Reductive carbonylation - An efficient and practical catalytic route for the conversion of aryl halides to aldehydes

Article abstract of DOI:10.1021/op060193w

Alternative routes for the introduction of aldehyde functionality are particularly desirable for fine chemical and pharmaceutical intermediates because of the wide range of further transformations that are possible. Catalytic processes are of particular interest for minimising waste, and therefore the reductive carbonylation of aryl halides has been explored. We have shown that high yields of aldehydes may be obtained for a wide selection of aryl iodides and bromides using mild conditions (3 bar of CO, temperatures 60-120°C) and silanes as hydride source. A choice of conditions (catalyst, base, solvent) is required to cover the range of aryl substituents varying in electron donation and steric influence. This is related to the competing needs of the several steps of this reaction, including oxidative addition, CO substitution, CO insertion, hydride transfer, and reductive elimination.

Full text of DOI:10.1021/op060193w

Organic Process Research & Development 2007, 11, 39−43
Reductive Carbonylation - an Efficient and Practical Catalytic Route for the
Conversion of Aryl Halides to Aldehydes
Laura Ashfield and Christopher F. J. Barnard*
Johnson Matthey Technology Centre, Blounts Court, Sonning Common, Reading RG4 9NH, UK
Abstract:
aldehydes under 1 bar of CO at 50 °C. Similar conditions
were applied by Smith et al. However, contamination with
Sn is highly undesirable for pharmaceutical products, and
5
Alternative routes for the introduction of aldehyde functionality
are particularly desirable for fine chemical and pharmaceutical
intermediates because of the wide range of further transforma-
tions that are possible. Catalytic processes are of particular
interest for minimising waste, and therefore the reductive
carbonylation of aryl halides has been explored. We have shown
that high yields of aldehydes may be obtained for a wide
selection of aryl iodides and bromides using mild conditions (3
bar of CO, temperatures 60-120 °C) and silanes as hydride
source. A choice of conditions (catalyst, base, solvent) is required
to cover the range of aryl substituents varying in electron
donation and steric influence. This is related to the competing
needs of the several steps of this reaction, including oxidative
addition, CO substitution, CO insertion, hydride transfer, and
reductive elimination.
3
other groups found R SiH to be equally effective. Pri-Bar
6
and Buchman demonstrated that poly(methylhydrosiloxane)
(PMHS) could be used at 50 psi of CO and 80 °C with Pd-
3
(0) or Pd(II). The reactivity of Et SiH was studied by Hidai
7
et al. for mixed metal Pd/Ru and Pd/Co systems, and they
identified routes to some of the byproducts. The conversion
of aryl/enol triflates to aldehydes was optimised by Kotsuki
8
et al. using Oct
3
SiH and other silanes under 1 atm of CO
/1,3-bis(diphenylphosphino)-
in DMF at 70 °C with Pd(OAc)
2
6
,9
propane as catalyst. Pri-Bar and Buchman also found that
sodium formate could be used as a hydrogen donor in the
absence of base in conjunction with 50 psi of CO. Cacchi et
1
0
al. recently developed the use of acetic formic anhydride
3
as an in situ CO source in conjunction with R SiH for the
conversion of aryl iodides.
In all these cases, the reactivity of the aryl halides follows
the expected pattern of ease of oxidative addition to Pd(0),
that is I > Br > Cl, with more extreme conditions being
required to obtain high yields with the bromides than for
the iodides, but with the chlorides being unreactive. Clearly,
reactions with aryl chlorides would be desirable from an
economic and practical point of view. Examples of this have
Introduction
The formation of reactive functional groups in selective
reactions from a choice of precursors is a matter of
fundamental interest to chemists and, in particular, for the
synthesis of fine and pharmaceutical chemicals. Aldehydes
are particularly desirable as functional groups because of the
wide range of further transformations that are possible.
However, simple routes to aldehydes have proved difficult
to develop. Stoichiometric reactions often involve harsh
conditions and result in significant quantities of waste
products. Therefore, catalytic processes to form aldehydes
have been a focus of interest for some time. Early work by
11
been demonstrated by Basset et al. using tricarbonyl-
12
2
(chloroarene)chromium with CO/H and Milstein et al.
using formate as hydrogen donor. In the latter case, activity
required the dippp ligand (1,3-bis(di-isopropylphosphino)-
propane) that provides an electron-rich complex with a
suitable chelate ring size for the best compromise between
stability and activity. The oxidative addition step was shown
to be significantly slower than the carbonylation reaction.
