B-Alkylcatecholboranes as a Source of Radicals for Efficient Conjugate Additions and Allylations

Article abstract of DOI:10.1055/s-2003-42430

B-Alkylcatecholboranes, easily prepared in situ by hydroboration of alkenes, are powerful radical precursors that can be used for carbon-carbon bond formation. Typical procedures for (a) conjugate addition to enones, (b) conjugate addition to activated al

Full text of DOI:10.1055/s-2003-42430

2740
PRACTICAL SYNTHETIC PROCEDURES
B-Alkylcatecholboranes as a Source of Radicals for Efficient Conjugate
Additions and Allylations
A
lkylcatecholbora
r
nes as
a
n
Source of
R
a
a
dicals ud-Pierre Schaffner, Barbara Becattini, Cyril Ollivier, Valéry Weber,
Philippe Renaud*
PSP
University of Berne, Department of Chemistry and Biochemistry, Freiestrasse 3,
3000 Berne 9, Switzerland
Fax +41(31)6313426; E-mail: philippe.renaud@ioc.unibe.ch
Received 11 September 2003
No12
Abstract: B-Alkylcatecholboranes, easily prepared in situ by hydroboration of alkenes, are powerful radical precursors that can be used for
carbon–carbon bond formation. Typical procedures for (a) conjugate addition to enones, (b) conjugate addition to activated alkenes such as
vinyl sulfones, and (c) direct allylation are described. Experimentally, these three one-pot reactions are easy to perform. No slow addition
of a reagent, a procedure frequently encountered in intermolecular radical additions, is required.
Key words: radicals, tin-free, hydroboration, allylation, conjugate addition
Procedure 1
O
(2 eq)
(5 eq)
HB
O
O
O
B
H2O (3 eq), DMPU (1 eq),
O2 (0.2 eq), CH2Cl2
O
Me2NCOMe (10 mol%)
O
CH2Cl2, ∆, 3h
1
2 (88%)
Procedure 2
O
O
(2 eq)
HB
SO Ph
(3 eq)
2
O
SPy
SO2Ph
4 (75%)
B
PTOC-OMe (3 eq)
150 W lamp, C6H6, 10 °C
O
Me2NCOMe (10 mol%)
CH2Cl2, ∆, 3h
3
S
OMe
O
PTOC-OMe:
N
O
Procedure 3
SO2Ph
O
O
(2 eq)
HB
O
B
SO2Ph
(1.2 eq)
SO2Ph
O
Me2NCOMe (10 mol%)
t-BuON=NOt-Bu (9 mol%)
CH2Cl2, ∆, 3h
CH2Cl2, reflux
5
6 (89%)
Scheme 1
For many years, organoboron chemistry has been a privi- intra- and intermolecular processes. In this context, we
leged field of research for synthetic organic chemists. Fol- have recently reported several procedures involving the
lowing the spectacular development of radical chemistry hydroboration of alkenes with catecholborane, followed
in organic synthesis, the use of organoboranes has recent- by treatment with a catalytic amount of a radical initiator
ly led to many novel and useful synthetic applications,1,2 [O2,
di-tert-butyl
hyponitrite
or
PTOC-OMe
particularly for the formation of carbon–carbon bonds in (PTOC = pyridine-2-thione-N-oxycarbonyl)] in the pres-
ence of a radical trap.3–9 We have demonstrated that these
B-alkylcatecholboranes are excellent radical precursors
and can be used for highly efficient radical additions to
, -unsaturated ketones (Procedure 1),3 for conjugate ad-
SYNTHESIS 2003, No. 17, pp 2740–2742
Advanced online publication: 14.10.2003
DOI: 10.1055/s-2003-42430; Art ID: Z13303SS.pdf
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
3

PRACTICAL SYNTHETIC PROCEDURES
Alkylcatecholboranes as a Source of Radicals
2741
ditions to various activated olefins using a Barton’s car- ment with 1.2 equivalents of 2,3-bis(phenylsulfonyl)pro-
bonate as chain transfer reagent (Procedure 2)5,10 and pene affords the allylated product in 89% yield. The
finally for allylation with allyl sulfones (Procedure 3)9 efficiency of this intermolecular allylation reaction using
(Scheme 1).
only 1.2 equivalents of the allylating agent is unique. A
large variety of allylsulfones have been reported to react
satisfactorily under these conditions.
