B(C6F5)3-Catalyzed Chemoselective Defunctionalization of Ether-Containing Primary Alkyl Tosylates with Hydrosilanes

Article abstract of DOI:10.1002/anie.201611813

Catalytic C(sp³)?O bond cleavage promoted by B(C₆F₅)₃ /Et₃SiH proceeds preferentially with primary tosylates in the presence of primary and secondary silyl ethers and aryl ethers. This reactivity difference enables the chemoselective defunctionalization of several 1,n-diols, and the efficiency of the new procedure is highlighted by the selective deoxygenation of the hydroxymethyl group of an orthogonally protected carbohydrate. Tosylates with an adjacent phenyl group are cleaved with anchimeric assistance.

Full text of DOI:10.1002/anie.201611813

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201611813
German Edition: DOI: 10.1002/ange.201611813
Deoxygenation
B(C6F5)3-Catalyzed Chemoselective Defunctionalization of Ether-
Containing Primary Alkyl Tosylates with Hydrosilanes
Indranil Chatterjee+, Digvijay Porwal+, and Martin Oestreich*
3
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Abstract: Catalytic C(sp ) O bond cleavage promoted by
B(C6F5)3 /Et3SiH proceeds preferentially with primary tosylates
in the presence of primary and secondary silyl ethers and aryl
ethers. This reactivity difference enables the chemoselective
defunctionalization of several 1,n-diols, and the efficiency of
the new procedure is highlighted by the selective deoxygenation
of the hydroxymethyl group of an orthogonally protected
carbohydrate. Tosylates with an adjacent phenyl group are
cleaved with anchimeric assistance.
T
he selective removal of hydroxy groups from sp3-hybridized
carbon atoms in the presence of other functional groups is still
an attractive challenge.[1] In a general sense, reductive alcohol
deoxygenation is achieved either directly in a single-step
procedure or by converting the hydroxy group into a more
reactive leaving group prior to the reduction step. Direct
defunctionalization using Lewis acids largely relies on inher-
ently reactive tertiary as well as benzylic and allylic alco-
hols.[2,3] Unactivated systems usually require two synthetic
operations, that is, the transformation of the alcohol into
a halide[4] or a thiocarbonyl ester[5] (Barton–McCombie
reaction) followed by radical reduction, often using tin
hydrides. Although in practice, halides and reactive sulfonates
are reduced by an excess of a borohydride, limitations that are
due to elevated reaction temperatures apply.[6] A recent
method makes use of catalytically generated CuI hydrides to
reduce primary alkyl triflates and primary/secondary
iodides.[7]
Scheme 1. B(C6F5)3-catalyzed selective cleavage of silyl ethers (known)
and tosylates in the presence of ether functional groups (planned).
Si=triorganosilyl, Ts=4-toluenesulfonyl.
tional groups, such as silyl and aryl ethers (Scheme 1, bottom).
We herein disclose a mild method for the two-step reductive
defunctionalization of various diols, ethers, and polyols using
B(C6F5)3 as the Lewis acid catalyst and Et3SiH as the
stoichiometric hydride source.
We began with converting primary alcohols into more
reactive sulfonates. Both tosylate 1a and triflate 1b were
found to undergo efficient reduction in the presence of
10 mol% B(C6F5)3 and slightly more than one equivalent of
Et3SiH in CH2Cl2 at room temperature (1!2; Scheme 2, top).
The same setup also enabled the hydrodehalogenation of the
related bromide 1c whereas a representative chloride was
The fact that borohydrides reductively cleave readily
available sulfonates led us to consider [HB(C6F5)3]ꢀ, which is
catalytically formed in situ from B(C6F5)3/hydrosilane combi-
nations,[8,9] as the reducing agent. Moreover, the groups of
Gagnꢀ[10,11] and Morandi[12] had recently demonstrated that,
based on seminal work by Gevorgyan, Yamamoto, and co-
workers,[2a,b] this catalyst/reagent system enables the regio-
and chemoselective deoxygenation of polyol- and 1,2-diol-
derived silyl ethers, respectively (Scheme 1, top). Their
impressive findings prompted us to develop a distinct strategy
for the highly chemoselective deoxygenation of primary
tosylates in the presence of other oxygen-containing func-
[*] Dr. I. Chatterjee,[+] D. Porwal,[+] Prof. Dr. M. Oestreich
Institut fꢀr Chemie, Technische Universitꢁt Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.de
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201611813.
