Copper-Catalyzed Oxidative Dimerizations of 3-N-Hydroxy-aminoprop-1-enes to form 1,4-Dihydroxy-2,3-diaminocyclohexanes with C2 Symmetry

Article abstract of DOI:10.1002/anie.201407987

This work describes the one-step construction of complex and important molecular frameworks through copper-catalyzed oxidations of cheap tertiary amines. Copper-catalyzed aerobic oxidations of N-hydroxyaminopropenes to form C₂-symmetric N- and

Full text of DOI:10.1002/anie.201407987

Angewandte
Chemie
DOI: 10.1002/anie.201407987
Synthetic Methods
Copper-Catalyzed Oxidative Dimerizations of 3-N-Hydroxy-amino-
prop-1-enes to form 1,4-Dihydroxy-2,3-diaminocyclohexanes with
C2 Symmetry**
Satish Ghorpade and Rai-Shung Liu*
Abstract: This work describes the one-step construction of
complex and important molecular frameworks through
copper-catalyzed oxidations of cheap tertiary amines.
Copper-catalyzed aerobic oxidations of N-hydroxyaminopro-
penes to form C2-symmetric N- and O-functionalized cyclo-
hexanes are described. Such catalytic oxidations proceed with
remarkable stereocontrol and high efficiency. Reductive cleav-
À
age of the two N O bonds of these products delivers 1,4-
dihydroxy-2,3-diaminocyclohexanes, which are important
skeletons of several bioactive molecules.
duce highly O- and N-functionalized cyclohexanes (6) with
excellent stereoselectivity (d.r. > 20:1) [Eq. (3)]. Subsequent
À
reductive cleavage of their N O bonds affords 1,4-dihydroxy-
2,3-diaminocyclohexanes (7) efficiently. Notably, these sub-
stances do not follow current process to generate alkenylni-
trone intermediates [Eq. (1)], despite the presence of a NCH2
moiety.
À
M
etal-catalyzed oxidative C H functionalizations of ami-
noalkane moieties have been a subject of intense interest
because of their practical significance.[1] Reported examples
focus mainly on the formation of iminium ions (I) which are
subsequently attacked by suitable nucleophiles [Eq. (1)].[2–6]
These resulting O- and N-containing cyclohexane frame-
works are found in bioactive molecules of various families as
exemplified by the species III–VI (Figure 1), and their
stereoselective synthesis inevitably requires long proce-
dures.[11–15] Some 1,2-diaminocyclitols (III)[12] are potent
glucocerebrosidase activators and promising pharmacological
chaperones for Gaucher disease. In contrast, several condur-
itols (IV) showed biological activity as glycosidase inhib-
itors.[13] The compounds (V) are alcohol derivatives of trans-
diaminocyclohexane dichloroplatinum (DACH-PtCl2), which
exhibits potent antitumor activity against P388 leukemia.[14]
Oseltamivir phosphate (VI; Tamiflu) is currently used for the
treatment of influenza.[15]
These reactions are appealing surrogates for the well-known
Mannich reaction[7] because tertiary amines (1) are readily
available and cheap reagents. N-Hydroxyaminoalkanes (1,
R’ = OH) are an important class of organic compounds,[8] and
À
their C H oxidative functionalization generate nitrone spe-
cies (I; R’ = OÀ) as depicted in Equation (1).[9] Alternatively,
a-carbonyl N-hydroxyamino species (3) undergo metal-free
oxidations to generate reactive amidoxyl radicals (II), which
[10]
À
then attack an alkene to form a new C O bond [Eq. (2)].
À
Despite numerous publications, the present N CH oxidative
functionalizations focus mainly on the Mannich-type reac-
tions, rather than on the construction of complicated frame-
works. Herein, we report the copper-catalyzed oxidative
dimerizations of 3-N-hydroxy-aminoprop-1-enes (5) to pro-
Table 1 presents optimization of the reaction conditions
for the oxidative dimerizations of the 3-N-hydroxy-1-propene
5a using various catalysts, oxidants, and solvents. We first
[*] S. Ghorpade, Prof. Dr. R.-S. Liu
Department of Chemistry, National Tsing Hua University
101, Sec. 2, Kuang-Fu Rd., Hsinchu 30013 (Taiwan)
E-mail: rsliu@mx.nthu.edu.tw
Homepage: http://chem-en.web.nthu.edu.tw/files/13-1117-
33454.php
[**] We thank the National Science Council, Taiwan for financial support
of this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201407987.
