Oxidation of hydroxyl-substituted organotrifluoroborates

Article abstract of DOI:10.1021/ja062974i

Potassium- and tetra-n-butylammonium organotrifluoroborates containing hydroxyl groups have been prepared and oxidized using several common oxidants. Aryl-, alkenyl-, and alkyltrifluoroborates containing both primary and secondary hydroxyl groups were oxi

Full text of DOI:10.1021/ja062974i

Published on Web 07/07/2006
Oxidation of Hydroxyl-Substituted Organotrifluoroborates
Gary A. Molander* and Daniel E. Petrillo
Roy and Diana A. Vagelos Laboratories, Department of Chemistry, UniVersity of PennsylVania,
Philadelphia, PennsylVania 19104-6323
Received April 28, 2006; E-mail: gmolandr@sas.upenn.edu
Table 1. Oxidation of TBA Trifluoroborate 1a
The transition metal-catalyzed cross-coupling reaction of orga-
nometallic reagents with organic electrophiles has transformed the
manner in which synthetic chemists design syntheses of complex
molecules.1 As a result, several classes of organometallic reagents
have become indispensable tools for selective carbon-carbon bond
formation. Organoboron reagents are often superior to other classes
of nucleophilic coupling reagents in their stability and/or functional
group compatibility.2 Additionally, they are more environmentally
sound and exhibit minimal toxicity issues.
Recently, potassium organotrifluoroborates have been demon-
strated to be useful coupling partners in the Suzuki-Miyaura
reaction,3 the rhodium-catalyzed 1,4-addition,4 as well as other
important synthetic reactions.5 Their primary advantages are that
they are air and moisture stable and can be prepared in large
quantities that can be stored indefinitely. In some cases, they show
enhanced reactivity compared to other organoboron compounds.6
Because organoboron reagents, including trifluoroborates, are
often used in complex molecule synthesis,7 it would be advanta-
geous to introduce functionality and manipulate them as ordinary
synthetic intermediates in a multistep synthetic sequence. This
would be in contrast to their normal use in synthesis, wherein the
organoboron moiety is employed in a coupling reaction immediately
after its introduction. In pursuit of this goal, we have shown that
potassium organotrifluoroborates are stable to oxidative conditions,8
including epoxidation9 and dihydroxylation.10
entry
conditions
% isolated yield
1
2
3
1% TPAP/NMO
Swern
Dess-Martin
91
90
86
Table 2. Oxidation of TBA Organotrifluoroboratesa
Alcohol oxidation is of fundamental importance in organic
synthesis.11 Herein we report a general reaction of organotrifluo-
roborates in which a primary or secondary alcohol is converted to
an aldehyde or ketone, while retaining the valuable carbon-boron
bond. Many common oxidation protocols are tolerated, and both
the potassium and the tetra-n-butylammonium (TBA) counterion
can be used.
The incorporation of a carbonyl moiety into an organoboron
compound would be a useful synthetic transformation, because
many hydroboration reagents, such as catecholborane12 and 9-BBN,13
are incompatible with ketones and aldehydes. Other reagents, such
as pinacolborane,14 are more tolerant, but often require transi-
tion metal catalysis to undergo hydroboration at ambient temper-
atures.
Many oxidation procedures are conducted in chlorinated solvents
in which polar organotrifluoroborates are insoluble. Consequently,
the TBA organotrifluoroborates were used at the outset of this study
because they are readily soluble in dichloromethane.15 To initiate
the study, the crystalline benzyl alcohol derivative 1a, prepared in
one step from the commercially available boronic acid, was
subjected to a variety of oxidative conditions (Table 1).
a Conditions: 1-2% TPAP, 1.1 equiv NMO, 4 Å molecular sieves,
CH2Cl2, rt, 18-20 h. b 93% conversion.
TPAP/NMO,16 Swern oxidation conditions,17 and Dess-Martin
periodinane18 were all successful, providing the 4-formylphenyl-
trifluoroborate 2a in good to excellent yields. In most cases, a simple
aqueous workup and concentration was all that was required to
isolate the pure oxidized product in high purity, with retention of
1
the trifluoroborate moiety, as determined by H, 11B, 13C, and 19F
NMR. Other common oxidation conditions, such as TEMPO/
bleach,19 TEMPO/PhI(OAc)2,20 and IBX,21 also gave the desired
product, albeit with byproducts that were not easily separable.
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10.1021/ja062974i CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Oxidation of Potassium Organotrifluoroboratesa
Scheme 1
means. Most importantly, it allows practitioners to expand the role
of organoborons in their synthetic planning, thus changing in a
fundamental manner strategic retrosynthetic analyses involving
boron-based cross-coupling.
Acknowledgment. The authors wish to thank NIH (GM 35249),
Amgen, Merck Research Laboratories, and Johnson Matthey for
their generous support of our program. Dr. Rakesh Kohli is
acknowledged for obtaining HRMS data.
Supporting Information Available: Experimental procedures,
compound characterization data, and NMR spectra for all new
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
a Conditions: 3 equiv IBX, acetone, reflux, 2 h. b Product isolated in
low yield.
References
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Because of its simplicity in execution, the TPAP/NMO system
was to chosen to oxidize a variety of TBA organotrifluoroborates
containing primary and secondary alcohols. The use of activated,
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The use of IBX is often limited to DMSO, or DMSO/THF
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to 4-bromobenzonitrile to provide 5 in 80% yield over two steps
after column chromatography (Scheme 1).
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can be oxidized under several common oxidation conditions. This
method allows access to ketone- and aldehyde-containing orga-
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