Enantioenriched 1-Tetralones via Rhodium-Catalyzed Arylative Cascade Desymmetrization/Acylation of Alkynylmalonates

Article abstract of DOI:10.1021/acs.orglett.9b03153

An efficient atom-economic rhodium-catalyzed asymmetric arylative cyclization to access enantioenriched 1-tetralones, bearing a quaternary carbon stereocenter, is described, involving a highly regioselective alkyne insertion, a 1,4-Rh shift, and an acylation step via the desymmetrization of the malonate moiety thanks to an appropriate chiral diene ligand.

Full text of DOI:10.1021/acs.orglett.9b03153

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Enantioenriched 1‑Tetralones via Rhodium-Catalyzed Arylative
Cascade Desymmetrization/Acylation of Alkynylmalonates
Aymane Selmani and Sylvain Darses*
́
PSL Universite Paris, Chimie ParisTech-CNRS, Institute of Chemistry for Life and Health Sciences (i-CLeHS), 11 rue Pierre et
Marie Curie, 75005, Paris, France
*
S Supporting Information
ABSTRACT: An efficient atom-economic rhodium-catalyzed
asymmetric arylative cyclization to access enantioenriched 1-
tetralones, bearing a quaternary carbon stereocenter, is described,
involving a highly regioselective alkyne insertion, a 1,4-Rh shift, and
an acylation step via the desymmetrization of the malonate moiety
thanks to an appropriate chiral diene ligand.
nantioenriched 1-tetralones are useful building blocks in
organic synthesis and represent important scaffolds in a
Scheme 1. Proposed Approach to Chiral 1-Tetralones via
Arylative Desymmetrization
1
E
wide range of natural products and in molecules of medicinal
2
and agrochemical interest. While a variety of methodologies
3
have been described to prepare racemic 1-tetralones, the
access routes to enantiomerically enriched 1-tetralones by
asymmetric catalysis are more rare and consist mainly in the
functionalization of the 2-position of already formed
4
tetralones. Given the importance of such substrates, more
direct asymmetric and catalytic pathways for synthesizing the
chiral 1-tetralone backbone in a single step, via the formation
of multiple C−C bonds (cascade reaction) from simple
substrates, would be highly desirable but are still in an early
stage. Some approaches for the catalytic formation of chiral
tetralones by intramolecular asymmetric cyclization reactions
have been described, but require multiple steps and tedious
8
,11
molecules,
but catalytic arylative cyclizations involving
12
desymmetrization have been scarcely explored.
5
preparation of the starting materials. To our knowledge, the
In order to access tetralones via the previously proposed
approach (Scheme 1), it is essential to control the
regioselectivity of the alkyne insertion. This regioselectivity
can be modulated by tuning the steric and electronic properties
of the R substituent. We had previously shown that, in the
presence of a 2-methylphenyl substituent, the aromatic ring of
the boronic acid was introduced selectively into position 2 in
only catalytic and enantioselective approach involving the
formation of multiple C−C bonds from simple substrates
consists of Tamura cycloadditions between homophthalic
6
13
anhydrides and nitroolefins or α,β-unsaturated N-trityl
7
imines.
In our continuous work in rhodium-catalyzed arylative
8c
8
the arylative cyclization of N-bridged yne-enoate derivatives.
cyclization, we sought to develop an enantioselective synthesis
However, under conventional conditions, the cyclization of
substrate 1, where R is 2-methylphenyl, in the presence of
phenylboronic acid leads to the formation of the expected
tetralone 2 accompanied by uncyclized compound 3, resulting
from the reverse insertion, in a ratio of 2:1 (Table 1, entry 1).
In order to promote the selective formation of 2 over 3,
other R substituents have been evaluated (Table 1), an
aliphatic substituent giving the opposite insertion. In the
presence of a 4-trifluomethylphenyl substituent (entry 2), no
cyclization occurred, and only regioisomers issued from the
insertion/protonation process were observed. In order to force
of chiral 1-tetralones from easily available propynylmalonates
and arylboronic acids (Scheme 1). This strategy relies on a
regioselective control of alkyne insertion, rhodium 1,4-
8
c,d,9
shift
to generate a new arylrhodium intermediate, and
finally desymmetrization by reaction of the arylrhodium with
one ester function, generating the ketone functionality and
creating a valuable quaternary stereogenic center. Such an
approach has been described by Murakami for the formation of
racemic 1-tetralones using symmetrical alkynes, but a mixture
of products, issued from nonregioselective insertion, was
8c
10
observed starting from unsymmetrical alkynes.
