Rhodium-Catalyzed Enantioselective Isomerization of meso-Oxabenzonorbornadienes to 1,2-Naphthalene Oxides

Article abstract of DOI:10.1002/anie.201700632

Herein we describe a rhodium-catalyzed enantioselective isomerization of meso-oxabicyclic alkenes to 1,2-naphthalene oxides. These potentially useful building blocks can be accessed in moderate to excellent yields with impressive enantioselectivities. Additionally, experimental findings supported by preliminary computations suggest that ring-opening reactions of bridgehead disubstituted oxabicyclic alkenes proceed through the intermediacy of these epoxides and may point to a kinetically and thermodynamically favored reductive elimination as the origin for the observed enantioselectivities.

Full text of DOI:10.1002/anie.201700632

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201700632
German Edition: DOI: 10.1002/ange.201700632
Asymmetric Catalysis
Rhodium-Catalyzed Enantioselective Isomerization of
meso-Oxabenzonorbornadienes to 1,2-Naphthalene Oxides
Andy Yen, Ken-Loon Choo, Shabnam K. Yazdi, Patrick T. Franke, Robert Webster,
Ivan Franzoni, Charles C. J. Loh, Amalia I. Poblador-Bahamonde, and Mark Lautens*
Abstract: Herein we describe a rhodium-catalyzed enantio-
selective isomerization of meso-oxabicyclic alkenes to 1,2-
naphthalene oxides. These potentially useful building blocks
can be accessed in moderate to excellent yields with impressive
enantioselectivities. Additionally, experimental findings sup-
ported by preliminary computations suggest that ring-opening
reactions of bridgehead disubstituted oxabicyclic alkenes
proceed through the intermediacy of these epoxides and may
point to a kinetically and thermodynamically favored reductive
elimination as the origin for the observed enantioselectivities.
T
he rhodium-catalyzed asymmetric ring-opening (ARO)
reaction of oxabicyclic alkenes offers a facile entry into
chiral hydronaphthalene frameworks that are ubiquitous
motifs found in a wide variety of biologically active natural
products [Scheme 1, Eq. (1)]. For this reason, the develop-
ment of the ARO reaction represents an area of increasing
interest by various research groups, with many new method-
ologies emerging over the past two decades since we first
[
1,2]
disclosed this transformation.
Over the course of our investigation into the intra-
molecular variant of the ARO reaction [Scheme 1, Eq. (2)],
[3]
Scheme 1. Development of the rhodium-catalyzed enantioselective iso-
merization of meso-oxabicycles.
we discovered a facile method for the conversion of meso-
bridgehead disubstituted oxabicycles into highly enantioen-
riched 1,2-naphthalene oxides. Specifically, when substrate 1,
bearing benzyl side chains [R = p-bromobenzyl, Scheme 1,
Eq. (4)] was subjected to the intramolecular ARO reaction
product was not observed; rather, compound 2 was found to
be the sole isolated product. The 1,2-naphthalene oxide
[4]
conditions using a [Rh(cod) OTf]/(R)-(S)-PPF-PtBu2 com-
structure of 2 was later confirmed by X-ray crystallography.
2
plex, the expected Friedel–Crafts type cycloisomerization
The ee was also found to be exceptional for the newly
characterized 1,2-naphthalene oxide product. Notably, the
observed transformation was not well precedented in the
literature, with the only relevant example reported by Tam in
[
*] A. Yen, K.-L. Choo, S. K. Yazdi, Dr. I. Franzoni, Prof. Dr. M. Lautens
Department of Chemistry, Davenport Chemical Laboratories
University of Toronto
2
006 using an achiral ruthenium Cp* catalyst [Scheme 1,
[
5]
Eq. (3)].
80 St. George Street, Toronto, Ontario M5S 3H6 (Canada)
E-mail: mlautens@chem.utoronto.ca
The development of catalytic asymmetric monoepoxida-
tion methodologies has contributed greatly to the field of
modern asymmetric synthesis owing to the fact that chiral
Dr. P. T. Franke
Carbogen Amcis AG
Hauptstraße 171, 4416 Bubendorf (Switzerland)
[6]
epoxides are important and versatile building blocks. The
most successful and well known examples of this class of
reactions include the Sharpless asymmetric epoxidation
Dr. R. Webster
Bayer Pharma Aktiengesellschaft
Aprather Web 18a, 42113 Wuppertal (Germany)
[7]
[8]
(
SAE) and the Jacobsen–Katsuki epoxidation. The pres-
Dr. C. C. J. Loh
Technische Universitꢀt Dortmund
Otto-Hahn-Straße 4a, 44227 Dortmund (Germany)
ent reaction does not require an external oxidant and features
complete atom economy by virtue of being a desymmetrizing
[9]
isomerization reaction. Furthermore, the use of the readily
available meso-oxabicyclic alkenes represents a complemen-
tary approach towards accessing vinyl epoxides by expanding
Dr. A. I. Poblador-Bahamonde
Department of Organic Chemistry, University of Geneva
30 Quai Ernest Ansermet, 1211 Geneva (Switzerland)
[10]
the scope of substrates available to the synthetic chemist.
