Catalytic asymmetric hydroxylative dearomatization of 2-naphthols: Synthesis of lacinilene derivatives

Article abstract of DOI:10.1039/c7sc02809a

An enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished using a N,N′-dioxide-scandium(iii) complex catalyst. Various substituted ortho-quinols could be obtained in high yields (up to 99%) and enantioselectivities (up to 95:5 er). This methodology could be applied in the synthesis of bioactive lacinilenes in a gram-scale reaction. Based on the experimental investigations and previous work, a possible catalytic model was proposed.

Full text of DOI:10.1039/c7sc02809a

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Catalytic Asymmetric Hydroxylative Dearomatization of 2-
Naphthols: Synthesis of Lacinilene Derivatives
Yu Zhang, Yuting Liao, Xiaohua Liu*, Xi Xu, Lili Lin and Xiaoming Feng*a
Received 00th January 20xx,
Accepted 00th January 20xx
An enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished by using a
N,N'-dioxide/scandium(III) complex catalyst. Various substituted ortho-quinol could be obtained in high yields (up to 99%)
and enantioselectivities (up to 95:5 er). This methodology could be applied in the synthesis of bioactive lacinilenes in
gram-scale version. Based on the experimental investigations and previous work, a possible catalytic model was proposed.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Substituted ortho-quinols are essential structural motifs in a
number of natural products and pharmaceuticals.1 For
instance, chiral lacinilene derivatives (Figure 1), a series of
phytoalexines isolated from the cotton plants have been
utilized as inhibiting growth of the cotton bacterial pathogen,
such as Xanthomonas campestris or malvacearum.2 Studies
have showed that the (S)-enantiomer of lacinilene C is more
active than the (R)-enantiomer.2c While these biological
activities provide
a
justification for development of
approaches to the synthesis of enantiomerically enriched
lacinilene derivatives, novel catalytic enantioselective methods
remain vacancy.2b,d
Scheme 1. Catalytic asymmetric hydroxylative dearomatization of phenols and
naphthols
synthesis of these cadinanes.3 Compared with other successful
dearomatization events of phenols or naphthols,4,5 to control
the chemo-, regio- and enantioselectivity of the asymmetric
hydroxylative dearomatization is more difficult,6 which might
meet serious side reactions in the presence of oxidants
including overoxidation of alkene functions, competitive para-
oxidation and homocoupling.6c,e Additionally, the ortho-quinol
product could undergo an unexpected α-ketol rearrangement,
which enhances the difficulty of controlling the reactivity and
selectivity.6a,7 In this respect, only few reports related to
asymmetric hydroxylative of phenols or naphthols has been
reported. Asymmetric oxidative dearomatization of phenolate
mediated by copper-sparteine-dioxygen complexes followed a
[4+2] dimerization cascade, giving bicyclo[2.2.2]octenones as
the final products.6a Several chiral hypervalent organoiodine
compounds were developed for the asymmetric hydroxylative
Figure 1. Represent active lacinilene derivatives bearing ortho-quinol structures.
Optically active lacinilene derivatives in nature were
proposed to be produced enzymically from oxidation of
dihydroxycadalenes, thus it is of practical interest to discover a
catalytic asymmetric oxidative dearomatization pattern to the
a.Key Laboratory of Green Chemistry & Technology, Ministry of Education, College
of Chemistry, Sichuan University, Chengdu 610064, China. E-mail:
liuxh@scu.edu.cn; xmfeng@scu.edu.cn; Fax: +86 28 85418249; Tel: +86 28
85418249.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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phenols and 1-naphthols dearomatization.6b-e Taking these
examples into account, we want to engage in discovering a Table 2. Substrate scope for 2-naphthols.a
new enantioselective strategies for the synthesis of ortho-
quinol moiety with improved efficiency and selectivity. Here,
we presented an efficient asymmetric hydroxylative
dearomatization of 2-naphthols catalyzed by a chiral N,N'-
dioxide-scandium(III) complex catalyst.8 The process could be
applied to the synthesis of various 1-hydroxy-1-alkyl-
naphthalen-2-one derivatives including lacinilene C methyl
ether and lacinilene D, in high to excellent yields and good
enantioselectivities under mild reaction condition.
