Efficient enantioselective synthesis of dihydropyrans using a chiral N, N ′-dioxide as organocatalyst

Article abstract of DOI:10.1021/ol400894j

The bifunctional organocatalyst C3 N,N′-dioxide has been successfully applied to the asymmetric cascade Michael/hemiacetalization reaction of α-substituted cyano ketones and β,γ-unsaturated α-ketoesters for the synthesis of multifunctionalized chiral dihydropyrans. The corresponding products were obtained in excellent yields (up to 99%) with high to excellent enantioselectivities (up to 99% ee).

Full text of DOI:10.1021/ol400894j

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Efficient Enantioselective Synthesis
of Dihydropyrans Using a Chiral
N,N0‑Dioxide as Organocatalyst
Juhua Feng, Xuan Fu, Zhenling Chen, Lili Lin, Xiaohua Liu, and Xiaoming Feng*
Key Laboratory of Green Chemistry & Technology, Ministry of Education,
College of Chemistry, Sichuan University, Chengdu 610064, P. R. China
xmfeng@scu.edu.cn
Received April 1, 2013
ABSTRACT
The bifunctional organocatalyst C3 N,N0-dioxide has been successfully applied to the asymmetric cascade Michael/hemiacetalization reaction of
r-substituted cyano ketones and β,γ-unsaturated r-ketoesters for the synthesis of multifunctionalized chiral dihydropyrans. The corresponding
products were obtained in excellent yields (up to 99%) with high to excellent enantioselectivities (up to 99% ee).
Dihydropyrans are important heterocyclic structures1
and have been found widely in natural and unnatural
products.2 These compounds exhibit intriguing biological
activities, such as cytotoxicity against some cancers, anti-
HCV entry, and anti-infectivity activities, and are widely
used in pharmaceuticals.3 Furthermore, dihydropyrans
are also useful intermediates for organic synthesis.4 There-
fore, this class of compounds has received significant
attention and results in a variety of synthetic methods,
such as multistep protocols via anionic, cationic, or radical
cyclization,5 [4 þ 2] cycloaddition,6 dioxanone Claisen
rearrangement,7 and ring-closing metathesis of enol
ethers.8 The cascade Michael/hemiacetalization reaction
(1) (a) Zheng, T.; Narayan, R. S.; Schomaker, J. M.; Borhan, B.
J. Am. Chem. Soc. 2005, 127, 6946. (b) Kang, S. Y.; Lee, K. Y.; Sung,
S. H.; Kim, Y. C. J. Nat. Prod. 2005, 68, 56. (c) Clarke, P. A.; Santos, S.
Eur. J. Org. Chem. 2006, 2045. (d) Li, J.; Ding, Y.; Li, X.-C.; Ferreira, D.;
Khan, S.; Smillie, T.; Khan, I. A. J. Nat. Prod. 2009, 72, 983. (e) Li, H.;
Loh, T. P. Org. Lett. 2010, 12, 2679. (f) Schmidt, E. Yu.; Trofimov, B. A.;
Zorina, N. V.; Mikhaleva, A. I.; Ushakov, I. A.; Skital’tseva, E. V.;
Kazheva, O. N.; Alexandrov, G. G.; Dyachenko, O. A. Eur. J. Org.
Chem. 2010, 6727. (g) Wang, J.; Crane, E. A.; Scheidt, K. A. Org. Lett.
2011, 13, 3086.
ꢀ
ꢀ
(2) (a) Marko, I. E.; Dobbs, A. P.; Scheirmann, V.; Chelle, F.;
Bayston, D. J. Tetrahedron Lett. 1997, 38, 2899. (b) Mangion, I. K.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 3696. (c) Yadav, J. S.;
Sunitha, V.; Reddy, B. V. S.; Das, P. P.; Gyanchander, E. Tetrahedron
Lett. 2008, 49, 855. (d) Magano, J. Chem. Rev. 2009, 109, 4398. (e) Sun,
J.; Xia, E. Y.; Wu, Q.; Yan, C. G. ACS Comb. Sci. 2011, 13, 421.
