Axial-to-Central Chirality Transfer for Construction of Quaternary Stereocenters via Dearomatization of BINOLs

Article abstract of DOI:10.1021/acs.orglett.9b03558

All-carbon quaternary stereocenters are versatile building blocks, and their asymmetric construction has attracted much attention. Herein, we disclose an axial-to-central chirality transfer strategy for the synthesis of chiral quaternary stereocenters via dearomatization of (S)-BINOLs. The reaction proceeded smoothly with a wide range of propargyl carbonates to afford chiral spiro-compounds in high yields with excellent enantioselectivities. In addition, the strategy was extended to kinetic resolution of rac-BINOLs albeit with moderate s value.

Full text of DOI:10.1021/acs.orglett.9b03558

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Axial-to-Central Chirality Transfer for Construction of Quaternary
Stereocenters via Dearomatization of BINOLs
Xiao-Long Min, Xu-Ran Xu, and Ying He*
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing 210094, China
S
* Supporting Information
ABSTRACT: All-carbon quaternary stereocenters are versatile building blocks, and their asymmetric construction has attracted
much attention. Herein, we disclose an axial-to-central chirality transfer strategy for the synthesis of chiral quaternary
stereocenters via dearomatization of (S)-BINOLs. The reaction proceeded smoothly with a wide range of propargyl carbonates
to afford chiral spiro-compounds in high yields with excellent enantioselectivities. In addition, the strategy was extended to
kinetic resolution of rac-BINOLs albeit with moderate s value.
generate all-carbon quaternary stereocenters via chirality
transfer strategy (Scheme 1, to be explored).6
ll-carbon quaternary stereocenters are widely dispersed
1
Ain natural products and pharmaceuticals. Correspond-
Axially chiral compounds, especially atropisomeric biaryls,
have received increasing attention from chemists due to their
promising performance in asymmetric catalysis and drug
discovery.7 However, atropisomeric biaryls are less explored
as for their memory of chirality.8 Basically, two reasons
contribute to these constraints: (a) the multistep procedures
and high cost during the preparation of desired enantiopure
biaryls; (b) dearomatization of biaryls9 usually require harsh
conditions with the risk of racemization. Recently, an axial-to-
central chirality transfer strategy has been reported by
palladium catalyzed dynamic kinetic resolution of racemic
biaryls (Scheme 2, a).10 A central-to-helical-to-axial-to-central
chirality transfer of 2,2′-biphenol by a photoresponsive
catalyst was also reported by the Feringa group (Scheme 2,
b). Moreover, the chiral switch system was successfully
applied to creation of other stereogenic elements.11
ingly, considerable progress has been made in developing
efficient catalytic systems for their asymmetric synthesis.2 The
challenges associated with enantioselective construction of
quaternary carbon stereocenters could be addressed by
several known synthetic strategies. First, C−C bond
formation reactions occur on a sp2-hybridized prochiral
carbon such as olefins, metal carbenoids, enolates and
enamines, etc. (Scheme 1, a−c). Second, desymmetrization
occurs on prochiral molecules with a prochiral quaternary
carbon or kinetic resolutions occur on racemic compounds
bearing quaternary stereocenters (Scheme 1, d and e).3−5
Nevertheless, few research studies have been reported to
Scheme 1. Synthetic Strategies to All-Carbon Quaternary
Stereocenters
Inspired by these precedents, we sought to explore a new
catalytic system to generate an all-carbon quaternary
stereocenter via dearomatization of biaryls. Taking the
efficiency of palladium-catalyzed asymmetric dearomatization
reactions, we envisioned that this goal might be achieved
through dearomatization of (S)- or (R)-BINOLs. We
hypothesized that propargyl carbonate is the suitable partner
because of its dual electrophilic property during the
palladium catalysis (Scheme 2, c).12 Herein, we present
palladium-catalyzed dearomatizations of enantiopure BINOLs
Received: October 8, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 2. Axial-to-Central Chirality Transfer of Biaryls
Table 1. Optimization of Reaction Conditions
leaving
group
yield
(3a, %)
yield
(4a, %)
b
b
c
entry ligand t (h)
3a/4a
1
2
3
4
5
6
7
8
9
L1
L2
L3
L4
L5
L6
L7
L8
L1
L8
L8
1.0
2.0
2.0
2.0
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OBoc
62
38
46
39
37
77
96
99
trace
52
37
trace
47
24
26
43
trace
trace
trace
45
trace
trace
>20:1
45:56
66:34
60:40
46:54
93:7
>20:1
>20:1
<1:20
>20:1
>20:1
20
0.5
0.5
0.2
1.0
10
8.0
d
10
11
OBz
a
Reaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), Pd2(dba)3 (5
b
mol %), ligand (10 mol %), DCM (1.0 mL), rt. Yield of isolated
products. 3a were obtained in >99% ee in all cases. Determined by
HPLC. Toluene as solvent.