R1
Sc(NTf2)3/L-PiPr2
R1
OH
Ts
N
O
OH
R2
O
(5 mol%)
R4
R4
DCM, 0 oC, 3-24 h
R2
Ph
R3
R3
2a
3
1
OH
OH
O
O
R
R
3b: R = Br, 3 h, 99% yield, 94:6 er
3c: R = OMe, 3 h, 99% yield, 94.5:5.5 er
3d: R = H, 3 h, 99% yield, 94:6 er
3e
: R = 4-Cl, 3 h, 95% yield, 94:6 er
OH
3f
: R = 2-MeO, 3 h, 99% yield, 93.5:6.5 er
O
3m
3g: R = 3-MeO, 3 h, 99% yield, 95:5 er
3h: R = 4-MeO, 3 h, 99% yield, 94.5:5.5 er
Ph
3i
3j
: R = 3,4-(MeO)2, 7 h, 99% yield, 93.5:6.5 er
: R = Piperonyl, 4 h, 99% yield, 95:5 er
Results and discussion
3.5 h, 99% yield, 94.5:5.5 er
3k: R = 2-Naphthyl, 5 h, 96% yield, 94:6 er
We selected the hydroxylative dearomatization of 1-
methylnaphthalen-2-ol 1a as the model substrate using 3-
phenyl-2-tosyl-1,2-oxaziridine 2a as the oxidant which was
proven chemoselective in a phase-transfer-catalyst and a base
condition (Table 1).[7a] Initially, the catalytic asymmetric
reaction was performed with 10 mol% of chiral N,N'-dioxide L-
PiPr2-Sc(OTf)3 complex in DCM at 30 oC, and the desired
product 3a could be obtained dominantly with 80:20 er
3l
: R = 3-Furyl, 3 h, 99% yield, 95:5 er
OH
O
3n
OH
OH
O
O
3 h, 99% yield, 95:5 er
OH
3pb
Ph
3o
O
3 h, 95% yield, 95:5 er
5 h, 99% yield, 92:8 er
3qb
OH
OH
3u
HO
O
3w
O
24 h, 66% yield, 91:9 er
Ph
OH
O
3h, 96% yield, 94.5:5.5 er
OH
3 h, 95% yield, 95:5 er
OH
3v
O
3z
O
n
Table 1. Optimization of the reaction conditionsa
n = 0, 3r: 3 h, 99% yield, 94:6 er
n = 1, 3s: 3 h, 99% yield, 94:6 er
O
O
3t
Et
n = 4, : 3 h, 99%yield, 94:6 er
3 h, 99% yield, 94.5:5.5 er
OH OH
3 h, 99% yield, 95:5 er
OH
OH
O
O
O
O
O
O
3aac
3y
3ab
3x
3 h
3 h
3 h
22 h
99% yield, 94.5:5.5 er
64% yieldd, 75:25 er
99% yield, 95:5 er
99% yield, 83.5:16.5 er
a Reaction conditions: The same as entry 7 in Table 1. b 10 mol% catalyst loading.
c L-PiEt2-Sc(OTf)3 (1:1, 5 mol%). d Total yield of 3ab and 4ab, 3ab/4ab = 87:13.
Yield
(%)b
96
Ratio
(3a/4a)c
73:27
E.r.
Entry
1
Metal salt
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(NTf2)3
Sc(NTf2)3
Sc(NTf2)3
Sc(NTf2)3
L*
(3a)c
whileas the α-ketol rearrangement byproduct 4a was isolated
in around one-fourth of a 96% total yield (Table 1, entry 1).
