Synthesis of boron- and silicon-containing amino acids through copper-catalysed conjugate additions to dehydroalanine derivatives

Article abstract of DOI:10.1002/ejoc.201500362

A copper-based catalytic technique for the regioselective hydroboration and hydrosilylation of dehydroalanine derivatives has been developed. This method introduces synthetically versatile boron and silicon groups, while simultaneously performing a cataly

Full text of DOI:10.1002/ejoc.201500362

Job/Unit: O50362
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Date: 15-04-15 11:32:13
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FULL PAPER
DOI: 10.1002/ejoc.201500362
Synthesis of Boron- and Silicon-Containing Amino Acids through Copper-
Catalysed Conjugate Additions to Dehydroalanine Derivatives
Francesca Bartoccini,[a] Silvia Bartolucci,[a] Simone Lucarini,[a] and Giovanni Piersanti*[a]
Keywords: Boron / Silicon / Copper / Amino acids / Homogeneous catalysis / Michael addition
A copper-based catalytic technique for the regioselective
tion of dehydroalanines and dehydropeptides for the synthe-
hydroboration and hydrosilylation of dehydroalanine deriva- sis of amino acids and peptides bearing unnatural side-
tives has been developed. This method introduces syntheti-
cally versatile boron and silicon groups, while simultaneously
chains. The products obtained were expediently converted
into valuable nonproteinogenic amino acid building blocks
performing a catalytic anti-Markovnikov hydrofunctionaliza- for polypeptide synthesis.
Introduction
Recently, there has been considerable interest in the gen-
eration of small molecules with organoboron and organo-
silicon functionalities due to the large number of applica-
tions of such molecules in organic synthesis (organometallic
partners in cross-coupling reactions), chemical biology, and
even as diagnostic and therapeutic agents.[1] Applications in
inhibitor design, imaging, drug-release technology, and in
mapping of inhibitor binding are also known.[2] The ap-
proval of bortezomib (marketed as Velcade® by Millennium
Pharmaceuticals), a proteosome inhibitor containing a
boronic acid group, for the treatment of multiple myeloma
in humans highlights the successful application of unnatu-
ral functional groups in a therapeutically relevant manner.[3]
The incorporation of silicon and boron into amino acids
and peptides to give improved physiochemical properties
and in vivo activity is particularly significant (Figure 1).
Additionally, boronic-acid-containing amino acids remain
one of the more promising classes of boron-neutron-capture
therapy (BNCT) agents.[4] Boron- and silicon-containing
amino acids are most often prepared through alkylation of
glycinimine or another synthetic equivalent with halo-
methyl boronate or halomethylsilane electrophiles,[5] or
through transmetallation of highly reactive organolithium/
organomagnesium reagents (alanine anion equivalents)
with electrophilic boron/silicon species.[6] These methods
have significant limitations, such as a difficult preparation,
the requirement of cryogenic conditions and additional
steps, and functional group incompatibility in the case of
transmetallations.
Figure 1. Examples of silyl- and boronic acid-containing amino
acids. TMS = trimethylsilyl.
Results and Discussion
Over the last few years, we have endeavoured to enlarge
the scope, utilization, and application of dehydroalanine de-
rivatives in synthesis.[7] To date, we have focussed our atten-
tion exclusively on C–C bond-forming processes, and we
have established that an array of indoles can be coupled
efficiently with different dehydroalanine electrophiles using
both a stoichiometric amount of a strong Lewis acid and an
organocatalytic manner.[7c,7e] We recently decided to at-
tempt to expand these coupling reactions to generate bonds
other than C–C bonds in a catalytic manner. In view of the
need for additional complementary methods for the synthe-
[a] Department of Biomolecular Sciences, University of Urbino
“Carlo Bo”,
Piazza del Rinascimento 6, 61029 Urbino (PU), Italy
E-mail: giovanni.piersanti@uniurb.it
http://www.uniurb.it/MedChem/PiersantiResearch/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500362.