c
d
to form all-carbon quaternary stereocenters via axial-to-central
chirality transfer.
We initiated our optimization by examining the reaction
parameters involving solvents, catalyst ligands, and leaving
groups using (S)-BINOL and methyl prop-2-yn-1-yl carbo-
nate as model substrates. Screening of solvents and catalysts
disclosed that DCM was the best solvent in the presence of
Pd2(dba)3 (see SI for details). When (R)-BINAP (L1) was
used as a ligand, more than 20:1 ratio of 3a/4a was obtained
albeit with moderate yield of the reaction (Table 1, entry 1).
Upon switching the ligand to L2−L5, 3a was generated in
low yield with decreased ratio of 3a/4a (Table 1, entries 2−
5). Reaction conducted with Pd2(dba)3/L6 afforded 3a in an
improved yield while maintaining excellent 3a/4a ratio at
shorter reaction time (Table 1, entry 6). Ultimately, the
change in ligand such as L7 and L8 gave us both high yields
of 3a along with high ratio of 3a/4a (Table 1, entries 7 and
8). It is noteworthy that when the reaction was performed in
toluene with L1 as a ligand, diether product 4a was obtained
exclusively (Table 1, entry 9). This observation highlights the
importance of the reaction system affording the different
selectivity between 3a and 4a. Interestingly, 4a could undergo
palladium-catalyzed isomerization to deliver dearomatizative
product 3a (see SI for details). Finally, different leaving
groups were also examined but resulted in decreased yield of
3a (Table 1, entries 10 and 11).
With the optimized reaction conditions in hand, we then
explored the scope and limitations of the reaction (Schemes
3 and 4). Delightfully, the reaction tolerated broad
substituent groups on arylpropargyl carbonates regardless of
electron effect and steric hindrance of aryl group.13 For
example, 3b was obtained in excellent yield with >99% ee.14
Various substituted groups at the para-positions of arenes
were well tolerated to generate products 3 in good to
excellent yields (Schemes 3, 3c−3j). Moreover, a range of
meta- and ortho-substituted, electron-poor and electron-rich
analogues gave high yields of dearomative products (3k−3p).
The substrates bearing multifunctional groups at aryl group of
2 also underwent smoothly to generate the desired products
(3q−3u). Steric hindrance was then proved to be
uninfluential to this reaction since hindered arylpropargyl
carbonates delivered the corresponding products in excellent
yields (3v and 3w). Finally, we noticed that heterocycle was
compatible with the reaction system (3x). More importantly,
in all cases, the reaction of (S)-BINOL with arylpropargyl
carbonates delivered the desired products in high Z/E
selectivity of 3. Meanwhile, the products were obtained in
absolute configuration of S without erosion of ee value.
