Efficient Access to Alanine Derivatives by 1,4-Additions of Potassium Trifluoro(organo)borates

Article abstract of DOI:10.1002/ejoc.200300462

Potassium trifluoro(organo)borates, highly stable and easily prepared organoboran derivatives, were able to react with a great variety of dehydroamino esters. This reaction, catalyzed by rhodium complexes, allowed the formation of alanine derivatives bearing a great variety of amino protecting groups in good to high yields.

Full text of DOI:10.1002/ejoc.200300462

FULL PAPER
Efficient Access to Alanine Derivatives by 1,4-Additions of Potassium
Trifluoro(organo)borates
[a]
[a]
[a]
Laure Navarre, Sylvain Darses,* and Jean-Pierre Genet*
Keywords: Borates / Rhodium / Amino esters / Catalysis
Potassium trifluoro(organo)borates, highly stable and easily
prepared organoboron derivatives, were able to react with a
ine derivatives bearing a great variety of amino protecting
groups in good to high yields.
great variety of dehydroamino esters. This reaction, cata- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
lyzed by rhodium complexes, allowed the formation of alan-
Germany, 2004)
Introduction
several advantages over trivalent organoboronic acids and
their derivatives: higher stability towards air and water, ease
of preparation and purification, and generally higher reac-
α-Amino acids are important building blocks, particu-
larly for combinatorial chemistry and drug discovery. A
wide range of approaches is available for the synthesis of
such compounds, the most important being the amination
of α-halo acids, the Strecker synthesis, multicomponent Ugi
or Petasis condensations and catalytic hydrogenations of
dehydroamino acids. Despite the great variety of well-
known and tried methods, the development of new general
synthetic protocols for α-amino acids is still an active field.
The synthesis of α-amino acids involving carbonϪcarbon
[10]
tivity in many processes.
In this paper, we wish to report the development of a
highly effective 1,4-addition of potassium trifluoro(organo)-
borates to various dehydroamino esters.
[
1]
Results and Discussion
Initially, we examined the 1,4-addition, catalyzed by rho-
bond formation by Michael addition to dehydroamino acid dium complexes, of potassium trifluoro(phenyl)borate with
derivatives is an alternative that has only been explored to dehydroamino ester 1a, which is known to be a poor
[
2,3]
limited extent.
Real improvements in this strategy have Michael acceptor (Table 1). As a rhodium source, cationic
recently been achieved with the 1,4-addition of soft or- [Rh(cod) ]PF6 was selected because it has proven to be
2
[
4]
ganometallic reagents catalyzed by rhodium(). Li et al. highly effective in carbometallation processes of potassium
first reported the use of organostannanes and an example trifluoro(organo)borates with enones and esters.
[5]
[12]
[13]
of the use of an organosilane[ in the carbometallation of
6]
α-phthalimidoacrylate derivatives. Organoboronic acids
Table 1. Optimization of the reaction conditions[a]
have also proven to be suitable for this reaction[ avoiding
7]
the use of toxic tin reagents. Two examples of an asymmet-
[
8]
ric version have recently been developed by Reetz and
[
9]
Frost. With the exception of the latter, all the reported
reactions concerned the carbometallation of electron-de-
ficient α-phthalimidoacrylate derivatives.
Entry Solvent
Ligand (3 mol %) Time [h] Conversion[b]
We have been involved for several years in the develop-
ment of potassium trifluoro(organo)borates[ in transition
metal-catalyzed reactions, mainly with respect to cross-
coupling reactions in the presence of palladium com-
10]
1
2
3
4
5
6
7
8
water
toluene/H O
dioxane/H
toluene/H O
toluene/H
toluene/H
toluene/H
toluene/H
Ϫ
Ϫ
Ϫ
PPh3
18
18
18
1
100 (40)
50
50
23
[
c]
2
[c]
2
O
[
c]
[
11]
2
plexes
and asymmetric 1,4-additions catalyzed by chiral
[
c]
[12]
2
2
2
2
O
O
O
O
PCy
3
1
1
1
1
40
100 (94)
80
rhodium complexes.
