Cis-2,6-Bis-(methanolate)-piperidine oxovanadium(V) complexes as catalysts for oxidative alkenol cyclization by tert-butyl hydroperoxide

Article abstract of DOI:10.1016/j.ica.2014.02.007

cis-2,6-Bis-(methanolate)-piperidine oxovanadium(V) complexes are Lewis acids able to catalyze oxidative cyclization of alkenols by tert-butyl hydroperoxide (TBHP). Terminal dimethyl-substituted (prenyl-type) 4-pentenols bearing an alkyl or a phenyl group in position 1 afford under such conditions 2,5-cis-derivatives of 2-(tetrahydrofuran-2-yl)-2-propanol as major and tetrahydropyran-3-ols as minor products (four examples). Oxidizing 1-phenyl-6-methylhept-5-en-1-ol yields a 75/25-mixture of the derived 2-(tetrahydropyran-2-yl)-2-propanol and an oxepan-3-ol, whereas 2-propenols give epoxides in up to 94% yield. Epoxidizing geraniol by TBHP in the presence of a vanadium catalyst prepared from (2S,6R)-2-diphenylmethanol-6- hydroxymethylpiperidine occurs enantioselectively. Highfield shifts of vanadium-51 resonances upon adding alkyl hydroperoxides to solutions of cis-2,6-bis-(methanolate)-piperidine vanadium(V) complexes point to vanadium(V) tert-butyl peroxy complex formation as key step for activating peroxides.

Full text of DOI:10.1016/j.ica.2014.02.007

Inorganica Chimica Acta xxx (2014) xxx–xxx
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Inorganica Chimica Acta
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cis-2,6-Bis-(methanolate)-piperidine oxovanadium(V) complexes
as catalysts for oxidative alkenol cyclization by tert-butyl hydroperoxide
⇑
Maike Dönges, Matthias Amberg, Georg Stapf, Harald Kelm, Uwe Bergsträßer, Jens Hartung
Fachbereich Chemie, Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Straße, D-67663 Kaiserslautern, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online xxxx
cis-2,6-Bis-(methanolate)-piperidine oxovanadium(V) complexes are Lewis acids able to catalyze
oxidative cyclization of alkenols by tert-butyl hydroperoxide (TBHP). Terminal dimethyl-substituted
(prenyl-type) 4-pentenols bearing an alkyl or a phenyl group in position 1 afford under such conditions
2,5-cis-derivatives of 2-(tetrahydrofuran-2-yl)-2-propanol as major and tetrahydropyran-3-ols as minor
products (four examples). Oxidizing 1-phenyl-6-methylhept-5-en-1-ol yields a 75/25-mixture of the
derived 2-(tetrahydropyran-2-yl)-2-propanol and an oxepan-3-ol, whereas 2-propenols give epoxides
in up to 94% yield. Epoxidizing geraniol by TBHP in the presence of a vanadium catalyst prepared from
(2S,6R)-2-diphenylmethanol-6-hydroxymethylpiperidine occurs enantioselectively. Highfield shifts of
vanadium-51 resonances upon adding alkyl hydroperoxides to solutions of cis-2,6-bis-(methanolate)-
piperidine vanadium(V) complexes point to vanadium(V) tert-butyl peroxy complex formation as key
step for activating peroxides.
Keywords:
Catalysis
Oxepane
Oxidation
Tetrahydrofuran
Tetrahydropyran
Vanadium
Ó 2014 Elsevier B.V. All rights reserved.
1. Introduction
Almost all vanadium compounds for activating TBHP in use
today are O-esters of ortho-vanadic acid, having one or two alkoxy
Oxovanadium(V) compounds are Lewis acids, able to activate
alkyl hydroperoxides [1,2] for converting prochiral alkenols into
epoxides [3], tetrahydrofurans [4,5], or tetrahydropyrans [6]
(Scheme 1). These target compounds are subunits of several
natural products (Fig. 1) and used as building blocks for preparing
secondary metabolites [7,8], artificial ionophores [9], molecular
devices [10], receptors, and other functional molecules [11,12].
The most important alkyl hydroperoxide used in science and
engineering for oxidizing alkenols is tert-butyl hydroperoxide
(TBHP) [13]. TBHP dissolves in polar and non-polar organic
solvents and is stable unless heated, photolyzed, protonated, or
treated with a reductant. TBHP is a nucleophile adding at room
temperature to alkyl vanadates to give vanadyl(V) peresters
[14,15]. The d0-metal center in peroxy vanadium(V) compounds
withdraws electrons from the peroxide functional group, causing
the peroxide entity to become an electrophile, able to oxidize
nucleophiles, such as alkenes. Oxidation by TBHP affords tert-
butanol as by-product, which has a sufficiently low boiling point
(bp 83 °C) for being evaporated from reaction mixtures and
used to prepare tert-butyl ethers or -esters serving as additives,
reagents, or solvents [16].
groups replaced by a chelate ligand, binding via oxygen and
nitrogen donor atoms to the metal. Auxiliaries of this kind alter
electron population and steric demand at vanadium, improving
chemoselectivity and directing stereoselectivity in alkenol oxida-
tion [5,17]. The most effective auxiliaries for controlling selectivity
in vanadium(V)-catalyzed oxidation by TBHP are bishydroxamates
for epoxidation of 2-propenols (allylic alcohols) and 3-butenols
(homoallylic alcohols), and Schiff base-derived iminodiolates for
oxidatively converting 4-pentenols into (tetrahydrofuran-2-yl)-
methanols [3,18–20].
Our interest in vanadium-catalyzed oxidation started with the
quest for controlling regio- (exo/endo) and stereoselectivity (cis/
trans) in synthesis of a medium-sized ethers from terpenol- and
acetogenin-derived alkenols, using peroxides as terminal oxidants
(Scheme 1) [5,21–24].
For many years, vanadium-catalyzed oxidation contributed to
advances in the field of oxidative alkenol cyclization, based on
otherwise unmatched 2,5-cis- and 2,4-trans-selectivity for tetrahy-
drofuran synthesis from terminal dimethyl-substituted (prenyl-
type) 4-pentenols [5,27–29]. In the course of an ongoing project
on tetrahydrofuran synthesis, we faced the problem of declining
chemoselectivity, as reaction times extended to several days, and
additional TBHP had to be added for attaining quantitative alkenol
conversion in oxidations catalyzed by oxovanadium(V) iminodio-
late complexes, such as 2d [30].
⇑
Corresponding author. Tel.: +49 631 205 2431; fax: +49 631 205 3921.
E-mail address: hartung@chemie.uni-kl.de (J. Hartung).
http://dx.doi.org/10.1016/j.ica.2014.02.007
0020-1693/Ó 2014 Elsevier B.V. All rights reserved.
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2
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
OH
OH
[ O ]
R
R
1
2
O
2-propenol
OH
OH
R
O
O
[ O ]
R
+
R
1
m
m
m
OH
4/5
4-pentenol (m = 1)
5-hexenol (m = 2)
exo-
endo-
oxidatively cyclized
Scheme 1. Products of alkenol oxidation by tert-butyl hydroperoxide ([O] = tert-butyl hydroperoxide in combination with an oxovanadium(V) complex (vide infra); s,
d = hydrogen, methyl, or aryl; R = hydrogen, alkyl, or aryl).
OH
H
H
H
O
O
O
AcO
OH
AcO
OH
H
cis-pityol
Pityophthorus pityographus
cis-vittatol
Ptleobius vittatus
waraterpol
Penicillium sp.
Fig. 1. Natural products from an exo-cyclized 4-pentenol (left), and from endo-cyclized alkenols (center and right) [21,25,26].
To solve the chemoselectivity problem, we searched for new
oxidation catalysts [31]. The most important result from the pres-
ent study shows that cis-2,6-bis-(methanolate)-piperidine vana-
dium(V) complexes are appropriate Lewis acids for activating
alkyl hydroperoxides with improved chemoselectivity compared
to previously used catalysts for this purpose. Prenyl-type 4-pente-
nols and a 5-hexenol furnish cyclic ethers in useful yields under
such conditions. Epoxidizing geraniol by TBHP in the presence of
a vanadium catalyst prepared from (2S,6R)-2-diphenylmethanol-
6-hydroxymethylpiperidine occurs enantioselectively. Highfield
shifts of vanadium-51 resonances upon adding alkyl hydroperox-
ides to solutions of cis-2,6-bis-(methanolate)-piperidine vana-
dium(V) complexes point to vanadium(V)-binding as key step for
activating peroxides.
2.2. cis-2,6-Bis-(hydroxymethyl)-piperidine oxovanadium(V)
complexes
2.2.1. 2,6-Disubstituted piperidines
For preparing cis-2,6-bis-(2-hydroxy-2-propyl)-piperidine (1a),
we treated 2,6-bis-(acetyl)-pyridine (3) [33] with an excess of
methyl magnesium iodide and reduced the resulting tertiary diol
by hydrogen, using palladium on charcoal as catalyst (Scheme 3).
By a similar approach we obtained cis-2,6-bis-(diphenylhydroxy-
methyl)-piperidine (1b) from 2,6-dimethyl pyridine-2,6-dicarboxy-
late (4) as diastereomerically homogeneous product.
For preparing aminodiol H2L3 (2S,6R)-(1c), benzyloxycarbonyl-
protected cis-2,6-bis-(acetyloxymethyl)-piperidine 5 was enantio-
selectively hydrolyzed using Aspergillus niger lipase as catalyst,
providing 2-acetyloxy-6-hydroxymethylpiperidine (2R,6S)-6 in an
enantiomeric ratio of 96:4 (Scheme 4) [34]. Oxidizing primary
alcohol (2R,6S)-6 with potassium permanganate furnishes the
derived carboxylic acid, which was treated with ethanol in the
presence of sulfuric acid for simultaneously esterifying the
piperidine-bound carboxyl group and for removing the acetyl
substituent in the side chain (Scheme 4). Hydrogenolysis of
N,O-protected amino acid (2S,6R)-7 in a suspension of palladium
on charcoal in ethyl acetate removes the Z-protecting group at
nitrogen, to provide amino acid ester (2S,6R)-8.
For monitoring enantiomeric purity of products along the syn-
thesis of (2S,6R)-1c, we esterified chiral alcohols, for example 6,
with an enantiopure 2-chloro-1,3-dioxaphospholane leading to
diastereomeric phosphites (Scheme 5). Diastereomeric phosphites
of this kind show baseline-separated phosphorous-31 NMR-reso-
nances, allowing to determine the enantiomeric purity of underly-
ing alcohols by integrating the NMR-signals [35].
2. Results and interpretation
2.1. General considerations
From a screening of Lewis acids [31,32] we selected oxovana-
dium(V) cis-2,6-bis-(methanolate)-piperidine complexes 2a–b
(Scheme 2) for catalyzing
p-bond oxidation of alkenols with
improved selectivity compared to previously used oxidation
catalysts. For assessing the benefits of the new vanadium(V)
compounds we investigated complex stability (Section 2.2), alkyl
hydroperoxide binding (Section 2.3), and selectivity in oxidative
cyclization (Sections 2.4 and 2.5). In order to test the effective-
ness of cis-2,6-bis-(methanolate)-piperidine vanadium(V) com-
plexes for controlling stereoselectivity of carbon–oxygen bond
formation, we used chiral 2,6-disubstituted piperidine (2S,6R)-1c
as auxiliary for enantioselectively epoxidizing prenyl-type
2-propenols (Section 2.6).
For finalizing synthesis of aminodiol (2S,6R)-1c, we heated ester
(2S,6R)-8 in a solution of tetrahydrofuran, containing an excess of
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
3
EtOH
25 °C
VO(OEt)3 + H2Ln
VO(Ln)(OEt)
1
2
aminodiol-type
iminodiol-type
N
N
H
Cs
N
H
C1
H
H
H
H
OH
OH
HO
OH
HO
OH
Cs
= CH3 for H2L1 (1a)
= Ph for H2L3
(2S,6R)-(1c)
H2L4 (1d)
Ph for H2L2 (1b)
Scheme 2. General method for preparing oxovanadium(V) complexes 2a–d VO(Ln)(OEt) from tridentate auxiliaries H2Ln (1a–d) and triethyl vanadate [n = 1–4, vide infra;
protons substituted by vanadium(V) are printed in bold; VO(L4)(OEt) crystallizes as EtOH-adduct from a solution of ethanol].
