Investigations into the C-deuteriation of aryl alkyl ketones using urea as a pro-base in the presence of a deuterium donor

Article abstract of DOI:10.1002/jlcr.1083

Results are reported on the regioselective C-deuteriation of a series of enolates derived from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro-base in the presence of a suitable deuterium donor. Copyright

Full text of DOI:10.1002/jlcr.1083

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS
J Label Compd Radiopharm 2006; 49: 641–652.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.1083
Research Article
Investigations into the C-deuteriation of aryl alkyl
ketones using urea as a pro-base in the presence of a
deuterium donor
Gregory S. Coumbarides1, Jason Eames2,*, Michael J. Suggate1 and Neluka
Weerasooriya1
1 Department of Chemistry, Queen Mary, University of London, Mile End Road,
London E1 4NS, UK
2 Department of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull
HU6 7RX, UK
Summary
Results are reported on the regioselective C-deuteriation of a series of enolates derived
from the deprotonation of aryl alkyl ketones using dilithiated urea as the pro-base in
the presence of a suitable deuterium donor. Copyright # 2006 John Wiley & Sons,
Ltd.
Received 30 March 2006; Revised 19 April 2006; Accepted 19 April 2006
Key Words: alkyl aryl ketones; D-enols; deuterium; enolates and internal deuterium
transfer
Introduction
Thermodynamic deuteriation of enolates has been shown to be a reliable and
efficient method for the synthesis of deuterium-labelled carbonyl derivatives.1
By comparison, kinetic deuteriation2 is known to be problematic and has been
shown to be dependent on the method used for enolate formation,3 the
structural nature of the enolate,4 D-source5 and potential additives.6
Kinetic formation of enolates through C-deprotonation of carbonyl
derivatives is well known,7 whereas, efficient C-deuteriation has proved to
be far more challenging.8,y
*Correspondence to: Jason Eames, Department of Chemistry, University of Hull, Cottingham Road,
Kingston upon Hull, HU6 7RX, UK. E-mail: j.eames@hull.ac.uk
y For enantioselective protonation of lithium enolates with reduced deuterium incorporation: see
Yanagisawa A, Kikuchi T, Kuribayashi T, Yamamoto H. Tetrahedron 1998; 54: 10253–10264.
Copyright # 2006 John Wiley & Sons, Ltd.

642
G. S. COUMBARIDES ET AL.
OLi + HN(i-Pr)2
O
O
D/H
H
1. LDA, -78oC
2. CD3CO2D
[D1]-1;90%
2a
1
([D]:[H] =2:98)
Scheme 1.
This is in-part due to the use of lithium amides9 (e.g. lithium diisopropy-
lamide, LDA) as Brꢀnsted bases to form the required lithium enolate, such as
2a,3 through simple deprotonation of the corresponding ketone derivative 1 at
C(2) (Scheme 1). Addition of a suitable deuterium source, such as [D4]-acetic
acid, to a preformed solution of lithium enolate 2a in THF invariably gave a
mixture of the required D-labelled and unwanted unlabelled ketones [D1]-1
and 1 ([D]:[H] = 2:98), respectively (Scheme 1).3 This is primarily due to the
presence of a competitive base, diisopropylamine (in 2a), formed by
deprotonation of the parent ketone 1 with lithium diisopropylamide (LDA)
(Scheme 1); this phenomenon has previously been reported by Seebach and co-
workers,10 and has led to the concept of internal proton return. This is where
the original hydrogen atom, H, present in the ketone 1 can be re-delivered
back to re-form the parent substrate 1 via the residual diisopropylamine on
addition of [D4]-acetic acid, thus leading to the partially deuteriated ketone
[D1]-1 (Scheme 1). Removal of the problematic11,z NH proton from the
enolate complex 2a (by sequential addition of MeLi) to give the corresponding
lithium enolate–lithium amide complex 3 (Scheme 2), or by ensuring the
residual amine was less basic12 has been shown to increase the levels of
deuterium incorporation. By comparison, deuteriation of ‘base-free’ enolates
(e.g. 2b) in the absence of the unwanted residual amine can lead to higher
levels of deuteriation (Scheme 2).13,} However, the obviously drawback for this
methodology is the requirement for the formation of the corresponding silyl
enol ether 4 (by trapping the original lithium enolate 2a with trimethylsilyl
chloride) (Scheme 2). The required ‘base-free’ enolate 2b can be liberated from
parent enol equivalent 4 using Stork’s methodology14 by simple addition of
methyl lithium (Scheme 2).