(3) (a) Lichtenthaler, F. W.; Nakamura, K.; Klotz, J. Angew. Chem.,
Int. Ed. 2003, 42, 5838. (b) Xu, Y.-M.; McLaughlin, S. P.; Gunatilaka,
A. A. L. J. Nat. Prod. 2007, 70, 2045. (c) Lin, S.; Shen, Y.-H.; Li, H.-L.;
Yang, X.-W.; Chen, T.; Lu, L.-H.; Huang, Z.-S.; Liu, R.-H.; Xu, X.-K.;
Zhang, W.-D.; Wang, H. J. Nat. Prod. 2009, 72, 650. (d) Zhang, H. J.;
Rothwangl, K.; Mesecar, A. D.; Sabahi, A.; Rong, L. J.; Fong, H. H. S.
J. Nat. Prod. 2009, 72, 2158.
(5) (a) Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang,
C.-K. J. Am. Chem. Soc. 1989, 111, 5335. (b) Kim, S.; Fuchs, P. L. J. Am.
Chem. Soc. 1991, 113, 9864. (c) Stamos, D. P.; Kishi, Y. Tetrahedron
Lett. 1996, 37, 8643. (d) Semeyn, C.; Blaauw, R. H.; Hiemstra, H.;
Speckamp, W. N. J. Org. Chem. 1997, 62, 3426. (e) Lian, Y.; Hinkle, R. J.
J. Org. Chem. 2006, 71, 7071. (f) Liu, W.; Zhou, J.; Zheng, C.; Chen, X.;
Xiao, H.; Yang, Y.; Guo, Y.; Zhao, G. Tetrahedron 2011, 67, 1768. (g)
Lambert, R. F.; Hinkle, R. J.; Ammann, S. E.; Lian, Y.; Liu, J.; Lewis,
S. E.; Pike, R. D. J. Org. Chem. 2011, 76, 9269.
(6) (a) Danishefsky, S. J.; Selnick, H. G.; Armistead, D. M.; Wincott,
F. E. J. Am. Chem. Soc. 1987, 109, 8119. (b) Evans, D. A.; Johnson, J. S.;
Olhava, E. J. J. Am. Chem. Soc. 2000, 122, 1635. (c) Leconte, S.;
Dujardin, G.; Brown, E. Eur. J. Org. Chem. 2000, 639. (d) Jørgensen,
K. A. Angew. Chem., Int. Ed. 2000, 39, 3558. (e) Huang, Y.; Rawal, V. H.
J. Am. Chem. Soc. 2002, 124, 9662. (f) Krauss, I. J.; Mandal, M.;
Danishefsky, S. J. Angew. Chem., Int. Ed. 2007, 46, 5576. (g) Ashtekar,
K. D.; Staples, R. J.; Borhan, B. Org. Lett. 2011, 13, 5732. (h) Fujiwara,
K.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2012, 134, 5512.
(7) (a) Burke, S. D.; Armistead, D. M.; Schoenen, F. J. J. Org. Chem.
1984, 49, 4320. (b) Sherry, B. D.; Maus, L.; Laforteza, B. N.; Toste, F. D.
J. Am. Chem. Soc. 2006, 128, 8132.
(4) (a) Li, P.; Chai, Z.; Zhao, S.-L.; Yang, Y.-Q.; Wang, H.-F.;
Zheng, C.-W.; Cai, Y.-P.; Zhao, G.; Zhu, S.-Z. Chem. Commun. 2009,
7369. (b) Li, G.; Kaplan, M. J.; Wojtas, L.; Antilla, J. C. Org. Lett. 2010,
ꢀ
12, 1960. (c) Aleman, J.; Marcos, V.; Marzo, L.; Garcıa Ruano, J. L. Eur.
