Journal of the American Chemical Society
Page 8 of 9
GM058160. We would like to thank the National Institutes of
Health for a supplement under Awards number 3-R01-
GM058160-14S1. We thank Dr. Peter Müller (Massachusetts
Institute of Technology, MIT) for X-ray structural analysis.
We thank Dr. Yiming Wang (MIT) and Dr. Michael Pirnot
J. F. J. Am. Chem. Soc. 2004, 126, 5344. f) Driver, M. S.; Hartwig, J. F. J.
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Am. Chem. Soc. 1995, 117, 4708. g) Driver, M. S.; Hartwig, J. F. J. Am.
Chem. Soc. 1997, 119, 8232. h) Driver, M. S.; Hartwig, J. F. J. Am. Chem.
Soc. 1996, 118, 7217.
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4) a) Reductive Elimination, R. Hoffmann, in IUPAC. Frontiers of
Chemistry, ed. K. J. Laidler, Pergamon Press, Oxford 1982, 247-263. b)
Tatsumi, K. ; Hoffmann, R. ; Yamamoto, A. and Stille, J. K. Bull. Chem.
Soc., Japan, 1981, 54, 1857.
15) a) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2008, 130, 13552. b) Milner, P. J.; Maimone, T. J.; Su, M.;
Chen, J.; Müller, P.; Buchwald, S. L. J. Am. Chem. Soc. 2012, 134, 19922.
(
MIT) for assistance in preparation of the manuscript. We
would like to kindly thank the reviewers for detailed sugges-
tions and corrections of the manuscript.
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6) a) Biscoe, M. R.; Barder, T. E.; Buchwald, S. L. Angew. Chem. Int.
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REFERENCES
Ed 2007, 46, 7232. b) Biscoe, M. R.; Fors, B. P.; Buchwald, S. L. J. Am.
Chem. Soc. 2008, 130, 6686.
17) Lee, H. G.; Milner, P. J.; Buchwald, S. L. J. Am. Chem. Soc. 2014,
136, 3792.
18) Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028.
19) These reactions are often carried with an excess of phosphine lig-
and relative to the palladium metal for a range of palladium sources (e.g.
1
) a) Schlummer, B.; Scholz, U. Adv. Synth. Catal. 2004, 346, 1599. b)
Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338 c)
Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. Acc. Chem. Res
1998, 31, 805. c) Affouard, C.; Crockett, R. D.; Diker, K.; Farrell, R. P.;
Gorins, G.; Huckins, J. R.; Caille, S. Org. Process Res. Dev. 2015, 19, 476.
d) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U. Adv. Synth. Catal.
2
006, 348, 23. e) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27. f)
Pd
2
dba3, Pd(OAc) ) See for example: a) Kataoka, N.; Shelby, Q.; Stam-
2
Federsel, H.-J.; Hedberg, M.; Qvarnstrom, F. R.; Tian, Org. Process Res.
Dev. 2008, 12, 512.
buli, J. P.; Hartwig, J. F. J. Org. Chem., 67, 5553. b) Surry, D. S.; Buchwald,
S. J. Am. Chem. Soc. 2007, 129, 10354. c) Fors, B. P.; Krattiger, P.; Striet-
er, E.; Buchwald, S. L. Org. Lett. 2008, 10, 3505. d) Ruiz-Castillo, P.;
Blackmond, D. G.; Buchwald, S. J. Am. Chem. Soc. 2015, 137, 3085. e)
Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Chem. Sci. 2013, 4, 916.
20) See supporting information for derivation of this equation.
21) For reaction temperatures of 110 °C, 100 °C, and 90 °C gas chro-
matography experiments were used to quantify the rate of reaction. The
differential form of equation (1) was used (see supporting information).
2
) a) Cooper, T. W. J.; Campbell, I. B.; Macdonald, S. J. F. Angew.
Chem., Int. Ed. 2010, 49, 8082. b) Roughley, S. D.; Jordan, A. M. J. Med.
Chem. 2011, 54, 3451. c) Walters, W. P.; Green, J.; Weiss, J. R.; Murcko,
M. A. J. Med. Chem. 2011, 54.
3
) a) Louie, J.; Hartwig, J. F. Tetrahedron Lett.1995, 36, 3609. b) Lou-
ie, J.; Paul, F.; Hartwig, J. F. Organometallics 1996, 15, 2794. c) Guram, A.
S.; Buchwald, S. J. Am. Chem. Soc. 1994, 116, 7901. d) Paul, F.; Patt, J.;
Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969. e) Hartwig, J. F.; Paul,
F. J. Am. Chem. Soc. 1995, 117, 5373.
!
!"
=
(!"!"#$%) !"
ꢀ!"
Where c is the conversion of the limiting reagent and takes a (dimen-
sionless) value between 0 and 1. For a temperature of 78 °C, the reaction
was not homogenous, and thus calorimetry (which employs stirring) was
used.