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F. Bartoccini, S. Bartolucci, S. Lucarini, G. Piersanti
FULL PAPER
sis of boron- and silicon-containing amino acids, we under-
We first studied the extension of this reaction to a diverse
took the challenge of achieving borylation and silylation of array of N-protected dehydroamino esters (1a–1f) not only
dehydroalanine derivatives to provide C–B and C–Si bonds, to access differently protected useful amino acids contain-
a transformation that could enable regiospecific and late- ing boron, but also to evaluate their influence on the reac-
stage incorporation of boron and silicon into dehydroamino tion yields. Of the amine protecting groups tested
acids and dehydropeptides in an umpolung process. At the (Scheme 1), acetyl (1a), Cbz (1b; Cbz = benzyloxycarbonyl),
time we began this investigation, there were no reports of Boc (1c), and Fmoc (1d; Fmoc = fluorenylmethoxy-
such reactions; however, last year, Lin and coworkers de- carbonyl) protecting groups gave good yields of the β-tri-
scribed copper catalysts that result in borylation of β-sub- fluoroborate alanine derivatives (i.e., 3a–3d). With a phthal-
stituted α-dehydroamino acid derivatives at room tempera- imido (1e; Phth) protecting group, we obtained a very ef-
ture or above.[8]
ficient addition. In contrast, the diphenylmethylene group
In this report, we describe a copper(I)-catalysed method (1f) was not compatible with the reaction conditions, giving
that accomplishes borylation and silylation reactions of an a by-product during trifluoroborate formation.
array of unactivated protected dehydroalanine derivatives.
Our observation for the first time that small dehydropeptide
electrophiles can serve as effective coupling partners for
borylations and silylations is particularly noteworthy. In ad-
dition, we report experimental details demonstrating the
capability of N-Boc β-pinacolboronate- and (dimethyl)-
phenylsilyl-alanine methyl esters (Boc
= tert-butoxy-
carbonyl) to be selectively deprotected to give either the free
amines or the free acids under mild reaction conditions, and
then to undergo some of the typical coupling reactions as-
sociated with peptide synthesis.
The C–B bond functionalization of acrylates and acryl-
amide mediated by copper is well established.[9] We recog-
nized that the method described by Yun 2006[9d] could be
used to selectively functionalize protected dehydroalanines,
formally a hydroboration reaction, by using bis(pinacolato)-
diboron (B2pin2) as the “boron” source, MeOH as the
“hydrogen” source, a catalytic amount of CuCl to generate Scheme 1. Borylation of α-dehydroamino acid derivatives (1a–1f).
Reagents and conditions: [a] 1. CuCl (5 mol-%), KOtBu (15 mol-
copper(I) tert-butoxide as the active catalyst, and a phos-
%), dppbz (5 mol-%), B2pin2 (1.3 equiv.), MeOH (2 equiv.), THF,
room temp., 20 h; 2. KHF2 (4 equiv.), THF, H2O, room temp., 20 h.
phine ligand in THF. Yun’s reaction conditions were ini-
tially applied to the commercially available methyl N-acet-
amidoacrylate. Changes to the reaction conditions included
modifying the Cu catalyst and loading, the solvent, the
Next, we evaluated the transfer of silicon nucleophiles
inert atmosphere, and the reaction temperature. However, onto the same dehydroalanine derivatives (i.e., 1a–1f) under
no increase in the yield was observed. Optimal turnover standard copper(I)-catalysed conditions, using Suginome’s
numbers and yields were seen with 5 mol-% CuCl. The reac- reagent (Me2PhSiBpin)[11] as the silicon pronucleophile. Al-
tion proceeded at room temperature for 20 h, and the ad- though silylboranes have been used extensively to promote
dition of the phosphine ligand 1,2-bis(diphenylphosphan- the silylborylation of various α,β-unsaturated carbonyl and
yl)benzene (dppbz) proved to be important for full conver- carboxyl compounds, conjugated alkynes, aldehydes, and
sion, based on 1H NMR spectroscopic data (see Supporting imines,[12] to the best of our knowledge their use for the
Information). Generally, the resulting β-pinacolboronate-α- synthesis of silane-containing amino acids has not been ex-
amino acid intermediate could not be isolated because of plored. As shown in Scheme 2, the use of commercially
its instability during flash chromatography.[8] Therefore, it available 1a, CuCl as the catalyst, and dppbz as the sup-
was transformed quantitatively into the corresponding porting ligand gave promising results, but required heating
potassium organotrifluoroborate by treating the crude reac- at 50 °C to achieve reasonable reaction times. Several simple
tion mixture with KHF2. The non-Lewis-acidic, salt-like N-protected dehydroalanine methyl esters, such as N-Cbz
potassium trifluoroborate amino acid thus prepared was a (1b), N-Boc (1c), N-Fmoc (1d), and phthalimido (1e) deriv-
nonhygroscopic, free-flowing powder or crystalline solid atives showed no variation in terms of yield or reactivity.