Palladium- or rhodium-catalyzed arylative cyclizations of
bifunctionalized substrates, initiated by organoboron reagents,
constitute a versatile approach to construct complex chiral
Received: September 5, 2019
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03153
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Formation of 1-Tetralones by Forcing the
Regioselectivity of Alkyne Insertion
Table 2. Chiral Dienes in the Desymmetrization of
Alkynylmalonates
a
a
b
c
entry
R
yield
2:3 ratio
1
2
3
4
5
6
7
8
9
2-MeC H
90
63
e
72
56
nd
nd
nd
2:1
d
−
2:1
2:1
2:1
2:1
2:1
6
4
4-CF C H
4
3
6
CO Me
2
2-Me-4-CF C H
3
3
6
2-iPrC H
6
4
f
1-Np
b
c
entry
Ln or Ar-MSBod (Ar = )
yield (%)
ee (%)
f
2-MeOC H
6
4
f
1
2
3
4
5
6
7
8
L1
L2
L3
L4
79
77
83
80
90
78
58
67
54
75
94
2
42
47
46
38
45
35
13
54
73
85
2,6-Me C H
3
2
6
2-CF C H
4
61
68
75
>99:1
>99:1
>99:1
3
6
1
1
0
1
2,4-(CF ) C H
3 2 6
3
g
2,4-(CF ) C H
3
2
6
3
1-Np
a
The reaction was conducted with 1 (0.3 mmol), phenylboronic acid
0.6 mmol), and [Rh(cod)OH] (1.5 mol %), in degassed methanol
at 60 °C for 14 h. Isolated yield. Ratio determined by H NMR.
:2.5 ratio of 3 and its regioisomer. Untractable mixture of
products. Not determined. Benzyl substituent in place of methyl and
E = CO Et.
2-Me-4-MeOC H3
6
(
2
b
c
1
2-iPrOC H4
6
d
e
2,6-(iPrO) C H
3
1
2
6
f
g
9
10
2,6-(Me) C H
2
6
3
2,6-(MeO) C H
2 6 3
2
1
1
Anthracen-9-yl
a
The reaction was conducted with 1a (0.3 mmol) and phenylboronic
the expected insertion through 1,4-addition, an ester
substituent was tested (entry 3), but an untractable mixture
of products was obtained. For most of the R substituents
evaluated, the 2:3 ratio was not modified and remained
desperately equal to 2:1 (entries 4−8). We were pleased to
find that an aromatic substituent, bearing at least a
trifluoromethyl group in the ortho position, afforded
exclusively the expected tetralone 2 with a good yield (entries
acid (0.6 mmol), in the presence of in situ generated chiral L*−
rhodium complex (3 mol % Rh) in degassed methanol at 60 °C.
b
c
Isolated yields. Ee were determined by HPLC analysis using a chiral
stationary phase (see Supporting Information).
aliphatic (Me, nBu, or CH CH Ph) or benzyl substituents
2
2
reacted smoothly to afford the expected chiral 1-tetralones with
high yields and enantioselectivities ranging from 84% to 90%,
depending on the arylboronic acid used. Even if tetralone 2d,
having a OBn substituent at the malonate junction, is obtained
with a good yield, the enantiomeric excess is meanwhile
moderate (64%). On the other hand, very good enantiose-
lectivities have been obtained with NHAc or NHBoc
substituents (85 to 96% ee), allowing an easy access to
enantiomerically enriched cyclic exotic amino acids bearing a
tetralone moiety. Compound 2f was also obtained on a larger
scale, starting from 1.2 mmol of starting material, with a 90%
yield and no erosion of the enantioselectivity.
9
and 10), cleaner reactions being observed in the case of 2,4-
bis(trifluoromethyl)phenyl (entry 10). This observation seems
general, as total regioselectivity, favoring the formation of
tetralone 2, is also observed when the methyl substituent on
the malonate is replaced by a benzyl group (entry 11).
After this successful switch in the regioselective insertion of
the alkyne moiety allowing selective formation of 1-tetralones
from alkynylmalonates, we envisioned the development of an
asymmetric version to access enantioenriched 1-tetralones
(
Table 2). Among the chiral ligands evaluated, only dienes led
14
to acceptable enantiomeric excesses. The disubstituted chiral
dienes L1−L4, developed by Hayashi, did not lead to
satisfactory results in term of enantioselectivity, the ee being
15
The structure of 1-tetralone 2j was confirmed unambigu-
ously by single-crystal X-ray analysis (Figure 1). The absolute
configuration of the stereogenic center of 2j was determined to
be (R) when anthracen-9-yl-MSBod was used as ligand.