To showcase the generality of this method, alkylpropargyl
carbonates were synthesized and subjected to the reaction
system (Scheme 4).15 The nonfunctional linear alkylpropargyl
carbonates were compatible with the reaction, leading to the
products in good to excellent yields (6a and 6b). The alkyl
groups could be changed to branched or cyclic substituents
which gave moderate to good yields, albeit with decreased Z/
E ratio in some cases (6c−6h). A variety of functional
alkylpropargyl carbonates were tolerated, affording the desired
products with moderate to high Z/E ratios (6i−6m). Lastly,
selected natural available aldehydes were used to synthesize
the corresponding propargyl carbonates which could also be
treated as candidates for the reaction. The products were
obtained with moderate yields with high Z/E ratios (6n−6p).
B
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 3. Substrate Scope of Arylpropargyl Carbonates
a
Reaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), Pd2(dba)3 (5 mol %), ligand (10 mol %), DCE (1.0 mL), 50 °C, 2 h. Yield of isolated
1
product. % ee was determined by chiral HPLC. Z/E ratio was determined by H NMR.
With respect to the BINOL derivatives, several disub-
stituted (S)-BINOLs were utilized in the reaction system. As
expected, the reaction proceeded smoothly to furnish the
desired products in excellent yields (Scheme 5, a). In
addition, linear propargyl carbonates were also tested and
found compatible to the reaction (Scheme 5, b). A late-stage
functionalization was also conducted, and excellent yield was
obtained without the erosion of diastereomeric ratio,
highlighting the strategy to modify glycoside derivatives
(Scheme 5, c).
In light of the axial-to-central chirality transfer reaction
system, we investigated the kinetic resolution of rac-BINOL
using 2a as the substrate. After evaluating a series of solvents
and ligands, s factor of 9.4 was obtained with 72% ee of (S)-
BINOL and 64% ee of (R)-3a (Scheme 6, see SI for details).
To further test the practicality of this method, a gram-scale
reaction of (S)-BINOL with 2a was carried out (Scheme 7).
To our delight, the loading of catalyst could be decreased to
1.0 mol % without the erosion of yield and enantioselectivity.
Then several transformations of 3a were carried out. For
example, a Pd/C-catalyzed hydrogenation of product 3a
afforded product 11 in excellent yield with high chemo-
selectivity. 3a was transformed into 12 in 94% yield under
acidic conditions. The absolute configuration was confirmed
by X-ray crystallographic analysis.16
Presumably, two competing reactions occur under the
reaction conditions (Scheme 8). First, propargyl carbonates
are activated by Pd and converted to highly reactive
intermediate I with a release of CO2.12e Next, the BINOL
hydroxy group attacks intermediate I to form π-allylpalladium
intermediate II. Intermediate III is formed after the
generation of MeOH from intermediate II. On the one
hand, intermediate III would undergo dearomatization to
deliver product 3a directly. On the other hand, the anionic
oxygen would attack the π-allylpalladium to afford product 4a
first, and then product 4a undergoes palladium-catalyzed
isomerization to dearomatizative product 3a (see SI for
details).
In summary, we have described herein a novel strategy to
construct all-carbon quaternary stereocenter scaffolds by axial-
to-central chirality transfer. This new highly chemo- and
stereoselective approach allows for the rapid construction of a
new class of spirocyclic molecules bearing an all-carbon
quaternary stereogenic center with high enantioselectivities
(>99% ee). Moreover, limited attempts were conducted to
realize the kinetic resolution of rac-BINOL with s factor of
C
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 4. Substrate Scope of Alkylpropargyl Carbonates
Scheme 6. Kinetic Resolution of rac-BINOL
Scheme 7. Gram-Scale Reaction and Synthetic
Transformations
Scheme 8. Proposed Mechanism of the Reaction
a
Reaction conditions: 1a (0.1 mmol), 5 (0.2 mmol), Pd2(dba)3 (5
mol %), ligand (10 mol %), DCE (1.0 mL), 50 °C, 2 h. Yield of
isolated product. % ee was determined by chiral HPLC. The Z/E ratio
1
and d.r. were determined by H NMR or HPLC.
