Intermolecular C-H and Si-H insertion reactions with halodiazoacetates

Article abstract of DOI:10.1055/s-0028-1083272

Ethyl halodiazoacetates react with a range of substrates in regioselective rhodium(II)-catalysed C-H and Si-H insertion reactions giving α-halocarbonyl products in up to 82% yield. The halodiazoacetates are a novel class of diazo compounds that can undergo intermolecular carbenoid C-H insertion reactions, thus broadening the synthetic utility of such reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083272

PAPER
91
Intermolecular C–H and Si–H Insertion Reactions with Halodiazoacetates
I
ntermolecular C–H
a
andSi–H
n
InsertionRe
n
actions with
e
H
alodiazoacetate
T
s
herese Bonge, Tore Hansen*
Department of Chemistry, University of Oslo, Sem Sælands vei 26, 0315 Oslo, Norway
Fax +47(22)855441; E-mail: torehans@kjemi.uio.no
Received 20 October 2008
NXS
DBU
EtOOC
H
EtOOC
X
Abstract: Ethyl halodiazoacetates react with a range of substrates
in regioselective rhodium(II)-catalysed C–H and Si–H insertion
reactions giving a-halocarbonyl products in up to 82% yield. The
halodiazoacetates are a novel class of diazo compounds that can un-
dergo intermolecular carbenoid C–H insertion reactions, thus
broadening the synthetic utility of such reactions.
N2
N2
CH2Cl2
0 °C, 5 min
1: X = Br
2: X = Cl
3: X = I
Scheme 1 Formation of halodiazoacetates
Key words: C–H insertion, Si–H insertion, diazo compounds,
rhodium, halides
sation in C–H insertion reactions would be a powerful
synthetic tool, generating a new C–C bond as well as in-
troducing both an ester functionality and a halogen that
can be utilised in further transformations. Around 1970,
Schöllkopf et al. reported the use of free carbenes gener-
ated by irradiation of 1 and 3, bromo- and iodoethoxy-
carbonylcarbene, in a C–H insertion reaction with
cyclohexane.13 Only 5–6% of the respective C–H inser-
tion products were detected, and no other substrates were
tested. However, the introduction of rhodium(II) catalysts
in the mid 1970s has since then resulted in an immense
improvement in the synthetic use of carbene reactions.
Modulation of reactivity through coordination of the car-
bene to the metal centre enables an increased level of both
regio- and stereoselectivity. Prompted by the desirable re-
activity shown by diazo compounds 1–3 in the rhodi-
um(II)-catalysed cyclopropanations, we decided to
investigate their effectiveness in rhodium(II)-catalysed
C–H insertions as well.
The development of methods for selective, catalytic C–H
activation is an area of immense current interest and great
practical importance.1–5 Through the functionalisation of
C–H bonds that traditionally have been considered inert,
new synthetic strategies are made available. One attrac-
tive method for derivatisation of C–H bonds is the metal-
catalysed decomposition of diazo compounds to metal
carbenoids that can insert into unactivated C–H bonds.5–8
This results in C–H insertion reactions of high regio- and
stereoselectivity, generating new C–C bonds while allow-
ing mild conditions. Whereas the field of intramolecular
metal carbenoid-induced C–H insertions is well estab-
lished,9 intermolecular versions have proved more chal-
lenging, with a rather limited choice of usable diazo
compounds. The area has been dominated by rhodium(II)-
stabilised donor/acceptor-substituted carbenoids,5,7,10
containing both an electron-withdrawing group, ensuring
high enough electrophilicity, and an electron-releasing
group, modulating their reactivity. With such carbenoids,
both yields and selectivity tend to be good. Examples of
C–H insertions with other classes of diazo compounds are
few and far between.6,11 The need for specialised, non-
commercial catalysts or inconvenient reaction procedures
significantly reduce their synthetic utility.
Cyclohexa-1,4-diene was selected as the substrate for the
initial experiments, as C–H insertion reactions are espe-
cially effective at allylic sites.11,14 A test experiment was
conducted, employing conditions analogous to the condi-
tions used in the previously described cyclopropanation
reaction:12 1 mol% Rh2(esp)2 dissolved in toluene was
added to a solution of freshly prepared 1 and cyclohexa-
1,4-diene in toluene at ambient temperature, and stirred
for 15 minutes. We were pleased to see that this gave 39%
of the C–H insertion product 4 (Scheme 2).
We recently described a novel method for very facile for-
mation of halodiazoacetates (Scheme 1).12 Ethyl diazo-
bromoacetate (1), -chloroacetate (2) and -iodoacetate (3)
are generated quantitatively from EDA in only five min-
utes reaction time, by stirring with DBU and an N-halo-
succinimide in dichloromethane.
