Molecular Addition Compounds. 17. Borane and Chloroborane Adducts with Organic Sulfides for Hydroboration

Article abstract of DOI:10.1021/jo0009090

The following sulfides have been examined as borane carriers in comparison with dimethyl sulfide and 1,4-oxathiane: tert-butyl methyl sulfide, isoamyl methyl sulfide, ethyl isoamyl sulfide, tert-butyl isoamyl sulfide, diisoamyl sulfide, tetrahydrothiophene, tetrahydro-thiopyran, thioanisole, 3-ethylthiotetrahydrofuran, bis(3-tetrahydrofuryl) sulfide, and bis(2-methoxyethyl) sulfide. Their complexing ability toward borane increases in the following order: thioanisole < ether-sulfides < dialkyl sulfides < dimethyl sulfide. Borane adducts of the sulfides are liquids above 0°C. The thioanisole adduct loses diborane at room temperature. The reactivity of the adducts toward 1-octene increases in the reversed order of the complexing ability of the sulfides. Diisoamyl sulfide has a mild, ethereal, agreeable aroma, its synthesis is economical and the borane adduct, 4.2 M in BH₃, is stable over prolonged periods at room temperature. The sulfide can be recovered from hydroboration-oxidation products by distillation. Consequently, diisoamyl sulfide is a new promising borane carrier. Bis(2-methoxyethyl) sulfide, easily synthesized from the low cost thiodiethanol, is three times more soluble in water than 1,4-oxathiane. Its borane adduct is 6.0 M in BH₃ and can substitute for more expensive borane-1,4-oxathiane in hydroboration reactions. Applications of these new borane adducts in the synthesis of mono- and dichloroborane adducts was also studied. The equilibrium ratios observed for the new chloroborane adducts were similar to that observed for dimethyl sulfide adducts. However, the hydroboration of 1-octene with these new chloroborane adducts are much faster than the corresponding adducts of dimethyl sulfide, which are currently used extensively.

Full text of DOI:10.1021/jo0009090

J . Org. Chem. 2000, 65, 6697-6702
6697
Molecu la r Ad d ition Com p ou n d s. 17. Bor a n e a n d Ch lor obor a n e
Ad d u cts w ith Or ga n ic Su lfid es for Hyd r obor a tion †
Marek Zaidlewicz,1 J osyula V. B. Kanth, and Herbert C. Brown*
H. C. Brown Center for Borane Research, 1393 Brown Building, Purdue University,
West Lafayette, Indiana 47907
hcbrown@purdue.edu
Received J une 14, 2000
The following sulfides have been examined as borane carriers in comparison with dimethyl sulfide
and 1,4-oxathiane: tert-butyl methyl sulfide, isoamyl methyl sulfide, ethyl isoamyl sulfide, tert-
butyl isoamyl sulfide, diisoamyl sulfide, tetrahydrothiophene, tetrahydro-thiopyran, thioanisole,
3-ethylthiotetrahydrofuran, bis(3-tetrahydrofuryl) sulfide, and bis(2-methoxyethyl) sulfide. Their
complexing ability toward borane increases in the following order: thioanisole < ether-sulfides <
dialkyl sulfides < dimethyl sulfide. Borane adducts of the sulfides are liquids above 0 °C. The
thioanisole adduct loses diborane at room temperature. The reactivity of the adducts toward 1-octene
increases in the reversed order of the complexing ability of the sulfides. Diisoamyl sulfide has a
mild, ethereal, agreeable aroma, its synthesis is economical and the borane adduct, 4.2 M in BH3,
is stable over prolonged periods at room temperature. The sulfide can be recovered from
hydroboration-oxidation products by distillation. Consequently, diisoamyl sulfide is a new promising
borane carrier. Bis(2-methoxyethyl) sulfide, easily synthesized from the low cost thiodiethanol, is
three times more soluble in water than 1,4-oxathiane. Its borane adduct is 6.0 M in BH3 and can
substitute for more expensive borane-1,4-oxathiane in hydroboration reactions. Applications of these
new borane adducts in the synthesis of mono- and dichloroborane adducts was also studied. The
equilibrium ratios observed for the new chloroborane adducts were similar to that observed for
dimethyl sulfide adducts. However, the hydroboration of 1-octene with these new chloroborane
adducts are much faster than the corresponding adducts of dimethyl sulfide, which are currently
used extensively.
Diborane is a versatile reagent with a multitude of
applications in organic and inorganic synthesis. Since it
is a pyrophoric gas, borane complexes with suitable
carriers are used. Borane-tetrahydrofuran (H3B:THF)
and borane-dimethyl sulfide (BMS) are the reagents of
choice for most hydroborations and reductions carried out
with diborane.2-4 It is used in a growing number of
syntheses of pharmaceuticals and other important
compounds.5-7 However, its large-scale applications are
hampered by some inconveniences of H3B:THF and BMS.
Thus, the commercially available H3B:THF is a dilute
solution (1.0 M in BH3) undergoing slow but significant
decomposition (cleavage of tetrahydrofuran with the loss
of hydride) creating storage and transportation problems.
BMS is free from these inconveniences. It is a neat
complex, 10.0 M in BH3, stable indefinitely. However, the
odoriferous, water insoluble, highly volatile, and flam-
mable dimethyl sulfide creates environmental and safety
problems. Recently, it has been demonstrated that 1,4-
oxathiane, having lower volatility and milder odor than
dimethyl sulfide, is a convenient borane carrier.8 It has
a limited solubility in water and can be easily oxidized
to the corresponding sulfoxide, which is miscible with
water. Borane-1,4-oxathiane is a liquid adduct, 8.0 M in
BH3, stable over prolonged periods. Unfortunately, the
commercially available reagent is relatively costly, as
compared to H3B:THF and BMS. Solid borane adducts
with bis-sulfides have also been reported.7 Clearly, there
is a need for economical, environmentally safe, and easy
to handle borane adducts. Consequently, this study has
been undertaken with an objective of developing a sulfide
for borane complexation meeting the following require-
ments: odorless or mild odor, low volatility, economical
synthesis, stable liquid borane adducts of high molarity
in BH3, soluble in various solvents.