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.201700632.
The possibility of accessing the versatile vinyl epoxide
moiety in highly enantioselective fashion under mild reaction
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

Angewandte
Communications
Chemie
conditions prompted us to examine the structural require-
ments to achieve this isomerization. Our initial hypothesis
was that epoxide formation from the oxabicyclic alkene
occurred in the absence of nucleophiles under the reaction
conditions. This process was thought to proceed through
oxidative addition of the rhodium catalyst into a bridgehead
CÀO bond, followed by formation of a rhodium p-oxoallyl
species, terminating with a reductive elimination to the
[
11]
observed epoxide.
The diacetylated model substrate 1a
was chosen to test this hypothesis.
On subjecting model substrate 1a to the reaction con-
ditions, it was found to undergo smooth and complete
transformation to the desired 1,2-naphthalene oxide in good
yield and excellent ee (Table 1, entry 1). Further studies to
Table 1: Screening of reaction conditions for the rhodium-catalyzed
enantioselective isomerization.
Entry [Rh]/PPF-PtBu
Solvent
[0.05m]
t
Yield
[%]
ee
[%]
2
[
a]
[c]
[c]
[d]
[e]
[
mol%]
[min]
[
b]
1
2
3
4
5
6
[Rh(cod) ]OTf [5/6]
THF
1,4-dioxane 30
THF
30
90 [88] 96
92 [98] 97
2
[Rh(cod) ]OTf [5/6]
2
[Rh(cod)Cl] [2.5/6]
30
30
30
30
n.r.
n.r.
<1
43
n.d.
n.d.
n.d.
n.d.
2
[Rh(cod)OH] [2.5/6] THF
2
[Rh(cod) ]OTf [2/3]
THF
THF
2
[Rh(cod) ]OTf [3/4]
2
[
a] (S)-(R)-PPF-PtBu was used for reaction optimization unless other-
2
wise stated. [b] (R)-(S)-PPF-PtBu was used. [c] Reactions conducted on
2
0
.2 mmol scale in 4 mL of solvent (0.05 m). [d] Yields determined by
1
H NMR spectroscopic analysis of the crude reaction mixture using
1
,3,5-trimethoxybenzene as the internal standard. Isolated yields are
reported in square brackets. [e] ee values are determined by HPLC
analysis on a chiral stationary phase. n.r. =no reaction. n.d.=not
determined.
Scheme 2. Substrate scope of the rhodium-catalyzed enantioselective
isomerization of bridgehead disubstituted meso-oxabicycles using [Rh-
(
cod) ]OTf/(R)-(S)-PPF-PtBu . [a] Reactions conducted using substrates
2
2
1
a–1j on 0.2 mmol scale in 4 mL of 1,4-dioxane (0.05m). [b] Isolated
delineate this newfound reaction were undertaken and it was
yields of 2a–2j are reported. ee values are determined by HPLC
analysis on a chiral stationary phase. [c] The epoxide of S5 can be
observed by H NMR spectroscopy.
found that the [Rh(cod) ]OTf/(R)-(S)-PPF-PtBu catalyst
2
2
1
system was necessary for the desired transformation
Table 1, entries 3 and 4). Additional solvent screening
(
experiments revealed that the reaction tolerates the use of
various other solvents, with 1,4-dioxane providing the desired
epoxide 2a in similar yield and ee to the initial case with THF
a variety of functional groups were synthesized and subjected
to our standard conditions (Scheme 2).
(
see Supporting Information). Lastly, decreasing the catalyst
The scope proved to be expansive, with various function-
alities being well tolerated, and the desired enantioenriched
1,2-naphthalene oxides were furnished in moderate to
excellent yields with consistently exceptional ee values
(Scheme 2). In addition to the model diacetate 2a, benzoate
diesters were also competent substrates for this transforma-
tion (2c–2 f, and 2h). Heteroaromatic diesters 2g and 2i also
underwent the desired transformation. Lastly, carbonate (2b)
and carbamate (2j) examples show that the reaction proceeds
irrespective of the electronic or steric character of the
hydroxy protecting groups.
and ligand loading led to diminished or no conversion
(
Table 1, entries 5 and 6).
