Asymmetric hydroxylative phenol dearomatization promoted by chiral binaphthylic and biphenylic iodanes

Article abstract of DOI:10.1002/anie.201403571

The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues. Although remarkable progress has recently been made in organoiodine-catalyzed reactions using a terminal oxidant in stoichiometric amounts, there is still a significant need for "flaskable" chiral iodane reagents. Herein, we describe the synthesis of new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO-mediated oxidation into either λ³- or λ⁵-iodanes, and the evaluation of their capacity to promote asymmetric hydroxylative phenol dearomatization (HPD) reactions. Most notably, a C₂-symmetrical biphenylic λ⁵-iodane promoted the HPD-induced conversion of the monoterpene thymol into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol)) with enantiomeric excesses of up to 94 %.

Full text of DOI:10.1002/anie.201403571

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Angewandte
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DOI: 10.1002/anie.201403571
Asymmetric Synthesis
Asymmetric Hydroxylative Phenol Dearomatization Promoted by
Chiral Binaphthylic and Biphenylic Iodanes**
Cyril Bosset, Romain Coffinier, Philippe A. Peixoto, Mourad El Assal, Karinne Miqueu, Jean-
Marc Sotiropoulos, Laurent Pouysꢀgu,* and Stꢀphane Quideau*
Abstract: The long-standing quest for chiral hypervalent
organoiodine compounds (i.e., iodanes) as metal-free reagents
for asymmetric synthesis continues. Although remarkable
progress has recently been made in organoiodine-catalyzed
reactions using a terminal oxidant in stoichiometric amounts,
there is still a significant need for “flaskable” chiral iodane
reagents. Herein, we describe the synthesis of new iodobi-
naphthyls and iodobiphenyls, their successful and selective
DMDO-mediated oxidation into either l3- or l5-iodanes, and
the evaluation of their capacity to promote asymmetric
hydroxylative phenol dearomatization (HPD) reactions.
Most notably, a C2-symmetrical biphenylic l5-iodane promoted
the HPD-induced conversion of the monoterpene thymol into
the corresponding ortho-quinol-based [4+2] cyclodimer (i.e.,
bis(thymol)) with enantiomeric excesses of up to 94%.
in intramolecular asymmetric oxygenative reactions, such as
phenol dearomatizing spirolactonization[3b,c] and alkene oxy-
lactonization[3d] with enantiomeric excesses (ee) above 90%,
the quest for novel chiral iodanes continues.
Our own contribution to this area of research led to the
identification of iodobinaphthyl A as a promising scaffold for
more challenging intermolecular asymmetric oxygenative
reactions, such as the hydroxylative phenol dearomatization
(HPD reaction), which we could accomplish with up to
50% ee through the in situ generation of the chiral iodane
using meta-chloroperbenzoic acid (m-CPBA) as the oxidant
(Scheme 1).[4] We were however unsatisfied with the difficul-
T
he chemistry of hypervalent organoiodine compounds, also
referred to as iodanes, has unarguably experienced an
impressive development since the early 1990s, as evidenced
by both the diversity of iodane reagents that are available
today and the number of chemical transformations that these
reagents can promote.[1,2] The initial incitement to the
development of l3- and l5-iodanes (i.e., IIII- and IV-based
compounds), which was mainly due to their useful oxidizing
properties and capacity to replace toxic heavy-metal-based
reagents in dehydrogenating and oxygenative reactions, has
paved the way to the exploitation of iodanes in various metal-
free reactions.[1,2] Major current and competing research
efforts focus on the design of chiral iodane structures for
asymmetric synthesis and organoiodine-catalyzed versions
thereof.[3] While remarkable progress has notably been made
Scheme 1. Asymmetric hydroxylative phenol dearomatization (HPD
reaction) using chiral biarylic iodanes generated in situ[4a] or ex situ
(this work).