Figure 1. Representative bioactive molecules.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Conditions for the oxidative dimerizations of 5a.
Table 2: Scope for the oxidative dimerizations.
Entry Catalyst
Oxidant
Solvent[a] Additive t [h] Yield[b] [%]
1
2
3
4
5
6
7
8
CuCl
CuBr
[IPrCuCl] O2
CuCl2
FeCl3
Co(OAc)2 O2
[IPrCuCl] O2
[IPrCuCl] O2
[IPrCuCl] H2O2
[IPrCuCl] tBuOOH THF
[IPrCuCl] DTBP
[IPrCuCl]
–
O2
O2
THF
THF
THF
THF
THF
THF
toluene
DCE
THF
–
–
–
–
–
–
–
–
9
9
9
9
9
10
9
9
63
70
84
25
67
76
69
55
71
75
68
–
O2
O2
9
4 ꢀ M.S.
4 ꢀ M.S. 12
9
10
11
12
13
THF
THF
THF
–
–
–
12
12[c]
12
–
O2
–
[a] [5a]=0.20m. [b] Product yields are reported after purification from
a silica gel column. [c] The recovery yield of 5a was 67 and 71% for
entries 12 and 13, respectively. M.S.=molecular sieves, THF=tetrahy-
drofuran.
tested the reaction with a CuCl catalyst (5 mol%) and O2
(1 atm) in THF under ambient conditions (258C, 9 h), which
led to 1,4-dihydroxy-2,3-diaminocyclohexane 6a as a single
diastereomeric product (d.r. > 20:1) with a yield of 63%
(entry 1). Among other copper catalysts tested, [IPrCuCl]
(IPr= 1,3-bis(diisopropylphenyl)imidazol-2-ylidene) gave the
best yield (84%) of 6a (entry 3), whereas CuBr and CuCl2
provided the same product in 70 and 25%, respectively
(entries 2 and 4). In the presence of O2, both FeCl3 and
Co(OAc)2 were also effective catalysts, thus yielding 6a in 67
and 76% yield, respectively (entries 5 and 6). The use of
[IPrCuCl] in toluene and 1,2-dichloroethane (DCE) gave 6a
in 69 and 55% yield, respectively (entries 7 and 8). With
[IPrCuCl], other oxidants such as H2O2, tert-butyl peroxide
(TBPO), and di-tert-butyl peroxide (DTBP) also give the
desired 6a in 68–75% yields (entries 9–11). In the absence of
an oxidant and metal catalyst, no reaction occurred over
a protracted period (12 h) with 67 and 71% recovery,
respectively, of the staring 5a (entries 12 and 13). The
structural characterization of 6a relies on X-ray diffraction.[16]
The ORTEP drawing (see the Supporting Information)
indicates the presence of C2 symmetry for the molecular
framework.
We prepared additional 2-substituted 3-N-hydroxy-1-
propenes (5b–u) to examine the generalization of such
oxidative dimerizations (Table 2). Most reactions were per-
formed with 5 mol% [IPrCuCl]/O2 in THF (258C, 11–16 h)
except for those involving 5j–l, for which the reactions were
run with [IPrCuCl]/tBuO2H (3 equiv) in THF (4 ꢀ M.S.,
258C, 11–12 h). In all cases, the resulting O- and N-function-
alized cyclohexanes 6b–u were obtained as a single diaste-
reomer (d.r. > 20:1). We tested the oxidations with the initial
substrates 5b–f, bearing variable aniline groups (R2 = 4-
XC6H4, X = F, Cl, Br, CO2Me and Me), and the resulting
products 6b–f were obtained in 74–83% yields. We also
[a] [6b]=0.20m. Product yields are reported after purification from
a silica gel column.
