Modified B-alkylcatecholboranes as radical precursors

Article abstract of DOI:10.1002/ejoc.201001120

Generation of radicals from B-alkylcatecholboranes represents an efficient tin-free procedure for the generation of alkyl radicals. A modified version of this method has been developed. The simple catechol is replaced by a dihydroxylated tetrahydroisoquin

Full text of DOI:10.1002/ejoc.201001120

FULL PAPER
DOI: 10.1002/ejoc.201001120
Modified B-Alkylcatecholboranes as Radical Precursors
Monique Lüthy,[a] Vincent Darmency,[a] and Philippe Renaud*[a]
Keywords: Radical reactions / Boranes / Hydroboration / Quinones
Generation of radicals from B-alkylcatecholboranes repre-
sents an efficient tin-free procedure for the generation of
alkyl radicals. A modified version of this method has been
lowed by treatment with the dihydroxytetrahydroisoquino-
line. The new alkylboronates of this type are suitable radical
precursors in a wide range of reactions such as sulfenylation,
developed. The simple catechol is replaced by a dihydrox- allylation, alkynylation, vinylation, and addition to quinones.
ylated tetrahydroisoquinoline, which can be separated from
the reaction products by simple extraction with an aqueous
acid solution. The modified alkyl radical precursors are easily
prepared from alkenes by hydroboration with BH3·Me2S fol-
This strategy is particularly useful when separation of reac-
tion products from catechol residues is problematic, as illus-
trated by a radical addition to 1,4-benzoquinone leading to
2-alkyl-1,4-hydroquinones.
after workup, nontoxic byproducts such as boronic acid de-
rivatives and catechol. Reaction products are usually easily
purified by filtration through silica gel. Filtration through
a small pad of aluminum oxide (basic or neutral) is suf-
ficient to remove all the boron- and catechol-derived by-
products. The removal of catechol derivatives by washing
the crude products with an aqueous base is also possible.
However, such purification strategies are inconvenient when
slightly acidic or polar products are formed. In such cases, a
large discrepancy between yields estimated by GC or NMR
analysis of the crude products and isolated yields is ob-
served as shown in the example depicted in Scheme 1.[7]
Introduction
Radical reactions have become a very useful synthetic
tool and are routinely applied for the synthesis of natural
products.[1] Industrial uses of radical reactions are, however,
despite some important exceptions, rather scarce. A major
reason for this is the fact that many radical processes are
still based on the use of triorganotin reagents. These rea-
gents are not only toxic, but they are also tedious to remove
from the final products. Therefore, the demand for prepara-
tive tin-free radical reactions has been growing over the last
decade.[2] Among the many strategies to avoid tin in radical
reactions, it was found that the use of organoboranes as
radical precursors is particularly promising. Indeed, they
generate efficiently radicals, and they produce nontoxic bor-
onic acid derivatives as byproducts.[3] Organoboranes can
be employed for a wide range of radical reactions involving
primary, secondary, and tertiary alkyl radicals. Recently, the
readily available B-alkylcatecholboranes were shown to be
unique precursors of alkyl radicals, and their efficiency for
a broad range of reactions was demonstrated.[4] First, an
efficient radical addition of in situ formed B-alkylcatechol- Scheme 1. Radical addition to 1,4-benzoquinone. Discrepancy be-
tween NMR yield determined by analysis of the crude product and
isolated yield.
boranes onto α,β-unsaturated enones and enals was re-
ported.[5] This reaction represents a modified and improved
version of the Brown–Negishi reaction.[6] More recently,
this reaction was extended to the addition of radicals onto
In view of these purification difficulties, a modified strat-
benzoquinones,[7] thus creating straightforward access to 2-
egy that facilitates isolation of products exhibiting polarity
substituted hydroquinones, which are common subunits in
and acidity similar to catechol was investigated. Modifica-
biologically active secondary metabolites (Scheme 1). B-
Alkylcatecholborane-mediated radical reactions produce,
tion of the catechol part of B-alkylcatecholboranes by in-
troducing an amino group will deliver amino-substituted
catechol-like byproducts that are expected to be easily re-
[a] Department of Chemistry and Biochemistry, University of Bern
moved by acidic workup. We report here the development
of such modified B-alkylcatecholboranes and their applica-
tions in radical chemistry such as the radical addition to
benzoquinones.