These boron ate complexes offer
[c]
c]
[c]
dppp
dppf
dppb
[
[
a]
Laboratoire de Synth e` se S e´ lective Organique et Produits
Naturels (UMR, 7573 CNRS), Ecole Nationale Sup e´ rieure de
Chimie de Paris,
80
[a]
Reactions were conducted with 0.5 mmol of dehydroamino ester
and 2 equiv. of RBF K, in the presence of 3 mol % of
[Rh(cod) ]PF /dppp at 110 °C. Determined by GC analysis. Be-
tween parentheses, isolated yields. Volumetric proportions 20:1.
11 rue Pierre et Marie Curie, 75231 Paris cedex 05, France
Fax: (internat.) ϩ 33-1-4427071062
E-mail: genet@ext.jussieu.fr
darses@ext.jussieu.fr
3
[
b]
2
6
[c]
Eur. J. Org. Chem. 2004, 69Ϫ73
DOI: 10.1002/ejoc.200300462
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
69

L. Navarre, S. Darses, J.-P. Genet
FULL PAPER
When the dehydroamino ester 1a was allowed to react Table 2. Arylalanine derivatives by rhodium-catalyzed conjugated
with potassium trifluoro(phenyl)borate 2a in the presence additions[
a]
of a catalytic amount of [Rh(cod) ][PF ] (3 mol %) without
2
6
additional ligands under refluxing conditions in water
(Table 1, entry 1), the Michael addition adduct 3a was iso-
lated in 40 % yield. Although complete consumption of the
starting material was observed, yields were low due to de-
composition of the substrate. The use of a cosolvent in the
reaction medium did not greatly improve the yields (entries
2
and 3). No reaction was observed without the catalyst,
but the combination of rhodium() and a phosphane ligand
resulted in an acceleration of the conjugate addition. Differ-
ent ligands were tested (entries 4 to 8) and monophos-
phanes like triphenylphosphane and tricyclohexylphos-
phane resulted in incomplete reactions: hydrodeboration of
potassium trifluoro(organo)borates was the major bypro-
duct. In contrast, diphosphanes ligands (entries 6 to 8) gave
higher conversions, the most efficient ligand being diphenyl-
phosphanylpropane (entry 6). Under these conditions, the
1,4-addition adduct 3a was obtained with complete conver-
sion of the starting material and isolated in a 94 % yield.
Various organoboron reagents and dehydroamino esters
were then examined under these optimized reaction con-
ditions (Scheme 1).
Scheme 1. The synthesis of arylalanine derivatives from 1,4-ad-
ditions of potassium trifluoro(organo)borates
The generality of these optimized conditions was first
tested on the very reactive α-phthalimidoacrylate derivative
1b by varying the substituent on the potassium trifluoro-
(
organo)borate. The synthesis of substrate 1b was realized
[14]
by the Trost α-addition reaction of acetylenic carboxylic
[
a]
Reactions were conducted with 0.5 mmol of dehydroamino ester
and 2 equiv. of RBF K 2, in the presence of 3 mol % of
Rh(cod) ]PF /dppp, in toluene/water, 20:1, at 110 °C.
acid derivatives. As shown in the table (Table 2, entries 1 to
1
[
3
5), a great variety of potassium aryltrifluoroborates were
2
6
able to carbometallate this type of dehydroamino ester, with
good to high efficiency. The nature of the substituents (elec-
tron-deficient or -releasing) does not seem to influence the (Boc), benzyloxycarbonyl (Z), or trifluoroacetyl (COCF3),
course of the Michael addition greatly. Reaction times were were tested under our conditions. To the best of our knowl-
largely below one hour, even with the ortho-substituted or- edge, this is the first time that these protecting groups have
ganoborate derivative 2c (entry 4). These results compete been tested in such catalytic 1,4-addition of organometallic
with and even surpass previously reported 1,4-additions on reagents on this class of substrate, perhaps because of their
this substrate in terms of higher yields and shorter reac- lower reactivity than α-phthalimidoacrylate derivatives 1b
[
7,8,11]
tion times.