[*] C. Bosset,[+] R. Coffinier,[+] Dr. P. A. Peixoto, M. El Assal,
Dr. L. Pouysꢀgu, Prof. S. Quideau
ties we encountered in the attempt to cleanly oxidize A
ex situ, because this prevented us from isolating and charac-
terizing the reacting iodane species. Mass spectrometric
analysis of the reaction medium indicated the possible
implication of a l5-iodane species, but an asymmetric
oxygen-transfer from a corresponding l3-iodane species
could not be entirely disregarded on the sole basis of this
analysis.[4a] Moreover, the efficient epoxidation of the primary
ortho-quinol product that was observed when using m-CPBA
in excess cast some doubts on its abilities to be used as
a general and chemoselective terminal oxidant in organo-
iodine-catalyzed variants of such reactions with oxygenation-
sensitive substrates (Scheme 1).[4a,c] We thus decided to
generate several chiral iodobiaryls to find a convenient
solution for their ex situ oxidation into iodanes and to
Univ. Bordeaux, ISM (CNRS-UMR 5255) and IECB
2 rue Robert Escarpit, 33607 Pessac Cedex (France)
E-mail: l.pouysegu@iecb.u-bordeaux.fr
s.quideau@iecb.u-bordeaux.fr
Dr. K. Miqueu, Dr. J.-M. Sotiropoulos
Univ. Pau et Pays de l’Adour, IPREM (CNRS-UMR 5254)
Hꢀlioparc, 2 avenue Pierre Angot, 64053 Pau Cedex 09 (France)
[+] These authors contributed equally to this work.
[**] Financial support from the Agence Nationale de la Recherche (ANR-
10-BLAN-0721), the CNRS, the Conseil Rꢀgional d’Aquitaine, and
the French Ministry of Research, including doctoral assistantships
for C.B., R.C., and M.E.A., is gratefully acknowledged. The authors
also wish to thank Dr. J. Brioche for his contribution to the
elaboration of this research project.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201403571.
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evalutate the performance of these “flaskable” iodanes in
asymmetric HPD reactions.
racemization during the subsequent chemical steps was
controlled by HPLC analysis on a chiral stationary phase
(see the Supporting Information). The C2-symmetrical diio-
dobinaphthyls 2a/b were similarly prepared, and partial
hydrogenation of the binaphthyl core gave access to the
diiodobiphenyl analogues 3a/b (Scheme 2, see the Supporting
Information). Atropisomeric resolution of compounds 2 and 3
was achieved using (S)-mandelic acid as chiral auxiliary. The
absolute configuration of (R)-2a and (R)-3a was confirmed
by X-ray analysis (CCDC-989095 and CCDC-989096).[7]
The benzyloxy iodobinaphthyl methyl ester 1b was then
chosen to identify an appropriate oxygenating reagent and
was thus subjected to all the oxidizing conditions previously
screened (see above). Only freshly prepared DMDO cleanly
oxidized 1b. The use of three equivalents of DMDO in
acetone at room temperature for 6 hours was necessary to
reach complete conversion of 1b into the iodosyl derivative
4b, which was isolated as a white powder in 94% yield
(Scheme 2). 13C NMR analysis was used to confirm the
oxidation state of its iodine center on the basis of the
chemical shift of the aromatic ipso carbon atom (Cipso-IIII) at
114.9 ppm (see the Supporting Information).[6] Again, no l5-
iodane was detected, even when a longer reaction time (up to
24 hours) or additional equivalents of DMDO were used. This
surprisingly selective DMDO-mediated oxygenation was next
applied to the other alkoxy iodobinaphthyls 1a,c–g, and again
full conversion into the corresponding iodosyl derivatives
4a,c–g was achieved in very good to excellent yields
(Scheme 2). The iodosyl carboxylic acids 4e–g were charac-
terized by NMR analyses as isomeric mixtures, which were
probably due to the co-existence in solution of their open and
benziodoxole cyclic forms (see the Supporting Information).
The C2-symmetrical diiodobinaphthyls 2a/b were similarly
oxidized upon treatment with six equivalents of DMDO to
afford the corresponding bis(l3-iodanes) 5a/b in good yields.
The diiodobiphenyl analogues 3a/b behaved differently under
these conditions. In contrast to the binaphthyl ester variants
1a–d and 2a, the bis(ester) 3a was cleanly converted into the
bis(l5-iodane) 6a, whereas the oxidation of bis(carboxylic
acid) 3b stopped at the bis(l3-iodane) stage 6b, as it is usually
observed with 2-iodobenzoic/3-iodonaphthoic acids under
these DMDO-mediated oxidation conditions (Scheme 2, see
the Supporting Information).
