Investigations into the C-deuteriation of enol acetates derived from aryl alkyl ketones

Article abstract of DOI:10.1002/jlcr.928

Results are reported on the regioselective C-deuteriation of a series of enol acetates (derived from the aryl alkyl ketones) using molecular deuterium as the D-source and palladium-on-barium sulphate as the mediator. The results presented highlight potent

Full text of DOI:10.1002/jlcr.928

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS
J Label Compd Radiopharm 2005; 48: 337–352.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.928
Research Article
Investigations into the C-deuteriation of enol acetates
derived from aryl alkyl ketones
Svitlana Buksha, Gregory S. Coumbarides, Marco Dingjan, Jason Eames*,
Michael J. Suggate and Neluka Weerasooriya
Department of Chemistry, Queen Mary, University of London, Mile End Road, London
E1 4NS, UK
Summary
Results are reported on the regioselective C-deuteriation of a series of enol acetates
(derived from the aryl alkyl ketones) using molecular deuterium as the D-source and
palladium-on-barium sulphate as the mediator. The results presented highlight
potential problems associated with the deuteriation of enol acetates. Copyright #
2005 John Wiley & Sons, Ltd.
Key Words: deuteriation; deuterium; enol acetates; hydrogenation; palladium and
reduction
Introduction
The use of molecular deuterium as a source of deuterium for selective metal-
mediated deuteriation is very well documented.1 These processes have been
shown to be predictable giving good to excellent levels of deuterium
incorporation.2 Metal-mediated reduction of symmetrical and non-symme-
trical carbon–carbon double bonds using molecular deuterium as the D-source
is well known.3 However, for activated enol equivalents,4 such as enol acetates
and silyl enol ethers, these processes are much less documented. Nakai has
reported the enantioselective protonation and deuteriation of the silyl enol
ether 1 using a chiral palladium (II) catalyst, (R)-3, to give access to the
enantiomerically enriched 2-methyltetralones (R)-2 and (R)-[D1]-2, respec-
tively (Scheme 1).5 However, the associated level of deuterium incorporation
at the C(2) position of 2-methyltetralone (R)-[D1]-2 was less than that expected
for the level of enantiomeric excess. This evidently indicated that some
background hydrogen atom transfer was partially responsible for lowering the
*Correspondence to: J. Eames, Department of Chemistry, Queen Mary, University of London, Mile End
Road, London E1 4NS, UK. E-mail: j.eames@qmul.ac.uk
Copyright # 2005 John Wiley & Sons, Ltd.
Received 9 October 2004
Revised 8 December 2004
Accepted 15 December 2004

338
S. BUKSHA ET AL.
PPh2
PPh2
H
H
O
OSiMe3
CH3
(R)-3
H
Me
{PdCl2[(R)-binap]} (5% mol)
AgOTf (5% mol), i-Pr2NH
DMF/H2O
(R)-2; 79% e.e.; 83%
1
O
D
Me
{PdCl2[(R)-binap]} (5% mol)
AgOTf (5% mol), i-Pr2NH
DMF/D2O
(R)-[D1]-2; (80% D); 80% e.e.; 79%
Scheme 1.
level of deuterium incorporation and potential enantiomeric excess. By
comparison, hydrogenation of the related enol acetate 4 (derived from
tetralone) using an achiral rhodium (I) catalyst has been shown to give the
reduced acetate 5 in good yield without loss of the acetate motif (Scheme 2).6
This reduction is clearly an alternative process to ketone formation.
OAc
OAc
[Rh(cod)2BF4]
H2 (g)
4
5; 58%
Scheme 2.
We now wish to report our study into the regioselective deuteriation of enol
acetates derived from aryl alkyl ketones. We comment on factors such as the
acceptable structural nature and substitution pattern for efficient deuteriation,
and discuss the role they play towards regioselective C-deuteriation.
Results and discussion
For this study, we were required to synthesize a series of related substituted
enol acetates 4, 6, 9, 11, 13 and 15 (Scheme 3). These enol derivatives were
synthesized from the parent phenyl ketones 2, 7, 8, 10, 12 and 14, either by
refluxing a solution of isopropenyl acetate7 in the presence of a catalytic
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INVESTIGATIONS INTO THE C-DEUTERIATION
339
Enol
Enol
Ketone
O
Yield
81%
Yield
Ketone
O
Acetate
Acetate
OAc
OAc
Me
Me
80%
MeO
MeO
6
2
10
11
OAc
O
O
OAc
90%
83%
13
7
12
4
O
OAc
O
AcO
83%
82%
OMe
OMe
14
15
8
9
Scheme 3.
amount of p-TsOH or by addition of perchloric acid to a stirred solution of
acetic anhydride in carbon tetrachloride8 to give the required enol acetates 4,
6, 9, 11, 13 and 15, respectively, in good yield (Scheme 3).9
We initially investigated the hydrogenation of enol acetate 6 in an attempt
to probe the stereochemical outcome of this reduction (Scheme 4). To prevent
further reduction of the potential product (e.g. syn-16), we chose to use toluene
as our reaction solvent and palladium-on-barium sulphate10,y as our mediator
due to its low reactivity. Addition of the enol acetate 6 to a stirred solution of
Pd-on-BaSO4 (1–2 mol%) in toluene, under a hydrogen atmosphere, gave,
after 48 h, the required syn-acetate 16 in good yield (Scheme 4). The
stereochemistry of this adduct was confirmedz by simple reduction of
2-methyltetralone 2 with sodium borohydride11 to give the alcohol anti-17
OH
OAc
OAc
H
H
H2
Me
H
Me
H
Me
MeLi, THF
Pd-on-BaSO4
then HCl
toluene
syn -16; 82%a
syn -17; 43%
6
a18; 18%
Scheme 4.
y This catalyst is commercially available from Aldrich (5% palladium-on-barium sulphate unreduced).
z The relative stereochemistry has been determined by a 400 MHz NOESY spectrum.
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340
S. BUKSHA ET AL.
as the major diastereoisomer, followed by acetylation to give the required anti-
acetate 16 (Scheme 5).