prepared their meta-substituted analogues 5g–i (R2 = 3-
XC6H4, X = Cl, Me, and OMe), which gave the desired
products 6g–i in 78–89%. The dimerizations of the ortho-
substituted analogues 5j–l (R2 = 2-X C6H4, X = Cl, Br, and
Me) were unsuccessful with [IPrCuCl] and O2, but the use of
[IPrCuCl] and tBuO2H (3 equiv) enabled the production of
desired compounds 6j–l in reasonable yields (51–68%). We
envisage that these ortho substituents are not favorable for
the coordination of copper with their hydroxyamino groups,
thus rendering the oxidation difficult. We also prepared the 3-
N-hydroxy-1-propenes 5m–o bearing various alkenyl sub-
stituents (R1 = 4-XC6H4, X = Br, Cl, and Me), and their
oxidative dimerizations proceeded smoothly with [IPrCuCl]/
O2 to give the desired 6m–o in 61-83% yields. For the
substrates 5p and 5q bearing a 2- and 3-thienyl group,
respectively, at the alkenyl moiety, their corresponding
products 6p (82%) and 6q (69%) were obtained. To our
delight, these catalytic oxidations were compatible with the
substrates 5r–u, bearing various alkyl groups at their amino or
alkenyl positions (R1 = Me, iPr or R2 = iPr or tBu), and their
desired dimerization products 6r–u were obtained in 72–81%
yields. These oxidative dimerizations failed to work with
those substrates bearing R1 = CO2Me and H, and thus
resulted in a complex mixture of products.
We also examined the access to the O- and N-containing
À
cyclohexanes 7 by employing reductive cleave of the N O
bonds of the products 6. The procedures[17] involved Pd/C and
H2 (1 atm) in MeOH/CH2Cl2 (1:1) near 258C. The results are
À
summarized in Table 3. As shown, this N O cleavage works
2
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
À
Table 3: Reductive cleavage of the N O bonds.
derivative 8c in 54% yield through an intramolecular
cyclization of the E-configured nitrone intermediate (E)-I’.
We thus exclude the role of nitrone intermediates (I’) in the
dimerization reactions because of their distinct chemoselec-
tivity. We tested further the dimerization of 5a with chiral
CuOTf/L2* [L2* = 2,2-bis{(4S)-(À)-4-isopropyloxazoline}-
propane], which enabled the production of (À)-6a in 19 and
27% ee in THF and toluene, respectively.[18] The observed
asymmetric induction of (À)-6a suggests that copper com-
À
plexes participate in the formation of the first asymmetric C
C bond during the course of the dimerization.
We postulate a mechanism in Scheme 1. Under O2, CuII
species are generated to coordinate with two molecules of the
N-hydroxy aminopropenes 5 to form Cu-5, which undergoes
a single-electron transfer (SET) to generate the radical cation
A, and subsequently yields the amidoxyl radical B.[10] We
[a] [6a]=0.04m. Product yields are reported after purification from
a silica gel column.
well for 6a–c and 6e, bearing various aniline groups (R2 = 4-
XC6H4, X = H, F, Cl, and CO2Me), thus yielding the desired
À
7a–c and 7e in satisfactory yields (78–85%). This N O
cleavage is applicable to their meta- or ortho-substituted
aniline analogues (6g–i and 6j–l), thus giving the highly
functionalized cyclohexanes 7g–i and 7j–l in 69–83% yields.
The cleavage also proceeded well with substrates 6n and 6o
comprising different R1 substituents (R1 = 4-XC6H4, X = Cl
and Me), and giving the compounds 7n and 7o, respectively,
in good yields. These reactions were compatible with the 2-
and 3-thienyl-containing species 6p and 6q, respectively, thus
yielding the corresponding products 7p (72%) and 7q (63%).
For the alkyl-substituted derivatives 6r–u, the reductive
cleavage delivered the compounds 7r–u in 67–81% yields.
Of these products, X-ray diffraction[16] of a representative
compound, 7b, was performed to confirm its structure as
having all hydroxy and amino groups in axial positions.
