Radical Deuteration with D2O: Catalysis and Mechanistic Insights

Article abstract of DOI:10.1021/jacs.7b12105

Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl iodides via radical pathway using D₂O as source of deuterium has been developed. The reaction is initiated and mediated by triethylborane in the presence of dodecanethiol as a catalyst. This method is compatible with a wide range of functional groups and provides the monodeuterated products in good yields and with a high level of deuterium incorporation. It opens promising opportunities for the development of enantioselective radical reactions. Moreover, a revision of the mechanism of the deoxygenation reaction of xanthates using R₃B and water (Wood deoxygenation) is presented.

Full text of DOI:10.1021/jacs.7b12105

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Communication
Radical Deuteration with D2O: Catalysis and Mechanistic Insights
Valentin Soulard, Giorgio Villa, Denis Patrick Vollmar, and Philippe Renaud
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b12105 • Publication Date (Web): 14 Dec 2017
Downloaded from http://pubs.acs.org on December 14, 2017
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Radical Deuteration with D2O: Catalysis and Mechanistic Insights
Valentin Soulard, Giorgio Villa, Denis Patrick Vollmar and Philippe Renaud*
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Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland
ABSTRACT: Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for
optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl
iodides via radical pathway using D O as source of deuterium has been developed. The reaction is initiated and
2
mediated by triethylborane in the presence of dodecanethiol as a catalyst. This method is compatible with a wide range
of functional groups and provides the monodeuterated products in good yields and high level of deuterium
incorporation. It opens promising opportunities for the development of enantioselective radical reactions. Moreover, a
revision of the mechanism of the deoxygenation reaction of xanthates using R
presented.
3
B and water (Wood deoxygenation) is
acting as a highly active catalyst. Taking advantage of the
thiol catalysis, we report also an efficient method for the
conversion of alkyl iodides to the corresponding
Over the last few years, the interest for the
incorporation deuterium atoms in drug candidates to
improve their metabolism and pharmacokinetic properties
has exploded.1-2 A significant number of deuterated drug
candidates (heavy drugs) have been synthesized and
submitted to clinical trials.3-4 Deutetrabenazine (Austedo®)
was the first deuterated drug to reach the market in 2017.5-
deuterated compounds with D
deuterium atoms.
2
O as a unique source of
6
Preparation of organic compounds that are selectively
labeled with a deuterium atom remains a challenging
synthetic problem.7 Alkyl halides are often used as
starting material to introduce a deuterium atom via
protonation of the corresponding organometallic
derivative but this method suffers from a low functional
group compatibility.8-11 Alternatively, the radical
deuteration using organotin deuterides has been
developed.12 Despite its efficiency and high functional
group compatibility, this method relies on toxic13 and
Scheme 1. Wood procedure for the deoxygenation of
alcohols with D O.
2
expensive deuterating agents prepared from LiAlD
contaminates the products even after careful
purification.13-14 Developing a radical procedure using
O as a source of deuterium atoms represents by far the
4
that
Attempts to use the method of Wood (Et
3
B, D O, air) for
2
the preparation of deuterated deoxycholesterol 2 starting
from the cholesteryl iodide 1a gave deceiving results.17
Only 7% of D-incorporation was obtained at best (table 1,
entry 1). Running the reaction under the exact same
conditions with the xanthate 1b afforded product 2 with
85% D-incorporation (Table 1, entry 2), in good agreement
with the report of Wood (95% and 88% D-incorporation
D
2
most appealing procedure in term of mildness (functional
group tolerance), sustainability and cost.15 Wood and co-
workers reported a very attractive method for Barton-
McCombie deoxygenation of alcohols employing H
2
O
(and D O) as the hydrogen (deuterium) atom source
2
(Scheme 1).16 This method was extended to deiodination,17
reductive addition18 and radical cyclization19 reactions. To
explain this unexpected reactivity of water, the O–H bond
is too strong to be involved in homolytic reactions,
with Me
3
B and and Bu B, respectively) (Table 1, entries 3
3
and 4). This striking difference of D-incorporation
between the xanthate and the iodide is not compatible
with the reported mechanism. Moreover, based on kinetic
and mechanistic investigations by Newcomb24-25 and us,22
it was anticipated that triethylborane would compete with
activation of the water molecule by complexation with
20-23
trialkylborane was proposed.18,
We report here, that
this mechanism represents in the deuteration process only
the R
3
B·D O complex as hydrogen atom donor for alkyl
2
a minor pathway, and that an in situ generated thiol is
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Page 2 of 6
radicals leading to low deuterium incorporation. The high
of xanthates (Scheme 2). Slow hydrolysis of either the
starting xanthate or the thiocarbonate by-product
provides the deuterated alkanethiol catalyst. After
hydrogen atom transfer to the alkyl radical, the
alkanethiyl radical26 reacts with triethylborane to afford an
1
2
3
4
level of deuteration obtained with xanthates such as 1b
remained puzzling.