With this information in hand, we next chose to investigate the deuteriation
of enol acetate 6 using our standard reduction protocol; addition of the enol
acetate 6 to a stirred solution of Pd-on-BaSO4 in toluene under a deuterium
atmosphere gave the deuteriated syn-acetate [D2]-16 in good yield (Scheme 6).
However, somewhat surprisingly, the levels and position of deuterium
incorporation were found to be lower than initially anticipated. A higher
level of deuterium incorporation had occurred at the more nucleophilic
carbon, C(2), of the enol acetate 6 than the C(1) position. This was evident
1
from the H NMR spectrum of syn-[D2]-16 by the presence of the unlabelled
C(1)H proton at 6.01 ppm (in [D1]-16) and a singlet for the corresponding
methyl group at 1.03 ppm (in [D1]-16/[D2]-16) (Scheme 6). In an attempt to get
a better understanding of these processes, we re-investigated these reductions,
and found the presence of a byproduct, naphthoxy acetate 18, which was
formed in approximately 20% yield. This byproduct was evidently derived
from dehydrogenation of the parent enol acetate 6. The loss and potential
hydrogen transfer during this deuteriation process is clearly undesirable due to
potential hydrogenation lowering the overall level of D-incorporation. To
ensure that no background hydrogen transfer had occurred from the reaction
solvent (toluene), we additionally performed the reaction in [D8]-toluene which
gave the acetate [D2]-16 with identical levels of hydrogen incorporation at
both C(1) and C(2) positions.
We next probed whether the structural nature of the tetralone framework
was responsible for the relative position and level of deuterium incorporation.
Under our standard hydrogenation and deuteriation conditions, we screened a
OAc
OH
O
H
H
Me
H
Me
H
Me
AcCl, Et3N
CH2Cl2
NaBH4
EtOH
17; 66%
anti -:syn - : 66:34
16; 44%
anti -:syn - : 66:34
2
Scheme 5.
OAc
OAc
D
OAc
H
OAc
D2
Me
Me
Me
D
Me
Pd-on-BaSO4
D
toluene
6
[D2]-16
18; 20%
[D1]-16
80%
C(1) ([D]:[H] = 77:23)
C(2) ([D]:[H] = 95:5)
Scheme 6.
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INVESTIGATIONS INTO THE C-DEUTERIATION
341
related series of enol acetates 4, 9 and 11, and found that these behaved
similarly to the enol acetate 6 leading to the partially deuterium labelled
acetates [D2]-5, [D2]-19 and [D2]-20 (Schemes 7 and 8). The relative position
and level of deuterium incorporation were characteristically higher at the more
nucleophilic C(2) position than the neighbouring C(1) position (Scheme 8).
We next turned our attention to screening two related enol acetates 13 and
15 (derived from indanone 12 and benzosuberone 14-see scheme 3) to examine
whether the ring size of the cycloalkyl was responsible for this partial
deuteriation (Schemes 7 and 8). Deuteriation of these enol acetates 13 and 15
under our standard conditions gave the partially deuteriated acetates [D2]-21
and [D2]-22 in good yield (Scheme 8). It appears that the indenyl skeleton in 13
promoted higher levels of D-incorporation at the C(1) position than both the
tetralenyl and benzocycloheptenyl skeletons within the enol acetates 4 and 15,
respectively (Scheme 8). As expected, the levels of deuterium incorporation at
the C(2) position were higher than those at the C(1) position.
In conclusion, we have shown that regioselective C-deuteriation of an enol
acetate (e.g. 6) can occur efficiently to give the corresponding acetate (e.g. syn-
[D2]-16) in good yield. The position and levels of deuterium incorporation
were found to be dependent on the structural nature of the enol acetate
precursor used; an indenyl acetate 13 gave higher levels of deuterium
incorporation than related enol acetates tetralenylacetate 4 and benzocyclo-
heptenylacetate 15. For all the cases studied so far, it appears that deuterium
H2
Enol
H2
Enol
Acetate
Yield
82%
Acetate
OAc
Acetate
Yield
66%
Acetate
OAc
OAc
OAc
H
Me
Me
H
MeO
MeO
16
OAc
6
11
20
OAc
OAc
OAc
OAc
53%
75%
90%
4
5
13
21
AcO
AcO
OAc
80%
OMe
OMe
22
15
9
19
Scheme 7.
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342
S. BUKSHA ET AL.
D2
D2
Enol
Enol
Acetate
OAc
Yield
24%b
Acetate
OAc
Yield
Acetate
Acetate
OAc
OAc
D/H
D/H
H
D
Me
D
Me
80%
MeO
11
MeO
[D2]-16:[D1]-16
C(1) ([D]:[H] = 77:23)
C(2) ([D]:[H] = 95:5)
6
[D2]-20:[D1]-20
C(1) ([D]:[H] = 84:16)
C(2) ([D]:[H] = 95:5)
OAc
D/H
OAc
OAc
OAc
D/H
H
H
D
74%
75%
D
13
[D2]-5:[D1]-5
C(1) ([D]:[H] = 56:44)
C(2) ([D]:[H] = 90:10)
[D2]-21:[D1]-21
C(1) ([D]:[H] = 94:6)
C(2) ([D]:[H] = >95:<5)
4
AcO
D/H
OAc
AcO
OAc
H
D/H
H
D
83%a
87%
D
OMe
OMe
15
[D2]-19:[D1]-19
C(1) ([D]:[H] = 67:33)
C(2) ([D]:[H] = 95:5)
[D2]-22:[D1]-22
C(1) ([D]:[H] = 45:55)
C(2) ([D]:[H] = 90:10)
9
a 9; 10%; b 11; 60%.
Scheme 8.
incorporation was more positionally selective at the C(2) position of an enol
acetate than at the corresponding C(1) position. We have yet to establish the
exact nature of this mechanism for this apparent regioselective C-deuteriation
process; however, progress towards this is currently under investigation in our
laboratory.
