One-pot multi-component synthesis and solid state structures of functionally rich polyether macrocycles

Article abstract of DOI:10.1002/adsc.201300462

Densely functionalized polyether macrocycles can be prepared in one pot in yields up to 60% by the rhodium(II)-catalyzed decomposition of methyl diazoacetoacetate in the presence of a variety of substituted or unsaturated 5- and 6-membered ring cyclic ethers. A comprehensive analysis of the solid state conformations of the macrocyclic geometries is detailed as well as novel mechanistic insights about the multi-component condensation reaction. Copyright

Full text of DOI:10.1002/adsc.201300462

FULL PAPERS
DOI: 10.1002/adsc.201300462
One-Pot Multi-Component Synthesis and Solid State Structures of
Functionally Rich Polyether Macrocycles
Mahesh Vishe,a Radim Hrdina,a Laure Guꢀnꢀe,b Cꢀline Besnard,b
and Jꢀrꢁme Lacoura,*
a
Organic Chemistry Department, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
Fax : (+41)-22-379-3215; e-mail: jerome.lacour@unige.ch
Laboratory of Crystallography, University of Geneva, quai Ernest-Ansermet 24, 1211 Geneva, Switzerland
b
Received: May 27, 2013; Revised: July 5, 2013; Published online: September 10, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300462.
Abstract: Densely functionalized polyether macrocy- tries is detailed as well as novel mechanistic insights
cles can be prepared in one pot in yields up to 60% about the multi-component condensation reaction.
by the rhodium(II)-catalyzed decomposition of
methyl diazoacetoacetate in the presence of a variety
of substituted or unsaturated 5- and 6-membered Keywords: catalysis; diazo carbonyl compounds; di-
ring cyclic ethers. A comprehensive analysis of the
ACHTUNGTRENrNGNU hodium complexes; macrocyclization; multi-compo-
solid state conformations of the macrocyclic geome- nent condensation reactions
Introduction
However, in this initial study,[3] only simple THF,
THP (tetrahydropyran) and 1,4-dioxane were utilized
The transition metal-catalyzed decomposition of as co-reactants. The side chains linking the
diazo compounds is a powerful method to promote dioxobutenoate motifs were therefore devoid of sub-
AHCTUNGTRENNUNG
synthetic transformations including not only cyclopro- stituents. In view of the actual importance of func-
panation, dimerization, insertion, dipolar addition, tionalized crown ether molecules for applications in
ylide generation (and subsequent rearrangement) re- the analytical, polymer, liquid crystals, supramolecular
actions,[1] but also macrocycle synthesis.[2] In this con- and catalysis fields,[6] it was deemed necessary to in-
text, our group has previously reported a four-compo- troduce as many chemical motifs and geometries on
nent synthesis of 16- and 18-membered macrocycles the side chains as possible. Herein, we report that this
using a-diazo-b-keto esters and simple cyclic ethers as can be achieved through the use of unsaturated or
reactants (Scheme 1).[3,4] This Rh(II)-catalyzed macro- substituted cyclic ether derivatives which afford in
cyclization, which is a formal [3+6+3+6][5] conden- a single step a variety of novel functionally rich unsa-
sation, displays interesting reactivity aspects including turated crown ethers. These crystalline materials were
the need for a high concentration in the diazo reac- analyzed by X-ray diffraction to reveal solid-state
tants (~1M) and a perfect regioselectivity. Under conformations which preserve key structural motifs
mild reaction conditions (20 or 608C), a large selec- despite the variety of the groups introduced and their
tion of diazo-keto ester reagents can be used to stereochemistry.
afford macrocyclic products in yields up to 75%.
Scheme 1. One-pot [3+6+3+6][5] condensation of a-diazoacetoacetates and 1,4-dioxane.
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Results and Discussion
608C for 60 min rather than at 208C for 3–4 h. The
elevated temperature conditions were preferred as fa-
vouring a better solubility of the Rh(II) catalyst and
of ethers 1d, 1i, 1o and 1p in toluene or dichlorome-
Functionalized Substrates and Reaction Conditions
Commercially available or readily prepared 5- and 6- thane.[8]
membered ring cyclic ethers 1a to 1p were selected
for the proposed study (Figure 1). When liquid, the
One-Pot Polyether Macrocycle Synthesis
With THP substrates 1a, 1b and 1c carrying chloro,
bromo or tosylate groups at the 4-position, respective-
ly, moderate to good yields (25–55%) of the corre-
sponding macrocycles were obtained (Scheme 2).