1. H3CMgI / THF
Et2O / 36 °C
N
N
H
2. H2 / Pd on C
EtOAc / 20 °C
H
H
O
O
O
O
HO
OH
3
H2L1 (1a)
38 %
1. PhMgBr / THF
CH2Cl2 / 0 °C
Ph
Ph
Ph
OH
H3CO
OCH3
Ph
N
N
2. H2 / Pd on C
HOAc / 80 °C
H
H
H
HO
4
H2L2 (1b)
60 %
Scheme 3. Two-step syntheses of cis-2,6-bis-(2-hydroxyprop-2-yl)-piperidine (1a) and cis-2,6-bis(diphenylhydroxymethyl)piperidine (1b).
phenylmagnesium chloride. Treating O-ethyl ester 8 with metha-
nol and sodium hydroxide, and subsequently with hydrochloric
acid, yields the hydrochloride salt of a-amino acid 9 (Scheme 6).
From the magnitude of scalar coupling constants and the Kar-
plus-relationship we concluded that the heterocyclic core of piper-
idines 1a–c exists in solutions of deuterochloroform in a chair
conformation, having substituents at carbons 2 and 6 bound equa-
torially, similar to the solid state structures of chiral piperidine 1c.
The same conformation is favored for the hydrochloride of amino
acid 9 in solution of deuterium oxide (D2O) and in the solid state
crystallize as yellow solids showing sharp melting points (Table 1).
Vanadium-51 NMR-spectra of complexes 2a–c recorded in 2/1-vol-
umes of ethanol and deuterochloroform show single lines, with the
shifts being only marginally solvent dependent (Section 4).
From fine structures of proton resonances of vanadium com-
plexes 2a and 2c we concluded that substituents at carbons 2
and 6 are bound equatorially to the piperidine nucleus adopting
a chair conformation. Resonances of axial protons of ligands 1a
and 1c are low field-shifted upon oxovanadium(V) binding
(Table 2). The strongest shift occurs for protons bound to carbons
2 and 6, and the least for protons bound in equatorial positions.
Proton- and carbon-13 NMR-chemical shifts of the ethoxo ligand
recorded for complexes 2a and 2c in solutions of perdeuterometh-
anol are nearly identical to values reported for ethanol dissolved in
perdeuteromethanol. From this information we assumed that
perdeuteromethanol displaces the ethoxo ligand in vanadium
complexes 2a and 2c.
(Fig. 2). X-ray diffraction analysis performed at 150 K using Cu K
a
radiation and the Flack-parameter for structure refinement fur-
thermore clarified the absolute configuration at stereogenic car-
bons 2 and 6 in 1c and 9, being in both instances 2S and 6R.
2.2.2. Preparing and structurally characterizing oxovanadium(V)
complexes
Oxovanadium(V) complexes 2a–c are obtained by mixing
aliquots of triethyl vanadate [36] and aminodiols 1a, 1b, or
(2S,6R)-1c in solutions of hot ethanol. The title compounds
In solid state structures of oxovanadium(V) complexes 2b and
2c, side chains are bound equatorially to piperidine carbons 2
and 6, whereas vanadium coordinates axially to the piperidine
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4
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
lipase (A.niger)
6
2
pH 7 / 40 °C
N
Z
5
N
Z
H
H
H
H
AcO
OAc
HO
OAc
(2R,6S)-6
82% (er = 96:4)
1. KMnO4 / H2O
2. EtOH / H2SO4
toluene / 100 °C
Aliquat 336
CH2Cl2 / 20 °C
H2 / Pd on C
EtOAc / 23 °C
2
6
2
6
EtO
EtO
N
H
N
Z
H
H
H
H
O
OH
O
OH
(2S,6R)-8
(2S,6R)-7
83% (er = 96:4)
79% (er = 96:4)
Scheme 4. Synthesis of chiral amino alcohol (2S,6R)-8 [Z = benzyloxycarbonyl; A. niger = Aspergillus niger; pH 7 adjusted with phosphate buffer; Aliquat 336 = quaternary
ammonium salt composed of a mixture of C8 (octyl) chains; for details on determining enantiomeric ratios (er) refer to text and Scheme 5].
O
O
O
O
H
H
H
H
O
O
O
O
NEt3
O
O
O
O
+
R*OH
P
Cl
P OR*
CDCl3 / 23 °C
97%
6
δ (31P) = – 175.6
δ (31P) = – 144.2 (major)
– 144.7 (minor)
Scheme 5. Derivatizing chiral alcohol 6 with an enantiomerically pure 2-chlorodioxaphospholane for determining enantiomeric purity [35].
6
2
1. NaOH
CH3OH / 24 °C
2. HCl aq. / 20 °C
EtO
PhMgCl
THF / 68 °C
N
H
H
H
O
OH
(2S,6R)-8
–
Ph
2
6
Cl
6
2
+
H2
HO
Ph
N
H
N
H
H
H
H
HO
OH
O
OH
(2S,6R)-1c
(2S,6R)-9 × HCl
55% (er = 96:4)
87%
Scheme 6. Conversion of chiral piperidine (2S,6R)-8 into H2L3 (2S,6R)-1c and hydrochloride salt of amino acid (2S,6R)-9 (er = enantiomeric ratio).
nitrogen (Fig. 3). Nitrogen and four oxygen donor atoms form a
distorted tetragonal pyramid, having the central ion offset by
0.49(2) Å (for 2b) or 0.54(2) Å (for 2c) from the basal plane toward
the apex (Table 3).
2.2.3. Relative stability of oxovanadium(V) complexes
When allowed to rest for 72 h in solutions of ethanol, 2/1-vol-
umes of ethanol and deuterochloroform, or in deuterochloroform,
signal intensity and vanadium-51 NMR-chemical shifts recorded
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
5
Fig. 2. Ellipsoid graphics (50% probability) of aminodiol (2S,6R)-1c (left) and hydrochloride salt of amino acid (2S,6R)-9 (right) in the solid state (150 K; hydrogen is drawn as
circle of an arbitrary radius).
Table 1
vanadium(V) oxychloride (VOCl3) in deuterochloroform (0 ppm),
is offset from resonances of vanadium complexes 2a–d, preventing
Yields and selected physical properties of vanadium compounds 2a–c.
VO(OEt)3 + H2Ln
VO(Ln)(OEt)
signal overlap.
Iminodiol H2L4 (1d) displaces aminodiolate auxiliaries in
piperidine complexes 2a–b, when heated in solutions of ethanol
(Table 5). cis-2,6-Bis-(hydroxymethyl)-piperidines 1a and 1b are
not able to displace iminodiol 1d from Schiff-base complex 2d
under similar conditions.
EtOH / 78 °C
1
2
a
b
Entry
1
2/%
d(51V)
mp (°C)
mV=O (cmÀ1
)
1
2
3
1a
1b
1c
2a/68
2b/63
2c/90
À486
À512
À479
134
192
168
967
996
978
From intensities of vanadium-51 resonances we concluded that
the ratio of products 2a or 2b versus 2d obtained from ligand sub-
stitutions is below 96:4. Assuming a 96/4-ratio of products 2a or
2b versus 2d we estimated that Schiff-base 1d binds by a factor
of 25 stronger to oxovanadium(V) than aminodiols 1a–b. From
similar lengths of vanadium–nitrogen bonds in 2b (Table 3, entry
5) and 2d [V1–N1 = 2.114(5) Å] [38] we reasoned that the imine
nitrogen in 2d binds similarly strong to vanadium than the amine
nitrogen in piperidines 2b and 2c. The major structural difference
between iminodiol 1d and aminodiols 1a–b is electron conjugation
a
Referenced versus VOCl3 in CDCl3 [d(51V) = 0] as external standard; spectra
recorded in EtOH/CDCl3 = 2:1 (v/v).
Recorded from samples pelletized in KBr.
b
Table 2
NMR chemical shifts and fine structures for axial piperidine protons in complexes 2a
and 2c, and shift differences between vanadium complexes and underlying
aminodiols (all values for CDCl3, 20 °C; s = methyl or phenyl; d = methyl or
hydrogen).
between the two O-donor atoms. The fully conjugated
extending between the two oxygen donor atoms allows the dian-
ion of Schiff-base 1d to form an additional -bond with vanadium
p-system
4
p
3
2
5
6
in complex 2d, by which is not possible in aminodiolate complexes
2a–b.
H
N
The valence electron configuration of vanadium(V) is s0d0.
H
H
Ligand binding provides four electrons by the oxido ligand (O2À
)
O
O
V
[31,39], six from the twofold negatively charged chelate ligand
(L4)2À, and two from the alkoxo ligand (ROÀ), leading to a valence
electron configuration s2d10
.
p
-Bonding between a filled molecular
Entry
Parameter
2–Hax
3–Hax
4–Hax
5–Hax
6–Hax
orbital of dianion (L4)2À showing appropriate
p-symmetry, and two
a
1
2
3
4
d(2a)
d(2a)–d(1a)
d(2c)
3.07/d
0.64
4.61/dd
0.98
1.62/qd
0.60
1.57/m
0.16
1.62/qd
0.60
3.07/d
0.64
further electrons from a donor binding in trans-position to the
vanadyl oxygen, such as a 4-pentenol (vide infra), leads to sixteen
valence electrons at vanadium in a solvated adduct of 2d, and only
fourteen in monosolvated adducts of 2a–b. We think that
electronic configuration at vanadium explains enhanced stability
of Schiff-base complex 2d, compared to aminodiolate derivatives
2a–b.
1.09/qd
0.21
1.32/qt
À0.02
1.55/qd
0.47
3.60/m
0.73
d(2c)–d(1c)
a
Shift value refers to the center of the multiplet.
for oxovanadium(V) piperidine complexes 2a and 2c remain
unchanged (Table 4, entries 1–3). From this information we con-
cluded that vanadium compounds 2a and 2c undergo no chemical
changes in solvents used for conducting oxidation catalysis (vide
infra).
2.3. Reactivity of vanadium complexes toward tert-butyl
hydroperoxide
For quantifying vanadium complexes 2a–c in solution, we
Oxovanadium piperidine complex 2a reacts with an excess of
developed an external standard by sealing in
a
capillary
a
TBHP in a 2/1-mixture of ethanol and deuterochloroform, leading
calibrated amount of tri-(tert-butyl) vanadate dissolved in
tetrahydrofuran in an atmosphere of argon. The chemical shift of
tri-(tert-butyl) vanadate at À672 ppm [37], referenced versus
to a new compound as evident from an upfield shifted
vanadium-51 resonance (Table 6, entries 1–6). The propensity of
the new compound to be formed increases with the initial
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
Fig. 3. Ellipsoid graphic (50% probability) of piperidine-derived oxovanadium complexes 2b (left) and 2c (right, ethyl part of the ethoxo-group is disordered over two
positions with site occupancies of 0.6 and 0.4) in the solid state (150 K; hydrogen is drawn as a circle of an arbitrary radius).
peroxy vanadium complex IIa as obvious alternative (Scheme 7)
Table 3
[6,15,40].
For testing the hypothesis that peroxy vanadium complex IIa is
Intramolecular vanadium heteroatom distances in solid state structures of complexes
2b and 2c.
responsible for an upfield shifted vanadium-51 resonance, we trea-
ted a solution of piperidine complex 2a in a 2/1-volume of ethanol
and deuterochloroform with 50 equivalents of 3-ethylpenten-3-yl
hydroperoxide [41,42]. The solution was heated for 2 min at
60 °C and allowed to rest for 12 h at room temperature, leading
to a mixture composed of 46% of starting material 2a and 43% of
a new compound, as deduced from a vanadium-51 resonance at
À545 ppm. Given the similarity of chemical shifts obtained by
treating 2a either with 3-ethylpent-3-yl hydroperoxide or tert-bu-
tyl hydroperoxide we assume that a highfield-shifted resonance by
ꢀ65 ppm points to intermediate peroxy vanadium complexes.
Entry
Pair of atoms
d/Å for 2b
d/Å for 2c
1
2
3
4
5
V1–O1
V1–O2
V1–O3
V1–O4
V1–N1
1.584(2)
1.860(2)
1.843(2)
1.789(2)
2.203(2)
1.592(3)
1.838(3)
1.828(2)
1.788(3)
2.204(3)
Table 4
Stability of piperidine-derived vanadium complexes 2a and 2c in organic solvents at
20–25 °C.
a
a
a
Entry
2
Solvent
24 h/%
48 h/%
72 h/%
2.4. Oxidation of 4-pentenols
b
1
2
3
a
a
c
EtOH/CDCl3
CDCl3
CD3OD
95
94
95
93
95
94
97
95
93
2.4.1. Reactivity of piperidine-derived vanadium complex 2b
To assess reactivity of oxovanadium(V) piperidine complexes
toward TBHP we monitored the time dependent evolution of sub-
strate consumption [1-phenyl-5-methylhex-4-en-1-ol (10a)] and
formation of [2-(tetrahydrofuran-2-yl)-2-isopropanol 11a and tet-
rahydropyranol 12a]. For referencing the data we used conditions
elaborated in a previous study on alkenol oxidation by TBHP, cata-
lyzed by Schiff base complex 2d [5,19].
The time-dependent experiment shows that 1 mol% of catalyst
2b suffices to attain a maximum yield of tetrahydrofuranyl-2-
isopropanol 11a, and a minor fraction of tetrahydropyranol 12a,
leaving a portion of unspent alkenol 10a after approximately 9 h
(Scheme 8). For quantitatively oxidizing substrate 10a under such
conditions, we raised the amount of catalyst 2b by a factor five,
a
Determined versus VO(tBu)3 as external standard in a sealed capillary (see
Section 4 and text).
EtOH/CDCl3 = 4:1 (v/v).
b
TBHP-concentration and the reaction temperature (Table 6, entries
7–10). Attempts to separate and purify the new vanadium com-
pound, for example by crystallization, failed. From an experiment
showing quantitative conversion of starting material 2a we recov-
ered from chromatographic purification aminodiol 1a almost
quantitatively (94%). From this information we concluded that
the highfield shifted vanadium resonance at À552 ppm does not
reflect oxidative changes in the tridentate auxiliary, pointing to
Table 5
Products obtained from the reaction between iminodiol 1d and aminodiol-derived vanadium complexes 2a–b.
EtOH / 78 °C
VO(L1,2)(OEt)
+
VO(L4)(OEt) + H2L1,2
N
OH
OH
2a–b
H2L4 (1d)
2da
1a–b
b
Entry
2
Yield 2d/%
Yield 1/%
1
2
a
b
88
95
1a: 92
1b: 97
a
Compound 2d crystallizes from ethanol as EtOH-adduct.
Determined versus VO(tBu)3 as external standard in a sealed capillary (see Section 4 and text).
b
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
7
Table 6
Vanadium-51 NMR-analysis of mixtures formed from vanadium complex 2a and TBHP.
VO(L1)(OEt)
+
tBuOOH
vanadium-51 NMR
solvent
TBHP
2a
δ = –488
a
b
Entry
nTBHP
c0TBHP (mM)
11.0
108
500
79
196
110
219
c0 (mM)
T (°C)
t
d(51V) [%]
2a
c
1
2
3
4
5
6
7
8
1.0
10
50
10
25
100
66
30.5
30.5
30.5
11.0
10.8
10.0
7.9
7.9
1.1
23
23
23
23
23
23
60?23
60?23
60?23
60?23
5 min
5 min
5 min
12 h
12 h
12 h
15 min
5 min
5 h
À488 [95]
À488 [94]
À487 [87]
À487 [89]
À488 [63]
c
c
À533 [traces]
À552 [7]
c
c
À552 [36]
À553 [89]
À553 [66]
À553 [79]
À553 [83]
À553 [99]
c
d
e
e
e
e
3.3
À488 [24]
À488 [19]
À488 [16]
f
1017
1017
1017
33.3
33.3
33.3
f
9
f
10
72 h
a
b
c
d
e
f
Molar equivalents of TBHP referenced versus 2a.
Determined versus VO(tBu)3 as external standard in a sealed capillary (see Section 4 and text).
Reaction in EtOH/CDCl3 = 1:1 (v/v).
Reaction in EtOH/CDCl3 = 7:1 (v/v).
The reaction mixture is warmed for two minutes at 60 °C and then allowed to cool to room temperature (23 °C).
Reaction in CDCl3.
H
O
O
O
L1V OEt
H OOtBu
L1V OEt
OOtBu
L1V OOtBu
+
EtOH
+
2a
Ia
IIa
δ = –488
δ = –552
Scheme 7. Proposed transesterification of vanadium complex 2a by TBHP into a derivative of tert-butylperoxy vanadate I, IIa.
leading for example to 80% of 5-phenyltetrahydrofuranyl-2-propa-
nol (11a) as mixture of stereoisomers, with a strong preference for
the cis-configured product. 6-Phenyl-2,2-dimethyltetrahydropy-
ran-3-ol (12a) forms in 14% as ꢀ30/70-mixture of cis/trans-stereo-
isomers, supplementing the mass-balance for alkenol-derived
products to 94% (Table 7, entry 4). A control experiment performed
by stirring alkenol 10a and TBHP for 72 h in a solution of chloro-
form at room temperature did not give products 11a and 12a.
Oxidizing alkenol 10a by TBHP in the presence of Schiff-base
catalyst 2d requires ten times more catalyst for attaining a similar
turnover rate than in the reaction catalyzed by piperidine complex
2b (Supplementary data).
formation, we reasoned that the mechanism of oxidative alkenol
cyclization catalyzed by piperidine–oxovanadium complexes 2a–
b comprises the same elementary reactions as oxidations catalyzed
by Schiff-base complex 2d (Scheme 9) [6]. According to this mech-
anism, alkenol 10 coordinates to Lewis-acidic alkyl peroxy com-
plex II. Transfer of an oxygen atom in loaded intermediate III to
the alkene entity occurs stereoselectively in a chair-like folded
conformer having the substituent in position one for steric reasons
bound equatorially, leading to intermediate IV. Rearrangement of
IV gives tetrahydrofuranyl-2-propanol 11 as major product and
liberates a vanadium complex VO(L)OR, which reacts with TBHP
for propagating the catalytic cycle (Scheme 9).
Quantitative conversion of alkenol 10a by TBHP also occurs in
solutions containing 0.1 mol% of vanadium catalyst 2a or 2b
(Table 7, entries 2 and 5) or 0.05 mol% by extending reaction times
to, for example, 168 h in case of nanomolar initial catalyst concen-
tration (Table 7, entries 3 and 6). Prolonged reaction times, how-
2.4.2. Structural variation of alkenol substrates
To test whether oxovanadium(V) piperidine complexes 2a–c
and Schiff base derived vanadium complex 2d show similar reac-
tivity/selectivity-pattern for substrates other than 1-phenyl-5-
methyl-4-hexenol (10a), we treated a primary (10b), an additional
secondary (10c), and a tertiary prenyl-type 4-pentenol (10d) with
TBHP and oxidation catalysts 2a–c (Scheme 10).
ever, gave rise to side products, such as
c-butyrolactone 13a in
up to 15–19%, causing yields of 2-(tetrahydrofuran-2-yl)-2-isopro-
panol 11a to decline (Table 7, entries 2–3 and 5–6).
Other terminal oxidants than TBHP, such as 1-phenylprop-1-yl
hydroperoxide (PPHP) [43], 1-methyl-1-phenylbut-1-yl hydroper-
oxide (MPBHP) [43], 1,2-dimethyl-1-phenylprop-1-yl hydroperox-
ide (DMPPHP) [43], or trityl hydroperoxide (TrHP) [43] give rise to
similar yields of 2-(tetrahydrofuran-2-yl)-2-propanol 11a and
tetrahydropyran-3-ol 12a from alkenol 10a, as exemplified in
reactions catalyzed by tetramethyl-substituted piperidine complex
2a (Table 7, entries 7–10 and Fig. 4).
From the reaction between prochiral alkenol 10b and TBHP,
catalyzed by chiral oxovanadium(V) piperidine complex 2c, we
isolated tetrahydrofuranyl-2-isopropanol 11b and 2,2-dimethyl-
tetrahydropyranol 12b (Scheme 10, top). Both products were ob-
tained as racemates, as determined by the dioxaphospholane
method described in Section 2.2.1 (cf. Scheme 5).
Oxidizing a racemic mixture of tert-butyl-substituted secondary
alkenol 10c with TBHP in a solution of chloroform, containing
5 mol% of catalyst 2a furnishes 2-[5-(tert-butyl)-tetrahydrofuran-
2-yl]-2-isopropanol (11c), 6-(tert-butyl)-2,2-dimethyltetrahydro-
From the 2,5-cis-selectivity for converting alkenol 10a into
2-(5-phenyltetrahydrofuran-2-yl)-2-propanol (11a), and the
experimental evidence from in situ-peroxy vanadium complex
pyranol (12c), and O-pivaloyl (Piv)-substituted
c-butyrolactone
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8
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
H
OH
OH
H
H
Ph
O
tBuOOH / 2b
O
Ph
+
Ph
CHCl3 / 20 °C
OH
H
( )-12a
10a
( )-11a
OH
H
H
1,2
1,0
0,8
0,6
0,4
0,2
0,0
O
Ph
ROH 10a
11a
H
Ph
O
OH
H
12a
0
1
2
3
4
5
6
7
8
9
10
11
time / h
Scheme 8. Relative rates of alkenol oxidation by TBHP, catalyzed by 1 mol% of aminodiol-derived vanadium complex 2b.
Table 7
Oxidation of 5-methyl-1-phenylhex-4-en-1-ol (10a) by alkyl hydroperoxides, catalyzed by aminodiol-type vanadium complexes 2a–b.a,b
H
OH
H
OH
H
Ph
O
ROOH / 2
O
O
Ph
O
+
+
Ph
CHCl3 / 20 °C
OH
H
OBz
( )-12a
13a
10a
( )-11a
Entry
2/mol%
ROOH
t (h)
Conv./%
11a/% (cis:trans)
12a/% (cis:trans)
13a/%
c
d
f
1
2
3
4
5
6
7
8
9
10
2a/5
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
24
48
168
24
48
168
24
24
24
24
quant.
quant.
quant.
quant.
quant.
quant.
98
99
98
79
82 (95:5)
60 (98:2)
60 (99:1)
80 (>99:1)
62 (98:2)
62 (99:1)
78 (>99:1)
77 (95:5)
78 (95:5)
43 (>99:1)
10 (41:59)
15 (48:52)
14 (50:50)
14 (31:69)
14 (50:50)
13 (48:52)
8 (40:60)
6 (37:63)
8 (44:56)
5 (50:50)
4
e
2a/0.1
19
17
g
g
f
2a/0.05
c
d
f
h
2b/5
–
e
2b/0.1
17
15
f
2b/0.05
c
j
h
2a/5
2a/5
2a/5
2a/5
PPHP
MPBHP
–
c
d
h
–
c
j
h
DMPPHP
–
k
l
h
TrHP
–
a
b
c
d
e
f
Conversion, yields and cis/trans-ratios were determined via GC using external standards. For abbreviation of alkyl hydroperoxides ROOH, see Fig. 4.
Starting material: 1 mmol of 10a; c010a = 95.6 mM for entries 1–9 and 89.2 mM for entry 10.
c04.78 mM (0.05 mmol).
1.5 mmol of alkyl hydroperoxide corresponding to an initial concentration of 143 mM.
c0 95.6
l
M (1.0
1.5 mmol of TBHP corresponding to an initial concentration of 35.9 mM.
c0 47.8
M (0.5 mol).
lmol).
g
h
j
l
l
Not detected (GC–MS).
1.5 mmol of alkyl hydroperoxide corresponding to an initial concentration of 144 mM.
k
l
c0 4.46 mM (0.05 mmol).
1.5 mmol of alkyl hydroperoxide corresponding to an initial concentration of 134 mM.
13c in yields and stereoselectivity similar to values obtained for
phenyl-derivative 10a (Scheme 10, center).
Linalool 10d, a tertiary 4-prenyl-type alkenol, furnishes linalool
oxide 11d as major product and epoxylinalool oxide 14 as minor
product, when treated with 0.5 mol% of tetramethyl-substituted
vanadium complex 2a (Scheme 10, bottom). Raising the catalyst/
substrate ratio from 5 Â 10À3 by a factor 10 raises the yield of
epoxide 14, reducing the yield of linalool oxide 11d from 77%
(0.48 mM, for 0.5 mol% of 2a; 8% of 14) via 62% (0.96 mM, for
1 mol% of 2a; 34% of 14) to 58% (4.79 mM, for 5 mol% of 2a; 38%
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
9
OOH
OOH
OOH
OOH
OOH
Ph
Ph
Ph
Ph
Ph
Ph
PPHP
MPBHP
DMPPHP
TBHP
TrHP
Fig. 4. Structure formulas and abbreviations used for alkyl hydroperoxides in this article: TBHP = tert-butyl hydroperoxide; PPHP = 1-phenylprop-1-yl hydroperoxide;
MPBHP = 1-methyl-1-phenylbut-1-yl hydroperoxide; DMPPHP = 1,2-dimethyl-1-phenylprop-1-yl hydroperoxide; TrHP = trityl hydroperoxide.
stereoselectivity-directing effects of aminodiolate auxiliaries in
2a–c seem to be similar from those exerted by the fully conjugated
planar auxiliary in Schiff-base-derived complex 2d.
O
H
/ ROH
OH
OH
O
LV OOR
11
II
2.5. Oxidizing a 5-hexenol
10
ROOH
6-Methyl-1-phenylhept-5-en-1-ol (15) furnishes (2-tetrahydro-
pyran-2-yl)-2-propanol 16, oxepan-3-ol 17, epoxy alcohol 18, and
ketone 19, when treated with TBHP in solutions of chloroform
containing 5 mol% of oxovanadium piperidine complex 2a or 2b
respectively (Scheme 11). The alkenol cyclization occurs cis-6-
exo-selectively, providing tetrahydropyran 16 with a cis/trans-ste-
reoselectivity of 98/2. Oxepan-3-ol 17, the product of oxidative
7-endo-cyclization is formed in smaller yields and with no obvious
stereo preference.
The results obtained from oxidizing 5-hexenol 15 in summary
show that the concept of oxidative alkenol cyclization extends be-
yond tetrahydrofuran formation, possibly providing access to a lar-
ger number of structurally important tetrahydropyrans, oxepanes,
or even oxocanes.
O
O
LV OR
LV OOR
H
H
O
O
O
III
IV
Scheme 9. Proposed catalytic cycle for 4-pentenol oxidation by alkyl hydroperox-
ides catalyzed by oxovanadium piperidine complexes.
of 14). The inherently low cis-selectivity for linalool oxide forma-
tion, already referred to in earlier studies [5,44], reflects according
to our interpretation the small difference in steric size between a
methyl- and a vinyl-group, as expressed by the A-value in cyclo-
hexane conformational analysis [45].
2.6. Epoxidizing 2-propenols
The reactivity/selectivity data obtained from oxidizing primary,
secondary, and tertiary substrates in summary shows that
piperidine-derived oxovanadium complexes 2a–c are Lewis-acids,
chemoselectively activating TBHP for oxidative tetrahydrofuran
synthesis from prenyl-type 4-pentenols. Regioselectivity- and
Oxidizing geraniol by TBHP using chiral oxovanadium(V) cata-
lyst 2c occurs specifically at the allylic double bond, providing
epoxy alcohol 20 in up to 94% yield (Table 8, entry 1). Yields and
enantioselectivity of product 20 depend on the solvent used, pro-
viding highest yields in solutions of chloroform, and highest
OH
O
OH
tBuOOH / 2c a
H
O
+
CHCl3 / 20 °C
OH
H
10b
10c
( )-11b (50%)
er = 48:52
( )-12b (36%)
er = 48:52
H
O
OH
H
OH
OH
tBuOOH / 2a b
H
O
O
O
+
+
CHCl3 / 20 °C
OH
H
( )-12c (11%)
cis:trans = 49:51
OPiv
13c (9%)
( )-11c (74%)
cis:trans = 95:5
OH
H
OH
tBuOOH / 2a c
H
O
O
O
+
CHCl3 / 20 °C
10d
11d (77%)
cis:trans = 54:46
14 (8%)
Scheme 10. Yields of purified products obtained from oxidation of alkenols 10b–d by TBHP, catalyzed by piperidine-derived vanadium complexes 2a and 2c.a 1.5 mol% of 2c.b
5 mol% of 2a; for 5 mol% of 2b (yields determined 1H NMR): 76% of 11c (cis:trans = 96:4), 10% of 12c (cis:trans = 50:50), 10% of 13c.c 0.5 mol% of 2a; for 5 mol% of 2a: 4 h
reaction time, 52% of 11d (cis:trans = 65:35) and 38% of 14.
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10
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
OH
H
H
H
OH
tBuOOH / 2a a
O
Ph
O
5
Ph
+
+
OH
Ph
1
CHCl3 / 20 °C
H
15
( )-16 (42%)
( )-17 (14%)
cis:trans = 98:2
cis:trans = 50:50
OH
O
O
Ph
Ph
18 (23%)
19 (19%)
Scheme 11. Products of 6-methyl-1-phenylhept-5-en-1-ol oxidation by TBHP in vanadium-catalyzed reaction.a 5 mol% of 2a; for 5 mol% of 2b (yields determined 1H NMR):
43% of 16 (cis:trans = 99:1), 21% of 17 (cis:trans = 50:50), 21% of 18, and 12% of 19.
tert-butyl hydroperoxide. Major advantages of the new oxidation
catalysts relate to improved chemical inertness of the saturated tri-
dentate auxiliary, enhanced reactivity, and improved chemoselec-
tivity, compared to oxidations catalyzed by iminodiol-derived
Schiff-base complex 2d.
Table 8
Selectivity in the oxidation of geraniol by TBHP, catalyzed by chiral oxovanadium(V)
complex 2c.a
tBuOOH / 2c
O
OH
OH
solvent / 20 °C
In view of the advantages for synthesis of hydroxyl-substituted
cyclic ethers via oxidative cyclization, we consider cis-2,6-bis-
(hydroxymethyl)-piperidine complexes of oxovanadium(V) as
leads for solving the standing problem on external stereo induction
in synthesis of tetrahydrofurans from alkenols. Chirality transfer
according to the concept pursued in the present project relies on
C1-symmetry of auxiliary 1c for controlling configuration at
vanadium in complex 2c (Fig. 5). So far we have no structural
evidence other than the solid state structure of 2c for assuming a
stereochemical relation between configuration of the auxiliary
and a vanadium(V) center. We are not aware of reports on config-
urational stability of stereotopic oxovanadium entities in solution.
Racemization of chiral oxovanadium compounds in the solid state
is documented [46]. The data from enantioselective geraniol epox-
idation and oxidation of further prochiral alkenols in this study
point a stereochemical leak along the sequence involved in stereo-
control of carbon–oxygen bond formation.
The arguments explaining the difficulties to enantioselectively
epoxidize geraniol with selectivity coming close to the titanium/
dialkyl tartrate system [47] led us to the conclusion to screen
in upcoming studies C2-symmetric aminodiols as auxiliaries.
C2-symmetry reduces the number of possible diastereomeric
transition structures, providing a promising approach for achieving
the goal to prepare chiral (tetrahydrofuran-2-yl)-methanols from
enantioselective 4-pentenol cyclization.
geraniol
20
b
Entry
Solvent
20/% (er)
1
2
3
4
5
CHCl3
CH2Cl2
C6H6
PhCH3
PhCF3
94 (44:56)
87 (50:50)
80 (39:61)
78 (43:57)
70 (44:56)
a
1.5 mol% of 2c, 24 h reaction time, quantitative conversion of geraniol.
determined by phosphorous-31 NMR after derivatizing 20 with a (1R,2S,5R)-
menthyl (R,R)-tartrate-derived 2-chloro-1,3,2-dioxaphospholane into the cor-
responding phosphite.
b
tBuOOH / 2c
O
OH
Ph
OH
Ph
CHCl3 / 20 °C
cinnamyl alcohol
21 (94%)
er = 44:56
Scheme 12. Synthesis of epoxy alcohol 21 from cinnamyl alcohol and TBHP,
catalyzed by chiral piperidine complex 2c.
enantioselectivity in a solution of benzene (Table 8, entry 3). No
epoxidation occurs upon adding TBHP alone to a solution of gera-
niol in chloroform.
Oxidizing cinnamyl alcohol by TBHP in a solution of chloroform
containing vanadium catalyst 2c furnishes epoxy alcohol 21 in 94%
yield, without noteworthy stereochemical preference (Scheme 12).
The results from (E)-2-propenol-oxidation in summary show
that TBHP and oxovanadium(V) piperidine complex 2c specifically
epoxidize the allylic carbon–carbon double bond, however in
comparatively low stereoselectivity.
VOL3(OEt)
N
H
H
H
HO
OH
H2L3 (1c)
2c
O
V
syn
V
O
or
anti
3. Concluding remarks
Piperidine-2,6-bismethanol-derived oxovanadium(V) com-
plexes 2a–c are potent Lewis-acids for catalyzing synthesis of
2-(tetrahydrofuran-2-yl)-2-propanols, 2-(tetrahydropyran-2-yl)-
2-propanols, oxepan-3-ols, and epoxides from alkenols and
epimers
single enantiomer
Fig. 5. Stereochemical aspects associated with oxovanadium complexation of chiral
piperidine H2L3 (1c).
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M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
11
4.2.4. (2R,6S)-2-Acetyloxymethyl-1-carbonyloxybenzyl-6-
hydroxymethyl-piperidine (2R,6S)-(6)
4. Experimental
A mixture of substituted piperidine 5 (740 mg, 2.04 mmol)
aqueous phosphate buffer (pH 7) [0.1 M aqueous sodium dihydro-
genphosphate (120 mL), 0.1 M aqueous sodium hydroxide (70 mL),
water (50 mL)] and A. niger-lipase (333 mg) was stirred at 40 °C for
24 h. The reaction mixture was saturated with sodium chloride and
extracted with ethyl acetate (3 Â 100 mL). Combined organic ex-
tracts were washed with brine (2 Â 80 mL), dried (MgSO4) and
4.1. General
For general laboratory practice and instrumentation see Ref.
[48] and the Supplementary data.
4.2. Synthesis of 2,6-substituted piperidines (1a–c) as ligands
concentrated at 40 °C in an aspirator vacuum to leave the title
20
compound. Yield: 537 mg (1.67 mmol, 82%), colorless oil, [a]
4.2.1. cis-2,6-Bis-(2-hydroxyprop-2-yl) piperidine (1a) [32]
D
+4.10 (c 3.80, CHCl3).
A mixture of 2,6-bis-(2-hydroxyprop-2-yl) pyridine (128 mg,
656 lmol), ethyl acetate (20 mL) and Pd/C (10% Pd, 200 mg) was
4.2.5. (2S,6R)-1-Carbonyloxybenzyl-2-ethoxycarbonyl-6-
hydroxymethyl-piperidine (2S,6R)-(7)
stirred at 20 °C under an atmosphere of H2 (pressure 550 kpa) for
72 h. The suspension was filtrated through a pad of Celite, dried
(MgSO4) and concentrated by evaporating the solvent at a temper-
(2R,6S)-2-acetyloxymethyl-1-carbonyloxybenzyl-6-hydroxy-
methyl-piperidine (2R,6S)-(6) obtained from Section 4.2.4 (2.40 g,
7.47 mmol) was dissolved in dichloromethane (50 mL) and treated
with a solution of methyltrioctylammoniumchloride (Aliquat 336,
318 mg, 0.79 mmol) in water (25 mL) and at a temperature of 4 °C
in portions over a period of 30 min with potassium permanganate
(2.38 g, 15.1 mmol). The slurry was stirred after complete addition
of potassium permanganate for 30 min at a temperature of 4 °C
and for 18 h at a temperature of 20 °C. Afterwards, a saturated
aqueous solution of NaHSO3 (60 mL) was added, the slurry was
stirred for 20 min at a temperature of 20 °C and treated with con-
centrated sulfuric acid to adjust a pH of 3–4 in the aqueous phase.
The layers were separated and the aqueous phase extracted with
dichloromethane (2 Â 60 mL). Combined organic layer and extracts
were washed with brine (50 mL), dried (MgSO4) and concentrated
at a bath temperature of 40 °C in an aspirator vacuum. The remain-
ing oil (2.18 g) was taken up in a mixture of ethanol (120 mL), tol-
uene (50 mL) and concentrated sulfuric acid (1.5 mL) and stirred
while being refluxed for 16 h. The mixture was allowed to cool to
room temperature and concentrated at a bath temperature of
40 °C in an aspirator vacuum. The residue was taken up in water
(50 mL), treated with a saturated aqueous solution of potassium
carbonate to adjust a pH of 7–8, and extracted with diethyl ether
(4 Â 50 mL). Combined organic extracts were successively washed
with a saturated aqueous NaHCO3-solution (50 mL), water (50 mL),
and brine (2 Â 40 mL). The clear organic solution was dried
(MgSO4) and concentrated at a bath temperature of 40 °C in an
aspirator vacuum, to afford a yellow oil, which was purified by
chromatography [ethyl acetate/pentane = 1:1 (v/v)]. Yield: 1.89 g
ature of 40 °C and
a pressure of 200 mbar. Yield: 112 mg
(556
l
mol, 85%), colorless solid, mp 48 °C. 1H NMR (CDCl3,
400 MHz) d1.02 (qd, Jq = 12.9 Hz, Jd = 4.0 Hz, 2 H), 1.13 (s, 6 H),
1.21 (s, 6 H), 1.41 (qt, Jq = 13.2 Hz, Jt = 3.8 Hz, 1 H), 1.68–1.72 (m,
2 H), 1.90–1.97 (m, 1 H), 2.43 (dd, J = 11.6, 2.4 Hz, 2 H), 2.78 (br
s, 3 H, OH, NH) 13C NMR (CDCl3, 101 MHz) d24.1, 24.5, 26.6, 27.3,
65.3, 71.5. Anal. Calc. for C11H23NO2 (201.31): C, 65.63; H, 11.52;
N, 6.96. Found: C, 65.71; H, 11.62; N, 7.05%.
4.2.2. 2,6-Bis-(1-hydroxy-1,1-diphenyl-methyl) pyridine
A
solution of 2,6-dimethyl pyridine-2,6-dicarboxylate (4)
(2.50 g, 12.8 mmol) in CH2Cl2 (20 mL) was added in a drop wise
manner to a cooled (0 °C) solution of phenyl magnesium bromide,
prepared from bromobenzene (9.66 g), magnesium turnings
(1.50 g) and tetrahydrofuran (30 mL). The resulting mixture was
stirred while being cooled to 0 °C in an ice bath for 30 min and
treated with an aqueous solution of satd. NH4Cl (40 mL). The mix-
ture was extracted with CH2Cl2 (3 Â 50 mL), dried (MgSO4) and
concentrated at a temperature of 40 °C and a pressure of 50 mbar.
The remaining yellow solid was purified by flash chromatography
[petroleum ether (boiling range 40–60 °C)/ethyl acetate = 2:1 (v/
v)]. Yield: 4.58 g, (10.3 mmol, 81%), colorless solid. Rf = 0.60
[petroleum ether (boiling range 40–60 °C)/ethyl acetate = 2:1 (v/
v)], mp 131–132 °C. 1H NMR (CDCl3, 400 MHz) d5.04 (s, 2 H,
OH), 7.06 (d, J = 7.8 Hz, 2 H), 7.18–7.37 (m, 20 H), 7.59 (t,
J = 7.8 Hz, 1 H).
(5.90 mmol, 79%), light yellow oil, Rf = 0.44 [ethyl acetate/pen-
À13.5 (c 1.00, CHCl3). 1H NMR (CDCl3,
20
4.2.3. cis-2,6-Bis-(1-hydroxy-1,1-diphenyl-methyl) piperidine (1b)
A mixture of 2,6-bis-(1-hydroxy-1,1-diphenyl-methyl) pyridine
(3.45 g, 7.78 mmol), acetic acid (100 mL) and palladium on char-
coal (10% palladium, 340 mg) was stirred at 80 °C under an atmo-
sphere of hydrogen gas (pressure 350 kpa) for 24 h. The suspension
was filtrated through a pad of Celite. The filtrate was basified with
an aqueous solution of sodium hydroxide (20%, w/w) to pH 12 and
extracted with dichloromethane (3 Â 150 mL). Combined organic
extracts were dried (MgSO4) and concentrated at a temperature
of 40 °C and a pressure of 50 mbar, to leave a solid, which was crys-
tallized from ethyl acetate (5 mL). The crop of crystals was thor-
oughly dried at room temperature and a pressure of 10À3 mbar.
Yield: 2.57 g (5.73 mmol, 74%), colorless solid, mp 179 °C. 1H
NMR (CDCl3, 600 MHz) d1.26–1.29 (m, 3 H), 1.32 (q, J = 10.5 Hz, 2
H), 1.75–1.78 (m, 1 H), 1.95 (br s, 1 H, NH), 3.47 (br s, 2 H, OH),
3.66 (dd, J = 8.6, 1.5 Hz, 2 H), 7.05 (t, J = 7.5 Hz, 2 H), 7.13–7.16
(m, 6 H), 7.25 (t, J = 7.5 Hz. 4 H), 7.40 (d, J = 7.5 Hz, 4 H), 7.43 (d,
J = 7.5 Hz, 4 H). 13C NMR (CDCl3, 151 MHz) d23.84, 24.85, 62.19,
78.62, 125.4, 125.5, 126.5, 126.8, 128.0, 128.4, 143.8, 145.1. Anal.
Calc. for C31H31NO2 (449.58): C, 82.82; H, 6.95; N, 3.12. Found: C,
82.72; H, 7.04; N, 3.11%.
tane = 1:1 (v/v)], [
a]
D
400 MHz) d1.21–1.33 (m, 3 H), 1.42–1.81 (m, 6 H), 2.15 (br s, 1
H, OH), 3.44–3.66 (m, 2 H), 4.09–4.23 (m, 2 H), 4.45–4.47 (m, 1
H), 4.87–4.94 (m, 1 H), 5.11–5.21 (m, 2 H), 7.30–7.38 (m, 5 H).
13C NMR (CDCl3, 101 MHz) d14.0, 16.8, 24.8, 26.0, 51.9, 53.6,
60.8, 61.8, 67.6, 127.8, 128.0, 128.4, 136.6, 172.8, 174.3. Anal. Calc.
for C17H23NO5 (321.37): C, 63.54; H, 7.21; N, 4.36. Found: C, 63.62;
H, 7.23; N, 4.41%.
4.2.6. (2S,6R)-2-Ethoxycarbonyl-6-hydroxymethyl piperidine (2S,6R)-
(8)
A stream of hydrogen was passed for 30 min through a slurry of
(2S,6R)-1-carbonyloxybenzyl-2-ethoxycarbonyl-6-hydroxy-
methyl-piperidine (2S,6R)-(7) (298 mg, 0.93 mmol), ethyl acetate
(30 mL) and palladium on charcoal (400 mg, 10% of palladium
loading). The reaction mixture was stirred for 8 h at a temperature
of 23 °C and then saturated again by passing a stream of hydrogen
through the mixture for 30 min. Stirring was again continued for
13 h at a temperature of 23 °C. The suspension was filtrated
through a pad of Celite, dried (MgSO4) and concentrated at a bath
temperature of 40 °C in an aspirator vacuum. The remaining oil
Please cite this article in press as: M. Dönges et al., Inorg. Chim. Acta (2014), http://dx.doi.org/10.1016/j.ica.2014.02.007

12
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
was purified by chromatography [ethyl acetate/methanol/pen-
4.3. Synthesis of oxovanadium(V) complexes
tane = 1:1:1 (v/v/v)]. Yield: 144 mg (0.77 mmol, 83%), colorless so-
lid, mp 59 °C, Rf = 0.58 [ethyl acetate/methanol/pentane = 1:1:1 (v/
4.3.1. General procedure
20
v/v)]. [
a]
À41.7 (c 1.20, acetone). 1H NMR (CDCl3, 400 MHz) d1.11
Neat triethyl vanadate (1 equiv.) was added to a solution of an
aminodiol 1a–c (1 equiv.) in ethanol. The resulting mixture was
heated to reflux for 1–2 h, stirred for 20–22 h at 24 °C, and concen-
trated at a bath temperature of 40 °C and a pressure of 150 mbar.
The remaining oil was crystallized from ethanol.
D
(qd, Jq = 12.7 Hz, Jd = 3.9 Hz, 1 H), 1.26 (t, J = 7.0 Hz, 3 H), 1.38 (qd,
Jq = 12.9 Hz, Jd = 3.5 Hz, 1 H), 1.44 (qt, Jq = 12.9 Hz, Jt = 3.7 Hz, 1 H),
1.52–1.54 (m, 1 H), 1.89–1.92 (m, 1 H), 2.01–2.03 (m, 1 H), 2.61 (br
s, 1 H, OH), 2.70–2.74 (m, 1 H), 3.34 (dd, J = 11.4, 2.9 Hz, 1 H), 3.47
(dd, J = 11.0, 7.9 Hz, 1 H), 3.63 (dd, J = 11.0, 3.5 Hz, 1 H), 4.17 (q,
J = 7.2 Hz,
1 H), 4.18 (q, J = 7.2 Hz, 1
H). 13C NMR (CDCl3,
101 MHz) d14.2, 24.0, 27.6, 29.2, 57.5, 58.7, 60.8, 66.5, 173.3. Anal.
Calc. for C9H17NO3 (187.24): C, 57.73; H, 9.15; N, 7.48. Found: C,
57.46; H, 9.22; N, 7.51%.
4.3.2. {cis-2,6-Bis[1,1-dimethylmethanolato(À1)]-piperid-2,6-
diyl}(ethanolato)oxidovanadium(V) (2a) [VO(L1)(OEt)]
Reactants: H2L1 (1a) (737 mg, 3.66 mmol), VO(OEt)3 (740 mg,
3.66 mmol), and ethanol (50 mL). Yield: 772 mg (2.48 mmol,
68%), dark yellow solid, mp 134 °C. 1H NMR (CD3OD, 400 MHz) d
1.17 (t, J = 7.1 Hz, 3 H), 1.20 (s, 6 H), 1.49 (s, 6 H), 1.62 (qd,
Jq = 11.7 Hz, Jd = 3.2 Hz, 2 H), 1.66–1.74 (m, 3 H), 2.04–2.10 (m, 1
H), 3.07 (d, J = 10.2 Hz, 2 H), 3.60 (q, J = 7.0 Hz, 2 H), 4.61 (s, 1 H,
NH). 13C NMR (CD3OD, 101 MHz) d 18.3, 21.5, 27.3, 28.6, 58.3,
81.3, 90.7. 51V NMR (ethanol/CDCl3 = 2:1; 105 MHz) d À486. 51V
4.2.7. (2S,6R)-6-Hydroxymethyl-2-(1-hydroxy-1,1-diphenylmethyl)
piperidine (1c)
In an atmosphere of nitrogen, a solution of (2S,6R)-2-ethoxycar-
bonyl-6-hydroxymethyl
piperidine
(2S,6R)-(8)
(120 mg,
0.64 mmol) in tetrahydrofuran (10 mL) was added in a drop wise
manner to a solution of phenyl magnesium chloride (1.06 mL,
1.92 mmol, in tetrahydrofuran) in tetrahydrofuran (5 mL). The
reaction mixture was stirred for 14 h at a temperature of 20 °C,
for 6 h while being boiled under reflux, and allowed to cool to room
temperature. Water (4 mL) was carefully added, followed by a sat-
urated aqueous solution of ammonium chloride (20 mL). The layers
were separated and the aqueous layer extracted with diethyl ether
(4 Â 25 mL). Combined organic layer and extracts were succes-
sively washed with water (20 mL), and brine (2 Â 30 mL). The clear
solution was dried (MgSO4) concentrated at a bath temperature of
40 °C in an aspirator vacuum. The remaining oil was purified by
chromatography [ethyl acetate/diethyl ether/pentane = 2:1:1 (v/v/
NMR (CDCl3, 105 MHz) d À488. IR (KBr)
m
max/cmÀ1 3406, 3166,
2968, 2934, 2860, 1647 (N–H), 1451, 1382, 1362, 1206, 1164,
1141, 1105, 1050, 967 (V@O). UV–Vis (EtOH) kmax/nm (lg
e
/m2 -
molÀ1) 204 nm (1594), 275 (703), 313sh (469), 346sh (282). Anal.
Calc. for C13H26NO4V (311.29): C, 50.16; H, 8.42; N, 4.50; Found:
C, 50.08; H, 8.20; N, 4.29%.
4.3.3. {cis-2,6-Bis[1,1-diphenylmethanolato(À1)]-piperid-2,6-
diyl}(ethanolato)oxidovanadium(V) (2b) [VO(L2)(OEt)]
Reactants: H2L2 (1b) (220 mg, 0.49 mmol), VO(OEt)3 (100 mg,
0.49 mmol), and ethanol (20 mL). Yield: 176 mg (0.31 mmol,
63%), pale yellow solid, mp 192 °C. 51V NMR (ethanol/CDCl3 = 2:1;
105 MHz) d À512. 51V NMR (CDCl3, 105 MHz) d À481/À486/À512/
À529 (0.07/0.14/1.00/0.20). 51V NMR (EtOH/CDCl3 = 2:1 (v/v),
v)]. Yield: 104 mg (0.35 mmol, 55%), colorless solid, mp 104 °C,
20
Rf = 0.41 [EtOAc/Et2O/Pentane = 2:1:1 (v/v/v)],
[a
]
D
À103.6 (c
0.70, CHCl3), 1H NMR (CDCl3, 400 MHz) d1.08 (qd, Jq = 11.8 Hz,
Jd = 3.5 Hz, 1 H), 1.23–1.37 (m, 4 H), 1.51–1.55 (m, 1 H), 1.75–
1.80 (m, 1 H), 2.17 (br s, 2 H, OH), 2.87 (tq, Jt = 7.3 Hz, Jq = 3.2 Hz,
1 H), 3.35 (dd, J = 10.5, 7.0 Hz, 1 H), 3.54 (dd, J = 10.8, 3.8 Hz, 1
H), 3.63 (dd, J = 10.2, 2.9 Hz, 1 H), 7.15 (t, J = 7.3 Hz, 1 H), 7.21 (t,
J = 7.3 Hz, 1 H), 7.24–7.28 (m, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 7.46
(d, J = 7.3 Hz, 2 H), 7.61 (d, J = 7.3 Hz, 2 H). 13C NMR (CDCl3,
101 MHz) d23.8, 25.4, 27.8, 57.9, 61.3, 67.3, 78.5, 125.6, 126.1,
126.4, 127.0, 128.0, 128.6, 144.4, 146.1. Anal. Calc. for C19H23NO2
(297.39): C, 76.73; H, 7.80; N, 4.71. Found: C, 76.35; H, 7.99; N,
4.51%.
105 MHz) d = À512. IR (KBr)
m
max/cmÀ1 3057, 3021, 2953, 2928,
2868, 1597 (N–H), 1491, 1448, 1416, 996 (V@O). UV–Vis (EtOH)
kmax/nm (lg
e
/m2 molÀ1) 203 nm (3064), 249 (1252). Anal. Calc.
for C33H34NO4V (559.57): C, 70.83; H, 6.12; N, 2.50. Found: C,
70.58; H, 6.29; N, 2.42%.
4.3.4. {cis-(2S,6R)-2-[1,1-diphenylmethanolato(À1)]-6-methanolato-
(À1)-piperid-2,6-diyl}(ethanolato)oxidovanadium(V) (2c)
[VO(L3)(OEt)]
Reactants: H2L3 (1c) (86.0 mg, 0.29 mmol), VO(OEt)3 (58.0 mg,
0.29 mmol), and ethanol (10 mL). Yield: 106 mg (0.26 mmol,
90%), pale yellow solid, mp 168 °C. 1H NMR (CD3OD, 600 MHz) d
1.09 (qd, Jq = 13.6 Hz, Jd = 3.1 Hz, 1 H), 1.17 (t, J = 7.2 Hz, 3 H),
1.15–1.19 (m, 1 H), 1.32 (qt, Jq = 12.9 Hz, Jt = 3.1 Hz, 1 H), 1.55
(qd, Jq = 13.3 Hz, Jd = 3.1 Hz, 1 H), 1.60–1.71 (m, 2 H), 3.57–3.62
(m, 1 H), 3.60 (q, J = 6.8 Hz, 2 H), 3.99–4.08 (m, 1 H), 4.61 (dd,
J = 11.6, 4.1 Hz, 1 H), 4.69 (dd, J = 9.9, 3.8 Hz, 1 H), 7.09 (t,
J = 7.5 Hz, 1 H), 7.18–7.23 (m, 3 H), 7.31–7.32 (m, 2 H), 7.36 (t,
J = 7.8 Hz, 2 H), 7.81 (d, J = 7.5 Hz, 2 H). 13C NMR (CD3OD,
151 MHz) d 18.4, 22.1, 26.9, 27.6, 58.3, 62.9, 67.9, 82.0, 97.9,
126.7, 127.3, 127.5, 128.1, 128.9, 129.4, 145.2. 51V NMR (EtOH/
CDCl3 = 2:1; 105 MHz) d À479. 51V NMR (CD3OD, 105 MHz) d
4.2.8. (2S,6R)-6-Hydroxymethyl-piperidine-2-carbonic acid
hydrochloride (9)
A
solution of (2S,6R)-2-ethoxycarbonyl-6-hydroxymethyl
piperidine (2S,6R)-(8) (100 mg, 0.53 mmol) in methanol (2 mL)
was treated with a 2 M aqueous solution of NaOH (2.5 mL). The
resulting mixture was stirred for 2 h at a temperature of 24 °C
and concentrated afterwards at a temperature of 40 °C in an aspi-
rator vacuum. The remaining aqueous solution was acidified with
dilute hydrochloric acid (pH 1–2) and set aside at a temperature
of 4 °C. The crop of crystals having separated after 3 days were col-
lected by filtration, washed with cold (À20 °C) tetrahydrofuran
(10 mL). Yield: 89 mg (0.46 mmol, 87%), colorless solid, mp
20
239 °C, [
a]
À27.0 (c 0.50, acetone). 1H NMR (CDCl3, 600 MHz)
À467. 51V NMR (CD3CN, 105 MHz) d À492. IR (KBr)
m
max/cmÀ1
D
d1.38 (qd, Jq = 12.7 Hz, Jd = 3.7 Hz, 1 H), 1.52–1.62 (m, 2 H), 1.80
(d, J = 14.9 Hz, 1 H), 1.89–1.95 (m, 1 H), 2.20–2.25 (m, 1 H), 3.19–
3.23 (m, 1 H), 3.59 (dd, J = 12.5, 7.5 Hz, 1 H), 3.75 (dd, J = 12.5,
3.7 Hz, 2 H). 13C NMR (CDCl3, 151 MHz) d22.2, 24.5, 26.5, 58.6,
58.9, 62.3, 172.8.
3435, 2936, 2861, 2361, 1654 (N–H), 1490, 1447, 1097, 1064,
978 (V@O). UV–Vis (EtOH) kmax/nm (lge ) 204 nm
/m2 molÀ1
(1170), 219sh (658), 246sh (291), 311sh (76). Anal. Calc. for C21H26-
NO4V (407.38): C, 61.91; H, 6.43; N, 3.44. Found: C, 62.01; H, 6.36;
N, 3.38%.
Please cite this article in press as: M. Dönges et al., Inorg. Chim. Acta (2014), http://dx.doi.org/10.1016/j.ica.2014.02.007

M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
13
4.3.5. [N-Oxidobenzyliden(À1)-2-
2-ol (14). Yield: 70.7 mg (0.38 mmol, 38%), mixture of cis/trans-iso-
mers. Rf = 0.15 [diethyl ether/pentane = 1:1 (v/v)].
aminophenolato(À1)](ethanol)(ethanolato)oxidovanadium(V) (2d)
[VO(L4)(OEt)] [6]
Reactants: H2L4 (1d) (2.13 g, 9.99 mmol), VO(OEt)3 (2.02 mg,
10.0 mmol) and ethanol (70 mL). Yield: 2.67 g (7.20 mmol, 72%),
dark brown crystals. 51V NMR (CDCl3/ethanol = 2:1, 158 MHz)
d = À538. 1H NMR (CDCl3, 400 MHz): d = 1.24 (m, 3 H, CH3), 1.70 (t,
3 H, J = 7.16 Hz), 3.72 (m, 2 H)), 5.55 (m, 2 H), 6.97–7.76 (m, 8 H),
4.4.5. Oxidation of 6-methyl-1-phenylhept-5-en-1-ol (15)
Reactants: 6-Methyl-1-phenylhept-5-en-1-ol (15) (102 mg,
0.5 mmol) in chloroform (2.5 mL), VO(L1)(OEt) (2a) (7.8 mg,
25 lmol) and TBHP (5.5 M solution in nonane, 135 lL, 743 mmol)
in chloroform (2.5 mL). Reaction time: 48 h at 20 °C. Eluent used
for chromatographic purification: petroleum ether/acetone = 3:1
(v/v). 6-Methyl-1-phenylhept-5-en-1-one (19). Yield: 19.4 mg
9.21 (s, 1 H). IR (KBr) m
max/cmÀ1 1609, 1545, 1370, 1299, 990 (V@O).
4.4. Vanadium-catalyzed oxidation of alkenols
(95
lmol, 19%). Rf = 0.82 [petrol ether/acetone = 3:1 (v/v)]. 2-(Tet-
rahydro-6-phenyl-2H-pyran-2-yl)-propan-2-ol
(16). Yield:
4.4.1. General method
45.9 mg (0.21 mmol, 42%), 98/2-mixture of cis/trans-isomers.
Rf = 0.53 [petrol ether/acetone = 3:1 (v/v)]. 4-(3,3-Dimethyloxi-
ran-2-yl)-1-phenylbutan-1-ol (18). Yield: 25.0 mg (114 lmol,
A solution of TBHP in nonane (5.5 M) was added to a solution of
VO(L)(OEt) (2) in chloroform. The resulting mixture was heated for
2 min at 60 °C and treated at 20 °C with a solution of the alkenol in
chloroform. The reaction mixture was stirred for the time specified
below at 20 °C and concentrated at bath temperature of 40 °C in an
aspirator vacuum. The remaining oil was purified by chromatogra-
phy using the eluent specified in the procedures outlined in Sec-
tions 4.4.2–4.4.5.
23%). Rf = 0.50 [petrol ether/acetone = 3:1 (v/v)]. 1H NMR (CDCl3,
600 MHz) d 1.23 (s, 3 H), 1.24 (s, 3 H), 1.28 (s, 6 H), 1.38–1.44
(m, 2 H), 1.53–1.56 (m, 4 H), 1.58–1.65 (m, 2 H), 1.73–1.79 (m, 2
H), 1.82–1.88 (m, 2 H), 2.12 (br s, 2 H, OH), 2.68 (t, J = 6.2 Hz, 2
H), 4.65–4.69 (m, 2 H), 7.25–7.29 (m, 2 H), 7.33–7.34 (m, 8 H).
13C NMR (CDCl3, 151 MHz) d18.7, 22.7, 24.8, 28.6, 28.6, 38.6,
38.7, 58.3, 58.4, 64.3, 64.4, 74.3, 74.5, 125.8, 127.5, 128.4, 144.6,
144.7. HRMS calcd. for C14H20O2 220.1463; found: 220.1503. 2,2-
4.4.2. Oxidation of 5-methylhex-4-en-1-ol (10b)
Reactants: 5-Methylhex-4-en-1-ol (10b) (87 mg, 0.5 mmol) in
Dimethyl-7-phenyloxepan-3-ol (17). Yield: 15.5 mg (70.5 lmol,
chloroform (2.5 mL), VO(L3)(OEt) (2c) (3.0 mg, 7.5
lmol,
14%), 50/50-mixture of cis/trans-isomers. Rf = 0.20 [petrol ether/
acetone = 3:1 (v/v)]. Isomer 1: 1H NMR (CDCl3, 600 MHz) d 1.25
(s, 3 H), 1.27 (s, 3 H), 1.38–1.43 (m, 2 H), 1.57–1.64 (m, 2 H),
1.80–1.85 (m, 2 H), 2.68 (br s, 1 H, OH), 3.80 (dd, J = 11.0, 2.0 Hz,
1 H), 4.65–4.67 (m, 1 H), 7.25–7.28 (m, 1 H), 7.31–7.35 (m, 4 H).
13C NMR (CDCl3, 151 MHz) d23.8, 25.1, 26.2, 32.7, 38.3, 74.0,
74.2, 76.0, 125.7, 127.5, 128.4, 144.6. HRMS calcd. for C14H20O2
220.1463; found: 220.1478. Isomer 2: 1H NMR (CDCl3, 600 MHz)
d 1.31–1.37 (m, 2 H), 1.51 (s, 3 H), 1.55 (s, 3 H), 1.65–1.72 (m, 2
H), 1.73–1.79 (m, 2 H), 2.68 (br s, 1 H, OH), 3.45 (dd, J = 10.2,
1.8 Hz, 1 H), 4.65–4.67 (m, 1 H), 7.25–7.28 (m, 1 H), 7.31–7.35
(m, 4 H). 13C NMR (CDCl3, 151 MHz) d22.8, 27.1, 29.1, 31.2, 38.7,
72.8, 74.4, 78.7, 125.8, 127.4, 128.3, 144.6. HRMS calcd. for
1.5 mol%) and TBHP (135
lL, 5.5 M solution in nonane, 0.75 mmol)
in chloroform (2.5 mL). Reaction time: 24 h at 23 °C. Eluent used
for chromatographic purification: diethyl ether/pentane = 1:2 (v/
v). 2-(Tetrahydrofuran-2-yl)-propan-2-ol (11b) [6]. Yield: 33 mg
(0.25 mmol, 50%, er = 48:52), colorless oil. Rf = 0.14 [diethyl ether/
pentane = 1:2 (v/v)]. 2,2-Dimethyl-tetrahydropyran-3-ol (12b)
[6]. Yield: 23 mg (0.18 mmol, 36%, er = 48:52), colorless oil.
Rf = 0.10 [diethyl ether/pentane = 1:2 (v/v)].
4.4.3. Oxidation of 2,2,7-trimethyloct-6-en-3-ol (10c)
Reactants: 2,2,7-Trimethyloct-6-en-3-ol (85 mg, 0.5 mmol)
(10c) in chloroform (2.5 mL), VO(L1)(OEt) (2a) (7.8 mg, 25
l
mol),
L; 743 mmol initial con-
L, 743 mmol after 24 h; 135 L, 743 mmol after
and TBHP (5.5 M solution in nonane, 135
centration; 135
l
C14H20O2–H2O 202.1358; found: 202.1356.
l
l
48 h) in chloroform (2.5 mL). Reaction time: 168 h at 20 °C. Eluent
used for chromatographic purification: diethyl ether/pentane = 1:1
(v/v). 2-(5-tert-Butyl-tetrahydrofuran-2-yl)-propan-2-ol (11c) [6].
4.5. Vanadium-catalyzed epoxidation of alkenols
4.5.1. General method
Yield: 68.8 mg (0.37
Rf = 0.50 [diethyl ether/pentane = 1:1 (v/v)]. 2,2-Dimethyl-6-tert-
butyl-tetrahydropyran-3-ol (12c) [6]. Yield: 10.2 mg (0.06 mol,
11%), 49/51-mixture of cis/trans-isomers. Rf = 0.37 [diethyl ether/
pentane = 1:1 (v/v)]. 3-Pivaloyloxy-2,2-dimethyl-tetrahydrodrofu-
l
mol, 74%), 95/5-mixture of cis/trans-isomers.
A solution of TBHP (5.5 M) in nonane was added to a solution of
VO(L3)(OEt) (2c) in the solvent specified in Sections 4.5.2–4.5.4.
The resulting mixture was heated for 2 min at 60 °C and treated
at 20 °C with a solution of the alkenol in the same solvent, 2c
was dissolved in. The reaction mixture was stirred for 24 h at a
temperature of 20 °C and concentrated at a bath temperature of
40 °C in an aspirator vacuum to leave an oil, which was purified
by chromatography [diethyl ether/pentane = 1:2 (v/v)].
l
ran-5-one (13c). Yield: 9.6 mg (0.05 lmol, 9%). Rf = 0.28 [diethyl
ether/pentane = 1:1 (v/v)]. 1H NMR (CDCl3, 400 MHz) d 1.22 (s, 9
H), 1.41 (s, 3 H), 1.45 (s, 3 H), 2.51 (dd, J = 18.6, 2.1 Hz, 1 H), 3.06
(dd, J = 18.6, 6.7, Hz, 1 H), 5.16 (dd, J = 6.7, 2.2, Hz, 1 H). 13C NMR
(CDCl3, 151 MHz) d21.6, 26.4, 27.0, 36.0, 38.9, 74.4, 86.4, 173.6,
177.5. Anal. Calc. for C11H18O4 (214.26): C, 61.66; H, 8.47; Found:
C, 61.60; H, 8.39%. GC/MS (EI): m/z (%) = 57 (100), 199 (15)
[M+ÀCH3], 215 (5) [M++H].
4.5.2. Oxidation of (2E)-3,7-dimethylocta-2,6-dien-1-ol in chloroform
Reactants:
0.5 mmol) in chloroform (2.5 mL), VO(L3)(OEt) (2c) (3.0 mg,
7.5 mol), and TBHP (5.5 M solution in nonane, 135 L, 743 mmol)
in chloroform (2.5 mL). {3-Methyl-3-[(3E)-4-methylpent-3-enyl]-
oxiran-2-yl}-methanol (20). Yield: 80 mg (0.47 mol, 94%,
er = 44:56). Rf = 0.14 [diethyl ether/pentane = 1:2 (v/v)].
(2E)-3,7-dimethylocta-2,6-dien-1-ol
(77 mg,
l
l
4.4.4. Oxidation of (R)-3,7-dimethyl-1,6-octadien-3-ol (10d)
Reactants: (R)-3,7-Dimethyl-1,6-octadien-3-ol (10d) (154 mg,
1.0 mmol) in chloroform (5 mL), VO(L1)(OEt) (2a) (15.6 mg,
l
0.05 mmol, 5 mol%) and TBHP (269
l
L, 5.5 M solution in nonane,
4.5.3. Oxidation of (2E)-3,7-dimethylocta-2,6-dien-1-ol in benzene
Reactants: (2E)-3,7-dimethylocta-2,6-dien-1-ol (77 mg,
0.5 mmol) in benzene (2.5 mL), VO(L3)(OEt) (2c) (3.0 mg, 7.5
mol)
and TBHP (5.5 M solution in nonane, 135 L, 743 mmol) in ben-
zene (2.5 mL). {3-Methyl-3-[(3E)-4-methylpent-3-enyl]-oxiran-2-
yl}-methanol (20). Yield: 68 mg (0.40 mol, 80%, er = 39:61).
Rf = 0.14 [diethyl ether/pentane = 1:2 (v/v)].
1.5 mmol) in chloroform (5 mL). Reaction time: 96 h at 20 °C.
Eluent used for chromatographic purification: diethyl ether/pen-
tane = 1:1 (v/v). 2-((5R)-Tetrahydro-5-methyl-5-vinylfuran-2-yl)-
propan-2-ol (11d). Yield: 88.4 mg (0.52 mmol, 52%) 65/35-mixture
of cis/trans-isomers. Rf = 0.33 [diethyl ether/pentane = 1:1 (v/v)].
2-((5R)-Tetrahydro-5-methyl-5-(oxiran-2-yl)-furan-2-yl)-propan-
l
l
l
Please cite this article in press as: M. Dönges et al., Inorg. Chim. Acta (2014), http://dx.doi.org/10.1016/j.ica.2014.02.007

14
M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
4.5.4. Oxidation of (2E)-3-phenylprop-2-en-1-ol
adsorbed were washed with ethyl acetate (2 mL) from the pad of
aluminum oxide. The resulting solution was identified by GC/MS.
For specification of reaction conditions, experimental data and
analysis see Supplementary data. 5-Methyl-1-phenyl-4-hexen-1-
ol (10a). GC/MS (tr = 16.94 min; 70 eV, EI): m/z (%) = 190 (13)
[M+], 172 (24), 157 (34), 147 (23), 142 (8), 134 (56), 128 (77),
120 (40), 115 (8), 107 (58), 91 (26), 79 (100), 69 (10), 55 (34).
cis-2-(5-Phenyltetrahydrofuran-2-yl)-propan-2-ol cis-(11a). GC/
MS (tr = 17.19 min; 70 eV, EI): m/z (%) = 207 (1) [M+], 147 (26),
129 (26), 117 (25), 104 (100), 91 (42), 77 (25), 59 (46), 51 (10).
trans-2-(5-Phenyltetrahydrofuran-2-yl)-propan-2-ol trans-(11a).
GC/MS (tr = 17.26 min; 70 eV, EI): m/z (%) = 207 (1) [M+], 147
(26), 129 (26), 117 (25), 104 (100), 91 (42), 77 (25), 59 (46), 51
(10). cis-2,2-Dimethyl-6-phenyltetrahydropyran-3-ol cis-(12a).
GC/MS (tr = 17.81 min; 70 eV, EI): m/z (%) = 188 (1), 148 (12), 130
(8), 117 (5), 104 (100), 91 (9), 78 (9), 59 (10). trans-2,2-Di-
Reactants: (2E)-3-Phenylprop-2-en-1-ol (67 mg, 0.5 mmol) in
chloroform (2.5 mL), VO(L3)(OEt) (2c) (3.0 mg, 7.5
mol), and TBHP
(5.5 M solution in nonane, 135 L, 743 mmol) in chloroform
l
l
(2.5 mL). (3-Phenyloxiran-2-yl)-methanol (21). Yield: 70 mg
(0.47 mmol, 94%, er = 44:56). Rf = 0.16 [diethyl ether/pentane = 1:2
(v/v)].
4.6. Ligand substitutions
To a solution of VO(L1)(OEt) (2a) or VO(L2)(OEt) (2b) (60
in ethanol (2 mL) was added a solution of N-(2-hydroxybenzyl-
iden)-2-aminophenol H2L4 (1d) (60
mol) in ethanol (2 mL). The
resulting mixture was heated under reflux for 5 h, allowed to cool
to room temperature and diluted with deuterochloroform (250 l).
A fraction of this solution (500 l) was transferred into an NMR-
lmol)
l
l
l
tube. A sealed capillary containing a calibrated solution of VO(tBu)3
(100 mM) in tetrahydrofuran was placed into this NMR-tube for
determining yields of vanadium complexes via vanadium-51
NMR-spectroscopy. The solution in the NMR-tube was afterwards
added to the rest of the reaction mixture and allowed to rest for
24 h at À20 °C. The dark solid which had crystallized was filtrated
off and the filtrate concentrated at a bath temperature of 40 °C and
a pressure of 120 mbar to leave an oily residue, which was ana-
lyzed by proton-NMR. The yields of products identified from pro-
ton-NMR are listed in Table 5.
methyl-6-phenyltetrahydropyran-3-ol
(tr = 17.88 min; 70 eV, EI): m/z (%) = 188 (1), 148 (12), 130 (8),
117 (5), 104 (100), 91 (9), 78 (9), 59 (10).
trans-(12a).
GC/MS
4.9.2. Variation of oxidation catalyst and alkyl hydroperoxides
A neat sample of 1-phenylprop-1-yl hydroperoxide (PPHP),
1-methyl-1-phenylbut-1-yl hydroperoxide (MPBHP), 1,2-di-
methyl-1-phenylprop-1-yl hydroperoxide (DMPPHP), or trityl
hydroperoxide (TrHP) (CAUTION: neat peroxides may decompose
by exploding violently when handled improperly) (150 mol%) were
added to a solution of VO(L1)(OEt) (2a) or VO(L2)(OEt) (2b) in chlo-
roform (5 mL). The resulting mixture was heated for 2 min at 60 °C,
allowed to cool to room temperature (ꢀ23 °C), and treated with a
solution of 5-methyl-1-phenylhex-4-en-1-ol (10a) (1 mmol) in
chloroform (5 mL). Stirring of the mixture at ambient temperature
(ꢀ23 °C) was continued for the time specified in Table 7. The mix-
ture afterwards was concentrated under reduced pressure at a
temperature of 40 °C and a pressure of 700 mbar, and the products
analyzed by GC using n-decane as external standard and authentic
references. Further specification of reaction conditions and the re-
sults are listed in Table 7 [6].
4.7. Stability of piperidine-derived vanadium(V) compounds
Solutions of vanadium compounds VO(L1)(OEt) (2a) and
VO(L3)(OEt) (2c) (0.05 mmol) in ethanol/deuterochloroform
(400
l
L/100
lL) or deuterochloroform (500
lL, both for 2a), or per-
deuteromethanol (250
lL for 2c) were transferred in an NMR-tube.
Vanadium-51 NMR-spectra of the solutions were recorded after 24,
48 and 72 h. A sealed capillary containing a calibrated solution of
tri-(tert-butyl) vanadate (100 mM) in tetrahydrofuran was placed
into this NMR-tube for determining yields of vanadium complexes
via vanadium-51 NMR-spectroscopy. The yields of products identi-
fied from proton-NMR are listed in Table 4.
Acknowledgements
4.8. Reactivity of vanadium(V) complexes toward TBHP
This work was supported by the Deutsche Forschungsgemein-
schaft (grant Ha1705/8–2), the state Rheinland Pfalz (scholarships
for G.S. and M.A.), and NanoKat (scholarship for M.D). This work
is part of Ph.D. theses of M.A. and G.S, and the Diploma thesis
of M.D.
tert-Butyl hydroperoxide was added to a solution of VO(L1)(OEt)
(2a) in the solvent specified in Table 6. The reaction mixture was
stirred at 23 °C, diluted with deuterochloroform, and transferred
into an NMR-tube for recording a vanadium-51 NMR-spectrum.
Reactions at 60 °C were heated for 2 min at 60 °C after adding a
sealed capillary containing a calibrated solution of tri-(tert-butyl)
vanadate (100 mM) in tetrahydrofuran for determining yields of
vanadium complexes. Specification of additional reaction parame-
ter and spectroscopic data are listed in Table 6.
Appendix A. Supplementary material
CCDC 985491-985494 contain the supplementary crystallo-
graphic data for piperidines (2S,6R)-1c (985492) and (2S,6R)-9
(985492) and for oxovanadium complexes 2b (985493) and 2c
(985494). These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Supplementary data associated with this article
can be found in the online version at http://dx.doi.org/10.1016/
j.ica.2014.02.007.
4.9. Oxidation of 5-methyl-1-phenyl-4-hexen-1-ol (10a)
4.9.1. General method for oxidation of 5-methyl-1-phenyl-4-hexen-1-
ol (10a) – turnover studies, sample preparation for GC/MS-analysis,
retention times and electron impact mass-spectrometric data
A solution of TBHP (430 lL, 3.5 m) in toluene was added in an
atmosphere of nitrogen to a solution of VO(L2)(OEt) (2b) or
VO(L4)(OEt) (2d) (5, 1 or 0.5 mol%) and n-decane (0.8–1.0 mmol)
in chloroform (3 mL). The mixture was stirred for 3 min and was
treated at 20 °C with a solution of 5-methyl-1-phenyl-4-hexen-1-
ol (10a) (1 mmol) in chloroform (1.93 mL). The reaction mixture
was stirred for 10 h at a temperature of 20 °C. Samples of the reac-
References
[1] F. Freeman, Oxidation by Vanadium Compounds, in: W.J. Mijs, C.R.H. De Jonge
(Eds.), Organic Synthesis by Oxidations with Metal Compounds, Plenum Press,
New York, 1986, p. 1.
[2] (a) R.A. Sheldon, Aspects of Homogeneous Catalysis, fourth ed., Reidel
Publishing, Dordrecht, 1981, p. 3;
tion mixture (30–100
lL) were taken once per hour and filtrated
(b) R.A. Sheldon, The Chemistry of Functional Groups: Peroxides, John Wiley,
Chichester, 1983, p. 161.
through a pad of neutral aluminium oxide. Organic products
Please cite this article in press as: M. Dönges et al., Inorg. Chim. Acta (2014), http://dx.doi.org/10.1016/j.ica.2014.02.007

M. Dönges et al. / Inorganica Chimica Acta xxx (2014) xxx–xxx
15
[3] (a) K.B. Sharpless, K.C. Michaelson, J. Am. Chem. Soc. 95 (1973) 6136;
(b) W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino, H. Yamamoto, Angew. Chem. 117
(2005) 463.
[25] A. Archelas, R. Furstoss, Tetrahedron Lett. 33 (1992) 5241.
[26] P. Henne, R. Thiericke, S. Grabley, K. Hütter, J. Wink, E. Jurkiewicz, A. Zeeck,
Lieb. Ann. Chem. 12 (1993) 565.
[4] T. Nakata, G. Schmid, B. Vranesic, M. Okigawa, T. Smith-Palmer, Y. Kishi, J. Am.
Chem. Soc. 100 (1978) 2933.
[5] J. Hartung, M. Greb, J. Organomet. Chem. 661 (2002) 67.
[6] J. Hartung, S. Drees, M. Greb, P. Schmidt, I. Svoboda, H. Fuess, A. Murso, D.
Stalke, Eur. J. Org. Chem. (2003) 2388.
[7] G.E. Veitch, E. Beckmann, B.J. Burke, A. Boyer, C. Ayats, S.V. Ley, Angew. Chem.
119 (2007) 7777.
[8] K. Mori, M. Komatsu, M. Kido, K. Nakagawa, Tetrahedron 42 (1986) 523.
[9] J. Rodríguez-López, F.P. Crisóstomo, N. Ortega, M. López-Rodríguez, V.S. Martín,
T. Martín, Angew. Chem., Int. Ed. 52 (2013) 3659.
[10] R. Ballardini, V. Balzani, A. Credi, M.T. Gandolfi, M. Venturi, Acc. Chem. Res. 34
(2001) 445.
[11] C.J. Pedersen, H.K. Frensdorff, Angew. Chem. 84 (1972) 16.
[12] B.R. Kusche, A.E. Smith, M.A. McGuirl, N.D. Priestley, J. Am. Chem. Soc. 131
(2009) 17155.
[27] J. Hartung, T. Gottwald, K. Špehar, Synthesis 11 (2002) 1469.
[28] P. Fries, D. Halter, A. Kleinschek, J. Hartung, J. Am. Chem. Soc. 133 (2011) 3906.
[29] J. Hartung, Y. Dumont, M. Greb, D. Hach, F. Köhler, H. Schulz, M. Casny´, D.
ˇ
Rehder, H. Vilter, Pure Appl. Chem. 81 (2009) 1251.
[30] M. Amberg, M. Dönges, G. Stapf, J. Hartung, manuscript submitted.
[31] J. Hartung, A. Ludwig, M. Demary, G. Stapf, in: K. Kustin, J.C. Pessoa, D.C. Crans
(Eds.), Vanadium: The Versatile Metal, American Chemical Society,
Washington DC, 2007, p. 38. Chapter 4.
[32] S. Drees, M. Greb, J. Hartung, P. Schmidt, in: W. Adam (Ed.), Peroxide
Chemistry – Mechanistic and Preparative Aspects of Oxygen Transfer, Wiley-
VCH, Weinheim, 2000.
[33] A. Klein, S. Elmas, K. Butsch, Eur. J. Inorg. Chem. 15 (2009) 2271.
[34] R. Chênevert, M. Dickman, J. Org. Chem. 61 (1996) 3332.
[35] (a) M. Amberg, U. Bergsträßer, G. Stapf, J. Hartung, J. Org. Chem. 73 (2008)
3907;
[13] (a) N.A. Milas, S.A. Harris, J. Am. Chem. Soc. 60 (1938) 2434;
(b) K.B. Sharpless, T.R. Verhoeven, Aldrichim. Acta 12 (1979) 63;
(c) J.G. Hill, B.E. Rossiter, K.B. Sharpless, J. Org. Chem. 48 (1983) 3607.
[14] D. Wischang, O. Brücher, J. Hartung, Coord. Chem. Rev. 255 (2011) 2204.
[15] V. Conte, F. Di Furia, G. Modena, J. Org. Chem. 53 (1988) 1665.
[16] S.W. Wright, D.L. Haagemann, A.S. Wright, L.D. McClure, Tetrahedron Lett. 42
(1997) 7345.
(b) M. Amberg, I. Kempter, U. Bergsträßer, G. Stapf, J. Hartung, Tetrahedron:
Asymmetry 22 (2011) 752.
[36] W. Prandtl, L. Hess, Z. Anorg. Chem. 82 (1913) 103.
[37] J. Spandl, I. Brüdgam, H. Hartl, Z. Anorg. Allg. Chem. 626 (2000) 2125.
[38] M.J. Clague, N.L. Keder, A. Butler, Inorg. Chem. 32 (1993) 4754.
[39] C.J. Ballhausen, H.B. Gray, Inorg. Chem. 1 (1962) 111.
[40] D. Rehder, Angew. Chem. 103 (1991) 152.
[17] (a) C.D. Crans, J.J. Smee, E. Gaidamauskas, L. Yang, Chem. Rev. 104 (2004) 849;
(b) T. Hirao, Chem. Rev. 97 (1997) 2707.
[18] (a) W. Zhang, H. Yamamoto, J. Am. Chem. Soc. 129 (2007) 286;
(b) Y. Hoshino, H. Yamamoto, J. Am. Chem. Soc. 122 (2000) 10452.
[19] N. Makita, Y. Hoshino, H. Yamamoto, Angew. Chem. 115 (2003) 971.
[20] J. Hartung, Pure Appl. Chem. 77 (2005) 1559.
[41] J.K. Kochi, J. Am. Chem. Soc. 84 (1962) 1193.
[42] E. Montaudon, X. Lubeigt, B. Maillard, J. Chem. Soc., Perkin Trans. 1 (1991)
1531.
[43] (a) W.P. Jackson, Synlett (1990) 536;
(b) D.E. Bissing, C.A. Matuszak, W.E. McEwen, J. Am. Chem. Soc. 86 (1964)
3824.
[21] D. Klimetzek, J. Bartels, W. Francke, J. Appl. Entomol. 107 (1989) 518.
[22] T. Kusumi, H. Uchida, Y. Inouye, M. Ishitsuka, H. Yamamoto, H. Kakisawa, J.
Org. Chem. 52 (1987) 4597.
[44] J. Hartung, P. Schmidt, Synlett (2000) 367.
[45] E.L. Eliel, S.H. Wilen, Organische Stereochemie, Wiley-VCH, Weinheim, 1998.
p. 421.
[23] S. Dötterl, D. Burkhardt, B. Weißbecker, A. Jürgens, A. Mosandl, J. Chromatogr.
A 1113 (2006) 231.
[24] K. Suenaga, T. Shibata, N. Takada, H. Kigushi, K. Yamada, J. Nat. Prod. 61 (1998)
515.
[46] R.L. Farmer, F.L. Urbach, Inorg. Chem. 11 (1970) 2562.
[47] T. Katsuki, K.B. Sharpless, J. Am. Chem. Soc. 102 (1980) 5974.
[48] J. Hartung, U. Bergsträsser, K. Daniel, N. Schneiders, I. Svoboda, H. Fuess,
Tetrahedron 65 (2009) 2567.
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