Investigations into the regioselective C-deuteration of acyclic and exocyclic enolates

Article abstract of DOI:10.1002/ejoc.200390103

Results are reported on the regioselective C-deuteration of a series of related acyclic and exocyclic enolates derived from substituted aryl ketones. We comment on factors, such as the presence of additives and the structural nature of the enolate, that influence the observed C-deuteration and discuss the role of the deuterium donor. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Full text of DOI:10.1002/ejoc.200390103

FULL PAPER
Investigations into the Regioselective C-Deuteration of Acyclic and Exocyclic
Enolates
Jason Eames,*[a] Gregory S. Coumbarides,[a] Michael J. Suggate,[a] and
Neluka Weerasooriya[a]
Keywords: Deuterium / Kinetic deuteration / Ketones / Lithium / Isotopic labeling
Results are reported on the regioselective C-deuteration of a
series of related acyclic and exocyclic enolates derived from
substituted aryl ketones. We comment on factors, such as the
presence of additives and the structural nature of the enolate,
that influence the observed C-deuteration and discuss the
role of the deuterium donor.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Regioselective C-deuteration of enolates to give perdeu-
terated ketones is well documented.[1] The most popular
methods involve deuteration under thermodynamic con-
trol,[2] which usually means using a large excess of a deuter-
ium donor (e.g., D2O and [D4]MeOH) in the presence of a
sub-stoichiometric amount of base or acid.[3] By compar-
ison, efficient C-deuteration under kinetic control[4] has
been shown to be far more difficult to achieve.[5] In particu-
lar, the method chosen to generate the required kinetic enol-
ate has been shown to have a detrimental effect on the over-
all level of D-incorporation in some cases; for example, the
presence of a base like diisopropylamine[6] has been shown
to lower deuterium incorporation through competitive in-
ternal proton return.[7]
We have recently reported an efficient method for the re-
gioselective C-deuteration of endocyclic enolates by addi-
tion of MeLi to a stirred solution of an enol acetate (e.g.,
1)[8] or silyl enol ether (e.g., 3)[9] and quenching the resulting
‘‘base’’ and ‘‘base-free’’ enolates 4 and 5 with [D4]acetic
acid to give the required 2-methyl tetralone 2-d1 with near
perfect D-incorporation (Scheme 1). We concluded from
this study that the structural nature of the endocyclic ‘‘base-
free’’ enolate played a minor role in the overall deuteration
pathway for efficient C-deuteration.[10]
Scheme 1
quired to synthesise a series of related substituted enols,
enol acetates 12Ϫ17 and silyl enol ethers 18Ϫ23. These enol
derivatives were synthesised from the parent phenyl ketones
6Ϫ11, by either refluxing a solution of isopropenyl acetate[8]
in the presence of a catalytic amount of pTsOH to give the
enol acetates 12,[11] 13,[12] 14,[13] 15, 16[14] and 17, or by
deprotonation with lithium diisopropylamide (LDA), fol-
lowed by addition of chlorotrimethylsilane to give the re-
quired silyl enol ethers 18,[15] 19,[16] 20,[17] 21, 22[18] and
23[19] (Scheme 2).[10] It should be noted here that, for
sterically hindered ketones like cyclobutyl, cyclopentyl and
cyclohexyl phenyl ketones 9, 10 and 11, a competitive re-
duction involving β-hydride transfer (from the lithium di-
isopropylamide) occurs to give the silyl ethers 27, 28 and
Results and Discussion
We now report our investigation into the study of the 29 in low to moderate yield (Scheme 2, Entries 4Ϫ6). This
kinetic deuteration of acyclic and exocyclic enolates and type of competitive reduction using lithium diisopropylam-
comment on the acceptable substitution pattern for efficient ide as a hydride donor has been documented previously.[20]
regioselective C-deuteration. For this study, we were re-
We initially probed the deuteration of a series of acyclic
and exocyclic enolates derived from enol acetates 12Ϫ17 by
direct addition of MeLi (2 equiv.) to generate the lithium
tert-butoxide enolate complex. Slow addition of [D4]acetic
acid at Ϫ78 °C gave the deuterated ketones 6Ϫ11-d1 with
[a]
Department of Chemistry, Queen Mary, University of London,
Mile End Road, London E1 4NS, UK
Fax: (internat.) ϩ 44-(0)20/7882-7794, -5251
E-mail: j.eames@qmul.ac.uk
634
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0204Ϫ0634 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 634Ϫ641

Regioselective C-Deuteration of Acyclic and Exocyclic Enolates
FULL PAPER
minor deuteration pathway, which may be due to competit-
ive O-deuteration (to give the corresponding [D]enol) being
a more efficient pathway (Scheme 3, Entry 4). This at first
seems surprising, however, it has been documented that C-
proton transfer involving cyclobutyl phenyl ketone is more
favoured than that of cyclopentyl phenyl ketone under both
kinetic[22] and thermodynamic control due to the α-carbon
atom (at C-2) having intermediate sp2/sp3 hybridisation.[24]
Scheme 2
moderate to good D-incorporation (Scheme 3). The sim-
plest case involving the acyclic enolate of acetophenone 6
(derived from the enol acetate 12) gave the best level of D-
incorporation ([D]/[H] ϭ 89:11; 81% yield; Scheme 3, Entry
1). Structural variation of acetophenone 6 at the C-2 posi-
tion by incorporation of a methyl group (in propiophenone
7), two methyl groups (in isobutyrophenone 8) or a car-
bocyclic ring (in cyclobutyl, cyclopentyl and cyclohexyl
phenyl ketone 9, 10 and 11, respectively) lowered the level
of deuterium incorporation (Scheme 2, Entries 2Ϫ6). Pre-
sumably, this is in part due to the increased steric demand
[a]
[b]
Scheme 3. Isotopic [D1]/[D0] ratio. Chemical yield.
