ligands and Catalysts; Zhou, Q-L., Ed.; Wiley-VCH:
Weinheim, Germany, 2011; Chapter 6. (c) Liu, Y.; Han, S-J.; Liu, W-B.,
Stoltz, B. M. Acc. Chem. Res. 2015, 48, 740.
(6) Yang, X-H.; Dong, V. M. J. Am. Chem. Soc. 2017, 139, 1774.
(19) Other Ag salts afford greater quantities of achiral 3a although
the er of 2a is largely invariant. Additionally, polar solvents lead to
greater product yields with CH2Cl2 proving optimal.
(7) Teng, H-L.; Luo, Y.; Wang, B.; Zhang, L.; Nishiura, M.; Hou, Z.
Angew. Chem., Int. Ed. 2016, 55, 15406.
(8) For other intermolecular enantioselective hydroaminations with
alkyl amines, see: (a) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem.
Soc. 2003, 125, 14286. (b) Reznichenko, A. L.; Nguyen, H. N.;
Hultzsch, K. C. Angew. Chem., Int. Ed. 2010, 49, 8984.
(20) Tani, K.; Behenna, D. C.; McFadden, R. M.; Stoltz, B. M. Org.
Lett. 2007, 9, 2529.
(21) 1,4-disubstituted dienes fail to generate hydroamination prod-
uct. Other substitution patterns deliver 1,4-hydroamination or a
complex mixture. See the Supporting Information.
(9) For intermolecular enantioselective hydroaminations with N-
nucleophiles other than amines, see: (a) Zhang, Z.; Du Lee, S.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2009, 131, 5372. (b) Sevov, C. S.;
Zhou, J. (S.); Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 11960.
(22) Product 2q is obtained in 53% yield, 12:1 2q:3q, and 93:7 er after
17 h at 0 ˚C with L5.
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