The evaluation of the structure of N,N'-dioxides showed that L-
PiPr2 was the optical ligand in terms of the enantioselectivity
albeit ligand L-PiMe2 and L-PiPr3 improved the yield of the
desired product 3a (entries 2-5). Fortunately, changing the
counterion of the scandium salt from –OTf to –NTf2 could
suppress the α-ketol rearrangement, delivering the quniol 3a
in a 99% yield with 92:8 er (Table 1, entry 6). Further
optimization of the reaction condition, such as decreasing the
temperature and the catalyst loading to 5 mol% resulted in
slightly improved enantioselectivity with maintained
effficiency (entry 7). Lowering the catalyst loading to 1 mol%
or the amount of the oxidant 2a decreased either the yield or
the selectivity a little (entries 8 and 9). We therefore chose
these reaction conditions (Table 1, entry 7) for further studies.
We next explored the substrate scope of 2-naphthols (Table
2). The introduction of bromo or methoxyl group at the
L-PiPr2
L-PrPr2
L-RaPr2
L-PiMe2
L-PiPr3
L-PiPr2
L-PiPr2
L-PiPr2
L-PiPr2
80:20
2
99
99
90
96
99
99
86
99
79:21
75:25
>95:5
89:11
>95:5
>95:5
>95:5
>95:5
63:37
53.5:46.5
60:40
3
4
5
73:27
6
92:8
7d
8e
9d,f
95:5
93.5:6.5
94.5:5.5
a
Unless otherwise noted, the reactions were performed with L*/Sc(III) (1:1, 10
mol%), 1a (0.10 mmol) and 2a (2.0 equiv) in DCM (1.0 mL) under N2 at 30 oC for
b
c
3 h. Isolated yield by silica gel chromatography. Determined by chiral HPLC
analysis. d 5 mol% catalyst loading at 0 oC. e 1 mol% catalyst loading at 0 oC for 4
h. f 2a (1.5 equiv) was used.).
2 | J. Name., 2012, 00, 1-3
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Concise synthesis of (-)-lacnilene D and (+)-lacinilene D
OBn
a-c
OH
MOMO
TBSO
9
1ae
66% yield for 3 steps
3ae
(R)-
X-ray crystal structure
e
d
Scheme 3. Control experiments.
OH
O
OH
O
HO
HO
O
f
O
f
HO
TBSO
OTBS
OH
99% yield, 95:5 er
(+)-Lacinilene D
19 = +162.11
99% yield, 95:5 er
but aromatization side product 1-ethyl-5-methylnaphthalene-
2,6-diol was obtained.2d,10 It was anticipated that the TBS
protecting group could be smoothly removed under neutral
condition, which might avoid the occurrence of aromatization
process. As expected, the TBS-substituted 2-naphthol 1ae
3ae
(S)-
99% yield, 95.5:4.5 er
(R)-3ae
99% yield, 95:5 er
(99% yield, 95.5:4.5 er
in gram scale)
(-)-Lacinilene D
[
]
D
19 = -177.58
[
]
D
Reaction Condition: a) HCl, MeOH; b) TBSCl, imidazole, DMF; c) 10 % Pd/C, H2 (balloon), EtOH;
d) Sc(NTf)3/L-PiPr2 (5 mol%), 2a, CH2Cl2, 0 oC; e) Sc(NTf)3/ent-L-PiPr2 (5 mol%), 2a, CH2Cl2, 0 oC;
f) TBAF, THF.
Concise synthesis of chiral lacinilene C methyl ether
could be easily synthesized from
9 in 66% yield after 3 steps,
OH
which was further enantioselectively oxidized into the product
O
O
O
O
O
O
OH
c
a
b
3ae in quantitative yield and 95:5 er, even it was performed in
82%
90%
60%
a gram scale. The absolute configuration of 3ae from L-PiPr2
-
1y
13
3y
OH
12
Sc(NTf2)3 complex catalysis was determined to be (R) by X-ray
crystal diffraction experiment.11 For the benifit of the further
diffirential biological activity study on each enantiomer of
chiral lacinilenes,2c (S)-lacinilene D was synthesized using ent-L-
PiPr2-Sc(NTf2)3 complex in a comparable result of 99% yield
and 95:5 er. Next, the synthesis of optically active lacinilene C
methyl ether was explored. The synthetic route began from
1,2-dihydronaphthalene 12, which could be easily accessed
from 2-methoxytoluene through four-step protocol.[2d]
Subsequent two-step oxidation could afford the 2-naphthol
derivative 1y in 49% yield, which underwent hydroxylative
dearomatization catalyzed by 0.1 mol% of Sc(NTf2)3/rac-L-PiPr2
complex to produce racemic lacinilene 3y in 90% yield.2d After
OH
O
OH
d
e
Ref.