In an attempt to increase the level of deuterium incorp-
of a substituted enolate, promoting O-deuteration to give oration, we probed an alternative method for the removal
the corresponding [D]enol. Loss of this deuterium label has of the acetate motif by using a nucleophilic deuterium
been shown to occur in related cases through tautomeris- donor, the lithium alkoxide 31-d1. We had originally as-
ation under aqueous workup to give the more thermodyn- sumed that direct addition of lithium alkoxide 31-d1
amically stable unlabelled starting ketone.[10] This ‘‘enol ef- (formed by addition of MeLi to a stirred solution of ethane-
fect’’ has been shown to occur with sterically hindered enol- diol 30-d2 in THF) to the acetate 12 would give the required
ates.[21] The presence of an additional ring at the C-2 posi- deuterated ketone (e.g. 6-d1) and acetate 33aϩb by intramo-
tion is slightly more intriguing. The cyclohexyl enol acetate lecular deuterium transfer within the tetrahedral interme-
17 behaves similarly to its noncyclic analogue isobutyro- diate alkoxide 32-d1 (Scheme 4). However, using this meth-
phenone 14, whereas the smaller carbocyclic analogues odology gave a slight over-incorporation of deuterium for
cyclobutyl and cyclopentyl enol acetates 15 and 16 gave the enol acetates 12 and 13 (Scheme 5, Entries 1 and 2) and
slightly lower D-incorporation. It is not surprising that a moderate to low D-incorporation for the remaining substi-
cyclopentyl ketone 10 gave lower C-deuteration than its tuted enol acetates 14Ϫ16-d1 (Scheme 5, Entries 3Ϫ5). This
cyclohexyl homologue 11, since formation of an exocyclic excess D-incorporation in acetophenone must come from
enolate is known to be more kinetically[22] and thermo- subsequent deprotonation of the resulting monodeuterated
dynamically[23] favoured. However, for cyclobutyl phenyl product (e.g., 6-d1) with lithium alkoxide 31-d1 or 33aϩb
ketone it appears that regioselective C-deuteration is a followed by deuterium exchange involving the intermediate
Eur. J. Org. Chem. 2003, 634Ϫ641
635

J. Eames, G. S. Coumbarides, M. J. Suggate, N. Weerasooriya
FULL PAPER
ethane-1,2-diol 30-d1. Incomplete D-incorporation may il-
lustrate competitive deuterium exchange resulting in O-deu-
teration leading to the corresponding [D]enol, tautomeris-
ation of which upon aqueous workup would allow the D-
label to be exchanged and lost. This lack of D-incorpora-
tion presumably illustrates the rate difference between effici-
ent D-transfer involving an oxygen atom based deuteron
donor and acceptor to form the corresponding [D]enol and
the less-favoured D-transfer pathway involving an oxygen-
based deuteron donor and the carbon atom acceptor of an
enol in 32-d1.[25] For related proton transfer processes, it has
been shown that proton transfer between highly electroneg-
ative atoms, such as two oxygen atoms, is at least a thou-
sand times faster than that between an oxygen atom and a
carbon atom.[25]
Scheme 5. [a] Isotopic [D1]/[D2] ratio. [b] Chemical yield. [c] Isotopic
[D1]/[D0] ratio.
Scheme 4
We have also focused on the use of silyl enol ethers
18Ϫ23 as a precursor for generating ‘‘base-free’’ lithium en-
olates to probe the effect of lithium tert-butoxide as an ad-
ditive in these processes. This additive is generated in situ
as a by-product from the addition of 2 equiv. of MeLi to
the corresponding enol acetate (e.g. 4). Addition of MeLi
to a stirred solution of silyl enol ethers 18Ϫ23 in THF, fol-
lowed by addition of [D4]acetic acid at Ϫ78 °C, gave the
required deuterated ketones 6Ϫ11-d1 with excellent to mod-
erate D-incorporation (Scheme 6).
The acyclic silyl enol ethers 18, 19 and 20 [derived from
acetophenone (6), propiophenone (7) and isobutyro-
phenone (8), respectively] gave near perfect deuterium in-
corporation (Ͼ 95%) (Scheme 6, Entries 1Ϫ3). The levels
of D-incorporation were found to be slightly higher when
using a ‘‘base-free’’ enolate (derived from a silyl enol ether)
than with a ‘‘base’’ enolate (derived from an enol acetate)
as the enolate precursor (Schemes 3 and 6). This difference
presumably reflects the more Lewis acidic nature of the li-
thium counterion present in a ‘‘base-free’’ enolate than that
of a ‘‘base’’ enolate (due to the presence of lithium tert-
butoxide) which presumably assists efficient C-deuteration
Scheme 6. [a] Isotopic [D1]/[D0] ratio. [b] Chemical yield. [c] Isotopic
when using a (carbonyl-) directing deuterium source like [D1]/[D2] ratio.
636
Eur. J. Org. Chem. 2003, 634Ϫ641

Regioselective C-Deuteration of Acyclic and Exocyclic Enolates
FULL PAPER
[D4]acetic acid.[10] No over-incorporation of deuterium oc- terium atom within these ketones 6Ϫ11-d1: a) the presence
curs when using [D4]acetic acid due to the low basicity of of an infrared CϪD stretching frequency at approximately
the intermediate conjugate base, lithium acetate.
The exocyclic silyl enol ethers 21, 22 and 23 with a cyclo-
2100 cmϪ1 [26]
J
;
b) the presence of a CϪD triplet (1:1:1,
C,D ϭ 19.6 Hz) in the 13C NMR spectra, and c) a negative
alkane positioned at C-2 (synthesised from cyclobutyl, isotope shift for the CϪD bond (with respect to the analog-
cyclopentyl and cyclohexyl phenyl ketones 9, 10 and 11) ous CϪH bond) in the 13C NMR spectra between 0.25 and
gave significantly lower levels of C-deuteration (Scheme 6, 0.47 ppm (Scheme 7).[27]
Entries 4Ϫ6). The presence of a cycloalkane ring at the C-
2 position must promote regioselective O-deuteration to ac-
count for the loss of the deuterium label. Of these derivat-
ives, the smaller cyclobutane ring in 21 appears to favour
C-deuteration under ‘‘base-free’’conditions (Scheme 6,
Entry 4) more so than under ‘‘base’’ conditions (Scheme 3,
Entry 4). This increase in D-selectivity may be due to
tighter deuterium transfer (within the transition state) pro-
moted by the minimal re-hybridisation[24] at the C-2 posi-
tion.
Attempts at ensuring efficient C-deuteration using a
weakly D-acidic source, such as [D1]tert-butyl alcohol (to
disfavour O-deuteration), resulted in only moderate D-in-
corporation (Scheme 6). The structural nature and D-acid-
ity of the D-source is additionally important; [D4]acetic
acid was found to give better levels of single C-deuteration
than [D1]tert-butyl alcohol. Over-incorporation of deuter-
ium was shown to occur for the enolate derived from the
silyl enol ether 18 (to give the acetophenone 6-d1/6-d2 ϭ
86:14); this must occur by competitive deprotonation of 6-
d1 by the conjugate base (lithium tert-butoxide) and sub-
sequent re-deuteration with [D1]tert-butyl alcohol. The
presence of an exo-carbocyclic ring at the C-2 position in
9, 10 and 11 appears to be a dominant factor preventing
efficient C-deuteration. Nevertheless, it is still surprising
that thermodynamic D-tautomerisation does not appear to
Scheme 7
occur under these conditions to promote regioselective C-
deuteration and thus re-formation of the more favourable
exo-double bond.