(Table 2). We were pleased to find that the various protect-
The scope of this carbometallation was further extended ing groups were not only tolerated under these reaction
by varying the nature of the amino protecting group (entries conditions but allowed access to a large variety of α-amino
6
to 14). Thus the standard protecting groups used in pep- esters in good yields. Particularly, Boc and Z protecting
tide synthesis such as acetyl (Ac), tert-butyloxycarbonyl groups were not removed under these conditions allowing
70
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 69Ϫ73

Efficient Access to Alanine Derivatives
FULL PAPER
the formation of protected α-amino acids that are attractive
for synthesis. Methyl N-(trifluoroacetylamino)acrylate (1f)
was very reactive (with a reactivity similar to that of 1b)
and allowed the formation of adduct 3k in a high yield
(94 %). Once again, this reaction was very efficient as
evident from the short reaction time, proving the high
reactivity of potassium trifluoro(organo)borates in carbo-
metallative processes catalyzed by rhodium.
We were also interested in testing the readily available, air
and water stable, potassium alken-1-yltrifluoroborate under
identical conditions. Preliminary results are summarized in
Table 3.
3
Figure 1. A comparison of the reactivity of PhBF K and
PhB(OH) with 1a
2
Table 3. The Michael addition of potassium alken-1-yltrifluorobor-
ate derivatives
[
a]
high yield. In this respect, the reactivity of potassium tri-
fluoro(organo)borate is unusual and further studies are un-
derway to understand this difference in reactivity observed
with these two boron species. The first step in this carbo-
metallation process is believed to be the transmetallation of
the organometallic partner with the rhodium() precur-
sor, the presence of an inductive period using potassium
trifluoro(organo)borate may be due to the slow trans-
metallation of the boron reagent with the cationic rhodium
catalyst. Furthermore, this period presumably corresponds
to the generation of either a more reactive boron reagent or
another active catalyst precursor. We are currently working
[
15]
[
a]
Reactions were conducted with 0.5 mmol of dehydroamino ester
and 4 equiv. of RBF
Rh(cod) ]PF /dppp, in toluene/water, 20:1, at 110 °C.
with 32 % of 3,4-isomer. Along with 30 % of 3,4-isomer.
1
[
3
K 2, in the presence of 3 mol % of on this process in order to identify the active species.
[b]
2
6
Along
[
c]
Conclusion
Even if the carbometallation of potassium (alken-1-yl)tri-
We have shown that potassium trifluoro(organo)borates
fluoroborates was not as efficient as that using aryl deriva- were able to carbometallate dehydroamino esters with high
tives, potassium trifluoro[(E)-2-(4-methylphenyl)ethenyl]- efficiency in the presence of a rhodium catalyst. This reac-
borate (2g) added smoothly to dehydroamino ester deriva- tion allowed the formation of various alanine derivatives in
tives affording alkenyl-substituted alanine derivatives in good to high yields (up to 98 %). In contrast to similar reac-
reasonable yields (entries 1Ϫ2). More particularly, potass- tions previously described, a variety of amino acid protect-
ium trifluoro(vinyl)borate (2h), a highly stable vinylating ing groups are tolerated under the reaction conditions used.
[
11b,11c]
agent,
acrylate (1a) affording methyl 2-(acetylamino)pent-4-enoate reactions and greater stability than other organometallic re-
3q) in 55 % yield (entry 3), together with an isomerization agents, potassium trifluoro(organo)borate appears to be a
was able to add to methyl N-acetylamino- Thanks to their high reactivity in transition metal-catalyzed
(
product (26 %). Lower yields obtained with (alken-1-yl)tri- promising alternative as reagent for various reactions. We
fluoroborates may be attributed to their higher tendency to are currently working on an asymmetric version of this re-
be reduced under these reaction conditions, but also to the action.
presence of isomers, due to the migration of the double
bond. Further improvements to carbometallate potassium
alken-1-yltrifluoroborate derivatives cleanly are underway.
The reactivities of phenylboronic acid and potassium tri-
Experimental Section
fluoro(phenyl)borate were also compared under these con- General Remarks: H NMR and 13C NMR spectra were recorded
1
ditions for their 1,4-addition to dehydroamino ester 1a (Fig- on a Bruker AC 200 or Avance 400 instruments; chemical shifts (δ)
are reported in ppm relative to Me
4
Si; coupling constants (J) are
ure 1). Under identical conditions, higher initial rates were
observed for the 1,4-addition of phenylboronic acid, but the
reaction stopped rapidly because of the competitive hydro-
deboration of the boron reagent. On the other hand, using
potassium trifluoro(phenyl)borate (2a), an induction period
of around twenty minutes is observed before the formation
of the conjugated adduct. After this initial period,
1
1
reported in Hz and refer to apparent peak multiplicities. B and
1
9
F NMR spectra were recorded on a Bruker Avance 400 instru-
11
ment at 128 and 376 MHz respectively using BF
3
·Et
2
O ( B NMR
1
9
spectra) and CFCl
3
( F NMR spectra) as an internal reference.