Freiestrasse 3, 3012 Bern, Switzerland
Fax: +41-31-631-3426
E-mail: philippe.renaud@ioc.unibe.ch
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001120.
Eur. J. Org. Chem. 2011, 547–552
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Lüthy, V. Darmency, P. Renaud
FULL PAPER
The generation of modified B-isopinocampheylcatechol-
borane 12a from 1a was examined in more detail. Our ini-
tial procedure (see Scheme 2) involves hydroboration with
BH3·Me2S (1 equiv.) followed by reaction with 7. Another
approach involving direct hydroboration of α-pinene (1a)
with modified catecholborane 14 should afford the same B-
isopinocampheylcatecholborane 12a (Scheme 3). To test
this hypothesis, catechol 7 was transformed into catechol-
borane 14 by treatment with BH3·Me2S (1 equiv.). Unfortu-
nately, presumably because of aggregation, borane 14 is
only partly soluble and irreproducible yields are obtained
for the hydroboration–sulfenylation of 1a. All attempts to
improve the solubility of 14 by varying the solvent did not
increase the yield or reproducibility and this approach was
abandoned. On the basis of these results, the formation of
B-alkylcatecholboranes through hydroboration of alkenes
with BH3·Me2S followed by reaction with tetrahydroiso-
quinoline 7 was selected for the rest of the work.
Results and Discussion
We started our investigations by testing different modi-
fied B-isopinocampheylcatecholborane analogues in the
highly efficient radical sulfenylation reaction depicted in
Scheme 2.[8] Desired organoboranes 8–12 are generated in
a one-pot process involving hydroboration of α-pinene (1a)
with a borane–dimethyl sulfide complex (1 equiv.) followed
by reaction with modified catechols 3–7.[9] The radical sulf-
enylation reaction with S-phenyl benzenethiosulfonate[10]
was then run according to the procedure previously de-
scribed by using di-tert-butyl hyponitrite (3 mol-%) as radi-
cal initiator in refluxing dichloromethane.[8] The reaction
involving aminocatechols 4–7 was then washed with a 10%
hydrochloric acid aqueous solution, which successfully re-
moved 4–7 allowing an easy isolation of product 13.
Scheme 3. Sulfenylation procedure involving generation of modi-
fied B-isopinocampheylcatecholborane 12a through hydroboration
with catecholborane 14.
Extension of the use of B-alkylcatecholboranes of type
12 for allylation, alkynylation, and vinylation procedures
was investigated (Scheme 4). Commercially available alk-
enes such as (–)-β-pinene (1b), (Ϯ)-α-pinene (1a), and 2,3-
Scheme 2. Testing a selection of catechol analogues in the sulf-
enylation of B-isopinocampheylborane.
The use of catechol 3 affords desired product 13 in 84% dimethyl-2-butene (1c) were selected for the generation of
yield, a yield close to that obtained when α-pinene is di- primary, secondary, and tertiary alkyl radicals, respectively.
rectly hydroborated with catecholborane according to the As radical traps, allyl sulfones 15 and 16, alkynyl sulfone
original procedure (90% yield).[8] 2,3-Dihydroxypyridine (4) 17, and vinyl sulfone 18 were chosen. Alkenes were hydro-
gives a very low yield (10%) of 13. The use of dopamine 5 borated with BH3·Me2S, treated with 7, and the in situ gen-
leads to a modest yield of 50%. It was assumed that the erated 12 was allowed to react with the different radical
intermediate organoboranes derived from 4 and 5 are traps in
a
dichloromethane/N,N-dimethylformamide
hardly formed or are undergoing oligomerization, presum- (DMF) solvent mixture at 40 °C. The radical process was
ably due to disturbing B–N interactions. Indeed, it is known initiated by a constant flow of air passing through the reac-
that boronic ester derivatives of 4 undergo macrocyclization tion vessel. A substoichiometric amount of oxygen (0.14 to
through the formation of dative B–N bonds.[11] In contrast 0.28 equiv.) was necessary to reach completion of the reac-
to these deceiving results, the overall one-pot sequences tions. Better yields were obtained when DMF was used a
using tetrahydroisoquinolines 6 or 7 (82 and 89% yield) are as a cosolvent; this was partly due to the better solubility
as efficient as the corresponding reaction with catechol 3. of the sulfone radical traps in the DMF-containing solvent
Tetrahydroisoquinolines 6 and 7 are synthesized from com- mixture. Neither neat dichloromethane nor neat DMF led
mercially available 6,7-dimethoxy-1,2,3,4-tetrahydroiso- to equally good results. Deviations in concentration of the
quinoline hydrochloride in two steps via the HBr salt of the reaction mixture did not affect the yield, but the 2:1 ratio
tertiary amine.[12] Because the isolation of N-methylated of CH2Cl2/DMF was the most efficient. Results depicted in
free amine 6 proved to be difficult, N-benzylated amine 7, Scheme 4 show that, despite some minor decreases in yield
which was easily isolated due to its increased hydropho- compared to the original method, consistently good results
bicity, was kept for further investigations.