Experimental
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). Palladium-on-barium sulphate (5% unreduced) was purchased from
Aldrich and used accordingly. Proton and carbon NMR spectra were recorded
on a Bruker 270 and 400 MHz Fourier transform spectrometer using an
internal deuterium lock. Chemical shifts are quoted in parts per million
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INVESTIGATIONS INTO THE C-DEUTERIATION
343
downfield from tetramethylsilane. Carbon NMR spectra were recorded with
broad proton decoupling. Infrared spectra were recorded on a Shimadzu 8300
FTIR instrument and mass spectra were recorded on a Kratos 50MSTC
spectrometer using a DS503 data system for high-resolution analysis. The
levels and positions of D-incorporation were determined by a combination of
proton and carbon NMR spectroscopy.
3,4-Dihydro-naphthalen-1-yl acetate 4
Tetralone 7 (0.65 g, 4.46 mmol) and p-toluenesulphonic acid (0.10 g,
0.58 mmol) were added to isopropenylacetate (9.09 g, 10.0 ml, 90.9 mmol).
The resulting mixture was heated at 1108C for 12 h. The solution was cooled to
room temperature, and extracted into ether (2 ꢀ 50 ml). The combined organic
layers were dried over MgSO4 and evaporated under reduced pressure. The
residue was purified by flash column chromatography on silica gel eluting with
light petroleum (b.p. 40–608C)–ether (19:1) to give the enol acetate 4 (0.69 g,
83%) as a white crystalline solid; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.42; vmax(film)/cmꢁ1 1758 (C¼¼O); dH (270 MHz, CDCl3) 7.15–7.10
(3 H, m, 3 ꢀ CH; Ar), 7.07–7.00 (1 H, m, CH; Ar), 5.70 (1 H, t, J=4.7, CH),
2.90 (2 H, t, J=8.4, CH2), 2.40–2.43 (2 H, m, CH2) and 2.25 (3 H, s, CH3); dC
(100 MHz, CDCl3) 169.3, 145.6, 136.3, 130.2, 127.8, 127.5, 126.3, 120.7, 115.1,
27.4, 22.0 and 20.5 (Found M+ 188.2262, C12H12O2, requires M, 188.2267).
1,2,3,4-Tetrahydro-naphthalen-1-yl acetate 5
Hydrogen gas (250 ml) was gradually added to a stirred solution of 3,4-
dihydronaphthalen-1-yl-acetate 4 (0.5 g, 2.7 mmol), toluene (3 ml) and Pd-on-
BaSO4 (0.1 g, 5% on BaSO4 unreduced), and the resulting solution was stirred
for 48 h. Ethyl acetate (5 ml) was added, and the mixture was filtered and
evaporated under reduced pressure. The residue was purified by flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1) to give acetate 5 (0.27 g, 53%) as a colourless oil; RF [light petroleum
(b.p. 40–608C)–ether (9:1)] 0.4; vmax(film)/cmꢁ1 1730 (C¼¼O); dH (270 MHz,
CDCl3) 7.52–7.05 (4 H, m, 4 ꢀ CH; Ar), 5.99 (1 H, br t, J=4.4, CHOAc), 2.98–
2.60 (2 H, m, CH2), 2.01 (3 H, s, CH3) and 2.00 (4 H, m, 2 ꢀ CH2); dC (67 MHz,
CDCl4) 171.0 (C¼¼O), 138.3 (i-C; Ar), 134.9 (i-C; Ar), 129.8, 129.4, 128.4 and
126.4 (4 ꢀ CH; Ar), 77.4 (CH–O), 29.4 (CH2), 29.3 (CH3), 21.8 (CH3) and 19.2
(CH2) (Found (M+NH4)+ 208.1329, C12H18NO2, requires M, 208.1332);
(m/z) 148.2 (100%, MꢁAc+H).
1,2-Dideutero-1,2,3,4-tetrahydro-naphthalen-1-yl acetate [D2]-5
Under the same conditions as acetate 5, 3,4-dihydronaphthalen-1-yl-acetate 4
(0.2 g, 1.1 mmol) in toluene (2 ml), Pd-on-BaSO4 (43 mg, 5% on BaSO4
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S. BUKSHA ET AL.
unreduced) and deuterium gas (250 ml) gave, after flash column chromato-
graphy on silica gel eluting with light petroleum (b.p. 40–608C)–ether (9:1), the
acetate [D2]-5 (0.16 g, 74%) as a colourless oil; vmax(film)/cmꢁ1 1730 (C¼¼O);
RF [light petroleum (b.p. 40–608C)–ether (9:1)] 0.40; dH (270 MHz, CDCl3)
7.52–7.05 (4 H, m, 4 ꢀ CH; Ar), 5.99 (1 H, br d, J=5.1, CHOAc),} 2.98–2.60
(2 H, m, CH2), 2.01 (3 H, s, CH3) and 2.00 (4 H, m, 2 ꢀ CH2); dC (67 MHz,
CDCl3) 170.8 (C¼¼O), 138.0 and 134.6 (2 ꢀ i-C; Ar), 129.5, 129.1, 128.1 and
126.1 (4 ꢀ CH; Ar), 69.8 (1 C, t, 1JCD=22 Hz; CD–O), 29.0 (CH2), 28.7 (1 C,
t, 1JCD=19 Hz at 100 MHz), 21.5 (CH3) and 18.8 (CH2). The isotopic shift at
C(1) (69.1 ppm) was 0.36 ppm (24.1 Hz) and C(2) (28.7 ppm) was 0.23 ppm
(15.4 Hz) (Found MD0 + NH4+ 208.1318, C12H18NO2, requires M, 208.1317);
(m/z) 210.1 (40%, MD2 + NH+4 ), 209.1 (10, MD1 + NH4+), 208.1 (3, MD0
+
NH+4 ), 151.1 (50, MD2 + H ꢁ Ac + H), 150.1 (100, MD1 + H ꢁ Ac + H)
and 149.1 (40, MD0 + H ꢁ Ac + H).
3,4-Dihydro-2-methyl-naphthalenyl acetate 6
2-Methyltetralone 2 (0.51 g, 3.2 mmol) was added to a conical flask containing
acetic anhydride (0.47 g, 0.43 ml, 4.6 mmol) and carbon tetrachloride (10 ml).