With the optimized conditions in hand, we set out to
investigate the scope of this reaction. From previous work
reported by our group, it was known that the parent
oxabicyclic alkene without bridgehead substitution decom-
poses under the reaction conditions in the presence of the
cationic rhodium catalyst, making bridgehead substitution an
[
3a]
apparent structural requirement for this transformation. To
this end, bridgehead disubstituted meso-oxabicycles bearing
2
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!

Angewandte
Communications
Chemie
For the simplest case, it was observed that the bridgehead
dimethylated substrate S5 forms the desired epoxide as
1
determined by H NMR spectroscopic analysis of the crude
reaction mixture. However, attempts to isolate this epoxide
were complicated by extensive decomposition to the naphthol
[
12]
in the presence of silica gel. The stability issue encountered
here and for later examples prompted the use of neutralized
[13]
chromatographic media (see Supporting Information). It
was eventually established that the stability of the epoxide
products, at least with respect to purification over neutralized
silica, coincided with the presence of the carbonyl function-
alities in the bridgehead tethered side chains. In general,
carbonyl-bearing epoxides were markedly more stable than
the corresponding benzyl ether-bearing epoxides, with at least
the model substrate 2a having been successfully purified over
untreated silica gel versus significant decomposition encoun-
tered for the various benzyl ether substrates 2k–2q
Scheme 4. Gram-scale synthesis of epoxide 2a. Isolated yield reported.
ee value determined by HPLC analysis on a chiral stationary phase.
The question of whether the oxygen atoms in the side
chains contributed to product stability was assessed by
subjecting diacetylated substrate 1r, bearing a longer carbon
tether, to the reaction conditions. Similar to substrate S5, it
was found that while the desired epoxide does form, it did not
lend itself to facile purification over neutralized silica. To our
dismay, successive chromatography led to an increasing
naphthol-to-epoxide ratio. We speculated that a ring-opening
reaction of substrate S5 and 1r under methanolysis conditions
previously reported by our group would furnish the more
(
Scheme 3). Again, a general insensitivity to the electronic
properties of the tethered side chains was observed, and the
reaction proceeds regardless of the nature of substitution on
the aromatic side chains.
This methodology is also amenable to scale-up, as
demonstrated by a gram-scale reaction of 1a that afforded
[
3a]
stable methanol adducts 3b and 3c, respectively, allowing
us to both indirectly establish the presence of these sensitive
molecules as well as evaluate the efficiency of the initial
epoxide forming step. On re-subjecting substrates S5 and 1r
to the reaction conditions with the indicated equivalents of
methanol, we were delighted to find that the desired products
2
a in comparable yields and with no apparent decrease in ee
(
Scheme 4).
3
b and 3c, respectively could be isolated in moderate to good
yields (unoptimized) and excellent ee values, in agreement
[14]
with our previous reports [Scheme 5, Eq. (1) and Eq. (2)].
In an effort to address whether or not ARO reactions of
oxabicycles proceed via the intermediacy of an epoxide,
methanolysis experiments of oxabicycle 1a and epoxide 2a
were carried out. The results (Scheme 6) show that meth-
anolysis proceeds smoothly to afford highly enantioenriched
Scheme 5. Enantioselective methanolysis of meso-bridgehead disubsti-
tuted oxabicyclic alkenes S5 and 1r. Reactions conducted using
substrates S5 and 1r on 0.2 mmol scale in 4 mL of 1,4-dioxane
(0.05m) with 50 equivalents of MeOH. [a] Relative stereochemistry of
OMe and OH established by 1D NOESY experiments to be trans.
Absolute configurations assigned based on X-ray crystal structure of
2a. [b] Isolated yields of 3b and 3c are reported. ee values are
determined by HPLC analysis on a chiral stationary phase.
Scheme 3. Substrate scope with respect to benzyl ether side chains. [a]
Reactions conducted using substrates 1k–1q on 0.2 mmol scale in
4
mL of 1,4-dioxane (0.05m). [b] Isolated yields of 2k–2q are reported.
ee values are determined by HPLC analysis on a chiral stationary
phase. [c] Examples 2p and 2q were synthesized using 7/9 mol% of
[
Rh(cod) ]OTf/(R)-(S)-PPF-PtBu respectively.