Resu lts a n d Discu ssion
Dialkyl sulfides of low molecular weight are attractive
for borane complexation since they may be expected to
form adducts of similar reactivity and stability to BMS.
Unfortunately, these compounds do not meet our require-
ments because of high volatility and unpleasant odor.
However, it has been noted in the early literature that
pure diisoamyl sulfide is exceptional among the lower
alkyl sulfides in having a pleasant, ethereal odor.9 Since
the isoamyl group also exhibits a profound fragrance
effect in other classes of compounds, e.g., esters and
ethers,10 we decided to prepare a series of isoamyl alkyl
† Communication no.
Research.
* To whom correspondence should be addressed. Phone: 765-494-
5316.
3 from H. C. Brown Center for Borane
Fax: 765-494-0239.
(1) Visiting Professor from Nicolaus Copernicus University, Torun.
(2) Brown, H. C. Organic Syntheses via Boranes; Aldrich Chemical
Co., Inc.: Milwaukee, 1997.
(3) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic
Press: London, 1988.
(4) Zaidlewicz, M.; Brown, H. C. Encyclopedia of Reagents for
Organic Synthesis; J . Wiley: New York, 1995; Vol. 1, p 634.
(5) Yardley, J . P.; Fletcher, H., III; Russell, P. B. Experientia 1978,
34, 1124.
(6) Renn, O.; Meatres, C. F. Bioconjugate Chem. 1992, 3, 563.
(7) Follet, M. Chem. Ind. 1986, 123.
(8) Brown, H. C.; Mandal, A. K. J . Org. Chem. 1992, 57, 4970.
(9) Finckh, J . Ber. 1894, 27, 1239.
10.1021/jo0009090 CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/02/2000

6698 J . Org. Chem., Vol. 65, No. 20, 2000
Ta ble 1. Bor a n e Ad d u cts w ith Or ga n ic Su lfid es
Zaidlewicz et al.
borane adduct
exchange with
BMSa (%)
11B NMR δc
hydroborationd
(min)
sulfide
dimethyl sulfide
isoamyl methyl sulfide
tert-butyl methyl sulfide
ethyl isoamyl sulfide
tert-butyl isoamyl sulfide
diisoamyl sulfide
tetrahydrothiophene
tetrahydrothiopyran
3-ethylthiotetrahydrofuran
bis(2-methoxyethyl) sulfide
1,4-oxathiane
bis(3-tetrahydrofuryl) sulfide
thioanisole
odor
[BH3]b
(ppm)
stench
10.0
5.8
6.6
5.2
4.3
4.2
8.1
7.5
5.8
6.0
8.0
4.6
3.0f
-20.3
-21.3
-24.6
-23.1
-25.9
-22.5
-20.6
-22.8
-24.5
-22.6
-23.0
-26.0
-20.6
45
10
10
10
10
15
15
15
5
ethereal, very strong
stench
ethereal, strong
ethereal, mild
ethereal, mild, agreeable
stench
46
39
44
32
40
46e
45
21
16
17
0
stench
stench
stench
5
5
5
stench, mild
stench
stench
0e
a
b
BMS and sulfide mixed at 1:1 molar ratio. Estimated by hydrolysis in water-glycerol-methanol (1:1:1), measuring hydrogen evolved.
c Neat. Hydroboration of 1-octene in THF at 20-25 °C. Concentration of the adduct 1 M. e Calculated from the exchange with borane-
d
tert-butyl methyl sulfide. f Unstable over longer periods.
sulfides and compare their odor and borane complexing
ability. The following sulfides which can be prepared from
readily available, low cost, starting materials have been
selected: diisoamyl sulfide, isoamyl methyl sulfide, ethyl
isoamyl sulfide, and tert-butyl isoamyl sulfide. Com-
mercially available tert-butyl methyl sulfide, tetrahy-
drothiophene, tetrahydrothiopyran and thioanisole have
also been included in the study.
Diisoamyl sulfide was prepared in high yield (90%) by
the reaction of isoamyl bromide with an aqueous solution
of sodium sulfide in the presence of a phase-transfer
catalyst (eq 1).
in water than 1,4-oxathiane and can be considered a
cheaper alternative to 1,4-oxathiane for borane complex-
ation. It possesses a less obnoxious odor and is much less
volatile than dimethyl sulfide.
The tetrahydrofuryl sulfides were also prepared. 3-Eth-
ylthiotetrahydrofuran was obtained by the free radical
addition of ethyl mercaptan to 2,3-dihydrofuran,13 and
bis(3-tetrahydrofuryl) sulfide by the reaction of 3-bro-
motetrahydrofuran with sodium sulfide (eqs 4 and 5).
H2O
2 i-AmBr + Na2S
8 i-Am2S (1)
n-Bu4NBr reflux, 6 h
The product is isolated by simple distillation in >99%
purity. It has an agreeable, mild, ethereal aroma and low
volatility. The mixed alkyl isoamyl sulfides were prepared
in high yields by a routine methodology according to eq
2.11 tert-Butyl isoamyl sulfide has a mild, but less
agreeable odor than diisoamyl sulfide. Methyl and ethyl
isoamyl sulfides have a strong ethereal odor.
However, 3-ethylthiotetrahydrofuran is only sparingly
soluble in water. Bis(3-tetrahydrofuryl) sulfide is twice
as soluble in water as 1,4-oxathiane, but both sulfides
have a typically unpleasant odor.