Br
COOEt
H
EtOOC
Br
Rh2Ln
+
N2
When used in rhodium(II)-catalysed intermolecular cy-
clopropanation reactions, halodiazoacetates 1–3 gave
high yields and good diastereoselectivity, illustrating how
these halogenated diazo compounds represent a novel
method for selective introduction of halogens. Their utili-
toluene
r.t., 15 min
1
4
Scheme
2
Synthesis of ethyl 2-bromo-2-(cyclohexa-2,5-di-
enyl)acetate
SYNTHESIS 2009, No. 1, pp 0091–0096
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1083272; Art ID: C04808SS
© Georg Thieme Verlag Stuttgart · New York
0
2
.
0
1
.2
0
0
9
Although a good catalyst in carbenoid cyclopropanation
reactions15,16 and nitrene C–H insertions,17 Rh2(esp)2 has
not yet been used successfully in a carbenoid C–H inser-

92
H. T. Bonge, T. Hansen
PAPER
tion reaction. A screening of catalysts was therefore per- 3, where rapid formation of free iodine was observed both
formed, using the same conditions (Table 1).
during workup and storage of the C–H insertion product.
Table 2 C–H Insertion Reaction of 1–3 with Cyclohexa-1,4-diene
Table 1 Catalyst Screening in the C–H Insertion Reaction of 1 with
Cyclohexa-1,4-diene
Entry
Diazo compound
Yield (%)a
Entry
Catalyst
Yield of 4 (%)a
1
2
3
ethyl diazobromoacetate (1)
ethyl diazochloroacetate (2)
ethyl diazoiodoacetate (3)
68
53
45
1
2
3
4
5
6
7
Rh2(TPA)4
Rh2(esp)2
68
39
29
18
15
0
Rh2(TFA)4
Rh2(OOct)4
Rh2(S-DOSP)4
Rh2(TMA)4
AgSbF6
a Isolated yield after silica gel chromatography.
In order to examine the reaction scope, C–H and Si–H in-
sertion reactions of 1 with a variety of substrates were car-
ried out (Table 3). In all of the reactions the desired C–H
or Si–H insertion products were formed, with yields vary-
ing from 82% with phthalan (entry 1) to 2% with the more
challenging substrate adamantane (entry 6). The regiose-
lectivity was high and predictable in all cases. The C–H
insertion reactions are known to take place preferentially
into the more electron-rich C–H bonds,10 and the results
were consistent with this: C–H insertion took place in the
allylic position of cyclohexa-1,4-diene (entry 2), at the
tertiary site in adamantane (entry 6), and into the C–H
bonds of sp3-centers a to oxygen or nitrogen in the cases
of phthalan, THF, and N,N-dimethylaniline (entries 1, 3,
and 4). No other regioisomers were observed.
0
a Measured by internal standard (2-naphthaldehyde) in 1H NMR anal-
ysis of crude reaction mixture.
The results from the screening showed that the yield of 4
was substantially affected by the ligands of the rhodi-
um(II) catalysts, but no obvious trends were observed.
The sterically encumbered tetrakis(triphenylaceta-
to)dirhodium(II) [Rh2(TPA)4], gave the highest yield;
68% (entry 1). The chiral catalyst Rh2(S-DOSP)4 is
known as an efficient catalyst in C–H insertions of donor/
acceptor-substituted diazo compounds,5 but gave only
15% of 4 (entry 5), highlighting the difference between
the two classes of diazo compounds. All of the tested cat-
alysts gave complete decomposition of 1; the only ob-
served by-products were the products from carbene
dimerisation. Even though both Rh2(esp)2 and AgSbF6
have been shown to favour cyclopropanation over C–H
insertion in the case of donor/acceptor-substituted diazo
compounds,15,18 no cyclopropanation products were ob-
served in any of the experiments.
Initially, all C–H insertion reactions were performed with
Rh2(TPA)4 as the catalyst. As Si–H insertions typically
are more favoured,19,20 the lower-priced Rh2(esp)2 was
used in these reactions. However, the results from the cat-
alyst screening in Table 1 turned out not to be transferable
to all of the C–H insertion substrates. In the reactions with
phthalan and THF (entries 1 and 3), yields with
Rh2(TPA)4 as the catalyst were rather low. Using
Rh2(esp)2, however, gave good yields of 82 and 63%, re-
spectively. This effect was not observed with neither N,N-
dimethylaniline (entry 4) nor cyclohexane (entry 5), for
which only trace amounts of product was observed when
Rh2(esp)2 was used. With adamantane (entry 6), yields
were similarly low employing both catalysts.
In order to examine solvent effects, an experiment was
performed using Rh2(TPA)4 and the standard conditions,
but with hexane instead of toluene. This lowered the yield
substantially, to 41%. Slow, dropwise addition of the dia-
zo compound to the substrate and catalyst, instead of bulk
addition, was also tried, but had no effect on the outcome
of the reaction. Neither did increasing the amount of cy-
clohexa-1,4-diene from two to five equivalents. Wanting
to keep the simplicity of the procedure, no further changes
in reaction conditions were tested.
