Fluorous dimethyl sulfide: A convenient, odorless, recyclable borane carrier

Article abstract of DOI:10.1021/ol026957j

(matrix presented) Borane gas and 2-(perfluorooctyl)ethyl methyl sulfide form a solid comprised of an approximately 1:1 mixture (fluorous BMS) of sulfide and the corresponding sulfide-borane. Fluorous BMS permits hydroboration of alkenes in a dichloromethane/perfluorinated hydrocarbon mixture with subsequent recycling of the fluorous sulfide by fluorous extraction. The use of fluorous BMS in the asymmetric reduction of ketones catalyzed by a chiral oxaborolidine catalyst, and in the reduction of other functional groups, is also reported.

Full text of DOI:10.1021/ol026957j

ORGANIC
LETTERS
2002
Vol. 4, No. 23
4175-4177
Fluorous Dimethyl Sulfide: A
Convenient, Odorless, Recyclable
Borane Carrier
David Crich* and Santhosh Neelamkavil
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received September 25, 2002
ABSTRACT
Borane gas and 2-(perfluorooctyl)ethyl methyl sulfide form a solid comprised of an approximately 1:1 mixture (fluorous BMS) of sulfide and
the corresponding sulfide-borane. Fluorous BMS permits hydroboration of alkenes in a dichloromethane/perfluorinated hydrocarbon mixture
with subsequent recycling of the fluorous sulfide by fluorous extraction. The use of fluorous BMS in the asymmetric reduction of ketones
catalyzed by a chiral oxaborolidine catalyst, and in the reduction of other functional groups, is also reported.
Borane is one of the most useful and ubiquitous of organic
reagents. It enables the hydroboration of alkenes and alkynes,
and the myriad of transformations arising from the so-formed
organoborane derivatives, and permits many other reductions
to be carried out under mild conditions. Nevertheless, the
pyrophoric nature of borane renders its use and transportation
hazardous such that it is most commonly employed coordi-
nated to either tetrahydrofuran (BH3‚THF)1 or dimethyl
sulfide (BH3‚SMe2, BMS),2 with the latter usually preferred
because of its greater stability and longevity. BMS, while
considerably more practical than borane itself, suffers from
the disadvantage of liberating stoichiometric dimethyl sulfide
in the course of its reactions, with all the adverse environ-
mental problems contingent on the release of such a
malodorous substance. This problem prompted Brown and
co-workers to introduce 1,4-thioxane3 as a less volatile carrier
for borane and, more recently, bis(hydroxyethyl) sulfide,4
which has the additional advantage of being water soluble
and, so, conveniently removable by aqueous extraction
following reductions by BH3‚S(CH2CH2OH)2.5 In this paper
we present 2-(perfluorooctyl)ethyl methyl sulfide (1) as a
readily prepared, odorless sulfide for complexation and
stablization of borane that is readily recycled by fluorous
extraction and which additionally possesses the considerable
advantage of not being pyrophoric.
Our interest in the development of recoverable, environ-
mentally friendly fluorous6 organoselenium7 and organosul-
fur8 reagents led us to consider the possibility of a nonvola-
(3) Brown, H. C.; Mandal, A. K. J. Org. Chem. 1992, 57, 4970-4976.
(4) Brown, H. C.; Zaidlewicz, M.; Dalvi, P. V.; Biswas, G. K. J. Org.
Chem. 2001, 66, 4795-4798.
(5) Other sulfides that have been introduced as carriers for borane include
1,2-bis(tert-butylthio)ethane and 1,4-bis(benzylthio)butane: Follet, M. Chem.
Ind. 1986, 123-128.
(6) (a) Horvath, I. T. Acc. Chem. Res. 1998, 31, 641-650. (b) Curran,
D. P. Angew. Chem., Int. Ed. 1998, 37, 1174-1196. (c) For a collection of
articles on fluorous reagents and catalysts see: Curran, D. P.; Gladysz, J.
A., Eds. Tetrahedron 2002, 58, issue 20.
(7) (a) Crich, D.; Hao, X.; Lucas, M. Tetrahedron 1999, 55, 14261-
14268. (b) Crich, D.; Hao, X. Org. Lett. 1999, 1, 269-272. (c) Crich, D.;
Barba, G. R. Org. Lett. 2000, 2, 989-991. (d) Crich, D.; Neelamkavil, S.;
Sartillo-Piscil, F. Org. Lett. 2000, 2, 4029-4031.
(1) (a) Brown, H. C.; Heim, P.; Yoon, N. M. J. Am. Chem. Soc. 1970,
92, 1637-1646. (b) Zaidlewicz, M.; Brown, H. C. In EROS; Paquette, L.
A., Ed.; Wiley: Chichester, UK, 1995; Vol. 1, pp 638-644.
(2) (a) Braun, L. M.; Braun, R. A.; Crissman, H. R.; Opperman, M.;
Adams, R. M. J. Org. Chem. 1971, 36, 2388-2389. (b) Lane, C. F. J. Org.
Chem. 1974, 39, 1437-1438. (c) Brown, H. C.; Mandal, A. K.; Kulkarni,
S. U. J. Org. Chem. 1977, 42, 1392-1398. (d) Zaidlewicz, M. In EROS;
Paquette, L. A., Ed.; Wiley: Chicester, UK, 1995; Vol. 1, pp 634-637.
10.1021/ol026957j CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/10/2002

