Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)-H Functionalization under Mild Reaction Conditions

Article abstract of DOI:10.1002/anie.201510014

Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp³)-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp³)-H functionalization reaction effectively with high regio- and chemoselectivity.

Full text of DOI:10.1002/anie.201510014

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201510014
German Edition: DOI: 10.1002/ange.201510014
Photochemistry
Generation of Alkoxyl Radicals by Photoredox Catalysis Enables
3
À
Selective C(sp ) H Functionalization under Mild Reaction Conditions
Jing Zhang, Yang Li, Fuyuan Zhang, Chenchen Hu, and Yiyun Chen*
Abstract: Reported herein is the first visible-light-induced
formation of alkoxyl radicals from N-alkoxyphthalimides, and
the Hantzsch ester as the reductant is crucial for the reaction.
The selective hydrogen atom abstraction by the alkoxyl radical
3
À
enables C(sp ) H allylation and alkenylation reactions under
mild reaction conditions at room temperature. Broad substrate
variations, including a structurally complexed steroid, undergo
3
À
the C(sp ) H functionalization reaction effectively with high
regio- and chemoselectivity.
T
he alkoxyl radical is a pivotal intermediate in chemical and
biological studies, and it is not only useful for mechanistic
investigations,[1] but also leads to various useful organic
transformations.[2] While alkoxyl radical chemistry has been
widely utilized in organic synthesis for decades, it remains
a formidable challenge to generate alkoxyl radicals bearing
sensitive functional groups under mild reaction conditions.
Nitrites,[3] nitrates,[4] hypohalites,[5] sulphenates,[6] and N-
alkoxylpyridine-2-thiones[7] are widely used alkoxyl radical
precursors, however, they are either unstable or prepared
under conditions which are incompatible with many func-
tional groups. N-alkoxyphthalimides, in contrast, are known
to be bench-stable and easily prepared from alcohols with
good functional-group compatibility.[8,9] However, the con-
ventional generation of alkoxyl radicals requires relatively
harsh reaction conditions.[2,10] For example, heating conditions
with azodiisobutyronitrile/tributyltin hydride is required for
N-alkoxyphthalimides to generate alkoxyl radicals,[8] and
compromises its synthetic scope and functional-group com-
patibilities (Scheme 1a). Recently, visible-light catalysis has
provided a useful new entry to the initiation of radical
reactions under mild reaction conditions with good func-
tional-group compatibility, however, alkoxyl radical genera-
tion under photoredox conditions is unknown (Sche-
3
À
Scheme 1. Generation of alkoxyl radicals enables selective C(sp ) H
functionalization. AIBN=2,2’-azobis(2-methylpropionitrile).
À
alkoxyl radical easily activates C H bonds by a selective
intramolecular 1,5-hydrogen atom transfer (1,5-HAT) reac-
tion because of the higher oxygen–hydrogen bond energy.[14]
3
À
However, compared to the widely used C(sp ) H function-
alization strategy with transition metals, an efficient inter-
À
molecular C C bond formation after an alkoxyl radical 1,5-
HAT is problematic and very difficult.[15,16] In previously
reported 1,5-HAT reactions induced by alkoxyl radicals,
reductive hydrogenations, oxidative cyclizations, and other
carbon–heteroatom bond formations are dominant,[8,17] and
3
À
the trapping of a C(sp ) radical intermediate for efficient C C
bond coupling reaction is very limited.[16] Herein we report
the first selective C(sp ) H allylation and alkenylation
reactions enabled by an alkoxyl radical 1,5-HAT under mild
photoredox conditions (Scheme 1c).