1
Heck showed that aryl and vinyl halides (bromide and
iodide) could be converted to aldehydes using a synthesis
gas mixture (CO/H
when using high pressure (>80 bar) and temperature
>80 °C). This severely restricts the applicability of this
2
) and a palladium(0) catalyst, but only
13
Most recently, the application of the proprietary ligand
di-1-adamantyl-n-butylphosphine (CataCXium A) was found
to be effective for the formylation of aryl and heteroaryl
(
methodology for scale-up beyond the laboratory, and several
groups have subsequently looked at this reaction with the
aim of achieving the same conversion under milder condi-
tions. Until very recently, the approach adopted was to use
a hydrogen transfer agent in place of hydrogen to promote
the elimination of the acyl species from the metal. Thus Stille
bromides using synthesis gas (1:1 CO/H
pressures than those previously possible. Typical reaction
2
) at much lower
(
(
5) Smith, A. B., III; Cho, Y. S.; Ishiyama, H. Org. Lett. 2001, 3, 3971.
6) Pri-Bar, I.; Buchman, O. J. Org. Chem. 1984, 49, 4009.
(7) Misumi, Y.; Ishii, Y.; Hidai, M. Organometallics 1995, 14, 1770.
(8) Kotsuki, H.; Datta, P. K.; Suenaga, H. Synthesis 1996, 470.
2
-4
and co-workers
3
found that Bu SnH was successful in
(9) Pri-Bar, I.; Buchman, O. J. Org. Chem. 1988, 53, 624.
converting aryl and vinyl iodides, bromides and triflates to
(10) Cacchi, S.; Fabrizi, G.; Goggiamani, A. J. Comb. Chem. 2004, 6, 692.
(
(
(
11) Mutin, R.; Lucas, C.; Thivolle-Cazat, J.; Dufaud, V.; Dany, F.; Basset, J.
M. J. Chem. Soc., Chem. Commun. 1988, 896.
12) Ben-David, Y.; Portnoy, M.; Milstein, D. J. Chem. Soc., Chem. Commun.
*
Corresponding author email: barnacfj@matthey.com.
(1) Schoenberg, A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96, 7761.
(2) Baillargeon, V. P.; Stille, J. K. J. Am. Chem. Soc. 1983, 105, 7175.
(3) Baillargeon, V. P.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 452.
(4) Scott, W. J.; Crisp, G. T.; Stille, J. K. J. Am. Chem. Soc. 1984, 106, 4630.
1989, 1816.
13) Klaus, S.; Neumann, H.; Zapf, A.; Strubing, D.; Huber, S.; Almena, J.;
Riermeier, T.; Gross, P.; Sarich, M.; Krahnert, W-R.; Rossen; K.; Beller,
M. Angew. Chem., Int. Ed. 2006, 45, 154.
1
0.1021/op060193w CCC: $37.00 © 2007 American Chemical Society
Vol. 11, No. 1, 2007 / Organic Process Research & Development
•
39
Published on Web 12/14/2006

Table 1. Performance of catalysts for reductive
carbonylation of 4-bromoacetanilide
yielda yielda
(%)
ArCHO ArH
conv.a
(%)
(%) select.a
entry
catalyst
(%)
1
2
3
4
5
6
7
8
9
[Pd(OAc)
[Pd(OAc)
[Pd(OAc)
2
2
2
]
]
]
3
3
3
3
/2xPPh
/dppf
/dppp
3
18
32
99
41
99
99
93
100
2
16
1
2
31
2
11
6
1
1
89
3
97
30
93
98
92
0
98
73
94
99
99
0
[PdCl
[PdCl
[PdCl
[PdBr
[PdCl
[PdCl
2
2
2
(PPh
2
) ]
(dppf)]
(dppp)]b
2
(BINAP)]
(d bpf)]
t
2
100
2
2
(dppe)]
0
0
a
As determined by GC-MS peak area ratio. b Isolated yield 92.5%
Figure 1. Palladium catalysts.
conditions were Pd(OAc) (0.25 mol %), ligand (0.75 mol
), TMEDA (0.75 equiv), CO/H (5 bar) for 16 h at 100 °C.