Experimental Section
General Remarks: All solvents were distilled before use. Tetrahy-
drofuran (THF) and diethyl ether were freshly distilled from so-
dium wire. Benzophenone was used as the indicator for THF. All
Conclusion
In conclusion, we have reported the kinetic deuteration
of a series of related acyclic and exocyclic enolates and have
commented on the similarities and differences of using
‘‘base-free’’ and ‘‘base’’ enolates. We have concluded that
increasing substitution at the C-2 position decreases the
likelihood of efficient regioselective C-deuteration. The
presence of a ring at the C-2 position significantly lowers
the overall level of D-incorporation. This is due to in-
creased O-deuteration allowing competitive [D]enol forma-
tion. This unwanted pathway is presumably responsible for
the loss of deuterium incorporation during the workup pro-
cedure, due to thermodynamic tautomerisation giving the
unlabelled parent ketone.[21] The structural nature and D-
acidity of the D-source was also found to be important:
[D4]acetic acid gave better levels of single C-deuteration
than [D1]tert-butyl alcohol.
reactions were carried out under nitrogen using oven-dried glass-
ware. Flash column chromatography was carried out using Merck
Kieselgel 60 (230Ϫ400 mesh). Thin layer chromatography (TLC)
was carried out on commercially available pre-coated plates (Merck
Kieselgel 60F254 silica). Proton and carbon NMR spectra were re-
corded with a JEOL EX 270 and Bruker AM 250, AMX 400 and
AM 600 Fourier transform spectrometers (using an internal deuter-
ium lock). Chemical shifts are quoted in ppm downfield from tetra-
methylsilane. Carbon NMR spectra were recorded with broad pro-
ton decoupling. Infrared spectra were recorded with a Shimadzu
8300 FTIR machine and mass spectra were recorded with a Kratos
50MSTC machine using a DS503 data system for high-resolution
analysis. The levels of D-incorporation were determined by a com-
bination of mass, proton and carbon NMR spectra.
Acetophenone 6-d1: A solution of MeLi (0.43 mL, 1.6  in diethyl
ether, 0.68 mmol) was added dropwise to the enol acetate 12
(0.10 g, 0.62 mmol) at room temperature. This resulting solution
was stirred for 1 h at room temperature and then cooled to Ϫ78
During the course of this study, we have noticed a num-
ber of characteristic features due to the presence of a deu- °C. [D4]Acetic acid (80 mg, 70 µL, 1.24 mmol) in THF (1 mL) was
Eur. J. Org. Chem. 2003, 634Ϫ641 637

J. Eames, G. S. Coumbarides, M. J. Suggate, N. Weerasooriya
FULL PAPER
added dropwise to this solution and 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 ϫ 20 mL), dried
(MgSO4) and the solvents were evaporated under vacuum. The res-
diethyl ether (19:1), 7-d1 [29] (50 mg, 80%) as an oil identical to that
reported above.
2-Isobutyrophenone 8-d1: In the same way as acetophenone 6-d1,
enol acetate 14 (76 mg, 0.39 mmol), MeLi (0.27 mL, 1.6  in di-
ethyl ether, 0.43 mmol) and [D4]acetic acid (51 mg, 50 µL,
idue was purified by flash chromatography on silica gel eluting with
[28]
light petroleum ether/diethyl ether (19:1) to give 6-d1
(61 mg,
0.78 mmol) gave, after column chromatography on silica gel eluting
81%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
[30]
with light petroleum ether/diethyl ether (19:1), 8-d1
(35 mg,
1
9:1] ϭ 0.31. IR (film): ν˜max ϭ 2231 (CD), 1685 (CϭO) cmϪ1. H
60%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
NMR (250 MHz, CDCl3): δ ϭ 8.04 (d, J ϭ 8.2 Hz, 2 H, 2 ϫ CH,
Ar), 7.62Ϫ7.47 (m, 3 H, 3 ϫ CH, Ar), 2.62 (m, 2 H, CH2D) ppm.
13C NMR (67.5 MHz, CDCl3): δ ϭ 198.1, 137.1, 133.1, 128.5,
9:1] ϭ 0.45.IR (film): ν˜max ϭ 2210 (CD), 1618 (CϭO) cmϪ1 1H
.
NMR (250 MHz, CDCl3): δ ϭ 7.94 (d, J ϭ 8.4 Hz, 2 H, 2 ϫ CH,
Ar), 7.58Ϫ7.43 (m, 3 H, 3 ϫ CH, Ar), 1.25 (s, 6 H, 2 ϫ CH3) ppm.
13C NMR (67.5 MHz, CDCl3): δ ϭ 204.6, 136.3, 132.8, 128.6,
1
128.3, 26.3 [1 C, t (1:1:1), JCD ϭ 19.6, CDCO] ppm. The isotopic
shift was 0.44 ppm (24.5 Hz at 62.5 MHz). C8H8DO requires
122.0716; found [M ϩ H] 122.0710.
1
128.4, 35.3 [1 C, t (1:1:1), JCD ϭ 19.6, CDCO], 19.1 ppm. The
isotopic shift was 0.43 ppm (29.0 Hz at 67.5 MHz). C10H11DO re-
quires 149.0951; found M 149.0958.
A solution of MeLi (0.36 mL, 1.6  in diethyl ether, 0.57 mmol)
was added dropwise to the silyl enol ether 18 (0.10 g, 0.52 mmol)
at room temperature. This resulting solution was stirred for 1 h at
room temperature and then cooled to Ϫ78 °C. [D4]Acetic acid
(66 mg, 60 µL, 1.04 mmol) in THF (1 mL) was added dropwise to
this solution and stirred for a further 30 min. The reaction was
quenched by the addition of water (10 mL). The solution was ex-
tracted with diethyl ether (3 ϫ 20 mL), dried (MgSO4) and the
solvents were evaporated under vacuum. The residue was purified
In the same way as acetophenone 6-d1, silyl enol ether 20 (0.2 g,
0.91 mmol), MeLi (0.62 mL, 1.6  in diethyl ether, 0.99 mmol) and
[D4]acetic acid (0.12 g, 0.10 mL, 1.82 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
diethyl ether (19:1), 8-d1 [30] (83 mg, 62%) as an oil identical to that
reported above.