Table 1. Deuteration of 1a, 1b and 1c using R
and air.
3
B, D O
2
5
ethyl radical that sustain the chain process and
a
6
7
8
9
thioborinic ester (R BSR’). Facile hydrolysis of the
2
thioborinic ester (Scheme 2, blue part) gives the
regenerated catalyst. Such a mechanism is supported by
the work of Mikhailov27 showing that in presence of of
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oxygen, trialkylborane R
the corresponding thioborinic ester and the corresponding
alkane RH. Interestingly, in the presence of
3
B react with a thiol R'SH to give
a
stoichiometric amount of an alcohol, only a catalytic
amount of the thiol was necessary to consume all the
trialkylborane. A few years later, a radical mechanism was
proposed for this reaction by Davies and Roberts.28 The
formation of the non-deuterated product results most
probably from hydrogen atom abstraction involving the
trialkyborane.24-25
Entr Substrat
Additive
(mol%)
R
3
B
Yield D-inc.
y
1
e
1a
1b
1b
1b
1c
1a
1a
Et
3
B
B
–
–
–
–
–
38%
20%
67%a
19%a
29%
7%
2
Et
3
85%
95%
88%
87%
64%
81%
316
416
5
Me
Bu
3
B
3
B
Et
Et
Et
3
B
B
B
6
3
3
C
12
H25SH (0.17) 53%
7
C
12
H25SH (1.0) 63%
A plausible hypothesis for the discrepancy between the
deuteration of the iodide 1a and the xanthate 1b is that,
under the reaction conditions (Lewis acidity of Et B,
3
presence of water, long reaction time), partial hydrolysis
of the xanthate (or of the ethyl methyl dithiocarbonate
formed during the reaction) is taking place generating
methanethiol (and ethanethiol) that can act as a catalyst in
the deuteration process. Since the presence of these
volatile thiols is difficult to detect, the dodecyl xanthate 1c
derived from cholesterol was prepared. The radical
deuteration of 1c afforded the deoxygenated product 2 in
similar yield and deuterium incorporation as the methyl
xanthate 1b. However, at the end of the reaction, the
presence of 0.17 mol% of dodecanethiol in the reaction
mixture was detected by gas chromatography. The total
amount of thiol in solution is possibly higher since we
could not detect the formation of ethanethiol due to its
volatility. The deuteration of the iodide 1a was repeated in
the presence of 0.17 mol% of dodecanethiol. A marked
increase in yield and deuterium incorporation (64%) was
observed (Table 1, entries 6). When 1 mol% of thiol was
used, 81% deuterium incorporation was reached, a result
similar to the one obtained for the xanthates 1a and 1b
(Table 1, entry 5). Therefore, it is reasonable to assume
that the main pathway for the deoxygenation of the
Scheme 2. Revised mechanism for the deoxygenation
of xanthate employing D
source.
2
O as the deuterium atom
Interestingly, our mechanistic study has shown that a
deiodination process involving D O may also be suitable
2
for the preparation of deuterated compounds (Table 1,
entry 7). Optimization of the procedure was performed
with 4-iodo-1-tosylpiperidine 3.29 As
a
catalyst,
dodecanethiol was used due to its low volatility and
neutral odor. As initiator and chain transfer reagent,
triethylborane (Et
3
B) was selected due to its commercial
xanthate in presence of D
catalyzed by an in situ generated thiol. The mechanism
involving the Et B·D complex represents minor
2
O and a trialkylborane is
availability. Me B would have been a better choice due to
3
the lack of stabilization of the methyl relative to the ethyl
radical (more efficient iodine atom transfer) and the lower
3
2
O
a
reaction pathway, as demonstrated by the low level of
deuteration during the deiodination process (Table 1,
entry 1). Since the hydrolysis of the xanthates is a slow
process, the thiol catalyzed reaction is favored by the long
reaction time (up to 24 h) necessary for the deoxygenation
hydrogen donor ability of Me
3
B relative to Et B (higher D-
3
incorporation). Unfortunately, this reagent is not
commercially available in Europe. In the initial
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Journal of the American Chemical Society
experiments, di-tert-butylhyponitrite (DTBHN) was
Entry R–I
R–Da
Yield D-inc.
1
chosen as an initiator.