While these conditions are clearly advantageous in
allowing formylation with a cheap reagent (CO/H ) under
relatively mild conditions, the reaction is shown to be very
specific to the di-1-adamantyl-n-butylphosphine. We have
therefore sought to exemplify the potential of the previously
2
%
2
Figure 2. Selection of catalysts for reductive carbonylation of
-bromoacetanilide.
2
4
(BINAP)] 5, or [PdCl
(triphenylphosphine) catalyst 1 was less effective. Chelate
ring size is an important factor in catalyst choice; [PdCl
2
(dppf)] 6; the monodentate bis-
developed R
3
SiH systems using a wider range of palladium
2
-
catalysts containing nonproprietary ligands. The increased
cost of the reducing agent may be offset by the lower ligand/
catalyst cost.
(dppe)] 2 has a bidentate phosphine ligand with a small bite
angle and is inactive in this reaction. It also appears that
these preformed catalysts have an advantage over those
2
generated in situ from Pd(OAc) and the ligand.
Results
Optimisation of Conditions. A selection of other aryl
bromides with differing electronic properties were reacted
under these conditions using 3 as catalyst. It was immediately
clear that a general optimisation of conditions to produce
the highest yield of aldehyde was not a suitable approach as
each substrate posed different challenges. For example,
Experiments were carried out using a Baskerville Multi-
Cell reactor, in which 10 simultaneous reactions could be
run under identical temperatures and pressures. Initial
investigations were carried out using 4-bromoacetanilide as
a model substrate. Conditions were adapted from the work
8
on triflates by Kotsuki et al. The reaction was heated at
4-bromotoluene with 3 in DMF with Et
SiH gave almost complete conversion to an aryl species
containing -OSiEt as evidenced by IR, NMR, and mass
spectroscopy. This was identified as the dimeric species
ArCH(OSiEt )CH(OSiEt )Ar (I, Ar ) tolyl) by comparison
3 3
N as base and Et -
9
0 °C for 18 h under 6 bar of CO, and in contrast to their
results, under these conditions satisfactory yields could be
obtained with Et SiH as well as the more expensive Oct
SiH. Other silanes, including Ph
3
3
3
-
SiH,
i
3
SiH, (EtO)
3
SiH, Pr
3
3
3
and PMHS, were also tested but only gave minimal conver-
sion of the starting material. The linear alkyl silanes are
preferable for this reaction, although PMHS was used
with an authentic sample prepared by silylation of the
alcohol. This may be formed via a benzoin condensation
from the aldehyde or possibly arise from a double carbony-
lation reaction. The same product was also obtained with
similar catalysts, such as 5 or 6, but more electron-rich
catalysts such as 7, 8, or, 9 gave poor conversion of the
starting material to the required aldehyde only. The use of
other solvents with 3 also gave poor conversion of the
starting material, but by changing the base to an inorganic
6
successfully with iodides by Pri-Bar and Buchman.
A selection of palladium catalysts was tested under these
conditions; the catalysts are shown in Figure 1, and results
are given in Table 1 and illustrated in Figure 2. High yields
of the aldehyde were achieved with catalysts containing
2 2
bidentate phosphine ligands, such as [PdCl (dppp)] 3, [PdBr -
40
•
Vol. 11, No. 1, 2007 / Organic Process Research & Development

salt, such as Na
2 3
CO , the unwanted side reaction could be
Table 2. Reductive carbonylation of aryl bromides
eliminated and high yields of the aldehyde were achieved.
The electron-rich substrate, 4-bromoanisole, is deactivated
towards oxidative addition of the aryl bromide to the catalyst.
It was found that this lack of reactivity could be overcome
by raising the reaction temperature to 120 °C. A screen of
catalysts revealed similar behaviour to 4-bromotoluene; for
example, 3 gave the triethylsilane derivative (I), and 8 gave
poor yields of both the triethylsilane derivative (I) and the
t
required aldehyde. The palladium(0) catalyst, [Pd(P Bu
3
)
2
]
10, however gave high yields of the aldehyde without any
side reactions. The results with this catalyst were reproducible
in a variety of solvents including THF, DMA, toluene, and
MeCN, but 1,4-dioxane proved to be preferable. It is
necessary to use an organic base with this substrate {Et-
i
(
2
Pr) N gave better yields than Et
3
N} as inorganic salts such
as Na
2
CO resulted in incomplete reaction and formed
3
significant quantities of anisole.