As rhodium(II)-catalysed decomposition of halodiazoace-
tates is fast at room temperature, the different yields of the
various products in Table 3 are most likely a direct conse-
quence of how efficiently the substrates trap the car-
benoid. The reactivity of the substrates seems to largely
mirror the reactivity observed in C–H insertions with do-
nor/acceptor-substituted diazo compounds,14 with C–H
bonds in allylic positions being more reactive than C–H
bonds a to oxygen, followed by those a to nitrogen. The
nonactivated substrates give the lowest yields, with ada-
mantane being a poorer substrate than cyclohexane. The
high yield in the reaction with phthalan might be ex-
plained by the fact that the reacting C–H bond is benzylic
as well as in a position to an oxygen atom, both of which
are activating factors. An experiment with cyclohepta-
1,3,5-triene as the substrate was also conducted. This gave
Following the standard procedure, and using Rh2(TPA)4
as catalyst, C–H insertion reactions of ethyl diazochloro-
acetate (2) and ethyl diazoiodoacetate (3) with cyclohexa-
1,4-diene were performed (Table 2). The reactions gave
yields of 53 and 45% of the C–H insertion products, re-
spectively (entries 2 and 3). Again, no cyclopropanation
products were observed. The lower yields of the reactions
of 2 and 3 compared to 1 may in part be explained by
product instability. This was especially clear in the case of
Synthesis 2009, No. 1, 91–96 © Thieme Stuttgart · New York

PAPER
Intermolecular C–H and Si–H Insertion Reactions with Halodiazoacetates
93
(2R*,3R*)-diastereomer, whereas Rh2(esp)2 gave a dr of
1.2:1, favouring the opposite diastereomer. The dr of the
products formed from THF (entry 3) was 2.5:1 in both
cases, with (2R*,3R*) as the major diastereomer. These
results are in the same area as the dr reported for reactions
of donor/acceptor-substituted diazo compounds.5
Table 3 Scope of C–H and Si–H Insertions with 1
Entry
1
Substrate
Product
Yield drb
(%)a
Br
COOEt
82c
35d
1.2:1c
1:2d
O
Rhodium(II)-catalysed Si–H insertion reactions are an-
other well-established, synthetically useful class of car-
benoid insertion into bonds of low polarity.19,20 A wide
range of diazo compounds readily partake in Si–H inser-
tion reactions, including compounds that react only poorly
in C–H insertion reactions. The products from Si–H inser-
tion reactions between 1 and triphenylsilane (entry 8) and
dimethylphenylsilane (entry 9) were isolated in yields of
51 and 25%, respectively. For diphenylsilane (entry 7) the
O
Br
2
3
4
68d
–
COOEt
Br
63c
10d
2.5:1c
2.5:1d
O
O
COOEt
Br
1
yield was measured to 80% by internal standard in H
Me
N
Me
40d
–
–
NMR spectroscopy. However, all attempts of purification
by chromatography resulted in decomposition of the prod-
uct; silica, neutral alumina and basic alumina all led to
rapid evolution of gas. The product from this decomposi-
tion reaction was isolated and characterised as disilane 5
(Figure 1).
N
COOEt
Me
Br
5
6
12d,e
COOEt
Ph
Ph
OH
Br
COOEt
Si Si
2c
–
Ph
H
Ph
5
Br
Figure 1 Product formed after attempted purification of ethyl 2-
bromo-2-diphenylsilylacetate on silica gel
Ph
Ph
H
H
7
8
9
80d,f
51c
–
–
–
Ph
Ph
Si
Si
Si
COOEt
Si
H
Assuming that the hydroxy group in 5 originated from wa-
ter present in the silica gel or alumina, we decided to ex-
amine the observed reaction: The Si–H insertion reaction
was repeated, but instead of the normal workup, three
equivalents of ethanol was added to the crude product
mixture. This resulted in evolution of gas. As always, the
Si–H insertion was performed using two equivalents of
diphenylsilane. 1H NMR analysis of the crude mixture af-
ter stirring with ethanol for one hour at room temperature
revealed that all of the excess diphenylsilane now had
been consumed, whereas the Si–H insertion product re-
mained. The mixture was then placed on a silica gel col-
umn, and once again gas evolution was observed. NMR
analysis after flash chromatography showed that the Si–H
insertion product now also had been consumed, and disi-
lane 6 (Figure 2) was isolated as the main product in a
yield of 24%.