Bor a n e Ad d u cts. Exchange reactions between BMS
and the sulfides were followed by 11B NMR. Except for
thioanisole and tetrahydrothiophene, BMS and the bo-
rane-sulfide adducts showed different chemical shifts,
enabling direct calculation from the spectrum of the
amount of borane taken by a sulfide at equilibrium of
1:1 mixtures. The results presented in Table 1 reveal the
following order of borane complexing ability: thioanisole
< ether-sulfides < dialkyl sulfides < dimethyl sulfide.
No uptake of borane from BMS was observed for bis(3-
tetrahydrofuryl) sulfide and thioanisole.
Borane adducts were prepared by saturating the neat
sulfides with diborane at 0 °C. All the adducts are liquids
above 0 °C. Their molarities are shown in Table 1. The
adducts are soluble in tetrahydrofuran, diethyl ether, and
dichloromethane, solvents typically used for hydrobora-
tion.
In contrast to the dialkyl sulfides, which are insoluble
in water, the lower molecular weight ether-sulfides, e.g.,
1,4-oxathiane,8 are more hydrophilic. Since water soluble
carrier would be advantageous in various applications
of its borane adduct, the following ether-sulfides were
prepared. Bis(2-methoxyethyl) sulfide, structurally re-
lated to 1,4-oxathiane, was prepared in an improved yield
from low cost thiodiethanol by the literature procedure12
(eq 3). The product is isolated by simple distillation and
the unreacted starting material can be recycled.
(11) (a) Reid, E. E. Organic Chemistry of Bivalent Sulfur; Chem.
Publ. Co.: New York, 1960; Vol. II, p 24. (b) Barrett, G. C. In
Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.;
Pergamon Press: Oxford, 1979; Vol. 3, p 33. (c) Gundermann, K. D.;
Hu¨mke, K. In Houben-Weyl Methoden der Organische Chemie; Kla-
mann, D., Ed.; G. Thieme: Stuttgart, 1985; Vol. 11E, p 158.
(12) Richter, F.; Augustine, F. B.; Koft, E., J r.; Reid, E. E. J . Am.
Chem. Soc. 1952, 74, 4076.
Bis(2-methoxyethyl) sulfide is three times more soluble
(10) The Merck Index, 11th ed.; Merck & Co., Inc.: Rahway, 1989;
p 4993.
(13) Hillers, S.; Viskne, S.; Kurgane, B.; Veinbergs, A.; Braukame,
M. USSR Pat. 525,312, 1977; Chem. Abstr. 1977, 88, 6703.

Molecular Addition Compounds
J . Org. Chem., Vol. 65, No. 20, 2000 6699
Sch em e 1
Sch em e 2
Dialkyl sulfide adducts are stable over prolonged
periods at room temperature. No change in molarity and
the 11B NMR spectrum of borane-diisoamyl sulfide
adduct and borane-ethyl isoamyl sulfide adduct over 10
months at room temperature was observed. The 11B NMR
spectra of the borane-ether-sulfide adducts showed only
a single absorption (quartet) in the range -20 to -26
ppm, indicating coordination of borane with the sulfur
atom. Thioanisole absorbs diborane to give a solution 5.0
M in BH3 at 0 °C. However, at room temperature the
solution loses diborane, the molarity decreasing to 3.0
M in a few days and then slowly further over a prolonged
period.
hydrogen peroxide than dimethyl sulfide.16 (-)-cis-Myr-
tanol was isolated by distillation in 82% yield and the
sulfide was readily recovered (eq 6).
A convenient procedure for small-scale generation of
diborane (5-50 mmol) modified from an earlier method,14
was developed for this study. Thus, a commercially
available 2.0 M sodium borohydride solution in triglyme
is added to the boron trifluoride adduct with diglyme or
triglyme at room temperature. Both reagents are liquids,
convenient to handle. Generation of diborane is smooth
and the yield is high (95%). No other gaseous products
are formed, making possible a visual observation of
diborane absorption in sulfides. The boron trifluoride
complexes with diglyme and triglyme are prepared by
mixing equimolar amounts of the boron trifluoride ether-
ate with diglyme or triglyme, and removing diethyl ether
under vacuum. The complexes are pale yellow liquids,
darkening slowly when kept at 0 °C. The darkening
exerted no significant effect on the yield of diborane
realized.
Hydroboration of 1-octene with borane-bis(2-methoxy-
ethyl) sulfide adduct was carried out in dichloromethane.
The sulfide could not be completely removed from the
organic phase by several washings with water. It was
oxidized to the corresponding sulfoxide with 5% aqueous
1
sodium hypochlorite (Chlorox). H and 11B NMR spectra
taken after removing the solvent showed only trioctylbo-
rane, which was isolated in 96% yield. The organoborane
was oxidized under standard conditions to give a mixture
of 1- and 2-octanol (94:6) in 94% yield (Scheme 1).
(+)-2-Carene was hydroborated with borane-bis(2-
methoxyethyl) sulfide adduct in THF at room tempera-
ture. A white precipitate of diisocaranylborane was
formed in a few minutes after mixing the reagents. It
can be removed by filtration at this stage. Oxidation of
the organoborane with hydrogen peroxide/sodium hy-
droxide and distillation gave a mixture of (-)-2-isocaranol
and the sulfide, which was removed by oxidation with
Chlorox. (-)-2-Isocaranol was isolated in 81% yield
(Scheme 2).
P r ep a r a tion of Mon och lor obor a n e a n d Dich lo-
r ob or a n e Ad d u ct s of Va r iou s Dia lk yl Su lfid es.
