Highly selective catalyst systems for the hydroformylation of internal olefins to linear aldehydes

Article abstract of DOI:10.1002/1521-3773(20010917)40:18<3408::AID-ANIE3408>3.0.CO;2-A

Readily accessible and highly efficient: Substituted 2,2′-bis(diphenylphosphanylmethyl)-1,1′-binaphthyl (NAPHOS) ligands 1 can be readily prepared from 2,2′-bis(dichlorophosphanylmethyl)-1,1′-binaphthyl. Especially ligands with electron-withdrawing aryl substituents (for example, 3,4,5-F₃C₆H₂ (instead of Ph), 1a) show a remarkable high activity and n:i selectivity in the rhodium-catalyzed hydroformylation of internal olefins (see scheme).

Full text of DOI:10.1002/1521-3773(20010917)40:18<3408::AID-ANIE3408>3.0.CO;2-A

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terminal olefin (Scheme 1, reaction c) must occur many times
faster (and with high n selectivity) than that of the internal
olefin (Scheme 1, reaction b).
Highly Selective Catalyst Systems for the
Hydroformylation of Internal Olefins to
Linear Aldehydes**
To date only a limited number of rhodium catalysts[ with
3]
Holger Klein, Ralf Jackstell, Klaus-Diether Wiese,
Cornelia Borgmann, and Matthias Beller*
[4]
sterically hindered phosphites have been shown to be
suitable for this purpose. Owing to the limited thermal
stability and the ease of hydrolysis of these ligands there is
considerable interest in new hydroformylation catalysts for
the selective conversion of internal olefins.[ Clearly phos-
phanes would offer advantages in terms of stability compared
to phosphite ligands.[ Regarding phosphane catalyst systems
there has been only one recent development, which was
described by van Leeuwen and co-workers, where modified
xanthene ligands were used for the hydroformylation of 2-
and 4-octene.[ With these ligands linear:branched (n:i) ratios
Dedicated to Professor Manfred Michalik
on the occasion of his 60th birthday
5]
The rhodium-catalyzed hydroformylation of aliphatic ole-
fins to give linear aldehydes constitutes the most important
homogeneously catalyzed process in industry today in terms
of volume produced.[1] More than seven million tons of
6]
various aldehydes and alcohols are produced in this way each
year. The hydroformylation of propene is especially impor-
tant for the production of n-butyraldehyde, used as a valuable
starting material for 2-ethylhexanol, which is currently the
most important plasticizer alcohol in use. Recently there has
been an increasing interest in the production of alternative
plasticizer alcohols due to environmental concern about
7]
[8]
up to 90:10 and catalyst turnover frequencies (TOF) of
�
1
1
12 h were achieved for the hydroformylation of 2-octene.
Herein we report the development of new rhodium catalyst
systems that enable the hydroformylation of different termi-
nal and internal olefins in excellent selectivities, which
represents a substantial improvement in efficiency of this
industrially important reaction.
[
2]
current products. For economic reasons internal olefins or
mixtures of internal and terminal olefins are the starting
materials of choice for new plasticizer alcohols, yet peferably
unbranched alcohols are the desired products due to better
physical properties of the resulting plasticizers. However, the
selective hydroformylation of internal olefins to give linear
aldehydes (and subsequently linear alcohols) is difficult
While studying the homogeneous and biphasic[9] hydro-
formylation of 1- and 2-pentene in the presence of phosphane-
modified cobalt catalysts,[ we became interested in similar
reactions with more active rhodium catalysts. Among the
various phosphanes tested for this reaction 2,2'-bis(diphenyl-
phosphanylmethyl)-1,1'-binaphthyl (NAPHOS,[ a structural
variation of the 2,2'-bis(diphenylphosphanylmethyl)biphenyl
10]
11]
(Scheme 1). To obtain linear aldehydes from internal olefins
(
BISBI) ligand), which resembles the backbone of the steri-
cally demanding phosphites, gave the best results (Table 1).
Table 1. Hydroformylation of 1- and 2-pentene with NAPHOS.[a]
Entry
Olefin
p
T
[8C]
Yield [b]
[%]
n:i
TOF
[h ]
�
1
[bar]
1
2
3
4
1-pentene
1-pentene
2-pentene
2-pentene
10
50
10
50
120
120
120
120
76
88
22
7
99:1
97:3
89:11
55:45
475
550
138
44
Scheme 1. Selective hydroformylation of internal olefins to give linear
aldehydes: a) Isomerizaton, b) hydroformylation of internal olefin,
c) hydroformylation of terminal olefin.