Perchloric acid (2 drops) was slowly added, and the flask was left to stand for
10 h. The reaction mixture was then poured into a cooled solution of saturated
aqueous sodium hydrogen carbonate (50 ml) and light petroleum (b.p. 40–
608C)–ether (50 ml). The resulting solution was stirred for 30 min and solid
sodium hydrogen carbonate was added until the pH had reached 7. The
organic layer was separated, and the aqueous layer was further extracted with
light petroleum (b.p. 40–608C)–ether (2 ꢀ 50 ml). The combined organic layers
were dried over MgSO4 and evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel eluting with light
petroleum (b.p. 40–608C)–ether (9:1) to give the enol acetate 6 (0.51 g, 80%) as
a colourless oil; RF [light petroleum (b.p. 40–608C)–ether (9:1)] 0.32;
v
max(film)/cmꢁ1 1716 (C¼¼O); dH (270 MHz, CDCl3) 7.18–7.08 (3 H, m,
3 ꢀ CH; Ar), 7.00 (1 H, d, J=7.5, CH; Ar) 2.85 (2 H, t, J=7.8, CH2), 2.36
(2 H, t, J=7.8, CH2), 2.32 (3 H, s, CH3C¼¼O) and 1.75 (3 H, s, CH3CH); dC
(100 MHz, CDCl3) 168.8, 140.1, 135.2, 131.0, 127.3, 126.9, 126.4, 124.1, 120.1,
28.9, 27.5, 20.5 and 16.8 (Found MH+ 202.2420, C13H15O2, requires MH,
202.2425).
5-Methoxy-3,4-dihydro-naphthalenyl acetate 9
5-Methoxytetralone
8
(1.0 g, 5.7 mmol) was added dropwise to
a
stirred solution of LDA [formed by addition of n-BuLi (2.5 ml, 2.5 M in
} Due to unlabelled position.
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INVESTIGATIONS INTO THE C-DEUTERIATION
345
hexane, 6.2 mmol) to diisopropylamine (0.57 g, 0.76 ml, 5.7 mmol)] in
THF (10 ml) at ꢁ788C. The resulting solution was stirred for 20 min.
Acetyl chloride (0.89 g, 0.80 ml, 11.4 mmol) was added dropwise and the
resulting solution was stirred for 3 h. Saturated aqueous NH4Cl (50 ml) was
added, and the resulting mixture was extracted with ether (3 ꢀ 50 ml).
The combined organic layers were dried over MgSO4 and evaporated under
reduced pressure. The residue was purified by flash column chromato-
graphy on silica gel eluting with light petroleum (b.p. 40–608C)–ether (19:1) to
give the enol acetate 9 (1.01 g, 82%) as a colourless oil; RF [light
petroleum (b.p. 40–608C)–ether (9:1)] 0.25; vmax(film)/cmꢁ1 1689 (C¼¼O);
dH (270 MHz, CDCl3) 7.26–7.34 (2 H, m, 2 ꢀ CH; Ar), 7.12 (1 H, t,
J=8.4, CH; Ar), 5.68 (1 H, t, J=4.7, CH), 3.84 (3 H, s, OCH3), 2.84
(2 H, t, J=8.6, CH2), 2.46–2.33 (2 H, m, CH2) and 2.27 (3 H, s, CH3);
dC (100 MHz, CDCl3) 176.9, 169.3, 156.1, 145.4, 131.4, 126.6, 115.6, 113.5,
110.6, 55.5, 22.1, 20.8 and 19.5 (Found M+ 218.0950, C13H14O3, requires M,
218.0943).
6-Methoxy-3,4-dihydro-naphthalen-1-yl acetate 11
Under the same conditions as enol acetate 4, 6-methoxytetralone 10 (1.0 g,
5.70 mmol), isopropenylacetate (36.4 g, 40.0 ml, 0.36 mol) and p-toluenesul-
phonic acid (0.10 g, 0.58 mmol) gave, after flash column chromatography on
silica gel eluting with light petroleum (b.p. 40–608C)–ether (19:1), acetate 11
(1.00 g, 81%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.23; vmax(film)/cmꢁ11691 (C¼¼O); dH (270 MHz, CDCl3) 7.01 (1 H, d,
J=8.1, CH; Ar), 6.69–6.65 (2 H, m, 2 ꢀ CH; Ar), 5.55 (1 H, t, J=4.6, CH),
3.78 (3 H, s, OCH3), 2.82 (2 H, t, J=7.9, CH2), 2.45–2.37 (2 H, m, CH2) and
2.27 (3 H, s, CH3); dC (100 MHz, CDCl3) 169.4, 158.0, 145.5, 138.3, 123.5,
122.8, 113.8, 112.7, 111.1, 74.3, 55.5, 27.9, 21.0 and 20.9 (Found M+ 218.0950,
C13H14O3, requires M, 218.0943).
3H-Inden-1-yl acetate 13
Under the same conditions as enol acetate 4, indanone 12 (1.0 g, 7.6 mmol),
isopropenylacetate (36.4 g, 40.0 ml, 0.36 mol) and p-toluenesulphonic acid
(0.10 g, 0.58 mmol) gave, after flash column chromatography on silica gel
eluting with light petroleum (b.p. 40–608C)–ether (19:1), enol acetate 13 (1.2 g,
90%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether (19:1)] 0.76;
vmax(film)/cmꢁ1 1760 (C¼¼O); dH (270 MHz, CDCl3) 7.31–7.24 (4 H, m,
4 ꢀ CH; Ar), 6.32 (1 H, t, J=2.4, CH), 3.41 (2 H, d, J=2.4, CH2) and 2.34
(3 H, s, CH3); dC (100 MHz, CDCl3) 168.2, 149.1, 141.7, 139.0, 126.2, 125.6,
124.1, 118.0, 115.5, 35.0 and 21.1 (Found M+ 174.1889, C11H10O2, requires
M, 174.1994).
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S. BUKSHA ET AL.
