Catalytic asymmetric intermolecular bromoesterification of unfunctionalized olefins

Article abstract of DOI:10.1021/ol501542r

An asymmetric intermolecular bromoesterification of unfunctionalized olefins catalyzed by (DHQD)₂PHAL is described. Optically active bromoesters can be obtained with up to 92% ee.

Full text of DOI:10.1021/ol501542r

Letter
pubs.acs.org/OrgLett
Catalytic Asymmetric Intermolecular Bromoesterification
of Unfunctionalized Olefins
Lijun Li,† Cunxiang Su,† Xiaoqin Liu,† Hua Tian,† and Yian Shi*,†,‡,§
†Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
‡State Key Laboratory of Coordination Chemistry, Center for Multimolecular Organic Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, China
§Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States
S
* Supporting Information
ABSTRACT: An asymmetric intermolecular bromoesterification of
unfunctionalized olefins catalyzed by (DHQD)2PHAL is described.
Optically active bromoesters can be obtained with up to 92% ee.
lectrophilic addition to olefins via a halonium ion allows
Esimultaneous introduction of two heteroatoms onto the
C−C double bond and represents one of the most classic and
important organic transformations.1 An asymmetric version of
such a transformation has great synthetic value and has been
actively pursued. In recent years, significant progress has been
made in asymmetric intramolecular halogenation of alkenes.2,3
For the intermolecular processes,4 a number of effective systems
have also been developed including aminohalogenation of
α,β-unsaturated carbonyl compounds by Feng;5 dihalogenation
of allylic alcohols by Nicolaou6 and Burns;7 bromoamination
of enecarbamates by Masson;8 oxyfluorination of enamides by
Toste;9 bromoesterification of allylic sulfonamides by Tang;10 and
bromohydroxylation of allylic alcohols by Ma.11 However, catalytic
asymmetric intermolecular halogenation of unfunctionalized
olefins still presents a formidable challenge (Scheme 1).12−15,10
Scheme 1. Catalytic Asymmetric Halogenation of Olefins
In our ongoing studies on asymmetric electrophilic addition to
olefins,16,17 we have explored asymmetric halogenation of olefins
containing no heteroatom directing groups with various catalytic
systems (Figure 1) and found that up to 92% ee can be obtained
with dimeric cinchona alkaloid (DHQD)2PHAL18,19 as catalyst.
Herein we wish to report our preliminary studies on this subject.
Our initial studies were carried out with 1,2-dihydronaph-
Figure 1. Selected examples of catalyst examined.
thalene (1a) as test substrate, benzoic acid (2a) as nucleophile,
and NBS (4a) as bromine source using various catalytic systems
in EtOAc at 0 °C. No desired product was formed when chiral
phosphoric acid 3a was used as catalyst (Table 1, entry 1).
A messy mixture was obtained with chiral phosphine−Sc(OTf)3
Received: May 29, 2014
Published: July 8, 2014
complex 3b as catalyst (Table 1, entry 2).16b Subsequently, chiral
© 2014 American Chemical Society
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Letter
a
a
Table 1. Studies of the Reaction Conditions
Table 2. Studies of the Nucleophiles
a
Reactions were carried out with substrate 1a (0.30 mmol), nucleophile
2 (0.36 mmol), catalyst 3e (0.030 mmol), and bromine source 4e
(0.36 mmol) in EtOAc (3.0 mL) at −30 °C for 48 h unless otherwise
b
c
noted. Isolated yield. Determined by chiral HPLC analysis. Mes =
2,4,6-trimethylphenyl; Nap = naphthyl.
a
Reactions were carried out with substrate 1a (0.30 mmol),
nucleophile 2a (0.36 mmol), catalyst 3 (0.030 mmol), and Br source
4 (0.36 mmol) in solvent (3.0 mL) at 0 °C for 24 h unless otherwise
were subsequently investigated with 1,2-dihydronaphthalene
(1a), catalyst 3e (10 mol %), and N-bromobenzamide (4e)
(1.2 equiv) in EtOAc at −30 °C (Table 2). The best ee was
achieved with 1-naphthoic acid (2d), giving bromoester 8a in
73% yield and 83% ee (Table 2, entry 4) (for the X-ray structure
of 8a, see Figure 2).
b
c
d
noted. At −30 °C for 48 h. At −50 °C for 48 h. Isolated yield.
e
Determined by chiral HPLC analysis.
cinchona alkaloid derivatives were investigated for the reaction.
While bromoester 5a was isolated in 43% and 46% yield with
quinine (3c) and quinidine (3d), only 3−4% ee was obtained
(Table 1, entries 3 and 4). Bromoester 5a was formed in 68% yield
and 56% ee with dimeric cinchona alkaloid (DHQD)2PHAL (3e)
(Table 1, entry 5). Other dimeric cinchona alkaloid catalysts
3f−h gave 5a essentially as a racemate (Table 1, entries 6−8). The
opposite enantiomer was obtained in 63% yield and 48% ee with
(DHQ)2PHAL (3i) (Table 1, entry 9). Among the bromine
sources examined (Table 1, entries 5, 10−13), N-bromobenza-
mide (4e) gave the highest enantioselectivity (65% ee) (Table 1,
entry 13). EtOAc was found to be the solvent of choice (Table 1,
entries 13−17). The ee increased to 75% as the reaction tem-
perature was lowered to −30 °C (Table 1, entry 18). However,
the yield was substantially reduced when the reaction was
carried out at −50 °C (Table 1, entry 19). Other nucleophiles
With the optimized reaction conditions in hand, the substrate
scope was subsequently investigated. As shown in Table 3, the
bromoesterification can be extended to 1,2-dihydronaphthalenes
