A mild radical procedure for the reduction of B-alkylcatecholboranes to alkanes

Article abstract of DOI:10.1021/ja055691j

A mild radical-mediated reduction of organoboranes is reported. The reducing agent is methanol complexed by the Lewis acidic B-methoxycatecholborane. Copyright

Full text of DOI:10.1021/ja055691j

Published on Web 09/23/2005
A Mild Radical Procedure for the Reduction of B-Alkylcatecholboranes to
Alkanes
Davide Pozzi, Eoin M. Scanlan, and Philippe Renaud*
Departement fu¨r Chemie und Biochemie, UniVersita¨t Bern, Freiestrasse 3, CH-3000 Bern 9, Switzerland
Received August 19, 2005; E-mail: philippe.renaud@ioc.unibe.ch
Organoboranes, such as B-alkylcatecholborane (2-alkyl-1,2,3-
benzodioxaborole), are easily prepared via hydroboration of
alkenes.1-3 Upon oxidative treatment with hydrogen peroxide or
other oxidizing agents, alcohols are formed, and the whole process
represents an anti-Markovnikov addition of water to alkenes.4
Reductive treatment of the intermediate alkylboranes leading to
alkanes is far less common despite the attractiveness of the
procedure for the reduction of double bonds. This transformation
is usually achieved by treatment under severe conditions with
propionic acid in diglyme at 162 °C,5-7 alkaline protonolysis,8,9
and hydrogenolysis at high temperature (190-225 °C).10,11 We have
recently discovered that B-alkylcatecholboranes are a very efficient
source of alkyl radicals under dioxygen and peroxide initiation
(Scheme 1).12,13 Several chain reactions involving alkoxyl and
pinane was slow, and a yield of 80% was obtained after 60 h.
Various alcohols were then tested to optimize the reaction condi-
tions. In contrast to our expectation, the acidity of the alcohol did
not seem to play an important role in this process. 2-Propanol, tert-
butyl alcohol, and hexafluoro-2-propanol gave the desired cis-3 in
less than 10% yield after 60 h under the conditions described above.
Trifluoroethanol and water gave cis-3 in 40 and g80% yield,
respectively.
Scheme 1
However, under very strict exclusion of oxygen (glovebox), the
reaction depicted in eq 2 affords only traces (e5%) of cis-3 after
3 days. Therefore, the role of oxygen was investigated. The reaction
is strongly accelerated when air is added slowly to the reaction
mixture following the addition of methanol (eq 3). Optimization
of the reaction conditions led to the following procedure: hydrobo-
ration (2 equiv of CatBH, 10 mol % of MeCONMe2, 5 h reflux in
CH2Cl2)18 followed by reduction of the organoborane by adding
MeOH (4 equiv) followed by air (0.3 equiv of O2) over 90 min in
refluxing CH2Cl2 (procedure A). Under these conditions, a yield
of 80% was obtained at the end of the oxygen addition. Similar
results were obtained by initiation with di-tert-butyl peroxide in
dichlorobenzene at 140 °C under microwave irradiation in 15 min
(procedure B). Different alcohols were tested: ethanol, 2-propanol,
and water gave similar results (GC yield g70%). However, tert-
butyl alcohol and 2-phenylethanol gave the reduced product cis-3
in low yield (23% in both cases).
sulfonyl radical intermediates were developed for the formation of
carbon-carbon bonds, such as conjugate additions and allylation
processes (Scheme 1, eq 1).14-16 Since radical reactions are
particularly mild, we decided to investigate the use of such a process
to achieve the reduction of B-alkylcatecholboranes. Moreover,
during the allylation of R-pinene 1, depicted in eq 1, we always
noticed the formation of a small amount (e5%) of cis-pinane cis-
3.16 The presence of cis-3 was attributed, without any experimental
support, to partial protonation of the intermediate organoborane by
the methanol used to deactivate the excess catecholborane. A careful
investigation of this process led us to develop a mild method for
the reduction of B-alkylcatecholboranes. A very unusual use of
methanol and related alcohols as reducing agent in a radical process
is described.
The reduction of R-pinene 1 to cis-pinane cis-3 was used as a
model reaction for our initial investigation (eq 2). The hydroboration
of 1 is carried out by heating in refluxing dichloromethane with 2
equiv of freshly distilled catecholborane and 10 mol % of N,N-
dimethylacetamide as catalyst.18 The excess catecholborane was
decomposed by addition of MeOH (4 equiv), and the reaction was
maintained at room temperature under nitrogen. The formation of
pinane 3 was monitored by GC analysis using phenylcyclohexane
as an internal standard. After 90 min, cis-pinane cis-3 was present
in less than 10% yield. The conversion of the organoborane to
The scope and limitations of the reaction were then investigated
for a series of different B-alkylcatecholboranes (Scheme 2). Good
yields were obtained with primary (eqs 4-6), secondary (eqs 7