8,9-Dihydro-7H-benzocyclohepten-5-yl acetate 15
Under the same conditions as enol acetate 4, benzosuberone 14 (1.3 g,
8.1 mmol), isopropenylacetate (36.4 g, 40.0 ml, 0.36 mol) and p-toluenesulpho-
nic acid (0.13 g, 0.75 mmol) gave, after flash column chromatography on silica
gel eluting with light petroleum (b.p. 40–608C)–ether (19:1), the acetate 14
(1.35 g, 83%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.45; vmax(film)/cmꢁ1 1747 (C¼¼O); dH (270 MHz, CDCl3) 7.25–7.17
(4 H, m, 4 ꢀ CH; Ar), 5.79 (1 H, t, J=5.9, CH), 2.83–2.71 (2 H, m, CH2), 2.13
(3 H, s, CH3), 2.19–2.12 (2 H, m, CH2) and 2.10–2.00 (2 H, m, CH3); dC
(100 MHz, CDCl3) 169.8, 145.7, 141.8, 134.3, 129.1, 128.1, 126.0, 125.4, 119.7,
33.7, 31.0, 25.3 and 20.9 (Found MH+ 203.2551, C13H15O2, requires MH,
203.2556).
1,2,3,4-Tetrahydro-2 methylnaphthalen-1-yl acetate 16
Under the same conditions as acetate 5, 3,4-dihydro-2-methylnaphthalen-yl
acetate 6 (0.2 g, 0.99 mmol) in toluene (3 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and hydrogen gas (250 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1), the acetate 16 (0.17 g, 82%) as a colourless oil; RF [light petroleum (b.p.
40–608C)–ether (9:1)] 0.43; vmax(film)/cmꢁ1 1078 (C–O); dH (270 MHz, CDCl3)
7.35 (1 H, d, J=7.4, CH; Ar), 7.25–7.14 (3 H, m, 3 ꢀ CH; Ar), 6.01 (1 H, d,
J=3.2, CH), 2.89–2.82 (2 H, m, CH2), 2.06 (3 H, s, CH3), 2.01–1.94 (1 H, m,
CH), 1.72–1.71 (2 H, m, CH2) and 1.03 (3 H, d, J=6.9, CH3); dC (100 MHz,
CDCl3) 170.9 (COCH3), 137.5 (i-CH; Ar), 135.1 (i-CH; Ar), 130.2, 128.9,
128.2 and 126.0 (4 ꢀ CH; Ar), 72.5 (CH–O), 33.0 (CHCH3), 28.8 (CH2C), 25.6
(CH2), 21.2 (CH3CO) and 16.9 (CHCH3). (Found (M+NH4)+, 222.1491,
C13H20NO2 requires M, 222.1489); (m/z) 204.1 (100%, M+); and napthox-
yacetate 18 (35 mg, 18%) as an oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.25; vmax(film)/cmꢁ1 1720 (C¼¼O); dH (270 MHz, CDCl3) 7.85 (1 H, d,
J=7.2, CH; Ar), 7.73 (1 H, d, J=7.6, CH; Ar), 7.65 (1 H, d, J=8.2, CH; Ar),
7.45 (2 H, qd, J=7.6 and 1.9, 2 ꢀ CH; Ar) , 7.33 (1 H, d, J=8.2, CH; Ar), 2.47
(3 H, s, CH3; Ac) and 2.30 (3 H, s, CH3); dC (67.5 MHz, CDCl3) 169.0 (C¼¼O),
144.3 (i-C; Ar), 133.2 (i-C; Ar), 128.7, 127.9, 127.0, 126.5, 126.4, 125.8, 125.5
and 120.7 (8 ꢀ CH; Ar), 20.6 and 16.4 (2 ꢀ CH3) (Found (M+NH4)+
218.1176, C13H16NO2, requires (M+NH4)+, 218.1176).
1,2-Dideutero-3,4-dihydro-2-methylnaphthalene-1-yl acetate [D2]-16
Under the same conditions as acetate 5, 3,4-dihydro-2-methyl-naphthalen-
1-yl-acetate 6 (0.72 g, 3.6 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and deuterium gas (250 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
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(9:1), the acetate [D2]-16 (0.58 g, 80%) as a colourless oil; RF [light petroleum
(b.p. 40–608C)–ether (9:1)] 0.50; vmax(film)/cmꢁ1 2083 (CD); dH (270 MHz,
CDCl3) 7.31–7.14 (4 H, m, 4 ꢀ CH; Ar), 6.00 (1 H, s, CH) (see foonote }), 2.87–
2.79 (2 H, m, CH2), 2.05 (3 H, s, COCH3), 1.81–1.68 (2 H, m, CH2) and 1.02
(3 H, s, CDCH3); dC (100 MHz, CDCl4) 170.9 (C¼¼O), 137.3 and 135.1 (2 ꢀ i-
C; Ar), 130.3, 128.9, 128.2 and 126.0 (4 ꢀ CH; Ar), 72.1 (CD–O), 32.4
(CDCH3), 28.5 (OCOCH3), 25.4 and 21.2 (2 ꢀ CH2) and 16.9 (CH3). (Found
Md0 + NH+4 222.1476, C13H14O2D2+NH+4 , requires M, 206.1473) and
(Found (M + NH+4 )+ 224.1614, C13H18NO2D2, requires M, 224.1614); (m/z)
224.1 (25%, MD2 + NH4+), 223.1 (15, MD1 + NH+4 ), 222.1 (2, MD0
+
NH+4 ), 165.2 (60, MD2 + H ꢁ Ac + H), 164.1 (100, MD1 + H ꢁ Ac + H)
and 163.1 (50, MD0 + H ꢁ Ac + H); the isotopic shift at C(1) (72.1 ppm) was
0.37 ppm (1 C, t, JCD=22 Hz) and C(2) (32.4 ppm) was 0.48 ppm (1 C, t,
1
1JCD=20 Hz); and naphthoxyacetate 18 (0.14 g, 20%) as an oil, which was
spectroscopically identical to that obtained previously.
1,2,3,4-Tetrahydro-2-methylnapthalen-1-ol syn-17
1,2,3,4-Tetrahydro-2-methylnapthalen-1-yl acetate 16 (0.1 g, 0.5 mmol) was
added dropwise to a stirred solution of MeLi (1.2 ml, 1.5 M in diethyl ether,
1.8 mmol) in THF (4 ml) at ꢁ788C. The resulting solution was stirred for 2 h.