J. Org. Chem. 2010, 4482. (d) Zacuto, M. J.; Tomita, D.; Pirzada, Z.; Xu,
F. Org. Lett. 2010, 12, 684. (e) Wang, H.-F.; Li, P.; Cui, H.-F.; Wang,
X.-W.; Zhang, J.-K.; Liu, W.; Zhao, G. Tetrahedron 2011, 67, 1774. (f) Zhu,
X.-B.; Wang, M.; Wang, S.-Z.; Yao, Z.-J. Tetrahedron 2012, 68, 2041.
r
10.1021/ol400894j
XXXX American Chemical Society

between nucleophilic reagents and R,β-unsaturated ke-
tones also provides an efficient method for the synthesis
of dihydropyrans. In asymmetric catalysis, only chiral
thiourea and cinchona alkaloid catalysts were applied in
this reaction.9 Therefore, the development of new asym-
metric catalytic systems for this reaction is still necessary.
ChiralN,N0-dioxides asmetal ligands or organocatalysts
have shown strong asymmetry-inducing capability for
many reactions.10 In the previous studies,11 chiral N,N0-
dioxides as organocatalysts exhibited the bifunctional
character that enabled simultaneous activation of the
reactants with amide-NH as Brønsted acid and the N-oxide
moiety as Brønsted base.12 We envisioned that the amide-
NH moiety of the N,N0-dioxide could activate β,γ-unsatu-
rated R-ketoesters and the N-oxide moiety activated the
R-substituted cyano ketones, and thus the reaction was
promoted. Herein, we report our efforts on developing N,
N0-dioxide organocatalysts for the asymmetric synthesis
of multisubstituted dihydropyrans through the cascade
Michael13/hemiacetalization reaction of R-substituted cya-
no ketones and β,γ-unsaturated R-ketoesters.
We initiated our study by examining the reaction
between methyl 2-oxo-4-phenylbut-(E)-3-enoate 1a and
3-oxo-3-phenylpropanenitrile 2a.14
A preliminary survey revealed that the linker of N,N0-
dioxides (Figure 1) had a significant effect on the enantios-
electivity (Table 1, entries 1ꢀ3). Chiral N,N0-dioxides
derived from 1,3-dibromopropane (C1) and cyclohexane-
1,2-diamine (C2) gave only 11% ee and 3% ee, respectively
(Table 1, entries 1 and 2). However, (1R,2R)-1,2-dipheny-
lethane-1,2-diamine-derived N,N0-dioxide C3 could give
Table 1. Optimization of the Reaction Conditionsa
time
yieldb
(%)
eec
entry cat. solvent (h)
additive
(%)
1
C1 THF
C2 THF
C3 THF
C4 THF
C5 THF
C6 THF
C7 THF
C8 THF
C3 Et2O
24 no
76
90
78
77
93
70
67
39
90
89
50
81
86
83
92
ꢀ11
3
2
24 no
24 no
24 no
24 no
24 no
24 no
24 no
24 no
3
55
ꢀ13
31
36
52
51
50
63
0
4
5
6
7
8
9
10
11
12d
13d,e
C3 MTBE 24 no
C3 MeOH 24 no
C3 MTBE 48 no
C3 MTBE 48 p-tBuC6H4COOH
68
71
78
86
14d,e,f C3 MTBE 72 p-tBuC6H4COOH
15d,e,f,g C3 MTBE 72 p-tBuC6H4COOH
Figure 1. Organocatalysts used in this study.
a Unless otherwise noted, all reactions were conducted with 1a
(0.12 mmol), 2a (0.10 mmol), additive (10 mol %), and catalyst
(10 mol %) in solvent (1.0 mL) under N2 at 0 °C. b Isolated yields.
c Determined by chiral HPLC analysis. d In 3.0 mL of MTBE. e 20 mg of
4 A MS was used. f At ꢀ30 °C. g 50 mol % of p-tBuC6H4COOH was
used. MTBE = methyl tert-butyl ether, MS = molecular sieves.
(8) (a) Ireland, R. E.; Meissner, R. S.; Rizzacasa, M. A. J. Am. Chem.
Soc. 1993, 115, 7166. (b) Sturino, C. F.; Wong, J. C. Y. Tetrahedron Lett.
1998, 39, 9623. (c) Shu, C.; Hartwig, J. F. Angew. Chem., Int. Ed. 2004,
43, 4794. (d) Stenne, B.; Timperio, J.; Savoie, J.; Dudding, T.; Collins,
S. K. Org. Lett. 2010, 12, 2032.
(9) (a) Zhao, S.-L.; Zheng, C.-W.; Wang, H.-F.; Zhao, G. Adv. Synth.