Synthesis of mono- and dichloroborane adducts from
methyl sulfide-borane constitutes one of its most valu-
able synthetic application, as these chloroborane adducts
hydroborate unhindered olefins with much improved
regioselectivities.4,17 Methyl sulfide forms very stable
monochloroborane adduct that hydroborate representa-
tive olefins at room temperature.18 The corresponding
Hyd r obor a tion . The hydroboration of 1-octene with
the adducts was carried out in tetrahydrofuran solution
(1.0 M) at room temperature following the progress of
the reaction by 11B NMR. The results are shown in Table
1. The reactivity of the adducts corresponds to the
complexing ability of the sulfides, the borane adducts
with ether-sulfides being more reactive than the adducts
with dialkyl sulfides. The hydroborations with the ether-
sulfide adducts were practically instantaneous. The 11B
NMR spectrum taken in 5 min showed complete trans-
formation of 1-octene into trioctylborane. The adducts
with dialkyl sulfides required 10-15 min to complete the
hydroboration, whereas, with the strongest adduct (BMS),
the reaction took 45 min.
Hydroborations on a preparative scale were carried out
with borane-diisoamyl sulfide adduct and borane-bis(2-
methoxyethyl) sulfide adduct. Thus, (-)-â-pinene was
reacted with borane-diisoamyl sulfide adduct and the
organoborane intermediate was oxidized with standard
30% hydrogen peroxide and 3.0 M sodium hydroxide used
in excess to suppress oxidation of the sulfide.15 It should
be noted that diisoamyl sulfide is less reactive toward
(16) Ishida, S. J . Chem. Soc. J pn. 1943, 64, 167, Chem. Abstr. 1947,
41, 3752a.
(17) (a) Brown, H. C.; Ravindran, N.; J . Org. Chem. 1977, 42, 2533.
(b) Brown, H. C.; Ravindran, N.; Inorg. Chem. 1977, 16, 938. (c) Brown,
H. C.; Zaidlewicz, M. Polish J . Appl. Chem. 1983, 26, 155.
(18) (a) Zaidlewicz, M.; Brown, H. C. Encyclopedia of Reagents for
Organic Synthesis; J . Wiley: New York, 1995; Vol. 2, p 3658. (b)
Reference 4, p 1689.
(14) Brown, H. C.; Tierney, P. A. J . Am. Chem. Soc. 1957, 80, 1552.
(15) Brown, H. C.; Mandal, A. K. J . Org. Chem. 1980, 45, 916.

6700 J . Org. Chem., Vol. 65, No. 20, 2000
Zaidlewicz et al.
dichloroborane is less reactive, but hydroboration can be
carried out with some procedural modifications such as
the addition of 1 equiv of BCl3.19 Unfortunately, these
synthetically important chloroborane adducts exist as
equilibrium mixtures and only ∼73% pure monochlo-
roborane and ∼85% pure dichloroborane (by 11B NMR)
can be obtained. Also, the unpleasant odor and volatility
of dimethyl sulfide make these reagents less convenient
for large-scale applications. Having prepared less volatile
and less odoriferous dialkyl sulfide-borane adducts, it was
of interest to see whether these adducts can be used for
the synthesis of the corresponding mono- and dichlorobo-
rane adducts. For this study the following dialkyl sulfides
were examined as chloroborane carriers in comparison
with methyl sulfide: ethyl sulfide, n-propyl sulfide,
isoamyl sulfide, 1,4-thioxane, thioanisole, tert-butyl meth-
yl sulfide, tert-butyl isoamyl sulfide.
i-Am2S:BH2Cl h i-Am2S:BHCl2 + i-Am2S:BH3
These equilibrium ratios did not change drastically
with the change in dialkyl sulfide. Though the adduct
exits in equilibrium, hydroboration of 1-octene and
R-pinene gave the corresponding dialkylchloroborane
cleanly. Also, the monochloroborane adducts of i-Am2S,
t-BuSMe, and t-BuSAmi hydroborate 1-octene much
faster than the borane adduct of dimethyl sulfide and
can even be carried out at 0 °C. The results are sum-
marized in Table 3.
The dialkyl sulfide-BCl3 adducts were prepared by
slowly passing boron trichloride gas into neat sulfide at
- 20 °C and warming the reaction flask slowly to room
temperature.
Similarly, dichloroborane-dialkyl sulfide adducts also
exist in equilibrium with the corresponding dichlorobo-
rane and boron trichloride adducts. In most of the cases,
the dichloroborane adduct can be obtained in ∼85%
purity (by 11B NMR). Table 3 summarizes the ratios of
various peaks observed in 11B NMR.
R2S + BCl3 -20 °C f rt8 R2S:BCl3
(7)
The adducts thus obtained show clean sharp signals
in 11B NMR and are stable at 0 °C indefinitely. Initially,
the preparation of mono- and dichloroborane-dialkyl
sulfide complexes was attempted by bubbling a sufficient
amount of diborane into a solution of dialkyl sulfide-
BCl3 complex in dialkyl sulfide according to the following
equations.
i-Am2S:BCl3 i-Am S:BH
i-Am S:BHCl
(2.55 equiv)
+
f
+
2
3
2
2
(2.0 equiv)
(1.0 equiv)
i-Am S:BH Cl i-Am S:BCl
(12)
3
+
2
2
2
(0.24 equiv)
(0.21 equiv)
i-Am2S:BHCl2 h i-Am2S:BH2Cl + i-Am2S:BCl3
R2S:BCl3 + 2 R2S + B2H6 0 °C8 3 R2S:BH2Cl
However, the hydroboration of 1-octene using these
dichloroborane adducts is much slower than that of the
corresponding monochloroborane adducts (see Table 3).
These hydroboration can be made faster by the addition
of one equivalent of boron trichloride as reported for
dimethyl sulfide-dichloroborane.19
4 R2S:BCl3 + 2 R2S + B2H6 0 °C8 6 R2S:BHCl2 (8)
However, using this procedure the chloroborane ad-
ducts were not obtained cleanly. Alternatively, the ad-
ducts were prepared by mixing dialkyl sulfide-BH3 and
dialkyl sulfide-BCl3 in appropriate ratios at room-
temperature according to the following equations.