Scheme 5. Substrate Scope and Late-Stage
Functionalization
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03558.
Experimental details, 1H, 13C NMR and other
characterization data, single-crystal X-ray analysis
(PDF)
Accession Codes
CCDC 1940195 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
9.4. The synthetic potential of the resulting products was
demonstrated with several transformations and late-stage
functionalization.
D
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Ed. 2019, 58, 5443−5446. (c) Nie, W.; Gong, J.; Chen, Z.; Liu, J.;
Tian, D.; Song, H.; Liu, X.-Y.; Qin, Y. Enantioselective Total
Synthesis of (−)-Arcutinine. J. Am. Chem. Soc. 2019, 141, 9712−
9718.
(4) (a) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda, A. H.
All-Carbon Quaternary Stereogenic Centers by Enantioselective Cu-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yhe@njust.edu.cn.
ORCID
Catalyzed Conjugate Additions Promoted by
a Chiral N-
Heterocyclic Carbene. Angew. Chem., Int. Ed. 2007, 46, 1097−
1100. (b) Liu, X.; Wang, P.; Bai, L.; Li, D.; Wang, L.; Yang, D.;
Wang, R. Construction of Vicinal All-Carbon Quaternary Stereo-
centers Enabled by a Catalytic Asymmetric Dearomatization
Reaction of β-Naphthols with 3-Bromooxindoles. ACS Catal.
2018, 8, 10888−10894. (c) Trost, B. M.; Nagaraju, A.; Wang, F.;
Zuo, Z.; Xu, J.; Hull, K. L. Palladium-Catalyzed Decarboxylative
Asymmetric Allylic Alkylation of Dihydroquinolinones. Org. Lett.
2019, 21, 1784−1788. (d) Zhang, C.-L.; Han, Y.-F.; Ye, S. N-
Heterocyclic Carbene-Catalyzed β-addition of Enals to 3-Alkyleny-
loxindoles: Synthesis of Oxindoles with All-Carbon Quaternary
Stereocenters. Chem. Commun. 2019, 55, 7966−7969. (e) Alexy, E.
J.; Zhang, H.; Stoltz, B. M. Catalytic Enantioselective Synthesis of
Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative
Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates. J.
Am. Chem. Soc. 2018, 140, 10109.
(5) For selected papers on chiral auxiliary induced all-carbon
quaternary stereocenters, see: (a) Groaning, M. D.; Meyers, A. I.
Chiral Non-Racemic Bicyclic Lactams. Auxiliary-Based Asymmetric
Reactions. Tetrahedron 2000, 56, 9843−9873. (b) Amat, M.;
Lozano, O.; Escolano, C.; Molins, E.; Bosch, J. Enantioselective
Synthesis of 3,3-Disubstituted Piperidine Derivatives by Enolate
Dialkylation of Phenylglycinol-Derived Oxazolopiperidone Lactams.
J. Org. Chem. 2007, 72, 4431−4439. (c) Takao, K.-i.; Sakamoto, S.;
Touati, M. A.; Kusakawa, Y.; Tadano, K.-i. Asymmetric Con-
struction of All-Carbon Quaternary Stereocenters by Chiral-
Auxiliary-Mediated Claisen Rearrangement and Total Synthesis of
(+)-Bakuchiol. Molecules 2012, 17, 13330. (d) Shen, X.; Zhao, J.; Xi,
Y.; Chen, W.; Zhou, Y.; Yang, X.; Zhang, H. Enantioselective Total
Synthesis of (+)-Nocardioazine B. J. Org. Chem. 2018, 83, 14507−
14517. (e) Freeman, J. L.; Brimble, M. A.; Furkert, D. P. A Chiral
Auxiliary-Based Synthesis of the C5−C17 trans-Decalin Framework
of Anthracimycin. Org. Chem. Front. 2019, 6, 2954−2963.