Results and discussion
We were interested in extending this methodology by developing a lithium
amide base which disfavoured internal proton return.10 For our study, we
chose to use urea 5 as our pro-base due to its non-basic nature (pKHAꢀ0),15
z For further information see References.8,10
} For further information see reference.3
Copyright # 2006 John Wiley & Sons, Ltd.
J Label Compd Radiopharm. 2006; 49: 641–652
DOI: 10.1002/jlcr

C-DEUTERIATION OF ARYL ALKYL
OLi +HN(i-Pr)2
643
OLi + LiN(i-Pr)2
O
H
1. LDA, -78oC
MeLi
3
2a
1
1. LDA, -78oC
2. Me3SiCl
87%
([D]:[H] =35:65)
CD3CO2D
OLi + Me4Si
O
OSiMe3
D
MeLi, -78oC
CD3CO2D
68%
([D]:[H] =>95:5)
2b
[D1]-1
4; 69%
Scheme 2.
and to ensure its conjugate base was sufficiently basic enough to deprotonate
an aryl alkyl ketone} the corresponding dilithiated urea 7 was used as the
parent base [5; pKA = 26.9].16 We first investigated the suitability of dilithium
amide 7 as a potential Brꢀnsted base for efficient enolate formation by probing
the deprotonation of tetralone 8 and 2-methyl-tetralone 1 (Scheme 4). The
required dilithiated urea 7 was formed by addition of n-BuLi (two equivalents)
to a stirred solution of urea 5 in THF at ꢁ788C as illustrated in Scheme 3.
Sequential addition of tetralone 8, followed by trimethylsilylacetate
(Me3SiOAc)k gave the corresponding silyl enol ether 9 in good yield (52%).
By comparison, addition of methyl iodide to the lithium enolate formed by
deprotonation of 2-methyl-tetralone 1, gave the corresponding 2,2-dimethyl-
tetralone 10 in 70% yield (Scheme 4). From these results, it appears lithium
enolate formation (for 8 and 1, respectively) occurs efficiently giving directly
the O-silylated enol and C-alkylated derivatives 9 and 10, respectively (Scheme
4). We next probed the de-deuteriation of 2-deuterio-2-methyl-tetralone [D1]-1
using dilithiated urea 7 to ensure that potential internal deuterium return was
negligible (Scheme 5). Addition of 2-deuterio-2-methyl-tetralone [D1]-1 to a
solution of preformed 7 in THF at ꢁ788C, followed an acetic acid quench gave
the required 2-methyl-tetralone 1 with virtually no deuterium remaining
([D]:[H]=52:>98) (Scheme 5). From these experiments, it appears that
dilithiated urea 7 is a suitable Brꢀnsted base for enolate formation and
versatile enough for a wide range of potential electrophiles (e.g. Me3SiOAc
and MeI) and acids (e.g. acetic acid) (Schemes 4 and 5).
} For a related ketone, e.g., acetophenone; pKa (enol OH) = 7.9 and pKa (carbonyl CH) =18.2.
k Using a more electrophilic Me3Si source (e.g. Me3SiCl) the yield was reduced to 33%; Weerasooriya N.
PhD Thesis, University of London, 2003.
Copyright # 2006 John Wiley & Sons, Ltd.
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644
G. S. COUMBARIDES ET AL.
OLi
H
OLi
O
n-BuLi
n-BuLi
O
THF, -78oC
THF, -78oC
H2N
NH
NH
LiHN
NH2
H2N
H2N
NH2
7
6
5
pKa = 26.916
pKa = 0.0615
Scheme 3.
OSiMe3
O
1. 7, -78oC
2. Me3SiOAc
(2 equiv.)
9; 52%
8
O
O
1. 7, -78oC
2. MeI(2 equiv.)
10; 70%
1
Scheme 4.
O
O
D
H
7, -78oC
then CH3CO2H
1; 90%
([D]:[H] =<2:>98)
[D1]-1
Scheme 5.