The activated electron-poor substrate, 4-bromobenzoni-
trile, gave almost complete conversion to the debrominated
benzonitrile with 3 in DMF with Et
also gave poor results with a mixture of that and the
triethylsilane derivative (I). This problem could be overcome
3
N. The catalysts 5 and
6
i
t
2 2
by the use of [PdCl (d ppf)] 7 or [PdCl (d bpf)] 8 which gave
good yields of the aldehyde and only a small amount of
benzonitrile. A wide range of solvents could be used
including DMF, NMP, 1,4-dioxane, and toluene, but THF
gave the best results. Acetonitrile appeared to increase the
proportion of benzonitrile formed, as did the use of inorganic
bases with any of the solvents.
Although 3 was deemed to be the most appropriate
catalyst for the reaction with 4-bromoacetanilide, the effect
of solvent and base on the reaction was investigated in light
of the results of work with the other substrates. Screens
showed that Na
followed by organic bases such as Et
2
CO
3
gave the highest yield of aldehyde
N. Other inorganic
3
bases increased the formation of acetanilide. The best solvent
was DMF.
a
b
As determined by GC-MS peak area ratio. Method A (see Experimental
Other conditions were also optimised to give the best
results. Variation of the amount of catalyst in the range 1-5
mol % had little effect on the distribution of products, but
at 1 mol% the reaction was noticeably slower, with signifi-
cant amounts (up to 60%) of starting material remaining after
c
d
Section). Method B (see Experimental Section). Method C (see Experimental
Section). e In this case the only other product is ArCH(OSiEt
)CH(OSiEt )Ar.
3
3
Scope of Reaction. The preferred conditions (see Ex-
perimental Section, Method A) were applied to a wider range
of aryl bromide substrates with differing electronic and steric
properties. The results are shown in Table 2.
18 h. Under the original conditions 2 equiv of Et
3
SiH and
2.1 equiv of base were used. It was found that by reducing
High yields were achieved for substrates with an elec-
tronically neutral substituent in the 4-position. These yields
were not compromised if a single substituent was present in
the 2-position, but the steric hindrance of 2,6 disubstitution
prevented the reaction from taking place. Substrates with an
electron-withdrawing group in the 4-position also gave good
results, with the exception of 1-bromo-4-nitrobenzene. Nitro-
substituted aromatics are known to sometimes show abnor-
mal reactivity due to their coordinating ability and high
either one of these components to 1 equiv higher yields of
aldehyde were obtained, but reducing the quantity of both
silane and base had a detrimental effect on results. As the
reduction in amount of base appeared to have a stronger
influence, all further experiments were carried out using 2
3
equiv of Et SiH and 1 equiv of the appropriate base. High
yields of aldehyde could still be achieved when the CO
pressure was lowered to 3 bar, but further decreases in
pressure lead to the formation of a more debrominated side
product from the more active substrates. Lowering the
temperature to 60 °C did not result in a satisfactory reaction
under the established conditions.
1
3,14
electron deficiency.
An electron-withdrawing group in
the 2-position, however, promoted reductive debromination
(14) Wang, B.; Bonin, M.; Micouln, L. Org. Lett. 2004, 6, 3481.
Vol. 11, No. 1, 2007 / Organic Process Research & Development
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41

Table 3. Reductive carbonylation of aryl iodides
2 3
Na CO system at 60 °C, except in the case of activated
substrates. Under these conditions near quantitative yields
of aldehyde are observed with aryl iodides, but almost no
reaction takes place with neutral or deactivated aryl bromides.
This is illustrated by the reaction of 1-bromo-4-iodobenzene
(Figure 3). For activated aryl bromides, e.g., 4-bromoben-
zonitrile, significant conversion to the aldehyde takes place
at 60 °C; a lower temperature would be required to give
similar selectivity.
An alternative method of achieving selectivity between
aryl iodides and aryl bromides is to use PMHS as the silane
6
instead of Et
3
SiH. Pri-Bar and Buchman were successful
in using PMHS for the reductive carbonylation of aryl
iodides, but with the conditions used in this study no reaction
took place with PMHS and aryl bromides. When PMHS was
used under the same conditions (3/DMF/Na CO at 90 °C)
2 3
with aryl iodides, however, near complete conversion took
place.