that was indefinitely stable to the atmosphere. The resulting Even the diphenylmethylene protecting group (1f) was com-
crude potassium trifluoroborate was recrystallized from patible with the silylation reaction conditions, giving the
acetone/diethyl ether to give the pure product, free of pin- product (i.e., 4f) in good yield.
acol. A significant advantage of the organotrifluoroborate
Based on these results, it appeared that a great variety of
product over the corresponding boronate is the easy purifi- boryl and silyl alanine derivatives could be readily obtained
cation of the former product by acetone/ether precipi- by this tandem metallation/protonation process. The scope
tation.[10]
of our racemic copper(I)-catalysed enamine addition is cer-
2
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Copper-Catalysed Conjugate Additions
offering a unique reactive handle for further modifications
or modulating their biological activity needs to be high-
lighted in future studies.
Scheme 2. Silylation of α-dehydroamino acid derivatives 1a–1f.
Reagents and conditions: [a] CuCl (5 mol-%), KOtBu (15 mol-%),
dppbz (5 mol-%), Me2PhSiBpin (1.3 equiv.), MeOH (2 equiv.),
THF, 50 °C, 20 h.
Scheme 3. Extended scope of the borylation and silylation. Forma-
tion of polypeptides 2g–2i and 4g–4h. Reagents and conditions:
[a] CuCl (5 mol-%), KOtBu (15 mol-%), dppbz (5 mol-%), B2pin2
(1.3 equiv.), MeOH (2 equiv.), THF, room temp., 20 h; For 1i: CuCl
(9 mol-%), KOtBu (27 mol-%), dppbz (9 mol-%), B2pin2
(1.3 equiv.), MeOH (2 equiv.), THF, room temp., 20 h. [b] CuCl
(5 mol-%), KOtBu (15 mol-%), dppbz (5 mol-%), Me2PhSiBpin
(1.3 equiv.), MeOH (2 equiv.), THF, 50 °C, 20 h.
tainly broad, as demonstrated by its compatibility with
common protecting groups on the nitrogen atom
(Schemes 1 and 2). However, our attempts to render this
reaction enantioselective with representative chiral ligands
did not meet with success. The regiochemical outcomes of
these reactions are certainly governed by the mode of ad-
dition of the boryl- or silyl-copper species, derived from
B2pin2 or Me2PhSiBpin and a copper(I) complex, across
the unsaturated C–C bond, and anti-Markovnikov selectivi-
ties were observed, as shown in Schemes 1 and 2.
These reactions achieved rather poor diastereoselectivity,
which clearly indicates and confirms the lack of stereocon-
trol in the protonation step, and further attests to the diffi-
culties in the enantioselective protonation of enamines.[14]
The broader utility of this protocol for the rapid synthe-
Bearing in mind the importance of applications of site-
specific peptide labelling and chemically modified pept-
ides,[13] we next tested whether the optimized reaction con- sis of bisprotected boron- and silicon-containing amino
ditions could be used for the direct borylation and silylation acids, such as 2c and 4c, was demonstrated by their facile
of some dehydropeptides. Dehydropeptides 1g–1i were eas- conversion into useful amino acid building blocks for solid-
ily prepared in good yields from serine derivatives by a cou- phase peptide synthesis, and their ability to undergo typical
pling reaction with the appropriate protected amino acid, reactions associated with peptide synthesis (Scheme 4). N-
and hydroxy group elimination (see Supporting Infor- Boc-protected borylated and silylated alanines 2c and 4c
mation, Schemes S1 and S2), without intermediate purifica- were coupled, after selective methyl ester hydrolysis using
tion steps. We successfully used our optimized reaction con- lithium hydroxide, with l-phenylalanine methyl ester using
ditions for the borylation and silylation of dehydroalanine- EDCI
[1-ethyl-3-(3-dimethylaminopropyl)carbodiimide]/
containing dipeptides 1g and 1h (Scheme 3) to give non- HOBt coupling conditions to produce dipeptides 2h and 4h
racemic 2g and 2h, and 4g and 4h, respectively, all as mix- in good yield. Removal of the N-Boc group and coupling