In the same way as acetophenone 6-d1, silyl enol ether 20 (0.20 g,
0.91 mmol), MeLi (0.62 mL, 1.6  in diethyl ether, 0.99 mmol) and
[D1]tert-butyl alcohol (0.14 g, 0.17 mL, 1.82 mmol) gave, after col-
by flash chromatography on silica gel eluting with light petroleum
[28]
ether (40Ϫ60 °C)/diethyl ether (19:1) to give 6-d1
(50 mg, 80%)
as an oil identical to that reported above.
umn chromatography on silica gel eluting with light petroleum
[30]
ether/diethyl ether (19:1), 8-d1
(83 mg, 62%) as an oil identical
A solution of MeLi (0.36 mL, 1.6  in diethyl ether, 0.57 mmol)
was added dropwise to the silyl enol ether 18 (0.10 g, 0.52 mmol)
at room temperature. This resulting solution was stirred for 1 h at
room temperature and then cooled to Ϫ78 °C. [D1]tert-Butyl alco-
hol (78 mg, 98 µL, 1.04 mmol) in THF (1 mL) was added dropwise
to this solution and stirred for a further 30 min. The reaction was
quenched by the addition of water (10 mL). The solution was ex-
tracted with diethyl ether (3 ϫ 20 mL), dried (MgSO4) and the
solvents were evaporated under vacuum. The residue was purified
to that reported above.
Cyclobutyl Phenyl Ketone 9-d1: In the same way as acetophenone
6-d1, enol acetate 15 (0.10 g, 0.62 mmol), MeLi (0.42 mL, 1.6  in
diethyl ether, 0.68 mmol) and [D4]acetic acid (87 mg, 80 µL,
1.36 mmol) gave, after column chromatography on silica gel eluting
[31]
with light petroleum ether/diethyl ether (19:1), 9-d1
(65 mg,
65%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
9:1] ϭ 0.49.IR (film): ν˜max ϭ 2209 (CD), 1682 (CO) cmϪ1 1H
.
by flash chromatography on silica gel eluting with light petroleum
NMR (250 MHz, CDCl3): δ ϭ 7.87 (d, J ϭ 7.2 Hz, 2 H, 2 ϫ CH,
Ar), 7.51Ϫ7.39 (m, 3 H, 3 ϫ CH, Ar), 2.41Ϫ2.23 (m, 4 H, 2 ϫ
CH2), 2.10Ϫ2.04 (m, 1 H, CHAHB), 1.91Ϫ1.87 (m, 1 H, CHAHB)
ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 201.1, 135.7, 132.9, 128.6,
[28]
ether (40Ϫ60 °C)/diethyl ether (19:1) to give 6-d1/6-d2
(49 mg,
72%) as an oil identical to that reported above.
Propiophenone 7-d1: In the same way as acetophenone 6-d1, enol
acetate 3 (55 mg, 0.32 mmol), MeLi (0.22 mL, 1.6  in diethyl
ether, 0.35 mmol) and [D4]acetic acid (44 mg, 40 µL, 0.64 mmol)
1
128.4, 41.9 [1 C, t (1:1:1), JCD ϭ 19.6. CDCO], 25.1, 18.3 ppm.
The isotopic shift was 0.29 ppm (28.9 Hz at 100 MHz). C11H11DO,
requires 161.0903; found [Mϩ] 161.0898.
gave, after column chromatography on silica gel eluting with light
[29]
petroleum ether/diethyl ether (19:1), 7-d1
(29 mg, 68%) as an
In the same way as acetophenone 6-d1, silyl enol ether 21 (0.10 g,
0.49 mmol), MeLi (0.3 mL, 1.6  in diethyl ether, 0.54 mmol) and
[D4]acetic acid (63 mg, 60 µL, 0.98 mmol) gave, after column chro-
oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether, 9:1] ϭ
0.40.IR (film): ν˜max ϭ 2241 (CD), 1687 (CϭO) cmϪ1 1H NMR
.
(250 MHz, CDCl3): δ ϭ 7.98 (d, J ϭ 8.2 Hz, 2 H, 2 ϫ CH, Ar),
7.58Ϫ7.42 (m, 3 H, 3 ϫ CH, Ar), 3.05Ϫ3.00 (m, 1 H, CHD), 1.25
matography on silica gel eluting with light petroleum ether/diethyl
[31]
(d, J ϭ 7.2 Hz, 3 H, CH3) ppm. 13C NMR (67.5 MHz, CDCl3):
ether (19:1), 9-d1
(50 mg, 72%) as an oil identical to that re-
1
ported above.
δ ϭ 201.5, 137.6, 133.5, 129.2, 128.6, 32.1 [1 C, t (1:1:1), JCD
ϭ
19.6, CDCO]. The isotopic shift was 0.25 ppm (25.9 Hz at
100 MHz). C9H10DO requires 136.0873; found [M ϩ H] 136.0867.
In the same way as acetophenone 6-d1, silyl enol ether 21 (0.10 g,
0.49 mmol), MeLi (0.3 mL, 1.6  in diethyl ether, 0.54 mmol) and
[D1]tert-butyl alcohol (73 mg, 92 µL, 0.98 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
diethyl ether (19:1), 9-d1 [31] (50 mg, 72%) as an oil identical to that
reported above.
In the same way as acetophenone 6-d1, silyl enol ether 19 (0.10 g,
0.48 mmol), MeLi (0.33 mL, 1.6  in diethyl ether, 0.53 mmol) and
[D4]acetic acid (31 mg, 30 µL, 0.96 mmol) gave, after column chro-
matography on silica gel eluting with light petroleum ether/diethyl
[29]
ether (19:1), 7-d1
(50 mg, 80%) as an oil identical to that re-
Cyclopentyl Phenyl Ketone 10-d1: In the same way as acetophenone
6-d1, enol acetate 16 (0.10 g, 0.45 mmol), MeLi (0.28 mL, 1.6  in
diethyl ether, 0.45 mmol) and [D4]acetic acid (52 mg, 50 µL,
ported above.
In the same way as acetophenone 6-d1, silyl enol ether 19 (0.10 g,
0.48 mmol), MeLi (0.33 mL, 1.6  in diethyl ether, 0.53 mmol) and
[D1]tert-butyl alcohol (72 mg, 90 µL, 0.96 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
0.81 mmol) gave, after column chromatography on silica gel eluting
[32]
with light petroleum ether/diethyl ether (19:1), 10-d1
(54 mg,
76%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
638
Eur. J. Org. Chem. 2003, 634Ϫ641

Regioselective C-Deuteration of Acyclic and Exocyclic Enolates
9:1] ϭ 0.47.IR (film): ν˜max ϭ 2119 (CD), 1679 (CO) cmϪ1
FULL PAPER
1H CHAHB), 2.26 (s, 3 H, CH3) ppm. 13C NMR (62.5 MHz, CDCl3):
.