2
2
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
PtBu complex forms an orthogonal pair with its correspond-
2
ing epoxide product bearing an absolute (1S, 2S) configu-
ration. The mismatched catalyst complex and substrate pair
may preclude the oxidative addition event leading to 3a,
which suggests a scenario where the epoxide exists in a rapid
equilibrium with its corresponding oxidative addition com-
plex that arises from oxidative insertion of the matching
rhodium catalyst complex into the epoxide CÀO bond.
Subsequent trapping by methanol furnishes the final product
(Scheme 7).
Scheme 6. Epoxides as intermediates in ARO. Reactions conducted
using substrates 1a (0.2 mmol) and 2a (0.14 mmol) in 4 mL of MeOH
(
1
0.05m). [a] Relative stereochemistry of OMe and OH established by
D NOESY experiments to be trans. Absolute configurations assigned
based on X-ray crystal structure of 2a. [b] Isolated yields of ent-3a and
a are reported. ee values determined by HPLC analysis on a chiral
3
stationary phase.
product ent-3a from oxabicycle 1a in good yields [Scheme 6,
Eq. (1)]. The same conditions were then employed for
epoxide 2a, which delivered the ring-opened product 3a in
comparable fashion, demonstrating that the intermediacy of
the epoxide is one feasible pathway for ARO reactions of
bridgehead disubstituted oxabicycles [Scheme 6, Eq. (2)].
Further experiments to elucidate the role of rhodium in
this ring-opening reaction were conducted. Predictably, the
absence of rhodium or methanol led to no ring-opened
product 3a, indicating that the catalyst is a necessary element
Scheme 7. Methanolysis of 1a and 2a. A matched catalyst complex–
substrate pair is required for conversion of 2a to 3a.
To further refine our mechanistic rationale for this
reaction, preliminary DFT studies were also undertaken.
For the dimethylated substrate S5 (Scheme 8a), it was found
that the corresponding epoxide is significantly energetically
À1
(
Table 2, entries 1 and 2). Interestingly, by subjecting epoxide
a (previously synthesized using the (R)-(S) enantiomer of
more favorable (DE = À15.8 kcalmol ). This result suggests
2
the PPF-PtBu ligand) to otherwise identical methanolysis
2
conditions that employ the enantiomeric (S)-(R)-PPF-PtBu2
catalyst complex leads only to decomposition and recovery of
the starting epoxide 2a (Table 2, entry 3).
The absence of ring-opening product in the ligand switch
experiment (Table 2, entry 3) suggests that the (R)-(S)-PPF-
Table 2: Participation of the rhodium catalyst in methanolysis.
Entry
t
[Rh]
catalyst
PPF-
PtBu2
Solvent
[0.05m]
Result
[% recovery]
[
a]
[a]
[b]
[
min]
1
2
3
90
60
60
No
Yes
Yes
No
(R)-(S)
(S)-(R)
MeOH
1,4-dioxane
MeOH
n.r.
[
c]
80
26
[
d]
À1
Scheme 8. Computational studies. Energies (kcalmol ) refers to zero-
[
a] If included, 5/6 mol% of [Rh(cod) ]OTf/PPF-tBu respectively was
point corrected energies calculated at the IEFPCM (1,4-dioxane)
M06L/6-31G(d,p)/SDDALL level of theory. Gibbs free energies are
presented in parenthesis. a) Relative energy difference between sub-
strate S5 and the corresponding epoxides. b) Potential energy profile
for the rhodium-catalyzed enantioselective isomerization of S5.
2
2
used. [b] Reactions conducted using substrate 2a on 0.1 mmol scale.
[
of the crude reaction mixture using 1,3,5-trimethoxybenzene as the
internal standard. For full details, see Supporting Information.
1
c] Isolated yield. [d] Yield determined by H NMR spectroscopic analysis
4
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!

Angewandte
Communications
Chemie
that the ring strain in the epoxide is less destabilizing than in
the starting oxabicyclic alkene. Analysis of the potential
energy profile for the isomerization reaction using (R)-(S)-
PPF-PtBu2 as the ligand (Scheme 8b) indicates that both
diastereomeric oxidative addition complexes II’ and II’’ are
6064; d) C. C. J. Loh, X. Fang, B. Peters, M. Lautens, Chem. Eur.