are obtained with secondary and tertiary radicals generated
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Modified B-Alkylcatecholboranes as Radical Precursors
from α-pinene (1a) and tetramethylethylene (1c) (19a–22a: boranes 12a/12c prepared from 2a/2c, the hydroboration
71–84%; 19c: 51%, 21c: 74%). The increase in yield from 64 step was less problematic. Indeed, Brown reported that
to 84% for vinylated product 22a is noteworthy. Reactions monoisopinocampheylborane 2a is best prepared indirectly
involving a primary radical derived from 1b gave moderate from the diisopinocampheylborane[14,16] even if direct ac-
yields. The moderate yields for 19b (38%) and 21b (65%) cess by hydroboration of 1a was reported.[17] The hydrobor-
results probably from difficulties in the hydroboration step. ation of 1c was performed according to a published pro-
Indeed, the hydroboration of unhindered alkenes does not cedure.[18]
stop at the monoalkylborane stage and terminal alkenes are
In order to further illustrate the interest of generating
known to proceed exclusively to the trialkylborane spe- radicals from modified B-alkylcatecholborane 12, the radi-
cies.[13] We observed that hydroboration of 1b with a sub- cal addition onto 1,4-benzoquinone was investigated. Re-
stoichiometric quantity of a borane dimethyl sulfide com- cently, we reported that alkyl radicals generated from B-
plex in dichloromethane afforded the trialkylborane within alkylcatecholboranes add onto 1,4-benzoquinone at either
10 min at room temperature, which is in accordance with the C-atom leading to substituted hydroquinones or at the
Brown’s findings using hexane as the solvent.[14] Neverthe- O-atom resulting in aryl ethers.[7] It was shown that compet-
less, an older study by Brown showed that trialkylboranes ing O-addition strongly depends on the bulkiness of the
can equilibrate to the monoalkylborane in the presence of alkyl radical. The new reaction procedure with in situ gen-
a diborane solution.[15] We assumed that such an equilibra- erated modified B-alkylcatecholboranes 12 afforded the 1,4-
tion would occur between the boronic species derived from conjugate addition products 23 and aryl ethers 24 in ratios
1b and the borane–dimethyl sulfide complex. In principle, comparable to the original method but with increased iso-
trialkylboranes are also radical precursors, although they lated yields (Scheme 5). This procedure involved the ad-
are less effective, as only one of the three alkyl groups is dition of a slight excess amount of 12 (1.1 equiv.) to 1,4-
efficiently transformed into the product.[3b,3d] For organo- benzoquinone (22) in dichloromethane containing DMPU.
Compared to the published procedure, the excess amount
of B-alkylcatecholboranes could be reduced from 2 to
1.1 equiv. and the use of water as an additive was aban-
doned, as it does not bring any yield enhancement.[7] As
anticipated, isolation and purification of the products is fa-
cilitated relative to the original method with type 8 organ-
oboranes, as an acidic workup enabled facile and complete
removal of 7 and all derivatives of 7. For example, hydro-
quinone 23d, which is formed in 93% NMR yield from 8d,
was only isolated in 74% yield (see Scheme 1). By using 12,
the 2-alkylated hydroquinone is now isolated in 88% yield.