NMR (250 MHz, CDCl3): δ ϭ 8.04 (d, J ϭ 8.1 Hz, 2 H, 2 ϫ CH, δ ϭ 169.0, 152.9, 133.4, 130.4, 128.9, 124.8, 102.1, 20.9 ppm.
Ar), 7.63Ϫ7.32 (m, 3 H, 2 ϫ CH, Ar), 2.02Ϫ1.91 (m, 4 H, 2 ϫ C10H10O2 requires 162.0573; found [MHϩ] 162.0572.
CH2), 1.89Ϫ1.61 (m, 4 H, 2 ϫ CH2) ppm. 13C NMR (67.5 MHz,
1-Phenylprop-1-enyl Acetate (13): In the same way as enol acetate
CDCl3): δ ϭ 202.8, 137.0, 132.7, 128.5, 128.4, 45.9 [1 C, t (1:1:1),
12, propiophenone (7) (1.00 g, 7.45 mmol, 0.99 mL), isopropenyl
1JCD ϭ 21.1, CDCO], 29.9, 26.3 ppm. The isotopic shift was
acetate (32 mL, 0.29 mol) and p-toluenesulfonic acid (0.14 g,
0.26 ppm (25.9 Hz at 100 MHz). C12H13DO, requires 175.1107;
0.73 mmol) gave, after column chromatography on silica gel eluting
found [M] 175.1115.
with light petroleum ether/diethyl ether (19:1) 13[12] (0.81 g, 62%)
as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether, 9:1] ϭ
In the same way as acetophenone 6-d1, silyl enol ether 22 (0.10 g,
0.41 mmol), MeLi (0.30 mL, 1.6  in diethyl ether, 0.45 mmol) and
[D4]acetic acid (53 mg, 50 µL, 0.82 mmol) gave, after column chro-
1
0.43. IR (film): ν˜max ϭ 1712 (CϭO), 1687 (CϭC) cmϪ1. H NMR
(250 MHz, CDCl3): δ ϭ 7.42Ϫ7.28 (m, 5 H, 5 ϫ CH; Ar), 5.91 (q,
J ϭ 7.1 Hz, 1 H, CH), 2.32 (s, 3 H, CH3), 1.72 (d, J ϭ 7.2 Hz, 3
H, CH3) ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 167.2, 146.4,
134.6, 128.8, 127.6, 126.0, 95.5, 17.9, 6.5 ppm. C11H12O2 requires
176.0837; found [Mϩ] 176.0829.
matography on silica gel eluting with light petroleum ether/diethyl
[32]
ether (19:1), 10-d1
(59 mg, 59%) as an oil identical to that re-
ported above.
In the same way as acetophenone 6-d1, silyl enol ether 22 (0.10 g,
0.41 mmol), MeLi (0.30 mL, 1.6  in diethyl ether, 0.45 mmol) and
[D1]tert-butyl alcohol (61 mg, 76 µL, 0.82 mmol) gave, after column
2-Methyl-1-phenylprop-1-enyl Acetate (14): In the same way as enol
acetate 12, isobutyrophenone (8) (2.00 g, 13.5 mmol, 2.0 mL), iso-
propenyl acetate (58 mL, 0.53 mol) and p-toluenesulfonic acid
(0.24 g, 1.26 mmol) gave, after column chromatography on silica
gel eluting with light petroleum ether/diethyl ether (19:1), 14[13]
(1.43 g, 56%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/di-
ethyl ether, 9:1] ϭ 0.55. IR (film): ν˜max ϭ 1716 (CϭO), 1600 (Cϭ
chromatography on silica gel eluting with light petroleum ether/
[32]
diethyl ether (19:1), 10-d1
(59 mg, 59%) as an oil identical to
that reported above.
Cyclohexyl Phenyl Ketone 11-d1: In the same way as acetophenone
6-d1, enol acetate 17 (50 mg, 0.21 mmol), MeLi (0.15 mL, 1.6  in
diethyl ether, 0.24 mmol) and [D4]acetic acid (28 mg, 30 µL,
1
C) cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ 7.71Ϫ7.24 (m, 5 H, 5
ϫ CH, Ar), 2.13 (s, 3 H, CH3), 1.79 (s, 3 H, CH3), 1.76 (s, 3 H,
CH3) ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 169.2, 141.3, 135.9,
128.9, 128.0, 127.8, 121.9, 20.7 19.8, 18.3 ppm. C12H14O2 requires
190.0994; found [Mϩ] 190.0989.
0.43 mmol) gave, after column chromatography on silica gel eluting
[33]
with light petroleum ether/diethyl ether (19:1), 11-d1
(28 mg,
67%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
9:1] ϭ 0.42.IR (film): ν˜max ϭ 2201 (CD), 1678 (CO) cmϪ1 1H
.
Cyclobutylidene(phenyl)methyl Acetate (15): In the same way as
enol acetate 12, cyclobutyl phenyl ketone (9) (1.00 g, 6.25 mmol),
isopropenyl acetate (35 mL, 0.318 mol) and p-toluenesulfonic acid
(0.14 g, 0.74 mmol) gave, after column chromatography on silica
gel eluting with light petroleum ether/diethyl ether (19:1), 15
(0.78 g, 62%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/di-
ethyl ether, 9:1] ϭ 0.68. IR (film): ν˜max ϭ 1681 (CϭO), 1596 (Cϭ
NMR (250 MHz, CDCl3): δ ϭ 8.0 (d, J ϭ 7.8 Hz, 2 H, 2 ϫ CH,
Ar), 7.61Ϫ7.39 (m, 3 H, 3 ϫ CH, Ar), 1.98Ϫ1.64 (m, 5 H, 2 ϫ
CH2, CHAHB), 1.61Ϫ1.23 (m, 5 H, 2 ϫ CH2, CHAHB) ppm. 13C
NMR (67.5 MHz, CDCl3): δ ϭ 204.5, 137.1, 133.4, 129.2, 128.9,
45.8 [1 C, t (1:1:1), JCD ϭ 19.5, CDCO], 30.0, 26.5 ppm. The
isotopic shift was 0.48 ppm (32.3 Hz at 67.5 MHz). C13H15DO, re-
quires 189.1264; found [M] 189.1258.