tile, recyclable fluorous analogue (2) of BMS. Contemplation
of (i) the need for g60% F by weight to facilitate recycling
by fluorous extraction, (ii) the need for an insulating spacer
between the sulfide and the fluorous group to modulate the
strongly electron-withdrawing ability of the latter, and (iii)
economic considerations steered us toward 2-(perfluoro-
octyl)ethyl methyl sulfide (1, 65.4% F) and the corresponding
borane adduct 2 (63.6% F). The synthesis of 1 was achieved
in a straightforward manner, in 76% overall yield, by the
displacement of iodide from 2-(perfluorooctyl)ethyl iodide
with potassium thioacetate followed by saponification with
concomitant alkylation of the thiolate with methyl iodide
(Scheme 1).9 The passage of borane gas, generated from BF3‚
soluble in FC-72 with which it forms a fine suspension. The
mixture is soluble in dichloromethane or benzotrifluoride13
(trifluoromethylbenzene). In practice we have found it
convenient to use either the solid mixture of 1 and 2 or a
suspension in FC-72.
A series of five hydroborations were conducted with a FC-
72 suspension of the mixture of 1 and 2 (1.7 M in 2) with
the results set out in Table 1. These reactions were conducted
Table 1. Hydroboration with Fluorous BMS (2)
Scheme 1. Preparation of Fluorous BMS
OEt2 and NaBH4,10 through the neat, liquid sulfide then
resulted in the formation of a white solid that was estimated
by 1H NMR spectroscopy to be an approximately 1:1 mixture
of 1 and 2.11 The 11B NMR spectrum of this mixture had a
single resonance at δ -22 ppm consistent with the formation
of 2. Likewise the ESI mass spectrum of the mixture
demonstrated a molecular ion at m/z 509 in full agreement
with this proposition. As anticipated both 1 and the mixture
of 1 and 2 were completely odorless. The solid mixture of
1 and 2 was only hydrolyzed slowly on standing in air at
room temperature and additionally showed no tendency to
ignite under those conditions; it was indefinitely stable under
a nitrogen atmosphere in the refrigerator. The considerable
stability of the solid mixture of 1 and 2 in air enables the
reagent to be weighed on a simple laboratory balance. This,
coupled with the ready determination of the stoichiometry
a The bulk of the reagent is recovered in its spent form, namely 1;
however, this is contaminated by small amounts of unreacted 2. As the
mixture is simply recycled by passage of borane gas, the small amount of
2 present was neither quantified nor separated.
under nitrogen in a biphasic mixture of FC-72 and dichlo-
romethane. On consumption of the olefin, the spent fluorous
phase was removed ready for recycling and the organic phase
was subjected to oxidative workup in the normal manner
with alkaline hydrogen peroxide. The majority (∼80%) of
1 and 2, depleted in 2, was recovered from the fluorous
phase, while a further 10% was recovered from the organic
phase following the oxidative workup and chromatography;
interestingly no oxidation of the sulfide to the sulfoxide or
sulfone was observed under the oxidative workup conditions.
The fluorous solution of 1 and 2 was then re-subjected to
treatment with borane following which it performed exactly
as the original sample. Of the five examples presented, the
first is straightforward and requires no comment. The second
example is the hydroboration of â-pinene and performs
exactly as expected from the precedent with BMS2 and with
1
of the mixture by integration of the H NMR spectrum,
affords a very ready, convenient method of adding precise
amounts of reagent to a reaction and stands in contrast to
the cumbersome determination of hydrogen released on
hydrolysis usually recommended for the dosage of BMS and
other boranes.12 Interestingly, despite its high fluorine
content, the solid mixture of 1 and 2 was only sparingly
(8) (a) Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001, 123, 7449-
7450. (b) Crich, D.; Neelamkavil, S. Tetrahedron 2002, 58, 3865-3870.
(9) We prefer this synthesis of fluorous BMS over the ones previously
described for the lower homologues as it avoids the need to work with
dimethyl disulfide.8a,b
(10) Zweifel, G.; Brown, H. C. Org. React. 1963, 13, 1-54.
(11) Interestingly, the 1:1 mixture of 1 and 2 is formed both when borane
is passed through neat 1 and when it is bubbled through solutions of 1 in
FC-72. In the former case the reaction mixture solidifies at this stoichiometry
whereas in the latter precipitation of the 1:1 mixture of 1 and 2 takes place.
(12) Brown, H. C. Organic Synthesis Via Boranes; Wiley: New York,
1975.
(13) Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450-451.
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Org. Lett., Vol. 4, No. 23, 2002