and 8), and tertiary (eq 9) alkyl groups. The reduction of 2-carene
15 leads to the monocyclic cis-para-menth-2-ene 16, resulting from
the ring opening of the cyclopropane ring, demonstrating that a
radical intermediate is involved (eq 10).19
Reaction of isolated B-pinylcatecholborane, prepared by hydro-
boration of R-pinene and purified by distillation, with methanol (4
equiv) under oxygen initiation affords the reduced product cis-3 in
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10.1021/ja055691j CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Procedure A: (1) C6H4O2BH (2 equiv), MeCONMe2
(0.1 equiv); (2) MeOH (4 equiv), Air (0.3 mol % of O2), CH2Cl2,
Reflux, 90 min
Scheme 3. Mechanistic Proposal
efficiency of the reaction indicates that the hydrogen transfer from
the complex B to the alkyl radical is a very critical step in the
whole process; (3) the inefficiency of the reaction with tert-butyl
alcohol and 2-phenylethanol can also be explained by rapid
fragmentation of the intermediate alkoxyl radicals, leading to methyl
and benzyl radicals.22
In conclusion, we have developed a method for the reduction of
organoboranes with alcohols under mild conditions. This is, to our
knowledge, the first radical-mediated reduction of organoboranes.
Moreover, the fact that the O-H bond of the alcohol complexed
by a Lewis acid is delivering the hydrogen atom is surprising and
offers new opportunities for the design of novel tin-free radical
reducing agents.
Acknowledgment. We thank the Swiss National Science
Foundation (Projects 20-103627 and 20C321-101069) and the
University of Bern for financial support, as well as BASF
Corporation for the gift of catecholborane.
less than 5% yield. However, when a mixture of catecholborane (1
equiv) and MeOH (4 equiv) is added to the pure B-pinylcatechol-
borane, cis-3 is obtained in 43% yield. This demonstrates that the
presence of MeO-BO2C6H4, resulting from the methanolysis of
the excess catecholborane, is an essential component of the reaction.
To investigate further the mechanism of the reaction, we
performed deuterium labeling experiments with R-pinene 1. Reac-
tion in methylene chloride-d2 initiated by oxygen (procedure A)
affords exclusively the nondeuterated pinane cis-3. Yields and
reaction time are similar to those in the reaction in nondeuterated
methylene chloride. Reactions with methanol-d1 (CH3OD) and -d4
(CD3OD) (procedure B) afford the deuterated pinane-d1, and the
reaction becomes very slow (e17% yield). By using methanol-d3
(CD3OH), the nondeuterated cis-3 is obtained in 43% yield
(conditions B). These results demonstrate that the transferred
hydrogen atom comes from the O-H bond of methanol. Similar
results were obtained when the reduction process was run in
refluxing methylene chloride using dioxygen as the initiator
(procedure A).
Supporting Information Available: Detailed experimental pro-
cedures and spectroscopic data for new compounds, and further
evidence for a radical mechanism based on the reaction of 2-phenyl-
methylenecyclopropane. This material is available free of charge via
the Internet at http://pubs.acs.org.
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A plausible mechanism is depicted in Scheme 3. Reaction of
the B-alkylcatecholborane with the initiator (oxygen or a tert-
butoxyl radical) affords the alkyl radical, which is then reduced by
B resulting from the complexation of MeOH by the Lewis acidic
MeO-BO2C6H4.20 The resulting radical C is closely related to the
radical ate complex A (Scheme 1) involved in the formation of
alkyl radical from B-alkylcatecholborane and is therefore stabilized
by delocalization.21 This radical leads eventually to MeO-BO2C6H4
and a methoxyl radical that can react with the alkylcatecholborane
to sustain the chain process. This mechanism fits well with the
experimental results: (1) the reaction is inhibited by 1,4-cyclo-
hexadiene, presumably due to hydrogen transfer to the methoxyl
radical; (2) the deuteration experiment leads to D-incorporation from
the O-D bond, the very strong effect on the reaction rate, and
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(17) Similar work using a water-trimethylborane complex as a reducing agent
appeared while this paper was in preparation: Spiegel, D.; Wiberg, K.
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I.; Cossy, J.; Ollivier, C.; Chuard, R.; Renaud, P. J. Org. Chem. 2002,
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(20) A virtually intramolecular hydrogen transfer from a water-Ti(III) complex
to a radical has already been proposed: Barrero, A. F.; Oltra, J. E.; Cuerva,
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(22) In the case of tert-butyl alcohol, steric hindrance may also disfavor the
formation of complex B or slow the reduction step.
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