Br
Ph
Ph
H
Ph
Ph
COOEt
COOEt
Si
Ph
Ph
Br
Ph
H
25c
Ph
Si
Me
Me
Me
Me
a Isolated yield after silica gel chromatography.
b Measured by 1H NMR analysis of the crude reaction mixture.
c Catalyst: Rh2(esp)2.
d Catalyst: Rh2(TPA)4.
e Cyclohexane was used both as reactant and solvent.
f Yield measured by internal standard (1,3,5-trimethoxybenzene) in
the 1H NMR analysis of the crude reaction mixture, as the product de-
composed.
cyclopropanes as the main product, and no C–H insertion
product was observed. This chemoselectivity contrasts
that of donor/acceptor-substituted diazo compounds, for
which C–H insertion is the dominating reaction.14
Ph
Ph
OEt
Si Si
Ph
H
Ph
In the cases of phthalan and THF, diastereomeric products
were formed. The relative stereochemistry of the diastere-
omers was assigned by comparison with an analogous
compound described in the literature.21 For phthalan (en-
try 1) the diastereomeric ratio (dr) was dependent on the
catalyst; Rh2(TPA)4 gave a dr of 1:2, favouring the
6
Figure 2 Product from the treatment of the crude mixture obtained
from the reaction of 1 with ethanol and silica gel
Synthesis 2009, No. 1, 91–96 © Thieme Stuttgart · New York

94
H. T. Bonge, T. Hansen
PAPER
at r.t. The solvent was evaporated in vacuo, and the crude product
was purified by flash chromatography (Tables 2 and 3).
To the best of our knowledge, this is the first example of
generation of disilanes from carbenoid Si–H insertion
products. Further examinations of this transformation are
currently carried out, and will be reported in due time.
Ethyl 2-Bromo-2-(cyclohexa-2,5-dienyl)acetate (4)
Yield: 0.084 g (0.3 mmol, 68%); colourless oil.
The products formed by C–H insertions of halodiazoace-
tates 1–3 are highly versatile building blocks in organic
synthesis. The greatest synthetic possibilities may be of-
fered by the halogen, due to the rapid development in cou-
pling chemistry, but a variety of other transformations are
also possible. One example of transformations of C–H in-
sertion product 4 is shown in Scheme 3.
1H NMR (300 MHz, CDCl3): d = 1.26–1.31 (t, J = 7.1 Hz, 3 H,
CH3), 2.62–2.66 (m, 2 H, CH2), 3.34–3.44 (m, 1 H, CH), 4.06–4.08
(d, J = 7.7 Hz, 1 H, CHBr), 4.20–4.27 (q, J = 7.1 Hz, 2 H, CH2),
5.54–5.60 (m, 1 H, CH), 5.81–5.93 (m, 3 H, CH).
13C NMR (75 MHz, CDCl3): d = 14.0 (CH3), 26.6 (CH2), 38.8 (CH),
51.1 (CHBr), 62.0 (CH2), 124.0 (CH), 124.6 (CH), 127.4 (CH),
128.4 (CH), 168.7 (COO).
MS (EI): m/z (%) = 244/246 (2.3/2.2, [M+]), 165 (53), 138 (25), 119
(18), 91 (100), 79 (93).
HRMS: m/z calcd for C10H1379BrO2: 244.0099; found: 244.0104 (D:
–2.2 ppm).
Br
COOEt
Br
COOEt
N3
COOEt
NaN3
DMF
DDQ
MeOH
82%
67%
Ethyl 2-Chloro-2-(cyclohexa-2,5-dienyl)acetate (Table 2, Entry
2)
4
7
8
Yield: 0.053 g (0.3 mmol, 53%); colourless oil.
Scheme 3 Transformation of 4
1H NMR (300 MHz, CDCl3): d = 1.30–1.35 (t, J = 7.1 Hz, 3 H,
CH3), 2.67–2.73 (m, 2 H, CH2), 3.42–3.51 (m, 1 H, CH), 4.21–4.23
(d, J = 6.4 Hz, 1 H, CHCl), 4.24–4.31 (q, J = 7.1 Hz, 2 H, CH2),
5.60–5.65 (m, 1 H, CH), 5.76–5.81 (m, 1 H, CH), 5.92–5.98 (m, 2
H, CH).
13C NMR (75 MHz, CDCl3): d = 14.1 (CH3), 26.4 (CH2), 39.5 (CH),
61.2 (CHCl), 62.0 (CH2), 123.3 (CH), 123.7 (CH), 127.8 (CH),
128.3 (CH), 168.5 (COO).
In this reaction sequence, the cyclohexadienyl ring of 4
was aromatised by oxidation with DDQ, giving 7 in 82%
yield. Exploiting the presence of the halogen, the C–H in-
sertion products can be used as precursors in the introduc-
tion of a range of other functional groups, here illustrated
by a substitution with azide. Treatment of 7 with sodium
azide gave 67% of 8.
MS (EI): m/z (%) = 200/202 (3.4/0.8, [M+]), 165 (10), 111 (24), 85
(51), 71 (69), 57 (100).
In summary, we have developed a quick and facile proce-
dure for C–H and Si–H insertion reactions of halodiazo-
acetates. Ethyl diazobromoacetate (1), -chloroacetate (2)
and -iodoacetate (3) insert regioselectively into C–H and
HRMS: m/z calcd for C10H1335ClO2: 200.0604; found: 200.0600 (D:
2.1 ppm).