Mass spectra were determined on a Ribermag instrument. High
resolution mass spectra were performed on a Varian MAT311 at
the Universit e´ Pierre et Marie Curie (Paris). Elemental analyses
potassium trifluoro(phenyl)borate reacted smoothly and were done at the Regional Service of Microanalysis (Universit e´ Pi-
quantitatively to afford N-acetylphenylalanine (3a) in a erre et Marie Curie). Thin layer chromatography was carried out
Eur. J. Org. Chem. 2004, 69Ϫ73
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
71

L. Navarre, S. Darses, J.-P. Genet
FULL PAPER
on silica-gel plates (Merck F254), spots were detected with UV light
(118 mg) according to the general procedure. R
f
ϭ 0.18 (cyclohex-
1
and revealed with KMnO
4
solution.
ane/ethyl acetate, 9:1). t
CDCl ): δ ϭ 1.42 (s, 9 H), 3.03 (dd, J ϭ 13.8, J ϭ 6.2 Hz, 1 H),
3.09 (dd, J ϭ 13.8, J ϭ 5.7 Hz, 2 H), 3.72 (s, 3 H), 3.78 (s, 3 H),
R
ϭ 14.4 min (A). H NMR (400 MHz,
2
3
GC analyses were performed on a HewlettϪPackard instrument
equipped with a J&W Scientific DB-1701 capillary column (15 m,
3
2
3
3
4
␾
ϭ 0.25 µm), using an ionization flame detector: program A: 70
4.55Ϫ4.60 (m, 1 H), 4.97 (br. d, J ϭ 7.8 Hz, 1 H), 6.67 (d, J ϭ
3
3
4
°C for 1 min then 20 °C/min up to 210 °C, program B: 150 °C for 1.7 Hz, 1 H), 6.71 (d, J ϭ 7.5 Hz, 1 H), 6.78 (dd, J ϭ 8.2, J ϭ
3
13
1
min then 20 °C/min up to 250 °C, program C: isotherm 250 °C.
]PF
was prepared according to published procedures.[16]
Toluene was distilled from CaH
1.7 Hz, 1 H), 7.20 (app. t, J ϭ 7.9 Hz, 1 H) ppm. C NMR (50
MHz, CDCl ): δ ϭ 28.2, 38.3, 52.2, 54.3, 55.1, 79.9, 112.4, 114.9,
121.6, 129.5, 137.5, 155.0, 159.6, 172.3 ppm. MS (CI: NH ) ϭ 327
[
Rh(cod)
2
6
3
2
.
3
ϩ
ϩ
ϩ
[
C
M ϩ NH
4
] , 310 [M ϩ H] , 271 [M Ϫ C
4
H
8
ϩ NH
4
] , [M Ϫ
Typical Procedure for the 1,4-Addition of Potassium Aryl- and
Alken-1-yltrifluoroborates to Dehydroamino Esters: A mixture of
dehydroamino ester (0.5 mmol), potassium trifluoro(organo)borate
ϩ
4
H
8
ϩ H] . HRMS calcd. for C16
H24NO : 310.1654; found
5
310.1650.
