Journal of the American Chemical Society
Communication
Acc. Chem. Res. 2010, 43, 1486. (b) Of aryl carbamates: Quasdorf,
K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.;
Blackburn, T.; Ramgren, S. D.; Houk, K. N.; Snieckus, V.; Garg, N. K.
J. Am. Chem. Soc. 2011, 133, 6352. (c) Of aryl methyl ethers: Tobisu,
M.; Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed. 2008, 47, 4866.
(d) Of oxygen leaving groups: Rosen, B. M.; Quasdorf, K. W.; Wilson,
D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev.
2011, 111, 1346.
(8) (a) Under the standard asymmetric cross-coupling conditions:
(1) lower ee and/or yield are obtained when arylsulfonamides in
which the aromatic group is hindered (mesityl) or very electron-poor
(nosyl) are employed as substrates; (2) during the course of a reaction,
the unreacted electrophile remains racemic, and the ee of the product
is constant; (3) essentially no C−C bond formation is observed in the
absence of NiBr2·diglyme, the ligand, or KOt-Bu. (b) For the
stereoconvergent Suzuki reaction illustrated in entry 3 of Table 2: (1)
the use of TBME, Et2O, or toluene, rather than i-Pr2O, as solvent
results in formation of the product in comparable ee but somewhat
diminished yield (∼65%); (2) on a gram scale, the coupling proceeds
in 90% ee and 79% yield; (3) with 5% NiBr2·diglyme/6% ligand, the
cross-coupling product is generated in 90% ee and 42% yield; (4) the
reaction is not highly water-sensitive (the addition of 0.1 equiv of
water leads to no loss in ee or yield); (5) use of 1.3 equiv of
alkylborane results in comparable enantioselectivity (89%) but lower
yield (53%).
good ee at room temperature. In contrast with our earlier
method for the catalytic asymmetric synthesis of amines, which
exclusively produced arylamines and was nitrogen-directed,2c for
carbamate- and sulfonamide-directed cross-couplings, oxygen is
the likely site of coordination to Ni. In particular, a structure−
enantioselectivity study of sulfonamides is consistent with
binding by oxygen, as is our observation that sulfones can
function as a directing group in these stereoconvergent Suzuki
reactions. This investigation has thus established for the first
time that sulfonamides and sulfones can serve as effective
directing groups in metal-catalyzed asymmetric C−C bond-
forming processes. With respect to the mechanism of Ni-
catalyzed Suzuki cross-couplings of unactivated secondary alkyl
electrophiles, we have determined that the stereochemistry of
the boron-bound carbon of a chiral trialkylborane is preserved
in the reaction product, consistent with transmetalation with
retention of stereochemistry and with structural integrity for
the resulting Ni−C bond in subsequent stages of the catalytic
cycle. A wide range of additional studies of cross-coupling
reactions of alkyl electrophiles are underway.
ASSOCIATED CONTENT
* Supporting Information
■
S
(9) Examples of Ni-catalyzed Suzuki cross-couplings of aryl fluorides
(perfluorinated arenes): Schaub, T.; Backes, M.; Radius, U. J. Am.
Chem. Soc. 2006, 128, 15964.
(10) In a preliminary study, when the R group of the sulfone was Me
or aryl, lower enantioselectivity was observed (∼80% ee).
(11) A homologue ((t-Bu)SO2(CH2)3CHClMe) cross-coupled in
49% ee and 85% yield.
(12) A previous report of the formation of an “ate” complex under
somewhat different conditions: Saito, B.; Fu, G. C. J. Am. Chem. Soc.
2007, 129, 9602.
Experimental procedures and compound characterization data.
This material is available free of charge via the Internet at
AUTHOR INFORMATION
Corresponding Author
■
Notes
(13) (a) Related mechanistic proposals for Ni/terpyridine-catalyzed
Negishi reactions: Jones, G. D.; Martin, J. L.; McFarland, C.; Allen,
O. R.; Hall, R. E.; Haley, A. D.; Brandon, R. J.; Konovalova, T.;
Desrochers, P. J.; Pulay, P.; Vicic, D. A. J. Am. Chem. Soc. 2006, 128,
13175. Lin, X.; Phillips, D. L. J. Org. Chem. 2008, 73, 3680. (b)
Overview of mechanistic issues regarding Ni-catalyzed cross-couplings
of unactivated alkyl halides: Hu, X. Chem. Sci. 2011, 2, 1867.
(14) For the cross-coupling illustrated in entry 3 of Table 2, we
determined that the rate law is first order in the Ni catalyst and in the
organoborane, but zeroth order in the electrophile.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Support has been provided by the National Institutes of Health
(National Institute of General Medical Sciences, grant R01-
GM62871) and the University of Basilicata (fellowship to F.T.).
We thank Dr. Jeffrey H. Simpson (Department of Chemistry
Instrumentation Facility) for assistance with NMR spectroscopy.
(15) To simplify the analysis of the coupling constants, we chose to
employ perdeuterated cyclohexyl bromide as the unactivated
secondary alkyl electrophile.
(16) A pioneering example of the use of this coupling-constant
strategy in the context of elucidating the mechanism of organometallic
reactions: Bock, P. L.; Boschetto, D. J.; Rasmussen, J. R.; Demers, J. P.;
Whitesides, G. M. J. Am. Chem. Soc. 1974, 96, 2814.
(17) After our mechanistic study was complete, Jarvo independently
reported that transmetalation in a Ni-catalyzed primary−primary
Suzuki cross-coupling, under conditions initially described by us
(Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 9602.), proceeds with
retention of stereochemistry: Taylor, B. L. H.; Jarvo, E. R. J. Org. Chem.
2011, 76, 7573.
(18) Analogous studies of the mechanism of transmetalation in
palladium-catalyzed Suzuki reactions of aryl electrophiles: (a) Ridgway,
B. H.; Woerpel, K. A. J. Org. Chem. 1998, 63, 458. (b) Matos, K.;
Soderquist, J. A. J. Org. Chem. 1998, 63, 461.
REFERENCES
■
(1) Reviews and leading references on directed reactions:
(a) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93,
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