Discussion
The range of results and conditions for this large variety of
catalyst systems is illustrative of the complexity of this reac-
tion in terms of the different reaction steps and the factors in-
fluencing them. An outline mechanism is shown in Scheme 1.
A great deal of study has been given to the oxidative addi-
1
5,16
tion of aryl halides to palladium,
by the groups of Buch-
wald and Hartwig in particular, and strongly donating phos-
t
3
phines having bulky substituents (e.g., P Bu ) have been
shown to be advantageous. This has been explained by the
relative stability of the Pd(0) and Pd(II) complexes. However,
less is known about the carbonyl insertion reaction, which
consists of initial substitution of carbon monoxide into the
coordination sphere and then insertion into the Pd-C bond.
It might be presumed that initial opening of the phosphine
chelate allows CO coordination and CO insertion will be
favoured by return of this phosphorus donor into the vacant
site created by ligand combination. The hydrogen transfer
step and the relative ease of reductive elimination from the
aryl and acyl intermediates are even less understood. How-
ever, the fact that it is possible by changing the conditions
to increase reaction via the acyl complex relative to dehalo-
genation via the aryl complex indicates that there are signif-
icant differences between the factors controlling these rates.
The results in Table 2 illustrate some of these points.
Substrates with electron-withdrawing groups in the 4-position
a
As determined by GC-MS peak area ratio.
over reductive carbonylation. Substrates with an electron-
donating group required a higher temperature for the reaction
to take place, and again yields were reduced when the
substituent is in the 2-position rather than the 4-position. The
conditions used for neutral substrates also gave excellent
results for the heteroaryl bromides, e.g., 3-bromopyridine.
Although aryl iodide substrates are less widely available
than their aryl bromide counterparts, they show increased
activity towards the oxidative addition step of the reductive
carbonylation reaction. This could be used to carry out a
selective carbonylation at the iodide of a mixed halide
substrate. The conditions under which a range of aryl iodides
undergoes reductive carbonylation was investigated with
particular emphasis on their reactivity in comparison to the
equivalent aryl bromides. Results are shown in Table 3.
For the aryl iodides it was found that a temperature of
t
give better yields with the bulky, electron-rich d bpf ligand
(Method B, see Experimental Section) than with dppp (Meth-
od A). It is expected that these substrates would react more
readily with the dppp catalyst than the alkyl substituted aryls,
at least with regard to oxidative addition, so the change in cata-
lyst performance must relate to later steps in the mechanism.
6
0 °C was adequate to give high yields in most cases. This
was even true of the deactivated, electron rich substrates and
good results could be obtained using the 3/DMF/Na CO
system as opposed to the palladium(0) catalyst that is
required for the equivalent aryl bromide. The same system
2
3
Conclusions
Efficient carbonylation of aryl iodides and bromides in
the presence of the hydrogen donor Et SiH can be achieved
3
3
was also used for the activated substrates as 8/THF/Et N
provided that the conditions are modified to suit the substrate.
In particular, the appropriate choice of catalyst, solvent, and
resulted in reductive dehalogenation. These conditions did
not prove to be suitable however, for the heteroaryl iodide.
Excellent selectivity between reaction at an aryl iodide
and at an aryl bromide can be achieved using the 3/DMF/
(15) Zapf, A.; Beller, M. Chem. Commun. 2005, 431.
(16) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046.
42
•
Vol. 11, No. 1, 2007 / Organic Process Research & Development

Figure 3. Iodide vs bromide selectivity.
Scheme 1. Outline mechanism for reductive carbonylation
General Procedure for the Reductive Carbonylation
of 4-Bromotoluene (Method A). To 4-bromotoluene (0.616 g,
-
3
-5
3
.6 × 10 mol), [PdCl
2
(dppp)] (0.053 g, 9 × 10 mol),
-
3
and Na CO
2
3
(0.381 g, 3.6 × 10 mol) were added DMF
-3
(
5 mL), mesitylene (0.25 mL, 1.8 × 10 mol) as reference,
-3
3
and Et
SiH (1.166 mL, 7.2 × 10 mol). Once sealed inside
the reactor the system was purged with CO several times. The
temperature was raised to 90 °C, and the reactor was charged
with 3 bar of CO. The reaction was stirred under these condi-
tions for 18 h after which the reactor was allowed to cool.
