Hydroxylation of olefins using molecular oxygen via alkylboronic esters

Article abstract of DOI:10.1016/S0040-4039(00)02337-6

Alkylboronic esters derived from olefins undergo a hydroxylation in the presence of triethylamine and molecular oxygen. Alcohols were obtained in good to excellent yields without alkaline treatment of the boronate ester intermediates. Radical-clock experiments allowed the comparison between radical and polar reaction paths.

Full text of DOI:10.1016/S0040-4039(00)02337-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1661–1663
Hydroxylation of olefins using molecular oxygen via alkylboronic
esters
Christine Cadot, Peter I. Dalko* and Janine Cossy*
Laboratoire de Chimie Organique associe´ au CNRS, ESPCI, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Received 20 July 2000; accepted 19 December 2000
Abstract—Alkylboronic esters derived from olefins undergo a hydroxylation in the presence of triethylamine and molecular
oxygen. Alcohols were obtained in good to excellent yields without alkaline treatment of the boronate ester intermediates.
Radical-clock experiments allowed the comparison between radical and polar reaction paths. © 2001 Elsevier Science Ltd. All
rights reserved.
Hydroxylation of olefins by hydroboration followed by
oxidation is one of the most general reactions in
organic chemistry.1 Due to the pivotal role of this
reaction, a variety of hydroborating agents as well as
oxidation conditions were elaborated allowing milder
and more selective reactions. Although treatment of
organoboranes with hydrogen peroxide in alkaline
media2 is widely appreciated, other reagents such as
sodium perborate,3 amine N-oxides,4 perbenzoic acid,5
sodium percarbonate,6 sodium hypochlorite,7 oxone8 or
electrochemical oxidation9 were developed and repre-
sent alternatives for this transformation. Despite the
general interest in the use of molecular oxygen in fields
spanning from biochemistry10 to homogeneous cataly-
sis,11 the use of oxygen for the transformation of
organoboranes to alcohols was seldom considered.12
radical by-products and allows to prepare the corre-
sponding hydroxylated compounds in synthetically
appreciable stereoselectivity and yields (Scheme 1).
R1
R1
R1
O2
OH
BX2
R2
R2
R2
Et3N
R3
R3
R3
Yields: 46-90%
de: 80 - >99%
Scheme 1.
Hydroboration with BH3·SMe2 in THF followed by
addition of catechol resulted in the formation of the
requisite alkylboronic esters.14–16 Triethylamine (1.5–2.5
equiv.) was introduced prior to oxidation and the reac-
tion mixture was flushed with a gentle stream of oxy-
gen. It is noteworthy that the hydrolysis of the
boronate ester intermediates occurred spontaneously
during the aqueous work-up. The isolated yields and
observed selectivity of the hydroxylation reactions are
summarized in Table 1. A control experiment without
triethylamine was performed and noted in Table 1.
The oxidation of trialkylboranes by molecular oxygen
is often limited as only two of the three-alkyl groups on
boron are converted to the desired oxidized products.
The reaction stops at the monoalkylboronic ester stage
due to a weak propensity of this intermediate to oxidize
further to the corresponding borate.12c Other hydrobo-
ration intermediates such as catechol-esters afford, in
turn, low yield in molecular oxygen promoted hydroxy-
lation due to the extensive polycondensation and other
free-radical side-reactions.13 We report here that the
oxidation of trialkylboranes by oxygen in the presence
of triethylamine decreases the formation of the free-
Oxidation of alkylboronic ester derived from 2-
methylindene 1a with molecular oxygen in the presence
of triethylamine (1.5 equiv.) afforded a mixture of
trans/cis diastereomers 1b and 1c in a 10:1 ratio17 (yield
85%)17b with a small amount of ketone (<5%). In a
parallel experiment, when triethylamine was omitted,
only traces of hydroxylated products were formed
beside the corresponding ketone (12%). Under identical
conditions, as used for the conversion of 1a, the
Keywords: alcohols; amines; boron and compounds; hydroxylation;
olefins.
* Corresponding authors. Fax: +33 (0)1 40 79 46 60; e-mail:
peter.dalko@espci.fr; janine.cossy@espci.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02337-6