previously obtained with BH3‚THF.20 A nitrile was reduced
to a primary amine in a straightforward manner and N-benzyl
levulinamide was converted to N-benzyl 4-hydroxypenty-
lamine thereby demonstrating the ability of fluorous BMS
to reduce both amides and ketones.
Table 2. Further Reductions with Fluorous BMS
Finally, we investigated the ability of fluorous BMS (2)
to regenerate the Corey-type oxaborolidine catalysts21 in an
asymmetric reduction (Scheme 2). In the event, reduction
Scheme 2. Oxaborolidine-Catalyzed Reduction with Fluorous
BMS
a The bulk of the reagent is recovered in its spent form, namely 1;
however, this is contaminated by small amounts of unreacted 2. As the
mixture is simply recycled by passage of borane gas, the small amount of
2 present was neither quantified nor separated.
of acetophenone in THF by an FC-72 solution of 2 catalyzed
by 10 mol % of 22 resulted in the formation of (R)-1-
hydroxyethylbenzene in 94% yield and 84% ee as determined
by chromatography over a Chircel OD column.
borane.14 The third example, the hydroboration of a trisub-
stituted alkene, proceeds with high yield and regio- and
stereoselectivity exactly as anticipated.15 The fourth example
illustrates the compatibility with functionality16 such as might
be found in a typical pharmaceutical. The final example is
a relatively unusual example of hydroboration in the presence
of a sulfoxide;17 the reduced regioselectivity observed in this
example is typical of that seen in BMS hydroborations of
other allyl ethers18 and alkenes substituted with electron-
withdrawing groups in general.19 Fluorous BMS (2) therefore
functions in hydroboration exactly as BMS itself but with
the considerable advantage that the reaction is odor-free and
may be conducted in an organic/fluorous biphasic mixture
with straightforward recycling of the fluorous solution.
In conclusion, solutions of fluorous BMS (2) perform in
a manner exactly analogous to BMS itself. The new reagent
possesses, however, several considerable advantages over its
well-established counterpart. First, it and the reduction
product 1 are completely odorless. Second, the spent fluorous
solution, enriched in 1, is readily regenerated by the passage
of borane gas. Third, both the solid mixture of 1 and 2, and
its suspension in FC-72 are quite stable under a nitrogen
atmosphere and show no tendency toward ignition in air.
Finally, the solid mixture of 1 and 2 may be readily weighed
in air and the stoichiometry determined by standard 1H NMR
spectroscopy, thereby permitting facile dispensation of
precise quantities of borane. These attributes combine to
suggest that fluorous suspensions of 1 and 2 might well be
suitable for large-scale industrial applications with simple
regeneration at a remote borane generation facility.
We subsequently used the fluorous suspension of 2,
typically in a biphasic manner with ready recycling, to
conduct a number of other reductions (Table 2). Thus,
treatment of nitroester 15 with the FC-72 solution of 2
enabled clean reduction of the ester without complications
from the nitro group. This result compares well to that
Acknowledgment. We thank the NSF (CHE 9986200)
for support of this work.
Supporting Information Available: Full experimental
details and characterization data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(14) Zweifel, G. W.; Brown, H. C. J. Am. Chem. Soc. 1964, 86, 393-
397.
(15) Brown, H. C.; Zweifel, G. W. J. Am. Chem. Soc. 1961, 83, 2544-
2551.
(16) Bruncko, M.; Crich, D.; Samy, R. J. Org. Chem. 1994, 59, 5543-
5549.
(17) Crich, D.; Dai, Z. Tetrahedron 1999, 55, 1569-1580.
(18) Corrie, J. E. T.; Papergeorgiou, G. J. Chem. Soc., Perkin Trans. 1
1996, 1583-1592.
(19) Smith, K.; Pelter, A. In ComprehensiVe Organic Synthesis; Trost,
B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 8, pp 703-731.
OL026957J
(20) Crich, D.; Neelamkavil, S. Org. Lett. 2002, 4, 2573-2575.
(21) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1987-
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