f
O
O
HO
O
1af
Lacinilene C ME
Lacinilene C
45% yield for two steps
99% yield, 83:17 er
[
]
D
19 = -237.29
Reaction condition: a) m-CPBA, TsOH H2O, TFE/DCM; b) Ce(SO4)2 4H2O, O2 (balloon), tBuOH;
c) Sc(NTf2)3/rac-L-PiPr2 (0.1 mol%), CH2Cl2, 35 oC; d) TMSCl, pyridine, CH2Cl2; e) CuCN, iPrMgCl,
BF3 Et2O, THF/Et2O; f) Sc(OTf)3/L-RaPr2 (5 mol%), CH2Cl2, 0 oC.
Scheme 2. Concise synthesis of chiral lacinilene C methyl ether, (-)-lacinilene D and (+)-
lacinilene D.
trimethylsilylation
and
copper
catalyzed
1,4-
C6- position of 2-naphthols had no obvious effect on the result.
addition/aromatization, 2-naphthol 1af could be attained in
45% yield for two steps. By treatment with oxaziridine 2a in
the presence of Sc(OTf)3/L-RaPr2, chiral lacinilene C methyl
ether could be obtained in quantitative yield and 83:17 er,
which could further transformed to lacinilene C according to
the literature.2b
And the 6-aryl substituted 2-naphthol derivatives 1d-1l
tethering various electron-donating and electron-withdrawing
substitution could undergo the transformations smoothly,
providing the products 3d
er. It was noteworthy that 6-alkenyl and alkynyl substituted
substrates 1m 1q were compatible with the reaction condition,
-3l in 95-99% yield and 93.5:6.5-95:5
-
To elucidate the stereochemical course of the oxidation
process, some control experiments were conducted (Scheme
3). The optically pure oxaziridine (S)-2a reacted with 2-
naphthol 1a in the presence of Sc(NTf2)3/L-PiPr2 complex,
affording the (R)-quinol 3a in 49% yield and 95.5:4.5 er with
the recovered oxaziridine (S)-2a in 45% yield.12d Using ent-L-
PiPr2 as the ligand, (S)-quinol 3a was obtained in 46% yield and
90:10 er with the recovered oxaziridine (S)-2a in 52% yield. It
inidicates that the chiral matched and mis-matched effect
between chiral ligand and chiral oxaziridine was not obvious in
this case compared to previous reports,12 and there might be
negligible interaction between the chiral catalyst and
oxaziridine.
and no aminohydroxylation of the unsaturated carbon-carbon
bond occurred, giving hydroxylative dearomatization product
3m
Additionally, 6-alkyl substituted 2-naphthols 3r
-
3q in good to excellent yields and enantioselectivities.9
-
3w bearing
methyl, ethyl, and butyl group were well tolerated,
accomplishing the asymmetric hydroxylative reaction with the
outcomes of 95-99% yield and 94:6-95:5 er. The installation of
substituents to 5- and 7- positions did not influence the
reaction efficiency (3x-3z). MOM-protected substrate 1z could
deliver the desired product 3z in good result without any
deprotection process occurred under the reaction condition.
However, the increase of steric hindrance at the ortho-
situation of 2-naphthol was harmful to the consequence (3aa
and 3ab).