3
À
By using the N-alkoxyphthalimide 1 and allyl sulfone 2 as
me 1b).[11,12]
the model substrates,[18] we first tested [Ru(bpy)3](PF6)2
3
(E0 II/I = À1.33 V vs. SCE in MeCN)[19] as the photocatalyst
À
The utilization of unactivated C(sp ) H bonds to engage
1/2
À
in new C C bond formation is desirable, but it is difficult to
under blue LED (lmax = 468 Æ 25 nm) irradiation (Table 1).
control the regioselectivity and chemoselectivity.[13] The
After screening various reaction conditions, including reduc-
tants and solvents (see Table S1 in the Supporting Informa-
3
À
tion), we gratifyingly observed the desired C(sp ) H allyla-
[*] J. Zhang, Y. Li, C. Hu, Prof. Dr. Y. Chen
State Key Laboratory of Bioorganic and Natural Products Chemistry,
Collaborative Innovation Center of Chemistry for Life Sciences,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences
tion adduct 3 in 75% yield by using diisopropylethylamine/
Hantzsch ester as reductants in 1,4-dioxane (entry 1). We then
optimized the concentration of the reaction and found that
0.1m of 1 is optimal for the reaction (entries 2 and 3). The use
345 Lingling Road, Shanghai 200032 (China)
E-mail: yiyunchen@sioc.ac.cn
of iridium-based photocatalysts, [Ir(dtbbpy)(bpy)2]PF6 (E0
1/
III/II = À1.51 V vs. SCE in MeCN)[20] and fac-[Ir(ppy)3] (E0
III/
2
1/2
F. Zhang, Prof. Dr. Y. Chen
School of Physical Science and Technology, ShanghaiTech University
100 Haike Road, Shanghai 201210 (China)
II = À2.19 V vs. SCE in MeCN),[21] accelerate the reaction
such that the reaction is complete after 3 hours, and the use of
tributylamine increases the product yield to 77% (entries 4–
6). The removal of the Hantzsch ester surprisingly shuts down
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201510014.
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3
À
Table 1: Optimization of the alkoxyl radical enabled C(sp ) H function-
alization.
Entry Reaction conditions[a]
t [h] Conv. [%][b] Yield [%][b]
1
2
3
4
5
6
7
8
[Ru(bpy)3](PF6)2, iPr2NEt, HE
entry 1, 0.05 m of 1
entry 1, 0.2 m of 1
[Ir(dtbbpy)(ppy)2]PF6, iPr2NEt, HE
fac-[Ir(ppy)3], iPr2NEt, HE
fac-[Ir(ppy)3], nBu3N, HE
fac-[Ir(ppy)3], nBu3N
24
24
24
3
3
3
24
3
3
>95
91
66
>95
>95
>95
<5
>95
<5
75
71
56
65
68
77
0
94 (90)
0
0
fac-[Ir(ppy)3], HE
9[c] fac-[Ir(ppy)3], N-Me HE
10[c] fac-[Ir(ppy)3], BNAH
3
<5
[a] Reaction conditions: 1 (0.10 mmol), 2 (0.30 mmol), photocatalyst
(0.001 mmol), Hantzsch ester (HE, 0.15 mmol), and additives
(0.20 mmol) in 1.0 mL 1,4-dioxane under nitrogen with 468 nm LED
irradiation. [b] Conversions and yields were determined by 1H NMR
analysis. Yields of isolated products are given within parentheses.
[c] N-Me HE (0.15 mmol), or BNAH (0.15 mmol) was used as the
reductant. bpy=2,2’-bipyridine, phth=phthalimide, ppy=phenylpyri-
dine.
Scheme 2. Mechanistic investigations of the alkoxyl radical enabled
3
À
C(sp ) H functionalization. HE=Hanztsch ester.
the reaction (entry 7), while the removal of the tributylamine
affords an optimal 94% yield (90% yield of isolated product;
entry 8). Other analogues of the Hantzsch ester, such as N-
methyl Hantzsch ester (N-Me HE) or 1-benzyl-1,4-dihydro-
nicotinamide (BNAH), are not effective (entries 9 and 10).
The light irradiation and photocatalyst are both important for
the reaction (see Table S1).
molecule, a characteristic b-fragmentation of the alkoxyl
radical (Scheme 2b).[24] We also carried out crossover experi-
3
À
ments to explore whether this C(sp ) H activation occurs
through intramolecular or intermolecular HAT (Scheme 2c).
When the N-alkoxyphthalimide 10 and the alcohol 11 are
both subjected to the reaction conditions, we only obtain the
allylation adduct 12 in 88% yield, and 3 is not observed. We
also prepared the deuterium-substituted N-alkoxyphthal-
imide 13 (D/H = 1:1) and subjected it to the reaction
conditions (Scheme 2d). The allylation adduct 14 is obtained
with D/H = 0.65:0.35, and the different migratory aptitudes
between the deuterium and hydrogen further provides
evidence for the alkoxyl radical 1,5-HAT.