With this information in hand, we next investigated the deuteriation of the
lithium enolate 2c (formed by deprotonation of 2-methyl-tetralone 1 using 7)
with a variety of deuterium sources (Scheme 6: Entry 4). From these
regioselective C-deuteriations, it appears the structural nature of the
deuterium donor was particularly important for controlling the regioselective
C-deuteriation of enolate 2c to give 2-deuterio-2-methyl-tetralone [D1]-1
(Scheme 6). For weakly D-acidic sources, like D2O and [D4]-MeOH these gave
moderately higher levels of D-incorporation than mildly D-acidic [D4]-acetic
acid (Scheme 6: Entry 4). Whereas, a more D-acidic source like DCl gave little
or no D-incorporation (Scheme 6: Entry 4). This effect is expected as an
increase in D-acidity has been shown to favour D-enol formation [D1]-11 by
promoting regioselective O-deuteriation (as illustrated in Scheme 7) which
leads to loss of the deuterium label through tautomerization during aqueous
work-up.3,4 It is interesting to note, the use of dilithiated urea 7 appears to be
Copyright # 2006 John Wiley & Sons, Ltd.
J Label Compd Radiopharm. 2006; 49: 641–652
DOI: 10.1002/jlcr

C-DEUTERIATION OF ARYL ALKYL
645
Hbase
O
O
O
D
H
base
(see table)
D-source
(seetable)
-78oC
2c
[D1]-1
1
D-source
DCl
[D4]-MeOH
D2O
[D4]-acetic acid
Entry
Base
72:28a
(78%)
<2:>98a
(90%)
52:48a
(72%)
55:45a
(67%)
1
2
LDA
83:17a
(72%)
35:65a
(87%)
62:38a
(78%)
58:42a
(81%)
LDA.MeLi
84:16a
(70%)
>95:5a
(68%)
>98:2a
(72%)
>98:2a
(60%)
under "base-free"
3
4
conditions via 2b
73:27a
(65%)
78:22a
(66%)
1:99a
(62%)
46:65a
(64%)
di-lithiated
urea 7
aisotopic[D]:[H]ratio.
Scheme 6.
O
OLi
H
OL
OLi
i
H2N
NH
LiHN
NH
7
2d
1
6
D-source
O
OD
D
O
H/D
[D1]-1
[D1]-11
O
OD
NH
[D1]-1
H2N
H2N
NHD
[D1]-5
Scheme 7.
Copyright # 2006 John Wiley & Sons, Ltd.
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646
G. S. COUMBARIDES ET AL.
more efficient at aiding regioselective C-deuteriation than lithium diisopropyl-
amide (LDA), with and without addition of methyl lithium (Scheme 6: Entries
2 and 1, respectively). For ‘residual base-free’ enolates, such as 2b, which do
not contain an additional competitive amine base, kinetic C-deuteriation with
D2O, [D4]-MeOH and [D4]-acetic acid is particularly efficient leading to the
required 2-deuterio-2-methyl-tetralone [D1]-1 in good yield with high
D-incorporation (Scheme 6: Entry 3). Efficient D-incorporation appears to
occur when using DCl with ‘base-free’ enolates in the presence and absence of
diisopropylamine (see Scheme 6: Entries 1 and 3), and this is may be due to a
combination of D-enol formation [D1]-11, and competitive thermodynamic
tautomerization.
We next turned our attention to the deuteriation of a wide variety of
structurally related aryl alkyl ketones 1, 8 and 12-15 using our developed
methodology (Scheme 8). In line with our preliminary study, the relative order
of deuterium incorporation was found to be: D2O > [D4]-MeOH > [D4]-
acetic acid > DCl (Scheme 8). However, it appears that selective deuteriation
under kinetic control, in particular for D2O had not occurred during the
lifetime of these reactions. This presumably was due to proton-deuterium
exchange under basic conditions involving the byproduct lithium
deuteroxide (LiOD), the mono-deuteriated ketone and an excess of deuterium
donor to give dideuteriated ketones. However, it is surprising to find that the
level of deuterium incorporation were not complete for ketones like 1 (to give
[D1]-1) which cannot under go this type of proton-deuterium exchange.
Whereas, for D-acidic deuterium donors, which contain intrinsically weaker
conjugate bases (e.g. [D4]-acetic acid) further deuterium incorporation appears
not to be a problem.