Shown in Equations (4) and (5) (Tf = trifluoromethane-
sulfonyl) are control experiments to assist the understanding
of the mechanism of the dimerization. Treatment of N-
hydroxyaniline (8a) with 2-phenyl-2-en-1-al (8b) with [IPr-
CuCl]/O2 in toluene (258C, 12 h) produced the quinoline
Scheme 1. Postulated mechanism and stereochemical course.
envisage that B becomes a stable allyl radical C by hydrogen
transfer. Concurrently, air oxidation of CuI to CuII, as with C,
enables the same SET to form the bis(allyl) radical D, further
inducing a dimerization to generate species E. Notably, E
should preferably have a trans configuration for two bulky
alkenyl groups to minimize steric hindrance. We envisage that
E tends to release CuI because of its highly substituted and
congested geometry, thus yielding the dimers F only in dl-
forms. This process rationalizes well the asymmetric induction
of the chiral copper catalyst [Eq. (5)]. As shown by the
ground-state staggered conformations, F undergoes SET to
generate the amidoxyl radical G to activate double radical/
alkene cyclizations,[10] thus yielding the tertiary carbon radical
H efficiently. CuII oxidation of these carbon radicals form to
activate double radical/alkene cyclizations,[10] thus yielding
the stable tertiary cation I, and ultimately giving the desired
compounds 6 upon ring closure. Such cascade radical
cyclizations are consistent with the stereochemical course of
these dimerizations.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
K. M. Harhammer, D. Mihovilovic, M. Schnꢂrch, Chem.
Commun. 2010, 46, 8836 – 8838; f) C. M. R. Volla, P. Vogel,
Org. Lett. 2009, 11, 1701 – 1704; g) M. O. Ratnikov, X. Xu, M. P.
Doyle, J. Am. Chem. Soc. 2013, 135, 9475 – 9479.
In this mechanism, we did not observe a 5-endo-trig
radical cyclization for the monomeric species B because this
process is not feasible according to the Baldwinꢁs rule.[19] In
contrast, the 5-exo-trig cyclization of G is operable in accord
with this rule. We postulated that its rigid staggered con-
formation allows the amidoxy radical close to its alkenyl
group to facilitate this process.
In summary, we report the copper-catalyzed aerobic
oxidation of N-hydroxyaminopropenes to form N- and O-
containing cyclohexane derivatives. Such oxidations proceed
with surprising stereocontrol and high efficiency. Reductive
[4] a) M.-Z. Wang, C.-Y. Zhou, M.-K. Wong, C.-M. Che, Chem. Eur.
J. 2010, 16, 5723 – 5735; b) S.-I. Murahashi, T. Naota, K.
Yonemura, J. Am. Chem. Soc. 1988, 110, 8256 – 8258; c) S.-I.
Murahashi, T. Naota, T. Kuwabara, T. Saito, H. Kumobayashi, S.
Akutagawa, J. Am. Chem. Soc. 1990, 112, 7820 – 7822; d) S.-I.
Murahashi, N. Komiya, H. Terai, T. Nakae, J. Am. Chem. Soc.
2003, 125, 15312 – 15313; e) S.-I. Murahashi, T. Saito, T. Naota,
H. Kumobayashi, S. Akutagawa, Tetrahedron Lett. 1991, 32,
5991 – 5994; f) S.-I. Murahashi, T. Nakae, H. Terai, N. Komiya, J.
Am. Chem. Soc. 2008, 130, 11005 – 11012; g) A. Yu, Z. Gu, D.
Chen, W. He, P. Tan, J. Xiang, Catal. Commun. 2009, 11, 162 –
166.
[5] a) A. J. Catino, J. M. Nichols, B. J. Nettles, M. P. Doyle, J. Am.
Chem. Soc. 2006, 128, 5648 – 5649; b) M. O. Ratnikov, M. P.
Doyle, J. Am. Chem. Soc. 2013, 135, 1549 – 1557; c) K. Alagiri,
K. R. Prabhu, Org. Biomol. Chem. 2012, 10, 835 – 842.
[6] a) A. Sud, D. Sureshkumar, M. Klussmann, Chem. Commun.
2009, 3169 – 3171; b) S. Singhal, S. L. Jain, B. Sain, Chem.
Commun. 2009, 2371 – 2372.
À
cleavage of the N O bonds of these functionalized cyclo-
hexanes affords 1,4-dihydroxy-2,3-diaminocyclohexanes
which are the structural skeletons of several bioactive
molecules. Our control experiments exclude the formation
of nitrone intermediates, whereas chiral copper catalysts can
induce asymmetric induction. We postulate a mechanism in
which the key step involves the coordination of CuII with two
À
allyl radicals to achieve a stereoselective C C bond forma-
tion. These dl-configured dimeric intermediates presumably
form amidoxyl radicals to undergo tandem radical/alkene
cyclizations with high stereocontrol, thus giving observed
products efficiently.
[7] a) G. Casiraghi, L. Battistini, C. Curti, G. Rassu, F. Zanardi,
Chem. Rev. 2011, 111, 3076 – 3154; b) B. B. Tourꢄ, D. G. Hall,
Chem. Rev. 2009, 109, 4439 – 4486.
[8] H. C. J. Ottenheijm, J. D. M. Herscheid, Chem. Rev. 1986, 86,
697 – 707.
Received: August 5, 2014
Published online: && &&, &&&&
[9] For copper-catalyzed aerobic oxidations of N-hydroxyamines to
nitrone species, see: a) G. W. Gribble, T. C. Barden, J. Org.
Chem. 1985, 50, 5900 – 5902; b) T. Sakurai, Y. Uematsu, O.
Tanaka, H. Inoue, J. Chem. Soc. Perkin Trans. 2 1992, 2163 –
2167; c) R. K. Kawade, C. C. Tseng, R.-S. Liu, Chem. Eur. J.
2014, DOI: 10.1002/chem.201404201.
[10] a) V. A. Schmidt, E. J. Alexanian, J. Am. Chem. Soc. 2011, 133,
11402 – 11405; b) B. C. Giglio, V. A. Schmidt, E. J. Alexanian, J.
Am. Chem. Soc. 2011, 133, 13320 – 13322; c) V. A. Schmidt, E. J.
Alexanian, Angew. Chem. Int. Ed. 2010, 49, 4491 – 4494; Angew.
Chem. 2010, 122, 4593 – 4596; d) C. Berti, L. Grierson, J. A.-M.
Grimes, M. J. Perkins, B. Terem, Angew. Chem. Int. Ed. Engl.
1990, 29, 653 – 655; Angew. Chem. 1990, 102, 684 – 685; e) V. A.
Schmidt, E. J. Alexanian, Chem. Sci. 2012, 3, 1672 – 1674;
f) R. K. Quinn, V. A. Schmidt, E. J. Alexanian, Chem. Sci.
2013, 4, 4030 – 4034.
Keywords: copper · cyclization · oxidation · radicals ·
.
synthetic methods
[1] For Selected reviews, see: a) S. A. Girard, T. Knauber, C.-J. Li,
Angew. Chem. Int. Ed. 2014, 53, 74 – 100; Angew. Chem. 2014,
126, 76 – 103; b) A. E. Wendlandt, A. M. Suess, S. S. Stahl,
Angew. Chem. Int. Ed. 2011, 50, 11062 – 11087; Angew. Chem.
2011, 123, 11256 – 11283; c) M. Klussmann, D. Sureshkumar,
Synthesis 2011, 353 – 369; d) C. Liu, H. Zhang, W. Shi, A. Lei,
Chem. Rev. 2011, 111, 1780 – 1824; e) C. Zhang, C. Tang, N. Jiao,
Chem. Soc. Rev. 2012, 41, 3464 – 3484.
[2] Selected examples, see: a) E. Boess, C. Schmits, M. Klussmann,
J. Am. Chem. Soc. 2012, 134, 5317 – 5325; b) J. Zhang, B. Tiwari,
C. Xing, X. Chen, Y. R. Chi, Angew. Chem. Int. Ed. 2012, 51,
3649 – 3652; Angew. Chem. 2012, 124, 3709 – 3712; c) M. Ghob-
rial, M. Schꢂrch, M. D. Mihovilovic, J. Org. Chem. 2011, 76,
8781 – 8793; d) J. Xie, Z.-Z. Huang, Angew. Chem. Int. Ed. 2010,
49, 10181 – 10185; Angew. Chem. 2010, 122, 10379 – 10383; e) F.