Ethyl 2-Iodo-2-(cyclohexa-2,5-dienyl)acetate (Table 2, Entry 3)
Si–H bonds of a range of substrates, with yields up to Yield: 0.065 g (0.2 mmol, 45%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 1.25–1.29 (t, J = 7.1 Hz, 3 H,
CH3), 2.44–2.68 (m, 2 H, CH2), 3.12–3.23 (m, 1 H, CH), 4.13–4.16
(d, J = 7.8 Hz, 1 H, CHI), 4.17–4.24 (m, 2 H, CH2), 5.55–5.61 (m,
1 H, CH), 5.85–5.92 (m, 3 H, CH).
13C NMR (75 MHz, CDCl3): d = 13.8 (CH3), 26.7 (CH2), 29.9
(CHI), 38.5 (CH), 61.8 (CH2), 124.8 (CH), 126.9 (CH), 127.2 (CH),
128.1 (CH), 170.3 (COO).
82%. The halodiazoacetates are a novel class of diazo
compounds that can be used in intermolecular carbenoid
C–H insertion reactions, thus broadening the synthetic
utility of such reactions. The products from the C–H inser-
tions of 1–3 are a-halocarbonyl compounds that can par-
take in a range of further transformations.
MS (EI): m/z (%) = 179 (8), 163 (100), 135 (15), 105 (84), 91 (29).
HRMS: m/z calcd for C10H12O2 (M+ – HI): 164.0837; found:
164.0841 (D: –2.3 ppm).
1H and 13C NMR spectra were recorded in CDCl3 on a Bruker
Avance spectrometer at 300 MHz and 75 MHz, respectively. Chem-
ical shifts (d) are reported in ppm relative to CHCl3 (7.24 and 77.00
ppm for 1H and 13C, respectively). Mass spectra were recorded on a
Micromas Q-Tof-2 mass spectrometer (ESI) or a Fissions Instru-
ments VG Prospec sector instrument at 70 eV (EI). For high-resolu-
tion MS measurements, perfluorokerosene was used as a reference
compound.
Ethyl 2-Bromo-2-(1,3-dihydroisobenzofuran-3-yl)acetate
(Table 3, Entry 1)
Yield: 0.117 g (0.4 mmol, 82%); light yellow oil.
Data reported for a mixture of both diastereomers (DS1 and DS2).
DS1 = (2R*,3R*).
Intermolecular C–H and Si–H Insertion Reactions with Halodi-
azoacetates; General Procedure
1H NMR (300 MHz, CDCl3): d = 1.24–1.31 (m, 2 × 3 H, CH3),
4.34–4.30 (m, 2 × 2 H, CH2), ca 4.26 (m, 1 H, CHBr, DS1), 4.46–
4.48 (d, J = 5.5 Hz, 1 H, CHBr, DS2), 5.02–5.12 (m, 2 H, CH2O,
DS2), 5.16–5.25 (m, 2 H, CH2O, DS1), 5.65–5.68 (m, 1 H, CHO,
DS1), 5.71–5.74 (m, 1 H, CHO, DS2), 7.14–7.57 (8 H).
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 14.1 (CH3), 47.9 (CH-
Br, DS1), 50.5 (CHBr, DS2), 62.1 (CH2), 62.3 (CH2), 73.2 (CH2O,
DS2), 73.7 (CH2O, DS1), 83.4 (CHO, DS1), 83.8 (CHO, DS2),
120.9 (CH), 121.2 (CH), 121.9 (CH), 123.6 (CH), 127.2 (CH),
128.6 (CH), 128.7 (CH), 137.4 (C), 137.5 (C), 139.6 (C), 139.8 (C),
167.5 (COO), 168.0 (COO).
N-Halosuccinimide (0.6 mmol) was added to a solution of EDA
(0.057 g, 0.5 mmol) and DBU (0.11 mL, 0.7 mmol) in CH2Cl2 (2.5
mL) at 0 °C, and the mixture was stirred for 5 min. The crude mix-
ture was washed with cold 20% aq Na2S2O3 (3 × 2 mL), dried
(MgSO4) at 0 °C and passed quickly through a silica gel column us-
ing cold CH2Cl2 as eluent. Toluene (5.0 mL) was added, and the
CH2Cl2 was removed in vacuo at 0 °C. The appropriate substrate
(1.0 mmol) was then added at 0 °C, and the temperature was slowly
increased to r.t. A solution of Rh2(TPA)4 (0.007 g, 0.005 mmol) in
toluene (1.0 mL) was added, and the mixture was stirred for 15 min
Synthesis 2009, No. 1, 91–96 © Thieme Stuttgart · New York

PAPER
Intermolecular C–H and Si–H Insertion Reactions with Halodiazoacetates
95
MS (EI): m/z (%) = 205 (47), 159 (33), 131 (39), 119 (100), 91 (68).
