Journal of the American Chemical Society
Communication
Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem., Int. Ed. 2012,
51, 5062. (c) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177.
(2) (a) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
(b) Hiyama, T.; Hatanaka, T. Pure Appl. Chem. 1994, 66, 1471.
(c) Hiyama, T. J. Organomet. Chem. 2002, 653, 58. (d) Nakao, Y.;
Hiyama, T. Chem. Soc. Rev. 2011, 40, 4893.
(3) For mechanistic insights also with rhodium catalyst see: Nakao, Y.;
Chen, J.; Imanaka, H.; Hiyama, T.; Ichikawa, Y.; Duan, W.-L.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 9137.
(4)(a)Denmark, S. E.;Choi, J.Y. J. Am. Chem. Soc.1999,121,5821. For
a review, see: (b) Chang, W.-T. T.; Smith, R. C.; Regens, C. S.; Bailey, A.
D.; Werner, N. S.; Denmark, S. E. In Organic Reactions; Denmark, S. E.,
Ed.; Wiley: Hoboken, 2011; Vol 75, pp. 213−746.
(5) (a) Murahashi, S.-I.; Tanba, Y.; Yamamura, M.; Moritani, I.
Tetrahedron Lett. 1974, 15, 3749. (b) Murahashi, S.-I. J. Organomet.
Chem. 2002, 653, 27.
resting state B-CF3 (−6.1 kcal/mol) to transition-state TSb-CF3
(4.1 kcal/mol), the overall barrier for the transfer of the phenyl
grouptothePd(II)-centeris10.2kcal/mol, withgenerationofthe
diarylpalladium(II) species F exergonic by 22.4 kcal/mol in THF.
Comparison of the computational results of our model
siloxane-based transfer agents A-H and A-CH3 with those of A-
CF3 (Scheme 5) clarifies the influence of the electronic and steric
properties of the latter in the efficiency of CCRs. Without
electron-withdrawing CF3 groups, the stability of lithium alkoxide
B-CH3 is significantly decreased (3.5 vs −6.1 kcal/mol), thus
resultinginamuchlowerbarrierfortheregenerationofPhLifrom
theresting lithiumalkoxide (7.7vs18.8 kcal/mol, from Bto TSa).
Experimentally, this process leads to unreacted aryl chloride with
no formation of the desired product. Absence of geminal CF3
groupsattheα-positionofoxygeninthefour-memberedcomplex
D-H dramatically increases the stability (−20.7 vs −4.2 kcal/
mol), making D-H the resting state for the transmetalation step.
This elevates the barrier for the transfer of phenyl group to the
Pd(II)-center (16.4 kcal/mol from D-H to TSb-H vs 10.2 kcal/
mol from B-CF3 to TSb-CF3), decelerating the transmetalation
process and the overall conversion.
(6) (a) Giannerini, M.; Fananas
́
-Mastral, M.; Feringa, B. L. Nat. Chem.
2013, 5, 667. (b)Hornillos, V.; Giannerini, M.;Vila, C.;Fananas-Mastral,
M.; Feringa, B. L. Org. Lett. 2013, 15, 5114. (c) Vila, C.; Hornillos, V.;
Giannerini, M.; Fananas-Mastral, M.; Feringa, B. L. Chem. - Eur. J. 2014,
̃
́
̃
́
̃
20, 13078.
(7) Lithium Compounds in Organic Synthesis; Luisi, R., Capriati, V.; Eds.;
Wiley-VCH: Weinheim, 2014.
(8) (a) Negishi, E.; Baba, S. J. Chem. Soc., Chem. Commun. 1976, No. 15,
596. (b) Baba, S.; Negishi, E. J. Am. Chem. Soc. 1976, 98, 6729.
(9) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047.
(10) (a) Smith, A. B., III; Hoye, A. T.; Martinez-Solorio, D.; Kim, W.;
Tong, R. J. Am. Chem. Soc. 2012, 134, 4533. (b) Martinez-Solorio, D.;
Hoye, A. T.; Nguyen, M. H.; Smith, A. B., III Org. Lett. 2013, 15, 2454.
(11) Son, E.-C.; Tsuji, H.; Saeki, T.; Tamao, K. Bull. Chem. Soc. Jpn.
2006, 79, 492.
In conclusion, a reusable, bench stable silicon-based transfer
agent (1) has been designed, synthesized, and validated for
effectiveroom-temperaturepalladium-catalyzedCCRsofaryland
heteroaryl chlorides with readily accessible aryl lithium reagents.