(6) For chirality transfer from axial molecules to all-carbon
quaternary stereocenter scaffolds, see: (a) Lapierre, A. J. B.; Geib, S.
J.; Curran, D. P. Low-Temperature Heck Reactions of Axially Chiral
o-Iodoacrylanilides Occur with Chirality Transfer: Implications for
Catalytic Asymmetric Heck Reactions. J. Am. Chem. Soc. 2007, 129,
494−495. (b) Sakamoto, M.; Kato, M.; Aida, Y.; Fujita, K.; Mino,
T.; Fujita, T. Photosensitized 2 + 2 Cycloaddition Reaction Using
Homochirality Generated by Spontaneous Crystallization. J. Am.
Chem. Soc. 2008, 130, 1132−1133.
(7) For selected reviews on the synthesis of axially chiral biaryl
compounds, see: (a) LaPlante, S. R.; Fader, L. D.; Fandrick, K. R.;
Fandrick, D. R.; Hucke, O.; Kemper, R.; Miller, S. P. F.; Edwards, P.
J. Assessing Atropisomer Axial Chirality in Drug Discovery and
Development. J. Med. Chem. 2011, 54, 7005−7022. (b) Loxq, P.;
Manoury, E.; Poli, R.; Deydier, E.; Labande, A. Synthesis of Axially
Chiral Biaryl Compounds by Asymmetric Catalytic Reactions with
Transition Metals. Coord. Chem. Rev. 2016, 308, 131−190.
(c) Wang, Y.-B.; Tan, B. Construction of Axially Chiral Compounds
via Asymmetric Organocatalysis. Acc. Chem. Res. 2018, 51, 534−547.
(d) Liao, G.; Zhou, T.; Yao, Q.-J.; Shi, B.-F. Recent Advances in the
Synthesis of Axially Chiral Biaryls via Transition Metal-Catalysed
Asymmetric C−H Functionalization. Chem. Commun. 2019, 55,
8514−8523. (e) Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.;
Gresser, M. J.; Garner, J.; Breuning, M. Atroposelective Synthesis of
Axially Chiral Biaryl Compounds. Angew. Chem., Int. Ed. 2005, 44,
5384−5427. (f) Bringmann, G.; Gulder, T.; Gulder, T. A. M.;
Breuning, M. Atroposelective Total Synthesis of Axially Chiral Biaryl
Natural Products. Chem. Rev. 2011, 111, 563−639.
Ying He: 0000-0001-9159-4606
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support from Natural
Science Foundation of Jiangsu Province (BK20180447), the
Fundamental Research Funds for the Central Universities
(30918011313, 30919011404) and the Opening Project of
Key Laboratory of Special Energy Materials (NUST),
Ministry of Education, China. We thank M.-F. Lv from
Nanjing University of Science & Technology for assistance
with the X-ray crystallographic collection and analysis. We
thank Prof. C.-Z. Tao from Jiangsu Ocean University for
helpful discussions.
REFERENCES
■
(1) For selected reviews on all-carbon quaternary stereocenters in
total synthesis, see: (a) Chen, W.; Zhao, H. Asymmetric
Construction of All-Carbon Quaternary Stereocenters in the Total
Synthesis of Natural Products. Sci. China: Chem. 2016, 59, 1065−
1078. (b) Hong, A. Y.; Stoltz, B. M. The Construction of All-
Carbon Quaternary Stereocenters by Use of Pd-Catalyzed
Asymmetric Allylic Alkylation Reactions in Total Synthesis. Eur. J.
Org. Chem. 2013, 2013, 2745−2759. (c) Pandey, G.; Mishra, A.;
Khamrai, J. Generation of All Carbon Quaternary Stereocenters at
the C-3 Carbon of Piperidinones and Pyrrolidinones and Its
Application in Natural Product Total Synthesis. Tetrahedron 2018,
74, 4903. (d) Long, R.; Huang, J.; Gong, J.; Yang, Z. Direct
Construction of Vicinal All-Carbon Quaternary Stereocenters in
Natural Product Synthesis. Nat. Prod. Rep. 2015, 32, 1584−1601.
