Alkyl Ethers as Traceless Hydride Donors in Br?nsted Acid Catalyzed Intramolecular Hydrogen Atom Transfer

Article abstract of DOI:10.1002/anie.201801953

A new protocol for the deoxygenation of alcohols and the hydrogenation of alkenes under Br?nsted acid catalysis has been developed. The method is based on the use of either a benzyl or isopropyl ether as a traceless hydrogen-atom donor, and involves an intramolecular hydride transfer as a key step, which is achieved in a regio- and stereoselective manner.

Full text of DOI:10.1002/anie.201801953

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Use of Alkyl Ethers as Traceless Hydride Donors in Brønsted
Acid-Catalyzed Intramolecular Hydrogen Atom Transfer
Authors: Dhika Aditya Gandamana, Bin Wang, Ciputra Tejo, Benoit
Bolte, Fabien Gagosz, and Shunsuke Chiba
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201801953
Angew. Chem. 10.1002/ange.201801953
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10.1002/anie.201801953
Angewandte Chemie International Edition
COMMUNICATION
Use of Alkyl Ethers as Traceless Hydride Donors in Brønsted
Acid-Catalyzed Intramolecular Hydrogen Atom Transfer
Dhika Aditya Gandamana,a Bin Wang,a Ciputra Tejo,a Benoit Bolte,b Fabien Gagosz*b,c and Shunsuke
Chiba*a
Dedicated to Professor Samir Z. Zard in celebration of his 63th birthday
Abstract: A new protocol for the deoxygenation of alcohols and the
hydrogenation of alkenes under Brønsted acid catalysis has been
developed. The method is based on the use of a benzyl or an
isopropyl ether as a traceless hydrogen atom donor and involves an
intramolecular hydride transfer as a key step that can be achieved in
regio- and stereoselective manners.
Brønsted acid catalysis (Scheme 1D). It is worth noting that the
majority of the processes involving intramolecular hydride shift
reported so far employ electron-deficient alkene/alkyne moieties
as hydride acceptors, whereas utilization of other types of
hydride acceptors remain elusive.[6]
A- 1,5-Hydride transfer processes
Intramolecular hydride shift has been shown over the
years to be an efficient synthetic tool for the atom-economical
functionalization of aliphatic C-H bonds under redox-neutral
conditions (Scheme 1A).[1] Proper electrophilic activation of the
substrate (I→II) triggers such a process, whereby a hydrogen
atom of a relatively electron-rich C-H bond is transferred onto a
hydride acceptor (A) (II→III). 1,5-Hydride shift, which proceeds
via a 6-membered ring transition state, is the most common
mode of the process. Subsequent nucleophilic trapping of the
transient carbocation III, that typically takes place in an
intramolecular manner, completes the process (III→IV). Most of
the chemistry developed so far on the basis of this concept has
capitalized on the functionalization of aliphatic C-H bonds,[1]
whereas relatively less attention has been paid to exploiting the
reductive event on the hydride acceptor. One major exception is
electrophilic
activation
1,5-H
shift
C
C
A
H
H
C
A
H
A
I
nucleophilic
trapping
(A : pro-electrophilic site)
III
II
C-H bond functionalization event
Nu
H
well exploited
C
A
IV
reductive event
underexploited
B- Evans-Tishchenko reaction
OH
O
O
R
R
O
SmI2
R’
(cat.)