To probe into the interaction between the catalysts and 2-
1
naphthol, H NMR analysis of the mixture of the components
To show the synthetic utility of current catalyst system, the
asymmetric synthesis of bioactive lacinilenes was carried out
(Scheme 2). Initially, the direct deproctection of the product 3z
under acidic condition formed the optically active lacinilene D,
was carried out (see SI for details). The chemical shift of 1-
methyl 2-naphthol 1a maintained nearly unchanged after
Sc(NTf2)3 was added. There was an obvious high-field shift for
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Notes and references
1
2
(a) D. Magdziak, S. J. Meek and T. R. R. Pettus, Chem. Rev.,
2004, 104, 1383; (b) S. P. Roche and J. A. Porco, Jr., Angew.
Chem. Int. Ed., 2011, 50, 4068.
(a) P. W. Jeffs and D. G. Lynn, J. Org. Chem., 1975, 40, 2958;
(b) J. P. McCormick, T. Shinmyozu, J. P. Pachlatko, T. R.
Schafer and J. W. Gardner, J. Org. Chem., 1984, 49, 34; (c) R.
D. Stipanovic, J. P. McCormick, E. O. Schlemper, B. C. Hamper,
T. Shinmyozu and W. H. Pirkle, J. Org. Chem., 1986, 51, 2500;
Figure 2. Proposed enantioselective catalytic model.
(d) K. Krohn and G. Zimmermann, J. Org. Chem., 1998, 63,
4140.
3
For selected examples of asymmetric oxidative
dearomatization in the biosynthesis of natural products: (a)
A. Bérubé, I. Drutu and J. L. Wood, Org. Lett., 2006, 8, 5421;
the most signals of 1a after mixing with Sc(NTf2)3/L-PiPr2
catalyst. It indicates that the chiral catalyst enables the 2-
naphthol reactive for hydroxylative reaction. Based on these
(b) L. H. Mejorado and T. R. R. Pettus, J. Am. Chem. Soc.,
2006, 128, 15625; (c) S. P. Cook, A. Polara and S. J.
Danishefsky, J. Am. Chem. Soc., 2006, 128, 16440; (d) J.
Gagnepain, F. Castet and S. Quideau, Angew. Chem. Int. Ed.,
2007, 46, 1533; (e) A. Rudolph, P. H. Bos, A. Meetsma, A. J.
results and our previous study on the chiral N,N'-dioxide-metal
complex catalysts,8,13 we suggested an enantioselective
catalytic model as shown in Figure 2. The ligand L-PiPr2 binds
to the scandium(III) center via four oxygens to form a
polycyclic octahedral metal complex catalyst. The 2-naphthol
coordinates to the metal center with at one of the vacant sites,
with its Re-face shielding by one amide unit of the ligand.
Minnaard and B. L. Feringa, Angew. Chem. Int. Ed., 2011, 50
5834.
,
4
For selected reviews on dearomatization reactions of
phenols and naphthols: (a) C.-X. Zhuo, C. Zheng and S.-L You,
Acc. Chem. Res., 2014, 47, 2558; (b) W.-T. Wu, L. Zhang and
S.-L. You, Chem. Soc. Rev., 2016, 45, 1570; (c) W. Sun, G. Li, L.
Hong and R. Wang, Org. Biomol. Chem., 2016, 14, 2164. For
selected recent examples, see: (d) Q. Yin, S.-G. Wang, X.-W.
Therefore, 2a preferably attacked
α-position of 2-naphthol
from the Si-face to generate the corresponding R-configured
product 3ae and imine byproduct. If substituent was
introduced into the C3 or C4 positions of 2-naphthol, the steric
hindrance discrimination between the two sides of the
hydroxyl group decreases, thus it is difficult to control the
face-selection. As a result, the enantioselectivity for the
generation of product 3aa and lacinilene C methyl ether is
lower than the others.
Liang, D.-W. Gao, J. Zheng and S.-L. You, Chem. Sci., 2015, 6,
4179; (e) S.-G. Wang, Q. Yin, C.-X. Zhuo and S.-L. You, Angew.
Chem. Int. Ed., 2015, 54, 647; (f) D. Yang, L. Wang, F. Han, D.
Li, D. Zhao and R. Wang, Angew. Chem. Int. Ed., 2015, 54
,
2185; (g) J. Nan, J. Liu, H. Zheng, Z. Zuo, L. Hou, H. Hu, Y.