This investigation commenced with the oxidation of 3-
iodo-2-naphthoic acid, a simple iodonaphthyl species chosen
as a model compound to identify suitable conditions for its
conversion into its corresponding l3- or l5-iodane (see the
Supporting Information). The screening of oxidizing systems
that were selected among those classically used in hypervalent
iodine chemistry[1,5] showed that effective oxygenation could
be achieved with either oxone in water/acetonitrile (1:1), m-
CPBA in dichloromethane, or 3,3-dimethyldioxirane
(DMDO) in acetone. In all three cases, the single iodane
that precipitated from the reaction mixture was identified as
an iodosyl derivative by 13C NMR analysis[6] and isolated in
83, 90, and 91% yields, respectively. X-ray analysis of the
translucent needles obtained by crystallization from DMSO
revealed the cyclic benziodoxole structure of this l3-iodane
(CCDC-953640, see the Supporting Information).[7] No iodyl
variant was detected in any of these oxidations, even when
using DMDO, which is usually used to generate such l5-
iodanes.
In light of these successful and selective oxidations of
a iodonaphthyl substrate into its corresponding l3-iodane, we
next decided to reconsider the ex situ oxidation of our
iodobinaphthyl A. We thus synthesized a series of structurally
related alkoxy iodobinaphthyls 1a–g (i.e., R2 = Me, Bn, trityl
(Tr), or supertrityl (sTr)) bearing either a methyl ester or
a carboxylic acid function in ortho position to the iodine
center (i.e., R1 = Me or H, Scheme 2; see also the Supporting
Information).[4a] Atropisomeric resolution was achieved by
semipreparative HPLC separation of their common racemic
binaphthylamine intermediate on a chiral stationary phase.
The absolute configuration of the (S)-atropisomer was con-
firmed by X-ray analysis (CCDC-989094).[7] The absence of
The capacity of these biarylic iodanes to deliver an oxygen
atom was next evaluated in the context of our benchmark
reaction, that is, the hydroxylative dearomatization of 2-
methylnaphthol (7).[4a] The most revealing experiments that
we conducted using the racemic alkoxybinaphthylic l3-
iodanes (Æ)-4a/b and 4e/f are summarized in Table 1. The
conversion of 7 into ortho-quinol 8, with the concomitant
formation of the undesired para-quinone 9 and dimer 10,[8]
was examined by 1H NMR analysis of the clean product
mixtures. Using one equivalent of the methoxybinaphthylic
iodane methyl ester (Æ)-4a in CH2Cl2, 7 was converted into
the ortho-quinol 8 and the para-quinone 9 in about 40% yield
each, together with only 10% of dimer 10 (Table 1, entry 1).
The lower solubility of 4b in CH2Cl2 led us to add 2,2,2-
trifluoroethanol (TFE), a fluorinated solvent commonly used
in iodane-mediated reactions.[9] A good compromise between
Scheme 2. Selective DMDO-mediated oxidation of alkoxy and C2-sym-
metrical iodobiaryls to their corresponding l3- or l5-iodanes. sTr =su-
pertrityl=C(4-tBu-C6H4)3, Tr=trityl=CPh3.
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Table 1: Preliminary evaluation of reaction conditions for hydroxylative
dearomatization of 2-methylnaphthol (7) mediated by binaphthylic l3-
iodane.
Table 2: Asymmetric hydroxylative dearomatization of 2-methylnaphthol
(7) mediated by biarylic l3- or l5-iodanes.[a]
Entry
Iodane [equiv]
T
t
Yield [%][b]
ee [%][c]
[8C]
[h]
9
8
1
2
3
4
5
6
7
8
9
(R)-4a [1.2]
(R)-4a [1.2]
(S)-4b [1.2]
(S)-4b [1.2]
(S)-4c [1.2]
(S)-4c [1.2]
(S)-4c [1.2]
(R)-4d [1.2]
(R)-6a [0.6]
(R)-6a [0.6]
RT
À40
RT
24
48
24
48
24
48
72
18
18
72
25
25
35
25
30
25
25
30
25
15
55
50
46
41
40
40
35
33
55
40
3 (6S)[d]
19 (6S)
15 (6R)
35 (6R)
36 (6R)
45 (6R)
53 (6R)
17 (6S)
50 (6S)
73 (6S)
Ent. Iodane [equiv] Conditions[a]
Conv.
[%][b]
Yield [%][b]
10
8
9
À40
1
2
3
(Æ)-4a [1.0]
(Æ)-4b [1.0]
(Æ)-4b [2.0]
CH2Cl2, 24 h
CH2Cl2/TFE (95:5), 24 h 88
CH2Cl2/TFE (95:5), 48 h 100
CH2Cl2, 24 h
CH2Cl2, 24 h
CH2Cl2/TFE (95:5), 48 h 41
91
40 41 10
40 20 28
51 49 n.d.