(2) For selected reviews on asymmetric synthesis of all-carbon
quaternary stereocenters, see: (a) Christoffers, J.; Mann, A.
Enantioselective Construction of Quaternary Stereocenters. Angew.
Chem., Int. Ed. 2001, 40, 4591−4597. (b) Quasdorf, K. W.;
Overman, L. E. Catalytic Enantioselective Synthesis of Quaternary
Carbon Stereocentres. Nature 2014, 516, 181−191. (c) Zeng, X.-P.;
Cao, Z.-Y.; Wang, Y.-H.; Zhou, F.; Zhou, J. Catalytic Enantiose-
lective Desymmetrization Reactions to All-Carbon Quaternary
Stereocenters. Chem. Rev. 2016, 116, 7330−7396. (d) Trost, B.
M.; Jiang, C. Catalytic Enantioselective Construction of All-Carbon
Quaternary Stereocenters. Synthesis 2006, 3, 369−396. (e) Douglas,
C. J.; Overman, L. E. Catalytic Asymmetric Synthesis of All-Carbon
Quaternary Stereocenters. Proc. Natl. Acad. Sci. U. S. A. 2004, 101,
5363−5367. (f) Christoffers, J.; Baro, A. Stereoselective Con-
struction of Quaternary Stereocenters. Adv. Synth. Catal. 2005, 347,
1473−1482. (g) Das, J. P.; Marek, I. Enantioselective Synthesis of
All-Carbon Quaternary Stereogenic Centers in Acyclic Systems.
Chem. Commun. 2011, 47, 4593−4623. (h) Bella, M.; Gasperi, T.
Organocatalytic Formation of Quaternary Stereocenters. Synthesis
2009, 2009, 1583−1614.
(3) (a) Pandey, G.; Khamrai, J.; Mishra, A. Generation of All-
Carbon Quaternary Stereocenters at the C-3 Carbon of Lactams via
[3,3]-Sigmatropic Rearrangement and Revision of Absolute Config-
uration: Total synthesis of (−)-Physostigmine. Org. Lett. 2018, 20,
166−169. (b) Tong, X.; Shi, B.; Liang, K.; Liu, Q.; Xia, C.
Enantioselective Total Synthesis of (+)-Flavisiamine F via Late-Stage
Visible-Light-Induced Photochemical Cyclization. Angew. Chem., Int.
E
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(8) Campolo, D.; Gastaldi, S.; Roussel, C.; Bertrand, M. P.;
Nechab, M. Axial-to-Central Chirality Transfer in Cyclization
Processes. Chem. Soc. Rev. 2013, 42, 8434−8466.
(9) For selected reviews on dearomatization reactions, see:
(a) Roche, S. P.; Porco, J. A. J. Dearomatization Strategies in the
Synthesis of Complex Natural Products. Angew. Chem., Int. Ed.
2011, 50, 4068−4093. (b) Zheng, C.; You, S.-L. Catalytic
Asymmetric Dearomatization by Transition-Metal Catalysis: A
Method for Transformations of Aromatic Compounds. Chem.
2016, 1, 830−857. (c) Sun, W.; Li, G.; Hong, L.; Wang, R.
Asymmetric Dearomatization of Phenols. Org. Biomol. Chem. 2016,
14, 2164−2176. (d) Wertjes, W. C. E.; Southgate, H.; Sarlah, D.
Recent Advances in Chemical Dearomatization of Nonactivated
Arenes. Chem. Soc. Rev. 2018, 47, 7996−8017. (e) Zhuo, C.-X.;
Zheng, C.; You, S.-L. Transition-Metal-Catalyzed Asymmetric Allylic
Dearomatization Reactions. Acc. Chem. Res. 2014, 47, 2558−2573.