(
2 6
2 equiv.), [Rh(cod) ]PF (7.0 mg, 3 mol %), and dppp (6.2 mg, 3
Methyl 2-Acetylamino-5-(p-tolyl)pent-4-enoate (3o): A colorless
liquid was obtained in a 63 % yield (82 mg) according to the gen-
mol %) were charged into a flask under argon, followed by addition
of a degassed toluene/water mixture (2 mL/0.1 mL) at room tem-
perature. The flask was placed in a preheated oil bath at 110Ϫ115
eral procedure. R
1
(
f
ϭ 0.46 (cyclohexane/ethyl acetate, 2:3). t
2.4 min (A). H NMR (200 MHz, CDCl ): δ ϭ 2.01 (s, 3 H), 2.33
s, 3 H), 2.64Ϫ2.73 (m, 2 H), 3.75 (s, 3 H), 4.73 (td, J ϭ 7.8, J ϭ
R
ϭ
1
3
°
C and the mixture was stirred until completion of the reaction
3
3
(followed by GC analysis). Purification by silica gel chromatogra-
3
3
3
5.6 Hz, 1 H), 5.99 (dt, J ϭ 15.8, J ϭ 7.8 Hz, 1 H), 6.10 (d, J ϭ
phy (eluent: cyclohexane/ethyl acetate) afforded analytically pure
products. Compounds 3a,
3
3
3
5
.8 Hz, 1 H), 6.42 (d, J ϭ 15.8 Hz, 1 H), 7.10 (d, J ϭ 8.1 Hz, 2
[
17]
[18]
[19]
[20]
[21]
[22]
[22]
3c,
3f,
3g,
3h,
3i,
3j,
3
13
H), 7.22 (d, J ϭ 8.1 Hz, 2 H) ppm. C NMR (50 MHz, CDCl
3
):
[
23]
[24]
[25]
[26]
k,
3l,
3m,
and 3q
show identical physical data to that
δ ϭ 21.1, 23.1, 35.8, 52.0, 52.4, 122.3, 126.1, 129.2, 134.0, 137.4, 1
previously reported in the literature.
ϩ·
6
1
2
9.7, 172.3 ppm. MS (70 eV): m/z (%) ϭ 261 (4) [M ], 202 (75),
43 (100). HRMS calcd. for
62.1437.
15 3
C H20NO : 262.1443; found
Methyl 3-(3-Methoxyphenyl)-2-phthalimidopropanoate (3b): A yel-
low solid obtained in a 90 % yield (153 mg) according to the gen-
eral procedure. R
f
ϭ 0.42 (cyclohexane/ethyl acetate, 4:1). m.p. 83
1
Methyl 2-Phthalimido-5-(p-tolyl)pent-4-enoate (3p): A colorless
liquid obtained in a 45 % yield (59 mg) according to the general
°
C. CPG: t ϭ 15.0 min (A). H NMR (200 MHz, CDCl ): δ ϭ
.54 (dd, J ϭ 10.5, J ϭ 5.7 Hz, 1 H), 3.60 (dd, J ϭ 10.6, J ϭ
.7 Hz, 1 H), 3.66 (s, 3 H), 3.77 (s, 3 H), 5.16 (dd, J ϭ 10.3, J ϭ
.2 Hz, 1 H), 6.57Ϫ6.69 (m, 3 H), 7.07 (td, J ϭ 7.6, J ϭ 1.1 Hz,
H), 7.66Ϫ7.72 (m, 2 H), 7.73Ϫ7.80 (m, 2 H) ppm. C NMR
): δ ϭ 34.6, 52.9, 53.1, 55.0, 112.7, 114.1, 121.1,
23.4, 129.5, 131.6, 134.1, 138.2, 159.6, 167.4, 169.3 ppm. MS
(339.34):
R
3
2
3
2
3
3
5
6
3
3
3
f R
procedure. R ϭ 0.40 (cyclohexane/ethyl acetate, 4:1). t ϭ 16.1 min
1
3
4
3
(C). H NMR (400 MHz, CDCl ): δ ϭ 2.27 (s, 3 H), 3.12Ϫ3.17
3
3
13
(m, 2 H), 3.77 (s, 3 H), 5.01 (dd, J ϭ 9.0, J ϭ 6.8 Hz, 1 H), 6.04
2
3
3
(
(
dt, J ϭ 15.8, J ϭ 7.4 Hz, 1 H), 6.38 (d, J ϭ 15.8 Hz, 1 H), 7.03
d, J ϭ 8.1 Hz, 2 H), 7.12 (d, J ϭ 8.1 Hz, 2 H), 7.70Ϫ7.82 (m, 2
H), 7.83Ϫ7.89 (m, 2 H) ppm. C NMR (63 MHz, CDCl ): δ ϭ
(50 MHz, CDCl
3
3
3
1
(
1
3
70 eV): m/z (%) ϭ 339 (11) [Mϩ·], 192 (100). C19
H17NO
3
5
2
1
1.2, 32.7, 49.4, 51.9, 123.6 (3 C), 126.1 (2 C), 129.2 (2 C), 131.7,
calcd. C 67.25, H 5.05, N 4.13; found C 66.44, H 5.00, N 4.04.