tures of diastereoisomers. For compounds 4g and 4h, the with N-Cbz-valine yielded dipeptides 2g and 4g, again in
two diastereomers were separable. When the reaction was decent yield. These results, along with those of Walkup[6c]
applied to the three-residue dehydroalanine-containing on (trimethylsilyl)alanine, indicate that at least the simple
peptide 1i, it was necessary to increase the catalyst loading β-borylated and β-silylated alanines 2c and 4c are not affec-
to 9 mol-% of Cu for 2i to be obtained in a decent yield. ted by the coupling and deprotection conditions usually as-
Notably, these reactions proceeded with comparable effi- sociated with solution-phase peptide synthesis.[15] The inter-
ciencies and selectivities for both N- and C-terminal as well change of N-protecting groups is relevant when a switch in
as internal dehydroalanine residues under an ambient atmo- the chemoselectivity of the protecting groups is required
sphere of air, which highlights the robust nature of this due to a change in synthetic approach. N-Boc-protected
user-friendly protocol. The potential of this approach for borylated and silylated alanines 2c and 4c were fully com-
late-stage diversification of enantiomerically pure peptides patible with a standard Boc-deprotection and Fmoc-repro-
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F. Bartoccini, S. Bartolucci, S. Lucarini, G. Piersanti
FULL PAPER
Scheme 4. Functionalization of N-Boc-β-boronate alanine methyl ester 2c and N-Boc β-(dimethyl)phenylsilyl-alanine methyl ester 4c.
Reagents and conditions: [a] 1. TFA (trifluoroacetic acid), CH2Cl2, room temp., 2 h; 2. FmocOSu [N-(9-fluorenylmethoxycarbonyloxy)-
succinimide], NaHCO3, H2O, dioxane, r.t., 20 h. [b] Me3SnOH, DCE (1,2-dichloroethane), 80 °C, 6 h. [c] 1. LiOH, THF, r.t., 16 h; 2. l-
Phe(OMe), HOBt, Et3N, CH2Cl2, EDCI, r.t., 20 h. [d] 1. TFA, CH2Cl2, r.t., 2 h; 2. Z-Val, HOBt, Et3N, CH2Cl2, EDCI, r.t., 20 h. [e] HCl
(6 n), 70 °C, 16 h.
tection sequence, which gave 2d and 4d (also obtainable by
direct hydrofunctionalization of 1d) in very good yields. In-
triguingly, the Fmoc protecting group in 2d and 4d re-
Experimental Section
General Methods: Reactions were run in air unless otherwise noted.
Flash column chromatography was carried out using Merck 230–
mained intact throughout the methyl ester hydrolysis with
400 Mesh silica gel. Analytical thin-layer chromatography (TLC)
trimethyltin hydroxide.[16] This gave the corresponding
was carried out on Merck silica gel plates (Silica Gel 60 F254),
carboxylic acids (i.e., 2l and 4l) in sufficiently pure form
that they could be used directly as nonproteinogenic amino
acid building blocks in Fmoc solid-phase peptide synthesis
(SPPS). Finally, heating 2c and 4c with HCl (6 n aq.) at
70 °C led to completely unprotected boron- and silicon-
containing α-amino acids 5[5f] and 6,[5e] respectively, with
simultaneous hydrolysis of the pinacolboronate in 2c, and
Si–C(Ph) bond cleavage in 4c.
which were visualized by exposure to ultraviolet light and an aque-
ous solution of cerium ammonium molybdate (CAM) or KMnO4.
1H, 13C, and 11B NMR spectra were recorded with a Bruker Avance
200 or 400 spectrometer, using CDCl3, CD3OD, [D6]DMSO, [D6]-
acetone, or D2O as solvent. Chemical shifts (δ scale) are reported
in parts per million (ppm), and the the solvent peak was used as
an internal reference. Coupling constants (J values) are given in
Hertz (Hz). In 13C NMR spectra, carbon atoms adjacent to boron
were not observed. ESI-MS spectra were recorded with a Waters
Micromass ZQ instrument. IR spectra were obtained with a Nico-
let Avatar 360 FTIR spectrometer, and absorbances are reported
in cm–1. Melting points were determined with a Buchi SMP-510
capillary melting point apparatus. Elemental analyses were per-
formed with a Carlo Erba analyser, and the results are within Ϯ0.4
of the theoretical values (C, H, N). See Supporting Information for
other details.