O
R
Me
O
OH
R’
the
Evans–Tishchenko
reaction
that
allows
the
R’
Me
H
+
diastereoselective reduction of β-hydroxy ketones in the
O
H
O
presence of SmI2 and an aldehyde (Scheme 1B).[2]
Sm
d.r. = >99:1
Me
H
In this context and following our ongoing interest in
hydrogen atom transfer reactions,[3] we wondered if alkyl ethers
could be used as traceless hydride donors in the reduction of a
transiently generated carbocation V (Scheme 1C).[4,5] In this
process, the hydrogen atom α to the ethereal oxygen in V would
migrate to the carbocation to produce a relatively stable
oxocarbenium ion VI. Subsequent hydrolysis would ultimately
deliver alcohol VII along with a ketone co-product derived from
the hydride donor moiety. We report herein the realization of this
concept, which has led to the regio- and stereoselective
deoxygenation of alcohols and hydrogenation of alkenes under
C- Alkyl ethers as hydride donors
traceless redox-active H donor
R
R
R'
1,5-H
shift
OH
O
R'
O
O
H2O
H
+
H
H
R
R'
+
V
VI
VII
D- Deoxygenation of alcohols and hydrogenation of alkenes using
stereoselective 1,5-hydride transfers (this work)
diastereoselective
reduction
[a]
D. A. Gandamana, Dr. B. Wang, Dr. C. Tejo, Prof. S. Chiba
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University, Singapore 637371 (Singapore)
E-mail: shunsuke@ntu.edu.sg
R
H
R
H
cat. TsOH
OH
R1
H
O
O
OH
R3
R2
R'
R'
or
*
R3
R2
CF3CH2OH
then H2O
R2
R1
R1
[b]
[c]
Dr. B. Bolte, Prof. F. Gagosz
Département de Chimie, UMR 7652 and 7653 CNRS, Ecole
Polytechnique, 91128 Palaiseau, France.
Prof. F. Gagosz
Scheme 1. Exploiting 1,5-hydride transfers in reductive processes
Department of Chemistry and Biomolecular Sciences, University of
Ottawa, K1N 6N5, Ottawa, Canada.
E-mail: fgagosz@uottawa.ca
We started our investigations with model substrate 1a-Bn,
a tertiary alcohol having a benzyl ether moiety as a potential
hydride donor, and attempted to find suitable reaction conditions
Supporting information for this article is given via a link at the end of
the document.the document.
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10.1002/anie.201801953
Angewandte Chemie International Edition
COMMUNICATION
for its deoxygenation (Scheme 2A). An extensive screening of
the reaction settings (see the SI for details) revealed that the
desired transformation could be optimally performed in
trifluoroethanol at 50 °C using TsOH as a catalyst (2 mol%).
Under these reaction conditions, the deoxygenated alcohol 2a
was rapidly produced in 85% isolated yield after aqueous work-
up of the reaction mixture. Among other alkyl ethers examined,[7]
isopropyl ether 1a-iPr was found to perform with a similar
efficiency, affording 2a in 78% yield.
carbinol center (see 2i). The deoxygenation of secondary benzyl
alcohols could also be achieved (see 1j) but an increase of the
reaction temperature to 80 °C was required in this case. We
found that the reduction of a non-benzylic carbon center was
possible (see 2k) albeit with lower efficiency (41%).
Ph
[a]
OH
H
TsOH (2 mol%)
O
OH
R2
R1
O
OH
R2
R1
R2
R1
or
CF3CH2OH, 50 °C
then H2O (work-up
)
A- Optimized reaction conditions for the deoxygenation
1-Bn
1-iPr
2b-k
[a]
R
PhCHO
or
acetone
TsOH (2 mol%)
OH
O
OH
Me
Ph
H
OH Ph
OH Et
OH
OH
+
Me
Ph
CF3CH2OH
50 °C, 15 min
Ph
Ph
Ph
Ph
then H2O (work-up)
2a
2b
2c
2d
2e
76%
[b]
[b]
1a-Bn (R = CH2Ph)
1a-iPr (R = i-Pr)
83% (86%)
84% (85%)
36% (45%)
85% from 1a-Bn
78% from 1a-iPr
OH Me
OH Me
Ph
OH
B- Mechanistic proposal for the deoxygenation of 1a-iPr
Ph
Br
OMe
2f
2g
2h
F3CH2CO
O
H
90%
65%
87%
1a-iPr
H
Me
OH
OH Me
C
Me
Me
OH
Ph
CF3CH2OH
Ph
2j [b,c]
O
Ph
H2O
-
H2O
Me
O
Me
Me
2k [c]
41%
Me
2i
94%
O
85% (79%)
H
OH
H
H
Me
Ph
2a
Me
Me
1,5-H shift
Scheme 3. Substrate scope: TsOH-catalyzed deoxygenation of alcohols 1-Bn
and 1-iPr. [a] Unless otherwise stated, the reactions were performed using
0.5 mmol of 1-Bn or 1-iPr and 2 mol% of TsOH in CF3CH2OH (0.1M) at 50 °C.