Scheme 4. Radical allylation, alkynylation, and vinylation of modi-
fied B-alkylcatecholboranes. Yields obtained by the previusly pub-
lished method using hydroboration with catecholborane are given
Scheme 5. Radical addition of modified B-alkylcatecholboranes
onto 1,4-benzoquinone.
in parentheses.[4]
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549

M. Lüthy, V. Darmency, P. Renaud
FULL PAPER
hydroisoquinoline (39.2 g, 63%) was collected by filtration as a col-
orless solid. M.p. 89–90 °C. 1H NMR (300 MHz, CDCl3): δ = 7.42–
7.28 (m, 5 H, arom. H), 6.60 (s, 1 H, arom. H), 6.49 (s, 1 H, arom.
H), 3.84 (s, 3 H, MeO), 3.81 (s, 3 H, MeO), 3.69 (s, 2 H, NCH2Ar),
3.55 (s, 2 H, NCH2Ar), 2.85–2.81 (m, 2 H, NCH2), 2.76–2.72 (m,
2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 147.7, 147.4,
138.6, 129.2, 128.4, 127.2, 126.9, 126.4, 111.7, 109.7, 62.9, 56.0,
55.8, 50.9, 28.9 ppm. HRMS (ESI): calcd. for C18H21NO2Na
306.1469; found 306.1465. Further data are in accordance with the
literature.[19] A mixture of 2-benzyl-6,7-dimethoxy-1,2,3,4-tetra-
As expected, purification is less tedious due to the absence
of the typical black slurry stemming from polymerized cate-
chol.
As already mentioned, a twofold excess of organoborane
was required in the original procedure with 8 to prevent the
oxidation of the hydroquinone products in the presence of
benzoquinone.[7] In the current procedure with 12, this ex-
cess amount could be reduced to 1.1 equiv. without observ-
ing the formation of 2-alkylated quinones. On the other
hand, an efficient preparation of 2-substituted quinones is hydroisoquinoline (47.3 g, 167 mmol) and HBr (48%, 600 mL) was
heated under reflux for 3 h and then stirred overnight at room tem-
perature, allowing the product to precipitate. The solid was filtered
and washed with cold EtOH, affording hydrobromide salt 7·HBr
as a colorless solid (53.1 g, 95%). Salt 7·HBr (15 g, 44.6 mmol) was
suspended in water (700 mL). A 4 n NaOH solution (11.5 mL) was
slowly added until basic pH and the initially white suspension
turned yellow. Free amine 7 was collected by filtration and washed
with cold water. Oven drying at 55 °C and 40 mbar for 60 h af-
forded 7 (10.2 g, 90%) as a bright yellow solid. M.p. 150–151 °C.
1H NMR (400 MHz, DMSO): δ = 8.61 (s, 2 H, OH), 7.33–7.22 (m,
5 H, arom. H), 6.45 (s, 1 H, arom. H), 6.35 (s, 1 H, arom. H), 3.57
(s, 2 H, NCH2Ar), 3.34 (s, 2 H, NCH2Ar), 2.63–2.53 (m, 4 H,
NCH2CH2Ar) ppm. 13C NMR (100 MHz, DMSO): δ = 143.6,
143.3, 138.6, 128.7, 128.2, 126.9, 125.1, 124.3, 115.1, 113.1, 61.9,
additionally possible by treating intermediate alkylboronate
12 with an excess amount of benzoquinone. As shown in
Scheme 6, quinone 25d was obtained in 65% yield from cy-
clohexene 1d by using a fivefold excess of 1,4-benzoquin-
one.
Scheme 6. One-pot radical preparation of 2-substituted quinones.
55.1, 50.5, 28.0 ppm. IR (neat): ν = 3162 (br.), 2822 cm–1. LRMS
˜
(EI): m/z (%) = 255 (79) [M]+, 226 (50), 178 (54), 164 (67), 136
(81), 120 (75), 91 (100), 77 (43), 65 (73). HRMS (EI): calcd. for
C16H17NO2 255.12593; found 255.12596. C16H17NO2 (255.31):
calcd. C 75.27, H 6.71, N 5.49; found C 75.35, H 6.74, N 5.52.