Saturated aqueous NH4Cl (10 ml) was added, and the resulting mixture was
extracted with ether (3 ꢀ 20 ml). The combined organic layers were dried over
MgSO4 and evaporated under reduced pressure. The residue was purified by
flash column chromatography on silica gel eluting with light petroleum (b.p.
40–608C)–ether (19:1) to give 1,2,3,4-tetrahydro-2-methylnapthalen-1-ol syn-
17 (44 mg, 43%) as a colourless oil; RF [light petroleum (b.p. 40–608C); ether
(9:1)] 0.12; vmax(film)/cmꢁ1 vmax(film)/cmꢁ1 3500 (OH); dH (270 MHz, CDCl3)
7.24–7.18 (4 H, m, 4 ꢀ CH; Ar), 4.56–4.50 (1 H, m, CHOH), 2.82–2.78 (2 H, m,
CH2), 1.88–1.80 (1 H, m, CH), 1.67–1.58 (2 H, m, CH2) and 1.12 (3 H, d,
J=6.7, CH3); dC (100 MHz, CDCl3) 138.7 and 136.7 (2 ꢀ i-C; Ar), 129.8,
129.0, 128.2 and 126.2 (4 ꢀ CH; Ar), 71.5 (CH–O), 34.2 (CHCH3), 28.9 and
24.8 (2 ꢀ CH2) and 16.9 (CH3).
Sodium borohydride reduction of 2-methyltetralone 2
Sodium borohydride (0.37 g, 9.8 mmol) was added to a stirred solution of
2-methyltetralone 2 (0.51 g, 3.2 mmol) in ethanol (10 ml). The resulting
solution was stirred for 2 h. HCl (10 ml, 3 M) was slowly added, followed by
an aqueous solution of NaOH (10 ml, 10%). Water (50 ml) was added, and the
resulting mixture was extracted with ether (3 ꢀ 50 ml). The combined organic
layers were dried over MgSO4, and evaporated under reduced pressure. The
residue was purified by flash column chromatography on silica gel eluting with
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S. BUKSHA ET AL.
light petroleum (b.p. 40–608C)–ether (9:1) to give a diastereoisomeric mixture
of anti- and syn-2-methyltetralols 17 (0.34 g, 66%) (ratio 66:34: anti-:syn-) as a
colourless oil; RF [light petroleum (b.p. 40–608C)–ether (1:1)] 0.44; vmax(film)/
cmꢁ1 3500 (OH); dH (270 MHz, CDCl3) 7.51 (1 H, m, CH; Ara), 7.34 (1 H, m,
CH; Ars), 7.22–7.05 (6 H, m, 6 ꢀ CH; Ara+s), 4.56 (1 H, d, J=3.2, CH–Os),
4.31 (1 H, d, J=7.6, CH–Oa), 2.90–2.70 (4 H, m, CH2a and CH2s), 1.94–1.50
(6 H, m, CH2a, CH2s, CHCH3a and CHCH3s) and 1.10 (6 H, d, J=6.5, CH3a
and CH3s); dC (67 MHz, CDCl3) 139.3, 139.11, 137.1 and 137.0 (4 ꢀ i-C;
Ara+s), 130.3, 130.2, 129.4, 129.0, 128.2, 127.6, 126.6 and 126.5 (8 ꢀ CH;
Ara+s), 75.5 (CH–Oa), 71.9 (CH–Os), 37.7 (CHCH3a), 34.6 (CHCH3s), 29.3
(CH2s), 28.5 (CH2a), 28.3 (CH2a), 25.1 (CH2s), 18.5 (CH3a) and 17.3 (CH3s);
(m/z) 162.2 (100%, M).
Acetylation of 2-methyltetralol 17
Acetyl chloride (0.17 g, 0.15 ml, 2.2 mmol) was added to a stirred solution of
anti- and syn-tetralols 17 (0.31 g, 1.9 mmol) and Et3N (0.22 g, 0.30 ml,
2.2 mmol) in dichloromethane (10 ml). The resulting solution was stirred for
24 h. Saturated aqueous NH4Cl (30 ml) was added, and the resulting mixture
was extracted with ether (3 ꢀ 20 ml). The combined organic layers were dried
over MgSO4 and evaporated under reduced pressure. The residue was purified
by flash column chromatography on silica gel eluting with light petroleum
(b.p. 40–608C)–ether (19:1) to give a diastereoisomeric mixture of anti- and
syn-1,2,3,4-tetrahydro-2-methylnaphthalen-1-yl acetate 16 (0.17 g, 44%) (ratio
66:34: anti-:syn-) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.50; vmax(film)/cmꢁ1 1715 (C¼¼O); dH (270 MHz, CDCl3) 7.46–7.05
(8 H, m, Ara and Ars), 6.02 (1 H, d, J=3.4, CH–Os), 5.74 (1 H, d, J=6.7, CH–
Oa), 2.88–2.70 (4 H, m, CH2a and CH2s), 2.25–1.50 (6 H, m, CHa, CHs, CH2a
and CH2s), 2.10 (3 H, s, CH3; Aca), 2.05 (3 H, s, CH3; Acs), 1.10 (3 H, d,
J=7.0, CH3; Acs) and 1.00 (3 H, d, J=7.1, CH3; Aca) (Found (M+NH4)+
222.1493, C13H20NO2, requires (M+NH4)+, 222.1489).
5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl acetate 19
Under the same conditions as acetate 5, 5-methoxy-3,4-dihydronaphthalen-1-
yl acetate 9 (0.23 g, 1.06 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and hydrogen gas (500 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1), acetate 19 (0.18 g, 80%) as a colourless oil; RF [light petroleum (b.p. 40–
608C)–ether (9:1)] 0.49; vmax(film)/cmꢁ1 1718 (C¼¼O); dH (270 MHz, CDCl3)
7.15 (1 H, t, J=7.7, CH; Ar), 6.90 (1 H, d, J=7.7, CH; Ar), 6.75 (1 H, d,
J=7.7, CH; Ar), 5.97 (1 H, t, J=4.8, CHO), 3.81 (3 H, s, OCH3), 2.88–2.78
(2 H, m, CH2), 2.60–2.54 (2 H, m, CH2), 2.09 (3 H, s, COCH3) and 1.92–1.86
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349
(2 H, m, CH2); dC (100 MHz, CDCl3) 171.1 (OCOCH3), 157.4 (COCH3), 136.0
and 127.4 (2 ꢀ i-C; Ar), 126.8, 121.7 and 109.5 (3 ꢀ CH; Ar), 70.3 (CH–O),
55.7 (COCH3), 39.2 (CH2), 28.9 (CH2), 20.8 (OCOCH3) and 18.4 (CH2).