33.5, 134.2 (2 C), 134.7, 137.3, 167.3, 169.4 ppm. MS (70 eV):
Ethyl 3-(2-Methylphenyl)-2-phthalimidopropanoate (3d): A yellow
solid obtained in a 98 % yield (165 mg) according to the general
ϩ·
m/z (%) ϭ 261 (4) [M ], 202 (75), 143 (100). HRMS calcd. for
21 4
C H20NO : 350.1392; found 350.1390.
procedure. R
f
ϭ 0.30 (cyclohexane/ethyl acetate, 9:1). m.p. 72 °C.
1
CPG: t ϭ 12.3 min (B). H NMR (200 MHz, CDCl
R
3
): δ ϭ 1.26
Typical Procedure for the Preparation of Potassium Trifluoro(or-
t, J ϭ 7.1 Hz, 3 H), 2.39 (s, 3 H), 3.50 (dd, 2J ϭ 14.5, 3J ϭ gano)borates: A solution of the Grignard reagent [prepared from
3
(
1
2
3
3
1.1 Hz, 1 H), 3.64 (dd, J ϭ 14.5, J ϭ 5.2 Hz, 1 H), 4.25 (q, J ϭ
the aryl bromide (200 mmol) and magnesium (200 mmol) in anhy-
3
3
7.1 Hz, 2 H), 5.15 (dd, J ϭ 11.1, J ϭ 5.2 Hz, 1 H), 6.95Ϫ7.08 drous THF or diethyl ether (150 mL)] was added dropwise (keeping
13
(
(
1
m, 4 H), 7.66Ϫ7.72 (m, 2 H), 7.73Ϫ7.80 (m, 2 H) ppm. C NMR the internal temperature below Ϫ60 °C) to a mechanically stirred
50 MHz, CDCl ): δ ϭ 14.1, 19.2, 32.3, 51.7, 62.0, 123.4, 125.9,
solution of trimethoxyborane (34.3 mL, 300 mmol, 1.5 equiv.) in
27.0, 129.6, 130.5, 131.6, 134.0, 134.9, 136.5, 167.4, 168.9 ppm. anhydrous THF (150 mL). The solution was placed at room tem-
3
ϩ·
MS (70 eV): m/z (%) ϭ 337 (6) [M ], 190 (57), 144 (100). perature (ca. 25°C) until the internal temperature reached 0 °C and
C
20
H19NO
4
(337.37): calcd. C 71.20, H 5.68, N 4.15; found C
the resulting suspension was poured into a saturated solution of
71.29, H 5.71, N 4.04.
KHF (85.9 g, 1.1 mol, 5.5 equiv.; Caution: use a Teflon vessel!) in
2
water (concentration of nearly 5 ). After 5 min of stirring at room
Ethyl 3-(3-Chlorophenyl)-2-phthalimidopropanoate (3e): A yellow
temperature the solvent was removed under vacuum (bath tempera-
ture: 50 °C) and the resulting solid was thoroughly dried under
high vacuum (0.1 Torr; the solid has to be completely dried). It was
then extracted four times with acetone (100 mL each time), the
solution was filtered, and the solvents evaporated (if the solid is
not completely dried, this procedure has to be repeated to avoid
the presence of impurities). The powder was dissolved in a mini-
mum amount of acetone, the solution was filtered and precipitation
of the salt was accomplished by the addition of diethyl ether (using
solid was obtained in a 75 % yield (134 mg) according to the gen-
eral procedure. R
f
ϭ 0.20 (cyclohexane/ethyl acetate, 9:1). m.p. 68
1
°
C. CPG: t ϭ 14.6 min (A). H NMR (200 MHz, CDCl
R
3
): δ ϭ
.26 (t, J ϭ 7.1 Hz, 3 H), 3.50 (dd, J ϭ 14.5, J ϭ 10.6 Hz, 1 H),
3
2
3
1
3
5
7
2
3
3
.55 (dd, J ϭ 14.5, J ϭ 5.8 Hz, 1 H), 4.25 (q, J ϭ 7.2 Hz, 2 H),
.11 (dd, 3J ϭ 10.6, 3J ϭ 5.8 Hz, 1 H), 7.06Ϫ7.17 (m, 4 H),
13
.67Ϫ7.72 (m, 2 H), 7.73Ϫ7.82 (m, 2 H) ppm. C NMR (50 MHz,
): δ ϭ 14.1, 34.4, 54.1, 62.2, 123.6, 127.0, 127.1, 129.8, 131.6,
34.2, 138.9, 167.3, 168.5 ppm. MS (70 eV): m/z (%) ϭ 357 (6)
CDCl
1
3
3
to 5 times the amount of acetone). The white solid was filtered,
ϩ·
[M
], 210 (100). C19
4
H16ClNO (357.79): calcd. C 63.78, H 4.51, N
washed thoroughly with diethyl ether, and dried under vacuum. In
3.91; found C 63.61, H 4.51, N 4.00.