48 35 12
n.d. 30
n.d. n.d. 41
RT
À40
À80
RT
RT
À80
4[c] (Æ)-4b [1.2]
100
35
5
6
(Æ)-4e [1.0]
5
(Æ)-4 f [1.0]
10
[a] Reactions run at room temperature using [7]=70 mm in the indicated
solvent. [b] Determined by 1H NMR analysis. [c] [7]=25 mm. n.d.=not
detected, TFE=2,2,2-trifluoroethanol.
[a] Reactions run using [7]=25 mm in CH2Cl2. [b] Determined by
1H NMR analysis; for clarity, formation of 10 (ca. 5–10% at RTand up to
40% at À808C) is not shown. [c] Enantiomeric excesses determined by
HPLC analysis of pure ortho-quinol 8 using a chiral stationary phase.
[d] Absolute configuration at C6 of the major enantiomer.
the solubility of 4b, the extent of conversion of 7 into 8–10
(88–100%), and the yield of 8 (40–51%) was found using
a 95:5 mixture of CH2Cl2/TFE (Table 1, entries 2 and 3).
Moreover, dimer 10 was not detected when a two-fold excess
of 4b was used (entry 3). Higher dilutions in pure CH2Cl2
were also tested, and comparable performances were
obtained when the reaction was run using a 25 mm (instead
of 70 mm) solution of 7 in CH2Cl2 and 1.2 equivalent of 4b
(Table 1, entry 4). The use of the carboxylic acid analogues
(Æ)-4e/f, which in solution adopt at least in part a cyclic
benziodoxole structure (see above), was unsatisfactory, as less
than 10% of ortho-quinol 8 was detected when the reaction
was performed in CH2Cl2 (Table 1, entry 5), CH2Cl2/TFE
(95:5; entry 6), or in other solvents such as TFE, DMF, or
DMSO. In particular, the lack of reactivity of 4e is somewhat
surprising, as the in situ m-CPBA-mediated oxidation of its
iodobinaphthyl precursor A (herein 1e) afforded an iodane
species that converted 7 into 8 in good to high yields (up to
83%).[4a] These observations led us to use the methyl ester
series of our alkoxybiarylic iodanes in the following study of
the asymmetric version of this HPD reaction.
The atropisomerically pure versions of the biarylic iodane
methyl esters 4–6 were thus next evaluated for their capacity
to convert 7 into an enantioenriched ortho-quinol 8. All
reactions were run using a 25 mm solution of 7 in CH2Cl2 and
a slight excess of iodane (i.e., 1.2 equiv of the alkoxybi-
naphthyls 4, and 0.6 equiv of the C2-symmetrical biaryls 5 and
6). The most significant results are summarized in Table 2.
The oxygen transfer was effective in all cases, and led to the
formation of 8 in acceptable yields of up to 55% and the para-
quinone 9 as by-product in 15–30% yield. An increasing steric
demand of the alkoxy group (i.e., OMe, OBn, and OTr) of the
binaphthylic l3-iodanes 4a–c positively influenced their
induction of asymmetry, up to an encouraging ee value of
36% at room temperature (Table 2, entries 1, 3, and 5). This
influence showed its limitation with the supertrityloxybinaph-
thylic iodane (R)-4d, the use of which led to a lower yield of 8
with only 17% ee (Table 2, entry 8), probably because this
highly bulky alkoxy group blocks the approach of the
substrate toward the hypervalent iodine center. A decrease
of the temperature down to À408C expectedly increased the
ee value for 4a–c to 19, 35, and 45%, respectively (Table 2,
entries 2, 4, and 6). At À808C, (6R)-8 was obtained with
53% ee using the l3-iodane (S)-4c at the expense of the
reaction time and yield (Table 2, entry 7).
The C2-symmetrical binaphthylic bis(l3-iodane) (R)-5a
afforded 8 in only about 30% yield and with ee values of only
25–30%, even at À408C (see the Supporting Information).
We were however gratified by the performances of the C2-
symmetrical biphenylic bis(l5-iodane) (R)-6a, which fur-
nished (6S)-8 in acceptable yields (40–55%) with ee values
of 50% at room temperature, and 73% at À808C (Table 2,
entries 9 and 10). The modulation of the dihedral angle
around the chiral biaryl axis, probably resulting from the
partial reduction of the binaphthylic core, and the IV-type
geometry (and reactivity) of the hypervalent iodine centers of
6a are plausible key factors of its better ability to induce
asymmetry.
Overall, the results of these model reactions enabled us to
identify a new chiral l5-iodane reagent that is capable of
reaching asymmetric inductions comparable with the best
results previously reported for such a challenging iodane-
mediated intermolecular oxygenative dearomatizing reac-
tion.[4a,10a] The yields of the transformation of 2-methylnaph-
thol (7) into an enantioenriched ortho-quinol 8 are lower than
those we previously observed in the case of the in situ
generation of iodane species using m-CPBA,[4a] but this
oxidant alone, as well as DMDO, mediates the partial
conversion of 7 into (Æ)-8 (see the Supporting Informa-
tion).[4c] Chiral iodanes, such as ex situ generated 6a, should
thus find valuable applications in asymmetric HPD reactions
of 2-alkylarenols.
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A series of 2-alkylphenols 11 was thus selected as starting
materials to evaluate the scope of the asymmetric oxygen-
transfer aptitude of 6a. Such alkylphenols are commonly used
test substrates in HPD/[4+2] cyclodimerization cascade
reactions that aim at the construction of the bicyclo-
[2.2.2]octenone framework.[10] Although reactions run with
6a in CH2Cl2 at À808C did not give any product, even after
four days, complete consumption of 11 was achieved at
À408C for 72 h, affording the corresponding ortho-quinol 12,
which spontaneously started to dimerize. Heating the reaction
mixture at 408C for 15 minutes permitted the completion of
this dimerization in the expected regio- and stereoselective
homochiral fashion.[10d,f] Upon treatment with (R)-6a, the
symmetrical 2,6-dimethyl- and 2,4,6-trimethylphenols (11a/b)
furnished the corresponding cyclodimers 13a and 13b in fair
yields and ee values (Table 3, entries 1 and 2). The nonsym-
metrical 2,3-dimethyl- and 2,3,5-trimethylphenols gave com-
plex mixtures of products that resulted from the formation of
ortho-quinones and/or nondimerizing 5-methylated ortho-
quinol intermediates (not shown).[10d,f] However, the treat-
ment of 2,5-dimethylphenol (11c) furnished the expected
cyclodimer 13c, which was isolated in 68% yield with 84% ee
using (R)-6a, and again with 84% ee, but in a reversed ratio
using (S)-6a (Table 3, entries 3 and 4). In the same fashion,
the conversion of the natural 2-methyl-5-isopropylphenol
(carvacrol, 11d) with (R)-6a afforded bis(carvacrol) as the
sole product in 71% yield with 68% ee in favor of the natural
dimer (+)-13d.[11a,b] The treatment of 11d with (S)-6a
furnished (À)-13d in 68% yield with 74% ee (Table 3,
entries 5 and 6). An even better induction of asymmetry
was observed by subjecting the regioisomer 5-methyl-2-
isopropylphenol (thymol, 11e) to (R)-6a. The cyclodimer
bis(thymol) (+)-13e was indeed obtained in 75% yield with
92% ee. A five-fold scale-up of this reaction confirmed this
remarkable result with the production of (+)-13e in 77%
yield with 94% ee (Table 3, entries 7 and 8). The structure of
(+)-13e was established by X-ray analysis and by comparison
with data reported for racemic 13e[10d,e,11c] (see the Supporting
Information). In none of these three 2,5-dialkylphenol cases
(11c–e) were detected products that could have resulted from
the oxygenation at the unsubstituted ortho position or from
other modes of dimerization. This l5-iodane-induced asym-
metric synthesis of terpenoid bicyclo[2.2.2]octenones consti-
tutes an efficient metal-free alternative to the enantioselec-
tive HPD approach mediated by the copper-sparteine-dioxy-
gen complex.[10b]
In conclusion, we have prepared a series of rare chiral
biarylic iodanes[12] in high yields by a selective ex situ DMDO-
mediated oxidation of alkoxylated iodobinaphthylic and C2-
symmetrical diiodobinaphthylic and diiodobiphenylic com-
pounds into either iodosyl or iodyl reagents. Evaluation of
these l3- and l5-iodanes for their capacity to promote the
enantioselective oxygen transfer in phenol dearomatization
reactions led to the identification of a novel biphenylic C2-
symmetrical bis(l5-iodane) as a highly efficient metal-free
reagent for asymmetric intermolecular oxygenative phenol
dearomatization reactions. Further studies toward its appli-
cation to the synthesis of other ortho-quinol-based natural
products and to other oxygen-transfer reactions, as well as
mechanistic experiments, are currently in progress and will be
reported in due course.
Table 3: Enantioselective hydroxylative dearomatization of 2-alkylphe-
nols 11 mediated by biphenylic l5-iodane 6a.[a]
Received: March 21, 2014
Revised: May 23, 2014
Published online: July 22, 2014
Entry Phenol
Iodane Cyclodimer
(R)-6a
Yield ee
[%][b] [%][c]
Keywords: asymmetric synthesis · dearomatization ·
.
hypervalent compounds · iodanes · natural products
1
2
52
41
40
58
[1] For a selection of recent books and reviews on hypervalent
iodine chemistry, see: a) V. V. Zhdankin, Hypervalent Iodine
Chemistry—Preparation, Structure, and Synthetic Applications of
Polyvalent Iodine Compounds, Wiley, Chichester, 2013; b) M. S.
Yusubov, V. V. Zhdankin, Curr. Org. Synth. 2012, 9, 247; c) A.
Duschek, S. F. Kirsch, Angew. Chem. 2011, 123, 1562; Angew.
Chem. Int. Ed. 2011, 50, 1524; d) V. V. Zhdankin, J. Org. Chem.
2011, 76, 1185; e) A. Varvoglis, Tetrahedron 2010, 66, 5739;
f) E. A. Merritt, B. Olofsson, Angew. Chem. 2009, 121, 9214;
Angew. Chem. Int. Ed. 2009, 48, 9052; g) V. V. Zhdankin, P. J.
Stang, Chem. Rev. 2008, 108, 5299; h) R. M. Moriarty, J. Org.
Chem. 2005, 70, 2893; i) Hypervalent Iodine Chemistry—Modern
Developments in Organic Synthesis in Topics Curr. Chem.,
Vol. 224 (Ed.: T. Wirth), Springer, Berlin, 2003.
(R)-6a
3
4
(R)-6a
(S)-6a
68
47
84
84
5
6
(R)-6a
(S)-6a
71
68
68 (+)[d]
74 (À)
7
(R)-6a
(R)-6a
75
77
92 (+)
94 (+)
8[e]
[2] For recent reviews on the use of iodanes in synthesis, see: a) R.
Bernini, G. Fabrizi, L. Pouysꢀgu, D. Deffieux, S. Quideau, Curr.
Org. Synth. 2012, 9, 650; b) D. F. Gonzꢁlez, F. Benfatti, J. Waser,
ChemCatChem 2012, 4, 955; c) Y. Kita, T. Dohi, K. Morimoto, J.
Synth. Org. Chem. Jpn. 2011, 69, 1241; d) L. F. Silva, Jr., B.
Olofsson, Nat. Prod. Rep. 2011, 28, 1722; e) E. A. Merritt, B.
[a] Reactions run using [11]=30 mm in CH2Cl2. [b] Isolated yield.
[c] Enantiomeric excesses determined by HPLC analysis of pure cyclo-
dimer 13 using a chiral stationary phase. [d] Optical rotation of the major
enantiomer. [e] Five-fold scale up (5 days).
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Olofsson, Synthesis 2011, 517; f) L. Pouysꢀgu, D. Deffieux, S.
Quideau, Tetrahedron 2010, 66, 2235; g) M. Uyanik, K. Ishihara,
Chem. Commun. 2009, 2086; h) H. Tohma, Y. Kita, Adv. Synth.
Catal. 2004, 346, 111.
[7] CCDC 953640 (B), 983782 ((+)-13e), 983783 ((À)-13e), 989094
((S)-15), 989095 ((R)-2a), 989096 ((R)-3a), and 989315 ((S)-1c)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[8] The para-quinone 9 is probably derived from 8 through an allylic
shift, followed by the oxidation of the resulting para-quinol or
the rearomatized para-hydroquinone. Dimer 10 is also a con-
taminant of commercially available 7, which is highly sensitive to
this oxidative dimerization.
[3] For reviews, highlights and a selection of recent publications on
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