Isolated yields are given. Yields in parentheses refer to the use of 1-Bn as the
substrates. Yields without parentheses refer to the use of 1-iPr as the
substrates. [b] The reaction was conducted using 0.3 mmol of 1j. [c] The
reaction was conducted at 80 °C.
A
Ph
B
Ph
Scheme 2. TsOH-catalyzed deoxygenation of alcohols 1a. [a] The reactions
were conducted using 0.3-0.5 mmol of 1a and 2 mol% of TsOH in CF3CH2OH
(0.1M) at 50 °C. [b] Isolated yields.
A mechanistic proposal for the formation of 2a from 1a-iPr
is depicted in Scheme 2B.[8] The reaction of 1a-iPr with TsOH
promotes its dehydration to afford the carbocation intermediate
A.[9] A subsequent 1,5-hydride transfer can then lead to the
formation of the oxocarbenium ion B,[10] which is then trapped by
trifluoroethanol to deliver ketal C. This last step is accompanied
by the regeneration of a proton that maintains the catalytic
turnover. Ketal C is finally hydrolyzed under aqueous work-up to
afford 2a with concomitant elimination of acetone.
We next investigated the substituent effect on the
stereoselectivity of the transformation (Scheme 4A).[11] We
wondered if the presence of a substituent at the position
adjacent to the hydroxyl group would allow 1,2-
diastereoinduction during the 1,5-hydride transfer step.
Interestingly, the reaction of 3a under the optimized reaction
conditions proceeded smoothly to afford 4a as
a single
diastereomer (Me groups in a relative syn configuration) in an
excellent yield. High efficiencies and perfect 1,2-syn
diastereoselectivity were also attained when structurally related
substrates bearing a benzyl (for 4b), an allyl (for 4c), a
benzyloxyethyl (for 4d), an isopropyl (for 4e) and a phenyl group
(for 4f) at the position adjacent to the hydroxyl group were
employed. Interestingly, the reaction of 3d having two benzyloxy
groups as potential hydride donors proceeded selectively via a
1,5-shift (not via a 1,6-shift). The installation of a butenyl group
at the carbinol position (3g) resulted in a slightly lower yield of
4g (67%) but the diastereoselectivity remained high (97:3).
Cyclohexanol derivative 3h was also shown to be a suitable
substrate for this transformation. It is worth noting that different
diastereomers 3h-(1R*,2R*) and 3h-(1S*,2R*) furnished the
Having optimized the reaction conditions, we next
investigated the scope and limitations of this deoxygenative
reaction using a variety of β-benzyloxy alcohols 1-Bn or β-
isopropoxy alcohols 1-iPr (Scheme 3). The method could be
applied to the formation of mono or bis-benzylic tertiary carbon
centers as exemplified by the formation of benzhydryl derivative
2b and benzyl derivatives 2c-2f. In these cases, the yields were
generally high (>80%) except for the formation of allyl derivative
2d. No significant difference in reactivity was observed among
isopropyl and benzyl ethers as hydride donors (see formation of
2b-d). The process tolerated substitution of different electronic
nature on the aromatic ring (see 2g-i) and was not influenced by
the presence of a sterically demanding o-tolyl group at the
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10.1002/anie.201801953
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COMMUNICATION
identical single diastereomer of 4h in excellent yields. These
results attest of the stereoconvergence of the process, which is
not affected by the stereochemistry at the carbinol centre. The
present 1,2-syn diastereoinduction could be rationalized by
invoking a 6-membered ring chair-like transition state in the key
1,5-hydride transfer step. In this model, represented for
substrate 3a in Scheme 4B-i, the more sterically demanding
phenyl group[12] on the carbocation and the methyl group at the
adjacent position would both adopt a pseudo-equatorial position
(TS D). For the formation of cyclohexane derivative 4h, the
selectivity could be explained by a transfer of the hydride onto a
pseudo-axial position of the cyclohexyl moiety via a cis decaline
type transition state E, in which the benzyloxymethyl tether
would be lying in the pseudo-equatorial position.