We next turned our attention to the deuteriation of a series of sterically
demanding phenyl alkyl and phenyl cycloalkyl ketones 16 and 17–19,
respectively as these were known to be difficult to deuteriate under kinetic
control (Scheme 9).4,19 Addition of these ketones 16–19 to a stirred solution of
preformed 7 in THF at ꢁ788C, followed by the addition of a suitable
deuterium source (e.g. D2O, [D4]-MeOH and [D4]-acetic acid), gave the
partially deuteriated ketones [D1]-16–19 in good yield (Scheme 9). The overall
levels of regioselective C-deuteriation were found to be similar4 to those
obtained using Stork’s14 ‘base-free’ enolate methodology and in fact near their
natural regioselectivity. By comparison, these levels of D-incorporation and
the yields were higher than those obtained using lithium diisopropylamide
(LDA) (See footnote }).3,4 It is particularly interesting to note that competitive
b-hydride reduction of ketones 17–19 does occur with the use of LDA, thus
lowering the overall yield of [D1]-17–19 through diminished enolate formation
(by approximately 7, 10 and 25%, respectively),4 whereas, using the dilithiated
urea 7 this does not occur.
Copyright # 2006 John Wiley & Sons, Ltd.
J Label Compd Radiopharm. 2006; 49: 641–652
DOI: 10.1002/jlcr

C-DEUTERIATION OF ARYL ALKYL
647
O
O
D
H
R
7,-78 oC
R
then D-source
( ) n
( ) n
D-source
[D4]-aceticacid
DCl
D2O
[D4]-MeOH
Product
O
Ketone
O
D
1:99a
(62%)
46:54a
(64%)
78:22a
(66%)
73:27a
(65%)
1
[D1]-1
O
O
D
1:99a
(71%)
20:80a
(69%)
78:22b
(66%)
80:20a
(65%)
8
[D1]-8
O
O
4:96a
(67%)
26:74a
(66%)
86:14b
(65%)
78:22a
(62%)
D
D
12
13
[D1]-12
O
O
5:95a
(63%)
20:80a
(59%)
71:29a
(55%)
68:32a
(58%)
[D1]-13
O
O
D
5:95a
(67%)
22:78a
(61%)
70:30b
(70%)
64:36b
(70%)
MeO
MeO
[D1]-14
14
O
O
D
1:99a
(69%)
42:58a
(60%)
70:30b
(70%)
55:45b
(62%)
MeO
MeO
[D1]-15
15
aisotopic [D]:[H] ratio; bisotopic [D1]:[D2] ratio.
Scheme 8.
Copyright # 2006 John Wiley & Sons, Ltd.
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648
G. S. COUMBARIDES ET AL.
O
O
D
H
7,-78oC
then D-source
( ) n
( ) n
D-source
D2O
Ketone
O
Product
O
[D4]-MeOH
[D4]-acetic acid
14:86a
(59%)
69:31a
(60%)
65:35a
(60%)
D
16
[D1]-16
O
O
30:70a
(57%)
D
65:35a
(58%)
60:40a
(62%)
17
[D1]-17
O
O
D
22:78a
(52%)
67:33b
(59%)
59:41a
(53%)
18
[D1]-18
O
D
O
25:77a
(60%)
65:35a
(58%)
60:40a
(62%)
19
[D1]-19
aisotopic [D]:[H] ratio.
Scheme 9.
In an attempt to find a suitable method for the formation of 2-deuterio-
2-methyl-tetralone [D1]-1, we next probed the thermodynamic deuteriation of
2-methyl-tetralone 1 under basic conditions (Scheme 10). Excellent levels of
deuterium incorporation ([D]:[H]:>98:52) were achieved by using lithium
hydroxide monohydrate (1 equivalent) as the base and [D4]-MeOH as the
deuterium donor and solvent (Scheme 10). It is important to note, using an
excess of lithium hydroxide monohydrate (e.g. three equivalents) lowered the
yield of 2-deuterio-2-methyl-tetralone [D1]-1 (from 99 to 28%) through
competitive aldol addition, and using D2O can lead to lower overall
D-incorporation due to reduced solubility of the substrate. This same level
of deuterium incorporation could be achieved by using its silyl enol ether
Copyright # 2006 John Wiley & Sons, Ltd.