5-Methoxy-1,2-dideutero-3,4-dihydro-naphthalen-1-yl acetate [D2]-19
Under the same conditions as acetate 5, 5-methoxy-3,4-dihydro-naphthalen-1-
yl acetate 9 (0.20 g, 1.06 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and deuterium gas (250 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1), the acetate [D2]-19 (0.19 g, 83%) as a colourless oil; RF [light petroleum
(b.p. 40–608C)–ether (9:1)] 0.70; vmax(film)/cmꢁ1 2071 (C–D); dH (270 MHz,
CDCl3) 7.15 (1 H, t, J=7.6, CH; Ar), 6.89 (1 H, d, J=7.6, CH; Ar), 6.77 (1 H,
d, J=7.6, CH; Ar), 5.95 (1 H, br d, J=4.6, CHO) (see footnote }), 3.81 (3 H, s,
OCH3; Ar), 2.85–2.78 (2 H, m, CH2), 2.06 (3 H, s, COCH3) and 1.92–1.81 (3 H,
m, CDH and CH2); dC (100 MHz, CDCl3) 170.8 (OCOCH3), 159.0, 139.6,
131.0, 126.9, 113.4, 112.5, 69.7 (1 C, t, 1JCD=20 Hz; CD–O), 55.3 (OCOCH3),
1
30.9 (1 C, t, JCD=20 Hz; CD), 28.7 (CH2), 21.5 (COCH3) and 18.5 (CH2)
(Found M+ 222.1221, C13H14O3D2, requires M, 222.1219). The isotopic shift
at C(1) (69.7 ppm) was 0.22 ppm.
6-Methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl acetate 20
Under the same conditions as acetate 5, 6-methoxy-3,4-dihydro-naphthalen-1-
yl acetate 11 (0.20 g, 1.06 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and H2 (500 ml) gave, after flash column chromatography
on silica gel eluting with light petroleum (b.p. 40–608C)–ether (9:1), acetate 20
(0.15 g, 66%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.59; vmax(film)/cmꢁ1 1719 (C¼¼O); dH (270 MHz, CDCl3) 7.25–7.20
(1 H, m, CH; Ar), 6.74–6.71 (1 H, m, CH; Ar), 6.62 (1 H, s, CH; Ar), 5.95–5.93
(1 H, m, CHOAc), 3.77 (3 H, s, OCH3), 2.85–2.73 (2 H, m, CH2), 2.10 (3 H, s,
CH3) and 1.96–1.89 (4 H, m, 2 ꢀ CH2); dC (100 MHz, CDCl3) 171.2
(OCOCH3), 159.6 (COCH3), 139.9 and 131.4 (2 ꢀ i-C; Ar), 126.5, 116.2 and
112.8 (3 ꢀ CH; Ar), 70.1 (CH–O), 55.7 (COCH3), 29.7 (CH2), 29.6 (CH), 21.4
(CH3) and 18.9 (CH2).
6-Methoxy-1,2-dideutero-3,4-dihydro-naphthalen-1-yl acetate [D2]-20
Under the same conditions as acetate 5, 6-methoxy-3,4-dihydro-naphthalen-1-yl
acetate 11 (0.20 g, 1.06 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on
BaSO4 unreduced) and deuterium gas (250 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1), acetate [D2]-20 (56 mg, 24%) as a colourless oil; RF [light petroleum (40–
608C)–ether (9:1)] 0.40; vmax(film)/cmꢁ1 2197 (C–D); dH (270 MHz, CDCl3) 7.25–
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7.15 (2 H, m, 2 ꢀ CH; Ar), 6.75 (1 H, dd, J=8.6 and 2.7, CH; Ar), 5.95 (1 H, br
d, J=3.4 Hz, CHOAc) (see footnote }), 3.78 (3 H, s, OCH3), 2.80–2.71 (2 H, m,
CH2), 2.10 (3 H, s, CH3) and 2.05–1.81 (3 H, m, CH2 and CHD); dC (100 MHz,
CDCl3) 170.0 (OCOCH3), 159.3 (COCH3), 139.5 and 131.0 (2 ꢀ i-C; Ar), 126.1,
113.4 and 112.5 (3 ꢀ CH; Ar), 69.6 (CD–O), 55.3 (COCH3), 30.9 (CH2), 28.7
(CD), 21.0 (CH3) and 18.4 (CH2) (Found M+ 222.1216, C13H14O3D2, requires
M, 222.1219). The isotopic shift at C(1) (69.6 ppm) was 0.20 ppm (1 C, t,
1
1JCD=23 Hz) and C(2) (28.7 ppm) was 0.58 ppm (1 C, t, JCD=20 Hz).
Indan-1-yl acetate 21
Under the same conditions as acetate 5, 3H-inden-1-yl acetate 13 (0.20 g,
1.15 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on BaSO4 unreduced)
and hydrogen gas (500 ml) gave, after flash column chromatography on silica
gel eluting with light petroleum (b.p. 40–608C)–ether (9:1), acetate 21 (0.15 g,
75%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether (9:1)] 0.39;
v
max(film)/cmꢁ1 1732 (C¼¼O); dH (270 MHz, CDCl3) 7.39 (1 H, d, J=2.0, CH;
Ar), 7.28–7.21 (3 H, m, 3 ꢀ CH; Ar), 6.18 (1 H, dd, J=6.9, CHCO), 3.10–3.07
(1 H, m, CHAHB), 2.90–2.78 (1 H, m, CHAHB), 2.50–2.45 (1 H, m, CHAHB),
2.11–2.07 (1 H, m, CHAHB) and 2.05 (3 H, s, CH3); dC (100 MHz, CDCl3)
170.0 (COCH3), 143.4 and 140.0 (2 ꢀ i-C; Ar), 127.9, 125.6, 124.5 and 123.7
(4 ꢀ CH; Ar), 77.3 (CH–O), 31.2 (CH2), 29.1 (CH2) and 20.3 (CH3).