(f) Zheng, C.; You, S.-L. Catalytic Asymmetric Dearomatization
(CADA) Reaction-Enabled Total Synthesis of Indole-Based Natural
Products. Nat. Prod. Rep. 2019, DOI: 10.1039/C8NP00098K.
(g) Ramesha, A. R.; Vishnumurthy, K.; Row, T. N. G.;
Chandrasekaran, S. Interesting Reaction of 2,2’-Binaphthol with
1,2-Dibromoethane: Synthesis of a Novel Spirodienone. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1999, 38B, 1015−1017.
(10) Yang, L.; Zheng, H.; Luo, L.; Nan, J.; Liu, J.; Wang, Y.; Luan,
X. Palladium-Catalyzed Dynamic Kinetic Asymmetric Transforma-
tion of Racemic Biaryls: Axial-to-Central Chirality Transfer. J. Am.
Chem. Soc. 2015, 137, 4876−4879.
(11) Pizzolato, S. F.; Stacko, P.; Kistemaker, J. C. M.; van
Leeuwen, T.; Otten, E.; Feringa, B. L. Central-to-Helical-to-Axial-to-
Central Transfer of Chirality with a Photoresponsive Catalyst. J. Am.
Chem. Soc. 2018, 140, 17278−17289.
(12) For selected recent papers, see: (a) Yoshida, M.; Higuchi, M.;
Shishido, K. Highly Diastereoselective Synthesis of Tetrahydroben-
zofuran Derivatives by Palladium-Catalyzed Reaction of Propargylic
Esters with Substituted β-Dicarbonyl Compounds. Tetrahedron
2010, 66, 2675−2682. (b) Nishioka, N.; Koizumi, T. Selective
Synthesis of Functionalized Allylic Compounds by Pd(0)-Catalyzed
Three-Component Reaction of Methyl Propargyl Carbonate with
Phenols and Nucleophiles. Tetrahedron Lett. 2011, 52, 3662−3665.
(c) Montgomery, T. D.; Nibbs, A. E.; Zhu, Y.; Rawal, V. H. Rapid
Access to Spirocyclized Indolenines via Palladium-Catalyzed
Cascade Reactions of Tryptamine Derivatives and Propargyl
Carbonate. Org. Lett. 2014, 16, 3480−3483. (d) Kenny, M.;
Christensen, J.; Coles, S. J.; Franckevicius, V. Regioswitchable
Palladium-Catalyzed Decarboxylative Coupling of 1,3-Dicarbonyl
Compounds. Org. Lett. 2015, 17, 3926−3929. (e) Ding, L.; You, S.-
L. Palladium(0)-Catalyzed Intermolecular Cascade Dearomatization
Reaction of β-Naphthol Derivatives with Propargyl Carbonates. Org.
Lett. 2018, 20, 6206−6210. (f) Ding, L.; Gao, R.-D.; You, S.-L.
Palladium(0)-Catalyzed Intermolecular Asymmetric Cascade Dear-
omatization Reaction of Indoles with Propargyl Carbonate. Chem. -
Eur. J. 2019, 25, 4330−4334.
(13) The reaction was performed at 50 °C. DCE was used instead
of DCM as solvent since low yields were obtained using substituted
propargyl carbonates as substrates at room temperature.
(14) The Z configuration of 3b was confirmed by NOE
experiment. The absolute configuration was confirmed by trans-
formation of 3a to 12. See SI for details.
(15) Due to lower Z/E ratio of products 6a, 6d, 6g, and 6i−6l, we
could not separate the product Z from the Z/E mixture. The HPLC
traces were omitted since the spectra were overlapped.
(16) CCDC 1940195.
F
DOI: 10.1021/acs.orglett.9b03558
Org. Lett. XXXX, XXX, XXX−XXX