We also demonstrated construction of a new chiral centre
by taking advantage of the diastereoselective nature of the
present 1,5-hydride transfer (Scheme 5). The literature-known
optically active Weinreb amide 3a-W (prepared from
commercially
available
methyl
(S)-3-hydroxy-2-
methylpropionate)[13] was first treated with PhMgBr to afford the
enantio-enriched β-benzyloxy phenyl ketone 3a’-(S) (99% ee).
Its subsequent treatment with MeMgCl followed by an acidic
work-up with a slight excess amount of AcOH delivered the
crude methyl phenyl carbinol 3a. The reaction of 3a in the
presence of TsOH (10 mol%) in trifluoroethanol at 50 °C
furnished 4a-(2R,3R) in 83% yield as a single diastereomer with
a high degree of enantiopurity (99% ee). Overall the one-pot
conversion of 3a’-(S) into 4a-(2R,3R) can be regarded as a
stereoselective deoxygenative methylation of the ketone moiety.
A- 1,2-Diastereoinduction: substrate scope [a]
substrate
BnO
product
HO
Me
Ph
substrate
BnO
product
Me
PhMgBr
(2 equiv)
OH
O
OH
O
ref 15
Me
HO
Me
HO Me
Ph
HO Me
Ph
Me
OMe
N
THF, 0 °C
Me
Me OMe
Ph
methyl (S)-3-hydroxy-
2-methylpropionate
3a-W
Me
Me
Me
Me
3a
4a 97%
3e
4e 85%
(d.r. = >99:1)
(d.r. = >99:1)
1) MeMgCl
(2 equiv)
THF, 0 °C, 2 h
2) TsOH
(10 mol%)
OBn O
HO
Me
BnO
HO
Me
Ph
HO Me
Ph
BnO
HO
Me
Ph
HO Me
[3a]
Ph
Ph
then
AcOH
(2.2 equiv)
and evaporation
CF3CH2OH
50 °C
then H2O
Ph
Me
Me
Ph
Ph
Ph
3b [b]
Ph
3a’-(S)
90%, 99%ee
4a-(2R,3R)
83%, 99%ee
(d.r. = >99:1)
4b 94%
(d.r. = >99:1)
3f
4f 88%
(d.r. = >99:1)
HO
HO
Me
BnO
HO Me
Ph
BnO
BnO
HO
Scheme 5. Synthesis of enantio-enriched 4a-(2R,3R).
Ph
Ph
Ph
Me
Me
We next examined the effect of a substituent located at the γ
position to the hydroxyl group (Scheme 6). The reaction of 5a-
(2S*,4S*) under the optimized reaction conditions afforded
alcohol 6a in 91% yield with a good 1,3-anti diastereoselectivity
(86:14). It should be noted that the reaction of another
diastereomer 5a-(2R*,4S*) afforded identical outcomes in terms
of yield and the diastereoselectivity. Installation of a p-tolyl group
at the carbinol position in 5b allowed for the synthesis of
dihydro-arturmerol 6b, which was reported to exhibit
acetylcholinesterase (AChE) inhibitory activity.[14] Replacement
of the isobutyl substituent with a smaller methyl group did not
affect the diastereoselectivity (for 5c). The origin of the 1,3-anti
diastereoinduction could be explained by the involvement of a 6-
membered ring chair-like transition state such as F, in which the
most sterically demanding groups occupy a pseudo-equatorial
position (exemplified with 5a in Scheme 6B). Interestingly, the
reaction of 5d, which possesses two adjacent stereocenters in
an anti relationship on the cyclohexane fragment, afforded the
deoxygenated compound 6d in high yield (83%) as a single
diastereomer (Scheme 6C). This transformation might proceed
via the rigid chair-like 6-membered ring transition state G shown
in Scheme 6C.