Catal. 2009, 351, 2811. (b) Yao, W.; Pan, L.; Wu, Y.; Ma, C. Org. Lett.
2010, 12, 2422.
moderate enantioselectivity (55% ee, Table 1, entry 3). In-
spired by the results, other N,N0-dioxides derived from 1,2-
diphenylethane-1,2-diamine were synthesized and examined.
Since these N,N0-dioxides have two chiral sources, the
matching of chiral linker and chiral N-oxide moiety was
investigated. The (1S,2S)-diamine and (S)-proline derived
chiral N,N0-dioxide C4 exhibited worse result than the
(10) Liu, X. H.; Lin, L. L.; Feng, X. M. Acc. Chem. Res. 2011, 44, 574.
(11) (a) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J. Am.
Chem. Soc. 1998, 120, 6419. (b) Shimada, T.; Kina, A.; Ikeda, S.;
Hayashi, T. Org. Lett. 2002, 4, 2799. (c) Malkov, A. V.; Bell, M.;
ꢁ
ꢀ
Castelluzzo, F.; Kocovsky, P. Org. Lett. 2005, 7, 3219. (d) Traverse,
J. F.; Zhao, Y.; Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2005, 7, 3151.
ꢁ
ꢀ
(e) Malkov, A. V.; Kocovsky, P. Eur. J. Org. Chem. 2007, 29. (f)
Gnanamani, E.; Someshwar, N.; Ramanathan, C. R. Adv. Synth. Catal.
2012, 354, 2101.
(12) (a) Wen, Y. H.; Gao, B.; Fu, Y. Z.; Dong, S. X.; Liu, X. H.; Feng,
X. M. Chem.;Eur. J. 2008, 14, 6789. (b) Cai, Y. F.; Wang, W. T.; Shen,
K.; Wang, J.; Hu, X. L.; Lin, L. L.; Liu, X. H.; Feng, X. M. Chem.
Commun. 2010, 46, 1250.
(14) The 1H and 13C NMR spectra of 3aa revealed a rapid equili-
brium between the cyclic hemiketal 3aa and the Michael-type product
3aa0. Such an equilibrium is very rapid and thus only one pair of
enantiomers is detected by HPLC. For studies on similar equilibriums
of related compounds, see: (a) Porter, W. R.; Trager, W. F. J. Hetero-
cycl. Chem. 1982, 19, 475. (b) Heimark, L. D.; Trager, W. F. J. Med.
Chem. 1984, 27, 1092. (c) Halland, N.; Velgaard, T.; Jørgensen, K. A.
J. Org. Chem. 2003, 68, 5067. (d) Chen, X.-K.; Zheng, C.-W.; Zhao,
S.-L.; Chai, Z.; Yang, Y.-Q.; Zhao, G.; Cao, W.-G. Adv. Synth. Catal.
2010, 352, 1648.
(13) (a) Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033. (b)
€
Krause, N.; Hoffmann-Roder, A. Synthesis 2001, 171. (c) Almas-i, D.;
ꢀ
Alonso, D. A.; Najera, C. Tetrahedron: Asymmetry 2007, 18, 299. (d)
Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701. (e) Vicario, J. L.; Badia,
D.; Carrillo, L. Synthesis 2007, 2065. (f) Christoffers, J.; Koripelly, G.;
€
Rosiak, A.; Rossle, M. Synthesis 2007, 1279. (g) Zhao, S.-L.; Zheng,
C.-W.; Zhao, G. Tetrahedron: Asymmetry 2009, 20, 1046.
B
Org. Lett., Vol. XX, No. XX, XXXX

(1R,2R)-diamine and (S)-proline derived C3 (Table 1,
entry 4 vs 3). Further investigation on the amino acid back-
bone revealed that (S)-proline-derived catalyst C3 was
superior to (S)-ramipril-derived C5 (Table 1, entry 3 vs 5).
It was also found that smaller or larger ring size of sub-
stituent on the nitrogen of the N-oxide moiety had no
beneficial effect on the enantioselectivity (Table 1, entries
6ꢀ8). In order to further improve the result, extensive
investigation on the reaction conditions was carried out.