[a] Reaction conditions: olefin (70.0 mmol; 40 mL solution), [Rh(acac)-
(
CO)
2
] (0.01 mol%; 20.7 ppm Rh), NAPHOS:Rh ˆ 5:1, t ˆ 16 h. [b] No
significant amounts (>1%) of other products apart from isomerized olefin
the catalyst has to perform a fast isomerization between the
internal and terminal olefin (Scheme 1: reaction a). Unfortu-
nately the thermodynamic equilibrium mixture contains in
general less than 5% of the terminal olefin (for this reason
isomerization should be avoided if terminal olefins are used as
starting material). In addition the hydroformylation of the
were detected.
As expected the rhodium-catalyzed hydroformylation of
the terminal olefin proceeds in the presence of NAPHOS in
good yields (76 ± 88%) and excellent selectivities (n:i ˆ 97:3 ±
99:1). However, much to our surprise NAPHOS also gives a
highly selective (n:i ˆ 89:11) catalyst system for the reaction
[
*] Prof. Dr. M. Beller, Dipl.-Chem. H. Klein, Dr. R. Jackstell
Institut für Organische Katalyseforschung (IfOK)
an der Universität Rostock e.V.
of 2-pentene at a low CO/H pressure (10 bar). Although the
2
�
1
[12]
yield (22%) is modest after 16 h (TOF ˆ 138 h ),
it is
Buchbinderstrasse 5 ± 6, 18055 Rostock (Germany)
Fax : (‡49)381-466-9324
important to note that this is only the second known
phosphane that allows a selective synthesis of linear aldehydes
from internal olefins. The even lower yield at 50 bar, can be
explained by the fact that the isomerization step, which is
necessary for the formation of the linear aldehyde from an
internal olefin, is faster at a lower CO pressure.
E-mail: matthias.beller@ifok.uni-rostock.de
Dr. K.-D. Wiese, C. Borgmann
Oxeno Olefinchemie GmbH
Industriepark Marl, Marl (Germany)
[
**] This work was supported by Oxeno Olefinchemie GmbH and the
State of Mecklenburg-West Pommerania. Dr. C. Fischer and Mrs. S.
Buchholz are thanked for their excellent technical support.
In view of this promising result, we were interested in the
synthesis of new substituted NAPHOS derivatives, especially
3408
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Angew. Chem. Int. Ed. 2001, 40, No. 18

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those with electron-withdrawing substituents on the aryl rings.
After considerable experimentation we developed a simple
and general synthesis for NAPHOS derivatives, which can be
were used as starting materials. As shown in Table 2 ligands
with electron-withdrawing substituents (5a ± c) led to much
more active and slightly more selective catalysts for the
hydroformylation of internal olefins compared to NAPHOS
and 5d.
[13]
performed without problems on a multigram scale.
2,2'-
with 2.5 equiva-
lents of n-butyllithium to give the double lithiated derivative 2
Scheme 2). Reaction of 2 with chlorobis(diethylamino)phos-
[
14]
Dimethyl-1,1'-binaphthyl (1) is lithiated
(
Table 2. Rhodium-catalyzed hydroformylation in the presence of substi-
[
15]
phane in n-hexane at � 708C yields 2,2'-bis[bis(diethylami-
no)phosphanylmethyl]-1,1'-binaphthyl (3), which is converted
directly to 2,2'-bis(dichlorophosphanylmethyl)-1,1'-binaphth-
yl (4) with gaseous hydrogen chloride in 44% overall yield
from 1.
[a]
tuted NAPHOS derivatives.
Entry
Olefin
p
T
[8C]
Yield [b]
[%]
n:i
TOF
� 1
[bar]
[h
]
1
2
3
4
5
6
7
8
9
0
1
2
3
5a
5a
5a
5a
5a
5b
5b
5b
5c
5c
5c
5c
5c
1-pentene
2-pentene
2-pentene
120
120
100
120
120
120
120
100
120
120
100
120
120
82
68
52
66
51
78
59
21
83
61
24
74
48
96:4
91:9
89:11
91:9
86:14
97:3
94:6
95:5
97:3
93:7
94:6
95:5
91:9
88:12
66:34
70:30
81:19
78:22
512
425
325
825
319
488
369
131
519
381
150
925
300
[
b]
2-butene
2-octene
[
c]
1-pentene
2-pentene
2-pentene
1-pentene
2-pentene
2-pentene
1
1
1
1
[
b]
2-butene
2-octene
[
c]
114)[
88
d]
f]
(
(
64
14
41
76
11
1
4
5c
4-octene[e]
120
43)[
475
69
1
1
5
6
5d
5d
1-pentene
2-pentene
120
120
[
a] Reaction conditions: pentene (73 mmol), solution (40 mL anisole ‡
isooctane as internal standard), p ˆ 10 bar, [Rh(acac)(CO) ] (0.01 mol%;
0.7 ppm Rh), ligand:Rh ˆ 5:1, t ˆ 16 h. [b] 2-Butene (146 mmol), anisole
30 mL), [Rh(acac)(CO) ] (0.005 mol%). [c] 2-Octene (73 mmol), solvent
28.5 mL; anisole toluene). [d] After reaction time of 56 h.