1
1
C) cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ 7.39Ϫ7.17 (m, 5 H, 5
In the same way as acetophenone 6-d1, silyl enol ether 23 (0.10 g,
0.39 mmol), MeLi (0.27 mL, 1.6  in diethyl ether, 0.43 mmol) and
[D4]acetic acid (50 mg, 40 µL, 0.78 mmol) gave, after column chro-
ϫ CH, Ar), 3.18 (t, J ϭ 7.6 Hz, 2 H, CH2), 2.81 (t, J ϭ 7.6 Hz, 2
H, CH2), 2.23 (s, 3 H, CH3), 2.12 (q, J ϭ 7.6 Hz, 2 H, CH2) ppm.
13C NMR (62.5 MHz, CDCl3): δ ϭ 168.7, 138.6, 131.8, 128.4,
127.2, 124.9, 118.2, 30.5, 28.9, 20.6, 17.7 ppm. C13H14O2 requires
202.0994; found [Mϩ] 202.0988.
matography on silica gel eluting with light petroleum ether/diethyl
[33]
ether (19:1), 11-d1
(45 mg, 64%) as an oil identical to that re-
ported above.
Cyclopentylidene(phenyl)methyl Acetate (16): In the same way as
enol acetate 12, cyclopentyl phenyl ketone (10) (1.00 g, 5.74 mmol),
isopropenyl acetate (32.0 mL, 0.29 mol) and p-toluenesulfonic acid
(0.13 g, 0.68 mmol) gave, after column chromatography on silica
gel eluting with light petroleum ether/diethyl ether (19:1), 16[14]
(0.72 g, 58%) as an oil. RF [light petroleum ether (40Ϫ60 °C)/di-
ethyl ether, 9:1] ϭ 0.65. IR (film): ν˜max ϭ 1679 (CϭO), 1596 (Cϭ
In the same way as acetophenone 6-d1, silyl enol ether 23 (0.10 g,
0.39 mmol), MeLi (0.27 mL, 1.6  in diethyl ether, 0.43 mmol) and
[D1]tert-butyl alcohol (58 mg, 73 µL, 0.78 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
[33]
diethyl ether (19:1), 11-d1
(45 mg, 64%) as an oil identical to
that reported above.
1
C) cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ 7.40Ϫ7.23 (m, 5 H, 5
1-Phenylvinyl Acetate (12): Acetophenone (6) (2.00 g, 1.9 mL,
17.0 mmol) and p-toluenesulfonic acid (0.30 g, 1.57 mmol) were ad-
ded to neat isopropenyl acetate (72 mL, 0.54 mol). The resulting
solution was refluxed at 110 °C for 12 h. The solution was cooled
to room temperature and extracted with diethyl ether (2 ϫ 100
mL). This solution was washed with water (3 ϫ 50 mL) and the
solvents were evaporated under reduced pressure to give a dark
orange oily residue. This residue was purified by flash column chro-
matography eluting with light petroleum ether/diethyl ether (19:1)
ϫ CH, Ar), 2.55 (t, J ϭ 7.1 Hz, 2 H, CH2), 2.38 (t, J ϭ 7.1 Hz, 2
H, CH2), 2.19 (s, 3 H, CH3), 1.76Ϫ1.68 (m, 4 H, 2 ϫ CH2) ppm.
13C NMR (62.5 MHz, CDCl3): δ ϭ 169.2, 138.2, 134.2, 128.5,
128.1, 127.4, 126.7, 31.9, 31.4, 27.6, 25.7, 20.8 9 ppm. C14H16O2
requires 216.1145; found [Mϩ] 216.1140.
Cyclohexylidene(phenyl)methyl Acetate (17): In the same way as
enol acetate 12, cyclohexyl phenyl ketone (11) (0.50 g, 2.66 mmol),
isopropenyl acetate (11.4 mL, 0.10 mol) and p-toluenesulfonic acid
to give 12[11] (2.70 g, 78%) as an oil; RF [light petroleum ether (50 mg, 0.26 mmol) gave, after column chromatography on silica
(40Ϫ60 °C)/diethyl ether, 9:1] ϭ 0.38. IR (film): ν˜max ϭ 1685 (Cϭ
gel eluting with light petroleum ether/diethyl ether (19:1), 17
O), 1598 (CϭC) cmϪ1
.
1H NMR (250 MHz, CDCl3): δ ϭ (0.31 g, 51%) as an oil. RF [light petroleum ether (40Ϫ60 °C)/di-
7.49Ϫ7.44 (m, 2 H, 2 ϫ CH, Ar), 7.38Ϫ7.29 (m, 3 H, 3 ϫ CH, ethyl ether, 9:1] ϭ 0.58. IR (film): ν˜max ϭ 1678 (CϭO), 1596 (Cϭ
Ar), 5.50 (d, J ϭ 2.4 Hz, 1 H, CHAHB), 5.05 (d, J ϭ 2.4 Hz, 1 H, C) cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ 7.36Ϫ7.16 (m, 5 H, 5
1
Eur. J. Org. Chem. 2003, 634Ϫ641
639

J. Eames, G. S. Coumbarides, M. J. Suggate, N. Weerasooriya
FULL PAPER
ϫ CH, Ar), 2.24Ϫ2.19 (m, 5 H, 2 ϫ CH2, CHAHB), 2.17 (s, 3 H,
CH), 2.69Ϫ2.52 (m, 1 H, CHCH2), 2.15Ϫ1.69 (m, 6 H, 3 ϫ CH2),
CH3), 1.68Ϫ1.51 (m, 5 H, 2 ϫ CH2, CHAHB) ppm. 13C NMR (62.5 0.40 [s, 9 H, Si(CH3)3]. 13C NMR (67.5 MHz, CDCl3): δ ϭ 143.0,
MHz, CDCl3): δ ϭ 169.5, 135.8, 129.3, 129.1, 128.5, 128.3, 128.1, 128.4, 127.6, 126.3, 78.3, 42.6, 25.0, 24.5, 17.8, 1.3 ppm.
125.6, 29.8, 28.4, 27.7, 27.2, 26.5, 20.9 ppm. C15H18O2 requires
[Cyclopentylidene(phenyl)methoxy]trimethylsilane (22): In the same
way as silyl enol ether 18, cyclopentyl phenyl ketone (10) (1.00 g,
230.1413; found [Mϩ] 230.1409.