Table 3. Reactions of Different R-Substituted Cyano Ketones
with 1a
entry
R1
R3
product yieldb (%) eec (%)
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3aa
3ab
3ac
3ad
3ae
3af
92
98
95
93
88
92
87
96
95
95
99
99
86
88
86
90
85
86
84
84
82
83
99
99
2
3-FC6H4
Table 2. Substrate Scope for the Asymmetric Michael/
Hemiacetalization Reaction of 2a and β,γ-Unsaturated
R-Ketoestersa
3
3-ClC6H4
3-BrC6H4
3-MeOC6H4
3-MeC6H4
4-MeC6H4
4-FC6H4
4
5d
6
7
3ag
3ah
3ai
8
9
4-ClC6H4
4-BrC6H4
10
11
12
3aj
2,6-Cl2C6H3 3-BrC6H4
2,6-Cl2C6H3 4-ClC6H4
3md
3mi
entry
R1
R2
product
yieldb (%)
eec (%)
1
Ph
Ph
Ph
Ph
Ph
Me
Et
3aa
3ba
3ca
3da
3ea
3fa
92
84
80
90
76
98
99
98
99
97
98
94
99
99
95
84
85
76
91
86
84
85
83
92
91
93
90
93
98
94
90
99
98
96
85
83
80
89
a Unless otherwise noted, all reactions were conducted with 1
(0.12 mmol), 2 (0.10 mmol), p-tBuC6H4COOH (50 mol %), 4 A MS
(20 mg), and C3 (10 mol %) in MTBE (3.0 mL) under N2 at ꢀ30 °C for
72 h. b Isolated yields. c Determined by HPLC analysis. d Reaction time: 120 h.
2
3
i-Pr
allyl
t-Bu
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4
5
6d
7
2-NO2C6H4
2-BrC6H4
Under the optimized reaction conditions, a range of β,γ-
unsaturated R-ketoesters 1 were examined with 2a, and the
results were summarized in Table 2. Substrates with Et,
i-Pr, and allyl groups on the ester moiety gave similar results
(Table 2, entries 1ꢀ4). More sterically hindered t-Bu group
afforded higher enantioselectivity (92% ee), but lower
yield (76%) (Table 2, entry 5). The substituents on the
aromatic ring of β,γ-unsaturated R-ketoesters affected the
results significantly. The substrates with electron-donating
or electron-withdrawing groups at the ortho position of
the aromatic ring obtained much better results, affording
the corresponding products in excellent yields with excellent
enantioselectivities (94ꢀ99% yields, 90ꢀ99% ee, Table 2,
entries 6ꢀ15). The substrates with substituent at the meta or
para position of the aromatic ring got slightly decreased
results (Table 2, entries 16ꢀ18). Notably, the catalytic
system was also suitable for aliphatic methyl 4-cyclohexyl-
2-oxobut-(E)-3-enoate, affording the desired product in
91% yield with 89% ee (Table 2, entry 19).Subsequently,
a broad spectrum of R-substituted cyano ketones as nucleo-
philes was probed. The reactions proceeded smoothly
with different 3-oxo-3-phenylpropanenitrile derivatives,
and good results were obtained (87ꢀ99% yields and
82ꢀ99% ee, Table 3).
3ga
3ha
3ia
8
2-FC6H4
9
2-ClC6H4
10
11
12
13
14
15d
16
17
18
19e,f
2-MeOC6H4
2-MeC6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
2,6-F2C6H3
2,6-Me2C6H3
3-MeC6H4
4-MeC6H4
4-ClC6H4
3ja
3ka
3la
3ma
3na
3oa
3pa
3qa
3ra
3sa
cyclohexyl
a Unless otherwise noted, all reactions were conducted with 1
(0.12 mmol), 2a (0.10 mmol), p-tBuC6H4COOH (50 mol %), 4 A MS
(20mg), andC3 (10 mol %) in MTBE (3.0 mL) under N2 at ꢀ30 °C for 72 h.
b Isolated yields. c Determined by HPLC analysis. d Reaction time: 96 h.
e Reaction time: 120 h. f The yield was determined by 1H NMR spectra.