We next examined the reactivity of the 1-tetralones, which
can further be functionalized thanks to its versatile functional
groups such as an ester, a ketone, and an exocyclic olefin. As an
illustration, the reactivity of the exocyclic double bond has
less than 50% (entries 1−4). It is only by the use of the C -
1
16
symmetric chiral Ar-MSBod dienes that significant enantio-
selectivities have been observed, in particular those bearing an
aromatic disubstituted in both ortho positions (entries 5−11).
We were pleased to find that the use of the chiral diene having
an anthracen-9-yl substituent, a very bulky group, allowed not
only an excellent yield but also a 85% enantiomeric excess in
the arylative cyclization of alkynylmalonate 1a (entry 11). It
should be noted that the substituent on the ester function of
the malonate has an influence on the enantioselectivity of the
reaction: with dimethyl or diethyl malonates 1a identical ee’s
were observed (85% ee) while, with a diisopropyl malonate,
the enantiomeric excess is only 68%.
17
been studied: the ruthenium-catalyzed oxidative cleavage of
tetralone 2p gave the corresponding chiral dihydro-
naphthoquinone 3p in 74% yield, with no erosion of the
enantioselectivity, a motif prevalent in a wide range of natural
18
and synthetic compounds (Scheme 3).
In summary, we have described, for the first time, an efficient
atom-economic asymmetric arylative cyclization to access
chiral enantioenriched 1-tetralones bearing a quaternary
carbon stereocenter. The success of the overall process relies
on a highly regioselective alkyne insertion, a 1,4-Rh shift, and
With these reaction conditions in hand, we examined the
reactivity of diversely substituted alkynylmalonates 1 with
arylboronic acids (Scheme 2). Alkynylmalonates bearing
B
DOI: 10.1021/acs.orglett.9b03153
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Chiral 1-Tetralones from Rh/Chiral Diene-
Catalyzed Arylative Desymmetrization of 1
Experimental procedures, description of the compounds,
and X-ray diffraction of 2j (PDF)
a
Accession Codes
CCDC 1926608 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-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
*
E-mail: sylvain.darses@chimie-paristech.fr.
ORCID
Sylvain Darses: 0000-0003-3350-1736
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́
A.S. thanks the Minister
̀
e de l’Education Nationale et de
l’Enseignement Super
́
ieur et de la Recherche for a grant. We
gratefully acknowledge Geoffrey Gontard and Lise-Marie
Chamoreau for the X-ray analyses (Sorbonne Universite,
Paris).
́
a
The reactions were conducted with 1 (0.3 mmol) and arylboronic
acid (0.6 mmol), in the presence of in situ generated chiral L*−
rhodium complex (3 mol % Rh) in degassed methanol at 60 °C.
Isolated yields indicated and ee were determined by HPLC analysis
using a chiral stationary phase (see Supporting Information). 90%
yield and 90% ee on reaction conducted with 1.2 mmol of starting
material.
REFERENCES
■
(1) For some recent examples, see: (a) Taber, G. P.; Pfisterer, D. M.;
b
Colberg, J. C. A New and Simplified Process for Preparing N-[4-(3,4-
Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine
and a Telescoped Process for the Synthesis of (1S-cis)-4-(3,4-
Dichlorophenol)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine
Mandelate: Key Intermediates in the Synthesis of Sertraline
Hydrochloride. Org. Process Res. Dev. 2004, 8, 385−388. (b) Yang,
R.-Y.; Kizer, D.; Wu, H.; Volckova, E.; Miao, X.-S.; Ali, S. M.;
Tandon, M.; Savage, R. E.; Chan, T. C. K.; Ashwell, M. A. Synthetic
methods for the preparation of ARQ 501 (β-Lapachone) human
blood metabolites. Bioorg. Med. Chem. 2008, 16, 5635−5643.
(
c) Pinto-Bazurco Mendieta, M. A. E.; Negri, M.; Jagusch, C.;
Muller-Vieira, U.; Lauterbach, T.; Hartmann, R. W. Synthesis,
̈
Biological Evaluation, and Molecular Modeling of Abiraterone
Analogues: Novel CYP17 Inhibitors for the Treatment of Prostate
Cancer. J. Med. Chem. 2008, 51, 5009−5018. (d) Ortega, R.; Hubner,
̈
H.; Gmeiner, P.; Masaguer, C. F. Aromatic ring functionalization of
benzolactam derivatives: New potent dopamine D3 receptor ligands.
Bioorg. Med. Chem. Lett. 2011, 21, 2670−2674. (e) Cueva, J. P.;
Gallardo-Godoy, A.; Juncosa, J. I., Jr.; Vidi, P. A.; Lill, M. A.; Watts, V.
J.; Nichols, D. E. Probing the Steric Space at the Floor of the D1
Dopamine Receptor Orthosteric Binding Domain: 7α-,7β-,8α-, and
Figure 1. X-ray crystal structure of (R)-2j.