1
3
the C NMR spectrum, the signal corresponding to the carbon
Methyl
2-(tert-Butyloxycarbonylamino)-3-(3-methoxyphenyl)pro-
atom in the α-position of the tetravalent boron atom was generally
[
27,11c]
panoate (3n): A colorless liquid was obtained in a 76 % yield not observed. Potassium trifluoro(organo)borates 2a,
72
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org Eur. J. Org. Chem. 2004, 69Ϫ73

Efficient Access to Alanine Derivatives
f,[27,11c] 2g,[11b,11c] and 2h[28] were prepared according to pub-
FULL PAPER
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2
lished procedures.
[
4]
Potassium Trifluoro(3-methoxyphenyl)borate (2b):[29] A white solid
was obtained from 1-bromo-3-methoxybenzene (200 mmol) ac-
cording to the general procedure in an 85 % yield (35.6 g), m.p. 188
[4a]
[4b]
complexes see:
T. Hayashi, Synlett 2001, 879Ϫ887.
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[
[
5]
6]
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°C (acetone/diethyl ether).
Potassium Trifluoro(2-methylphenyl)borate (2c):[29] A white solid
was obtained from 1-bromo-3-methoxybenzene (200 mmol) ac-
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Potassium (3-Chlorophenyl)trifluoroborate (2d): A white solid was
obtained from 1-bromo-3-chlorobenzene (200 mmol) according to
4313Ϫ4327.
[11] [11a]
S. Darses, J. P. Genet, J. L. Brayer, J. P. Demoute, Tetra-
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1
[11c]
diethyl ether). H NMR (400 MHz, [D
(
6
]acetone): δ ϭ 7.04Ϫ7.13
]ace-
tone): δ ϭ 125.9, 129.0, 130.7, 132.2, 133, 1 ppm. B NMR
S.
13
m, 2 H), 7.37Ϫ7.43 (m, 2 H) ppm. C NMR (50 MHz, [D
6
1
1
[11d]
1875Ϫ1883. See also:
hedron Lett. 2001, 42, 9099Ϫ9103. [
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]acetone): δ ϭ 6.5 (q, J ϭ 52 Hz) ppm. 1 F NMR
9
G. A. Molander, B. W.
(
(
128 MHz, [D
376 MHz, [D
6
6
]acetone): δ ϭ Ϫ145.5 (br. q, J ഠ 56 Hz).
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G. A. Molander, B. Biol-
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[
M. Pucheault, S. Darses, J. P. Genet, Tetrahedron Lett.
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2
1
diethyl ether). H NMR (200 MHz, [D
(
6
]acetone): δ ϭ 7.33Ϫ7.45
13
m, 2 H), 7.67Ϫ7.86 (m, 4 H), 8.11 (s, 1 H) ppm. C NMR
50 MHz, [D ]acetone): δ ϭ 125.1, 125.4, 126.3, 128.2, 128.8, 131.2,
31.6, 133.8, 134.4 ppm. 11B NMR (128 MHz, [D
]acetone): δ ϭ
.41 (br) ppm. 19F NMR (376 MHz, [D
]acetone): δ ϭ Ϫ142.1 (br.
[13]
[14]
(
6
1
7
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
73