Hydroboration with pyridine borane at room temperature

Article abstract of DOI:10.1021/ja043743j

Treatment of pyridine borane (Py·BH₃) with iodine, bromine, or strong acids affords activated Py·BH₂X complexes that are capable of hydroborating alkenes at room temperature. Evidence is presented for an unusual hydroboration mechanism involving leaving group displacement. In contrast to THF·BH₃, hydroboration with Py·BH₂I selectively affords the monoadducts. The crude hydroboration products are converted into synthetically useful potassium alkyltrifluoroborate salts upon treatment with methanolic KHF₂. Copyright

Full text of DOI:10.1021/ja043743j

Published on Web 03/29/2005
Hydroboration with Pyridine Borane at Room Temperature
Julia M. Clay and Edwin Vedejs*
Department of Chemistry, UniVersity of Michigan, Ann Arbor, Michigan 48109
Received October 14, 2004; E-mail: edved@umich.edu
Table 1. Hydroboration of â-methylstyrene with L‚BH2X
Hydroboration has been an essential reaction in synthetic organic
chemistry since Brown’s discovery that borane etherates are reactive
at room temperature.1,2 Diverse hydroborating agents including THF
borane, dimethyl sulfide borane, 9-BBN, and thexylborane are
readily available and offer many options for selective hydrobora-
tion.1 However, each has limitations as well as advantages and all
are air-sensitive. The far more stable pyridine borane (py‚BH3) has
also been considered as a hydroborating agent,3a,b but heating to
75-100 °C is required for dissociation to free borane, a prerequisite
for π-complexation of the olefin and eventual hydroboration.
Hindered amine boranes dissociate more readily and react at lower
temperatures, but they are air-sensitive.3c The remaining challenge
is to obtain high reactivity without compromising reagent stability
and practicality.
a
entry
L
‚
BH3
activation
time (h)
7:8
yield (%)
b
1
2
3
4
5
6
Py‚BH3
I2
2
12
2
2
2
15:1
>20:1
10:1
10:1
2.4:1
3.5:1
92
Py‚BH3
Br2
10d
72
b
Py‚BH3
TfOHc
c
Py‚BH3
HNTf2
I2
90
Lut‚BH3
13d
62
b
Me2S‚BH2Ie
2
a 1:1 ratio, L‚BH3/alkene, room temperature. b 50 mol %. c 100 mol %.
d Reaction quenched prior to completion. e Preformed (ref 7).
We have explored the possibility of activating Py‚BH3 by
replacing one of the hydrides with a good leaving group (Scheme
1; Py‚BH2X (1) with X ) I, Br, OTf, NTf2). If this approach is
Table 2. Alkyne Hydroboration
Scheme 1
entry
L
alkyne
R
R
′
10:11
yield (%)
1
2
3
4
5
6
7
8
9
Py
Py
Py
Lut
Me2S
Py
Py
Py
9a
9b
9c
9a
9a
9d
9e
9f
Ph
CH3
CH3
CH3
CH3
15:1
>20:1
1:2
1.2:1
30:1
64
NA
NA
51
46
66
63
61
64
pCF3Ph
pMeOPh
Ph
Ph
Ph
C3H7
CH3
CH3
CH3
C2H5
C3H7
C5H11
cC6H11
10:1
1.5:1
3:1
Py
9g
1). This improved selectivity, compared to the 5:1 ratio using
BH3‚THF,6 suggests that activation produces a unique hydroborating
agent and does not simply release BH3. Activation of Py‚BH3 with
bromine gave higher selectivity, but a much slower reaction (entry
2), while TfOH and HNTf2 (entries 3 and 4) induced faster but
less selective hydroborations.
used, the strength of the B-N bond would no longer be problematic,
provided that departure of the new leaving group X leads to
hydroboration. This might occur by some process equivalent to SN2-
like displacement of X to form the olefin π-complex 2 (path A) or
an SN1-like heterolysis via 5 (path B), followed by 4-center addition
of B-H (3) to give 4. A third possibility is dissociation of 1 to
BH2X (6, path C), conventional hydroboration, and complexation
with pyridine to afford 4. Prior studies show that intramolecular
hydroborations using activated, unsaturated amine and phosphine
boranes are consistent with internal versions of paths A or B.4 We
now report that a similar hydroboration pathway is also viable as
an intermolecular process.
Several amine boranes and activation methods were compared
to see if intermolecular hydroboration according to Scheme 1 is
possible. The best results were achieved when commercially
available pyridine borane (Py‚BH3) was activated with 50 mol %
of I2 in dichloromethane to generate Py‚BH2I (1; rapid hydrogen
evolution).5 Addition of â-methylstyrene followed by oxidative
workup gave alcohol products (92%; 15:1 ratio, 7/8; entry 1, Table
Next we compared the reagent 1 (X ) I) with Lut‚BH2I (Table
1, entry 5; from lutidene borane + I2) and the known Me2S‚BH2I
(entry 6).7 Different hydroboration regioselectivity was found in
each case, and unique 11B NMR signals were observed prior to the
addition of alkene (Py‚BH2I, δ -28.5 ppm; Lut‚BH2I, δ -34.5
ppm; Me2S‚BH2I, δ -20.5 ppm). The NMR data do not exclude
the presence of BH2I in equilibrium with L‚BH2I in one or more
cases, but the regioselectivity results (entries 1, 5, and 6) prove
that dissociation (as in path C) cannot be the only reaction pathway.
The hydroboration of 1-Ph-1-propyne (9) with BH3‚THF is
reported to give a 3:1 ratio of 10/11, while sia2BH, thexylBH2,
catecholborane, and Br2BH‚SMe2 afford mostly 11.8 In contrast,
Py‚BH2I produces a striking 15:1 selectivity favoring 10 (Table 2,
entry 1), an effect that is amplified for p-CF3Ph-1-propyne and
reversed for the p-MeOPh analogue (entries 2 and 3). Related trends
are reported for styrene hydroboration.9 Lut‚BH2I reacts nonselec-