Conclusions
In summary, we have reported the regioselective transfer
of boron and silicon nucleophiles onto dehydroalanine de-
rivatives as well as dehydropeptides to give β-boronated and
silylated amino acids and peptides in a catalyst-controlled
reaction for the first time. The value of this strategy as an
expedient means for a rapid, general, and mild synthetic
route to a new class of orthogonally N- and C-protected
boron- and silicon-containing amino acids was underlined
by the ability of these amino acids to be selectively depro-
tected and incorporated into peptides using solution-phase
methodology. Moreover, they can be easily converted into
suitable noncanonical amino acid building blocks for spe-
cific incorporation into a peptide framework by SPPS.
While the majority of the reported products are α-amino
acid pinacolboranes and dimethylphenylsilyl derivatives, a
succinct method for the synthesis of the corresponding tri-
fluoroborate derivatives, which are more stable, and which
can act as new nucleophilic alanine equivalents, has also
been described. This transformation can serve as a starting
point for the construction of boron and silicon amino-acid-
derived peptides. Further studies addressing the scope and
utility of this process are in progress.
General Procedure for the Copper(I)-Catalysed Borylation of De-
hydroalanines 1a–1e and Dehydropeptides 1g–1i: A mixture of CuCl
(1 mg, 0.01 mmol), KOtBu (3.5 mg, 0.03 mmol), and 1,2-bis(di-
phenylphosphanyl)benzene (dppbz; 5 mg, 0.01 mmol) in anhydrous
THF (0.12 mL) was stirred for 30 min in a sealed tube. B2pin2
(66 mg, 0.26 mmol) in THF (0.12 mL) was added. The reaction
mixture was stirred for 10 min, and then the appropriate dehy-
droalanine 1a–1e or dehydropeptide 1g–1i (0.2 mmol) in THF
(0.12 mL) was added to the reaction mixture, followed by MeOH
(16 μL, 0.4 mmol). The reaction mixture was stirred at the room
temperature for 20 h, and then it was filtered through a short plug
of silica gel. The crude product was used for the following reaction
without further purification (for 2a–2e), or it was purified by flash
chromatography (for 2g–2i).
Note: the hydroboration products were unstable, so the purification
operation should be quick.
Methyl
2-{[(9H-Fluoren-9-yl)methoxy]carbonylamino}-3-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate (2d): The general
procedure for CuI-catalysed borylation was followed using methyl
4
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Copper-Catalysed Conjugate Additions
2-{[(9H-fluoren-9-yl)methoxy]carbonylamino}acrylate (1d). The
resulting residue was purified by flash chromatography (gradient,
cyclohexane/EtOAc, 9:1 to 7:3) to give 2d (71 mg, 79%) as a
colourless oil. TLC (cyclohexane/EtOAc, 7:3): Rf = 0.23 (CAM).
1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 7.5 Hz, 2 H), 7.62
triazadodecan-12-oate and (5S, 8S, 11S)-Methyl 11-Benzyl-5-iso-
propyl-3,6,9-trioxo-1-phenyl-8-[(4,4,5,5-tetramethyl-1,3,2-dioxabor-
olan-2-yl)methyl]-2-oxa-4,7,10-triazadodecan-12-oate (2i): The ge-
neral procedure for CuI-catalysed borylation was followed using
Z-l-Val-ΔAla-l-Phe-OMe (1i) CuCl (1.8 mg, 0.018 mmol), KOtBu
(t, J = 7.5 Hz, 2 H), 7.41 (t, J = 7.5 Hz, 2 H), 7.323 (t, J = 7.5 Hz, (6 mg, 0.054 mmol), and (dppbz; 8 mg, 0.018 mmol). The resulting
1 H), 7.320 (t, J = 7.5 Hz, 1 H), 5.65 (br. d, J = 8.5 Hz, 1 H), 4.58
(dd, J = 15.0, 6.5 Hz, 1 H), 4.43–4.34 (m, 2 H), 4.26 (t, J = 7.0 Hz,
residue was purified by flash chromatography (CH2Cl2/acetone,
9:1) to give 2i (57 mg, 47%) as a mixture of two diastereoisomers,
1 H), 3.75 (s, 3 H), 1.36 (t, J = 6.5 Hz, 2 H), 1.27 (d, J = 4.0 Hz, as a yellowish oil. TLC (CH2Cl2/acetone, 9:1): Rf = 0.46 (CAM).