J. 2015, 21, 13883 – 13887; e) C. C. J. Loh, M. Schmid, B. Peters,
X. Fang, M. Lautens, Angew. Chem. Int. Ed. 2016, 55, 4600 –
4
604; Angew. Chem. 2016, 128, 4676 – 4680.
3] a) R. Webster, C. Bçing, M. Lautens, J. Am. Chem. Soc. 2009,
31, 444 – 445; b) C. C. J. Loh, M. Schmid, R. Webster, A. Yen,
[
1
°
À1
formed at the same rate (DDE = 0.7 kcalmol ) and that
S. K. Yazdi, P. T. Franke, M. Lautens, Angew. Chem. Int. Ed.
2016, 55, 10074 – 10078; Angew. Chem. 2016, 128, 10228 – 10232.
À1
they are in equilibrium (DE = 1.2 kcalmol ). The subsequent
°
reductive elimination step for II’ is both kinetically (DDE =
[4] CCDC 1527906 (2a), 1527907 (ent-2a), and 1527908 (2l) contain
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
5] For the first report of a ruthenium-catalyzed isomerization of
oxabenzonorbornadienes to 1,2-naphthalene oxides, see: a) K.
Villeneuve, W. Tam, J. Am. Chem. Soc. 2006, 128, 3514 – 3515;
for studies towards the development of an asymmetric variant,
see: b) A. Allen, P. Le Marquand, R. Burton, K. Villeneuve, W.
Tam, J. Org. Chem. 2007, 72, 7849 – 7857; for a similar epoxide
isolated from the attempted asymmetric cyclodimerization of
oxanorbornadienes, see: c) T. Nishimura, T. Kawamoto, K.
Sasaki, E. Tsurumaki, T. Hayashi, J. Am. Chem. Soc. 2007,
À1
°
À2.9 kcalmol ) and thermodynamically (DDE = À2.8 kcal
À1
mol ) favored over II’’ leading to complex III’ where the
stereochemistry of the epoxide moiety matches with the
absolute configuration determined experimentally when the
[
(
R)-(S)-PPF-PtBu ligand is used. This may mark the rare
2
instance of a reductive elimination as the enantiodetermining
[15]
step.
In summary, we have demonstrated the first rhodium-
catalyzed enantioselective isomerization of meso-oxabenzo-
norbornadienes to 1,2-naphthalene oxides. This methodology
delivers potentially useful building blocks in moderate to
excellent yields with consistently impressive enantioselectiv-
ities. Efforts to access enantioenriched products from the
stereospecific ring-opening reactions of this class of com-
pounds are underway in our laboratories.
129, 1492 – 1493.
[6] For reviews on catalytic asymmetric epoxidation, see: a) Q. H.
Xia, H. Q. Ge, C. P. Ye, Z. M. Liu, K. X. Su, Chem. Rev. 2005,
105, 1603 – 1662; b) H. Adolfsson, D. Balan in Aziridines and
Epoxides in Organic Synthesis (Ed.: A. K. Yudin), Wiley-VCH,
Weinheim, 2006, pp. 185 – 228.
[
[
7] T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974 –
5976.
Acknowledgements
8] a) W. Zhang, J. L. Loebach, S. R. Wilson, E. N. Jacobsen, J. Am.
Chem. Soc. 1990, 112, 2801 – 2803; b) E. N. Jacobsen, W. Zhang,
A. R. Muci, J. R. Ecker, L. Deng, J. Am. Chem. Soc. 1991, 113,
We thank Solvias AG, Umicore, and Johnson Matthey for the
generous donation of ligands and rhodium catalysts. Dr. Alan
Lough (University of Toronto) is gratefully acknowledged for
single-crystal X-ray analysis. I.F. thanks the Collaborative
Research and Training Experience (CREATE) program for
a postdoctoral fellowship. C.C.J.L. thanks the Deutsche
Forschungsgemeinschaft (DFG) for a postdoctoral fellowship
7063 – 7064; c) R. Irie, K. Noda, Y. Ito, T. Katsuki, Tetrahedron
Lett. 1991, 32, 1055 – 1058; for a review, see: d) E. M. McGar-
rigle, D. G. Gilheany, Chem. Rev. 2005, 105, 1563 – 1602.
9] For selected examples of rhodium-catalyzed isomerizations, see:
a) K. Hiroya, Y. Kurihara, K. Ogasawara, Angew. Chem. Int. Ed.
Engl. 1995, 34, 2287 – 2289; Angew. Chem. 1995, 107, 2445 –
2448; b) K. Tanaka, S. Qiao, M. Tobisu, M. M. Lo, G. C. Fu, J.