Those are in line with the reported result for unsubsti-
tuted THP reacting with ethyl a-diazoacetoacetate
(31%).[9,10] Analogous derivatives 1d, 1e and 1f (X=
Ph, CO2Me, OTBS) performed equally well or better
since products 3d, 3e and 3f were obtained in 42 to
60% yields.[11] A rather large variety of groups are
thus compatible, in particular the nucleofugal ones
that are not easily tolerated under Williamson ether
synthesis conditions.
Interestingly, NMR analyses indicated the presence
of two sets of signals for products 3a to 3f reflecting
the presence of stereogenic centers adjacent to sub-
stituents X and hence the occurrence of meso and
chiral (racemic) stereoisomers (Scheme 2). In all six
examples, a strict 1:1 integration ratio was measured
among the stereoisomers. The importance of this even
distribution will be addressed when the mechanism of
the macrocyclization is discussed. In most instances,
a separation of the isomers was possible by column
chromatography. When possible,[12] X-ray diffraction
analyses were collected on the isolated species to
define their relative configuration (vide infra); some-
Figure 1. Functionalized cyclic ether precursors.
ethers were used directly as solvents in the presence thing otherwise difficult to determine by NMR spec-
of methyl a-diazoacetoacetate (ca. 1M) and troscopy only.
Rh2A Then, doubly substituted substrates were examined.
(Oct)4 (1 mol%) as catalyst[7] while solid com-
2
CHTUNGTRENNUNG
pounds were utilized in concentrated toluene or With geminal derivatives 1g, 1h and 1i, the resulting
CH2Cl2 solutions. In general, reactions were per- products were isolated in 45%, 15% and 23% yields,
formed on a 0.5–1.0 mmol scale of diazo reagent 2 at respectively (Scheme 3); the presence of electron-
Scheme 2. Macrocyclization of 4-substituted THP derivatives yielding chiral (racemic) and meso products 3a to 3f.
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One-Pot Multi-Component Synthesis and Solid State Structures of Functionally Rich Polyether Macrocycles
Scheme 3. Macrocyclization of 4,4’-disubstituted cyclic
ethers yielding products 3g to 3i.
Scheme 5. Macrocyclization of enantiopure (3S,4S)-1k.
(Scheme 5); its isolation in 35% yield being a positive
withdrawing substituents being favourable over elec- result in view of the elaborate nature of the com-
tron-donating ones.[13] The fact that the geminal pound.
groups do not improve the macrocyclization yields
will be considered during the mechanistic discussion
At that stage, only ether substrates with sp3-hybrid-
ized carbon atoms had been used leading to com-
Three different trimethylsilyl-protected 1,4-anhy- pounds 3 with “flexible” chains between the two con-
droerythritol derivatives were also used, meso-1j, rac- served 2,3-dimethoxybut-2-enoate units. An effort
1k and (3S,4S)-1k.[14] These cyclic ethers were pre- was made to introduce aromatic groups and double
pared according to reported procedures.[15] With bonds on the cyclic ether precursors to increase the
meso-1j, in line with the results obtained for 1a to 1f, conformational rigidity of resulting products 3. 1,3-Di-
a 1:1 ratio of racemic and meso stereoisomers was ob- hydroisobenzofuran 1l and olefins 1m to 1p (Figure 1)
tained (3j, 38%, Scheme 4). A statistical mixture of were thus used as substrates allowing furthermore to
isomers was also afforded in the case of rac-1k to give test the limits of the macrocyclization against tradi-
À
meso-3k/rac-3k (40%). In both instances, the relative tional cyclopropanation and activated C H insertion
configuration of the products was determined by X- reactions that could possibly compete.
ray crystallographic analysis (meso isomers, see the
Aromatic macrocycle 3l was isolated with a 47%
Supporting Information).
yield (Scheme 6). Interestingly, with substrate 1m con-
Nevertheless, when enantiopure (3S,4S)-1k was taining an endocyclic C=C bond, the reaction pro-
used, only (6S,7S,14S,15S)-3k was afforded ceeded equally well to form 3m (40%). With sub-
Scheme 4. Macrocyclization of 3,4-disubstituted meso-1j and rac-1k yielding racemic and meso products of 3j and 3k.