To gain mechanistic insights on this novel alkoxyl radical
formation, we first tested the 1-naphthalene-substituted N-
À
alkoxyphthalimide 4, which does not have d-C H bonds.
Under the optimized reaction conditions and without allyl
acceptors, we observed the 1-naphthalenylmethanol 5 as the
alkoxyl radical reduction adduct in 61% yield (Scheme 2a,
entry 1). When formic acid is added to the reaction, 5 is
obtained in an increased yield of 82% (entry 2). Interestingly,
when the sodium carbonate base is added, the yield of 5 is
decreased to 50%, and in addition, the 1-naphthaldehyde 6 is
observed in 17% yield (entry 3). As the formation of the 1-
naphthaldehyde is due to the intramolecular elimination of
the N-alkoxyphthalimide radical anion,[11] these results col-
lectively suggest that the protonation of the N-alkoxyphthal-
imide radical anion is important for the alkoxyl radical
formation, and is similar to the coordination of the N-
alkoxyphthalimide radical anion by tributyltin in the AIBN/
Bu3SnH system.[8,22]
Based on mechanistic investigations above, we propose
that fac-[Ir(ppy)3] is photoexcited to fac-[Ir(ppy)3]* and
reduced by the Hantzsch ester to IrII (Scheme 3).[25] The
resulting IrII intermediate reduces the N-alkoxyphthalimide
We also carried out luminescence quenching experiments
with fac-[Ir(ppy)3]. The Hantzsch ester effectively quenches
the photoexcited fac-[Ir(ppy)3]*, and suggests that the
reductive quenching is the major reaction pathway to
generate the IrII intermediate.[23] When the N-alkoxyphthal-
3
À
imide 7 is used, we observe allylation at the d-C(sp ) H
3
position (8) together with the allylation adduct 9, which is
À
Scheme 3. Mechanistic proposal of the alkoxyl radical enabled C(sp )
missing a two-carbon unit, by elimination of the acetaldehyde
H functionalization.
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by single-electron transfer to yield the N-alkoxyphthalimide
radical anion, which is further protonated by the Hantzsch
ester radical cation to facilitate the formation of the alkoxyl
radical.[26] Finally, the alkoxyl radical undergoes 1,5-HAT
reaction and subsequent intermolecular carbon radical trap-
and indole-containing heterocycles all react smoothly to give
3
À
the C(sp ) H allylation adducts 19–21, with slightly decreased
reaction yields. The a-heteroatom activation is not necessary
À
for the reaction and the benzyl C H bonds react to give 22
and 23 in good yields.[29] The unactivated tertiary C H bonds
À
À
ping to yield the C C bond-coupling adduct. In the photo-
also react smoothly to give 24 and 25 in 63% and 58% yield,
respectively,[30] as they are slightly less reactive than those
with neighboring activating groups.[31]
redox system, the Hantzsch ester is crucial for both the
electron transfer and proton transfer of the reaction, and may
explain the inhibition of the reaction when it is removed.[27]
We next explored the substrate scope and found that the
As the alkoxyl radical is known to be highly reactive, we
next tested the regioselectivity of the reaction (Scheme 4):
The N-alkoxyphthalimide substrates with both d- and e-
À
reaction works well for a-heteroatom-activated C H bonds,
3
3
À
À
such as with para-methoxy substitution, to give the allylated
15 in 91% yield (reaction conditions: entry 8 in Table 1),
whereas the para-fluoro and ortho-iodo substituents gave 16
C(sp ) H bonds give the d-C(sp ) H activation adducts 26
3
À
and 12 exclusively, and the e-C(sp ) H functionalization
adducts were not observed, thus showcasing the selectivity of
the reaction.[32] Methine, methylene, and methyl C H bonds
À
(80%) and 17 (76%), respectively (Scheme 4). Notably, this
3
À
d-C(sp ) H functionalization is not affected by the steric bulk
activated by an oxygen atom react well to give 26, 12, and 27,
on the aryl ring, that is, the 2,4,6-trimethyl-substituted arene
respectively. The allyl acceptors can be extended to phenyl-
18 is obtained in 75% yield. We explored whether hetero-
substituted allyls and give the products 28–30 in 62–75%
3
À
cycles could be tolerated under the reaction conditions,
yields. This C(sp ) H functionalization is not only applicable
3
3
3
3
2
À
À
À
a substrate class with which many C(sp ) H activation
to C(sp ) C(sp ) bond formation, but also to C(sp ) C(sp )
methods encounter difficulties.[28] The thiophene-, pyridine-,
bond formation. With aryl vinyl sulfones as the radical
acceptor,[33] the C(sp ) H alkenylation products are obtained
3
À
smoothly and exclusively with an E configuration under the
reaction conditions depicted in entry 8 in Table 1. The vinyl
sulfones substituted with phenyl, para-chlorophenyl, and
para-methoxylphenyl groups react to give the alkenes 31–36
smoothly, among which aryl vinyl sulfones with electron-
deficient substitution give higher yields.