Wang and X. Luan, Angew. Chem. Int. Ed., 2015, 54, 2356; (h)
D. Yang, L. Wang, M. Kai, D. Li, X. Yao and R. Wang, Angew.
Chem. Int. Ed., 2015, 54, 9523; (i) S.-G. Wang, X.-J. Liu, Q.-C.
Zhao, C. Zheng, S.-B. Wang and S.-L. You, Angew. Chem. Int.
Ed., 2015, 54, 14929; (j) L. Yang, H. Zheng, L. Luo, J. Nan, J.
Liu, Y. Wang and X. Luan, J. Am. Chem. Soc., 2015, 137, 4876;
(k) J. Zheng, S.-B. Wang, C. Zheng and S.-L. You, J. Am. Chem.
Soc., 2015, 137, 4880; (l) Q. Cheng, Y. Wang and S.-L. You,
Angew. Chem., Int. Ed., 2016, 55, 3496; (m) H.-F. Tu, C. Zheng,
R.-Q. Xu, X.-J. Liu and S.-L. You, Angew. Chem. Int. Ed., 2017,
56, 3237; (n) D. Shen, Q. Chen, P. Yan, X. Zeng and G. Zhong,
Angew. Chem. Int. Ed., 2017, 56, 3242.
For selected review on recent asymmetric oxidative
dearomatization of phenols and naphthols: (a) “Asymmetric
Oxidative Dearomatization Reaction”: M. Uyanik and K.
Ishihara in Asymmetric Dearomatization Reactions (Ed.: S.-L.
You), Wiley-VCH, Weinheim, 2016 Chap. 6, pp. 129-152. For
examples: (b) T. Dohi, A. Maruyama, N. Takenaga, K. Senami,
Y. Minamitsuji, H. Fujioka, S. B. Caemmerer and Y. Kita,
Angew. Chem. Int. Ed., 2008, 47, 3787; (c) M. Uyanik, T. Yasui
and K. Ishihara, Angew. Chem. Int. Ed., 2010, 49, 2175; (d) M.
Uyanik, T. Yasui and K. Ishihara, Tetrahedron, 2010, 66, 5841;
Conclusions
In summary, we have described
a
highly chemo- and
enantioselective hydroxylative dearomatization of 2-naphthol
derivatives with oxaziridine catalyzed by a chiral N,N'-dioxide-
Sc(NTf2)3 complex catalyst. The desired substituted ortho-quinols
with one quaternary carbon stereogenic center were afforded with
high enantioselectivities and reactivity (up to 99% yield and 95:5
er). The α-ketol rearrangement byproducts were efficiently
suppressed. This new procedure has been successfully applied to
the catalytic asymmetric synthesis of the phytoalexines lacinilenes.
The application of the N,N'-dioxide/metal catalyst system in the
synthesis of other bioactive molecules will be explored.
5
(e) T. Oguma and T. Katsuki, J. Am. Chem. Soc., 2012, 134
,
20017; (f) T. Dohi, N. Takenaga, T. Nakae, Y. Toyoda, M.
Yamasaki, M. Shiro, H. Fujioka, A. Maruyama and Y. Kita, J.
Am. Chem. Soc., 2013, 135, 4558; (g) M. Uyanik, T. Yasui and
K. Ishihara, Angew. Chem. Int. Ed., 2013, 52, 9215; (h) T.
Oguma and T. Katsuki, Chem. Commun., 2014, 50, 5053; (i) S.
J. Murray and H. Ibrahim, Chem. Commun., 2015, 51, 2376; (j)
D.-Y. Zhang, L. Xu, H. Wu and L.-Z. Gong, Chem. Eur. J., 2015,
21, 10314; (k) N. Jain, S. Xu and M. A. Ciufolini, Chem. Eur. J.,
2017, 23, 4542.
Acknowledgements
The study was funded by the National Natural Science
Foundation of China (Nos.21290182, 21432006 and
21625205).
6
For selected examples of asymmetric hydroxylative
dearomatization: (a) S. Dong, J. Zhu and J. A. Porco, Jr., J. Am.