12 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 173.4, 155.8, 143.8,
141.28, 141.27, 127.6, 127.0, 125.2, 125.1, 119.9, 83.7, 67.0, 52.3,
50.6, 47.1, 24.8, 24.6 (carbon adjacent to boron was not observed)
ppm. 11B NMR (128 MHz, CDCl3, BF3·OEt2): δ = 33.0 ppm. IR
1H NMR (400 MHz, CDCl3): δ = 7.36–7.20 (m, 16 H), 7.17–7.07
(m, 4 H), 6.96–6.93 (m, 4 H), 5.32 (br. d, J = 8.5 Hz, 2 H), 5.14–
5.06 (m, 4 H), 4.78–4.74 (m, 2 H), 4.62–4.57 (m, 2 H), 4.04–4.00
(m, 2 H), 3.66 (s, 6 H), 3.10–3.02 (m, 2 H), 2.17–2.04 (m, 2 H),
1.29 (dd, J = 16.0, 8.0 Hz, 2 H), 1.25 (s, 24 H), 1.08 (dd, J = 16.0,
8.0 Hz, 2 H), 0.83 (d, J = 7.0 Hz, 6 H), 0.80 (d, J = 7.0 Hz, 6 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 171.5, 170.7, 156.3, 136.2,
135.9, 129.25, 129.22, 128.55, 128.52, 128.51, 128.2, 128.07, 128.04,
127.07, 127.01, 83.8, 83.7, 67.0, 60.1, 53.6, 53.5, 52.2, 52.1, 49.8,
37.9, 37.8, 31.3, 30.8, 25.0, 24.8, 24.6, 24.5, 19.0, 17.6 (carbon adja-
cent to boron was not observed) ppm. 11B NMR (132 MHz,
(film): ν = 3311, 1728, 1712 cm–1. MS (ESI): m/z = 452 [M + 1].
˜
C25H30BNO6 (451.22): calcd. C 66.53, H 6.70, N 3.10; found C
66.71, H 6.63, N 3.18.
(R)-Methyl
2-[(S)-2-(Benzyloxycarbonylamino)-3-methylbutan-
amido]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
and (S)-Methyl 2-[(S)-2-(Benzyloxycarbonylamino)-3-methylbutan-
amido]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoate
(2g): The general procedure for CuI-catalysed borylation was fol-
lowed using Z-l-Val-ΔAla-OMe (1g). The resulting residue was
purified by flash chromatography (CH2Cl2/acetone, 9:1) to give 2g
(55 mg, 59%) as a mixture of two diastereomers, as a yellowish oil.
TLC (CH2Cl2/acetone, 9:1): Rf = 0.5 (CAM). 1H NMR (200 MHz,
CDCl3): δ = 7.35 (s, 10 H), 6.78 (br. d, J = 8.0 Hz, 1 H), 6.68 (br.
d, J = 8.0 Hz, 1 H), 5.50 (br. d, J = 9.0 Hz, 1 H), 5.43 (br. d, J =
9.0 Hz, 1 H), 5.18–5.05 (m, 4 H), 4.81–4.71 (m, 2 H), 4.14–4.02 (m,
2 H), 3.70 (s, 6 H), 2.24–2.09 (m, 2 H), 1.36–1.22 (m, 4 H), 1.22 (s,
24 H), 1.01–0.90 (m, 12 H) ppm. 13C NMR (50 MHz, CDCl3): δ
= 172.9, 170.4, 156.2, 136.2, 128.5, 128.1, 128.0, 83.9, 83.8, 67.0,
60.1, 52.3, 48.8, 31.6, 31.3, 24.8, 24.6, 19.1, 18.8, 17.8, 17.6 (carbon
adjacent to boron was not observed) ppm. 11B NMR (64 MHz,
CDCl , BF ·OEt ): δ = 36.2 ppm. IR (film): ν = 3302, 1736, 1703,
˜
3
3
2
1648 cm–1. MS (ESI): m/z = 610 [M + 1]. C32H44BN3O8 (609.32):
calcd. C 63.06, H 7.28, N 6.89; found C 62.83, H 7.21, N 6.95.
