Organocatalytic Enantioselective Vinylogous Pinacol Rearrangement Enabled by Chiral Ion Pairing

Article abstract of DOI:10.1002/anie.201609911

An enantioselective pinacol rearrangement of functionalized (E)-2-butene-1,4-diols was developed. In the presence of a catalytic amount of a chiral BINOL-derived N-triflyl phosphoramide, these 1,4-diols rearranged to β,γ-unsaturated ketones in excellent yields and enantioselectivities. The formation of a chiral ion pair between the intermediary allylic cation and the chiral phosphoramide anion was postulated to be responsible for the highly efficient chirality transfer. These chiral building blocks were further converted into enantioenriched polysubstituted tetrahydrofuran and tetrahydronaphthalene derivatives.

Full text of DOI:10.1002/anie.201609911

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Communications
Chemie
International Edition: DOI: 10.1002/anie.201609911
German Edition: DOI: 10.1002/ange.201609911
Rearrangements
Hot Paper
Organocatalytic Enantioselective Vinylogous Pinacol Rearrangement
Enabled by Chiral Ion Pairing
Hua Wu, Qian Wang, and Jieping Zhu*
Abstract: An enantioselective pinacol rearrangement of func-
tionalized (E)-2-butene-1,4-diols was developed. In the pres-
ence of a catalytic amount of a chiral BINOL-derived N-triflyl
phosphoramide, these 1,4-diols rearranged to b,g-unsaturated
ketones in excellent yields and enantioselectivities. The for-
mation of a chiral ion pair between the intermediary allylic
cation and the chiral phosphoramide anion was postulated to
be responsible for the highly efficient chirality transfer. These
chiral building blocks were further converted into enantioen-
riched polysubstituted tetrahydrofuran and tetrahydronaph-
thalene derivatives.
P
inacol rearrangements, which convert 1,2-diols into
ketones under acidic conditions, are a blueprint for a group
of carbenium-based molecular reorganization processes.[1] As
such reactions generate a new stereogenic center, the ability
to control the stereochemical outcome would significantly
expand their synthetic utility. However, several factors
intrinsic to the reaction mechanism have made this endeavor
highly demanding. First, the regioselective generation of one
of the two possible carbenium intermediates under strongly
acidic conditions is difficult. Second, differentiation of the
prochiral faces of highly reactive planar carbocation inter-
mediates is a formidable challenge as it falls out of the reach
of typical Lewis acid and Brønsted acid catalysis. As a matter
of fact, Antillaꢀs chiral phosphoric acid (CPA) catalyzed
rearrangement of indolyl diols is the only example of an
enantioselective pinacol rearrangement to date (Sche-
me 1a).[2] In this transformation, the benzylic cation is
generated regioselectively and stabilized in the form of
conjugated iminium species A,[3] thereby facilitating the
transfer of chiral information. Indeed, imines are the most
widely exploited substrates in CPA-catalyzed asymmetric
transformations.[4,5]
Scheme 1. Chiral Brønsted acid catalyzed pinacol rearrangements.
À
C C bond shift a ring-strain-releasing process (Scheme 1b).
While the synthetic significance of these transformations is
self-evident, constraints imposed on the substrate structure
have nevertheless limited the full exploitation of the pinacol
rearrangement. In connection with our ongoing studies of
organocatalytic enantioselective transformations,[9] we
became interested in the chiral contact ion pairs[10] formed
between a CPA and cationic intermediates other than
iminium species,[11,12] and we chose allylic cations[13] as our
playground. We herein report a catalytic enantioselective
vinylogous pinacol rearrangement of 1,4-diols 1 to b,g-
unsaturated ketones 2 (Scheme 1c) and provide evidence
that supports the hypothesis that chiral allylic contact ion pair
B is a key intermediate for the transfer of chirality. The
vinylogous pinacol rearrangement is known[14] and has been
utilized in complex natural product synthesis.[15] However, its
asymmetric version was still unknown at the outset of this
work.
To circumvent the aforementioned challenges, a number
of efficient catalytic enantioselective semipinacol rearrange-
ments have been developed.[6–8] Two key structural elements
have been strategically incorporated into the substrates of
these reactions in order to a) regioselectively generate the
cationic intermediate or its equivalent and b) render the 1,2-
(E)-1,1-Bis(4-methoxyphenyl)-4,4-diphenylbut-2-ene-1,4-
diol (1a) was chosen as the model substrate. In the presence
of chiral phosphoric acid (S)-3a (0.1 equiv), 1a underwent
a pinacol rearrangement to afford b,g-unsaturated ketone 2a
as the only detectable regioisomer in 42% yield with 22% ee
(Table 1, entry 1). Other CPAs such as TRIP (3b, entry 2) and
STRIP (3c, entry 3) failed to improve the reaction outcome.
However, a dramatic increase in yield was observed when
N-triflyl phosphoramides (Figure 1),[16] which are stronger
Brønsted acids, were used as catalysts, with 3 f providing the
best result (entries 4–7). Using 3 f as the catalyst, the reaction
conditions were further optimized by varying the solvent,
additive, and reaction temperature. Importantly, adding 4 ꢁ
molecular sieves (M.S.) significantly increased the yield and
enantiopurity of the product. Overall, the best conditions
consisted of performing the reaction in methyl tert-butyl ether
[*] Dr. H. Wu, Dr. Q. Wang, Prof. Dr. J. Zhu
Laboratory of Synthesis and Natural Products
Institute of Chemical Sciences and Engineering
Ecole Polytechnique Fꢀdꢀrale de Lausanne
EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland)
E-mail: jieping.zhu@epfl.ch
Homepage: http://lspn.epfl.ch
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201609911.
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Table 1: Optimization of the reaction conditions.[a]
Entry
B*-H
Solvent
T [8C]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
10
11
12
13[d]
14[d]
15[d]
16[d]
3a
3b
3c
3d
3e
3 f
3g
3 f
3 f
3 f
3 f
3 f
3 f
3 f
3 f
3 f
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCM
THF
CH3NO2
Et2O
Et2O
DME
25
25
25
25
25
42
52
35
95
92
97
98
92
94
72
68
71
95
96
99
94
22
28
25
10
12
38
11
56
74
65
4
84
89
90
91
91
25
25
À20
À20
À20
À20
À20
À20
À20
À20
À40
MTBE
MTBE
[a] Reaction conditions: 1a (0.05 mmol, Ar=4-MeOC6H4), B*-H
(0.005 mmol), solvent (1.0 mL), 12 h. [b] Yield of isolated product.
[c] Determined by supercritical fluid chromatography on a chiral sta-
tionary phase. [d] 4 ꢁ molecular sieves (40 mg) were added. DCM=di-
chloromethane, DME=1,2-dimethoxyethane.
Figure 1. Structures of representative CPAs and chiral phosphora-
mides.
Scheme 2. Scope of the vinylogous pinacol rearrangement. [a] At room
temperature. [b] At 08C.
(MTBE, 0.05m) at À208C in the presence of 3 f (0.1 equiv)
and 4 ꢁ molecular sieves. Under these conditions, ketone 2a
was isolated in 99% yield with 91% ee (entry 15).[17]
can play the same role to afford the corresponding enan-
tioenriched ketones (2r–2u) in excellent yields with high
enantioselectivities.
On gram scale, the rearrangement reaction of 1a also
proceeded smoothly to afford 2a in 89% yield with 87% ee.
Recrystallization (CH2Cl2/MeCN) furnished the desired
product in enantiopure form. The absolute configuration of
2a was determined by X-ray crystallography,[18] and the
configurations of the other b,g-unsaturated ketones were
assigned accordingly.
A possible reaction pathway is depicted in Scheme 3.
Hydrogen bonding between 1,4-diol 1 and N-triflyl phosphor-
amide 3 f should generate two possible intermediates C and
D, which might be in equilibrium. It was assumed that
dehydration of C leading to allylic cation/chiral phosphor-
amide anion pair E would be a kinetically faster process than
dehydration of D owing to the resonance contribution of the
4-methoxy group in E. Therefore, the reaction would be
pulled towards the formation of ion pair E following the
Curtin–Hammett principle, which leads to the observed high
regioselectivity of the rearrangement process. A subsequent
Next, the scope of this vinylogous pinacol rearrangement
was examined. A variety of substrates bearing electron-rich,
electron-neutral, and electron-deficient aryl moieties under-
went the desired regioselective rearrangement to generate
b,g-unsaturated ketones 2 in high yields with excellent
enantioselectivities (Scheme 2). Substituents at the para,
meta, and ortho positions were well tolerated (2a–2o).
Electron-poor aromatic moieties migrated equally well
upon conducting the reaction at 08C or at room temperature
(2h–2m, 2o). A naphthyl-substituted 1,4-diol participated in
this asymmetric 1,2-shift process to provide 2p in good yield
and enantioselectivity. Finally, a benzyl-substituted 1,4-diol
afforded the corresponding product 2q in excellent yield,
albeit with diminished enantioselectivity.
It is clear that the 4-methoxyphenyl group very efficiently
controls the regioselective generation of the carbenium
intermediate. Pleasingly, other substituents that are capable
of stabilizing the cationic intermediate, such as 3,4-
dimethoxyphenyl as well as 2- and 3-thiophene moieties,
2
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Scheme 3. Possible reaction pathway for the regio- and enantioselec-
tive vinylogous pinacol rearrangement of 1,4-diols.
Scheme 5. Synthetic transformations of chiral b,g-unsaturated ketone
2a.
enantioselective 1,2-shift of the R group in E, assisted by the
chiral phosphoramide anion, would produce the enantioen-
riched ketone 2 with concurrent release of F, which, upon
tautomerization, would regenerate catalyst 3 f. The impor-
tance of the resonance contribution of the methoxy group is
readily seen in the conversion of 1n into 2n, which results
from the selective migration of the 3-methoxyphenyl group at
the expense of the 4-methoxyphenyl group.[19]
A series of experiments were performed to support the
proposed mechanism of this enantioselective pinacol rear-
rangement. First, submitting racemic b,g-unsaturated ketone
2a to our standard reaction conditions led only to the
recovery of (Æ)-2a without any enantioenrichment. There-
fore, the formation of enantioenriched 2a did not occur by
a non-stereoselective pinacol rearrangement to (Æ)-2a fol-
lowed by CPA-catalyzed enantioselective protonation of its
enol form.[20] Second, performing the reaction of 1g in the
presence of EtOH (6.0 equiv) under otherwise identical
conditions afforded ethoxylated product 4 in racemic form
and 98% yield (Scheme 4a). Should the reaction proceed
Further transformations of b,g-unsaturated ketone 2a
were performed to illustrate the synthetic potential of our
reaction (Scheme 5). Chemoselective CBS reduction[22] with
catalyst (S)-6 afforded syn-7 and its anti isomer in yields of
80% and 11%, respectively. Treatment of diastereomerically
pure syn-7 with N-bromosuccinimide (NBS)[23] afforded
tetrahydrofuran 8, an analogue of sacidumlignan D,[24] in
87% yield. Hydrogenation of 2a (Pd/C, H2, EtOAc) furnished
saturated ketone 9 in 91% yield. Reduction of 9 with sodium
borohydride produced intermediate 10 as a mixture of two
diastereomers (7:1 d.r.). Friedel–Crafts cyclization of 10 in
trifluoroacetic acid (TFA)[25] then provided tetrahydronaph-
thalene 11 in 87% yield (5:1 d.r.).[26]
In conclusion, we have developed the first enantioselec-
tive vinylogous pinacol rearrangement of 1,4-diols catalyzed
by a chiral N-triflyl phosphoramide. The formation of a chiral
contact ion pair between the intermediary allylic cation and
the conjugated base of the chiral Brønsted acid was proposed
to be responsible for the observed enantioselectivity. The
utility of this transformation was illustrated by the subsequent
conversion of the resulting b,g-unsaturated ketones into
enantioenriched polysubstituted tetrahydrofuran and tetra-
hydronaphthalene derivatives.
Acknowledgements
Scheme 4. Control experiments.
Financial support from the EPFL (Switzerland) and the Swiss
National Science Foundation (SNSF) is gratefully acknowl-
edged. We thank Dr. Rosario Scopelliti for the X-ray
structural analysis of compound 2a.
through an SN2’ mechanism, rearrangement via postulated
transition state C (or D) should be competitive, leading to
product 2g. Furthermore, if the reaction indeed proceeded
through an SN2’ mechanism, migration of the electron-rich
aryl group (4-methoxyphenyl), which has a higher migratory
aptitude, via TS D would dominate, leading to an isomer of
2g. However, these scenarios did not occur under our
conditions. Finally, the reaction of (Z)-2-butene-1,4-diol 1v
under our standard conditions provided dihydrofuran 5 in
98% yield, indicating that in this case, the ring closure is much
faster than the double-bond isomerization via the allylic
cation (Scheme 4b).[21]
Keywords: chiral Brønsted acids · 1,4-diols · ion pairs ·
organocatalysis · pinacol rearrangements
[1] R. Fittig, Justus Liebigs Ann. Chem. 1860, 114, 54.
[2] T. Liang, Z. Zhang, J. C. Antilla, Angew. Chem. Int. Ed. 2010, 49,
9734; Angew. Chem. 2010, 122, 9928.
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ˇ
´
[3] For an asymmetric a-iminol rearrangement, see: X. Zhang, R. J.
Staples, A. L. Rheingold, W. D. Wulff, J. Am. Chem. Soc. 2014,
136, 13971.
132, 8536; c) I. Coric, B. List, Nature 2012, 483, 315; d) Z. Chen,
J. Sun, Angew. Chem. Int. Ed. 2013, 52, 13593; Angew. Chem.
2013, 125, 13838; e) Z. Sun, G. A. Winschel, P. M. Zimmerman,
P. Nagorny, Angew. Chem. Int. Ed. 2014, 53, 11194; Angew.
Chem. 2014, 126, 11376; for a thiourea-catalyzed example, see:
f) S. E. Reisman, A. G. Doyle, E. N. Jacobsen, J. Am. Chem. Soc.
2008, 130, 7198.
[4] a) T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew. Chem. Int.
Ed. 2004, 43, 1566; Angew. Chem. 2004, 116, 1592; b) D.
Uraguchi, M. Terada, J. Am. Chem. Soc. 2004, 126, 5356.
[5] For recent reviews on chiral phosphoric acids, see: a) D. Parmar,
E. Sugiono, S. Raja, M. Rueping, Chem. Rev. 2014, 114, 9047;
b) J. Lv, S. Luo, Chem. Commun. 2013, 49, 847; c) P. Li, H.
Yamamoto, Top. Curr. Chem. 2011, 37, 161; d) J. Yu, F. Shi, L.-Z.
Gong, Acc. Chem. Res. 2011, 44, 1156; e) D. Kampen, C. M.
Reisinger, B. List, Top. Curr. Chem. 2010, 291, 395; f) M. Terada,
Synthesis 2010, 1929; g) M. Hatano, K. Ishihara, Synthesis 2010,
3785; h) A. Zamfir, S. Schenker, M. Freund, S. B. Tsogoeva, Org.
Biomol. Chem. 2010, 8, 5262; i) X. Yu, W. Wang, Chem. Asian J.
2008, 3, 516; j) T. Akiyama, Chem. Rev. 2007, 107, 5744.
[6] For selected examples of organocatalytic processes, see: a) Q.-W.
Zhang, C.-A. Fan, H.-J. Zhang, Y.-Q. Tu, Y.-M. Zhao, P. Gu, Z.-
M. Chen, Angew. Chem. Int. Ed. 2009, 48, 8572; Angew. Chem.
2009, 121, 8724; b) E. Zhang, C.-A. Fan, Y.-Q. Tu, F.-M. Zhang,
Y.-L. Song, J. Am. Chem. Soc. 2009, 131, 14626; c) J.-B. Peng, Y.
Qi, A.-J. Ma, Y.-Q. Tu, F.-M. Zhang, S.-H. Wang, S.-Y. Zhang,
Chem. Asian J. 2013, 8, 883; d) F. Romanov-Michailidis, L.
Guꢂnꢂe, A. Alexakis, Angew. Chem. Int. Ed. 2013, 52, 9266;
Angew. Chem. 2013, 125, 9436; e) F. Romanov-Michailidis, L.
Guꢂnꢂe, A. Alexakis, Org. Lett. 2013, 15, 5890; f) F. Romanov-
Michailidis, M. Romanova-Michaelides, M. Pupier, A. Alexakis,
Chem. Eur. J. 2015, 21, 5561.
[7] For selected examples of transition-metal-catalyzed processes,
see: a) B. M. Trost, T. Yasukata, J. Am. Chem. Soc. 2001, 123,
7162; b) B. M. Trost, J. Xie, J. Am. Chem. Soc. 2008, 130, 6231;
c) F. Kleinbeck, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 9178.
[8] For reviews, see: a) T. J. Snape, Chem. Soc. Rev. 2007, 36, 1823;
b) B. Wang, Y.-Q. Tu, Acc. Chem. Res. 2011, 44, 1207; c) S.-H.
Wang, B.-S. Li, Y.-Q. Tu, Chem. Commun. 2014, 50, 2393; for
general reviews on asymmetric organocatalytic rearrangements,
see: d) A. Moyano, N. El-Hamodouni, A. Atlamsani, Chem. Eur.
J. 2010, 16, 5260; e) G. Valero, A. Moyano in Comprehensive
Enantioselective Organocatalysis: Catalysts, Reactions, and Ap-
plications, Vol. 3 (Ed.: P. I. Dalko), Wiley-VCH, Weinheim,
2013, Chapter 40.
[12] For ammonium and episulfonium salts, see: G. L. Hamilton, T.
Kanai, F. D. Toste, J. Am. Chem. Soc. 2008, 130, 14984.
[13] For chiral Brønsted acid catalyzed enantioselective transforma-
tions involving allylic cations, see: a) M. Rueping, U. Uria, M.-Y.
Lin, I. Atodiresei, J. Am. Chem. Soc. 2011, 133, 3732; b) P.-S.
Wang, X.-L. Zhou, L.-Z. Gong, Org. Lett. 2014, 16, 976; c) M.-Y.
Zhuang, H.-F. Du, Org. Biomol. Chem. 2014, 12, 4590.
[14] a) R. E. Lutz, R. G. Bass, D. W. Boykin, J. Org. Chem. 1964, 29,
3660; b) K. Saito, Y. Horie, T. Mukai, T. Toda, Bull. Chem. Soc.
Jpn. 1985, 58, 3118; c) M. Smet, J. V. Dijk, W. Dehaen,
Tetrahedron 1999, 55, 7859; d) R. Sekiya, K. Kiyo-oka, T.
Imakubo, K. Kobayashi, J. Am. Chem. Soc. 2000, 122, 10282;
e) L.-L. Zhu, X.-X. Li, W. Zhou, X. Li, Z.-L. Chen, J. Org. Chem.
2011, 76, 8814.
[15] L. Jørgensen, S. J. McKerrall, C. A. Kuttruff, F. Ungeheuer, J.
Felding, P. S. Baran, Science 2013, 341, 878.
[16] S. A. Yamamoto, D. Nakashima, H. Yamamoto, J. Am. Chem.
Soc. 2006, 128, 9626.
[17] For an alternative approach involving dual organocatalysis, see:
X. Mo, D. G. Hall, J. Am. Chem. Soc. 2016, 138, 10762.
[18] CCDC 1487213 (2a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[19] Treatment of symmetric (E)-1,1,4,4-tetrakis(4-methoxyphenyl)-
but-2-ene-1,4-diol (1w) under the standard conditions afforded
rearranged product 2w in 97% yield with 26% ee (see the
Supporting Information). Migration of the Ar group of high
migratory aptitude before formation of the contact ion pair, and
hence low chiral communication, could be responsible for the
low enantioselectivity.
[20] C. H. Cheon, H. Yamamoto, J. Am. Chem. Soc. 2008, 130, 9246.
[21] The benzylic cation might be stabilized in the form of a para-
quinone methide. For CPA-catalyzed nucleophilic additions
involving para-quinone methides, see: Z. Wang, Y. F. Wong, J.
Sun, Angew. Chem. Int. Ed. 2015, 54, 13711; Angew. Chem. 2015,
127, 13915.
[22] E. J. Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. 1987,
109, 5551.
[23] a) D. J. Hart, V. Leroy, G. H. Merriman, D. G. J. Young, J. Org.
Chem. 1992, 57, 5670; b) J. K. Rout, C. V. Ramana, J. Org. Chem.
2012, 77, 1566.
[24] For the isolation, see: a) L.-S. Gan, S.-P. Yang, C.-Q. Fan, J.-M.
Yue, J. Nat. Prod. 2005, 68, 221; for a recent synthesis from our
laboratory, see: b) T. M. Ha, C. Chatalova-Sazepin, Q. Wang, J.
Zhu, Angew. Chem. Int. Ed. 2016, 55, 9249; Angew. Chem. 2016,
128, 9395.
[9] a) G. Dagousset, J. Zhu, G. Masson, J. Am. Chem. Soc. 2011, 133,
14804; b) J.-B. Denis, G. Masson, P. Retailleau, J. Zhu, Angew.
Chem. Int. Ed. 2011, 50, 5356; Angew. Chem. 2011, 123, 5468;
c) Y. Su, M. J. Bouma, L. Alcaraz, M. Stocks, M. Furber, G.
Masson, J. Zhu, Chem. Eur. J. 2012, 18, 12624; d) T. Buyck, Q.
Wang, J. Zhu, Angew. Chem. Int. Ed. 2013, 52, 12714; Angew.
Chem. 2013, 125, 12946; e) J.-B. Gualtierotti, D. Pasche, Q.
Wang, J. Zhu, Angew. Chem. Int. Ed. 2014, 53, 9926; Angew.
Chem. 2014, 126, 10084; f) Y. Zhang, Y.-F. Ao, Z.-T. Huang, D.-
X. Wang, M.-X. Wang, J. Zhu, Angew. Chem. Int. Ed. 2016, 55,
5282; Angew. Chem. 2016, 128, 5368; g) Y. Wang, Q. Wang, J.
Zhu, Chem. Eur. J. 2016, 22, 8084.
[10] For selected reviews, see: a) J. Lacour, V. Hebbe-Viton, Chem.
Soc. Rev. 2003, 32, 373; b) Z. Zhang, P. R. Schreiner, Chem. Soc.
Rev. 2009, 38, 1187; c) R. J. Phipps, G. L. Hamilton, F. D. Toste,
Nat. Chem. 2012, 4, 603; d) M. Mahlau, B. List, Angew. Chem.
Int. Ed. 2013, 52, 518; Angew. Chem. 2013, 125, 540; e) K. Brak,
E. N. Jacobsen, Angew. Chem. Int. Ed. 2013, 52, 534; Angew.
Chem. 2013, 125, 558; f) D. Seidel, Synlett 2014, 25, 783; g) N.
Busschaert, C. Caltagirone, W. V. Rossom, P. A. Gale, Chem.
Rev. 2015, 115, 8038.
[25] R. Malhotra, A. Ghosh, R. Ghosh, S. Chakrabarti, S. Dutta, T. K.
Dey, S. Roy, S. Basu, S. Hajra, Tetrahedron: Asymmetry 2011, 22,
1522.
[26] For examples, see: a) Y.-H. Kuo, S.-T. Lin, R.-E. Wu, Chem.
Pharm. Bull. 1989, 37, 2310; b) A. M. A. P. Fernandes, L. E. S.
Barata, P. H. Ferri, Phytochemistry 1994, 36, 533; c) R. B.
Teponno, S. Kusari, M. Spiteller, Nat. Prod. Rep. 2016, 33, 1044.
[11] For selected examples of oxocarbenium ion pairs, see: a) M.
Terada, H. Tanaka, K. Sorimachi, J. Am. Chem. Soc. 2009, 131,
Received: October 10, 2016
Published online: && &&, &&&&
ˇ
´
3430; b) I. Coric, S. Vellalath, B. List, J. Am. Chem. Soc. 2010,
4
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Communications
Rearrangements
H. Wu, Q. Wang, J. Zhu*
&&&& — &&&&
Organocatalytic Enantioselective
Vinylogous Pinacol Rearrangement
Enabled by Chiral Ion Pairing
Pair and reorganize: In the presence of
a chiral BINOL-derived N-triflyl phos-
phoramide, functionalized (E)-2-butene-
1,4-diols undergo an enantioselective
pinacol rearrangement to b,g-unsatu-
rated ketones. The formation of a chiral
contact ion pair between the allylic cation
and the conjugated base of the chiral
Brønsted acid might be responsible for
the observed enantioselectivity.
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