Procedures
Procedure 1 depicts a radical-mediated conjugate addition
of organoboranes to enones.3 1-Methylcyclopent-1-ene
Applications
(1) is hydroborated with commercially available cate- We have recently demonstrated that rhodium(I)-catalyzed
cholborane using N,N-dimethylacetamide as catalyst.11 hydroboration is perfectly compatible with radical reac-
Water (3 equiv), ethyl vinyl ketone (5 equiv), DMPU (1 tions. For instance, enantioselective hydroboration of nor-
equiv) are added successively to the solution of the inter- bornene (7) with [Rh(COD)Cl]2/(S,S)-BDPP as catalyst
mediate B-alkylcatecholborane. Traces of air are suffi- furnished the -S-pyridyl ester 8 after conjugate addition
cient to initiate the chain process, after treatment and of the intermediate boronate to methyl acrylate in the
purification by flash chromatography, 1-(2-methylcyclo- presence of PTOC-OMe (Scheme 2).8 Desulfurization
pentyl)pentan-3-one (2) is obtained in 88% yield. This re- with zinc in acetic acid afforded the ester 9 in 85% ee.
action is presumably occurring via formation of a
transient boron enolate. DMPU is essential to obtain good
yield, however, its exact role is still obscure. The oxygen
initiated procedure is suitable for a wide range of , -un-
saturated ketones and aldehydes. Other radical traps such
as unsaturated esters and amides as well as vinyl sulfones
do not react under these conditions.
Procedure 2 represents the conjugate addition of the cy-
clohexyl radical to phenyl vinyl sulfone.5 This reaction re-
quires the use of PTOC-OMe (Barton carbonate) as chain
transfer reagent. The Barton carbonate acts also as an ini-
tiator by providing a methoxycarbonyloxyl radical upon
irradiation with a standard 150 W tungsten lamp. This
Scheme 2
oxyl radical reacts rapidly with the B-alkylcatecholborane
to afford a nucleoplilic cyclohexyl radical that adds to
Cyclization reactions starting from dienyl systems are
also possible. A typical example is shown in Scheme 3.
The regioselective hydroboration of the , -unsaturated
lactone 10 followed by treatment with PTOC-OMe af-
fords the bicyclic lactone 11. The versatility of the thiopy-
ridyl group is demonstrated by the efficient conversion of
11 to the -methylenelactone 12.7
phenyl vinyl sulfone. The radical adduct has some electro-
philic character due to its substitution by an electron-with-
drawing group and therefore reacts rapidly with the
electron-rich thiocarbonyl group of the PTOC-OMe to af-
ford the -S-pyridyl sulfone 4 together with the methoxy-
carbonyloxyl radical necessary to sustain the chain
reaction. The remarkable reactivity difference between
the three radicals involved is the key point for the success
of this reaction. The reaction can be run in a one-pot pro-
cedure without any slow addition of the chain transfer re-
agent. This represent a clear advantage relative to the tin
hydride-mediated conjugate addition. Moreover, the pro-
cess is nonreductive and furnishes products bearing a S-
pyridyl group than can be removed or transformed into a
variety of functional groups. This procedure can be ex-
tended to a wide range of radical traps such as methyl
acrylate, dimethyl fumarate, N-phenylmaleimide, phenyl
vinyl sulfone and phenyl vinyl sulfoxide.