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active olefin moieties, this procedure provides an in-
teresting orthogonality to the classical RCM condi-
tions.
Mechanistic Insight
Prior to this study, a mechanistic rationale was pro-
posed to explain the macrocyclization.[3] It is detailed
in Scheme 8. It involves the metal-catalyzed genera-
tion of electrophilic metal carbenoids A and additions
of cyclic ethers to yield oxonium ylide intermediates
B and C. Then, in a single elemental step, two ylides
of type C react and generate the macrocycle in two
synchronous nucleophilic attacks of the O-enolate of
each moiety onto the oxonium electrophilic a-carbon
of the other. In this mechanistic proposition, a few re-
activity aspects were assumed and we saw in the re-
sults obtained in this study the opportunity to chal-
lenge some of these assumptions.
Scheme 6. Products 3l and 3m.
In fact, we considered that the formation of prod-
ucts 3a to 3f as 1:1 mixtures of racemic and meso ste-
reoisomers may help determine which of the ylide
species B or C react in the following dimerization
step. Metal-bound intermediates B of prochiral sub-
strates should be sensitive to the presence of chiral
enantiopure Rh(II) catalysts while intermediates C
Scheme 7. Macrocyclization of ethers containing exocyclic
double bond yielding products 3n to 3p.
strates 1n to 1p possessing exocyclic double bonds, would be indifferent.[1a,16] Hashimoto-, Davies- and
products 3n to 3p were obtained in lower yields (15 to Pirrung-type complexes (Figure 2) were thus selected
25%, Scheme 7). Yet, as these compounds possess re- as catalysts for the macrocyclization of chloro-substi-
Scheme 8. Mechanistic rationale including a synchronous dimerization of oxonium ylide intermediates C (X=O, CH2).
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One-Pot Multi-Component Synthesis and Solid State Structures of Functionally Rich Polyether Macrocycles
THP. This reaction had not been performed in the
previous study and product 3q (Scheme 9, X=CH2)
was obtained in a 60% yield, better than for 3g, 3h
and 3i. This tends to indicate that a Thorpe–Ingold
effect is not involved.[20]
Structural Analysis
Finally, twelve of the eighteen macrocycles were ana-
lyzed successfully by X-ray diffraction.[21] The struc-
tures are displayed in the Supporting Information.
Two of them, 3g and 3l, are presented in Figure 3.
Of importance, it was noticed that the methyl
dioxoACTHNURGTNEbUNG utenoate segments adopt the exact same solid
state conformation in all macrocycles, and this twice
per structure. The adopted geometry is presented in
Figure 3 and detailed on Figure 4 and Figure 5; atoms
Cn, O1, C2, C3, O4 and C5 composing the motifs are
displayed in particular.
Figure 2. Hashimoto-, Davies- and Pirrung-type chiral
Rh(II) catalysts.
Globally, these five consecutive atoms, along with
the ester and the neighbouring methyl groups, are es-
tuted THP 1a.[17] Importantly, in all instances, the 1:1 sentially coplanar indicative of a strong conjugation
ratio between chiral and meso stereoisomers of 3a re- occurring from oxygen atoms O4 to the ester moiet-
mained unchanged and the chiral product was ob- ies. In fact, analysis of the twelve structures reveals
tained in null or very low enantiomeric purity (ee that atoms O4 are sp2-hybridized (average bond dis-
<9%).[18] This tends to favour a mechanism that in- tance dC3 O4 ~1.358 ꢃ and bond angle C3 O4 C5~
À
À
À
volves metal-free intermediates C rather than metal 120.48) which imposes essentially the presence of ad-
bound species B.[19]
jacent carbon atoms C5 in the O1 C2 C3 O4
À
À
À
It was also considered that the present study might plane.[22] The situation is different for oxygen atoms
help determine whether the final dimerization occurs O1 that adopt an sp3-hybridization;[23,24] the O1 Cn
À
À
in a single elemental step as displayed in Scheme 8 or bond being oriented almost perpendicular to the O1
through a stepwise mechanism as shown on Scheme 9. C2 C3 O4 plane. This inclination can be clearly ob-
In the latter case, the nucleophilic attacks of the O- served on Figure 5. The Cn O1 C2 C3 dihedral
À
À
À
À
À
enolate moieties occur consecutively instead of con- angles can be either positive or negative (Æ99.98).
comitantly. In this stepwise approach, the first and
Two possible orientations, upward or downward,
second attacks are inter- and intramolecular, respec- are then possible for the subsequent chains linking
tively. Intermediate D (Scheme 9) may then relax to the two dioxobutenoate fragments. In most of the
an all-anti conformation and the pending cyclization macrocycles (10 out 12), a combination of upward
À
reaction could then benefit from a Thorpe–Ingold and downward orientations of the O1 Cn bonds is
effect.
observed.[25] This results in a parallel disposition of
The reactions of substrates 1g to 1i possessing gemi- the planes of the two dioxobutenoate fragments, irre-
nal substituents at the 4,4’-positions were thus scruti- spective of the aliphatic or unsaturated, naked or sub-
nized again, in particular in comparison with the reac- stituted character of the links. The nature of the
tion of methyl a-diazoacetoacetate 2 with regular chains plays however a role in the distance between
Scheme 9. Stepwise dimerization of oxonium ylides C to give intermediate D and final products 3g, 3h, 3i (X=CR2) or 3q
(X=CH2).
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Figure 3. ORTEP views of the crystal structures of 3g and 3l. Thermal ellipsoids are drawn at 50% probability.
are positioned with angles of 84.18 and 78.68 respec-
tively and, as a consequence, the structures adopt
bowl-shaped arrangements (see the Supporting Infor-
mation). So far, these curved geometries seem to
occur only in chiral (racemic) entities while meso and
other non-chiral structures prefer to adopt parallelo-
gram motifs.
Conclusions
Figure 4. Lateral view of the structurally conserved methyl
In summary we have explored the scope of the
dioxo butenoate segment. The grey parallelogram is defined
Rh(II)-catalyzed [3+6+3+6] macrocyclization reac-
tion by studying the decomposition of methyl diazo-
AHCTUNGTREGaNNUN cetoacetate in the presence of a variety of substitut-
À
À
À
by the O1 C2 C3 O4 plane.
ed or unsaturated 5- to 6-membered ring cyclic ethers.
Novel macrocycles carrying a large array of functional
groups, some not easily tolerated under other macro-
cyclization conditions, were prepared in yields up to
60%. Some novel mechanistic insights were further-
more afforded. These crystalline materials were ana-
lyzed by X-ray diffraction to reveal well-defined
solid-state conformations.
Figure 5. Front view of the methyl dioxobutenoate segment.
Average dihedral angle Cn O1 C2 C3 is Æ99.98.
À
À
À
Experimental Section
the parallel planes which are separated from 0.27 ꢃ
(3k) up to 3.76 ꢃ (3l).
General Remarks
Alternatively, for compounds rac-3a and rac-3b
(Table 1), both O1 Cn bonds are oriented upward (or
downward). The planes of the dioxobutenoate motifs stated. H NMR chemical shifts are given in ppm relative to
NMR spectra were recorded on 300, 400 or 500 MHz spec-
À
trometer at room temperature (258C) unless otherwise
1
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One-Pot Multi-Component Synthesis and Solid State Structures of Functionally Rich Polyether Macrocycles
Table 1. Solid-state conformations of macrocycles 3: Distance and angles between the dioxobutenoate planes, parallelogram
(e.g., 3g, left) or bowl-shaped (e.g., 3b, right) geometries.
Entry[a]
Compound
Distance (ꢃ)
Angle
Stereochemistry
Geometries
1
2
3
4
5
6
7
8
3k
3q
3h
3p
3j
0.271
0.473
0.821
0.910
1.368
1.469
2.220
2.703
3.759
–
0.008
0.008
0.008
0.008
0.008
0.008
0.008
0.008
0.008
0.748
78.68
84.18
meso
–
–
–
meso
–
–
meso
–
–
racemic
racemic
parallelogram
parallelogram
parallelogram
parallelogram
parallelogram
parallelogram
parallelogram
parallelogram
parallelogram
“parallelogram”
bowl-shaped
3i
3g
3f
3l
3m
3b
3a
9
10
11
12
–
–
bowl-shaped
[a]
À
À
À
Compounds are classified with increasing both distance and then angles between O1 C2 C3 O4 planes.
Me4Si with the solvent resonance used as the internal stan-
dard (CDCl3 d=7.26 ppm). 13C NMR (125 or 101 MHz)
chemical shifts were given in ppm relative to Me4Si with the
solvent resonance used as the internal standard (CDCl3 =
77.16 ppm). IR spectra were recorded using an ATR sam-
pler and are reported in wave numbers (cmÀ1). Melting
points (mp) were measured in open capillary tubes and are
uncorrected. Optical rotations were measured in a thermo-
statted (208C) 10.0 cm long microcell at 589 nm (Na) or
435 nm (Hg) and are reported as follows: [a]D [c (gmLÀ1],
solvent). Electrospray mass spectra (ESI+) were obtained by
the Department of Mass Spectrometry of the University of
Geneva. All reactions involving air-sensitive compounds
were carried out under dry nitrogen or argon by means of
an inert gas/vacuum double manifold line and standard
Schlenk techniques. Flash column chromatography was per-
formed with silica gel 40–63 or alumina (neutral Brockmann
I, 50–200 mm).
imidazole and 1.2 equivalents of TBSCl (per OH group) at
208C and the reaction mixture was stirred for 3 h. The reac-
tion was quenched with NH4Cl solution, product was ex-
tracted with diethyl ether (3ꢄ20 mL). The organic layers
were collected, dried over MgSO4 and after filtration, the
solvent was removed under reduced pressure. The products
were purified using column chromatography on silica gel
using mobile phases as stated in the Supporting Informa-
tion.
General Procedure for the TMS Protection of
Alcohols
To the solution of corresponding alcohol (14.6 mmol) in
20 mL of CH2Cl2 were added 3 equivalents (43.8 mmol) of
Et3N and by 2.5 equivalents of TMSCN at 208C and the re-
action mixture was stirred for 3 h. The reaction was
quenched with NH4Cl solution, product was extracted with
diethyl ether (3ꢄ20 mL). The organic layers were collected,
dried over MgSO4 and after filtration, the solvent was re-
moved under reduced pressure. The products were purified
using column chromatography on silica gel using mobile
phases as stated in the Supporting Information.
General Procedure for the TBS Protection of
Hydroxylated Substrates
To the solution of corresponding alcohol (14.6 mmol) in
20 mL of CH2Cl2 were added 2 equivalents (29.2 mmol) of
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W. Zeghida, M. Austeri, L. Guꢀnꢀe, J. Lacour, Angew.
Chem. 2012, 124, 5949–5953; Angew. Chem. Int. Ed.
2012, 51, 5847–5851; b) D. Rix, R. Ballesteros-Garrido,
W. Zeghida, C. Besnard, J. Lacour, Angew. Chem.
2011, 123, 7446–7449; Angew. Chem. Int. Ed. 2011, 50,
7308–7311.
General Synthesis of Macrocycles 3a to 3q
To a flame-dried Schlenk tube was added Rh2ACTHNUGTRNE(UNG Oct)4 (7.8 mg,
10.0 mmol, 1 mol%) under an N2 atmosphere. Then, the cor-
responding ether 1 was added neat (1.0 mL) or as a solid
(6.0 mmol, 6 equivalents) along with a solvent (1 mL, tolu-
ene or CH2Cl2). The resulting solution was heated to 608C,
to which was then added dropwise methyl diazoacetoatetate
2 (142 mg, 1.0 mmol). Continuous heating and stirring were
applied at 608C for 1 hour. The reaction was then stopped
by removing the solvent under vacuum. The crude reaction
mixture was analyzed by NMR spectroscopy and then sub-
mitted to a chromatographic purification (column filled with
neutral alumina or silica gel).
[5] For THF derivatives, the process is of course a [3+5+
3+5] condensation reaction.
[6] a) S. Shirakawa, K. Maruoka, Angew. Chem. Int. Ed.
2013, 52, 4312–4348; b) B. Zheng, F. Wang, S. Dong, F.
Huang, Chem. Soc. Rev. 2012, 41, 1621–1636; c) M.
Kaller, S. Laschat, in: Liquid Crystals, Vol. 318, (Ed.:
C. Tschierske), Springer, Berlin, Heidelberg, 2012,
pp 109–192; d) F. A. Christy, P. S. Shrivastav, Crit. Rev.
Anal. Chem. 2011, 41, 236–269; e) G. W. Gokel, M. M.
Daschbach, Coord. Chem. Rev. 2008, 252, 886–902;
f) G. W. Gokel, W. M. Leevy, M. E. Weber, Chem. Rev.
2004, 104, 2723–2750.
Acknowledgements
[7] Rh2ACHTUNGTRENNUG(Oct)4 was selected over Rh2HCATUNGTERNN(UGN OAc)4 because of its
We thank the University of Geneva, the Swiss National Sci-
ence Foundation, the NCCR Chemical Biology, the COST
Action CM0802 and the State Secretariat for Education and
Science for financial support. We acknowledge the contribu-
tions of the Sciences Mass Spectrometry (SMS) platform at
the Faculty of Sciences, University of Geneva.
good solubility in ethers or in organic co-solvents.
[8] In all instances, molecular nitrogen was immediately re-
leased upon the addition of the diazo reagent to the
mixtures of cyclic ethers and Rh2ACTHNUTRGNEN(UG Oct)4.
[9] F. R. Fintelman Dias, Synlett 2013, 397–398.
[10] For the exact reaction of 2 and unsubstituted THP,
please see ref.[3]
[11] In these reactions and the next, modest yields are ob-
tained due to the competing formation of byproducts
of carbenoid dimerizations and reactions with diazo re-
actants generating tetrasubtituted olefins and hydra-
zine-1,2-diylidene adducts. 9-Membered ring products,
which would be formed by an intramolecular attack,
are not generated as the 5-endo-tet reaction is highly
disfavoured for stereochemical reasons. See: R. Balles-
teros-Garrido, D. Rix, C. Besnard, J. Lacour, Chem.
Eur. J. 2012, 18, 6626–6631.
[12] It is the case for compounds rac-3a, rac-3b and meso-
3f.
[13] In the dimerization of ylide intermediates C (see
Scheme 8), the presence of electron-withdrawing
groups is favourable for activating the electrophilic
oxonium moieties towards the O-enolate nucleophilic
attacks.
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[4] For recent articles from our group on the reactivity of
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[19] In the proposed mechanism (Scheme 8), substituents
on the cyclic ether moieties are oriented in opposite di-
rections during the dimerization step. As a consequence,
they do not interact. There is no energy difference be-
tween the diastereomeric transition states and hence
the 1:1 ratio between chiral and meso stereoisomers.
[20] In the stepwise mechanism (Scheme 9), if the first of
the two steps is rate determining, then an increase in
reaction rate is not expected from the presence of the
two geminal substituents.
[21] CCDC 933811 to CCDC 933822 contain the supple-
mentary 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.
À
À
À
[22] The mean dihedral angle value for C2 C3 O4 C5 is
14.98 with values ranging from 0.88 to 30.98.
[17] a) M. C. Pirrung, J. C. Zhang, Tetrahedron Lett. 1992,
33, 5987–5990; b) S. Hashimoto, N. Watanabe, T. Sato,
M. Shiro, S. Ikegami, Tetrahedron Lett. 1993, 34, 5109–
5112; c) H. M. L. Davies, (Wake Forest University,
USA), U.S. Patent WO9611928A1, 1996; d) R. Hrdina,
L. Guꢀnꢀe, D. Moradela, J. Lacour, Organometallics
2013, 32, 473–479.
[18] The analysis was performed by CSP-HPLC: Chiral-
pakꢇ IC, n-hexane/THF 95/5, 0.5 mLminÀ1, 238C, re-
tention times 52.73 and 59.24 min for the two enantio-
mers.
[23] Oxygens O1, that are attached to the double bond like
atoms O4, could be in principle sp2-hybridized. Howev-
er, the mean bond distance dC2 O1 ~1.382 ꢃ and bond
À
À
À
angle C2 O1 Cn~113.68 are good indications of an
sp3-hybridization.
[24] n equals 16 or 18 depending on the ring size.
[25] It is also the case for the macrocycles derived from
THF and 1,4-dioxane. See ref.[3] for further informa-
tion.
Adv. Synth. Catal. 2013, 355, 3161 – 3169
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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