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DOI: 10.1002/jlcr

C-DEUTERIATION OF ARYL ALKYL
649
O
O
OSiMe3
99%
60%
1.MeLi,-78oC
D
LiOH.H2O
[D4]-MeOH
2.D2O
4
1
[D1]-1
([D]:[H] = >98:<2)
Scheme 10.
precursor 4 under Stork’s14 ‘base-free’ conditions, but the yield is generally
lower (Scheme 10).2,3
Experimental
General
All solvents were distilled before use. Tetrahydrofuran (THF) and ether were
freshly distilled from sodium wire. Benzophenone was used as the indicator for
THF. All reactions were carried out under nitrogen using oven-dried
glassware. Flash column chromatography was carried out using Merck
Kieselgel 60 (230–400 mesh). Thin layer chromatography (TLC) was carried
out on commercially available pre-coated plates (Merck Kieselgel 60F254
silica). Proton and carbon NMR spectra were recorded on a Bruker AM 250
Fourier transform spectrometer using an internal deuterium lock. Chemical
shifts are quoted in parts per million downfield from tetramethylsilane.
Carbon NMR spectra were recorded with broad proton decoupling. Infrared
spectra were recorded on a Shimadzu 8300 FTIR spectrometer and mass
spectra were recorded on a Kratos 50MSTC spectrometer using a DS503 data
system for high-resolution analysis. The levels of D-incorporation were
determined by a combination of mass, proton and carbon NMR spectra.
Representative procedure for deuteriation of 2-methyl-tetralone 1 to give
2-deuterio-2-methyl-tetralone [D1]-1 using the dilithium amide 7
n-BuLi (0.25 ml, 2.5 M in hexane, 0.62 mmol) was added dropwise to a
solution of urea 5 (0.37 mg, 0.62 mmol) in THF at room temperature and
stirred for 1 h. The resulting solution was cooled to ꢁ788C. 2-Methyl-tetralone
1 (0.1 g, 0.62 mmol) in THF (1 ml), was slowly added and the reaction mixture
was stirred for 30 min. The chosen deuterium donor (e.g. [D4]-acetic acid
(0.79 mg, 71 ml, 1.24 mmol)) in THF (1 ml) was added dropwise and the
resulting mixture was stirred for a further 30 min. The reaction was quenched
by the addition of water (10 ml). The solution was extracted with diethyl ether
(3 ꢂ 20 ml), dried (over MgSO4) and evaporated under reduced pressure. The
residue was purified by flash chromatography on silica gel eluting with light
Copyright # 2006 John Wiley & Sons, Ltd.
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650
G. S. COUMBARIDES ET AL.
petroleum (40–608C):diethyl ether (9:1) to give 2-methyl-tetralone-[D1]-1
(63 mg, 63%) as an oil; RF (light petroleum (40–608C):diethyl ether (9:1)]
0.5; vmax (film); cmꢁ1 2106 (C–D) and 1683 (CO); dH (250 MHz, CDCl3) 8.00
(1 H, d, J=7.7, CH; Ar), 7.47 (1 H, d, J=7.7, CH; Ar), 7.25 (1 H, t, J=7.7,
CH; Ar), 7.22 (1 H, d, J=7.7, CH; Ar), 3.00 (2 H, m, CH2C=CH), 2.20 (1 H,
dt, J=13.2 and 4.4, CHAHB), 1.87 (1 H, m, CHAHB) and 1.28 (3 H, s,
CH3CD); dC (62.5 MHz, CDCl3) 200.8 (C=O), 144.2 (i-C; Ar), 133.1 (i-C;
1
Ar), 132.4, 128.7, 127.4 and 126.6 (4 ꢂ CH; Ar), 42.0 (1 C, t [1:1:1], JC,D
=
19.0, CDMe), 31.3 and 28.8 (2 ꢂ CH2) and 15.3 (CH3) (Found MH+,
162.1034. C11H12DO requires MH+, 162.1029); m/z 162 (100%, MH+). The
isotopic shift was 0.5 ppm (75.4 Hz at 150 MHz).