1662
C. Cadot et al. / Tetrahedron Letters 42 (2001) 1661–1663
Table 1. Hydroxylation of olefins via alkylboronic esters
chol and oxidation by molecular oxygen in the presence
of Et3N afforded, respectively, a mixture of regioiso-
mers 2b–2c, 4b–4c and 6b–6c with a marked preference
for the less substituted alcohols. When 1-phenylcyclo-
hexene 3a was oxidized, the trans hydroxy compound
3b was obtained exclusively. The hydroboration of enol
ether 5a produced, after oxidation and an aqueous
workup, the corresponding 1,2-diols 5b and 5c in mod-
est yield (46%). Basic nitrogen-containing products do
not change the reactivity of the system. Hydroxylation
of quinine 7a using excess of borane reagent18 followed
by oxidation and decomplexation of the aminoborane
intermediate in refluxing ethanol produced the desired
alcohol 7b.
OH
OH
+
1c
1b
1a
(10 : 1)
(10 : 1)
85%
10%
with Et3N
without Et3N
OH
OH
+
2c
2a
2b
with Et3N
69% (9 : 1)
47%
without Et3N
(9.5 : 1)
The mechanism of the reaction and in particular the
role of the Et3N was intriguing. According to the
general consensus, the initial oxidation produces a per-
oxide which may evolve to the alcohol by intermolecu-
lar redox reactions.12 The parallel polar and radical
mechanisms operating in this transformation were
probed by a radical-clock experiment19 (Scheme 2).
Ph
Ph
OH
3a
3b (only isomer detected)
with Et3N
without Et3N
64%
12%
OH
OH
+
Hydroboration of carene 8 under Fu’s condition20 fol-
lowed by oxidation with O2/Et3N afforded a 1:2 mix-
ture of alcohols 10 and 11 (yield 90%). The presence of
the two isomers confirms the supposed concurrent radi-
cal and polar paths (Scheme 3). Although the parallel
mechanisms match the classical free-radical fragmenta-
tion and intermolecular redox reaction established ear-
lier,12 it does not explain the effect of the additive. The
trialkylamine intervenes probably in more than one
process. It may serve to quench the perborate ester
intermediates forming the corresponding alkyl borates
and amine N-oxide (Scheme 3).21 This mild decomposi-
tion depletes the ketone-forming and polycondensation
free-radical paths increasing the yield of the hydroxyla-
tion products. On the other hand, the amine-oxide
formed in this reaction oxidizes the alkylboronic ester
(such as 9) according to the earlier proposed mecha-
nism.4 The product distribution reflects the relative
rates of the competing reactions.
BnO
BnO
BnO
4a
4b
4c
with Et3N
without Et3N
(11 : 1)
(10 : 1)
71%
54%
+
OH
OTMS
OH
OH
OH
5b
5a
5c
with Et3N
46% (4 : 1)
12% (4 : 1)
without Et3N
Ts
N
Ts
Ts
OH
N
N
OH
6b
with Et3N
without Et3N
6a
6c
(2 : 1)
81%
64%
(5 : 1)
HO
Typical procedure: To a solution of borane–dimethyl-
sulfide complex (1.2 mmol, 600 mL, 2.0 M in THF), the
olefin 1a (neat, 1.0 mmol) was added in one portion at
0–5°C under an inert atmosphere. The mixture was
stirred for 4 h at rt and triethylamine (210 mL, 1.5
mmol) was added in one portion at 0°C. After 5 min at
0–5°C a solution of catechol (132 mg, 1.2 mmol) in
THF (400 mL) was introduced, the reaction mixture was
stirred for 2.5 h and a gentle stream of dry oxygen was
bubbled through the reaction mixture for 1 h. The
mixture was stirred vigorously for an additional 11 h by
maintaining the oxygen atmosphere over the reaction
mixture. The slightly rose colored solution was diluted
with CH2Cl2 (10 mL), washed with a saturated solution
of NaHCO3 (2×20 mL), dried over Na2SO4 and concen-
trated under reduced pressure. The residue was purified
by flash chromatography on silica gel (pentane/ethyl
acetate: 4/1) to afford the desired alcohols.
N
HO
N
HO
H3CO
H3CO
N
N
7b (only isomer detected)
7a
with Et3N
without Et3N
62%
44%
Reaction conditions: (i) BH3·SMe2 in THF (1.2 equiv.), 0–5°C, then
rt, 4 h; (ii) Et3N (1.5 equiv.), then catechol (1.2 equiv.), THF, 0–5°C
then rt, 2.5 h; (iii) O2, rt, 12 h.
hydroxylation of terminal olefins such as 2a, 4a and 6a
followed similar trends. Accordingly, hydroboration
using BH3·SMe2 in THF followed by addition of cate-

C. Cadot et al. / Tetrahedron Letters 42 (2001) 1661–1663
1663
CH3CON(Me)2 (10%),
R
O2
catecholborane (2 equiv.)
OH
+
Et3N
THF, rt
then H2O
(90%)
OH
8
9
11
10
O
R =
B
1 : 2
O
Scheme 2.
5. Johnson, J. R.; Van Campen, M. A. J. Am. Chem. Soc.
1938, 60, 121–124.
6. Kabalka, G. W.; Wadgaonkar, P. P.; Shoup, T. M.
O
•
O-O-B
Et3N
O2
•
O
9
Tetrahedron Lett. 1989, 30, 5103–5104.
7. Brown, H. C. US Patent, 3,439,046, 1969.
8. Webb, K. S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117–
5120.
9. Taguchi, T.; Takahashi, Y.; Itoh, M.; Suzuki, A. Chem.
Lett. 1974, 1021–1022.
10. In Active Oxygen in Biochemistry; Valentine, J. S.; Foote,
C. S.; Greenberg, A.; Liebman, J. F., Eds.; Blackie:
London, 1995.
Et3N(O)
O
O
O
O
O
B
B
O
O
O
O
Et3N(O)
Et3N
B
9
O
11. See for example: Wirth, T. Angew. Chem., Int. Ed. 2000,
39, 334–335.
12. (a) Brown, H. C.; Midland, M. M.; Kabalka, G. W.
Tetrahedron 1986, 42, 5523–5530; (b) Davies, A. G.;
Roberts, P. B. J. Chem. Soc. B 1969, 311–321; (c) Wilke,
G.; Heimbach, P. Liebigs Ann. Chem. 1962, 652, 7–21; (d)
Mirviss, S. B. J. Org. Chem. 1967, 32, 1713–1717.
13. Brown, H. C.; Midland, M. M. Tetrahedron 1987, 43,
4059–4070.
Scheme 3.
Acknowledgements
The Fondation pour la Recherche Me´dicale (grant No.:
40001838-01) is gratefully acknowledged for financial
support.
14. (a) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91,
1179–1191; (b) Lane, C. F.; Kabalka, G. W. Tetrahedron
1976, 32, 981–990.
15. 1H NMR analyses in selected cases of the crude mixtures
showed the presence of minor amounts of isomers
alongside with the desired product.
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