Conclusions
A modified version of the method involving B-alkyl-
catecholboranes as radical precursors has been developed. Phenyl(2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)sulfane (13): A solu-
tion of (Ϯ)-α-pinene (1a; 159 μL, 1 mmol) and borane–dimethyl
sulfide (90% in dimethyl sulfide, 105 μL, 1 mmol) in CH2Cl2
(1.0 mL) was heated under reflux for 3 h and cooled to room tem-
perature afterwards. This solution was added by cannula to a sus-
pension of catechol analogue 7 (255 mg, 1 mmol) in CH2Cl2
(2.0 mL) at 0 °C over a period of 15 min. Evolution of hydrogen
was observed. More CH2Cl2 (1.0 mL) was added. and the reaction
mixture was stirred for 1.5 h at room temperature. S-Phenyl benz-
enethiosulfonate (300 mg, 1.2 mmol), di-tert-butyl hyponitrite (5–
9 mg, 0.03–0.05 mmol), and CH2Cl2 (0.5 mL) were added, and the
The simple catechol has been replaced by dihydroxylated
tetrahydroisoquinoline 7, which can be separated from the
reaction products by simple extraction with an aqueous
acid solution. The modified alkyl radical precursors are
generated in situ from alkenes by hydroboration with com-
mercially available borane–dimethyl sulfide complex fol-
lowed by treatment with modified catechol 7. The new alk-
ylboronates of type 12 are suitable radical precursors for
a wide range of reaction such as sulfenylation, allylation,
alkynylation, vinylation, and addition to quinones. This mixture was heated under reflux. After 1 h, more di-tert-butyl hy-
ponitrite (5–9 mg, 0.03–0.05 mmol) was added, and the mixture
was heated for another hour under reflux. After allowing the reac-
tion to stir overnight at room temperature, it was worked up.
EtOAc (10 mL) and a 10% aqueous HCl solution (10 mL) were
added, and some remaining precipitate was removed by filtration.
The layers were separated, the aqueous layer was back-extracted
with EtOAc (10 mL), and the organic layer was washed again with
a 10% aqueous HCl solution (10 mL). The combined organic lay-
ers were washed with brine, dried with MgSO4, filtered, and con-
centrated under reduced pressure. Purification by flash chromatog-
raphy (pentane/Et2O, 98:2) afforded 13 (202 mg, 82%) as an insepa-
rable mixture with a minor quantity of side product PhSSPh. Data
for 13: 1H NMR (300 MHz, CDCl3): δ = 7.44–7.40 (m, 2 H, arom.
H), 7.32–7.18 (m, 3 H, arom. H), 3.39 (ddd, J = 9.8, 7.2, 5.8 Hz, 1
H, CHS), 2.56–2.46 (m, 1 H), 2.32 (dtd, J = 9.8, 6.2, 2.2 Hz, 1 H),
2.14–2.04 (m, 2 H), 1.96–1.90 (m, 1 H), 1.83 (td, J = 6.0, 2.0 Hz,
1 H), 1.20 (s, 3 H, Me), 1.12 (d, J = 7.2 Hz, 3 H, Me), 1.02 (s, 3 H,
Me), 0.98 (d, J = 9.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 136.8, 131.7, 128.9, 126.6, 48.2, 44.5, 42.2, 38.8, 37.8, 33.5, 27.9,
23.5, 21.6 ppm. Further data are in accordance with the litera-
ture.[8]
strategy is particularly useful when separation of reaction
products form catechol residues is an issue.
Experimental Section
2-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol (7): A mixture of
6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
hydrochloride
(50.4 g, 219.6 mmol), absolute ethanol (730 mL), and triethylamine
(30.6 mL, 219.6 mmol) was stirred at room temperature for 1 h.
Then, additional amounts of triethylamine (30.6 mL, 219.6 mmol)
and benzyl bromide (26.1 mL, 219.6 mmol) were added, and the
mixture was stirred at room temperature for 3.5 h. The cloudy
orange solution was filtered to remove some precipitated Et3N salt,
and ethanol was removed under reduced pressure. The orange resi-
due was dissolved in CH2Cl2 and washed with brine (2ϫ). The
organic layer was dried with Na2SO4 and filtered through a pad of
silica gel, which was packed with a solution of 2% Et3N in CH2Cl2.