Yang, J. Li, J. Xie, Z.-Z. Huang, Org. Lett. 2010, 12, 5214 – 5217;
f) L. Zhao, C.-J. Li, Angew. Chem. Int. Ed. 2008, 47, 7075 – 7078;
Angew. Chem. 2008, 120, 7183 – 7186; g) E. Boess, D. Sure-
shkumar, A. Sud, C. Wirtz, C. Farꢃs, M. Klussmann, J. Am.
Chem. Soc. 2011, 133, 8106 – 8109; h) O. Baslꢄ, C.-J. Li, Green
Chem. 2007, 9, 1047 – 1050; i) Y. Shen, M. Li, S. Wang, T. Zhan,
Z. Tan, C.-C. Guo, Chem. Commun. 2009, 953 – 955; j) O. Baslꢄ,
C.-J. Li, Chem. Commun. 2009, 4124 – 4126; k) J.-S. Tian, T.-P.
Loh, Angew. Chem. Int. Ed. 2010, 49, 8417 – 8420; Angew. Chem.
2010, 122, 8595 – 8598.
[11] For the stereoselective synthesis of the epimers of the 1,4-
dihydroxy-2,3-diaminocyclohexanes 7, see: C. Boga, C. Fiorelli,
D. Savoia, Synthesis 2006, 285 – 292.
[12] A. Trapero, A. Llebaria, ACS Med. Chem. Lett. 2011, 2, 614 –
619.
[13] A. Arcelli, V. Cere, F. Peri, S. Pollicino, A. Riccib, Tetrahedron:
Asymmetry 2002, 13, 191 – 196.
[14] S. Hanessian, J. Wang, Can. J. Chem. 1993, 71, 2102 – 2108.
[15] J. Magano, Tetrahedron 2011, 67, 7875 – 7899.
[16] CCDC 1013973 (6a) and 1013974 (7b) contains the supplemen-
tary 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] a) R. A. Stockman, A. Sinclair, L. G. Arini, P. Szeto, D. L.
Hughes, J. Org. Chem. 2004, 69, 1598 – 1602; b) C. Ji, M. J.
Miller, Tetrahedron Lett. 2010, 51, 3789 – 3791; c) T. Sasaki, S.
Eguchi, T. Suzuki, J. Org. Chem. 1982, 47, 5250 – 5255.
[18] A summary of asymmetric dimerizations of 5a using various
chiral copper catalysts and solvents is provided in Table S1 of the
Supporting Information.
[3] a) W. Han, A. R. Ofial, Chem. Commun. 2009, 5024 – 5026; b) P.
Liu, C.-Y. Zhou, S. Xiang, C.-M. Che, Chem. Commun. 2010, 46,
2739 – 2741; c) G. Kumaraswamy, A. N. Murthy, A. Pitchaiah, J.
Org. Chem. 2010, 75, 3916 – 3919; d) E. Shirakawa, N. Uchiyama,
T. Hayashi, J. Org. Chem. 2011, 76, 25 – 34; e) M. Ghobrial,
[19] J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 738 – 741.
4
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Synthetic Methods
S. Ghorpade, R.-S. Liu*
&&&& — &&&&
Copper-Catalyzed Oxidative
À
Dimerizations of 3-N-Hydroxy-
aminoprop-1-enes to form 1,4-Dihydroxy-
2,3-diaminocyclohexanes with
C2 Symmetry
Skeletons! Copper-catalyzed aerobic oxi-
dations of N-hydroxyaminopropenes to
form C2-symmetric N- and O-functional-
ized cyclohexanes are described. The
catalytic oxidations proceed with remark-
able stereocontrol and high efficiency.
Reductive cleavage of the two N O
bonds of these products delivers 1,4-
dihydroxy-2,3-diaminocyclohexanes,
which are important skeletons of several
bioactive molecules.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!