Ethyl 2-Bromo-2-diphenylsilylacetate (Table 3, Entry 7)
Yield: 80%, determined by internal standard (1,3,5-trimethoxyben-
HRMS (ESI): m/z calcd for C12H1379BrO3 + Na: 306.9945; found:
306.9939 (D: –2.2 ppm).
zene) in the 1H NMR spectrum of the crude product mixture.
1H NMR (300 MHz, CDCl3): d = 1.04–1.08 (t, J = 7.1 Hz, 3 H,
CH3), 3.99–4.11 (m, 2 H, CH2), 4.20–4.21 (d, J = 2.9 Hz, 1 H, CH-
Br), 5.31–5.23 (d, J = 2.9 Hz, SiH), 7.55–7.67 (m, 6 H, CH), 7.81–
7.95 (m, 4 H, CH).
Ethyl 2-Bromo-2-(tetrahydrofuran-2-yl)acetate (Table 3, Entry
3)
Yield: 0.078 g (0.3 mmol, 63%); colourless oil.
Data reported for mixture of both diastereomers (DS1 and DS2).
DS1 = (2R*,3R*).
13C NMR (75 MHz, CDCl3): d = 13.7 (CH3), 30.5 (CHBr), 61.9
(CH2), 128.1 (CH), 130.6 (CH), 134.7 (C), 135.6 (CH), 169.0
(COO).
MS (EI): m/z (%) = 348/350 (1.7/1.7, [M+]), 269 (58), 227 (60), 183
(100), 151 (56), 105 (63), 91 (40) (measured for crude product mix-
ture.)
1H NMR (300 MHz, CDCl3): d = 1.23–1.30 (m, 2 × 3 H, CH3),
1.70–2.20 (m, 2 × 2 H, CH2), 3.79–3.93 (m, 2 × 2 H, CH2O), 3.99–
4.02 (d, J = 8.9 Hz, 1 H, CHBr, DS2), 4.17–4.25 (m, 2 × 2 H, CH2),
ca. 4.19 (m, 1 H, CHBr, DS1), 4.26–4.33 (m, 1 H, CHO, DS1),
4.33–4.40 (m, 1 H, CHO, DS2).
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 13.9 (CH3), 25.7 (CH2,
DS2), 26.1 (CH2, DS1), 29.6 (CH2, DS1), 29.9 (CH2, DS2), 47.5
(CHBr, DS2), 49.0 (CHBr, DS1), 62.0 (CH2, DS2), 62.0 (CH2,
DS1), 68.9 (CH2O, DS1), 69.4 (CH2O, DS2), 79.0 (CHO, DS2),
79.2 (CHO, DS1), 168.1 (COO, DS1), 168.5 (COO, DS2).
HRMS: m/z calcd for C16H1679BrO2Si: 347.0103; found: 347.0090
(D: 3.6 ppm).
Ethyl 2-Bromo-2-triphenylsilylacetate (Table 3, Entry 8)
Yield: 0.109 g (0.3 mmol, 51%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 0.89–0.99 (t, J = 7.1 Hz, 3 H,
CH3), 3.75–4.00 (m, 2 H, CH2), 4.39 (s, CHBr), 7.35–7.48 (m, 9 H,
CH), 7.63–7.67 (m, 6 H, CH).
13C NMR (75 MHz, CDCl3): d = 13.6 (CH3), 31.6 (CHBr), 61.9
(CH2), 127.9 (CH), 130.3 (CH), 131.3 (C), 136.3 (CH), 169.8
(COO).
MS (EI): m/z (%) = 424/426 (0.3/0.3, [M+]), 345 (8), 259 (100), 227
(66), 181 (21), 105 (17), 77 (9).
HRMS (EI): m/z calcd for C22H2179BrO2Si: 424.0494; found:
424.0510 (D: –3.7 ppm).
MS (EI): m/z (%) = 157 (7), 111 (13), 71 (100), 43 (24).
HRMS (ESI): m/z calcd for C8H1379BrO3 + Na: 258.9945; found:
258.9943 (D: –1.1 ppm).
Ethyl 2-Bromo-3-(N-methyl-N-phenylamino)propanoate
(Table 3, Entry 4)
Yield: 0.057 g (0.2 mmol, 40%); light yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.22-1.26 (t, J = 7.1 Hz, 3 H,
CH3), 2.98 (s, 3 H, CH3), 3.75–3.82 (dd, J = 5.1, 15.1 Hz, 1 H,
CH2), 3.97–4.04 (dd, J = 9.5, 15.1 Hz, 1 H, CH2), 4.12–4.22 (m, 2
H, CH2), 4.36–4.41 (dd, J = 5.1, 9.5 Hz, 1 H, CHBr), 6.66–7.34 (m,
5 H, CH).
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 39.3 (CH3), 41.3 (CH-
Br), 56.6 (CH2), 62.2 (CH2), 112.2 (CH), 119.8 (CH), 129.4 (CH),
147.9 (C), 169.3 (COO).