containing various substituents such as F, Cl, Br, CO2Me, CHO,
NO2, Ph, OMe, and Me, giving the corresponding bromoesters
in 47−81% yield with 74−92% ee (Table 3, entries 1−12).
The enantioselectivity was influenced by the electronic property
of the substituents. Generally, electron-withdrawing groups
provided higher enantioselectivity (89−92%) (Table 3, entries
2−7, 11, and 12), while electron-donating groups gave lower ee’s
(Table 2, entries 9 and 10). 6,7-Dihydro-5H-benzocycloheptene
(1m) and 1H-indene (1n) were also found to be suitable
substrates for the reaction, producing the corresponding
bromoesters in up to 82% ee (Table 3, entries 13 and 14).
When terminal olefin 1o was subjected to the reaction
condition, bromoester 8o was obtained in 69% ee (Table 3,
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Organic Letters
Letter
a
Table 3. Asymmetric Bromoesterification of Olefins
Figure 2. X-ray structures of compounds 8a and 11a.
Scheme 2
Figure 3. Proposed transition-state model for bromoesterification.
entry 15). Lower ee’s were obtained for trans-β-methylstyrene
and 1-phenylcyclohexhene (Table 3, entries 16 and 17). The
absolute configurations of 8a (Figure 2) and 8o were determined by
comparing the optical rotations of the corresponding bromo-
hydrins20 with the reported ones upon reduction with DIBAL-H
(Scheme 2).
While a precise understanding of the origin of the
enantioselectivity awaits further study, a plausible transition
state model is proposed in Figure 3.3b,r,w,x,6,10 The tertiary amines
of the catalyst are likely to be protonated by acid nucleophile under
the reaction conditions. The proton of the quaternary ammonium
salt could form a hydrogen-bond with N-bromobenzamide (4e) to
activate and direct it toward the double bond of the substrate,
which is located in the chiral pocket via π,π-stack with the
quinoline of the catalyst. The phthalazine nitrogen could also form
a hydrogen bond with the acid to increase its nucleophilicity and
direct its attack to the reacting site.
In summary, we have developed an efficient enantioselective
intermolecular bromoesterification of unfunctionalized olefins
with dimeric cinchona alkaloid (DHQD)2PHAL as catalyst,
N-bromobenzamide as bromine source, and 1-naphthoic acid as
nucleophile, giving the corresponding bromoesters in up to 92% ee.
The current reaction process demonstrates the feasibility of
achieving high enantioselectivity for intermolecular halogenation
of unfunctionalized olefins, which has been extremely challenging.
Further efforts will be devoted to understanding the mechanism,
expanding the substrate scope, as well as developing more effective
catalytic systems.
a
Reactions were carried out with substrate 1 (0.50 mmol), 2d
(0.60 mmol), 3e (0.050 mmol), and 4e (0.60 mmol) in EtOAc
b
(5.0 mL) at −30 °C for 72 h unless otherwise noted. With 4e
(1.00 mmol) for 5 days. For entries 1 and 15, the absolute configu-
rations were determined by comparing the optical rotations of the
corresponding bromohydrins with the reported ones upon reduction
with DIBAL-H. For entries 2−14, the absolute configurations were
tentatively assigned by analogy. For entries 16 and 17, the stereo-
c
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, characterizations, X-ray structures,
data for determination of enantiomeric excess, and NMR spectra.
This material is available free of charge via the Internet at http://
pubs.acs.org.
d
chemistry indicated is relative stereochemistry. Isolated yield.
e
Determined by chiral HPLC analysis.
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Organic Letters
Letter
(ad) Ke, Z.; Tan, C. K.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2014,
136, 5627.
AUTHOR INFORMATION
■
Corresponding Author
(4) For a leading review of asymmetric intermolecular halogenation of
olefins, see: Chen, J.; Zhou, L. Synthesis 2014, 586.
(5) (a) Cai, Y.; Liu, X.; Hui, Y.; Jiang, J.; Wang, W.; Chen, W.; Lin, L.;
Feng, X. Angew. Chem., Int. Ed. 2010, 49, 6160. (b) Cai, Y.; Liu, X.; Jiang,
J.; Chen, W.; Lin, L.; Feng, X. J. Am. Chem. Soc. 2011, 133, 5636. (c) Cai,
Y.; Liu, X.; Li, J.; Chen, W.; Wang, W.; Lin, L.; Feng, X. Chem.Eur. J.
2011, 17, 14916. (d) Cai, Y.; Liu, X.; Zhou, P.; Kuang, Y.; Lin, L.; Feng,
X. Chem. Commun. 2013, 49, 8054.
(6) Nicolaou, K. C.; Simmons, N. L.; Ying, Y.; Heretsch, P. M.; Chen, J.
S. J. Am. Chem. Soc. 2011, 133, 8134.
(7) Hu, D. X.; Shibuya, G. M.; Burns, N. Z. J. Am. Chem. Soc. 2013, 135,
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(8) Alix, A.; Lalli, C.; Retailleau, P.; Masson, G. J. Am. Chem. Soc. 2012,
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*E-mail: yian@lamar.colostate.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Basic Research Program
of China (973 program, 2011CB808600), the National Natural
Science Foundation of China (21172221), and the Chinese
Academy of Sciences for the financial support.
(9) Honjo, T.; Phipps, R. J.; Rauniyar, V.; Toste, F. D. Angew. Chem.,
Int. Ed. 2012, 51, 9684.
(10) Zhang, W.; Liu, N.; Schienebeck, C. M.; Zhou, X.; Izhar, I. I.;
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(11) Zhang, Y.; Xing, H.; Xie, W.; Wan, X.; Lai, Y.; Ma, D. Adv. Synth.
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