Am. Chem. Soc. 2000, 122, 10270 – 10271.
[
(
LO 2065/1-1). We also thank Carmine Chiancone (Univer-
[
10] For reviews on vinyl epoxides in organic synthesis, see: a) B.
Olofsson, P. Somfai in Aziridines and Epoxides in Organic
Synthesis (Ed.: A. K. Yudin), Wiley-VCH, Weinheim, 2006,
pp. 315 – 347; b) J. He, J. Ling, P. Chiu, Chem. Rev. 2014, 114,
sity of Geneva) for technical support.
Conflict of interest
8037 – 8128.
[
11] a) M. Lautens, K. Fagnou, Proc. Natl. Acad. Sci. USA 2004, 101,
5455 – 5460; b) K. Fagnou in Modern Rhodium-Catalyzed
Organic Reactions (Ed.: P. A. Evans), Wiley-VCH, Weinheim,
The authors declare no conflict of interest.
2
005, pp. 173 – 190.
Keywords: allylic compounds · asymmetric catalysis ·
enantioselectivity · isomerization · rhodium
[
12] For studies on the aromatization of arene oxides, see: a) G. J.
Kasperek, T. C. Bruice, J. Am. Chem. Soc. 1972, 94, 198 – 202;
b) S. N. Rao, R. A. More OꢀFerrall, S. C. Kelly, D. R. Boyd, R.
Agarwal, J. Am. Chem. Soc. 1993, 115, 5458 – 5465.
[
[
[
13] For the preparation of the neutralized silica gel used in this study,
see: V. Nagy, A. Agꢁcs, E. Turcsi, J. Deli, Phytochem. Anal. 2009,
[
1] For seminal reports of the rhodium-catalyzed ARO reaction,
20, 143 – 148.
see: a) M. Lautens, K. Fagnou, T. Rovis, J. Am. Chem. Soc. 2000,
14] For a recent DFT study on the original ARO reaction, see: Z.-H.
122, 5650 – 5651; b) K. Fagnou, M. Taylor, M. Lautens, Org. Lett.
Qi, Y. Zhang, Y. Gao, Y. Zhang, X.-W. Wang, Y. Wang, Sci. Rep.
2000, 2, 1677 – 1679; c) M. Lautens, K. Fagnou, M. Taylor, T.
2017, 7, 40491.
Rovis, J. Organomet. Chem. 2001, 624, 259 – 270; d) M. Lautens,
K. Fagnou, J. Am. Chem. Soc. 2001, 123, 7170 – 7171; e) M.
Lautens, K. Fagnou, D. Yang, J. Am. Chem. Soc. 2003, 125,
15] An enantiodetermining reductive elimination has been pro-
posed for the asymmetric palladium-catalyzed carboamination
of alkenes: B. A. Hopkins, J. P. Wolfe, Angew. Chem. Int. Ed.
14884 – 14892.
2012, 51, 9886 – 9890; Angew. Chem. 2012, 124, 10024 – 10028.
[
2] For selected examples of the rhodium-catalyzed ARO reaction,
see: a) M. Lautens, K. Fagnou, S. Hiebert, Acc. Chem. Res. 2003,
36, 48 – 58; b) P. Leong, M. Lautens, J. Org. Chem. 2004, 69,
2194 – 2196; c) L. Zhang, C. M. Le, M. Lautens, Angew. Chem.
Manuscript received: January 18, 2017
Int. Ed. 2014, 53, 5951 – 5954; Angew. Chem. 2014, 126, 6061 –
Final Article published: && &&, &&&&
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Asymmetric Catalysis
A. Yen, K.-L. Choo, S. K. Yazdi,
P. T. Franke, R. Webster, I. Franzoni,
C. C. J. Loh, A. I. Poblador-Bahamonde,
M. Lautens*
&&&& — &&&&
Rhodium-Catalyzed Enantioselective
Isomerization of meso-
Oxabenzonorbornadienes to 1,2-
Naphthalene Oxides
An enantioselective isomerization of
bridgehead-disubstituted meso-oxabicy-
clic alkenes catalyzed by a cationic [Rh-
(cod) ]OTf/(R)-(S)-PPF-PtBu catalyst
potentially useful building blocks in
asymmetric synthesis. The involvement
of these epoxides as intermediates in
asymmetric ring opening reactions of
oxabicyclic alkenes is also explored.
2
2
system is described. The enantioenriched
,2-naphthalene oxide products are
1
6
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!