Scheme 3. Formation of Chiral Dihydronaphthoquinones
8
β-Methyl Substituted Dihydrexidine Analogues. J. Med. Chem. 2011,
4, 5508−5521. (f) Odagi, M.; Furukori, K.; Takayama, K.; Noguchi,
5
K.; Nagasawa, K. Total Synthesis of Rishirilide B by Organocatalytic
Oxidative Kinetic Resolution: Revision of Absolute Configuration of
(
(
+)-Rishirilide B. Angew. Chem., Int. Ed. 2017, 56, 6609−6612.
g) Umihara, H.; Yokoshima, S.; Inoue, M.; Fukuyama, T. Total
Synthesis of (−)-Morphine. Chem. - Eur. J. 2017, 23, 6993−6995.
(2) (a) Allen, J. G.; Danishefsky, S. J. The Total Synthesis of
(±)-Rishirilide B. J. Am. Chem. Soc. 2001, 123, 351−352. (b) Charest,
M. G.; Siegel, D. R.; Myers, A. G. Synthesis of (−)-Tetracycline. J.
Am. Chem. Soc. 2005, 127, 8292−8293. (c) Yao, S.; Tang, C.-P.; Ke,
C.-Q.; Ye, Y. Abietane Diterpenoids from the Bark of Cryptomeria
fortunei. J. Nat. Prod. 2008, 71, 1242−1246. (d) Stoessl, A.; Stothers,
J. B. Tetrahydroaltersolanol B, a hexahydroanthronol from Alter-
nariasolani. Can. J. Chem. 1983, 61, 378−382. (e) Devkota, K. P.;
Covell, D.; Ransom, T.; McMahon, J. B.; Beutler, J. A. Growth
an acylation step via the desymmetrization of the malonate
moiety thanks to an appropriate chiral diene ligand.
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.9b03153.
C
DOI: 10.1021/acs.orglett.9b03153
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Inhibition of Human Colon Carcinoma Cells by Sesquiterpenoids and
(5) (a) Ishida, N.; Sawano, S.; Murakami, M. Synthesis of 3,3-
disubstituted α-tetralones by rhodium-catalysed reaction of 1-(2-
haloaryl)cyclobutanols. Chem. Commun. 2012, 48, 1973−1975.
(b) Hu, Z.-P.; Zhuang, Z.; Liao, W.-W. Asymmetric Synthesis of
Dihydronaphthoquinones Containing Adjacent Stereocenters via a
Sulfa-Michael Addition Triggered Ring-Expansion Approach. J. Org.
Chem. 2015, 80, 4627−4637. (c) Zhang, G.; Yang, S.; Zhang, X.; Lin,
Q.; Das, D. K.; Liu, J.; Fang, X. Dynamic Kinetic Resolution Enabled
by Intramolecular Benzoin Reaction: Synthetic Applications and
Mechanistic Insights. J. Am. Chem. Soc. 2016, 138, 7932−7938.
(6) Nath, U.; Pan, S. C. Organocatalytic Asymmetric Tamura
Cycloaddition with α-Branched Nitroolefins: Synthesis of Function-
alized 1-Tetralones. J. Org. Chem. 2017, 82, 3262−3269.
Tetralones of Zygogynum calothyrsum. J. Nat. Prod. 2013, 76, 710−
714. (f) Leng, J.; Qin, H.-L.; Zhu, K.; Jantan, I.; Hussain, M. A.; Sher,
M.; Amjad, M. W.; Naeem-ul-Hassan, M.; Ahmad, W.; Bukhari, S. N.
A. Evaluation of multifunctional synthetic tetralone derivatives for
treatment of Alzheimer’s disease. Chem. Biol. Drug Des. 2016, 88,
8
89−898. (g) Rajagopalan, N.; Nelson, K. M.; Douglas, A. F.;
Jheengut, V.; Alarcon, I. Q.; McKenna, S. A.; Surpin, M.; Loewen, M.
C.; Abrams, S. R. Abscisic Acid Analogues That Act as Universal or
Selective Antagonists of Phytohormone Receptors. Biochemistry 2016,
5
5, 5155−5164. (h) Legoabe, L. J.; Van der Walt, M. M.;
Terre’Blanche, G. Evaluation of 2-benzylidene-1-tetralone derivatives
as antagonists of A and A adenosine receptors. Chem. Biol. Drug Des.
1
2
2
(
018, 91, 234−244.
(7) Collar, A. G.; Trujillo, C.; Connon, S. J. Highly Enantio- and
Diastereoselective Catalytic Asymmetric Tamura Cycloaddition
Reactions. Chem. - Eur. J. 2019, 25, 7270−7274.