Given the excellent regioselectivity and chemoselectivity,
3
À
À
we tested this C(sp ) H allylation on site-selective C H
functionalization of complex molecules, as it represents an
attractive approach for late-stage modification of complex
molecules.[34] When the N-alkoxyphthalimide-substituted ste-
roid 37 is subjected to the reaction conditions, the allylation
adduct 39 is obtained stereoselectively on gram scale in 65%
yield, with complete stereoretention (Scheme 5).[35]
Scheme 5. Late-stage modification of complexed molecules.
In conclusion, we have developed the first visible-light-
induced formation of alkoxyl radicals from N-alkoxyphthal-
imides, and the Hantzsch ester plays a crucial role in the
3
À
photoredox system. Activated and unactivated C(sp ) H
bonds react to yield selective allylation and alkenylation
adducts with excellent regio- and chemoselectivity under mild
reaction conditions. Additional reactivity of alkoxyl radicals
and their applications in modifications of complex molecules
or biomolecules are under investigation in our laboratory.
3
À
Scheme 4. Substrate scope of the alkoxyl radical enabled C(sp ) H
functionalization. Reaction conditions: entry 8 in Table 1. Yields are
those of isolated products.
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[17] a) C. G. Francisco, R. Freire, A. J. Herrera, I. Perez-Martin, E.
Acknowledgments
Suµrez, Org. Lett. 2002, 4, 3337; b) C. G. Francisco, R. Freire,
A. J. Herrera, I. Perez-Martin, E. Suµrez, Tetrahedron 2007, 63,
8910; c) H. Zhu, J. C. T. Leung, G. M. Sammis, J. Org. Chem.
2015, 80, 965.
Financial support was provided by National Basic Research
Program of China 2014CB910304, National Natural Science
Foundation of China 21272260, 21472230 “Thousand Talents
Program” Young Investigator Award.
[18] F. Bertrand, F. Le Guyader, L. Liguori, G. Ouvry, B. Quiclet-
Sire, S. Seguin, S. Z. Zard, C. R. Acad. Sci. Ser. IIc 2001, 4, 547.
[19] C. R. Bock, J. A. Connor, A. R. Gutierrez, T. J. Meyer, D. G.
Whitten, B. P. Sullivan, J. K. Nagle, J. Am. Chem. Soc. 1979, 101,
4815.
[20] I. M. Dixon, J. P. Collin, J. P. Sauvage, L. Flamigni, S. Encinas, F.
Barigelletti, Chem. Soc. Rev. 2000, 29, 385.
[21] L. Flamigni, A. Barbieri, C. Sabatini, B. Ventura, F. Barigelletti,
Top. Curr. Chem. 2007, 281, 143.
À
Keywords: allylic compounds · C H functionalization ·
photochemistry · alkoxyl radicals · reaction mechanisms
How to cite: Angew. Chem. Int. Ed. 2016, 55, 1872–1875
Angew. Chem. 2016, 128, 1904–1907
[22] The protonation of the N-alkoxyphthalimide radical anion is
similar to the coordination by tributyltin in the AIBN/Bu3SnH
system to induce alkoxyl radical formation, see: Refs. [8] and [11].