Scheme 2. Screening of primary and secondary sulfonates and bro-
mides (top) and chemoselectivity of sulfonate over bromide removal
(bottom). LG=leaving group, Tf=trifluoromethanesulfonyl.
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barely converted (not shown; see the Supporting Information
for details). The chemoselectivity of the reaction with respect
to sulfonate against bromide removal is clearly in favor of the
tosylate (6!7; Scheme 2, bottom). The above reactions all
showed full conversion within a reaction time of 12 h.
Conversely, tosylate 3a, which was derived from the corre-
sponding secondary alcohol, furnished hydrocarbon 4 in
diminished yield owing to competing elimination; bromide 3c
reacted cleanly in near-quantitative yield (3!4; Scheme 2).
Unlike acyclic substrates 1 and 3, cyclic tosylate 5 exclusively
underwent elimination.
With the initial finding that B(C6F5)3 catalyzes the
reductive cleavage of primary tosylates, we turned towards
the chemoselective deoxygenation of orthogonally protected
1,n-diols. We opted for TBDMS protection on one end of the
diol for its ease of deprotection. It must be noted, however,
that the less bulky EtMe2Si group is also fully compatible with
the reductive removal of the tosylate.[10a] Diols with longer
carbon chains underwent chemoselective cleavage of the
tosylate in high yields (8/10/12!9/11/13; Scheme 3, top).
Figure 1. Mechanistic explanation of rearrangements proceeding by
anchimeric assistance.
This reaction is likely to involve the aforementioned three-
membered silyl oxonium ion (Figure 1, right).
We next focused on the chemoselective removal of
tosylates in the presence of aryl ethers (Scheme 4). It must
be emphasized that Gevorgyan, Yamamoto, and co-workers
have already reported on B(C6F5)3-catalyzed reductive ether
cleavage with Et3SiH at room temperature.[2b] Applying our
Scheme 4. Chemoselective cleavage of tosylates in the presence of aryl
ethers. [a] Determined by 1H NMR spectroscopy with 1,3,5-trimethoxy-
benzene added after the reaction. [b] Yield of isolated product after
flash column chromatography on silica gel. [c] Et3SiH (2.4 equiv).
standard procedure, we tested ethylene glycol derivative 21a,
which reacted with moderate selectivity (21a!22a). How-
ever, high yields were achieved for 21b–d, which are derived
from the higher diol hexane-1,6-diol. Substituents at the aryl
ring that are often prone to interfere with transition-metal-
catalyzed or radical reductions were tolerated (21b–d!22b–
d). A CF3 group was also compatible but the corresponding
product was obtained in low yield (21e!22e). Tosylate 21 f
with an additional methyl ether did not afford the desired
compound; both tosylate removal and methyl-ether cleavage
occurred while the methylene linkage was left intact. The free
phenol was still isolated in decent yield with double the
amount of Et3SiH (21 f!22 f).
Scheme 3. Chemoselective cleavage of tosylates in the presence of silyl
ethers. [a] Determined by 1H NMR spectroscopy with 1,3,5-trimethoxy-
benzene added after the reaction. [b] Yield of isolated product after
flash column chromatography on silica gel. TBDMS=tert-butyldime-
thylsilyl.
However, the 1,2- and 1,3-diols 14 and 16 were transformed
into the rearranged products 15 and 17, respectively, with
neighboring-group participation (14/16!15/17; Scheme 3,
middle). These defunctionalization reactions pass through
phenonium ions (Figure 1, left) rather than three- or four-
membered cyclic silyl oxonium ions[10a] (not shown) as
confirmed by deuterium labeling with Et3SiD (14/16![2H]-
15/[2H]-17). The situation changes with aliphatic 18 where
anchimeric assistance by an adjacent aryl group is not
possible; the regioisomers 19 and 20 were formed in an
almost equimolar ratio (18!19 and 20; Scheme 3, bottom).
The defunctionalization also proceeded smoothly in the
presence of an alkene without competing hydrosilylation
(23!24; Scheme 5, top). The cyclic ether in tosylated
tetrahydrofurfuryl alcohol remained untouched (25!26;
Scheme 5, bottom). To highlight the utility of the new
method, we selected a carbohydrate, TBDMS-protected 1,2-
3
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deoxy-d-glucose 27, with several delicate C(sp ) O linkages
(Scheme 5, bottom). The standard setup furnished 28, which
was directly converted into 29 by a known procedure[13] (27!
28!29). The unprotected tetrahydropyran 29 was isolated in
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[1] For an authoritative review, see: J. M. Herrmann, B. Kçnig, Eur.
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[3] Recently, Dai and Li disclosed a one-pot, two-step deoxygena-
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(CH2OH!CHO!CH3); see: X.-J. Dai, C.-J. Li, J. Am. Chem.
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[4] For a general review on reductive hydrodehalogenation, see: F.
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Scheme 5. Chemoselective defunctionalization of primary tosylates in
the presence of an alkene (top) and various ether linkages (bottom).
68% overall yield, confirming that the present cleavage of
primary tosylates is a valuable method for the preparation of
sugar analogues. Selective deuteration of 27 was also feasible
with Et3SiD (27![2H]-28![2H]-29).
In conclusion, we have reported the straightforward
deoxygenation of primary alcohols in the form of their
easily generated tosylates in the presence of other oxygen-
[8] For a review on B(C6F5)3-catalyzed hydrosilane activation, see:
M. Oestreich, J. Hermeke, J. Mohr, Chem. Soc. Rev. 2015, 44,
2202 – 2220.
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3
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from B(C6F5)3/Et3SiH selectively cleaves the C(sp ) OTs
linkage at room temperature without interference from
3
3
ꢀ
ꢀ
C(sp ) OTBDMS or C(sp ) OAr ethers, for example. The
excellent chemoselectivity was illustrated by the defunction-
alization of the hydroxymethyl group of an orthogonally
protected sugar molecule.
Acknowledgements
This research was supported by the German Academic
Exchange Service (predoctoral fellowship to D.P., 2014–
2018) and the Cluster of Excellence “Unifying Concepts in
Catalysis” of the Deutsche Forschungsgemeinschaft
(EXC 314/2). M.O. is indebted to the Einstein Foundation
(Berlin) for an endowed professorship.
Conflict of interest
[13] Y. Kaburagi, Y. Kishi, Org. Lett. 2007, 9, 723 – 726.
The authors declare no conflict of interest.
Keywords: alcohols · boron · deoxygenation · reduction · silanes
Manuscript received: December 5, 2016
Final Article published: && &&, &&&&
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Angewandte
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Communications
Deoxygenation
I. Chatterjee, D. Porwal,
M. Oestreich*
&&&& — &&&&
B(C6F5)3-Catalyzed Chemoselective
Defunctionalization of Ether-Containing
Primary Alkyl Tosylates with Hydrosilanes
The weakest link: Hydrosilanes activated
by B(C6F5)3 are known to cleave ethers as
well as silyl ethers. However, more reac-
tive tosylates are cleaved prior to those
ethers, which allows for the chemoselec-
tive deoxygenation of diols and polyols.
Other functional groups such as carboxyl
groups are also tolerated. Defunctionali-
zation of phenethyl tosylate motifs pro-
ceeds with anchimeric assistance (rear-
rangement).
4
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