2
2
(
(
2
‡
a
[
e] 4-Octene (73 mmol), solvent (10 mL; anisole ‡ toluene). [f] After a
reaction time of 96 h.
In the case of 2-pentene the ligand 5a (IPHOS) led to the
most active catalyst system, especially at 1008C (Table 2,
Scheme 2. Synthesis of substituted NAPHOS derivatives. The yield of the
final step of 4 !5 is given in parentheses below the Ar groups of 5a ± d.
�
1
entry 3; TOF ˆ 325 h ). The largest amount of n-aldehydes
(
Table 2, entries 7, 8; n/i ˆ 94:6 (95:5); 120 (100)8C) was
obtained in the presence of 5b. Significantly higher catalyst
Reaction of the new central building block 4 with Grignard
reagents provides an efficient synthesis of a number of new
NAPHOS derivatives. As shown in Scheme 2 mainly fluori-
nated ligands were synthesized due to the electron-with-
drawing nature of the substituents. In general such electron-
deficient substituents in aryl diphosphanes (with large bite
angles) have a positive effect on the activity and the
linear:branched selectivity of hydroformylation catalysts in
activities but similar selectivities (up to 95:5) (Table 2, entries
�
1
4 and 12; TOF ˆ 825 and 925 h , respectively) were observed
with the industrially important olefin 2-butene. These are the
highest selectivities known so far for the hydroformylation of
internal olefins to give linear aldehydes with phosphane
ligands. Interestingly, the catalyst activities in the presence of
5a ± c do not significantly differ for 1- and 2-pentene (compare
entries 1,2 or 6,7 or 9,10 in Table 2). Thus the isomerization of
1-pentene is most likely similar in rate or faster than the
hydroformylation step.
[
16]
case of primary olefins.
This can be explained by a
preference for the diequatorial over the equatorial ± apical
[
17]
binding mode of the ligand.
In addition the new ligands 5a ± c also allow a selective
hydroformylation of higher internal olefins. With 2-octene a
n:i ratio of 91:9 was obtained in the presence of 5c (Table 2,
The best yields in the Grignard coupling were obtained with
,5-bis(trifluoromethyl)-1-bromobenzene and 1-bromo-3,5-
3
�
1
difluorobenzene (89 and 83%, respectively), while 1-bromo-
,4,5-trifluorobenzene and 1-bromo-3,5-dimethylbenzene
entry 13; TOF ˆ 300h ). However in the case of 4-octene the
selectivity is comparably low (Table 2, entry 14; n:i ˆ 66:34)
after 16 h. To understand this different behavior the reactions
of 2- and 4-octene in the presence of 5c (Table 2, entries 13
and 14, respectively) were monitored by removing samples
from the autoclave, which were taken during the reaction. The
results are displayed in Figure 1 and 2. The conversion of 2-
and 4-octene reveals significant differences. Utilizing 2-octene
3
gave only moderate coupling yields (61 and 43, respectively;
non-optimized).
The rhodium-catalyzed hydroformylation with the new
ligands was performed at a synthesis gas pressure of 10 bar
[
18]
and 120 as well as 1008C. Apart from 1- and 2-pentene
other internal olefins such as 2-butene, 2-octene, and 4-octene
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and ligand 5a (M
treated with isooctane (2 mL as internal standard) and 1-pentene (8 mL,
3.0 mmol). This mixture was added to the autoclave, which was
subsequently pressurized to 5 bar with synthesis gas (CO:H
r
ˆ 1194.73; 44 mg, 36.5 mmol) in anisole (30 mL) was
7
2
ˆ 1:1). The
autoclave was then heated to 1208C and the pressure adjusted to 10 bar.