4 | J. Name., 2012, 00, 1-3
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Journal Name
ARTICLE
Chem. Soc., 2008, 130, 2738; (b) J. K. Boppisetti and V. B.
Birman, Org. Lett., 2009, 11, 1221; (c) S. Quideau, G. Lyvinec,
M. Marguerit, K. Bathany, A. Ozanne-Beaudenon, T.
Buffeteau, D. Cavagnat and A. Chénedé, Angew. Chem. Int.
Ed., 2009, 48, 4605; (d) K. A. Volp and A. M. Harned, Chem.
Commun., 2013, 49, 3001; (e) C. Bosset, R. Coffinier, P. A.
Peixoto, M. El. Assal, K. Miqueu, J.-M. Sotiropoulos, L.
Pouységu and S. Quideau, Angew. Chem. Int. Ed., 2014, 53
9860.
,
7
8
(a) C. Grandclaudon and P. Y. Toullec; Eur. J. Org. Chem.,
2016, 260; (b) M. Uyanik, T. Mutsuga and K. Ishihara; Angew.
Chem. Int. Ed., 2017, 56, 3956.
For reviews on chiral N,N′-dioxides: (a) X. H. Liu, L. L. Lin and
X. M. Feng, Acc. Chem. Res., 2011, 44, 574; (b) X. H. Liu, L. L.
Lin and X. M. Feng, Org. Chem. Front., 2014,
recent examples: (c) Q. Yao, Y. T. Liao, L. L. Lin, X. B. Lin, J. Ji,
X. H. Liu and X. M. Feng, Angew. Chem. Int. Ed., 2016, 55
1, 298; For
,
1859; (d) Y. Xia, L. L. Lin, F. Z. Chang, Y. T. Liao, X. H. Liu and X.
M. Feng, Angew. Chem. Int. Ed., 2016, 55, 12228; (e) Y.
Zhang, Y. T. Liao, X. H. Liu, Q. Yao, Y. H. Zhou, L. L. Lin and X.
M. Feng, Chem. Eur. J., 2016, 22, 15119; (f) Y. T. Liao, X. H.
Liu, Y. Zhang, Y. L. Xu, Y. Xia, L. L. Lin and X. M. Feng, Chem.
Sci., 2016, 7, 3775.
9
(a) D. J. Michaelis, C. J. Shaffer and T. P. Yoon, J. Am. Chem.
Soc., 2007, 129, 1866; (b) D. J. Michaelis, M. A. Ischay and T.
P. Yoon, J. Am. Chem. Soc., 2008, 130, 6610.
10 We tested HCl, AlCl3/NaI, BBr3, TMSBr to remove the MOM-
protecting group, but the corresponding lacinilene D was not
observed. The reactions would undergo as follows:
See the reference 2d in detail.
11 CCDC 1536822
(
3ae
)
contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre.
12 (a) P.-L. Shao, X.-Y. Chen and S. Ye, Angew. Chem., Int. Ed.,
2010, 49, 8412; (b) S. X. Dong, X. H. Liu, Y. Zhu, P. He, L. L. Lin
and X. M. Feng, J. Am. Chem. Soc., 2013, 135, 10026; (c) K. S.
Williamson, J. W. Sawicki and T. P. Yoon, Chem. Sci., 2014, 5,
3524; (d) X. B. Lin, S. Ruan, Q. Yao, C. K. Yin, L. L. Lin and X. M.
Feng, X. H. Liu, Org. Lett., 2016, 18, 3602.
13 X-ray single-crystal structure of N,N'-dioxide−Sc(III): Y. L. Liu,
D. J. Shang, X. Zhou, X. H Liu and X. M. Feng, Chem. Eur. J.,
2009, 15, 2055.
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Chemical Science
Page 6 of 6
View Article Online
DOI: 10.1039/C7SC02809A
A highly enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished by using a
N,N'-dioxide-scandium(III) complex catalyst. This methodology could be applied in the synthesis of bioactive lacinilenes in gram-scale
version.