Journal of the American Chemical Society
Article
(5) For pioneering studies, see: (a) Ismagilov, R. F. J. Org. Chem. 1998,
63, 3772−3774. (b) Luukas, T. O.; Girard, C.; Fenwick, D. R.; Kagan, H.
B. J. Am. Chem. Soc. 1999, 121, 9299−9306. (c) Johnson, D. W., Jr.;
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(6) Pellissier, H. Chirality from Dynamic Kinetic Resolution; Royal
Society of Chemistry: London, 2011.
(7) For two very recent examples of catalytic enantioconvergent
reactions (not DKR), see: (a) Terada, M.; Ota, Y.; Li, F.; Toda, Y.;
Kondoh, A. J. Am. Chem. Soc. 2016, 138, 11038−11043. (b) Kainz, Q.
M.; Matier, C. M.; Bartoszewicz, A.; Zultanski, S. L.; Peters, J. C.; Fu, G.
C. Science 2016, 351, 681−684. In addition to the mechanisms
illustrated in Figure 3, other pathways for enantioconvergence are
possible (e.g., interconverting intermediates).
(8) For overviews and leading references, see: (a) Rachwalski, M.;
Vermue, N.; Rutjes, F. P. J. T. Chem. Soc. Rev. 2013, 42, 9268−9282.
(b) Steinreiber, J.; Faber, K.; Griengl, H. Chem. - Eur. J. 2008, 14, 8060−
8072. (c) Wolf, C. Dynamic Stereochemistry of Chiral Compounds; Royal
Society of Chemistry: Cambridge, 2008.
Figure 9. Product ee as a function of catalyst ee for a palladium-catalyzed
enantioconvergent coupling (eq 6).
(9) Stereoconvergence can also be achieved without the formation of
an intermediate; however, such processes are rare. For example, see: Ito,
H.; Kunii, S.; Sawamura, M. Nat. Chem. 2010, 2, 972−976.
of such transformations. In the context of two previously
reported enantioconvergent processes, we have demonstrated
that, by investigating the relationship between eeP and eeCAT
both at low and at high conversion, it is possible to gain insight
into the origin of a nonlinear effect, i.e., due to higher-order
species versus intrinsic.
(10) For examples of catalytic enantioconvergent reactions for which
an NLE study has been reported, see: (a) Fujiwara, Y.; Fu, G. C. J. Am.
Chem. Soc. 2011, 133, 12293−12297. (b) Wang, X.; Guo, P.; Han, Z.;
Wang, X.; Wang, Z.; Ding, K. J. Am. Chem. Soc. 2014, 136, 405−411.
(c) Jin, M.; Adak, L.; Nakamura, M. J. Am. Chem. Soc. 2015, 137, 7128−
7134. (d) Nakajima, K.; Shibata, M.; Nishibayashi, Y. J. Am. Chem. Soc.
2015, 137, 2472−2475. The possible complication of an intrinsic (vide
infra) nonlinear effect was not discussed in these reports.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
(11) Our conclusions also apply when the reaction proceeds via the
two-step mechanism shown in Figure 3b and the catalyst is not 100%
(12) The instantaneous enantioselectivity in the model described by
Thus, if eeSM > 0, then X < 1, which leads to product enantioselectivity
Mathematical analysis and experimental procedures
that is lower than erCAT
.
AUTHOR INFORMATION
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Corresponding Authors
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Support has been provided by the National Institutes of Health
(National Institute of General Medical Sciences: R01-
GM62871), the Swedish Research Council (Grant No.: 350-
2012-6645), and the Polish National Science Centre (Grant No.:
2014/15/D/ST5/02579). We thank Dr. David G. VanderVelde
(NMR Facility), Dr. Scott C. Virgil (Center for Catalysis and
Chemical Synthesis, supported by the Gordon and Betty Moore
Foundation), and Dr. Xu Quan for assistance.
(13) Kalek, M.; Fu, G. C. J. Am. Chem. Soc. 2015, 137, 9438−9442.
(14) For leading references, see: Fan, Y. C.; Kwon, O. Chem. Commun.
2013, 49, 11588−11619.
(15) Lussem, B. J.; Gais, H.-J. J. Am. Chem. Soc. 2003, 125, 6066−6067.
̈
(16) For a review with leading references, see: Moreno-Manas, M.;
Pleixats, R. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York, 2002; Vol. 2,
pp 1707−1767.
(17) Our observed selectivity factor (s ∼ 70) for the reaction in eq 6 is
comparable to that reported for the kinetic resolution of this allylic
carbonate by this chiral catalyst (Pd2(dba)3·CHCl3/ligand 3) with 2-
mercaptopyrimidine as the nucleophile: Gais, H.-J.; Jagusch, T.;
Spalthoff, N.; Gerhards, F.; Frank, M.; Raabe, G. Chem. - Eur. J. 2003,
9, 4202−4221.
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(18) The NLE that we observe (Figure 9) is not due to an interaction
between the enantioenriched product and the catalyst. Thus, addition of
enantiopure product, at the outset of the reaction, has no effect on the
course of the reaction.
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