Con clu sion s
The complexing ability of the sulfides toward borane
increases in the following order: thioanisole < ether-
sulfides < dialkyl sulfides < dimethyl sulfide. The
reactivity of the corresponding borane adducts toward
1-octene increases in the reversed order. Diisoamyl
sulfide has a mild, ethereal agreeable aroma. Its synthe-
sis is simple and the borane adduct, 4.2 M in BH3, is a
liquid above 0 °C, stable over prolonged periods at room
temperature. Consequently, it is a new promising borane
carrier. Bis(2-methoxyethyl) sulfide can be used for
borane complexation as a less costly alternative to 1,4-
oxathiane. The mono- and dichloroborane adducts of
these dialkyl sulfides can be prepared, however, these
adducts exists in equilibrium as in the case of dimethyl
sulfide-chloroborane adducts. The equilibrium distribu-
tions are slightly better for isoamyl sulfide tert-butyl
methyl sulfide and tert-butyl isoamyl sulfides. The hy-
droboration of 1-octene with these monochloroborane
adducts is very fast and complete within 30 min. Also,
isoamyl sulfide-BH2Cl does not possess the unpleasant
odor of typical sulfur compounds. Accordingly, the present
study provides dialkyl sulfides that are nonvolatile, with
a more agreeable smell that are advantageous as borane
and chloroborane carriers, with improved reactivities,
R2S:BCl3 + 2 R2S:BH3
2 R2S:BCl3 + R2S:BH3
9
rt8 3 R2S:BH2Cl
rt8 3 R2S:BHCl2
9
(9)
Using this procedure, the corresponding mono- and
dichloroborane adducts were obtained as major products.
The required monochloroborane adduct were in equilib-
rium with dialkyl sulfide-BH3 and dialkyl sulfide-
BHCl2 (similar to that reported for dimethyl sulfide). For
example, during the preparation of isoamyl sulfide-BH2-
Cl preparation, the product isoamyl sulfide-BH2Cl (75%)
is in equilibrium with the corresponding BHCl2 (12%) and
BH3 (13%) adducts.
i-Am2S:BCl3 i-Am S:BH
i-Am S:BH Cl
2 2
(2.25 equiv)
+
f
+
2
3
(1.0 equiv)
(2.0 equiv)
i-Am2S:BHCl2 i-Am S:BH
(0.36 equiv)
+
(10)
3
2
(0.39 equiv)
(19) Brown, H. C.; Ravindran, N.; Kulkarni, S. U.; J . Org. Chem.
1980, 45, 2533.

Molecular Addition Compounds
dialkyl sulfide
J . Org. Chem., Vol. 65, No. 20, 2000 6701
Ta ble 2. P r ep a r a tion of Mon och lor obor a n e Ad d u cts of Dia lk yl Su lfid esa
R2S:BH2Cl
R2S:BHCl2
R2S:BH3
hydroborationb
(h)
% (11B NMR)
% (11B NMR)
% (11B NMR)
methyl sulfide
ethyl sulfide
n-propyl sulfide
isoamyl sulfide
1,4-oxathiane
73 (-7.2, t)
74 (-9.8, t)
76 (-9.1, t)
75 (-9.3, t)
63 (-7.9, t)
62 (-5.7, t)
73 (-7.5, t)
76 (-9.5, t)
75 (-7.2, t)
15 (+1.6, d)
14 (+2.8, d)
14 (+1.2, d)
13 (+1.2, d)
18 (+8.1, d)
20 (+3.0, d)
15 (+1.3, d)
12.5 (+2.5, d)
13 (+1.6, d)
12 (-20.6, q)
12 (-24.1, q)
10 (-23.1, q)
11 (-23.2, q)
19 (-23.4, q)
18 (-21.2, q)
12 (-20.9, q)
11.5 (-25.3, q)
12 (-20.6, q)
2.0
1.5
1.5
0.5
0.5
thioanisole
0.25
0.25
0.25
2.0
tert-butyl methyl sulfide
tert-butyl isoamyl sulfide
methyl sulfidec
a
b
Equilibrium ratios observed after 48 h at room temperature. Hydroboration of 1-octene in CH2Cl2 at 20-25 °C. Concentration of the
adduct 1 M. c Peaks observed for a commercial sample of dimethyl sulfide-monochloroborane adduct.
Ta ble 3. P r ep a r a tion of Dich lor obor a n e Ad d u cts of Dia lk yl Su lfid esa
R2S:BHCl2
R2S:BH2Cl
R2S:BCl3
hydroborationb
(h)
dialkyl sulfide
methyl sulfide
% (11B NMR)
% (11B NMR)
% (11B NMR)
86 (+1.7, d)
85 (+0.9, d)
84 (+1.1, d)
83 (+1.1, d)
83 (+8.1, d)
86 (+3.0, d)
85 (+1.5, d)
86 (+2.4, d)
86 (+1.8, d)
6.4 (-7.2, t)
11 (-9.9, t)
10 (-9.3, t)
10 (-9.4, t)
7 (-7.9, t)
7.6 (+7.0, s)
4 (+6.9, s)
6 (+7.0, s)
7 (+7.1, s)
8 (+8.2, s)
8 (+8.1, s)
7.6 (+6.8, s)
6.5 (+7.0, s)
8 (+7.2, s)
24.0
24.0
12.0
6.0
4.0
6.0
3.0
3.0
24.0
ethyl sulfide
n-propyl sulfide
isoamyl sulfide
1,4-oxathiane
thioanisole
6 (-5.7, t)
tert-butyl methyl sulfide
tert-butyl isoamyl sulfide
methyl sulfidec
7.4 (-7.3, t)
7.5 (-9.5, t)
7 (-7.1, t)
a
b
Equilibrium ratios observed after 48 h at room temperature. Hydroboration of 1-octene in CH2Cl2 at 20-25 °C. Concentration of the
adduct 1 M. c Peaks observed for a commercial sample of dimethyl sulfide-monochloroborane adduct.