3c
4c 89%
(d.r. = >99:1)
3g
4g 69%
(d.r. = 97:3)
BnO
HO
Me
HO
Ph
HO Me
HO Ph
1
2
Ph
OBn
Ph
OBn
4h 95%
(d.r. = >99:1)
3d
4d 67%
(d.r. = >99:1)
3h-(1R*,2R*) [b]
3h-(1S*,2R*) [b,c]
4h 94%
(d.r. = >99:1)
B- Origin of the diastereoselectivity
H
Me
H2O
- PhCHO
H
Ph
O
(i)
3a
3h
4a
Me
H
- H2O
Ph
H
D
H
Ph
H2O
H
Ph
(ii)
4h
H
O
- H2O
- PhCHO
H
E
Scheme 4. 1,2-Diastereoinduction in the deoxygenation of alcohols. [a] The
reactions were conducted using 0.5 mmol of alcohol as single
3
a
diastereomer and 2 mol% of TsOH in CF3CH2OH (0.1M) at 50 °C. Isolated
yields and diastereomeric ratio of 4 are given. [b] The reaction was conducted
using 5 mol% of TsOH at 80 °C. [c] 0.39 mmol of 3h-(1S*,2R*) was used.
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10.1002/anie.201801953
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COMMUNICATION
A- 1,3-Diastereoinduction: substrate scope [a]
This work demonstrates the use of alkyl ethers as traceless
hydride donors for the deoxygenation of alcohols and the
hydrogenation of alkenes under Brønsted acid catalysis. The
reductive process described herein, which is based on an
intramolecular 1,5-hydride shift onto a transient carbocation,
exhibits high degree of efficiency and stereoselectivity. The
present concept will be extended and exploited in the
development of other types of reductive processes, especially
asymmetric variants.
substrate
product
yield (d.r.)
BnO
HO
Me
Ph
HO Me
Ph
91% (86:14)
6a
6a
5a-(2S*,4S*)
BnO
HO Me
92% (89:11)
82% (88:12)
Ph
5a-(2R*,4S*)[b]
HO
HO
Me
TsOH[a]
Ph
BnO
HO Me
H
H
OH Me
R2
Me
O
(2 mol%)
p-Tol
p-Tol
5b-(2S*,4S*)
O
R1
Ph
R1
6b
CF3CH2OH
50 °C
then
H2O (work-up)
H
R1
R2
R2
BnO
HO Me
Me
7
8
89% (88:12)
Me
5c-(2S*,4S*)
Ph
Me
Ph
6c
Me OH Me
HO
R1
Me
O
OH Me
B- Origin of the diastereoselectivity
Me
Ph
Ph
N
Ph
8a (= 6a)
81% (86:14)
H
H
8b R1= Me 81% (85:15)
8c R1= Cy 99% (83:17)
O
H2O
- PhCHO
H
Me
Ph
H
5a
8d 84% (89:11)
O
6a
- H2O
H
OH Me
F
Ph
Me OH Me
OH Me
Ph
Ph
BnO
C- 1,2,3-Diastereoinduction
Me
Ph
TsN
BnO
HO
Me H
Ph
HO Me
H
8e 80% (87:13)
8f 82% (85:15)
8g 26% (88:12)
[a]
Me
O
H
Ph
Ph
H
H
H
Scheme 7. TsOH-catalyzed hydrogenation of alkenes 7. [a] The reactions
were conducted using 0.3-0.5 mmol of alkenes 7 and 2 mol% of TsOH in
CF3CH2OH (0.1M) at 50 °C. Isolated yields and diastereomeric ratio (d.r.) of
the products are given. Cy = cyclohexyl
Ph
G
H
5d[c]
(d.r. = 78:22)
6d 83%
(d.r. = >99:1)
Scheme 6. 1,3- and 1,2,3-Diastereoinduction in the deoxygenation of alcohols.