The product was washed through with tert-butyl methyl ether, and
the solvents were removed under reduced pressure. The residue was
triturated with pentane and 2-benzyl-6,7-dimethoxy-1,2,3,4-tetra-
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Modified B-Alkylcatecholboranes as Radical Precursors
2,6,6-Trimethyl-3-[2-(phenylsulfonyl)allyl]bicyclo[3.1.1]heptane (20a):
accordance with the literature.[7] Data for 24c: 1H NMR (300 MHz,
A solution of (Ϯ)-α-pinene (1a; 160 μL, 1 mmol) and borane–di- CDCl3): δ = 6.87–6.82 (m, 2 H, arom. H), 6.74–6.68 (m, 2 H, arom.
methyl sulfide (90% in dimethyl sulfide, 105 μL, 1 mmol) in
CH2Cl2 (1.0 mL) was heated under reflux for 3 h and cooled to
room temperature afterwards. This solution was added by cannula
to a suspension of 7 (255 mg, 1 mmol) in CH2Cl2 (2.0 mL) at 0 °C
over a period of 15 min, and the cannula was rinsed with CH2Cl2
(0.5 mL). Evolution of hydrogen was observed. The reaction mix-
ture was then stirred for 1.5 h at room temperature while becoming
a clear solution and changing color continuously from yellow to
red. The solution was concentrated under a flow of N2 to about
2 mL of solvent, resulting in a 0.5 m solution. Sulfone 15 (387 mg,
1.2 mmol) and DMF (1.0 mL) were added, and the reaction mix-
ture was heated at 40 °C. Air (60 mL/h) was constantly bubbled
into the mixture by syringe pump over a period of 2 h. After al-
lowing the reaction mixture to stir overnight at room temperature,
Et2O and a 10% aqueous HCl solution were added, and some re-
maining precipitate was removed by filtration. The layers were sep-
arated, the aqueous layer was back-extracted with Et2O, and the
organic layer was washed again with a 10% aqueous HCl solution.
The combined organic layers were washed with brine, dried with
Na2SO4, filtered, and concentrated under reduced pressure. Purifi-
cation by flash chromatography (cyclohexane/TBME, 9:1) afforded
20a (259 mg, 81%) as a colorless liquid. 1H NMR (400 MHz,
CDCl3): δ = 7.91–7.85 (m, 2 H, arom. H), 7.64–7.50 (m, 3 H, arom.
H), 6.41 (s, 1 H, C=CHH), 5.79 (s, 1 H, C=CHH), 2.49 (dd, J =
15.4, 3.6 Hz, 1 H, CHH–C=C), 2.24 (dtd, J = 9.6, 6.2, 2.1 Hz, 1
H, CHH–C=C), 2.05 (dd, J = 15.0, 10.3 Hz, 1 H), 1.95–1.78 (m, 3
H), 1.73–1.68 (td, J = 5.8, 1.9 Hz, 1 H), 1.54 (quint.-like d, J = 7.0,
1.8 Hz, 1 H), 1.21 (ddd, J = 12.9, 5.6, 2.4 Hz, 1 H), 1.13 (s, 3 H,
Me), 0.93 (d, J = 7.2 Hz, 3 H, Me), 0.85 (s, 3 H, Me), 0.61 (d, J =
9.7 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.5, 139.4,
133.5, 129.3, 128.4, 124.7, 48.1, 43.9, 41.8, 40.6, 38.7, 34.2, 34.1,
H), 4.54 (s, 1 H, OH), 1.92 (sept., J = 6.8 Hz, 1 H, CHMe2), 1.14
(s, 6 H, Me), 1.01 (d, J = 6.8 Hz, 6 H, Me2CH) ppm. Further data
are in accordance with the literature.[7]
2-Cyclohexylcyclohexa-2,5-diene-1,4-dione (25d): Cyclohexene (1d,
170 μL, 1.65 mmol) was added to a solution of borane–dimethyl
sulfide (90% in dimethyl sulfide, 175 μL, 1.65 mmol) in CH2Cl2
(1.5 mL) at 0 °C. The mixture was stirred for 3 h at 0 °C, and a
white precipitation was observed. A suspension of 7 (421 mg,
1.65 mmol) in CH2Cl2 (4.0 mL) was added slowly by dropping fun-
nel to the organoborane mixture at 0 °C. Evolution of hydrogen
was observed. The funnel was rinsed with CH2Cl2 (6.5 mL). The
orange reaction mixture was stirred for 2 h at room temperature.
