Journal of the American Chemical Society
Article
(7) For an overview of the synthesis and applications of
alkylboronates and related compounds, see: Boronic Acids; Hall, D.
G., Ed.; Wiley−VCH: Weinheim, 2011.
(20) These are the conditions reported in: Zhou, J.; Fu, G. C. J. Am.
Chem. Soc. 2003, 125, 14726−14727.
(21) For example, see: Lu, Z.; Wilsily, A.; Fu, G. C. J. Am. Chem. Soc.
2011, 133, 8154−8157.
(8) For a few recent examples of the synthesis and applications of
tertiary boronate esters, see: (a) Bagutski, V.; Elford, T. G.; Aggarwal,
V. K. Angew. Chem., Int. Ed. 2011, 50, 1080−1083. (b) Elford, T. G.;
Nave, S.; Sonawane, R. P.; Aggarwal, V. K. J. Am. Chem. Soc. 2011, 133,
16798−16801. (c) Guzman-Martinez, A.; Hoveyda, A. H. J. Am. Chem.
Soc. 2010, 132, 10634−10637. (d) O’Brien, J. M.; Lee, K.; Hoveyda, A.
H. J. Am. Chem. Soc. 2010, 132, 10630−10633. (e) Stymiest, J. L.;
Bagutski, V.; French, R. M.; Aggarwal, V. K. Nature 2008, 456, 778−
782.
(22) For noteworthy early mechanistic studies by others, see:
(a) 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, 13175−13183. (b) Lin, X.;
Phillips, D. L. J. Org. Chem. 2008, 73, 3680−3688. (c) Phapale, V. B.;
Bunuel, E.; Garcia-Iglesias, M.; Cardenas, D. J. Angew. Chem., Int. Ed.
2007, 46, 8790−8795.
(23) For reviews and leading references on possible mechanisms for
nickel-catalyzed cross-couplings of alkyl electrophiles, see: (a) Hu, X.
Chem. Sci. 2011, 2, 1867−1886. (b) Phapale, V. B.; Cardenas, D. J.
Chem. Soc. Rev. 2009, 38, 1598−1607.
(24) One would anticipate that a Ni−BX2 or a Ni−BX3 intermediate
would exhibit different reactivity from a Ni−alkyl, due to the trivalency
of boron (Ni−BX2) or the charge associated with a boron “ate”
complex (Ni−BX3).
(25) For example, see: Lu, Z.; Fu, G. C. Angew. Chem., Int. Ed. 2010,
49, 6676−6678.
(26) For related observations for nickel-catalyzed Suzuki reactions of
unactivated alkyl halides, see ref 25.
(27) Use of a stereochemical probe (see ref 14b) provided results
fully consistent with a radical intermediate in our nickel-catalyzed
Miyaura borylations of unactivated alkyl electrophiles. Thus, both of
the secondary bromides underwent cyclization/borylation to furnish
the same ratio of diastereomers as observed for reductive cyclizations
with Bu3SnH, consistent with a common intermediate for the two
processes (a secondary alkyl radical that adds to the pendant olefin).
(28) In a preliminary investigation, we have obtained moderate ee
(61%), but modest yield, in a nickel/pybox-catalyzed enantioselective
borylation of a racemic halide. For leading references to applications of
enantioenriched alkylboronates in organic synthesis, see: (a) Scott, H.
K.; Aggarwal, V. K. Chem.Eur. J. 2011, 17, 13124−13132.
(b) Crudden, C. M.; Glasspoole, B. W.; Lata, C. J. Chem. Commun.
2009, 6704−6716.
(9) For leading references to metal-catalyzed borylations of aryl,
alkenyl, and activated alkyl (allyl and benzyl) electrophiles, see:
(a) Ishiyama, T.; Miyaura, N. In Boronic Acids; Hall, D. G., Ed.; Wiley-
VCH: Weinheim, 2011; Vol. 1, pp 135−169. (b) Miyaura, N. Bull.
Chem. Soc. Jpn. 2008, 81, 1535−1553.
(10) For an early review, see: Seebach, D. Angew. Chem., Int. Ed.
1979, 18, 239−258.
(11) (a) Yang, C.-T.; Zhang, Z.-Q.; Tajuddin, H.; Wu, C.-C.; Liang,
J.; Liu, J.-H.; Fu, Y.; Czyzewska, M.; Steel, P. G.; Marder, T. B.; Liu, L.
Angew. Chem., Int. Ed. 2012, 51, 528−532. (b) Ito, H.; Kubota, K. Org.
Lett. 2012, 14, 890−893.
(12) For example, see: Zultanski, S. L.; Fu, G. C. J. Am. Chem. Soc.
2011, 133, 15362−15364.
(13) Under the conditions employed in Tables 1−3, in the absence
of NiBr2·diglyme, no borylation (<1% yield) of unactivated primary,
secondary, or tertiary halides was observed.
(14) For example, see: (a) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004,
́
126, 1340−1341. (b) Gonzalez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc.
2006, 128, 5360−5361. (c) Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007,
129, 9602−9603.
(15) For example, see: (a) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 14726−14727. (b) Reference 5b.
(16) Under the same conditions, borylations of a primary allylic and a
primary benzylic bromide were not efficient.
(17) Notes: (a) Under the standard conditions: when a borylation
was conducted in a capped vial under an atmosphere of air, the yield of
the product was unaffected; the addition of 0.10 equiv of water led to a
small (5%) decrease in yield; use of TBME, CPME, Et2O, or DME as
the solvent led to a somewhat lower yield (Table 2, entry 3: 66−85%);
functional groups such as a TIPS-substituted alkyne, an enolizable
ketone, an aryl fluoride, and a trifluoromethyl group were compatible
with the borylation process, whereas a nitro group and an aryl iodide
were not; a highly hindered unactivated secondary bromide (t-
BuCHBrCH2CH2Ph), an unactivated secondary chloride, an unac-
tivated secondary tosylate, and an activated secondary bromide ((1-
bromoethyl)benzene) were not suitable coupling partners; for the
coupling illustrated in entry 3 of Table 2, use of 2.5% NiBr2·diglyme/
3.3% ligand 1 provided the product in 85% yield, whereas use of 1.0%
NiBr2·diglyme/1.3% ligand 1 furnished the alkylboronate in 69% yield;
in the case of entry 2 of Table 2, use of the enantiomer of ligand 1 led
to a 2:1 (β:α) mixture of diastereomers. (b) The Brønsted basicity of
the reaction medium is substantially attenuated by complexation of the
alkoxide to boron; thus, when enantioenriched 1,2-diphenylbutan-1-
one was added to a borylation process, it could be recovered at the end
of the reaction in essentially quantitative yield (>95%) and with little
erosion in ee (<10%; complete racemization occurs in the absence of
pinB−Bpin).
(18) Under our standard borylation conditions, use of pinacolborane
instead of pinB−Bpin did not generate a significant quantity of the
desired product.
(19) Under the standard conditions: the catalytic borylation
illustrated in entry 6 of Table 3 proceeded in 70% yield on a gram
scale, whereas use of 5% NiBr2·diglyme/6.6% ligand 1 furnished a 56%
yield on a gram scale; if TBME, CPME, Et2O, or DME was employed
as the solvent, a significantly lower yield was observed; an unactivated
tertiary chloride, an activated tertiary chloride, and a highly hindered
tertiary alkyl bromide were not useful coupling partners.
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dx.doi.org/10.1021/ja304068t | J. Am. Chem. Soc. 2012, 134, 10693−10697