[a] The reactions were conducted using 0.5 mmol of alcohol 5 and 2 mol% of
TsOH in CF3CH2OH (0.1M) at 50 °C. Isolated yields and diastereomeric ratio
(d.r.) of 6 are given. [b] The reaction was conducted using 0.36 mmol of 5a-
(2R*,4S*). [c] The reaction was conducted using 0.36 mmol of 5d.
Acknowledgements
This work was supported by funding from Nanyang
Technological University (for S.C.), the Singapore Ministry of
Education (Academic Research Fund Tier 1: 2015-T1-001-040
for S.C.), Ecole Polytechnique (for F.G.) and the Natural
Sciences and Engineering Research Council (for F.G.). Prof. D.
Pratt (University of Ottawa) is acknowledged for helpful
discussion on the reaction mechanism.
Finally, we examined the use of alkenes as an alternative
source of carbocations under the Brønsted acid catalysis.[15] The
optimized reaction conditions for the deoxygenation of alcohols
were applicable to the hydrogenation of alkenes (Scheme 7).
For instance, the reaction of homoallylic alcohol O-benzyl ether
7a proceeded smoothly to produce 8a (= 6a) in 81% yield with a
good 1,3-anti diastereoselectivity (d.r. = 86:14). This result is
very similar to that obtained for the deoxygenation of 5a
(Scheme 6A), indicating that both reactions proceed via the
Keywords: Hydrogen atom transfer • Brønsted acid • alcohols •
alkenes • reduction
formation of
a
common carbocation intermediate. The
[1]
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2014, 53, 5010; Angew. Chem. 2014, 126, 5110; b) L. Wang, J. Xiao,
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D. A. Evans, A. H. Hoveyda, J. Am. Chem. Soc. 1990, 112, 6447.
For our works on gold- and Brønsted-acid catalyzed hydride transfer
reactions, see: a) Q. Zhao, F. Gagosz, Adv. Synth. Catal. 2017, 359,
3108; b) B. Bolte, F. Gagosz, J. Am. Chem. Soc. 2011, 133, 7696; c) I.
Dias-Jurberg, Y. Odabachian, F. Gagosz, J. Am. Chem. Soc. 2010, 132,
3543.
investigation of the substrate scope revealed that various
primary and secondary alkyl groups could be installed as R1 to
generate products (8b-f) in good yields and diastereoselectivity.
Notably, nitrogen-containing substituents such as a phthalamide
(8d) or a piperidine (8f) were tolerated. The transformation also
exhibited selective 1,5-hydride shift over 1,6-shift in the case of
7e having two benzyloxy groups. The reduction process could
also be applied to benzyl substituted alkene 7g, but, while the
diastereoselectivity was similarly high, a noticeable drop in the
yield was observed.
[2]
[3]
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10.1002/anie.201801953
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COMMUNICATION
[4]
For selected examples on the use of alkyl ethers as hydride donors,
see: a) Z. Jiao, S. Zhang, C. He, Y. Tu, S. Wang, F. Zhang, Y. Zhang,
H. Li, Angew. Chem. Int. Ed. 2012, 51, 8811; Angew. Chem. 2012, 124,
8941; b) F. Cambeiro, S. Lopez, J. A. Varela, C. Saa, Angew. Chem.
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McQuaid, D. Sames, J. Am. Chem. Soc. 2009, 131, 402; e) P. A.
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Shikanai, H. Murase, T. Hata, H. Urabe, J. Am. Chem. Soc. 2009, 131,
3166; h) S. Bhunia, R. Liu, J. Am. Chem. Soc. 2008, 130, 16488; h) G.