DMPU (200 μL, 1.65 mmol) and 1,4-benzoquinone (22, 892 mg,
8.25 mmol) were successively added, and the solution was stirred
at room temperature for 2 h. Et2O and a 10% aqueous HCl solu-
tion were added, and some remaining precipitate was removed by
filtration. The layers were separated, the aqueous layer was back-
extracted with Et2O, and the organic layer was washed again with
a 10% aqueous HCl solution. The combined organic layers were
washed with brine, dried with Na2SO4, filtered, and concentrated
under reduced pressure. Purification by flash chromatography (pen-
tane/Et2O, 95:5) afforded 25d (204 mg, 65%) as a greenish-brown
1
solid. M.p. 49–51 °C. H NMR (300 MHz, CDCl3): δ = 6.72 (d, J
= 10.1 Hz, 1 H, CH=CH), 6.66 (dd, J = 10.1, 2.4 Hz, 1 H,
CH=CH), 6.47 (dd, J = 2.3, 1.1 Hz, 1 H, C=CH), 2.71–2.61 (m, 1
H, CH–C=C), 1.82–1.71 (m, 5 H), 1.45–1.29 (m, 2 H), 1.24–1.07
(m, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 188.2, 187.2,
154.1, 137.1, 136.0, 130.9, 36.5, 32.1, 26.4, 26.1 ppm. IR (neat): ν
˜
= 2934, 2852, 1645, 1597, 1446, 1306 cm–1. HRMS (ESI): calcd.
for C12H14O2Na 213.0891; found 213.0896. Spectral data are in
accordance with the literature.[20]
33.9, 28.1, 22.9, 21.4 ppm. IR (neat): ν = 2902 (br.), 1446, 1303,
˜
1145, 1081 cm–1. LRMS (EI): m/z (%) = 319 (7) [M + H]+, 263
(11), 177 (70), 161 (48), 143 (62), 137 (87), 121 (78), 107 (77), 93
(83), 81 (90), 55 (90), 41 (100). Further data are in accordance with
the literature.[4a]
Supporting Information (see footnote on the first page of this arti-
cle): Full experimental data and spectra of new compounds.
Acknowledgments
2-(2,3-Dimethylbutan-2-yl)benzene-1,4-diol (23c) and 4-(2,3-Dimeth-
ylbutan-2-yloxy)phenol (24c): At 0 °C, 2,3-dimethyl-2-butene (1c,
195 μL, 1.65 mmol) was added to borane–dimethyl sulfide (90% in
dimethyl sulfide, 175 μL, 1.65 mmol) and it was stirred for 2.5 h
under neat conditions at 0 °C. The mixture was diluted with
CH2Cl2 (0.5 mL), and it was slowly added by cannula to a suspen-
sion of 7 (421 mg, 1.65 mmol) in CH2Cl2 (4.0 mL) at 0 °C. Evol-
ution of hydrogen was observed. The cannula was rinsed with
CH2Cl2 (2.5 mL). The reaction mixture was stirred for 2 h at room
temperature, while becoming a clear yellow solution. It was then
diluted with CH2Cl2 (3 mL). DMPU (200 μL, 1.65 mmol) and 1,4-
benzoquinone (22, 162 mg, 1.5 mmol) were successively added, and
the solution was stirred at room temperature for 2 h. Et2O and a
10% aqueous HCl solution were added, and some remaining pre-
cipitate was removed by filtration. The layers were separated, the
aqueous layer was back-extracted with Et2O, and the organic layer
was washed again with a 10% aqueous HCl solution. The com-
bined organic layers were washed with brine, dried with Na2SO4,
filtered, and concentrated under reduced pressure. Purification by
flash chromatography (pentane/Et2O, 4:1, 3:1) afforded 23c (61 mg,
21%) as an off-white solid and 24c (189 mg, 65%) as a yellowish
solid. Data for 23c: 1H NMR (300 MHz, CDCl3): δ = 6.73–6.71
(m, 1 H, arom. H), 6.53–6.52 (m, 2 H, arom. H), 4.40 (s, 1 H, OH),
4.36 (s, 1 H, OH), 2.60 (sept., J = 6.9 Hz, 1 H, CHMe2), 1.29 (s, 6
H, Me), 0.76 (d, J = 6.9 Hz, 6 H, Me2CH) ppm. Further data are in
This work was supported by the Swiss National Science Founda-
tion (grants 21-67106.01 and 7SUPJ062348). We thank BASF Cor-
poration for donation of chemicals.
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