Procedure 3 illustrates the radical allylation of organobo-
ranes with allylsulfones.9 In situ hydroboration of (–)- -
pinene 5 with catecholborane, followed directly by treat-
Scheme 3
Synthesis 2003, No. 17, 2740–2742 © Thieme Stuttgart · New York

2742
A.-P. Schaffner et al.
PRACTICAL SYNTHETIC PROCEDURES
Anal. Calcd for C19H23NO2S2 (361.52): C, 63.13; H, 6.41. Found: C,
63.20, H, 6.47.
1-(2-Methylcyclopentyl)pentan-3-one (2)
Freshly distilled catecholborane (0.64 mL, 6.0 mmol) was added
dropwise at 0 °C to a solution of 1-methylcyclopent-1-ene (1; 0.247
g, 3.0 mmol) and N,N-dimethylacetamide (28.0 L, 0.3 mmol) in
CH2Cl2 (2.0 mL) under N2. The reaction mixture was heated under
reflux for 3 h. H2O (0.16 mL, 9 mmol) was added at 0 °C and the
solution was stirred for 15 min at r.t. CH2Cl2 (8 mL), 1,3-dimethyl-
hexahydro-2-pyrimidone (DMPU; 0.36 mL, 3 mmol), and pent-1-
en-3-one (1.26 g, 15 mmol) were successively added to this solu-
tion. Air (60 mL, 0.5 mmol O2) was introduced over 2 h with a sy-
ringe (needle placed just above the reaction surface). After stirring
for 2 h at r.t., the mixture was treated with aq sat. solution of NH4Cl
(10 mL) and extracted with Et2O (3 × 20 mL). The combined organ-
ic layers were dried (MgSO4), filtered, and concentrated under re-
duced pressure. Purification by flash chromatography over silica gel
(Et2O–hexane, 5:95) afforded 2 (443 mg, 88%) as a colorless oil.
Phenyl 1-{[(1S,2R,3R,5S)-2,6,6-Trimethylbicyclo[3.1.1]hept-3-
yl]methyl}vinyl Sulfone (6)
Freshly distilled catecholborane (0.64 mL, 6 mmol) was added
dropwise at 0 °C to a solution of (–)- -pinene (5; 409 mg, 3.0
mmol) and N,N-dimethylacetamide (28.0 L, 0.3 mmol) in CH2Cl2
(2.0 mL) under N2. The reaction mixture was heated under reflux
for 3 h. MeOH (0.15 mL, 3.6 mmol) was added at 0 °C and the so-
lution was stirred for 15 min at r.t. 2,3-Bis(phenylsulfonyl)propene
(1.160 g, 3.6 mmol) and di-tert-butyl hyponitrite (15 mg, 3 mol%)
were added, and the solution was heated at reflux, while adding di-
tert-butyl hyponitrite (15 mg, 3 mol%) every 1 h. After 3 h, the re-
action mixture became black and the reaction was stopped. Evapo-
ration of the solvent under reduced pressure followed by
purification of the residue by flash chromatography over silica gel
(hexane–EtOAc, 4:1) afforded 6 (0.848 g, 89%) as a colorless oil.
1H NMR (300 MHz, CDCl3): = 7.93–7.83 (m, 2 H), 7.64–7.45 (m,
3 H), 6.41 (s, 1 H), 5.80 (s, 1 H), 2.52 (dd, J = 15.1, 3.7 Hz, 1 H),
2.24 (m, 1 H), 2.06 (m, 1 H), 1.95–1.69 (m, 3 H), 1.54 (m, 1 H), 1.23
(m, 2 H), 1.13 (s, 3 H), 0.93 (m, 3 H), 0.86 (s, 3 H), 0.61 (d, J = 9.6
Hz, 1 H).