5.74 mmol), LDA (4.2 mL, 1.5  in THF, 6.31 mmol) and chloro-
trimethylsilane (0.69 g, 0.80 mL, 6.31 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
diethyl ether (19:1), 22 (0.71 g, 50%) as an oil and 28[34,35] (0.14 g,
10%) as an oil. 22: RF [light petroleum ether (40Ϫ60 °C)/diethyl
(β-Styryloxy)trimethylsilane (18): Acetophenone (6) (1.00 g,
8.32 mmol) was slowly added dropwise to a stirred solution of LDA
(6.1 mL, 1.5  in THF, 9.16 mmol) in THF (50 mL) at Ϫ78 °C
and stirred for 20 min. Me3SiCl (0.99 g, 1.2 mL, 9.16 mmol) was
added and this solution was stirred for 3 h. A solution of NH4Cl
(50 mL) was added and the mixture was extracted with diethyl ether
(3 ϫ 50 mL). The combined organic layers were dried (MgSO4)
and the solvents evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel eluting
with light petroleum ether/diethyl ether (19:1) to give 18[15] (1.34 g,
84%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
1
ether, 9:1] ϭ 0.92. IR (film): ν˜max ϭ 1639 (CϭC) cmϪ1. H NMR
(250 MHz, CDCl3): δ ϭ 7.69Ϫ7.05 (m, 5 H, 5 ϫ CH, Ar),
2.59Ϫ2.38 (m, 4 H, 2 ϫ CH2), 2.02Ϫ1.56 (m, 4 H, 2 ϫ CH2), 0.06
[s, 9 H, Si(CH3)3] ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 140.9,
139.7, 127.6, 126.8, 125.9, 109.2, 31.1, 30.4, 27.7, 25.9, 0.7 ppm.
C15H22OSi requires 246.1440; found [Mϩ] 246.1432. 28: RF [light
petroleum ether (40Ϫ60 °C)/diethyl ether, 9:1] ϭ 0.93. 1H NMR
(250 MHz, CDCl3): δ ϭ 7.38Ϫ7.25 (m, 5 H, 5 ϫ CH, Ar), 4.62 (d,
J ϭ 8.4 Hz, 1 H, CH), 2.37Ϫ2.18 (m, 1 H, CHCH2), 2.18Ϫ1.91
(m, 4 H, 2 ϫ CH2) 1.88Ϫ1.65 (m, 4 H, 2 ϫ CH2), 0.20 [s, 9 H,
Si(CH3)3] ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 144.6, 128.4,
127.6, 126.6, 79.2, 47.7, 29.6, 29.5, 25.6, 25.5, 1.4 ppm.
1
9:1] ϭ 0.71. IR (film): ν˜max ϭ 1627 (CϭC). H NMR (250 MHz,
CDCl3): δ ϭ 7.65Ϫ7.58 (m, 2 H, 2 ϫ CH, Ar), 7.37Ϫ7.21 (m, 3
H, 3 ϫ CH, Ar), 4.91 (d, J ϭ 1.6 Hz, 1 H, CHAHB), 4.42 (d, J ϭ
1.6 Hz, 1 H, CHAHB), 0.24 [s, 9 H, Si(CH3)3] ppm. 13C NMR (62.5
MHz, CDCl3): δ ϭ 159.1, 134.1, 128.5, 127.5, 126.0, 90.2, 0.18
ppm. C11H16OSi requires 192.0859; found [MHϩ] 192.0863.
[Cyclohexylidene(phenyl)methoxy]trimethylsilane (23): In the same
way as silyl enol ether 18, cyclohexyl phenyl ketone (11) (1.00 g,
5.31 mmol), LiHMDS (5.8 mL, 1.0  in THF, 5.84 mmol) and
chlorotrimethylsilane (0.63 g, 0.74 mL, 5.84 mmol) gave, after col-
umn chromatography on silica gel eluting with light petroleum
ether/diethyl ether (19:1), 23 (0.98 g, 68%) as an oil and 29[34,35]
(0.35 g, 25%) as an oil. 23: RF [light petroleum ether (40Ϫ60 °C)/
diethyl ether, 9:1] ϭ 0.90. IR (film): ν˜max ϭ 1647 (CϭC). 1H NMR
(250 MHz, CDCl3): δ ϭ 7.29Ϫ7.21 (m, 5 H, 5 ϫ CH, Ar),
2.31Ϫ2.29 (m, 2 H, CH2), 2.12Ϫ2.08 (m, 2 H, CH2), 1.57Ϫ1.45
(m, 6 H, 3 ϫ CH2), 0.20 [s, 9 H, Si(CH3)3] ppm. 13C NMR (62.5
MHz, CDCl3): δ ϭ 148.9, 136.7, 128.9, 127.7, 126.4, 113.1, 32.9,
30.9, 28.9, 1.2 ppm. C16H24OSi requires 260.1712; found [Mϩ]
260.1708. 29: RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
9:1] ϭ 0.91. 1H NMR (250 MHz, CDCl3): δ ϭ 7.38Ϫ7.18 (m, 5 H,
5 ϫ CH, Ar), 4.45 (d, J ϭ 7.1 Hz, 1 H, CH), 3.35Ϫ3.13 (m, 1 H,
CHCH2), 1.98Ϫ1.18 (m, 10 H, 5 ϫ CH2), 0.20 [s, 9 H, Si(CH3)3].
13C NMR (67.5 MHz, CDCl3): δ ϭ 139.4, 137.1, 128.3, 125.7, 78.2,
39.2, 27.1 25.2, 1.3 ppm.
(1-Phenylprop-1-enyloxy)trimethylsilane (19): In the same way as si-
lyl enol ether 18, propiophenone 7 (1.00 g, 7.45 mmol), LDA (5.5
mL, 1.5  in THF, 8.19 mmol) and chlorotrimethylsilane (0.89 g,
1.0 mL, 8.19 mmol) gave, after column chromatography on silica
gel eluting with light petroleum ether/diethyl ether (19:1), 19[16]
(1.00 g, 65%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/di-
ethyl ether, 9:1] ϭ 0.73. IR (film): ν˜max ϭ 1686 (CϭC).1H NMR
(250 MHz, CDCl3): δ ϭ 7.46Ϫ7.41 (m, 2 H, 2 ϫ CH; Ar),
7.30Ϫ7.15 (m, 3 H, 3 ϫ CH; Ar), 5.30 (q, J ϭ 6.9 Hz, 1 H, CH),
1.74 (d, J ϭ 7.1 Hz, 3 H, CH3), 0.12 [s, 9 H, Si(CH3)3]. 13C NMR
(62.5 MHz, CDCl3): δ ϭ 156.3, 137.0, 133.6, 128.9, 127.9, 88.2,
8.2, 0.12. C12H19OSi requires 206.1127; found [MHϩ] 206.1135.