4
) DPPF = 1,1'-bis(diphenylphosphino)ferrocene. BINAP = 2,2'-
bis(diphenylphosphine)-1,1'-binaphthalene
5) a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc. 1996,
1
18, 7215. b) Louie, J.; Driver, M. S.; Hamann, B. C.; Hartwig, J. F. J. Org.
Chem. 1997, 62, 1268. c) Wolfe, J. P.; Buchwald, S. L. 1999, 38, 2413.
) a) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998,
9, 2367. b) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett.
998, 39, 617. c) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaugh-
2
2) The values determined in this study are comparable to those
‡
‡
found for platinum based reductive eliminations. The ΔH and ΔS for
the reductive elimination of biaryl from Pt(PPh (C -pCH has
been reported to be 17.6 kcal/mol and -23 cal /(mol K). For the reduc-
tive elimination of ethane from Pt(Me I(PMePh ), the reported values
are 31 kcal/mol and 21 cal /(mol K). For the reductive elimination of
,1,1-trifluoroethane from cis-PtH(CH CF )(PPh the reported values
range from 25.4 to 23.9 kcal/mol and 7.8 to 2 cal /(mol K) and are de-
pendent upon the reaction solvent. For references, see a) Brown, M. P.;
Puddephatt, R. J.; Upton, C. E. E. J. Organomet. Chem. 1973, 49, C61. b)
Braterman, P. S.; Cross, R. J.; Young, G. B. J. Chem. Soc., Dalton Trans.
1977, 1892. c) Michelin, R. A.; Faglia, S.; Uguagliati, P. Inorg. Chem.
6
3
)
2
6
H
4
)
3 2
3
1
3
)
2 2
nessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64.
7) a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722. b) Anderson, K. W.; Tundel, R. E.; Ikawa, T.; Altman, R. A.;
Buchwald, S. L. Angew. Chem., Int. Ed., 2006, 45, 6523. c) Wolfe, J. P.;
Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65,
1
2
3
)
3 2
1
158.
) a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369.
8
b) Hartwig, J. F. Acc. Chem. Res., 41, 1534. c) Kataoka, N.; Shelby, Q.;
Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67, 5553.
9) a) Wolfe, J. P.; Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6359. b)
Marcoux, J.-F.; Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1997, 62, 1568.
c) Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 13848. d) Stauf-
fer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F. Org. Lett.
1
983, 22, 1831.
3) We attribute the difference to three factors: 1) The calculation of
2
the rate constant under catalytic conditions inherently overestimates the
stability of the amido complex IV since it does not consider other ele-
mentary steps such as oxidative addition, possible off-cycle palladium
species, or low level impurities that may deactivate a portion of the cata-
lyst. 2) The extrapolation to 40 °C is well outside the studied tempera-
ture range of 78 to 110 °C and 3) the effect of changing the solvent from
2
000, 2, 1423.
1
0) Basolo, F.; Pearson, R. G. Mechanisms of Inorganic Reactions A
nd
Study of Metal Complexes in Solutions; 2 ed.; John Wiley and Sons: New
York 1967.
11) a) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Organome-
tallics 1996, 15, 2745. b) Widenhoefer, R. A.; Organometallics 1996, 15,
1
,4-dioxane to benzene-d
the reaction has an unknown role on the rate of the reductive elimination.
4) Catalyst decomposition over the course of the reaction is also an
6
(and solvated base, amine, and aryl halide) of
2
alternative possibility and cannot be ruled out as the cause of decreasing
reaction rate.
2
I. A. J. Am. Chem. Soc. 1998, 120, 9205. b) Hartwig, J. F. Inorg. Chem.
2007, 46, 1936.
3
534.
2) a) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int.
Ed., 1995, 34, 1348. b) Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995,
1
5) a) Mann, G.; Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei,
3
9
6, 3609. c) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983,
27.
2
6) Reid, S. M.; Boyle, R. C.; Mague, J. T.; Fink, M. J. J. Am. Chem.
Soc. 2003, 125, 7816.
7) It was determined that additional L8 improved the rate of reac-
13) a) Boncella, J. M.; Villanueva, L. A. J. Organometal. Chem. 1994,
465, 297. b) Villanueva, L. A.; Abboud, K. A.; Boncella, J. M. Organome-
tallics 1994, 13, 3921. c) Stambuli, J. P.; Incarvito, C. D.; Buhl, M.; Hart-
wig, J. F. J. Am. Chem. Soc. 2004, 126, 1184. d) Klinkenberg, J. L.; Hart-
wig, J. F. J. Am. Chem. Soc. 2010, 132, 11830. e) Yamashita, M.; Hartwig,
2
tion. This is most consistent with the formation of an off-cycle palladium
species for which re-association with the ligand forms the active catalyst.
8
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