[1] a) E. A. Theodorakis, K. M. Wilcoxen, Chem. Commun. 1996,
1927; b) E. A. Theodorakis, X. Xiang, P. Blom, Chem. Commun.
1997, 1463; c) W. Adam, G. N. Grimm, S. Marquardt, C. R. Saha-
Moller, J. Am. Chem. Soc. 1999, 121, 1179.
ˇ
ˇ
´
[2] a) G. J. Rowlands, Tetrahedron 2010, 66, 1593; b) Z. Cekovic,
Tetrahedron 2003, 59, 8073; c) S. Chiba, H. Chen, Org. Biomol.
Chem. 2014, 12, 4051; d) C. G. Francisco, A. J. Herrera, E.
Suµrez, J. Org. Chem. 2002, 67, 7439; e) J. Hartung, Eur. J. Org.
Chem. 2001, 619.
[23] In luminescence quenching experiments with fac-[Ir(ppy)3], the
Kq for the Hanztsch ester is 1.7 ” 107 mÀ1 sÀ1 while for N-
alkoxyphthalimide 1 is 1.8 ” 105 mÀ1 sÀ1. When considered along
[3] D. H. R. Barton, J. M. Beaton, L. E. Geller, M. M. Pechet, J.
Am. Chem. Soc. 1960, 82, 2640.
[4] G. D. Vite, B. Fraser-Reid, Synth. Commun. 1988, 18, 1339.
[5] C. Walling, R. T. Clark, J. Am. Chem. Soc. 1974, 96, 4530.
[6] A. L. J. Beckwith, B. P. Hay, G. M. Williams, J. Chem. Soc. Chem.
Commun. 1989, 1202.
with the oxidation potentials of N-alkoxyphthalimide
1
IV/
(E0 red = À1.35 V vs. SCE in MeCN) and fac-[Ir(ppy)3] (E0
1/2
1/2
III* = À1.73 V vs. SCE in MeCN), a minor oxidative quenching
mechanism cannot be excluded (see Schemes S1–S4).
[24] a) C. Walling, A. Padwa, J. Am. Chem. Soc. 1963, 85, 1593;
b) D. V. Avila, C. E. Brown, K. U. Ingold, J. Lusztyk, J. Am.
Chem. Soc. 1993, 115, 466; c) A. Boto, D. Hernandez, R.
Hernandez, E. Suµrez, J. Org. Chem. 2003, 68, 5310.
[7] A. L. J. Beckwith, B. P. Hay, J. Am. Chem. Soc. 1988, 110, 4415.
[8] S. Kim, T. A. Lee, Y. Song, Synlett 1998, 471.
[9] H. Zhu, J. G. Wickenden, N. E. Campbell, J. C. T. Leung, K. M.
Johnson, G. M. Sammis, Org. Lett. 2009, 11, 2019.
[25] The fac-[Ir(ppy)3] can also be reduced by the Hanztsch ester to
IrII in the dark, however the efficiency is very low. See: K. A.
Hollister, E. S. Conner, M. L. Spell, K. Deveaux, L. Maneval,
M. W. Beal, J. R. Ragains, Angew. Chem. Int. Ed. 2015, 54, 7837;
Angew. Chem. 2015, 127, 7948.
[26] The Hantzsch ester can also be photoexcited and thus reduce the
N-alkoxyphthalimide in the absence of fac-[Ir(ppy)3], but it is
not the major pathway of the N-alkoxyphthalimide reduction;
see Ref. [12a].
[27] M. H. Larraufie, R. Pellet, L. Fensterbank, J. P. Goddard, E.
Lacote, M. Malacria, C. Ollivier, Angew. Chem. Int. Ed. 2011, 50,
4463; Angew. Chem. 2011, 123, 4555.
[28] a) H. A. Malik, B. L. H. Taylor, J. R. Kerrigan, J. E. Grob, K. N.
Houk, J. Du Bois, L. G. Hamann, A. W. Patterson, Chem. Sci.
2014, 5, 2352; b) Y. J. Liu, H. Xu, W. J. Kong, M. Shang, H. X.