2
3
4
5
6
7
8
9
89% 92%
48% 98%b
1
2
3
4
5
6
3
5
6
7
8
9
4
Table 2. Optimization of the radical deiodination of 3
with D O as a source of deuterium.
2
15 78% 96%
16 91% 94%
17 93% 96%
18 82%c 91%
19 87%d,e 95%
Entry
Initiator
DTBHN
DTBHN
DTBHN
DTBHN
DTBHN
DTBHN
Aira
n-C12
H
25SH Yield D-inc.
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1
2
3
4
5
6
7
–
71%
96%
89%
88%
77%
89%
89%
32%
82%
89%
92%
93%
90%
92%
1 mol%
2 mol%
5 mol%
10 mol%
5 mol%b
1 mol%
85%f 85%
20
a) Reaction at room temperature. b) Et
used instead of n-C12
2
BS(n-C12H25) was
7
10
84%f,g 89%c
H
25SH.
In the absence of catalyst, the reaction gave as expected
a low level of D-incorporation (32%) and a moderate yield
(Table 2, entry 1). The use of 1 mol% of dodecanethiol
significantly increases the yield (96%) and the D-
incorportation (82%) (entry 2). Increasing the amount of
catalyst has a positive effect on the D-incorporation (up to
90%) but the yield decreased (Table 2, entries 3–5). This
result can be rationalized by the fact that increasing the
concentration of the thiol favor the hydrogen transfer to
the ethyl radical before it can abstract an iodine atom.
Under these conditions, full consumption of the starting
iodide 3 is difficult to reach. It is remarkable to note that
the catalyst was used in its non-deuterated form. We
assumed that the thiol is immediately converted to the
corresponding thioborinic ester, consuming rapidly all the
S–H hydrogen atoms.27 This reaction is presumably
initiated by traces of residual oxygen in the solvent. In
order to check this, the reaction was run with 5 mol% of
8
9
1a
11
2
73%h 93%
21 79% 77%
22 84%i 96%
23 78%b 83%
24 43% 91%
10 12
11 13
12 14
a) Major isomer shown when applicable. b) Using 5
equivalents of dodecanethiol. c) exo/endo 5:1 d) Yield
determined by GC using nonadecane as an internal
standard. e) cis/trans 3:1. f) exo/endo 95:5. g) Initiation with
DTBHN (1 equiv) at 60 °C and 5 mol% of dodecanethiol.
h) α/β 3:1. i) trans/cis ≥95:5.
preformed n-docecyl diethylthioborinate (n-C12
H
25SBEt )
2
(Table 2, entry 6). Under these conditions, the yield and D-
incorporation match the ones obtained with 5 mol% of the
thiol (Table 2, entry 4). To avoid contamination by H O, all
2
initial experiments (Table 2, entries 1–6) were performed
with di-tert-butylhyponitrite (DTBHN) as an initiator
rather than air. However, slow addition of air30 dried by
bubbling through concentrated sulfuric acid, gave
excellent results with 1 mol% of catalyst (Table 2, entry 7).
The optimized procedure involving initiation with dry air
and 1 mol% of dodecanethiol was tested with a broad
range of iodides. Results are summarized in Table 3.
A series of secondary alkyl iodides was investigated
first (Table 3, entries 1–8). The reaction afforded the
deiodinated product in 73–93% yields and high level of
deuterium incorporation (80–96%). The presence of
functional groups containing C–H bonds that are prone to
hydrogen atom abstraction by thiyl radical such as amides
(entries 1–4), lactones (entry 5 and 7), silyl ether (entry 7),
benzylic and allylic systems (entries 6 and 8) are well
tolerated. By using 5 mol% of the thiol catalyst, a very
high level of deuterium incorporation can be reached but
the yield went down due to incomplete conversion.
Similar results were obtained with tertiary iodides (Table
3, entries 9–11) with a more important fluctuation of the
Table 3. Scope of the thiol catalyzed deuterative
deiodination process.
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Page 4 of 6
level of deuterium incorporation (77–96%). Finally, a
Scheme 3. Proposed mechanism for the radical
1
2
3
4
5
6
7
8
primary alkyl iodide was tested (Table 3, enty 12). As
anticipated, the deuterated compound was obtained in
lower yield (43%) due to a slower iodine atom transfer
between the ethyl radical and the substrate31 but with a
good level of deuterium incorporation. The mechanism of
the deiodination process is depicted in Scheme 3. At first,
the non-deuterated dodecanethiol is converted to the
thioborinic ester by a rapid reaction with triethylborane
(the thiol is added to the triethylborane solution before
deuteration of alkyl iodides catalyzed by a thiol.