After 16 h the autoclave was cooled in an ice bath and the pressure was
released. A sample was taken immediately and analyzed by GC.
All hydroformylation experiments were conducted under isobaric con-
ditions. Synthesis gas (purity 99.97 ± 99.997%) was purchased from Aga
Gas GmbH, Berlin (Germany).
Received: March 27, 2001 [Z16857]
[1] a) Rhodium Catalyzed Hydroformylation (Eds.: P. W. N. M. van Leeu-
Figure 1. Yield (^) and n selectivity (
formylation of 2-octene with 5c.
&
) of the rhodium-catalyzed hydro-
wen, C. Claver), Kluwer, Dordrecht, 2000; b) B. Cornils, J. Mol. Catal.
1
999, 143, 1 ± 3; c) C. W. Kohlpaintner, C. D. Frohning in Applied
Homogeneous Catalysis with Organometallic Compounds, Vol. 1
Eds.: B. Cornils, W. A. Herrmann), VCH, Weinheim, 1996, p. 1;
(
d) K. Weissermel, H.-J. Arpe, Industrielle Organische Chemie, VCH,
Weinheim, 1994.
[2] Chem. Ind. 1998, 18 May, 379.
[3] P. W. N. M. van Leeuwen, P. C. Kamer, J. N. H. Reek, P. Dierkes,
Chem. Rev. 2000, 100, 2741 ± 2769.
[
4] E. Billig, A. G. Abatjoglou, D. R. Bryant, US Patent 4748261, 1988; E.
Billig, A. G. Abatjoglou, D. R. Bryant, US Patent 4769498, 1988.
5] a) M. Beller, B. Zimmermann, H. Geissler, Chem. Eur. J. 1999, 5,
[
1
301 ± 1305; b) D. Selent, K.-D. Wiese, D. Röttger, A. Börner, Angew.
Chem. 2000, 112, 1694 ± 1696, Angew. Chem. Int. Ed. 2000, 39, 1639 ±
642; c) B. Breit, W. Seiche, Synthesis 2001, 1 ± 36; d) D. Selent, D.
Hess, K.-D. Wiese, D. Röttger, C. Kunze, A. Börner, Angew. Chem.
001, 113, 1739 ± 1741, Angew. Chem. Int. Ed. 2001, 40, 1696 ± 1698.
1
2
[
[
6] Phosphites readily undergo side reactions with the produced alde-
hydes at the required reaction temperature. These side reactions are
not observed with phosphanes.
7] a) L. A. van der Veen, P. C. J. Kamer, P. W. N. M. van Leeuwen,
Angew. Chem. 1999, 111, 349 ± 351; Angew. Chem. Int. Ed. 1999, 38,
Figure 2. Yield (^) and n selectivity (
formylation of 4-octene with 5c.
&
) of the rhodium-catalyzed hydro-
3
36 ± 338; b) H. Geissler, L. A. van der Veen, P. W. N. M. van Leeu-
the n:i ratio decreases from 94:6 after 2 h to 88:12 after 56 h.
In contrast, with 4-octene the n:i ratio increases from 45:55
after 3 h to 70:30 after 31 h and then remains approximately
constant. It seems that in case of 2-octene the isomerization
towards the 1-octene is significantly faster than that to give
wen, P. C. J. Kamer, European Patent 982314, 2000.
8] Turnover frequencies (TOFs) are defined here as mol aldehyde per
mol rhodium per hour after 20 ± 30% conversion. The concentration
of alkene used in our work is about three times higher. Thus higher
rates are expected and a good comparison with the values in
reference [7] cannot be made yet.
9] Aqueous-Phase Organometallic Catalysis (Eds.: B. Cornils, W. A.
Herrmann), VCH, Weinheim, 1998.
10] M. Beller, J. G. E. Krauter, J. Mol. Catal. 1999, 143, 31 ± 39.
11] a) K. Tamao, H. Yamamoto, H. Matsumoto, N. Miyake, T. Hayashi, M.
Kumada, Tetrahedron Lett. 1977, 16, 1389 ± 1392; b) W. A. Hermann,
R. Schmid, C. W. Kohlpaintner, T. Priermeier, Organometallics 1995,
[
3
-octene. The isomerization is much slower for 4-octene,
[
hence hydroformylation of the internal double bond occurs
preferentially. Interestingly, the hydroformylation of 4-octene
still proceeds after 80 h, which underlines the high catalyst
stability.