Representative procedure for silylation of tetralone 8 to give silyl enol ether 9
using the dilithium amide 7
n-BuLi (0.25 ml, 2.5 M in hexane, 0.62 mmol) was added dropwise to a
solution of urea 5 (0.37 mg, 0.62 mmol) in THF at room temperature and
stirred for 1 h. The resulting solution was cooled to ꢁ788C. Tetralone 8 (90 mg,
0.62 mmol) in THF (1 ml), was slowly added and the reaction mixture was
stirred for 30 min. Trimethylsilylacetate (0.17 g, 1.24 mmol) was added
dropwise and the resulting mixture was stirred for a further 2 h. The reaction
was quenched by the addition of water (10 ml). The solution was extracted
with diethyl ether (3 ꢂ 20 ml), dried (over MgSO4) and evaporated under
reduced pressure. The residue was purified by flash chromatography on silica
gel eluting with light petroleum (40–608C):diethyl ether (9:1) to give 1-
trimethylsilyloxy-tetral-1-ene 9 (70 mg, 52%) as an oil; RF ((light petroleum
(40–608C):diethyl ether (9:1)) 0.93; nmax(film); cmꢁ1 1687 (C=C); dH(270
MHz, CDCl3) 7.38 (1 H, d, J=7.7, CH; Ar), 7.10 (3 H, m, 3 ꢂ CH; Ar), 5.19
(1 H, t, J=4.5, C=CH), 2.78 (2 H, t, J=7.7, CH2C=CH), 2.31 (2 H, m, CH2)
and 0.21 (9 H, s, Siꢁ(CH3)3); dC(100 MHz, CDCl3) 147.8 (i-C; Ar), 136.8
(C=CO), 133.4 (i-C; Ar), 127.2, 126.9, 126.2 and 121.8 (4 ꢂ CH; Ar), 105.2
(C=CO), 39.1, 28.2 and 22.2 (3 ꢂ CH2) and 0.2 (Siꢁ(CH3)3); m/z 145 (30%,
M – SiMe3) and 219.1 (100, MH+).
Representative procedure for methylation of 2-methyl-tetralone 1 to form 2,2-
dimethyl-tetralone 10 using the dilithium amide 7
n-BuLi (0.25 ml, 2.5 M in hexane, 0.62 mmol) was added dropwise to a
solution of urea 5 (0.37 mg, 0.62 mmol) in THF at room temperature and
stirred for 1 h. The resulting solution was cooled to ꢁ788C. 2-Methyl-tetralone
1 (0.1 g, 0.62 mmol) in THF (1 ml), was slowly added and the reaction mixture
was stirred for 30 minutes. Methyl iodide (0.18 g, 1.24 mmol) in THF (1 ml)
was added dropwise and the resulting mixture was stirred for 12 h. The
reaction was quenched by the addition of water (10 ml). The solution was
Copyright # 2006 John Wiley & Sons, Ltd.
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C-DEUTERIATION OF ARYL ALKYL
651
extracted with diethyl ether (3 ꢂ 20 ml), dried (over MgSO4) and evaporated
under reduced pressure. The residue was purified by flash chromatography on
silica gel eluting with light petroleum (40–608C):diethyl ether (9:1) to give
2,2-dimethyl-tetralone-10 (76 mg, 70%) as an oil; RF (light petroleum (40–
608C):ether (9:1)) 0.6; nmax (film); cmꢁ1 1680 (C=O); dH(250 MHz, CDCl3)
8.05 (1 H, d, J=7.5, CH; Ar), 7.45 (1 H, t, J=7.5, CH; Ar), 7.29 (1 H, t,
J=7.5, CH; Ar), 7.20 (1 H, d, J=7.5, CH; Ar), 2.98 (2 H, t, J=6.5,
CH2C=CH), and 1.99 (2 H, t, J=6.5, CH2) and 1.20 (6 H, s, 2 ꢂ CH3); dC
(62.5 MHz, CDCl3) 203.2 (C=O), 143.8 (i-C; Ar), 133.4 (i-C; Ar), 131.8, 129.1
128.4 and 127.0 (4 ꢂ CH; Ar), 42.0 (CMe2), 37.1 and 26.1 (2 ꢂ CH2), and 24.8
(2 ꢂ CH3) (Found MH+, 175.1120. C12H15O requires MH, 175.1123).
2-deuterio-2-methyl-3,4-dihydronaphthlene-1-one [d1]-1
LiOH ꢃ H2O (21 mg, 0.5 mmol) was added to a stirred solution of 2-
methyltetralone 3 (80 mg, 0.5 mmol) in [D4]-MeOH (1.6 ml). The mixture
was stirred for 24 h, extracted into diethyl ether (2 ꢂ 10 ml) and concentrated
to give 2-deuterio-2-methyltetralone [D1]-1 (80 mg, 99%) ([D]:[H] =>98:52)
as an oil, which was spectroscopically identical to that previously obtained.3
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