1,2-Dideutero-inden-1-yl acetate [D2]-21
Under the same conditions as acetate 5, 3H-inden-1-yl acetate 13 (0.20 g,
1.15 mmol) in toluene (2 ml), Pd-on-BaSO4 (40 mg, 5% on BaSO4 unreduced)
and deuterium gas (250 ml) gave, after flash column chromatography on silica
gel eluting with light petroleum (b.p. 40–608C)–ether (9:1), acetate [D2]-21
(0.15 g, 75%) as a colourless oil; RF [light petroleum (b.p. 40–608C)–ether
(9:1)] 0.43; vmax(film)/cmꢁ1 2123 (C–D); dH (270 MHz, CDCl3) 7.39 (1 H, d,
J=8.2, CH; Ar), 7.28–7.21 (3 H, m, 3 ꢀ CH; Ar), 6.18 (1 H, br d, J=3.9,
CHCO) (see footnote }), 3.08 (1 H, dd, J=16.1 and 8.4, CHAHB), 2.90 (1 H,
dd, J=16.1 and 5.7, CHAHB), 2.09–2.06 (1 H, dd, 8.4 and 5.7, CHD) and 2.06
(3 H, s, CH3); dC (100 MHz, CDCl3) 170.0 (C¼¼O), 143.4 and 139.9 (2 ꢀ i-C;
Ar), 127.9, 125.6, 124.5 and 123.9 (4 ꢀ CH; Ar), 76.9 (CD–O), 31.0 (CD), 29.1
(CH2) and 20.3 (COCH3). (Found (M+NH4)+ 196.1299, C11H14NO2D2,
requires M, 196.1301). The isotopic shift at C(1) (76.9 ppm) was 0.31 ppm (1 C,
1
1
t, JCD=23 Hz) and C(2) (31.0 ppm) was 0.24 ppm (1 C, t, JCD=20 Hz).
6,7,8,9-Tetrahydro-5H-benzocyclohepten-5-yl acetate 22
Under the same conditions as acetate 5, 8,9-dihydro-7H-benzocyclohepten-5-
yl acetate 15 (0.16 g, 0.8 mmol) in toluene (1.5 ml), Pd-on-BaSO4 (40 mg, 5%
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INVESTIGATIONS INTO THE C-DEUTERIATION
351
on BaSO4 unreduced) and hydrogen gas (500 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(19:1), acetate 22 (0.15 g, 90%) as a colourless oil; RF [light petroleum (b.p.
40–608C)–ether (19:1)] 0.37; vmax(film)/cmꢁ1 1732 (C¼¼O); dH (270 MHz,
CDCl3) 7.30–7.26 (1 H, m, CH; Ar), 7.17–7.13 (3 H, m, 3 ꢀ CH; Ar), 5.94 (1 H,
dd, J=7.7 and 1.9, CHOAc), 3.01–2.92 (1 H, m, CHAHB), 2.79–2.70 (1 H, m,
CHAHB), 2.13 (3 H, s, CH3), 1.96–1.52 (4 H, m, 2 ꢀ CH2) and 1.82–1.69 (2 H,
m, CH2); dC (100 MHz, CDCl3) 170.0 (COCH3), 141.4 and 140.2 (2 ꢀ i-C; Ar),
135.7, 129.7, 127.5 and 126.0 (4 ꢀ CH; Ar), 75.9 (CH–O), 33.4, 27.6 and 27.2
(3 ꢀ CH2), and 21.3 (COCH2).
6,7-Dideutero-8,9-dihydro-5H-benzocyclohepten-5-yl acetate [D2]-22
Under the same conditions as acetate 5, 8,9-dihydro-7H-benzocyclohepten-5-
yl acetate 15 (0.16 g, 0.8 mmol) in toluene (1.5 ml), Pd-on-BaSO4 (40 mg, 5%
on BaSO4 unreduced) and deuterium gas (250 ml) gave, after flash column
chromatography on silica gel eluting with light petroleum (b.p. 40–608C)–ether
(9:1), acetate [D2]-22 (0.14 g, 87%) as a colourless oil; RF [light petroleum (b.p.
40–608C)–ether (9:1)] 0.37; vmax(film)/cmꢁ1 2130 (C–D) and 1732 (C¼¼O); dH
(270 MHz, CDCl3) 7.24–7.16 (1 H, m, CH; Ar), 7.17–7.11 (3 H, m, 3 ꢀ CH;
Ar), 5.94 (1 H, d, J=8.1, CHOAc) (see footnote }), 2.97 (1 H, dd, J=4.7 and
13.9, CHAHB), 2.76 (1 H, dd, J=13.9 and 1.9, CHAHB), 2.13 (3 H, s, CH3),
1.93–1.81 (3 H, m, CH2 and CHD), 1.73–1.53 (2 H, m, CH2); dC (100 MHz,
CDCl3) 170.0 (COCH3), 141.3 and 140.2 (2 ꢀ i-C; Ar), 129.7, 127.5 and 126.0
1
(3 ꢀ CH; Ar), 75.9 (CD–O), 35.7 (CH2), 33.7 (1 C, quintet, JCD=20 Hz,
CDH), 27.2 (CH2), 17.1 (CHD) and 21.3 (COCH3); (m/z) 224.1 (30%, MD2 +
NH+4 ), 223.1 (50, MD1 + NH4+), 222.1 (30, MD0 + NH+4 ), 164.2 (60, MD2
+
H – Ac + H), 163.1 (100, MD1 + H – Ac + H) and 162.1 (60, MD0 + H – Ac
+H). The isotopic shift at C(1) (75.9 ppm) was 0.40 ppm (1 C, t,
1JCD=20 Hz).
Acknowledgements
We thank GOSS Scientific Instruments Ltd and AstraZeneca (David J.
Wilkinson, Loughborough, UK) for their interest and generous support. We
are also grateful to the EPRSC National Mass Spectrometry Service
(Swansea) for mass determination.
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Copyright # 2005 John Wiley & Sons, Ltd.
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