The reaction was filtered, and the filtrate was analysed by
GC-MS to determine the conversion and yield of aldehyde.
General Procedure for the Reductive Carbonylation
of 4-Bromobenzonitrile (Method B). To 4-bromobenzoni-
-
3
t
trile (0.655 g, 3.6 × 10 mol) and [PdCl
2
(d bpf)] (0.065 g,
-5
9
1
× 10 mol) were added THF (5 mL), mesitylene (0.25 mL,
-3 -3
3
.8 × 10 mol)asreference,Et
N(0.504mL,3.6 × 10 mol),
-
3
and Et
3
SiH (1.166 mL, 7.2 × 10 mol). Once sealed inside
the reactor the system was purged with CO several times. The
temperature was raised to 90 °C, and the reactor was charged
with 3 bar of CO. The reaction was stirred under these condi-
tions for 18 h after which the reactor was allowed to cool.
The reaction was filtered, and the filtrate was analysed by
GC-MS to determine the conversion and yield of aldehyde.
General Procedure for the Reductive Carbonylation
base must be made. This methodology provides a suitable
alternative to the use of proprietary ligands such as Cat-
aCXium A. Furthermore, this approach offers the prospect
of adaptation to the conversion of aryl chlorides.
Much progress has been made in recent years by many
17
t
groups studying C-C coupling reactions of aryl chlorides.
of 4-Bromoanisole (Method C). To [Pd(P Bu ) ] (0.046 g,
3
2
-5
It has been shown that oxidative addition of aryl chlorides
can be promoted, even at room temperature, using sterically
demanding and electron-donating phosphines (cf. ref 12).
Thus, the initial oxidative addition should no longer be a
barrier to reactivity. However, a balance between the
oxidative addition, carbonyl insertion, hydride transfer, and
reductive elimination steps still needs to be found, so careful
screening will be required to develop suitable catalysts. This
is the focus of ongoing work.
9 × 10 mol) were added dioxane (5 mL), mesitylene (0.25
-3
mL, 1.8 × 10 mol) as reference, 4-bromoanisole (0.451
-3
i
-3
mL, 3.6 × 10 mol), Et( Pr) N (0.658 mL, 3.6 × 10 mol),
2
-
3
and Et SiH (1.166 mL, 7.2 × 10 mol). Once sealed inside
3
the reactor the system was purged with CO several times. The
temperature was raised to 120 °C, and the reactor was charged
with 3 bar of CO. The reaction was stirred under these condi-
tions for 18 h, after which the reactor was allowed to cool.
The reaction was filtered, and the filtrate was analysed by
GC-MS to determine the conversion and yield of aldehyde.
Product Isolation. 4-Acetamidobenzaldehyde prepared
from 4-bromoacetanilide according to method A (2.16mmol
substrate) was isolated by filtration of the reaction solution
and evaporation of the solution to low volume. The slurry
was taken up in acetone and chromatographed on silica using
hexane/acetone eluant. The product was isolated by evapora-
tion under reduced pressure and washed with hexane. The
product was collected by filtration and dried in air. Yield:
3.25 g (1.99 mmol, 92.5%).
Experimental Section
All solvents and reagents were obtained from commercial
suppliers and used without further purification. All catalysts
and ligands may be obtained from Johnson Matthey Catalysts
or Alfa Aesar. Reactions were performed in a Baskerville
1
0 × 30 mL Multi-Cell Pressure Reactor rated to 50 bar
and 200 °C. Analysis of the reaction mixture was carried
out by GC-MS using a Perkin-Elmer AutoSystem XL gas
chromatograph with a TurboMass mass spectrometer. Condi-
tions used: 1.0 µL sample injection; column, 30 m × 0.25
mm and DF 0.25 µm Elite Series PE-5MS; injection port
Note Added after ASAP Publication: Errors in Figure
1
in the version published on the Internet December 14, 2006,
320 °C; initial temperature 130 °C, hold 4 min, ramp at
30 °C/min to 300 °C, hold 5 min; split ratio 100/1; MS scan
40.0 to 400.0 EI+ (centroid).
have been corrected in the version published ASAP Decem-
ber 15, 2006, and in the print version.
Received for review September 21, 2006.
OP060193W
(17) Sturmer, R. Angew. Chem., Int. Ed. 1999, 38, 3307.
Vol. 11, No. 1, 2007 / Organic Process Research & Development
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