3) For some examples, see: (a) Liard, A.; Quiclet-Sire, B.; Saicic, R.
N.; Zard, S. Z. A new synthesis of α-tetralones. Tetrahedron Lett.
1
997, 38, 1759−1762. (b) Nishimura, T.; Ohe, K.; Uemura, S.
(8) (a) Serpier, F.; Flamme, B.; Brayer, J.-L.; Folleas, B.; Darses, S.
́
Chiral Pyrrolidines and Piperidines from Enantioselective Rhodium-
Oxidative Transformation of tert-Cyclobutanols by Palladium
Catalysis under Oxygen Atmosphere. J. Org. Chem. 2001, 66,
Catalyzed Cascade Arylative Cyclization. Org. Lett. 2015, 17, 1720−
́
1723. (b) Serpier, F.; Brayer, J.-L.; Folleas, B.; Darses, S. Access to
1455−1465. (c) Yu, J.; Zhao, H.; Liang, S.; Bao, X.; Zhu, C. A
facile and regioselective synthesis of 1-tetralones via silver-catalyzed
ring expansion. Org. Biomol. Chem. 2015, 13, 7924−7927. (d) Xia, Y.;
Lu, G.; Liu, P.; Dong, G. Catalytic activation of carbon−carbon bonds
in cyclopentanones. Nature 2016, 539, 546−550. (e) Chang, S.;
Holmes, M.; Mowat, J.; Meanwell, M.; Britton, R. α-Arylation and
Ring Expansion of Annulated Cyclobutanones: Stereoselective
Synthesis of Functionalized Tetralones. Angew. Chem., Int. Ed. 2017,
Polyfunctionalized Chiral Piperidines through Enantioselective
Addition−Carbocyclization Cascade Reaction Catalyzed by a
Rhodium(I)−Diene Complex. Org. Lett. 2015, 17, 5496−5499.
(c) Claraz, A.; Serpier, F.; Darses, S. Organoboron Initiated Rh-
Catalyzed Asymmetric Cascade Reactions: A Subtle Switch in
Regioselectivity Leading to Chiral 3-Benzazepine Derivatives. ACS
Catal. 2017, 7, 3410−3413. (d) Selmani, A.; Serpier, F.; Darses, S.
From Tetrahydrofurans to Tetrahydrobenzo[d]oxepines via a
Regioselective Control of Alkyne Insertion in Rhodium-Catalyzed
Arylative Cyclization. J. Org. Chem. 2019, 84, 4566−4574.
(9) For some examples of reactions involving a 1,4-shift, see:
(a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. Rhodium-
Catalyzed Hydroarylation of Alkynes with Arylboronic Acids: 1,4-
Shift of Rhodium from 2-Aryl-1-alkenylrhodium to 2-Alkenylarylrho-
dium Intermediate. J. Am. Chem. Soc. 2001, 123, 9918−9919.
(b) Shintani, R.; Okamoto, K.; Hayashi, T. Rhodium-Catalyzed
Isomerization of α-Arylpropargyl Alcohols to Indanones: Involve-
ment of an Unexpected Reaction Cascade. J. Am. Chem. Soc. 2005,
127, 2872−2873. (c) Shintani, R.; Tsurusaki, A.; Okamoto, K.;
Hayashi, T. Highly Chemo- and Enantioselective Arylative Cycliza-
tion of Alkyne-Tethered Electron-Deficient Olefins Catalyzed by
Rhodium Complexes with Chiral Dienes. Angew. Chem., Int. Ed. 2005,
44, 3909−3912. (d) Matsuda, T.; Shigeno, M.; Murakami, M.
Asymmetric Synthesis of 3,4-Dihydrocoumarins by Rhodium-
Catalyzed Reaction of 3-(2-Hydroxyphenyl)cyclobutanones. J. Am.
Chem. Soc. 2007, 129, 12086−12087. (e) Panteleev, J.; Menard, F.;
Lautens, M. Ligand Control in Enantioselective Desymmetrization of
Bicyclic Hydrazines: Rhodium(I)-Catalyzed Ring-Opening versus
Hydroarylation. Adv. Synth. Catal. 2008, 350, 2893−2902. (f) Sasaki,
K.; Nishimura, T.; Shintani, R.; Kantchev, E. A. B.; Hayashi, T.
Rhodium/diene-catalyzed tandem 1,4-shift/1,4-addition of (E)-1,2-
diphenylethenylboronic acid to enones: density functional theory
modeling and asymmetric catalysis. Chem. Sci. 2012, 3, 1278−1283
and references cited .
5
6, 748−752. (f) Arunprasath, D.; Devi Bala, B.; Sekar, G.
