C O M M U N I C A T I O N S
Table 2. Tandem Functionalization of Methyl Groups
Scheme 1
Scheme 2
a Conditions: (A) B2pin2, 5 mol % 1, neat, 150 °C; (B) 1-bromo-4-tert-
butylbenzene (2 equiv), CsOH (4 equiv), Pd(dba)2 (10 mol %), and
Fc(PiPr2)2 (10 mol %) in toluene, 100 °C; (C) Same as B, but CsF and
DMF used in place of CsOH and toluene; (D) H2O2 and KOH in THF and
H2O; (E) KHF2 in MeOH. b Yields calculated by GC. c Yields calculated
by 1H NMR. d Yield based on the reaction of B2pin2 with R-H to form
R-Bpin and H2.
The difference between the reactions with excess of substrate
and with substrate as limiting reagent can be rationalized by the
relative rates for reaction of an unsaturated rhodium boryl inter-
mediate with the HBpin side product and with the organic reagent.
In separate work,8 we have shown that the catalytic process occurs
by dissociation of HBpin from Cp*Rh(Bpin)2(H)(X) to generate
Cp*Rh(Bpin)(X) (X ) H, Bpin) and that the partitioning of this
intermediate between reaction with alkane and HBpin affects the
rate. When the organic substrate is neat and present in excess
quantities, it competes more effectively with HBpin for the binding
site on the catalyst than when it is the limiting reagent. In this case,
the conversion of the organic substrate to the alkylboronate ester
is higher.
group. The products from these reactions can be converted directly
from the crude reactions to alcohols, alkylarenes, and alkyltrifluo-
roborates.
Acknowledgment. We thank the NSF (CHE-03019071) and
Shell Chemicals for support of this work. J.L. thanks the NIH
(GM069172) for a postdoctoral fellowship, and M.T. thanks
Mitsubishi for partial support.
Supporting Information Available: Procedures for synthesis and
characterization of reaction products. This material is available free of
To investigate the electronic effects of the heteroatoms on the
borylation process, we conducted reactions in ethyl butyl ether and
in N,N-diethyl-3-aminopentane. As shown in Scheme 1, the
reactions occurred preferentially at the methyl group closer to the
heteroatom, and the effect of the more electronegative oxygen in
the ether was larger than that of the more coordinating and basic
nitrogen in the amine. The same selectivity was observed from an
intermolecular competition between ethyl butyl ether and dibutyl
ether, after correcting for the ratio of alkyl groups. Consistent with
preferential reaction at the less electron-rich methyl group, reaction
of a mixture of (perfluoro-n-octyl)ethane and octane formed a 94:6
ratio of products that favored borylation of the fluoroalkane.
To exploit the diverse reactivity of organoboranes, we developed
procedures to conduct sequential borylations of alkyl groups and
conversion of the boronate esters to alkylarenes,9 alcohols, and
alkyltrifluoroborates, which are more reactive than boronate esters10
(Scheme 2 and Table 2). The coupling of alkyl boronate esters with
aryl halides is not straightforward, and previous coupling of pinacol
alkylboronic esters required thallium9b or alkyllithium9c reagents.
However, treatment of the crude reaction with 4-tert-butylbro-
mobenzene, 1,1′-bis(diisopropylphosphino)ferrocene, Pd(dba)2, and
base led to a moderate to excellent yield of product from sequential
C-H functionalization and cross-coupling (entries 1-3). Alterna-
tively, the products from the functionalization process were
converted to the corresponding alcohol by addition of aqueous
alkaline H2O2 (entry 4) to the crude reaction solution or to the
corresponding alkyl trifluoroborates by analogous addition of
methanolic KHF2 (entries 5 and 6).
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In summary, we have shown that molecules containing nitrogen,
oxygen, and fluorine undergo rhodium-catalyzed C-H activation
and borylation at the least hindered and least electron-rich methyl
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