Ethyl 2-Bromo-2-dimethylphenylsilylacetate (Table 3, Entry 9)
Yield: 0.038 g (0.1 mmol, 25%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 0.51 (s, 3 H, CH3), 0.53 (s, 3 H,
CH3), 1.05–1.10 (t, J = 7.1 Hz, CH3), 3.80 (s, 1 H, CHBr), 3.94–
4.11 (m, 2 H, CH2), 7.32–7.43 (m, 3 H, CH), 7.50–7.55 (m, 2 H,
CH).
MS (EI): m/z (%) = 285/287 (7.4/7.4, [M+]), 132 (18), 120 (100),
104 (11), 77 (30).
HRMS: m/z calcd for C12H1679BrNO2: 285.0364; found: 285.0363
(D: 0.4 ppm).
13C NMR (75 MHz, CDCl3): d = –4.5 (CH3), –4.2 (CH3), 14.0
(CH3), 34.5 (CHBr), 61.7 (CH2), 127.9 (CH), 130.1 (CH), 133.5
(C), 134.0 (CH), 169.8 (COO).
MS (EI): m/z (%) = 300/302 (0.1/0.1, [M+]), 221 (21), 165 (34), 135
(100), 103 (68), 75 (21).
HRMS (EI): m/z calcd for C12H1779BrO2Si: 300.0181; found:
300.0192 (D: –3.7 ppm).
Ethyl 2-Bromo-2-cyclohexylacetate (Table 3, Entry 5)
Yield: 0.015 g (0.06 mmol, 12%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 1.25–1.30 (t, J = 7.1 Hz, 3 H,
CH3), 1.51–1.66 (m, 10 H), 1.79–1.87 (m, 2 H), 1.97–2.02 (m, 3 H),
3.92 (s, 1 H, CHBr), 4.15–4.23 (m, 2H, CH2).
13C NMR (75 MHz, CDCl3): d = 14.1 (CH3), 28.3 (CH), 36.5 (CH2),
39.0 (CH2), 59.8 (CHBr), 61.5 (CH2), 164.6 (COO).
1,1,2,2-Tetraphenyldisilanol (5)
1H NMR (300 MHz, CDCl3): d = 4.96 (s, 1 H, OH), 5.63 (s, 1 H,
SiH), 7.34–7.46 (m, 8 H, CH), 7.55–7.67 (m, 12 H, CH).
MS (EI): m/z (%) = 205 (8), 166 (100), 138 (31), 95 (45), 55 (35).
13C NMR (75 MHz, CDCl3): d = 127.9 (CH), 130.2 (CH), 134.3
(CH), 134.9 (C).
Ethyl 2-Bromo-2-adamantylacetate (Table 3, Entry 6)
Yield: 0.03 g (0.01 mmol, 2%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 1.25–1.30 (t, J = 7.1 Hz, 3 H,
CH3), 1.51–1.66 (m, 10 H), 1.79–1.87 (m, 2 H), 1.97–2.02 (m, 3 H),
3.92 (s, 1 H, CHBr), 4.15–4.23 (m, 2 H, CH2).
MS (EI): m/z (%) = 382 (4, [M+]), 381 (5), 303 (73), 226 (100), 181
(24), 105 (11).
HRMS (EI): m/z calcd for C24H2179BrOSi2 (M+ – H): 381.1131;
found: 381.1122 (D: 2.4 ppm).
13C NMR (75 MHz, CDCl3): d = 14.1 (CH3), 28.3 (CH), 36.5 (CH2),
39.0 (CH2), 59.8 (CHBr), 61.5 (CH2), 164.6 (COO).
1-Ethoxy-1,1,2,2-tetraphenyldisilane (6)
Yield: 0.050 g (0.1 mmol, 24%); colourless oil.
MS (EI): m/z (%) = 300/302 (0.4/0.4, [M+]), 272 (2), 177 (2), 135
(100), 91 (5).
HRMS: m/z calcd for C14H2179BrO2: 300.0725; found: 300.0723 (D:
0.8 ppm).
1H NMR (300 MHz, CDCl3): d = 1.34–1.39 (t, J = 7.0 Hz, 3 H,
CH3), 3.95–4.02 (q, J = 7.0 Hz, 2 H, CH2), 5.73 (s, 1 H, SiH), 7.37–
7.53 (m, 8 H, CH), 7.66–7.81 (m, 12 H, CH).
13C NMR (75 MHz, CDCl3): d = 18.3 (CH3), 58.9 (CH2), 127.9
(CH), 130.2 (CH), 134.3 (C), 134.9 (CH).
Synthesis 2009, No. 1, 91–96 © Thieme Stuttgart · New York

96
H. T. Bonge, T. Hansen
PAPER
MS (EI): m/z (%) = 382 (11), 349 (8), 303 (75), 226 (100), 181 (36),
105 (21).