B. Bajracharya, N. K. Pahadi, I. D. Gridnev, Y. Yamamoto, J. Org.
Chem. 2006, 71, 6204; i) S. J. Pastine, K. M. McQuaid, D. Sames, J.
Am. Chem. Soc. 2005, 127, 12180; j) M. Yoshimatsu, N. Hatae, H.
Shimizu, T. Kataoka, Chem. Lett. 1993, 1491.
[8]
[9]
While not shown in Scheme 2B, all steps of the catalytic cycle could be
reversible.
For reviews on generation and use of carbocations, see: a) T. Akiyama,
K. Mori, Chem. Rev. 2015, 115, 9277; b) R. R. Naredla, D. A. Klumpp,
Chem. Rev. 2013, 113, 6905.
[10] Deuterium labelling experiments clearly supported the intramolecular
nature of the hydride transfer step. See the SI for more details.
[11] For reports on catalytic asymmetric processes involving intramolecular
hydride transfer, see: a) Y. K. Kang, D. Y. Kim, Chem. Commun. 2014,
50, 222; b) K. Mori, K. Ehara, K. Kurihara, T. Akiyama, J. Am. Chem.
Soc. 2011, 133, 6166; c) W. Cao, X. Liu, W. Wang, L. Lin, X. Feng, Org.
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Am. Chem. Soc. 2009, 131, 13226.
[12] The relative steric demands are evaluated on the basis of the A-values
for a phenyl group (2.8 kcal/mol) and a methyl group (1.74 kcal/mol).
For A-values of various substituents, see: E. L. Eliel, S. H. Wilen, M. P.
Doyle, Basic Organic Stereochemistry, Wiley, 2001, p. 444.
[5]
[6]
[7]
For our recent work on use of Bn ether as a traceless redox-active H-
radical donor, see: G. H. Lonca, D. Y. Ong, T. M. H. Tran, C. Tejo, S.
Chiba, F. Gagosz, Angew. Chem. Int. Ed. 2017, 56, 11440; Angew.
Chem. 2017, 129, 11598.
[13] I. Paterson, K.-S. Yeung, C. Watson, R. A. Ward, P. A. Wallace,
Tetrahedron, 1998, 54, 11935.
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benzylic alcohol as a hydride acceptor, see: a) S.-S. Li, L. Zhou, L.
Wang, H. Zhao, L. Yu, J. Xiao, Org. Lett. 2018, 20, 138; b) L. Zhen, J.
Wang, Q.-L. Xu, H. Sun, X. Wen, G. Wang, Org. Lett. 2017, 19, 1566.
The reactions of ethyl and p-methoxybenzyl ethers were shown to be
less efficient (see the SI for more details).
[14] M. Fujiwara, N. Yagi, M. Miyazawa, J. Agric. Food Chem. 2010, 58,
2824.
[15] For an elegant reductive Hosomi–Sakurai reaction that involves
hydrogenation of alkenes by 1,5-hydride shift with stoichiometric use of
Brønsted acids, see: A. Bauer, N. Maulide, Org. Lett. 2018, 20, 1461.
This article is protected by copyright. All rights reserved.

10.1002/anie.201801953
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Dhika Aditya Gandamana, Bin Wang,
Ciputra Tejo, Benoit Bolte, Fabien
Gagosz* and Shunsuke Chiba*
Page No. – Page No.
Use of Alkyl Ethers as Traceless
Hydride Donors in Brønsted Acid-
Catalyzed Intramolecular Hydrogen
Atom Transfer
A new protocol for the deoxygenation of alcohols and the hydrogenation of alkenes
under Brønsted acid catalysis has been developed. The method is based on the
use of a benzyl or an isopropyl ether as a traceless hydrogen atom donor and
involves an intramolecular hydride transfer as a key step that can be achieved in
regio- and stereoselective manners.
This article is protected by copyright. All rights reserved.