Noteworthy, the only stoichiometric waste product in this cross-
coupling protocol is LiCl! Subsequent DFT calculations
demonstrated that the preferred transmetalation step involves
the lithium alkoxide,23 which leads to a palladium(II) alkoxide
undergoing σ-bond metathesis. The geminal CF3 groups at the
benzylic position of new transfer agent have two beneficial effects:
(a) increased barrier for the regeneration of aryl lithium reagents,
inhibiting the formation of homocoupling products; and (b)
decreased barrier for transferring aryl groups to the Pd(II)-center,
facilitating the conversion. Experimental studies exploring vinyl
and other lithium reagents are ongoing.
(12) (a) Yamamoto, Y.; Takeda, Y.; Akiba, K. Tetrahedron Lett. 1989,
30, 725. (b) Cho, I.; Meimetis, L.; Britton, R. Org. Lett. 2009, 11, 1903.
(13) Image of crystal structure of 1 generated using: Legault, C. Y.
CYLview, 1.0b;Universite
́
de Sherbrooke: Quebec, Canada, 2009
(14) (a) Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Chem. Sci. 2013, 4,
916. (b) Bruno, N. C.; Buchwald, S. L. Org. Lett. 2013, 15, 2876.
(c) Bruno, N. C.; Niljianskul, N.; Buchwald, S. L. J. Org. Chem. 2014, 79,
4161.
(15) (a)Tamao, K.;Ishida, N.;Tanaka, T.;Kumada, M. Organometallics
1983, 2, 1694. (b) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
Commun. 1984, No. 1, 29.
(16) DeGoey, D. A.; Grampovnik, D. J.; Flentge, C. A.; Flosi, W. J.;
Chen, H.-J.; Yeung, C. M.; Randolph, J. T.; Klein, L. L.; Dekhtyar, T.;
Colletti, L.;Marsh, K. C.;Stoll, V.; Mamo, M.; Morfitt, D. C.;Nguyen, B.;
Schmidt, J. M.;Swanson, S.J.;Mo, H.;Kati, W.M.;Molla, A.;Kempf, D. J.
J. Med. Chem. 2009, 52, 2571.
ASSOCIATED CONTENT
* Supporting Information
TheSupportingInformationisavailablefreeofchargeontheACS
■
S
Crystallographic data (CIF)
Experimental details and data, and complete ref 20 (PDF)
(17) Nicolaou, K. C.; Scarpelli, R.; Bollbuck, B.; Werschkun, B.; Pereira,
M. M. A.; Wartmann, M.; Altmann, K. H.; Zaharevitz, D.; Gussio, R.;
Giannakakou, P. Chem. Biol. 2000, 7, 593.
(18) (a) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009,
131, 6961. (b) Dick, G. R.; Knapp, D. M.; Gillis, E. P.; Burke, M. D. Org.
Lett. 2010, 12, 2314. (c) Dick, G. R.; Woerly, E. M.; Burke, M. D. Angew.
Chem., Int. Ed. 2012, 51, 2667.
(19) Tymonko, S. A.; Smith, R. C.; Ambrosi, A.;Ober, M. H.; Wang, H.;
Denmark, S. E. J. Am. Chem. Soc. 2015, 137, 6200.
(20) All calculations were performed with: Gaussian 09, Revision D.01;
Gaussian Inc.: Wallingford, CT, 2013; see the SI.
(21)Forrelatedcomputationalstudies, see:(a)Barder, T. E.;Biscoe,M.
R.; Buchwald, S. L. Organometallics 2007, 26, 2183. (b) Bonney, K. J.;
Schoenebeck, F. Chem. Soc. Rev. 2014, 43, 6609 and references therein.
(22) For structures of key intermediates and transition states, see the SI.
(23) 29Si NMR experiments confirmed quantitative formation of
alkoxide intermediate 12 (δ −9.13 ppm) upon addition of PhLi to 1 (δ
AUTHOR INFORMATION
■
Corresponding Authors
Present Address
§Department of Chemistry, Niagara University, NewYork 14109,
United States.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the NIH (GM-29028) and the
NSF (CHE-1361104). Calculations were performed on the
XSEDE, supported by the NSF (OCI-1053575).
REFERENCES
■
(1) (a) Metal-catalyzed Cross-coupling Reactions, 2nd ed.; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004. (b) Seechurn, C. C. J.;
D
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX