Journal of the American Chemical Society
Page 4 of 6
(5) For an attempt with low enantioselectivity: Zhuang, M.; Du, H.
Asymmetric Rearrangement of Racemic Epoxides Catalyzed by Chiral
Brønsted Acids. Org. Biomol. Chem. 2013, 11, 1460.
By proper design of the tetrasubstituted epoxides and suitable
choice of the catalysts, this reaction proceeded with broad scope,
excellent efficiency and functional group compatibility as well as
high regio- and stereocontrol under mild conditions (typically
without cryogenic conditions). Low catalyst loading was also
demonstrated. This reaction also represents an attractive comple-
ment to the existing strategies (e.g., α-arylation of ketones) for the
synthesis of chiral ketones bearing α-quaternary stereocenters.
The observation of positive non-linear effects and the nontrivial
kinetic feature also provided important insights into the mecha-
nism. The chiral products are useful precursors to a wide range of
chiral molecules containing all-carbon quaternary stereocenters.
1
2
3
4
5
6
7
8
(6) During the preparation of this manuscript, a closely related work
appeared: Wu, H.; Wang, Q.; Zhu, J. Catalytic Enantioselective Pinacol
and Meinwald Rearrangements for the Construction of Quaternary Stereo-
centers. J. Am. Chem. Soc. 2019, 141, 11372. In this work, only chiral
cyclohexanones were demonstrated (without acyclic ketones).
(7) (a) McMurry, J. E.; Felming, M. P. New Method for the Reductive
Coupling of Carbonyls to Olefins. Synthesis of β-Carotene. J. Am. Chem.
Soc. 1974, 96, 4708-4909. (b) Duan, X.-F.; Zeng, J.; Lü, J.-W.; Zhang, Z.-
B. A Facile Synthesis of Tetraarylethenes via Cross McMurry Coupling
between Diaryl Ketones. Synthesis 2007, 713
(8) (a) Gualandi, A.; Cozzi, P. G. Stereoselective Organocatalytic Al-
kylations with Carbenium Ions. Synlett 2013, 24, 281. (b) Wendlandt, A.E.;
Vangal, P.; Jacobsen, E.N. Quaternary Stereocenters via an Enantiocon-
vergent Catalytic SN1 Reaction. Nature 2018, 556, 447. (c) Tsuji, N.;
Kennemur, J. L.; Buyck, T.; Lee, S.; Prévost, S.; Kaib, P. S. J.; Bykov, D.;
Farès, C.; List, B. Activation of Olefins via Asymmetric Brønsted Acid
Catalysis. Science 2018, 359, 1501.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
(9) (a) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Enantioselective
Mannich-type Reaction Catalyzed by a Chiral Brønsted Acid. Angew.
Chem., Int. Ed. 2004, 43, 1566. (b) Uraguchi, D.; Terada, M. Chiral
Brønsted Acid-catalyzed Direct Mannich Reactions via Electrophilic
Activation. J. Am. Chem. Soc. 2004, 126, 5356. (c) Parmar, D.; Sugiono,
E.; Raja, S.; Rueping, M. Complete Field Guide to Asymmetric BINOL-
Phosphate Derived Brønsted Acid and Metal Catalysis: History and Clas-
sification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding,
Ion Pairing, and Metal Phosphates. Chem. Rev. 2014, 114, 9047.
Experimental procedures and compound characterization (PDF)
X-ray data (CIF)
AUTHOR INFORMATION
Corresponding Author
(10) Giacalone, F.; Gruttadauria, M.; Agrigento, P.; Noto, R. Low-
loading Asymmetric Organocatalysis. Chem. Soc. Rev. 2012, 41, 2406.
(11) (a) Wang, Z.; Sun, J. Recent Advances in Catalytic Asymmetric
Reactions of o-Quinone Methides. Synthesis 2015, 47, 3629. (b) Caruana,
L.; Fochi, M.; Bernardi, L. The Emergence of Quinone Methides in
Asymmetric Organocatalysis. Molecules 2015, 20, 11733. (c) El-Sepelgy,
O.; Haseloff, S.; Alamsetti, S. K.; Schneider, C. Brønsted Acid Catalyzed,
Conjugate Addition of β-Dicarbonyls to In Situ Generated ortho-Quinone
Methides-Enantioselective Synthesis of 4-Aryl-4H-Chromenes. Angew.
Chem., Int. Ed. 2014, 53, 7923. (d) Hsiao, C.-C.; Liao, H.-H.; Rueping, M.
Enantio- and Diastereoselective Acess to Distant Stereocenters Embedded
within Tetrahydroxanthenes: Utilizing ortho-Quinone Methides as Reac-
tive Intermediates in Asymmetric Brønsted Acid Catalysis. Angew. Chem.,
Int. Ed. 2014, 53, 13258. (e) Zhao, W.; Wang, Z.; Chu, B.; Sun, J. Enanti-
oselective Formation of All-carbon Quaternary Stereocenters from Indoles
and Tertiary Alcohols Bearing a Directing Group. Angew. Chem., Int. Ed.
2015, 54, 1910. (f) Wang, Z.; Ai, F.; Wang, Z.; Zhao, W.; Zhu, G.; Lin, Z.;
Sun, J. Organocatalytic Asymmetric Synthesis of 1,1-Diarylethanes by
Transfer Hydrogenation. J. Am. Chem. Soc. 2015, 137, 383. (g) Lin, J.-S.;
Li, T.-T.; Liu, J.-R.; Jiao, G.-Y.; Gu, Q.-S.; Cheng, J.-T.; Guo, Y.-L.;
Hong, X.; Liu, X.-Y. Cu/Chiral Phosphoric Acid-Catalyzed Asymmetric
Three-Component Radical-Initiated 1,2-Dicarbofunctionalization of Al-
kenes. J. Am. Chem. Soc. 2019, 141, 1074. (h) Zhao, J.-J.; Sun, S.-B.; He,
S.-H.; Wu, Q.; Shi, F. Catalytic Asymmetric Inverse-Electron-Demand
Oxa-Diels–Alder Reaction of In Situ Generated ortho-Quinone Methides
with 3-Methyl-2-Vinylindoles. Angew. Chem., Int. Ed. 2015, 54, 5460. (i)
Xie, Y.; List, B. Catalytic Asymmetric Intramolecular [4 + 2] Cycloaddi-
tion of In Situ Generated ortho-Quinone Methides. Angew. Chem., Int. Ed.
2017, 56, 4936. (j) Qian, D.; Wu, L.; Lin, Z.; Sun, J. Organocatalytic
Synthesis of Chiral Tetrasubstituted Allenes from Racemic Propargylic
Alcohols. Nat. Commun. 2017, 8, 567.
(12) For closely related asymmetric (semi-)pinacol rearrangement, typ-
ically to generate cyclic or tertiary stereocenters, see: (a) Zhang, Q.-W.;
Fan, C.-A.; Zhang, H.-J.; Tu, Y.-Q.; Zhao, Y.-M.; Gu, P.; Chen, Z.-M.
Brønsted Acid Catalyzed Enantioselective Semipinacol Rearrangement for
the Synthesis of Chiral Spiroethers. Angew. Chem., Int. Ed. 2009, 48,
8572. (b) Liang, T.; Zhang, Z.; Antilla, J. C. Chiral Brønsted Acid Cata-
lyzed Pinacol Rearrangement. Angew. Chem., Int. Ed. 2010, 49, 9734. (c)
Wang, B.; Tu, Y.-Q. Stereoselective Construction of Quaternary Carbon
Stereocenters via a Semipinacol Rearrangement Strategy. Acc. Chem. Res.
2011, 44, 1207. (d) Snyder, S. A.; Thomas, S. B.; Mayer, A. C.; Breazza-
no, S. P. Total Syntheses of Hopeanol and Hopeahainol A Empowered by
a Chiral Brønsted Acid Induced Pinacol Rearrangement. Angew. Chem.,
Int. Ed. 2012, 51, 4080. (e) Chai, Z.; Rainey, T. J. Pd(II)/Brønsted Acid
Catalyzed Enantioselective Allylic C−H Activation for the Synthesis of
Spirocyclic Rings. J. Am. Chem. Soc. 2012, 134, 3615. (f) Romanov-
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Financial support was provided by Hong Kong RGC (16302617,
16302318, 16311616) and Shenzhen Science and Technology
Innovation Committee (JCYJ20170818113708560,
JCYJ20160229205441091).
REFERENCES
(1) (a) Das, J. P.; Marek, I. Enantioselective Synthesis of All-Carbon
Quaternary Stereogenic Centers in Acyclic Systems. Chem. Commun.
2011, 47, 4593. (b) Quasdorf, K. W.; Overman, L. E. Catalytic Enantiose-
lective Synthesis of Quaternary Carbon Stereocentres. Nature 2014, 516,
181. (c) Liu, Y.; Han, S.-J.; Liu, W.-B.; Stoltz, B. M. Catalytic Enantiose-
lective Construction of Quaternary Stereocenters: Assembly of Key Build-
ing Blocks for the Synthesis of Biologically Active Molecules. Acc. Chem.
Res. 2015, 48, 740.
(2) (a) Hamada, T.; Chieffi, A.; Åhman, J.; Buchwald, S. L. An Im-
proved Catalyst for the Asymmetric Arylation of Ketone Enolates. J. Am.
Chem. Soc. 2002, 124, 1261. (b) Liao, X.; Weng, Z.; Hartwig, J. F. Enan-
tioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by
Difluorphos Complexes of Palladium and Nickel. J. Am. Chem. Soc. 2008,
130, 195. (c) Kano, T.; Hayashi, Y.; Maruoka, K. Construction of a Chiral
Quaternary Carbon Center by Catalytic Asymmetric Alkylation of 2-
Arylcyclohexanones under Phase-transfer Conditions. J. Am. Chem. Soc.
2013, 135, 7134. (d) Felker, I.; Pupo, G.; Kraft, P.; List, B. Design and
Enantioselective Synthesis of Cashmeran Odorants by Using “Enol Catal-
ysis”. Angew. Chem., Int. Ed. 2015, 54, 1960. (e) Yang, X.; Toste, F. D.
Asymmetric Addition of α-Branched Cyclic Ketones to Allenamides
Catalyzed by a Chiral Phosphoric Acid. Chem. Sci. 2016, 7, 2653.
(3) (a) House, H. O. The Acid-catalyzed Rearrangement of the Stilbene
Oxides. J. Am. Chem. Soc. 1955, 77, 3070. (b) Meinwald, J.; Labana, S. S.;
Chadha, M. S. Peracid Reactions. III. The Oxidation of Bicy-
clo[2.2.1]heptadiene. J. Am. Chem. Soc. 1963, 85, 582.
(4) (a) Shen, Y.-M.; Wang, B.; Shi, Y. Enantioselective Synthesis of 2-
Aryl Cyclopentanones by Asymmetric Epoxidation and Epoxide Rear-
rangement. Angew. Chem., Int. Ed. 2006, 45, 1429. (b) Shen, Y.-M.;
Wang, B.; Shi, Y. Enantioselective Synthesis of 2-Alkyl-2-aryl Cyclopen-
tanones by Asymmetric Epoxidation of Tetrasubstituted Cyclobutylidene
Olefins and Epoxide Rearrangement. Tetrahedron Lett. 2006, 47, 5455.
ACS Paragon Plus Environment