9
5766
J. AM. CHEM. SOC. 2005, 127, 5766-5767
10.1021/ja043743j CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Chart 1
tively (entry 4), but Me2S‚BH2I gives 10 with only traces of 11
(entry 5). Other alkynes (entries 8 and 9) are hydroborated with
low regioselectivity, similar to the results with BH3‚THF.8
The simplest interpretation of the pyridine and lutidine borane
results (Tables 1, 2) is that the ligand (L ) Py or Lut) remains
attached to boron in the product-determining step for each reaction
(Table 1, entries 1 and 5; Table 2, entries 1 and 4). However, the
data require only that the Py‚BH2I reagent follows a pathway
different from path C (Scheme 1), assuming that the reaction of
Me2S‚BH2I involves dissociation to free BH2I.
Rate-determining dissociation of 1 (X ) I) to 5 (path B) is ruled
out because the rate of methylstyrene hydroboration with Py‚BH2I
increases with alkene concentration (qualitatively, first order in
alkene). The strong counterion dependence for hydroboration
regiochemistry (Table 1) also argues against formal dissociation
in an SN1-like mechanism, but neither the rate nor the regiochem-
istry data can rule out pathways where the conversion from 5 to 3
is rate-limiting if species analogous to tight ion pairs are involved.
Path A (Scheme 1) is the simplest rationale that is consistent with
facile hydroboration from Py‚BH2I at room temperature. By way
of analogy, Ryschkewitsch et al. have reported that Py‚BH2I reacts
readily with nitrogen nucleophiles, resulting in iodide displacement
in an SN2-like process.5b Of course, the alkene is a much weaker
nucleophile, and thus it would be premature to conclude that it can
be sufficiently reactive to trigger the simplest version of path A.
Furthermore, tight ion pair versions of path B cannot be ruled out,
and other mechanistic variants remain to be evaluated.
to afford the corresponding potassium alkyltrifluoroborates 19 in
59-84% yield (Table 4). In all cases, ESMS with negative ion
detection revealed the presence of 1:1 adducts, but not 2:1 adducts.
On the other hand, use of excess alkene allowed the ESMS detection
of a substantial signal for 17.
Table 4. Preparation of Potassium Alkyltrifluoroborates 19
entry
alkene
R
R
′
R
′′
yield (%)
1
2
3
4
5
18a
18b
18c
18d
18e
Ph
C4Hg
H
Ph
Ph
H
H
H
H
84
76
82
61
59
-C4H8-
CH3
-C4H8-
H
Molander has shown that alkyltrifluoroboratesalts are attractive
reagents for Suzuki coupling applications,12 but preparation of these
salts required the use of catecholborane or BBr2H‚SMe2. The
Py‚BH2I hydroboration is a simple alternative that cleanly affords
the 1:1 adducts 19 and provides a high-yielding and convenient
route to useful organoborane substrates.
In conclusion, we have presented evidence for an unusual
hydroboration mechanism involving leaving group displacement
from activated pyridine boranes 1. Hydroboration with Py‚BH2I is
easily controlled to give the monoadducts and does not require
handling sensitive trivalent boranes.
Good functional group compatibility was observed with the
Py‚BH2I reagent (Table 3). Hydroboration of 12 followed by
oxidative workup gave >95% primary alcohols 13 (NMR assay).
Complete conversion of ester, amide, and amine substrates 12d-g
required 2 equiv of Py‚BH2I, but no reduction of these functional
groups was observed within 2 h at room temperature. On the other
hand, reduction of ketones and carboxylic acids (12, R ) C(O)Me
or CO2H) was fast compared to hydroboration of the alkene.
Table 3. Functional Group Compatibility
Acknowledgment. This work was supported by NIH (CA17918;
GM067146).
Supporting Information Available: Experimental procedures and
characterization data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
entry
alkene
R
yield (%)
1
2
3
4
5
6
7
12a
12b
12c
12d
12e
12f
n-C6H13
OBn
OTBS
OBz
NBn2
NHBn
NHBz
98
83
83
84a,b
74a
80a
89a,b
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12g
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a 2:1:1 py‚BH3/l2/alkene; 2 h at room temperature; NaOOH/MeOH.
b Oxidative workup: NaBO3‚H2O, THF/H2O.
Monoalkyl boronic acid derivatives cannot be generated directly
from unhindered alkenes using BH3‚THF because the initially
formed monoalkylborane is more reactive in hydroboration than is
the parent BH3.10 However, the Py‚BH2I method forms the 1:1
adducts considerably faster than 2:1 adducts, as might be expected
according to path A (Scheme 1). Thus, hydroboration of 1-dodecene
12a was monitored after quenching in MeOH using positive ion
detection ESMS. Strong signals for the 1:1 adducts 14 (Z ) MeO,
Py) were observed, together with a weak signal for the 2:1 adduct
(11) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J.
Org. Chem. 1995, 60, 3020.
(12) (a) Molander, G. A.; Rivero, M. Org. Lett. 2001, 3, 393. (b) Molander,
G. A.; Yun, C.-S.; Ribagorda, M.; Biolatto, B. J. Org. Chem. 2003, 68,
5534.
11
15 (Chart 1). Subsequent treatment with KHF2 allowed assay in
the negative ion detection mode. A strong signal for 16 was
observed, but 17 was not detected after precipitation from aceto-
nitrile. Preparative experiments were performed from alkenes 18
JA043743J
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