References
(1) Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001, 2437.
(2) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson,
T. H. Acc. Chem. Res. 1995, 28, 154.
HRMS (EI): m/z calcd for C24H21OSi2 (M+ – Et): 381.1131; found:
381.1115 (D: 4.1 ppm).
(3) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507.
(4) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102,
1731.
(5) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103,
2861.
(6) Díaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.;
Pérez, P. J. Dalton Trans. 2006, 5559.
(7) Davies, H. M. L.; Nicolai, J. Org. Biomol. Chem. 2005, 3,
Ethyl 2-Bromo-2-phenylacetate (7)22
A suspension of 4 (0.149 g, 0.61 mmol) and DDQ (0.275 g, 1.2
mmol) was stirred in toluene (5 mL) for 1 h at r t. The crude mixture
was filtered, concentrated in vacuo, and purified by silica gel chro-
matography; yield: 0.121 g (0.50 mmol, 82%); colourless oil.
1H NMR (300 MHz, CDCl3): d = 1.23–1.30 (t, J = 7.1 Hz, 3 H,
CH3), 4.17–4.23 (m, 2 H, CH2), 5.32 (s, 1 H, CH), 7.30–7.38 (m, 3
4176.
Harom), 7.49–7.56 (m, 2 Harom).
(8) Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417.
(9) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds:
From Cyclopropanes to Ylides; Wiley: New York, 1998,
112.
(10) Davies, H. M. L.; Loe, Ø. Synthesis 2004, 2595.
(11) Müller, P.; Tohill, S. Tetrahedron 2000, 56, 1725.
(12) Bonge, H. T.; Pintea, B.; Hansen, T. Org. Biomol. Chem.
2008, 6, 3670.
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 46.8 (CH), 62.5 (CH2),
128.6 (2 × CHarom), 128.8 (2 × CHarom), 129.2 (CHarom), 135.9
(Carom), 168.3 (COO).
MS (EI): m/z (%) = 242/244 (2.5/4.5, [M+]), 169/171 (49/49), 163
(100), 135 (14), 91 (29).
HRMS: m/z calcd for C10H1179BrO2: 241.9942; found: 241.9946 (D:
–1.5 ppm).
Ethyl 2-Azido-2-phenylacetate (8)23
(13) Schöllkopf, U.; Reetz, M. Tetrahedron Lett. 1969, 20, 1541.
(14) Davies, H. M. L.; Antoulinakis, E. G. J. Organomet. Chem.
2001, 617-618, 47.
A mixture of 7 (0.115 g, 0.47 mmol) and NaN3 (0.047 g, 0.71 mmol)
was stirred in anhyd DMF (1 mL) under argon for 3 h at r t. After
the addition of H2O (4 mL), the crude mixture was extracted with
CH2Cl2 (3 × 1 mL). The combined organic layers were washed with
H2O (2 × 4 mL), dried (MgSO4), and concentrated in vacuo; yield:
0.065 g (0.32 mmol, 67%); light yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.19–1.25 (t, J = 7.1 Hz, 3 H,
CH3), 4.15–4.24 (q, J = 7.1 Hz, 2 H, CH2), 4.90 (s, 1 H, CH), 7.36
(br s, 5 H, CH).
(15) Davies, H. M. L.; Coleman, M. G.; Ventura, D. L. Org. Lett.
2007, 9, 4971.
(16) Bonge, H. T.; Hansen, T. Synlett 2007, 55.
(17) Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am.
Chem. Soc. 2004, 126, 15378.
(18) Thompson, J. L.; Davies, H. M. L. J. Am. Chem. Soc. 2007,
129, 6090.
(19) Bagheri, V.; Doyle, M. P.; Taunton, J.; Claxton, E. E. J. Org.
Chem. 1988, 53, 6158.
(20) Landais, Y.; Planchenault, D. Tetrahedron Lett. 1994, 35,
4565.
13C NMR (75 MHz, CDCl3): d = 13.9 (CH3), 62.5 (CHN3), 65.2
(CH2), 127.5 (CH), 129.0 (CH), 129.1 (CH), 133.9 (C), 169.0
(COO).
(21) Guindon, Y.; Guerin, B.; Chabot, C.; Ogilvie, W. J. Am.
Chem. Soc. 1996, 118, 12528.
(22) Guieysse, D.; Salagnad, C.; Monsan, P.; Remaud-Simeon,
M. Tetrahedron: Asymmetry 2003, 14, 317.
(23) Heras, M.; Ventura, M.; Linden, A.; Villalgordo, J. M.
Tetrahedron 2001, 57, 4371.
MS (EI): m/z (%) = 205 (2.1, [M+]), 180 (9), 134 (61), 104 (87), 77
(100).
HRMS: m/z calcd for C10H11N3O2: 205.0851; found: 205.0842 (D:
4.6 ppm).
Synthesis 2009, No. 1, 91–96 © Thieme Stuttgart · New York