Stereoselective Construction of α-Tetralone-Fused Spirooxindoles
via Pd-Catalyzed Domino Carbene Migratory Insertion/Conjugate
Addition Sequence. Org. Lett. 2017, 19, 5280−5283. (g) Plaza, M.;
Paraja, M.; Florentino, L.; Valdes, C. Domino Synthesis of Benzo-
́
Fused β,γ-Unsaturated Ketones from Alkenylboronic Acids and N-
Tosylhydrazone-Tethered Benzonitriles. Org. Lett. 2019, 21, 632−
6
(
35.
4) For some examples, see: (a) Lan, Q.; Wang, X.; Shirakawa, S.;
Maruoka, K. Phase-Transfer Catalyzed Asymmetric Conjugate
Additions of β-Ketoesters to Acetylenic Ketones. Org. Process Res.
Dev. 2010, 14, 684−686. (b) Odagi, M.; Furukori, K.; Watanabe, T.;
Nagasawa, K. Asymmetric α-Hydroxylation of Tetralone-Derived β-
Ketoesters by Using a Guanidine−Urea Bifunctional Organocatalyst
in the Presence of Cumene Hydroperoxide. Chem. - Eur. J. 2013, 19,
16740−16745. (c) Roiban, G.-D.; Agudo, R.; Ilie, A.; Lonsdale, R.;
Reetz, M. T. CH-activating oxidative hydroxylation of 1-tetralones
and related compounds with high regio- and stereoselectivity. Chem.
Commun. 2014, 50, 14310−14313. (d) Chen, W.; Chen, M.; Hartwig,
J. F. Diastereo- and Enantioselective Iridium-Catalyzed Allylation of
Cyclic Ketone Enolates: Synergetic Effect of Ligands and Barium
Enolates. J. Am. Chem. Soc. 2014, 136, 15825−15828. (e) Odagi, M.;
Furukori, K.; Yamamoto, Y.; Sato, M.; Iida, K.; Yamanaka, M.;
Nagasawa, K. Origin of Stereocontrol in Guanidine-Bisurea Bifunc-
tional Organocatalyst That Promotes α-Hydroxylation of Tetralone-
Derived β-Ketoesters: Asymmetric Synthesis of β- and γ-Substituted
Tetralone Derivatives via Organocatalytic Oxidative Kinetic Reso-
lution. J. Am. Chem. Soc. 2015, 137, 1909−1915. (f) Sim, S.-B. D.;
Wang, M.; Zhao, Y. Phase-Transfer-Catalyzed Enantioselective α-
Hydroxylation of Acyclic and Cyclic Ketones with Oxygen. ACS
Catal. 2015, 5, 3609−3612. (g) Yu, L.; Wu, X.; Kim, M. J.;
Vaithiyanathan, V.; Liu, Y.; Tan, Y.; Qin, W.; Song, C. E.; Yan, H.
Asymmetric Synthesis of 2-Thiocyanato-2-(1-aminoalkyl)-substituted
(10) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M. Ketone
Synthesis by Intramolecular Acylation of Organorhodium(I) with
Ester. J. Am. Chem. Soc. 2005, 127, 1390−1391.
(11) For some examples, see: (a) Cauble, D. F.; Gipson, J. D.;
Krische, M. J. Diastereo- and Enantioselective Catalytic Carbome-
tallative Aldol Cycloreduction: Tandem Conjugate Addition−Aldol
Cyclization. J. Am. Chem. Soc. 2003, 125, 1110−1111. (b) Shintani,
R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. Catalytic
Asymmetric Arylative Cyclization of Alkynals: Phosphine-Free
Rhodium/Diene Complexes as Efficient Catalysts. J. Am. Chem. Soc.
2005, 127, 54−55. (c) Shintani, R.; Tsurusaki, A.; Okamoto, K.;
Hayashi, T. Highly Chemo- and Enantioselective Arylative Cycliza-
tion of Alkyne-Tethered Electron-Deficient Olefins Catalyzed by
Rhodium Complexes with Chiral Dienes. Angew. Chem., Int. Ed. 2005,
44, 3909−3912. (d) Tsukamoto, H.; Matsumoto, T.; Kondo, Y.
1-Tetralones and 1-Indanones with Tetrasubstituted Carbon Stereo-
genic Centers via Cooperative Cation-Binding Catalysis. Adv. Synth.
Catal. 2017, 359, 1879−1891. (h) Shang, M.; Cao, M.; Wang, Q.;
Wasa, M. Enantioselective Direct Mannich-Type Reactions Catalyzed
by Frustrated Lewis Acid/Brønsted Base Complexes. Angew. Chem.,
Int. Ed. 2017, 56, 13338−13341. (i) Rao, X.; Li, N.; Bai, H.; Dai, C.;
Wang, Z.; Tang, W. Efficient Synthesis of (−)-Corynoline by
Enantioselective Palladium-Catalyzed α-Arylation with Sterically
Hindered Substrates. Angew. Chem., Int. Ed. 2018, 57, 12328−12332.