In conclusion, our study demonstrates that a thiol
generated in situ is acting as
a catalyst in the
triethylborane-water mediated xanthates deoxygenation
process reported by Wood and co-workers. Based on this
observation, a thiol-catalyzed deuterative deiodination
reaction has been developed. The reaction chain process is
mediated by Et
3
B and uses D O as a source of deuterium
2
9
atom. Beside its obvious synthetic interest, this reaction
offers new opportunities to develop catalytic
enantioselective reactions.33-36 Work in this direction is
currently in progress.
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adding the D O and the iodide). This is a fast radical
2
process, initiated by traces amount of oxygen.27-28
Interestingly, very high level of deuteration can be
obtained even when a large amount of non-deuterated
thiol is used. This may be due to the fast conversion of the
thiol to the thioborinic ester before the reaction start or to
the fact that the non-deuterated thiol is reacting faster
ASSOCIATED CONTENT
Supporting
Information.
The
Supporting
Information is available free of charge on the ACS
with the ethyl radical than the thiol-d due to a kinetic
1
istotope effect.24-25 In other word, the non-productive
hydrogen atom transfer to the ethyl radical consumed
selectively the non-deuterated catalyst. Hydrolysis of the
Publications website.
Experimental procedures and characterization of all new
products
Copies of 1H- and 13C-NMR spectra
thioborinic ester with D
the real catalyst of the reaction. The chain reaction starts
with an ethyl radical generated by the reaction of Et
2
O afforded the dodecanethiol-d ,
1
AUTHOR INFORMATION
Corresponding Author
3
B
with oxygen (initiation step). This ethyl radical abstracts
the iodine atom generating the alkyl radical. Deuteration
Philippe Renaud
of the radical by the dodecanethiol-d
product together with a thiyl radical that sustains the
chain process by reacting with Et B. The lower conversion
1
gave the deuterated
E-mail: philippe.renaud@dcb.unibe.ch
3
ORCID
obtained when a higher catalyst loading was used results
from the competitive deuteration of the ethyl radical
relative to the the iodine atom transfer process leading to
a non-productive chain reaction.32 The formation of the
non-deuterated product can be explained by a competitive
Philippe Renaud: 0000-0002-9069-7109 890
Giorgio Villa: 0000-0002-0802-7502
Valentin Soulard: 0000-0001-5300-7837
Notes
reaction involving Et
3
B as a source of hydrogen atom. A
The authors declare no competing financial interest.
rate constant k
H
= 0.6 × 104 M–1 s–1 has been reported for the
hydrogen atom transfer from Et
radical.24-25
3
B to a secondary alkyl
ACKNOWLEDGMENT
The Swiss National Science Foundation (Project
200020_152782 and 200020_172621), the State Secretariat
for Education, Research and Innovation (SBFI Nr.
C14.0096) and the COST Action CM1201 (short-term
scientific mission of VS) are gratefully acknowledged for
their support. We thank Dr. Julien Furrer and Mr. Ilche
Gjuroski for their support in measuring 2H-NMR-spectra.
REFERENCES
1. Zhu, Y.; Zhou, J.; Jiao, B., ACS Med. Chem. Lett. 2013, 4,
349-352.
2. Zhang, Y.; Tortorella, M. D.; Wang, Y.; Liu, J.; Tu, Z.; Liu,
X.; Bai, Y.; Wen, D.; Lu, X.; Lu, Y.; Talley, J. J., ACS Med.
Chem. Lett. 2014, 5, 1162-1166.
3. Katsnelson, A., Nat. Med. 2013, 19, 656.
4. Mullard, A., Nat. Rev. Drug Discov. 2016, 15, 219-221.
5. Schmidt, C., Nat. Biotech. 2017, 35, 493-494.
6. New
Drug
Application
(NDA):
208082.
https://www.accessdata.fda.gov/scripts/cder/daf/index
.cfm?event=overview.process&varApplNo=208082.
ACS Paragon Plus Environment
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Page 5 of 6
Journal of the American Chemical Society
7. Maltais, F.; Jung, Y. C.; Chen, M.; Tanoury, J.; Perni, R. B.;
Mani, N.; Laitinen, L.; Huang, H.; Liao, S.; Gao, H.; Tsao,
H.; Block, E.; Ma, C.; Shawgo, R. S.; Town, C.; Brummel,
C. L.; Howe, D.; Pazhanisamy, S.; Raybuck, S.; Namchuk,
M.; Bennani, Y. L., J. Med. Chem. 2009, 52, 7993-8001.