90%, n20 ) 1.4465; 1H NMR (CDCl3), δ, 9.05 (d, J ) 6 Hz,
and should therefore be able to substitute for the corre-
sponding dimethyl sulfide compounds.
D
6H, CH3), 1.47 (q, J ) 6 Hz, 2H, CH2), 1.67 (septet, J ) 6 Hz,
1H, CH), 2.09 (s, 3H, CH3), 2.49 (t, J ) 6 Hz, 2H, CH2).
Eth yl Isoa m yl Su lfid e. Prepared from isoamyl bromide
and ethyl mercaptan: yield 75%, bp 54-55/15 mmHg (lit.22
Exp er im en ta l Section
bp 158-159 °C), n20 ) 1.4488; 1H NMR (CDCl3), δ, 0.92 (d, J
D
All glassware was oven-dried for several hours at 120 °C,
assembled while hot, and cooled in a stream of dry nitrogen
gas. Syringes were assembled and fitted with needles while
hot. Techniques for handling air-sensitive compounds de-
scribed elsewhere were followed.20 All manipulations and
reactions with air-sensitive compounds were carried out under
) 6 Hz, 6H, CH3), 1.25 (t, J ) 6 Hz, 2H, CH2), 1.47 (q, J ) 6
Hz, 2H, CH2), 1.67 (septet, J ) 6 Hz, 1H, CH), 2.54 (q, J ) 6
Hz, 2H, CH2).
ter t-Bu tyl Isoa m yl Su lfid e. Prepared from isoamyl bro-
mide and tert-butyl mercaptan: 86% yield, bp 55-56 °C/7
mmHg, n20 ) 1.4460; 1H NMR (CDCl3), δ, 0.92 (d, J ) 6 Hz,
D
1
nitrogen atmosphere. H and 11B NMR spectra were recorded
6H, CH3), 1.32 (s, 9H, CH3), 1.45 (q, 2H, CH2), 1.68 (septet,
1H, CH), 2.52 (t, J ) 6 Hz, 2H, CH2).
on a 300 MHz multinuclear instrument. The 11B chemical
shifts are in δ relative to boron trifluoride diethyl etherate.
Optical rotations were measured on an automatic polarimeter.
GC analyses were carried out on a chromatograph equipped
with FID and CI-100A integrator. The following columns were
used, 12 ft × 0.125 in column packed with 10% Carbowax 20M,
SE-30 on Chromosorb W (100-120 mesh). Microanalyses were
performed at the Microanalytical Laboratory, Purdue Univer-
sity.
Diisoa m yl Su lfid e. Isoamyl bromide (21.88 g, 0.21 mol)
and tetrabutylammonium bromide (1.61 g, 5 mmol) were added
to a solution of sodium sulfide nonahydrate (24.02 g, 0.10 mol)
in water (50 mL), and the mixture was refluxed with stirring
for 6 h. The organic layer was separated, and the aqueous layer
was extracted with pentane. The extract was combined with
the organic layer and dried with anhydrous magnesium
sulfate. Distillation gave 15.85 g, 91% of a colorless liquid: bp
Ma ter ia ls. Borane-methyl sulfide (BMS), tert-butyl methyl
sulfide, tetrahydrothiophene, tetrahydrothiopyran, dimethyl
sulfide, thioanisole, 1,4-oxathiane, thiodiethanol, and boron
trichloride were commercial products. Tetrahydrofuran was
freshly distilled from a small quantity of benzophenone ketyl
prior to use. Diglyme, (+)-2-carene [R]23D ) +92.0° (neat), and
(-)-â-pinene [R]23D ) -20.8° (neat) were distilled from a small
amount of lithium aluminum hydride under vacuum. Boron
trifluoride diethyl etherate was distilled from a small amount
of calcium hydride under vacuum.
Isoa m yl Meth yl Su lfid e. Typ ica l P r oced u r e. Sodium
methoxide (5.90 g, 0.11 mol) was dissolved in methanol (50
mL). Isoamyl mercaptan (10.42 g, 0.10 mol) was added and
the mixture was left at room temperature for 1 h. Methyl
iodide (15.61 g, 0.11 mol) was added and the mixture was
refluxed for 2 h. Water was added and the mixture was
extracted with pentane. The extracts were combined and dried
over anhydrous magnesium sulfate. The product was isolated
by distillation and redistilled from lithium aluminum hy-
dride: 10.64 g, bp 54-55 °C/35 mmHg (lit.21 bp 136-138 °C),
49-50 °C/0.1 mmHg, n20D ) 1.4514 (lit.23 bp (corr) 214.3-214.8
1
°C, n20 ) 1.4520), >99% GC pure; H NMR (CDCl3), δ, 0.95
D
(d, J ) 6 Hz, 12H, CH3), 1.47 (q, J ) 6 Hz, 4H, CH2), 1.68
(septet, J ) 6 Hz, 2H, CH), 2.51 (t, J ) 6 Hz, 4H, CH2).
3-Eth ylth iotetr a h yd r ofu r a n . Ethyl mercaptan (12.43 g,
0.1 mol) was added to a mixture of 2,3-dihydrofuran (7.00 g,
0.1 mol) and benzoyl peroxide (0.1 g) at room temperature.