D
DOI: 10.1021/acs.orglett.9b03153
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Enantioselective Arylative Cyclization of Allenyl Aldehydes with
Arylboronic Acids under Pd(II)-diphosphine Catalysis. Org. Lett.
Asymmetric Arylation of N-Tosylarylimines. J. Am. Chem. Soc. 2004,
126, 13584−13585. (b) Okamoto, K.; Hayashi, T.; Rawal, V. H.
Simple Chiral Diene Ligands Provide High Enantioselectivities in
Transition-Metal-Catalyzed Conjugate Addition Reactions. Org. Lett.
2008, 10, 4387−4389. (c) Okamoto, K.; Hayashi, T.; Rawal, V. H.
Electronic and steric tuning of chiral diene ligands for rhodium-
catalyzed asymmetric arylation of imines. Chem. Commun. 2009,
4815−4817. (d) Roy, I. D.; Burns, A. R.; Pattison, G.; Michel, B.;
Parker, A. J.; Lam, H. W. A second-generation ligand for the
enantioselective rhodium-catalyzed addition of arylboronic acids to
alkenylazaarenes. Chem. Commun. 2014, 50, 2865−2868.
2
008, 10, 1047−1050. (e) Shintani, R.; Isobe, S.; Takeda, M.;
Hayashi, T. Rhodium-Catalyzed Asymmetric Synthesis of Spirocarbo-
cycles: Arylboron Reagents as Surrogates of 1,2-Dimetalloarenes.
Angew. Chem., Int. Ed. 2010, 49, 3795−3798. (f) Williams, F. J.; Jarvo,
E. R. Palladium-Catalyzed Cascade Reaction for the Synthesis of
Substituted Isoindolines. Angew. Chem., Int. Ed. 2011, 50, 4459−4462.
(g) Shen, K.; Han, X.; Lu, X. Cationic Pd(II)-Catalyzed Highly
Enantioselective Arylative Cyclization of Alkyne-Tethered Enals or
Enones Initiated by Carbopalladation of Alkynes with Arylboronic
Acids. Org. Lett. 2012, 14, 1756−1759. (h) Johnson, T.; Choo, K.-L.;
Lautens, M. Rhodium-Catalyzed Arylative Cyclization for the
Enantioselective Synthesis of (Trifluoromethyl)cyclobutanols. Chem.
(16) (a) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. Readily
Available [2.2.2]-Bicyclooctadienes as New Chiral Ligands for Ir(I):
Catalytic, Kinetic Resolution of Allyl Carbonates. J. Am. Chem. Soc.
2004, 126, 1628−1629. (b) Gendrineau, T.; Chuzel, O.; Eijsberg, H.;
-
Eur. J. 2014, 20, 14194−14197. (i) Li, Y.; Xu, M.-H. Rhodium-
Catalyzed Asymmetric Tandem Cyclization for Efficient and Rapid
Access to Underexplored Heterocyclic Tertiary Allylic Alcohols
Containing a Tetrasubstituted Olefin. Org. Lett. 2014, 16, 2712−
Genet, J.-P.; Darses, S. C -symmetric monosubstituted chiral diene
1
ligands in asymmetric rhodium-catalyzed 1,4-addition reactions.
Angew. Chem., Int. Ed. 2008, 47, 7669−7672. (c) Selmani, A.;
Serpier, F.; Darses, S. Chiral Bicyclo[2.2.2]octa-2,5-dienyltrifluor-
2
715. (j) Zhang, X.; Han, X.; Lu, X. Cationic Pd(II)-Catalyzed
oborate Derivative as a Useful and Stable Precursor of C -Symmetric
Cyclization of N-Tosyl-aniline Tethered Allenyl Aldehydes with
Arylboronic Acids: Diastereo- and Enantioselective Synthesis of
Tetrahydroquinoline Derivatives. Org. Lett. 2015, 17, 3910−3913.
1
Chiral Dienes. Org. Lett. 2019, 21, 4378−4382.
(17) Yang, D.; Zhang, C. Ruthenium-Catalyzed Oxidative Cleavage
of Olefins to Aldehydes. J. Org. Chem. 2001, 66, 4814−4818.
(
12) (a) Bocknack, B. M.; Wang, L.-C.; Krische, M. J.
́
18) (a) Fronza, M.; Murillo, R.; Slusarczyk, S.; Adams, M.;
(
Desymmetrization of enone-diones via rhodium-catalyzed diastereo-
and enantioselective tandem conjugate addition-aldol cyclization.
Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 5421−5424. (b) He, Z.-T.;
Tian, B.; Fukui, Y.; Tong, X.; Tian, P.; Lin, G.-Q. Rhodium-Catalyzed
Asymmetric Arylative Cyclization of meso-1,6-Dienynes Leading to
Enantioenriched cis-Hydrobenzofurans. Angew. Chem., Int. Ed. 2013,
Hamburger, M.; Heinzmann, B.; Laufer, S.; Merfort, I. In vitro
cytotoxic activity of abietane diterpenes from Peltodon longipes as
well as Salvia miltiorrhiza and Salvia sahendica. Bioorg. Med. Chem.
2
011, 19, 4876−4881. (b) Nematollahi, A.; Aminimoghadamfarouj,
N.; Wiart, C. Reviews on 1,4-naphthoquinones from Diospyros L. J.
Asian Nat. Prod. Res. 2012, 14, 80−88. (c) Widhalm, J. R.; Rhodes, D.
Biosynthesis and molecular actions of specialized 1,4-naphthoquinone
natural products produced by horticultural plants. Hortic. Res. 2016, 3,
5
2, 5314−5318. (c) Keilitz, J.; Newman, S. G.; Lautens, M.
Enantioselective Rh-Catalyzed Domino Transformations of Alkynyl-
cyclohexadienones with Organoboron Reagents. Org. Lett. 2013, 15,
16046.
1148−1151. (d) Partridge, B. M.; Solana Gonzalez, J.; Lam, H. W.
́
Iridium-Catalyzed Arylative Cyclization of Alkynones by 1,4-Iridium
Migration. Angew. Chem., Int. Ed. 2014, 53, 6523−6527. (e) Clarke,
C.; Incerti-Pradillos, C. A.; Lam, H. W. Enantioselective Nickel-
Catalyzed anti-Carbometallative Cyclizations of Alkynyl Electrophiles
Enabled by Reversible Alkenylnickel E/Z Isomerization. J. Am. Chem.
Soc. 2016, 138, 8068−8071. (f) Karad, S. N.; Panchal, H.; Clarke, C.;
Lewis, W.; Lam, H. W. Enantioselective Synthesis of Chiral
Cyclopent-2-enones by Nickel-Catalyzed Desymmetrization of
Malonate Esters. Angew. Chem., Int. Ed. 2018, 57, 9122−9125.
(13) For the regioselective insertion of aryl-substituted alkynes, see:
(a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. Rhodium-
Catalyzed Hydroarylation of Alkynes with Arylboronic Acids: 1,4-
Shift of Rhodium from 2-Aryl-1-alkenylrhodium to 2-Alkenylarylrho-
dium Intermediate. J. Am. Chem. Soc. 2001, 123, 9918−9919.
(b) Lautens, M.; Yoshida, M. Regioselective Rhodium-Catalyzed
Addition of Arylboronic Acids to Alkynes with a Pyridine-Substituted
Water-Soluble Ligand. Org. Lett. 2002, 4, 123−125. (c) Lautens, M.;
Yoshida, M. Rhodium-Catalyzed Addition of Arylboronic Acids to
Alkynyl Aza-Heteroaromatic Compounds in Water. J. Org. Chem.
2
003, 68, 762−769. (d) Genin, E.; Michelet, V.; Genet, J.-P. Efficient
synthesis of trisubstituted alkenes in an aqueous-organic system using
a versatile and recyclable Rh/m-TPPTC catalyst. Tetrahedron Lett.
2
004, 45, 4157−4161. For the specific case of propargylic amines,
see: (e) Arcadi, A.; Aschi, M.; Chiarini, M.; Ferrara, G.; Marinelli, F.
Rhodium- and Palladium-Catalyzed Hydroarylation of Propargylic
Amines with Arylboronic Acids. Adv. Synth. Catal. 2010, 352, 493−
498. (f) Panteleev, J.; Zhang, L.; Lautens, M. Domino Rhodium-
Catalyzed Alkyne Arylation/Palladium-Catalyzed N Arylation: A
Mechanistic Investigation. Angew. Chem., Int. Ed. 2011, 50, 9089−
9
(
092.
14) Enantioselectivities obtained with diphosphine ligands: (R)-
binap 28%, (R)-dtbm-segphos 7%, (S)-difluorphos 27%, (R,R)-Me-
duphos 8%.
(15) (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.;
Shintani, R.; Hayashi, T. C2-Symmetric Bicyclo[2.2.2]octadienes as
Chiral Ligands: Their High Performance in Rhodium-Catalyzed
E
DOI: 10.1021/acs.orglett.9b03153
Org. Lett. XXXX, XXX, XXX−XXX