Dai, J. Q. Yu, Nature 2014, 515, 389.
ˇ
ˇ
´
[10] a) Z. Cekovic, J. Serb. Chem. Soc. 2005, 70, 287; b) J. Hartung, F.
Gallou, J. Org. Chem. 1995, 60, 6706; c) J. Sperry, Y. C. Liu,
M. A. Brimble, Org. Biomol. Chem. 2010, 8, 29.
[11] A single example using N-alkoxylphthalimides under photo-
redox conditions was reported, however no alkoxyl radical was
observed, see: M. Zlotorzynska, G. M. Sammis, Org. Lett. 2011,
13, 6264.
[12] For examples using N-acyloxyphthalimides to generate carboxyl
radicals under photoredox conditions, see: a) K. Okada, K.
Okamoto, N. Morita, K. Okubo, M. Oda, J. Am. Chem. Soc.
1991, 113, 9401; b) M. J. Schnermann, L. E. Overman, Angew.
Chem. Int. Ed. 2012, 51, 9576; Angew. Chem. 2012, 124, 9714;
c) G. Kachkovskyi, C. Faderl, O. Reiser, Adv. Synth. Catal. 2013,
355, 2240; d) J. Yang, J. Zhang, L. Qi, C. Hu, Y. Chen, Chem.
Commun. 2015, 51, 5275.
[13] a) X. Chen, K. M. Engle, D. H. Wang, J. Q. Yu, Angew. Chem.
Int. Ed. 2009, 48, 5094; Angew. Chem. 2009, 121, 5196; b) T. W.
Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; c) R. Jazzar, J.
Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur.
J. 2010, 16, 2654; d) T. Newhouse, P. S. Baran, Angew. Chem. Int.
Ed. 2011, 50, 3362; Angew. Chem. 2011, 123, 3422; e) H. Li, B. J.
Lia, Z. J. Shi, Catal. Sci. Technol. 2011, 1, 191.
[14] L. Feray, N. Kuznetsov, P. Renaud, Radicals in Organic Synthesis,
Vol. 2 (Eds.: P. Renaud, M. B. Sibi), Wiley-VCH, Weinheim,
2001, chap. 3.6.
[29] a) H. G. Korth, P. Lommes, R. Sustmann, J. Am. Chem. Soc.
1984, 106, 663; b) H. Zipse, Top. Curr. Chem. 2006, 263, 163.
[30] The ester of 1-naphthalenylmethanol is used to visualize the
substrates more easily.
[31] R. S. Davidson, Q. Rev. Chem. Soc. 1967, 21, 249.
[32] a) A. E. Dorigo, K. N. Houk, J. Am. Chem. Soc. 1987, 109, 2195;
b) A. E. Dorigo, M. A. Mccarrick, R. J. Loncharich, K. N. Houk,
J. Am. Chem. Soc. 1990, 112, 7508.
[33] a) N. S. Simpkins, Tetrahedron 1990, 46, 6951; b) A. El-Awa,
M. N. Noshi, X. M. du Jourdin, P. L. Fuchs, Chem. Rev. 2009, 109,
6920; c) J. Xiang, P. L. Fuchs, J. Am. Chem. Soc. 1996, 118, 11986.
[34] J. Wencel-Delord, F. Glorius, Nat. Chem. 2013, 5, 369.
[35] See the Supporting Information for characterization details.
[15] D. P. Curran, W. Shen, J. Am. Chem. Soc. 1993, 115, 6051.
À
[16] Examples of isolated intermolecular C C bond formations by
alkoxyl radical 1,5-HAT were reported and used either a large
´
excess of reagents or specialized tin reagents. See: a) G. Petrovic,
ˇ
ˇ
´
Z. Cekovic, Tetrahedron Lett. 1997, 38, 627; b) A. Martín, I.
Perez-Martin, L. M. Quintanal, E. Suµrez, Tetrahedron Lett.
2008, 49, 5179; c) E. I. León, A. Martin, I. Perez-Martin, L. M.
Quintanal, E. Suµrez, Eur. J. Org. Chem. 2012, 3818.
Received: October 27, 2015
Revised: November 30, 2015
Published online: December 17, 2015
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