8. MacWood, G. E.; Urey, H. C., J. Chem. Phys. 1936, 4, 402-
406.
9. Leblanc, M. E.; Morse, A. T.; Leitch, L. C., Can. J. Chem.
1956, 34, 354-358.
10. Pocker, Y.; Exner, J. H., J. Am. Chem. Soc. 1968, 90, 6764-
6773.
1
2
3
4
5
6
7
8
9
11. Caldwell, R. A., J. Org. Chem. 1970, 35, 1193-1194.
12. Curran, D. P.; Ramamoorthy, P. S., Tetrahedron 1993, 49,
4841-4858.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13. Boyer, I. J., Toxicology 1989, 55, 253-298.
14. Crich, D.; Sun, S., J. Org. Chem. 1996, 61, 7200-7201.
15. During the writing of this manuscript, the of deuteration and
tritiation of pharmaceutical compounds mediated by thiols
using isotopically labeled water was reported: Loh, Y. Y.;
Nagao, K.; Hoover, A. J.; Hesk, D.; Rivera, N. R.; Colletti,
S. L.; Davies, I. W.; MacMillan, D. W. C., Science 2017,
358, 1182-1187.
16. Spiegel, D. A.; Wiberg, K. B.; Schacherer, L. N.; Medeiros,
M. R.; Wood, J. L., J. Am. Chem. Soc. 2005, 127, 12513-
12515.
17. Medeiros, M. R.; Schacherer, L. N.; Spiegel, D. A.; Wood,
J. L., Org. Lett. 2007, 9, 4427-4429.
18. Allais, F.; Boivin, J.; Nguyen, V. T., Beilstein J. Org. Chem.
2007, 3, 46-47.
19. Davy, J. A.; Mason, J. W.; Moreau, B.; Wulff, J. E., J. Org.
Chem. 2012, 77, 6332-6339.
20. Boivin, J.; Nguyen, V. T., Beilstein J. Org. Chem. 2007, 3,
45-47.
21. Hioe, J.; Karton, A.; Martin, J. M. L.; Zipse, H., Chem. Eur.
J. 2010, 16, 6861-6865.
22. Povie, G.; Marzorati, M.; Bigler, P.; Renaud, P., J. Org.
Chem. 2013, 78, 1553-1558.
23. Povie, G.; Renaud, P., Chimia 2013, 67, 250-252.
24. Jin, J.; Newcomb, M., J. Org. Chem. 2007, 72, 5098-5103.
25. Jin, J.; Newcomb, M., J. Org. Chem. 2008, 73, 4740-4742.
26. For a review on the chemistry of thiyl radicals, see: Dénès,
F.; Pichowicz, M.; Povie, G.; Renaud, P., Chem. Rev. 2014,
114, 2587-2693.
27. Mikhailov, B. M.; Bubnov, Y. N., Zh. Obs. Khim. 1960, 31,
160-166.
28. Davies, A. G.; Roberts, B. P., Acc. Chem. Res. 1972, 5, 387-
392.
29. Ollivier, C.; Renaud, P., J. Am. Chem. Soc. 2000, 122, 6496-
6497.
30. Curran, D. P.; McFadden, T. R., J. Am. Chem. Soc. 2016,
138, 7741-7752.
31. Povie, G.; Ford, L.; Pozzi, D.; Soulard, V.; Villa, G.;
Renaud, P., Angew. Chem. 2016, 128, 11387-11391.
32. Extension of the reaction to debromination is not expected
to work since the competitive deuteration of the ethyl
radical is expected to be faster than the bromine atom
transfer step. Exceptionnally reactive bromides may
represent an exception.
33. Haque, M. B.; Roberts, B. P.; Tocher, D. A., J. Chem. Soc.,
Perkin Trans. 1 1998, 2881-2890.
34. Dang, H.-S.; Elsegood, M. R. J.; Kim, K.-M.; Roberts, B. P.,
J. Chem. Soc. Perk. Trans. 1 1999, 2061-2068.
35. Cai, Y.; Roberts, B. P., J. Chem. Soc., Perkin Trans. 2 2002,
1858-1868.
36. Brill, Z. G.; Grover, H. K.; Maimone, T. J., Science 2016,
352, 1078-1082.
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Graphic for Table of Content
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Et3B, D2O , R’SH (cat.)
air, rt
R I
R D
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- R = prim-, sec-, tert-alkyl
- D-incorporation 77–98%
- R’SH = n-C12H25SH
R–I
Et• + Et2BOD Et3B + D2O
R’S•
R’S–D
- 1 mol% catalyst loading
Et–I
R•
R–D
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