[
[
In conclusion we have shown that NAPHOS-type ligands
induce excellent selectivities for the conversion of internal
olefins to linear aldehydes. Based on our newly developed
synthesis of 4, variously substituted NAPHOS derivatives
have been synthesized on a multigram scale. We believe the
interesting features and the easy synthesis of this ligand class
will lead to further applications for industrially important
hydroformylation reactions, although for a practical applica-
tion the activity and long-time stability still have to be
improved.
1
4, 1961 ± 1968.
[12] Turnover frequencies (TOFs) are given as mol aldehyde per mol
rhodium per hoour after 16 h conversion.
13] Synthesis of 4 and 5a: A solution of nBuLi in hexane (33.2 mL, 1.6m,
[
5
3 mmol) was concentrated in vacuum. After the mixture had been
cooled to 08C, diethyl ether (25 mL) and N,N,N',N'-tetramethylethy-
lenediamine (7.9 mL) were added. A solution of 1 (5 g) in diethyl ether
(
30 mL) was then added slowly with stirring and cooling. The mixture
was kept for 24 h at room temperature and for a further 4 h at 08C.
The precipitate was filtered off and washed with hexane (2 Â 25 mL).
The product was treated with hexane (50 mL) and cooled to � 708C. A
mixture of chlorobis(diethylamino)phosphane (7.5 mL, 35.4 mmol)
and hexane (25 mL) was added dropwise to the stirred suspension.
After slowly warming up to room temperature the mixture was stirred
for a further 12 h (until the red color had completely disappeared).
The solid was filtered off and extracted with toluene (2 Â 50 mL). The
solvents and excess of chlorobis(diethylamino)phosphane were then
removed in vacuum. The residue was dissolved in hexane and HCl gas
was bubbled through the solution with external ice cooling and stirring
until saturation (about 1 h). The mixture was filtered and the
precipitate washed with hexane (2 Â 25 mL). The combined filtrates
were concentrated to a volume of 50 mL and kept overnight at
Experimental Section
General: All reactions were carried out under an argon atmosphere. For the
hydroformylation experiments
a 100-mL stainless steel autoclave
(
Parr Co.) equipped with a magnet-driven propeller stirrer or a 160-mL
stainless steel autoclave (Parr Co.) stirred magnetically were used.
Example of a typical hydroformylation experiment (Table 2, entry 1): A
solution of [Rh(acac)(CO)
2
] (7.3 mmol, 1.88 mg; acac ˆ acetylacetonate)
3410
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ino Heck ± Diels ± Alder reaction of bicyclopropylidene (1).[2]
This sequence involves the Heck-type coupling of bicyclo-
propylidene (1)[ with haloarenes and -alkenes to form
�
308C. The resulting crystals were collected, washed with a minimum
amount of cold hexane, and dried in vacuum. Yield of 4: 2.9 g (44%
related to 1). Mg turnings (302 mg, 12.4 mmol) were placed in a three-
necked flask (100 mL) and treated with diethyl ether (10 mL). A
3]
1-substituted allylidenecyclopropanes which then undergo
solution
of
3,5-bis(trifluoromethyl)-1-bromobenzene
(3.6 g,
1
2.4 mmol) in diethyl ether (10 mL) was added dropwise to the
[4‡2] cycloadditions with dienophiles yielding 7-substituted
spiro[2.5]oct-7-enes in a one-pot operation. In the course of a
more extensive study of this methodology we became aware
of a new reaction mode through the isolation of the side
product 3, the formation of which can only be rationalized by
an intermolecular nucleophilic attack of an acetate anion
stemming from the catalyst precursor on an intermediate p-
allylpalladium species 8 (Scheme 1).[
magnetically stirred mixture. After 1 h the solution was transferred
into a dropping funnel and slowly added to a solution of 4 (1.5 g,
3.1 mmol) in THF (25 mL). The mixture was then heated at reflux
until the reaction was complete (ꢀ2 h). After removal of the solvents
in vacuum the residue was dissolved in toluene. The solution was
2 4
washed with degassed water and dried with anhydrous Na SO . The
toluene was removed in vacuum, and the residue was recrystallized
from acetone/methanol. Yield of 5a: 3.3 g (89%).
4]
[
[
[
14] L. M. Engelhardt, W.-P. Leung, C. L. Raston, G. Salem, P. Twiss, A. H.
White, J. Chem. Soc. Dalton Trans. 1988, 2403 ± 2409.
15] J. Sakaki, W. B. Schweizer, D. Seebach, Helv. Chim. Acta 1993, 76,
2654 ± 2665.