Solvent screening showed the enantioselectivity could be
improved to 63% ee in MTBE (Table 1, entry 10), while
racemic product was obtained in polar solvent, such as
MeOH (Table 1, entry 11). Under lower concentration,
68% ee could be obtained (Table 1, entry 12). Addition of
p-tBuC6H4COOH15 could further improve the enantio-
selectivity to 71% ee (Table 1, entry 13). Under lower
reaction temperature and increasing the amount of addi-
tive to 50 mol %, catalyst C3 could efficiently catalyze the
reaction and afford the corresponding dihydropyran in
92% yield with 86% ee (Table 1, entry 15).
To evaluate the synthetic potential of the catalytic
system, gram-scale synthesis of the dihydropyran 3ma
was performed. By treatment of 3.0 mmol of 2a under
the optimized conditions, the corresponding 3ma was
obtained in 99% yield (1.20 g) with 99% ee (Scheme 1).
The structure of the catalyst C3 was determined by
X-ray crystallographic analysis,16 which showed the intra-
molecular hydrogen bonding interactions between the
NꢀH proton of the amide and the oxygen of N-oxide, as
(15) The role of the acid additive might be to break down the
intramolecular hydrogen bonds between the N-H proton of the amide
and the oxygen of N-oxide present in catalyst, and thus, the N-H proton
and the N-oxide could be free for the activation of the substrates.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 1. Gram-Scale Asymmetric Synthesis of 3ma
well as the intermolecular hydrogen bonding interactions
between the oxygen of N-oxide and the hydrogen of H2O
(Figure 2). The intramolecular hydrogen bonds were also
1
confirmed by the H NMR spectra, in which the N-H
proton of the amide in catalyst C3 showed a strong deshield-
ing effect, with a broad peak shape at δ=12.01ppm(seethe
Supporting Information for details). These results implied
that the N-H moiety of the amide in catalyst C3 might
act as a Brønsted acid, and the N-oxide moiety might
act as a Brønsted base. The absolute configuration of
the product of 4-bromobenzyl 2-oxo-4-phenylbut-(E)-
3-enoate was determined to be 2S,4R by comparison
of the literature.9a,17 On the basis of the above informa-
tion and the previous studies on N,N0-dioxides,10,11
a
transition state was proposed to illustrate the activation
mode (Figure 2). The intramolecular H-bonds of catalyst
C3 were released and transformed to activate the two
substrates simultaneously (see the Supporting Information
for details). One of the N-H moieties of the amide activated
the β,γ-unsaturated R-ketoester through hydrogen bonds,
while the enolate form of the R-substituted cyano ketone
could be activated by the N-oxide on the other side. The
Si face of β,γ-unsaturated R-ketoester was shielded by
the cyclohexyl moiety, and the R-substituted cyano ketone
could attack from the Re face of β,γ-unsaturated R-ketoester
to form the product of the 4R configuration.
In summary, we have developed an efficient chiral N,N0-
dioxide catalyst for the asymmetric reaction of R-substi-
tuted cyano ketones with β,γ-unsaturated R-ketoesters.
The reaction performed well over a range of substrates, giving
the corresponding products in excellent yields (up to 99%)
Figure 2. Crystal structure of C3 and proposed transition-state
model for the Michael addition step.
with high to excellent enantioselectivities (up to 99% ee).
Further investigation on the application of such kind of
N,N0-dioxides to other reactions is in progress.
Acknowledgment. We thank the National Natural
Science Foundation of China (Nos. 21021001 and
21290182) and the National Basic Research Program of
China (973 Program: No. 2010CB833300) for financial
support.
Supporting Information Available. Experimental pro-
cedures, spectral and analytical data for the products, and
crystal CIF. This material is available free of charge via
the Internet at http://pubs.acs.org.
(16) CCDC 922463 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
the Cambridge Crystallographic Data Centre via www.ccdc. cam.ac.uk/
data_request/cif.
(17) The product of 4-bromobenzyl 2-oxo-4-phenylbut-(E)-3-enoate
was obtained in 37% yield with 77% ee.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX