Rongalite-Promoted on Water Synthesis of Functionalised Tellurides and Ditellurides

Article abstract of DOI:10.1002/adsc.201901536

The on water reaction of sodium telluride with electrophiles has been explored. Na₂Te, generated in situ through the rongalite (sodium hydroxymethanesulfinate)-promoted reduction of elemental tellurium, reacts with a wide variety of electrophil

Full text of DOI:10.1002/adsc.201901536

Title: Rongalite-promoted <i>on water</i> synthesis of functionalised
tellurides and ditellurides
Authors: Damiano Tanini, Lorenzo Ricci, and Antonella Capperucci
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Rongalite-promoted on water synthesis of functionalised
tellurides and ditellurides
Damiano Tanini,a* Lorenzo Riccia and Antonella Capperuccia
a
University of Florence, Department of Chemistry "Ugo Schiff", Via della Lastruccia 3-13, I-50019 Sesto Fiorentino,
Italy.
Phone: +39 05545735-50/-52; fax +39055 4574913; e-mail: damiano.tanini@unifi.it
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The on water reaction of sodium telluride with electrophiles has been explored. Na2Te, generated in situ
through the rongalite (sodium hydroxymethanesulfinate)-promoted reduction of elemental tellurium, reacts with a wide
variety of electrophiles, including strained heterocycles, haloalkanes, Michael acceptors, and aryl diazonium salts,
providing simple and rapid access to a broad range of novel functionalised symmetrical tellurides. The methodology
well tolerated the presence of versatile functional groups such as alchohols, amines, esters, nitriles, and sulfones and
allowed the incorporation of tellurium atoms into biologically relevant natural-derived products. Furthermore, in the case
of the nucleophilic ring opening of epoxides, a judicious tuning of the reaction conditions enabled the synthesis of
unreported -hydroxy- and -amino-ditellurides, which were further employed as precursors of new functionalised
unsymmetrical dialkyl tellurides. The thiol-peroxidase catalytic activity of hydroxy-ditellurides has also been
investigated in order to compare their antioxidant properties with those of homologous tellurides.
Keywords: Tellurides; Ditellurides; On water, Rongalite; Antioxidants, Glutathione peroxidase
Introduction
substituted -hydroxy- and -amino- tellurides were
demonstrated to be excellent mimics of GPx[9b,c,f] and
also exhibited remarkable activity as carbonic
anhydrase activators[13] and inhibitors.[14]
Chalcogen-containing organic molecules are of
significant importance in organic chemistry, material
science, medicinal chemistry, and biology.[1] In
particular, organotellurium compounds play a central
role in organic synthesis, readily undergoing
However, while diaryl-ditellurides[15] and diaryl or
aryl-alkyl-tellurides[16] have been widely studied,
dialkyl substituted analogues have been far less
explored and the development of a general and
nucleophilic,
electrophilic,
and
radicophilic
reactions.[2] These transformations, which often occur
with good regio- and stereo-selectivity, have been
widely employed in an array of functional group
conversions,[3] as well as in the formation of new
carbon-carbon bonds[4] and in the synthesis of natural
products.[5] The chemistry of organotellurides has
also been applied in the development of new
catalysts[6] and functional materials.[7] Furthermore, a
number of organotellurium derivatives have been
studied for their biological activities as thioredoxine
reductase modulators,[8] glutathione peroxidase
mimics,[9] cancer cells growth inhibitors,[8,10] and
antibacterials.[11]
convenient
route
towards
functionalised
organotellurides would be highly desirable.
Symmetrical dialkyl tellurides and ditellurides are
commonly prepared through the reaction of alkali
tellurides and ditellurides with haloalkanes[2a,17] or
alkyl tosylates.[2a,18] Other methods involve the
insertion of tellurium into the carbon-metal bond of
organolithium compounds or Grignard reagents.[2,19]
Further functionalisable -halo dialkyl tellurides and
ditellurides can be accessed from terminal alkenes
and tellurium tetrahalides.[20] In this context, despite
their interest, tellurides and ditellurides bearing O-
and N-containing functionalities have been scarcely
explored.
In this scenario, functionalised dialkyl tellurides
and ditellurides are arguably one of the most
interesting and versatile classes of organotellurium
derivatives, representing valuable compounds both in
organic synthesis and in biology. In addition, the
promising catalytic and pharmacological properties of
O- and N-containing organochalcogenides have
prompted researchers to design and synthesise novel
functionalised organochalcogenides.[9,12] Suitably
Only a few examples of -amino substituted
systems,
including
tellurocystine
and
tellurolanthionine derivatives, obtained from suitable
-haloamines[17a,b] or -lactones[21] have been
reported. In this context, the nucleophilic ring-
opening-reaction (NROR) of strained heterocycles[22]
such as epoxides, aziridines and thiiranes, as well as
the telluro-Michael addition, could represent
1
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
powerful as yet unexploited tools to access O-, N-,
and S-containing symmetrical dialkyl tellurides and
ditellurides.
The reaction mixture was then treated with an excess
(1.7 eq.) of benzyl glycidyl ether, in order to test
whether the so generated Na2Te could be employed in
‘on water’ NRORs of epoxides. Pleasingly, after
stirring the reaction mixture at ambient temperature
for 2 h, the oxirane was smoothly converted into the
corresponding -hydroxy telluride 2a, which was
isolated in 70% yield after simple extraction in ethyl
acetate, without purification (Scheme 1).
During the course of our studies on the reactivity
of chalcogen-containing nucleophiles, we developed
a ring-opening-based procedure for the synthesis of
-hydroxy-and -amino-tellurides from Li2Te and
epoxides or aziridines. Lithium triethylborohydride
(LiHBEt3) was used as reducing agent to in situ
generate Li2Te from elemental tellurium.[23] This
methodology is the sole example of synthesis of
hydroxy- and amino- functionalised symmetrical
tellurides through NROR of three-membered
heterocycles and, to the best of our knowledge,
represents the most general and reliable procedure to
access this class of organochalcogenides. However,
its Achilles’ heel is the rather low yield and the
always required purification step (due to the presence
of triethylborane and tellurium-containing side-
products) with the consequent use of toxic volatile
organic compounds (VOCs) and production of large
amount of solvent waste. The formation of
unsymmetrical -hydroxy ethyltellurides, presumably
occurring through the triethyl borotritelluroate-
induced ring-opening of epoxides,[23,24] represents an
additional drawback of this route, limiting its
scalability and hampering its application to the
synthesis of ditellurides.
In order to further optimise the reaction,
envisioning the generation of Na2Te as the critical
step, we evaluated whether the use of ultrasound
irradiation would have improved the efficiency of the
tellurium
reduction.
Gratifyingly,
complete
dissolution of Te(0) and formation of the purple
Na2Te solution were achieved irradiating the aqueous
mixture at 80 °C for 1h. Subsequent treatment with
benzyl glycidyl ether led to the formation of -
hydroxy telluride 2a in 82% yield.
Having established the optimal conditions, we next
explored the scope of the reaction, which was found
to be wide, encompassing a large variety of
electrophiles (Table 1). Epoxides worked well in this
transformation, enabling the regioselective synthesis
of variously substituted tellurides, including protected
glycidol derivatives 2a,b as well as -hydroxy
tellurides 2c,d, obtained from propylene oxide and
1,2-epoxy-5-hexene, respectively.
To address these limitations, we considered the use
of on water conditions and evaluated whether sodium
hydroxymethanesulfinate (HOCH2SO3Na, rongalite,
1),[25] a cheap and versatile reducing agent, could be
employed to generate tellurolate anions able to react
with functionalised electrophiles under mild and
environmentally friendly conditions.
Herein, we describe the successful development of
a novel procedure for the synthesis of functionalised
symmetrical dialkyl tellurides through the on water[26]
reaction of Na2Te with a wide array of electrophiles,
including three-membered heterocycles, alkyl halides,
electron-deficient alkenes and alkynes. Diaryl
tellurides could also be synthesised exploiting the
reactivity of diazonium salts with Na2Te.
Furthermore, in the case of NROR of strained
heterocycles, a judicious tuning of the reaction
stoichiometry enabled the synthesis of novel further
functionalisable ditellurides, bearing hydroxy or
amino moieties.
Scheme 1. Rongalite-promoted on water synthesis of -
hydroxy telluride 2a. US irradiation was provided by using
an ultrasonic bath. 70% of isolated yield was achieved
a
performing the reduction step in oil bath, at 90 °C for 2h.
Intriguingly, the reaction of epichlorohydrin with
Na2Te under the standard conditions gave the
telluride 2c, bearing a methyl group instead of the
expected chloromethyl moiety at the C-2. The
dehalogenated product 2c is reasonably formed
through a chalcogen-mediated reduction, following
]
an SN2X mechanism.[28
The ring opening reaction was also extended to
natural-product-derived epoxides such as eugenol
oxide and limonene oxide, providing the
corresponding functionalised tellurides 2e and 2f.
Therefore, the reaction well tolerated protected
alcohols (Table 1, entries 1,2), olefins (Table 1,
entries 2,4,7), and phenols (Table 1, entry 6).
Furthermore, both mono- and poly-substituted
epoxides were successfully employed, affording the
ring opening products with excellent regioselectivity
on the less hindered position of the three-membered
ring. Butadiene diepoxide was also treated with
Na2Te under the standard conditions, providing high
Results and Discussion
We commenced our studies by generating sodium
telluride from elemental tellurium and sodium
hydroxymethanesulfinate
1
using Tschugaeff’s
method.[27] Thus, elemental tellurium (1.0 eq.) was
treated with rongalite (2.5 eq.) and NaOH (5.0 eq.) at
90 °C, using H2O as the solvent. The reduction of
Te(0) to Na2Te, highlighted by the grey to purple
colour change of the reaction mixture, along with
almost complete dissolution of elemental grey
tellurium, was achieved with a reaction time of 2 h.
2
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
yield
of
the
dihydroxy-substituted
Prompted by these results, we further explored the
scope of the reaction by varying the nature of the
electrophile. Pleasingly, both primary and secondary
alkyl bromides could be converted into the
corresponding dialkyl tellurides 5a and 5b in
excellent yield (Table 1, entries 11,12).
As expected, the tellurenylation reaction did not
occur when tertiary alkyl halides, such as tBuBr, were
reacted with Na2Te under the standard conditions. For
these substrates, the E2 process is indeed favoured
over the SN1 reaction in the presence of strong bases
and nucleophiles. In addition, this methodology could
not be applied to the synthesis of dibenzyl tellurides.
Indeed, reduction of the C-Br bond – with the
consequent formation of toluene – takes place upon
treatment of benzyl bromide with Na2Te under the
above-described conditions. A tellurium-mediated
SN2X-type mechanism presumably accounts for this
process.[28]
tetrahydrotellurophene 2g, arising from the ring
opening of one of the two oxirane ring followed by
an intramolecular ring closure occurring onto the
second epoxide function.[29] The reaction scope was
also extended to include aziridines[30] and thiiranes,
enabling the synthesis of the -amino telluride 3 and
the dithiatellurepane 4.
Table 1. Reaction scope of on water synthesis of
functionalised dialkyl tellurides.
This on water methodology was also amenable to
Michael acceptors, thus providing a simple and direct
access to novel functionalised tellurides (Table 1,
entries 13-16). Indeed, tellurium-containing bis-ester
6a, bis-nitrile 6b, and bis-sulfone 6c were smoothly
achieved through a clean unprecedented telluro-
Michael addition of Na2Te to electron-deficient
alkenes, such as methyl acrylate, acrylonitrile, and
phenyl vinyl sulfone. In addition, divinyl telluride 6d,
bearing two ester functionalities, was obtained in
good yield and excellent stereoselectivity (Z/E ratio >
98:2) upon treatment of methyl propiolate with Na2Te
under the standard conditions (Table 1, entry 16).[31]
An attractive feature of this protocol is that, in
almost all cases, simple extraction using ethyl acetate,
which is a recommended solvent the CHEM21
guide,[32] provided pure tellurides 2-6, thus avoiding
chromatographic purification and limiting the use of
toxic VOCs and the production of large amount of
solid waste.
Scheme 2. Synthesis of diaryl tellurides 7a-e from
diazoniun salts and Na2Te. Isolated yields are reported.
Notably, also aryl diazonium salts proved to be
effective substrates for this rongalite-promoted
tellurenylation methodology. A range of differently
substituted aryl amines were convereted into the
corresponding valuable[33] diaryl tellurides 7a-e upon
aIsolated yield, after EtOAc extraction, is reported.
Chromatographic purification was not required. bMixture of
diastereoisomers. cChromatographic purification was required.
1
dZ/E ratio > 98:2 (d.r. determined by H NMR). US irradiation
was provided by using an ultrasonic bath. Slightly lower yields
(5-10%) were observed upon performing the reduction step under
conventional heating (oil bath at 90 °C for 2 h).
treatment with Na2Te through
a
copper-free
Sandmeyer-type
reaction[34]
(Scheme
2).
3
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
Unfortunately, the use of anilines bearing nitro-,
cyano-, and hydroxy- groups did not lead to the
formation of the expected diaryl tellurides.
gave no improvements in terms of 8a:2a ratio. On the
other hand, the use of ethylene glycol or acetonitrile
(Table 2, entries 8, 9) led to the essentially selective
formation of the telluride 2a.
Having developed a novel on water methodology
for the synthesis of -functionalised tellurides, we
sought to evaluate whether a related rongalite-
mediated procedure could be exploited for the
synthesis of symmetrical functionalised ditellurides.
We envisaged that the exquisite nucleophilicity of
tellurium anions in H2O could also be harnessed to
develop an environmentally friendly route towards -
functionalised ditellurides, simply tuning the
stoichiometry of the reaction.
Scheme 3. Formation of tellurides and ditellurides from
intermediate 9.
We began our studies by establishing the optimal
reaction conditions to synthesise -hydroxy
ditelluride 8a. Initially we sought to access 8a by
exploiting the reactivity of benzyl glycidyl ether and
ditelluride dianions (Te22─), generated in situ from
elemental tellurium and rongalite. Thus, Te(0) was
The use of different bases such as Cs2CO3 or KOH
proved to be detrimental to the 8a:2a ratio. Finally,
we considered the effect of the concentration.
Surprisingly, when the reaction was performed in 0.5
mL of H2O (Table 2, entry 12) the 8a:2a ratio
decreased from 5:1 to 2:1, thus demonstrating that the
formation of ditellurides is disfavoured by higher
concentrations. On the contrary, we were pleased to
notice that the 8a:2a ratio resulted improved under
diluted conditions. Only ca. 10% of telluride 2a was
indeed detected upon performing the reaction in 6 mL
of H2O ([Na2Te]0 = 0.08 M) and with 0.6 eq. of
epoxide (Table 2, entry 13). Under these conditions,
the desired -hydroxy ditelluride 8a could be
obtained in 68% yield. Higher dilution (Table 2, entry
14) gave neither selectivity nor yield improvements.
Such a striking “dilution effect” was not observed
when other solvents, including MeOH and DMF,
were used.
treated
with
1.0
eq.
of
sodium
hydroxymethanesulfinate in H2O at 90 °C in order to
generate Na2Te2. However, after stirring for 2 h, both
the purple colour of the reaction mixture and the
presence of unreacted black tellurium were
suggestive of the formation of Na2Te, instead of the
expected dark red Na2Te2. Furthermore, when the
mixture was treated with benzyl glycidyl ether, the -
hydroxy telluride 2a was the sole tellurium-
containing product detected in the crude material,
hence confirming that Na2Te2 was not formed under
the above described reaction conditions. Neither
variating the reaction temperature nor increasing the
reaction time allowed to form Na2Te2. We also
attempted to obtain Na2Te2 through dismutation of
Na2Te (vide infra) and elemental tellurium.[18a]
However, albeit different conditions were evaluated,
no reaction occurred and black unreacted tellurium
was always observed. In all cases, treatment of the
mixture with benzyl glycidyl ether yielded
exclusively the telluride 2a. Thus, we sought to
approach the problem from a different perspective
and evaluated the possibility to access ditellurides by
oxidative dimerization of sodium alkyltellurolates,
generated in situ through NROR of epoxides with
Na2Te (Scheme 3). The key intermediate 9 is both a
strong nucleophile and an easily oxidisable species.
Therefore, it can afford the telluride 2 upon reacting
with a second molecule of epoxide or undergo
oxidation to provide the ditelluride 8 (Scheme 3). The
stoichiometry of the reaction is arguably the crucial
parameter that needs to be considered in order to
modulate the outcome of the reaction towards the
formation of 2 or 8.
Table 2. Optimisation of the reaction conditions.
An equimolar mixture of telluride 2a and
ditelluride 8a was indeed formed upon reacting
Na2Te with 1.0 eq. of benzyl glycidyl ether. Notably,
we found that the 8a:2a ratio could be appreciably
improved by decreasing the amount of epoxide
(Table 2, entries 1-4). Particularly, less than 15% of
-hydroxy telluride 2a was detected when using 0.4
eq. of benzyl glycidyl ether (Table 2, entry 4).
Evaluation of different solvents (Table 2, entries 5-9)
aReactions were performed using 0.5 mmol of Te(0); b[Na2Te]0 =
0.25 M; c[Na2Te]0 = 1.0 M; d[Na2Te]0 = 0.08 M; e[Na2Te]0 = 0.05
M; 8a:2a ratio was determined by H NMR. The epoxide was
f
1
added when Te(0) was completely consumed.
4
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
With the optimised conditions in hand, we next
Table 3. Spectroscopic properties of functionalised
dialkyl-chalcogenides and -dichalcogenides.
explored the scope of the tellurenylation ring opening
reaction by varying the nature and the structure of the
strained heterocycle. The robustness of the procedure
was demonstrated by the preparation of a range of
new variously substituted and functionalised
ditellurides (Scheme 4). Glycidol derivatives
protected as benzyl-, allyl-, and isopropyl-ethers were
efficiently converted into the corresponding -
hydroxy ditellurides 8a-c in rather good yield through
an highly regioselective ring opening route.
Monosubstituted epoxides bearing methyl or n-butyl
substituents, also underwent telluride-promoted ring-
opening to give the desired ditellurides 8d-e.
a 125Te NMR (δ, ppm, CDCl3); PhTeTePh was used as external
standard (δ = 420 ppm). b 77Se NMR (δ, ppm, CDCl3); PhSeSePh
To further demonstrate the utility of this
tellurenylation reaction, we applied the methodology
to natural-product-derived strained heterocycles. For
example, functionalised ditellurides 8f and 8g were
successfully achieved from eugenol and limonene
oxides, respectively. Remarkably, both tri- and di-
substituted epoxides were shown to be viable
substrates, enabling the synthesis of functionalised
ditellurides 8g and 8h in rather good yield. Having
demonstrated that the scope of this procedure
encompasses a wide variety of epoxides, we
wondered whether it could be enlarged to enclose
aziridines, in order to provide access to -amino
ditellurides. Thus, enantioenriched N-Tosyl and N-
Boc aziridines, synthesised from L-valine, were
treated with Na2Te under the optimised reaction
conditions. Pleasingly, the expected -amino
ditellurides 10a and 10b were formed in 64% and
61% yield, with complete stereospecificity and
excellent regioselectivity.
c
was used as external standard (δ = 461 ppm). Ar = 3-MeO-,4-
OH-C6H3.
The 125Te NMR chemical shift of these unreported
dialkyl ditellurides was recorded in order to compare
their resonance frequencies with those of the related
dialkyl tellurides (Table 3 and ESI). The 125Te NMR
chemical shift of ditellurides resulted just slightly
shielded (5-10 ppm) with respect to that of the
corresponding tellurides. Notably, this trend contrasts
with the huge differences observed for the 77Se NMR
chemical shift of the selenium containing analogues;
indeed, the 77Se NMR resonance frequencies of -
functionalised diselenides resulted shifted downfield
(up to 230 ppm) when compared with those of the
corresponding selenides.[35] Therefore, unlike 77Se
NMR spectroscopy in the case of selenides and
diselenides, 125Te NMR is not a completely reliable
tool to establish whether tellurides, ditellurides, or a
mixture of the two is formed.[36] Typical direct and
geminal 125Te-13C and geminal 125Te-1H spin-spin
coupling constants have also been measured (see
Table S1 and S2, ESI).
To demonstrate the versatility and the synthetic
utility of the obtained functionalised dialkyl
ditellurides, we sought to employ this unreported
organotellurium derivatives as precursors of
potentially
valuable
polyfunctionalised
unsymmetrical dialkyl tellurides (Table 4).
Thus, -hydroxy ditellurides 8a-c,g were subjected
to NaBH4-promoted reduction to afford the
corresponding alkyl tellurolates, which were in situ
treated with suitable electrophiles to yield variously
substituted unsymmetrical tellurides. Both alkyl
halides and strained heterocycles could be efficiently
employed, enabling the synthesis of the
corresponding unsymmetrical tellurides 11-15.
Particularly, this route provided access to
polyfunctionalised natural-product-derived systems
such as the triol 12, obtained by ring-opening of
(S)─glycidol, and the diol 14, arising from the
limonene-derived ditelluride 8g. Furthermore, the
telluride 15, bearing both the hydroxyl and the amino
group, was easily synthesised through the
regioselective and stereospecific ring opening of (S)-
2-benzyl N-Tosyl aziridine. Unfortunately, Michael
acceptors such as methyl vinyl ketone or methyl
Scheme 4. Synthesis of -hydroxy- and -amino-dialkyl
ditellurides. Isolated yields are reported. aMixture of
diastereoisomers. bRacemic.
5
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
acrylate were found to be scarcely reactive under
these conditions, only traces of the desired
hydroxy-ditellurides 8 proved to be poorer catalysts
with respect to homologous tellurides 2; for example,
conjugated adducts being observed (Table 4, entries 6, the thiol-peroxidase-like activity of telluride 2g was
7). These results are in line with our recent findings
on the reactivity of structurally related functionalised
diselenides with electron-deficient olefins under
reducing conditions.[37]
found to be ten-fold higher than the related ditelluride
8f. The kinetic of the reactions involved in the two
distinct pathways operating for tellurides and
ditellurides reasonably accounts for the observed
different catalytic properties of compounds 2 and
8.[9f,39]
Table 4. Synthesis of functionalised unsymmetrical
tellurides.
Notably,
the
dihydroxy-substituted
tetrahydrotellurophene 2g exhibited excellent GPx-
like properties (Figure 1). Noticeably, 2g represents
the tellurium-containing analogue of DHSred (trans-
3,4-dihydroxyselenolane), a water-soluble selenide
synthesised and widely studied by Iwaoka et al.[40]
Figure 1. Oxidation of DTTred with H2O2 in the presence
of Te-containing catalysts (1 mol%). Reaction conditions:
[DTTred]0 = 0.14 M, [H2O2]0 = 0.14 M, [catalyst] = 0.014
M, CD3OD (0.6 mL). In the control experiment the
reaction was run with no catalyst. The mean ± SD values
of three separate experiments are reported.
aIsolated yield is reported. bMixture of diastereoisomers.
Table 5. Comparison of the thiol-peroxidase like activity
of -hydroxy- chalcogenides and dichalcogenides
according to the DTT method.
As stated above, a number of organotellurium
compounds have been employed as glutathione-
peroxidase (GPx) mimics, being often capable to
efficiently reduce harmful hydrogen peroxide to
water by using thiols as co-substrate. In this context,
the GPx-like activity of O-, N-, and S-containing
dialkyl- and aryl-alkyl tellurides has been recently
reported.[9b,13,38] However, the catalytic antioxidant
activity of homologous functionalised ditellurides
remained unexplored, mainly because of the lack of
methodologies for their synthesis. Therefore, having
developed a route to access unreported substituted
ditellurides, their thiol-peroxidase-like activity was
next pursued in order to compare their catalytic
properties with those of structurally related
functionalised tellurides.[9b,38] The dithiothreitol
(DTT) oxidation assay was chosen as model method.
Results of this investigation are summarised in the
Figure 1 and in the Table 5. -Hydroxy ditellurides
8a,b behaved as effective catalyst, promoting
complete DTT oxidation within 6 minutes from the
addition of H2O2. The eugenol-derived ditelluride 8f,
which bears on the same skeleton two tellurium
atoms and two phenolic moieties, displayed slightly
lower catalytic properties (Figure 1). Intriguingly,
a1 mol% of tellurium-containing catalysts 2 or 8 and 10 mol% of
selenium-containing catalysts 18 or 19 were used for the test. bT50
is the time required, in seconds, to halve the initial thiol
concentration after the addition of H2O2; data in parenthesis are
the experimental error. Dithiothreitol (DTT) oxidation was
1
c
monitored by the mean of H NMR spectroscopy. Ar = 3-MeO-
4-OH-C6H3.
6
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
As expected,[1j,9b,9f,38] replacing tellurium with
multiplicity (s = singlet, d = doublet, t = triplet, ap d =
apparent doublet, m = multiplet, dd = doublet of doublet,
bs = broad singlet, bd = broad doublet, ecc.), coupling
constant (J) or line separation (ls), and assignment. Where
reported, NMR assignments are made according to spin
systems, using, where appropriate, 2D NMR experiments
(COSY, HSQC, HMBC) to assist the assignment.
selenium brought about a dramatic decrease of the
thiol-peroxidase properties (Table 5). However, in
contrast to the behaviour of telluride 2 and
ditellurides 8, -hydroxy-diselenide 19 was only
slightly less active than selenide 18.
Conclusion
General Procedure for the synthesis of functionalised
tellurides 2-6. A 10 mL vial was charged with elemental
tellurium (128 mg, 1.0 mmol, 1.0 eq.), sodium
hydroxymethanesulfinate dihydrate (385 mg, 2.5 mmol,
2.5 eq.), NaOH (200 mg, 5.0 mmol, 5.0 eq.) and H2O (3
mL). The vial was sealed and the reaction mixture was
heated at 80 °C for 1 h under ultrasound irradiation. The
colour of the suspension turned from grey to purple, thus
indicating the reduction of Te(0) to Te2─. Complete
dissolution of black elemental tellurium and formation of a
purple solution was achieved. Then, ultrasound irradiation
was stopped and the electrophile (epoxide, aziridine, alkyl
halide, or Michael acceptor; 1.7 mmol, 1.7 eq.) was
introduced into the vial. The reaction mixture was allowed
to cool to r.t. and stirred for additional 4 h. Afterwards, the
mixture was treated with saturated aq. NH4Cl (2 mL) and
then EtOAc (5 mL) was added. The organic phase was
collected and the aqueous phase was extracted with EtOAc
(2 x 5 mL). The combined organic phases were dried over
Na2SO4 and concentrated under reduced pressure to yield
the desired β-hydroxy telluride 2-6. If not differently
specified (see ESI for details), simple ethyl acetate
extraction provided dialkyl tellurides pure enough to be
used without further purification.
In conclusion, we have developed a novel on water
procedure to access variously functionalised dialkyl
tellurides through the reaction of Na2Te with
electrophiles under mild conditions. The use of
sodium hydroxymethanesulfinate, a cheap and water
soluble reducing agent, was critical to the success of
the reaction. The scope of the procedure proved to be
broad and was demonstrated over a wide array of
electrophiles, including strained heterocycles,
haloalkanes, electron-deficient alkenes and alkynes,
which were efficiently converted into the
corresponding tellurides. Notably, in almost all cases
simple ethyl acetate extraction provided pure
tellurides, thus avoiding chromatographic purification
and limiting the use of toxic VOCs and the
production of large amount of solid waste.
Furthermore, a fine tuning of the stoichiometry of the
reaction enabled the synthesis of -hydroxy- and -
amino-ditellurides by NROR of epoxides and
aziridines with Na2Te. Such unprecedented
ditellurides were further employed as precursors of
new functionalised unsymmetrical dialkyl tellurides.
Finally, the synthesised organotellurium derivatives
showed remarkable GPx-like properties.
General Procedure for the synthesis of -hydroxy- and
-amino-ditellurides 8 and 10. A 25 mL vial was charged
with elemental tellurium (128 mg, 1.0 mmol, 1.0 eq.),
sodium hydroxymethanesulfinate dihydrate (385 mg, 2.5
mmol, 2.5 eq.), NaOH (200 mg, 5.0 mmol, 5.0 eq.) and
H2O (12 mL). The vial was sealed and the reaction mixture
was heated at 80 °C for 1 h under ultrasound irradiation.
The colour of the suspension turned from grey to purple,
thus indicating the reduction of Te(0) to Te2─. The
ultrasound irradiation was stopped and the epoxide or the
aziridine (0.6 mmol, 0.6 eq.) was then added dropwise.
The reaction mixture was cooled at r.t. and stirred for
additional 4 h. Afterwards, the mixture was treated with
saturated aq. NH4Cl (2 mL) and then EtOAc (5 mL) was
added. The organic phase was collected and the aqueous
phase was extracted with EtOAc (2 x 5 mL). The
combined organic phases were dried over Na2SO4 and
concentrated under reduced pressure. The residue was
purified by flash column chromatography to yield the
desired β-hydroxy- or -amino-ditelluride.
Experimental Section
General information. All commercial materials were
purchased from various commercial sources and used as
received, without further purification. Flash column
chromatography purifications were performed with Silica
gel 60 (230-400 mesh). Thin layer chromatography was
performed with TLC plates Silica gel 60 F254, which was
visualised under UV light, or by staining with an ethanolic
acid solution of p-anisaldehyde followed by heating. High
resolution mass spectra (HRMS) were recorded by
Electrospray Ionization (ESI). Reactions were performed
in demineralised water.
1H and 13C NMR spectra were recorded in CDCl3 using
Varian Mercury 400, Bruker 400 Ultrashield, and Varian
Gemini 200 spectrometers operating at 400 MHz and 200
MHz (for 1H), 100 MHz and 50 MHz (for 13C). 125Te NMR
spectra were recorded using a Bruker 400 Ultrashield
spectrometer, operating at 126 MHz. NMR signals were
referenced to nondeuterated residual solvent signals (7.26
ppm for 1H, 77.0 ppm for 13C). Diphenyl ditelluride
(PhTe)2 was used as an external reference for 125Te NMR
(δ = 420 ppm). Chemical shifts () are given in parts per
million (ppm), and coupling constants (J) are given in
General procedure for the synthesis of unsymmetrical
functionalised tellurides. NaBH4 (0.75 mmol, 3.0 eq.)
was portionwise added to a solution of functionalised
dialkyl ditelluride 8 (0.25 mmol, 1.0 eq.) in EtOH (2 mL)
at 0°C under inert atmosphere (N2). After 10 min, the
electrophile (0.45 mmol, 1.8 eq.) was slowly added and the
reaction mixture was allowed to warm to room temperature
and stirred for additional 1 h. The reaction was quenched
1
Hertz (Hz), rounded to the nearest 0.1 Hz. H NMR data
are reported as follows: chemical shift, integration,
7
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10.1002/adsc.201901536
Advanced Synthesis & Catalysis
by addition of saturated aq. NH4Cl (2 mL) and diluted with
EtOAc (5 mL), The layers were separated and the aqueous
layer was extracted with EtOAc (3 x 3 mL), dried over
Na2SO4, filtered and concentrated under vacuum. The
crude material was purified by flash chromatography to
yield unsymmetrical -functionalised tellurides.
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We thank MIUR-Italy (‘‘Progetto Dipartimenti di Eccellenza
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Advanced Synthesis & Catalysis
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FULL PAPER
Rongalite-promoted on water synthesis of
functionalised tellurides and ditellurides
Adv. Synth. Catal. Year, Volume, Page – Page
Damiano Tanini,* Lorenzo Ricci, Antonella
Capperucci
11
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