(2-Methyl-1-phenylprop-1-enyloxy)trimethylsilane (20): In the same
way as silyl enol ether 18, isobutyrophenone (8) (1.00 g,
6.75 mmol), LDA (5.0 mL, 1.5  in THF, 7.42 mmol) and chloro-
trimethylsilane (0.81 g, 0.94 mL, 7.42 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
diethyl ether (19:1), 20[17] (0.78 g, 45%) as an oil; RF [light petro-
leum ether (40Ϫ60 °C)/diethyl ether, 9:1] ϭ 0.93. IR (film): ν˜max ϭ
1673 (CϭC) ppm. 1HNMR (250 MHz, CDCl3): δ ϭ 7.32Ϫ7.22 (m,
5 H, 5 ϫ CH, Ar), 1.79 (s, 3 H, CH3), 1.69 (s, 3 H, CH3), 0.10 [s,
9 H, Si(CH3)3] ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 143.6,
139.1, 129.2, 127.6, 127.0, 112.8, 19.7, 18.2, 0.32 ppm. C13H21OSi
requires 221.1362; found [MHϩ] 221.1370.
Acknowledgments
We thank the EPSRC, the Faculty of Natural Science at Queen
Mary, University of London, London University Central Research
Fund, The Nuffield Foundation, The Royal Society and GOSS Sci-
entific Instruments Ltd for their generous support.
[Cyclobutylidene(phenyl)methoxy]trimethylsilane (21): In the same
way as silyl enol ether 18, cyclobutyl phenyl ketone (9) (0.50 g,
3.12 mmol), LDA (2.3 mL, 1.5  in THF, 3.43 mmol) and chloro-
trimethylsilane (0.37 g, 0.44 mL, 3.43 mmol) gave, after column
chromatography on silica gel eluting with light petroleum ether/
diethyl ether (19:1), 21 (0.36 g, 49%) as an oil; RF [light petroleum
ether (40Ϫ60 °C)/diethyl ether, 9:1] ϭ 0.85; and 27[34,35] (51 mg,
7%) as an oil; RF [light petroleum ether (40Ϫ60 °C)/diethyl ether,
9:1] ϭ 0.88. 21: IR (film): ν˜max ϭ 1627 (CϭC).1H NMR (250 MHz,
CDCl3): δ ϭ 7.27Ϫ7.03 (m, 5 H, 5 ϫ CH, Ar), 2.87Ϫ2.79 (m, 2
H, CH2), 2.74Ϫ2.67 (m, 2 H, CH2), 1.97Ϫ1.84 (m, 2 H, CH2), 0.04
[s, 9 H, Si(CH3)3]. 13C NMR (62.5 MHz, CDCl3): δ ϭ 140.7, 137.8,
127.9, 126.6, 125.7, 123.2, 31.1, 29.7, 18.2, 0.6. C14H20OSi requires
[1]
J. Currie, J. H. Bowie, K. M. Downard, J. C. Sheldon, J. Chem.
Soc., Perkin Trans. 2 1989, 1973; J. A. Deyrup, M. F. Betkouski,
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S. A. Galton, R. Abbas, J. Org. Chem. 1973, 38, 1973; V. I.
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3683.
R. W. Murray, D. L. Shiang, M. Singh, J. Org. Chem. 1991,
[3]
1
232.1170; found [Mϩ] 232.1164. 27: H NMR (250 MHz, CDCl3):
56, 3677; L. Crombie, R. V. Dove, J. Chem. Soc., Perkin Trans.
1 1996, 1695.
δ ϭ 7.39Ϫ7.25 (m, 5 H, 5 ϫ CH, Ar), 4.58 (d, J ϭ 8.1 Hz, 1 H,
640
Eur. J. Org. Chem. 2003, 634Ϫ641

Regioselective C-Deuteration of Acyclic and Exocyclic Enolates
FULL PAPER
[4] [4a]
P. E. Pfeffer, L. S. Silbert, J. M. Chrinko, Jr., J. Org. Chem.
Oxford Chemistry Primer Number 6, Oxford University Press,
Oxford, 2000, p. 67.
[21]
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[4c]
E. Vedejs, A.
V. R. Bodepudi, W. J. le Noble, J. Org. Chem. 1994, 59, 3265.
W. Kruger, N. Lee, S. T. Sakata, M. Stec, E. Suna, J. Am.
Chem. Soc. 2000, 122, 4602.
P. E. Pfeffer, L. S. Silbert, J. M, Chrinko, Jr, J. Org. Chem.
1972, 37, 451.
T. Laube, J. D. Dunitz, D. Seebach, Helv. Chim. Acta 1985,
68, 1373.
[22] [22a] W. D. Emmons, M. F. Hawthorne, J. Am. Chem. Soc. 1956,
[22b]
78, 5593.
H. Schechter, M. J. Cullis, R. E. Dessy, Y. Oku-
zumi, A. Chen, J. Am. Chem. Soc. 1962, 84, 2905.
[5]
[6]
[23]
For cyclobutyl phenyl ketone (9), pKa (carbonyl CH) ϭ 24.9
(in DMSO); cyclopentyl phenyl ketone (10), pKa (carbonyl
CH) ϭ 25.8 (in DMSO) and cyclohexyl phenyl ketone (11),
pKa (carbonyl CH) ϭ 26.4 (in DMSO). Further information
can be found at http://www.chem.wisc.edu/areas/reich/pkat-
able/index.htm (leading reference see: F. G. Bordwell, Acc.
Chem. Res. 1988, 21, 456).
D. J. Cram in Fundamentals of Carbanion Chemistry, Academic
Press, London, 1965, chapter 2, p. 47.
M. Eigen, Angew. Chem. Int. Ed. Engl. 1964, 3, 1.
H. O. House, V. Kramar, J. Org. Chem. 1963, 28, 3362.
S. Berger, D. W. K. Diehl, J. Am. Chem. Soc. 1989, 111, 1240.
Authentic samples of these silyl ether derivatives were syn-
thesised by reduction of the corresponding ketones 9, 10 and
11 with NaBH4 in EtOH [to give the corresponding secondary
alcohol 1-cyclobutyl-1-phenylethanol (69%), 1-cyclopentyl-1-
phenylethanol (72%) and 1-cyclohexyl-1-phenylethanol (56%)],
followed by silylation (Me3SiCl and Et3N in CH2Cl2) to give
27, 28 and 29 in 57, 62 and 55% yield, respectively.
[7] [7a]
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