16] a) J. D. Unruh, J. R. Christenson, J. Mol. Catal. 1982, 14, 19 ± 34;
b) C. P. Casey, E. L. Paulsen, E. W. Beuttenmueller, B. R. Proft, L. M.
Petrovich, B. A. Matter, D. R. Powell, J. Am. Chem. Soc. 1997, 119,
11817 ± 11825.
[
[
17] L. A. van der Veen, M. D. K. Boele, F. R. Bregman, P. C. J. Kamer,
P. W. N. M. van Leeuwen, K. Goubitz, J. Fraanje, H. Schenk, C. Bo, J.
Am. Chem. Soc. 1998, 120, 11616 ± 11626.
18] Preformation of the rhodium/phosphane catalyst mixture does not
lead to superior product yields.
Nucleophilic Trapping of p-Allylpalladium
Intermediates Generated by
Carbopalladation of Bicyclopropylidene:
A Novel Three-Component Reaction**
Scheme 1. Mechanism of the nucleophilic trapping of p-allylintermediate
8. A) 5 mol% Pd(OAc) , 10 mol% TFP, 5.0 equiv LiOAc, K CO , Et NCl,
MeCN, 808C, 24 h.
2
2
3
4
Hanno Nüske, Mathias Noltemeyer, and
Armin de Meijere*
The p-allylpalladium intermediate 8 must be formed after
the initial carbopalladation and b-hydride elimination by
readdition of the hydridopalladium species onto the newly
formed double bond[ via a s-allylpalladium complex 9. The
ligand tris-(a-furyl)phosphane (TFP), which is known to
retard b-hydride elimination[ and thus favor the readdition
of the hydridopalladium complex onto the double bond,
proved to be best for this reaction, and the yield of the allyl
acetate 3 could be raised up to 50% by using LiOAc as an
additional source of acetate.
Dedicated to Professor Barry M. Trost
on the occasion of his 60th birthday
5]
The construction of complex molecules from simple start-
ing materials is a challenging task for chemists. One of the
most elegant ways to achieve this is by utilizing so-called
domino reactions.[1] Multicomponent reactions such as the
Mannich and the Ugi reaction are examples of all-intermo-
lecular domino reactions. Recently, our group has published a
new all-carbon-coupling three-component reaction, the dom-
6]
In view of previous observations on the nucleophilic
substitution reactions on 1,1-dimethyleneallylpalladium inter-
[
*] Prof. Dr. A. de Meijere, Dr. H. Nüske
Institut für Organische Chemie
[7]
mediates, stabilized enolates and other carbon nucleophiles
Georg-August-Universität Göttingen
Tammannstrasse 2, 37077 Göttingen (Germany)
Fax : (‡49)551-399475
were tested. These were generated by separately deprotonat-
ing malononitriles and diethyl malonates with sodium hydride
and then adding to the reaction mixture from 1, the palladium
precatalyst, and iodobenzene (2) to give the malonic acid
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
Dr. M. Noltemeyer
Institut für Anorganische Chemie
Georg-August-Universität Göttingen
Röntgenstrukturabteilung
[8]
derivatives 11a ± c in up to 77% yield. In accordance with
[7]
earlier findings, only products of the nucleophilic attack at
the sterically less encumbered terminus of the allyl moiety
were obtained (Scheme 2).
Tammannstrasse 4, 37077 Göttingen (Germany)
[
**] Cyclopropyl Building Blocks in Organic Synthesis, Part 73. This work
was supported by the Fonds der Chemischen Industrie and Bayer AG.
We are indebted to Dr. B. Knieriem, Göttingen, for his careful
proofreading of the final manuscript. Part 72: A. de Meijere, M. von
Seebach, S. I. Kozhushkov, S. Cicchi, T. Dimoulas, A. Brandi, Eur. J.
Org. Chem. 2001, in press; Part 71: A. de Meijere, S. I. Kozhushkov, D.
Faber, V. Bagutskii, R. Boese, T. Haumann, R. Walsh, Eur. J. Org.
Chem. 2001, in press.
Especially interesting is the possible preparation of amino
acid derivatives by this method. With OꢁDonnellꢁs nucleo-
[9]
philic glycine equivalent 12 the methylenecyclopropane
derivative 13, a substituted isomer of hypoglycin A in a
protected form,[ was obtained in 76% yield (Scheme 3).
Glycine methyl ester 14a, in the presence of triethylamine in
10]
Angew. Chem. Int. Ed. 2001, 40, No. 18
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