An increase in temperature was observed after 5 min and the
mixture was kept at 25-30 °C by cooling with water. After 1
h, no further increase of temperature was observed. The
mixture was left overnight and the product was isolated by
distillation: 24.85 g (94%), bp 46 °C/0.1 mmHg, n20D ) 1.4866
(lit.13 bp 106-108 °C/35 mmHg, n20 ) 1.4930); 1H NMR
D
(CDCl3) δ 1.28 (t, J ) 6 Hz, 3H, CH3), 1.83 (m, 1H, CH2), 2.28
(m, 1H, CH2), 2.60 (q, J ) 6 Hz, 2H, CH2), 3.35 (m, 1H, CH),
3.58 (dd, J ) 6 Hz, 6.5 Hz, 1H, CH2), 3.83 (m, 1H, CH2), 3.91
(m, 1H, CH2), 4.08 (dd, J ) 6 Hz, 6.5 Hz, 1H, CH2).
Bis(3-t et r a h yd r ofu r yl) Su lfid e. 3-Bromotetrahydrofu-
ran22 (31.70 g, 0.21 mol) was dissolved in ethanol (70 mL), and
(22) Ipatieff, V. N.; Friedman, B. S. J . Am. Chem. Soc. 1939, 61,
71.
(20) Reference 2, p 191.
(21) (a) Obermeyer, J . Ber. 1887, 20, 2918. (b) Anderson, H. H. J .
Chem. Eng. Data 1964, 9, 272.
(23) Ayers, G. W., J r.; Agruss, M. S. J . Am. Chem. Soc. 1939, 61,
83.

6702 J . Org. Chem., Vol. 65, No. 20, 2000
Zaidlewicz et al.
a solution of sodium sulfide nonahydrate (24.00 g, 0.1 mol) in
water (40 mL) was added. The mixture was refluxed for 1 h.
Ethanol was removed under water aspirator vacuum, solid
potassium carbonate was added to saturate the aqueous
solution, and the product was extracted with diethyl ether.
The extract was dried with anhydrous magnesium sulfate.
Distillation gave 12.01 g (69%) of a colorless liquid: bp 90-
diethyl ether. The extracts were combined with the THF
solution, dried over magnesium sulfate and octanol was
isolated by distillation, 10.60 g, 90.5%, bp 99-100 °C/20
mmHg. GC analysis (Carbowax 20M) showed 1-octanol 94%
and 2-octanol (6%).
(-)-2-Isoca r a n ol. (+)-2-Carene (14.96 g, 0.11 mol), [R]23
D
) + 92.0° (neat), was added to a solution of borane-bis(2-
methoxyethyl)sulfide adduct (8.2 mL, 50 mmol) in tetrahy-
drofuran (50 mL) at 10-20 °C. A white precipitate was formed
in 5 min. 11B NMR spectrum showed no borane signal and only
a signal at δ, 31.1 ppm. After 1 h, water was added and the
organoborane was oxidized under nitrogen by the addition of
3.0 M sodium hydroxide (30 mL, 90 mmol) and 30% hydrogen
peroxide (12 mL, 120 mmol) at 20-30 °C, stirred for 2 h and
then for 1 h at 40 °C. The mixture was saturated with
potassium carbonate, the organic phase was separated and the
aqueous phase was extracted with diethyl ether. The extracts
were combined with the THF solution, washed with saturated
brine and dried over magnesium sulfate. Distillation gave a
mixture of bis(2-methoxyethyl) sulfide and the product alcohol.
The distillate was dissolved in diethyl ether (25 mL) and added
dropwise with vigorous stirring to Chlorox (80 mL) at 20-25
°C. After 1 h, the organic solution was separated, the aqueous
solution was extracted with diethyl ether, the extract was
combined with the organic solution, dried over magnesium
sulfate and distilled to give 12.52 g (81%) of (-)-2-isocaranol:
bp 50-52 °C/0.05 mmHg, [R]23D ) -31° (neat) (lit.27 bp 50-52
91 °C/0.05 mmHg, n20 ) 1.5126; MS EI/CI, 70 eV, 174 (M+,
D
2), 73 (16), 71 (22), 70 (100), 69 (15); 1H NMR (mixture of
diastereomers) (CDCl3) δ 1.84 (m, 2H, CH2), 2.30 (m, 2H, CH2),
3.35 (quintet, J ) 6 Hz, 2H, CH), 3.57 (m, 2H, CH2), 3.83 (m,
4H, CH2), 4.04 (m, 2H, CH2). Anal. Calcd for (C8H14O2S)
(174.27) 55.18%: C, 8.10; H, 18.40. Found: 54.79%; C, 8.11;
H, 18.78.
Bis(2-m eth oxyeth yl) Su lfid e. A solution of thiodiethanol
(12.22 g, 0.1 mol) and p-toluenesulfonic acid monohydrate (0.95
g, 5 mmol) in methanol (12.82 g, 0.4 mol) was heated for 10 h
at 150 °C in an autoclave provided with a glass liner. The
product was isolated by distillation: 9.91 g (66%), bp 55-56
°C/0.1 mmHg (lit.12 bp 202.2-202.6 °C), n20D ) 1.4609; 1H NMR
(CDCl3) δ 2.75 (t, J ) 6 Hz, 4H, CH2), 3.37 (s, 6H, CH3), 3.57
(t, J ) 6 Hz, 4H, CH2).
Bor a n e-Su lfid e Ad d u cts. Bor a n e-Diisoa m yl Su lfid e.
Typ ica l P r oced u r e. Diborane generated as described else-
where2 was passed at 0 °C through a bubbler containing a
magnetic stirring bar and neat diisoamyl sulfide (8.67 g, 50
mmol). Excess diborane was absorbed in the next bubbler
containing tetrahydrofuran (10 mL) over mercury until the
borane concentration in tetrahydrofuran reached 1.0 M. The
borane-sulfide adduct, a colorless liquid, was stirred overnight
at room temperature prior to disconnecting the bubblers and
then analyzed for active hydride by a standard procedure using
water-glycerol-methanol (1:1:1) hydrolyzing mixture. Borane
concentration 4.2 M in BH3: 11B NMR δ -22.5 ppm.