1H NMR (360 MHz, CDCl3): = 2.41 (m, 4 H), 1.80 (m, 3 H), 1.54
(m, 2 H), 1.40 (m, 1 H), 1.32 (m, 1 H), 1.23 (m, 2 H), 1.23–1.13 (m,
3 H), 1.05 (t, J = 7.3 Hz, 3 H), 0.96 (d, J = 7 Hz, 3 H).
13C NMR (90.5 MHz, CDCl3): = 212.2, 47.2, 41.5, 40.5, 35.8,
34.7, 32.1, 28.7, 23.3, 19.3, 7.8.
MS (EI): m/z: 169 [M+ + 1], 151, 139, 121, 95, 93, 81, 69, 57.
13C NMR (75 MHz, CDCl3): = 149.3, 139.2, 133.4, 129.1, 128.2,
124.6, 47.9, 43.7, 41.6, 38.6, 34.2, 34.1, 33.9, 27.9, 22.8, 21.2.
Anal. Calcd for C11H20O (168.15): C, 78.51; H, 11.98. Found: C,
78.45, H, 11.94.
MS (EI): m/z = 319 [M+ + 1], 246, 218, 177, 137, 81, 55, 41.
HRMS (ESI-MS): m/z calcd for C19H27O2S ([M + 1]+): 319.1731;
2-{[2-Cyclohexyl-1-(phenylsulfonyl)ethyl]sulfanyl}pyridine (4)
Freshly distilled catecholborane (0.64 mL, 6.0 mmol) was added
dropwise at 0 °C to a solution of cyclohexene (0.247 g, 3.0 mmol)
and N,N-dimethylacetamide (28.0 L, 0.3 mmol) in CH2Cl2 (2.0
mL) under N2. The reaction mixture was heated under reflux for 3
h. MeOH (0.15 mL, 3.6 mmol) was added at 0 °C and the solution
was stirred for 15 min at r.t. CH2Cl2 was evaporated under vacuum
with strict exclusion of O2. A yellow solution of PTOC-OMe (9
mmol) [freshly prepared by stirring the sodium salt of N-hydroxy-
pyridine-2-thione (1.41 g, 9.45 mmol) and methyl chloroformate
(0.7 mL, 9 mmol) in benzene (15 mL) for 1 h in the dark] was added
to the solution followed by phenyl vinyl sulfone (2.52 g, 15 mmol)
and DMPU (0.36 mL, 3 mmol). The mixture was irradiated at 10 °C
with a 150 W tungsten lamp for 14 h, and treated with aq 1 N NaOH
(20 mL). The aqueous layer was extracted with CH2Cl2 and the
combined organic phases were washed with brine (30 mL), dried
(MgSO4), and concentrated under reduced pressure. The crude
product was purified by flash chromatography over silica gel (hex-
ane–EtOAc, 4:1) to afford 4 (0.892 g, 88%) as a white solid. For an-
alytical purpose, a sample was recrystallized from EtOH; mp 80–
81 °C.
found: 319.1729.
Acknowledgment
This work was supported by the Swiss National Science Foundation
(grant 21-67106.01 and 7SUPJ062348). We thank Callery Chemi-
cal Company (Pittsburgh) and Z & S Handel AG (Kloten) for the
generous gift of catecholborane.
References
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1H NMR (360 MHz, CDCl3): = 8.20 (d, J = 5.0 Hz, 1 H), 7.88 (d,
J = 7.3 Hz, 2 H), 7.43–7.26 (m, 4 H), 6.95 (d, J = 7.7 Hz, 1 H), 6.89
(dd, J = 7.3, 5.4 Hz, 1 H), 5.80 (dd, J = 12.2, 3.1 Hz, 1 H), 2.19
(ddd, J = 14.5, 9.5, 2.7 Hz, 1 H), 1.86–1.77 (m, 2 H), 1.74–1.56 (m,
5 H), 1.31–1.00 (m, 4 H), 0.96–0.83 (m, 1 H).
13C NMR (90 MHz, CDCl3): = 122.7, 120.7, 63.6, 34.5, 33.9, 33.8,
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Synthesis 2003, No. 17, 2740–2742 © Thieme Stuttgart · New York