(-)-cis-Myr ta n ol. A 4.2 M borane-diisoamyl sulfide adduct
(5.0 mL, 21 mmol) was dissolved in THF (20 mL) and (-)-â-
°C/0.05 mmHg, [R]23 ) -31.1° (neat)).
D
P r ep a r a tion of Bor on Tr ich lor id e Ad d u cts. The pro-
cedure followed for all dialkyl sulfides is identical and the
procedure followed for isoamyl sulfide is representative. An
oven-dried RB flask provided with septum inlet and a stirring
bar was cooled under dry nitrogen gas. The flask was charged
with isoamyl sulfide (8.72 g, 50 mmol) and the reaction flask
was further cooled to -18 °C. Boron trichloride (5.86 g, 50
mmol) gas was slowly condensed in to the reaction flask using
a double-ended needle under nitrogen atmosphere. As soon the
vigorous reaction subsides, the contents were slowly brought
to room temperature to obtain a white solid that is air and
moisture sensitive. The 11B NMR examination in dichlo-
romethane showed a single signal at +7.1 ppm.
P r ep a r a tion of Mon och lor obor a n e Ad d u cts of Dia lk yl
Su lfid es. The procedure followed for all dialkyl sulfides is
identical and the procedure followed for isoamyl sulfide is
representative. An oven dried RB flask provided with septum
inlet and a stirring bar was cooled under dry nitrogen gas.
The flask was charged with isoamyl sulfide-boron trichloride
complex (2.91 g, 10 mmol). and isoamyl sulfide-borane adduct
(4.8 mL, 4.2 M, 20 mmol). The contents were further stirred
at room temperature and the progress of reaction was followed
by 11B NMR examination of the reaction mixture in dichlo-
romethane solvent. The results are presented in Table 2.
P r ep a r a t ion of Dich lor ob or a n e Ad d u ct s of Dia lk yl
Su lfid es. The procedure followed for all dialkyl sulfides is
identical and the procedure followed for isoamyl sulfide is
representative. An oven-dried RB flask provided with septum
inlet and a stirring bar was cooled under dry nitrogen gas.
The flask was charged with isoamyl sulfide-boron trichloride
complex (5.82 g, 20 mmol) and isoamyl sulfide-borane adduct
(2.4 mL, 4.2 M, 10 mmol). The contents were further stirred
at room temperature and the progress of reaction was followed
by 11B NMR examination of the reaction mixture in dichlo-
romethane solvent. The results were presented in Table 3.
pinene (8.86 g, 64 mmol), [R]23 ) -20.8° (neat), 91% ee, was
D
added at 0 °C. The mixture was kept at room temperature for
1 h and oxidized by the addition of 3.0 M sodium hydroxide
(10 mL, 30 mmol) and 30% hydrogen peroxide (7 mL, 70 mmol)
keeping the temperature during the addition below 30 °C and
then stirring at room temperature for 3 h. The mixture was
saturated with potassium carbonate, the THF layer was
separated and the aqueous layer was extracted with diethyl
ether. The extracts were combined with the THF solution,
dried over magnesium sulfate and distilled using a Widmer
column to give a first fraction, 4.25 g, bp 45-58 °C/0.1 mmHg
composed of diisoamyl sulfide (77%) and cis-myrtanol (23%)
and a second fraction which is pure cis-myrtanol, 7.96 g (82%),
bp 58-60 °C/0.1 mmHg, n20 ) 1.4907, [R]20 ) -19.4° (neat)
D
D
(lit.26 bp 65-67 °C/0.2 mmHg, n20D ) 1.4911, [R]22D ) -19.5°).
Tr ioctylbor a n e. A 6.0 M borane bis(2-methoxyethyl) sul-
fide adduct (5.0 mL, 30 mmol) was dissolved in dichlo-
romethane (30 mL) and 1-octene (10.10 g, 90 mmol) was added
dropwise with cooling to keep the temperature at 20-25 °C.
The reaction was complete in 5 min as indicated by 11B NMR.
The solution was vigorously stirred with water, dried over
magnesium sulfate and the solvent was removed under
vacuum. 1H NMR spectrum showed the sulfide present.
Diethyl ether was added, followed by 5% sodium hypochlorite
solution (Chlorox, 40 mL) and the mixture was stirred keeping
the temperature at 20-25 °C. After 1 h, the organic phase
was separated, washed with water and dried over magnesium
sulfate. Ether was removed under vacuum to give trioctylbo-
rane: 9.84 g, 94%, 11B NMR δ 86 ppm. 1H NMR spectrum did
not indicate bis(2-methoxyethyl) sulfide. Tetrahydrofuran (30
mL) was added, followed by 3.0 M sodium hydroxide (10 mL,
30 mmol) and 30% hydrogen peroxide (10 mL, 100 mmol). The
mixture was stirred for 2 h at room temperature and then 1 h
at 40 °C, saturated with potassium carbonate, the organic
layer was separated and the aqueous layer was extracted with
Ack n ow led gm en t. Financial support of this study
from the Herbert C. Brown Center for Borane Research
is gratefully acknowledged. We are thankful to Camphor
& Allied Products Ltd., Bombay, India for a generous
gift of (+)-2-carene.
J O0009090
(24) Buys, H. R.; Altona, C.; Havinga, E. Tetrahedron 1968, 24, 3019.
(25) Reference 2, p 241.
(26) Reference 2, p 25, 99 (note 1).
(27) Brown, H. C.; Vara Prasad, J . V. N.; Zaidlewicz, M. J . Org.
Chem. 1988, 53, 2911.