General Procedure for the Synthesis of Potassium β-Trifluoroborate
Alanine Methyl Esters (3a–3e): A solution of KHF2 (4.5 m aq.;
62.5 mg, 0.8 mmol) was added to a solution of crude boronate de-
rivatives 2a–2e (0.2 mmol) in THF (2 mL). The mixture was stirred
at room temperature for 20 h. The solvents were evaporated under
reduced pressure, and the resulting residue was triturated with hot
acetone, and then crystallized from acetone/Et2O.
N-Acetyl Potassium β-Trifluoroborate Alanine Methyl Ester (3a):
Following the general procedure for the synthesis of potassium β-
trifluoroborate alanine methyl esters, compound 3a (28 mg, 56%
over two steps) was obtained as a white solid. 1H NMR (200 MHz,
[D6]acetone): δ = 6.86 (br. s, 1 H), 4.18 (ddd, J = 11.5, 8.5, 6.0 Hz,
1 H), 3.56 (s, 3 H), 1.83 (s, 3 H), 0.56 (br. s, 2 H) ppm. 13C NMR
(50 MHz, [D6]acetone): δ = 175.7, 168.7, 51.4, 50.5, 22.0 (carbon
adjacent to boron was not observed) ppm. 11B NMR (64 MHz,
CDCl , BF ·OEt ): δ = 33.4 ppm. IR (film): ν = 3316, 1736, 1708,
˜
3
3
2
1658 cm–1. MS (ESI): m/z = 463 [M + 1]. C23H35BN2O7 (462.25):
calcd. C 59.75, H 7.63, N 6.06; found C 59.48, H 7.69, N 6.02.
(S)-Methyl 2-[(R)-2-(tert-Butoxycarbonylamino)-3-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)propanamido]-3-phenylpropanoate
and (S)-Methyl 2-[(S)-2-(tert-Butoxycarbonylamino)-3-(4,4,5,5-tet-
ramethyl-1,3,2-dioxaborolan-2-yl)propanamido]-3-phenylpropanoate
(2h): The general procedure for CuI-catalysed borylation was fol-
lowed using N-Boc-ΔAla-l-Phe-OMe (1h). The resulting residue
was purified by flash chromatography (CH2Cl2/MeOH, 96:4) to
give 2h (51 mg, 54%) as a mixture of two diastereomers, as a yel-
lowish oil. TLC (CH2Cl2/MeOH, 96:4): Rf = 0.2 (CAM). 1H NMR
(400 MHz, CDCl3): δ = 7.29–7.20 (m, 6 H), 7.11–7.10 (m, 4 H),
7.03 (br. d, J = 7.0 Hz, 1 H), 6.95 (d, J = 7.0 Hz, 1 H), 5.38 (d, J
= 8.0 Hz, 1 H), 5.32 (d, J = 8.0 Hz, 1 H), 4.82–4.78 (m, 2 H), 4.37–
4.31 (m, 2 H), 3.67 (s, 3 H), 3.66 (s, 3 H), 3.13 (dd, J = 14.0, 6.0 Hz,
1 H), 3.11 (dd, J = 14.0, 6.0 Hz, 1 H), 3.07 (dd, J = 14.0, 6.0 Hz,
1 H), 3.04 (dd, J = 14.0, 6.0 Hz, 1 H), 1.42 (s, 9 H), 1.40 (s, 9 H),
1.25 (dd, J = 16.0, 5.0 Hz, 2 H), 1.21 (s, 12 H), 1.20 (s, 12 H), 1.11
(dd, J = 16.0, 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 172.4, 172.3, 171.6, 171.5, 155.8, 155.6, 135.9, 129.30, 129.28,
128.50, 128.47, 127.0, 83.7, 83.6, 79.9, 79.8, 53.44, 53.36, 52.13,
52.09, 50.9, 38.0, 37.8, 28.3, 24.9, 24.8, 24.6, 24.5 (carbon adjacent
to boron was not observed) ppm. 11B NMR (128 MHz, CDCl3,
[D ]acetone, BF ·OEt ): δ = 4.7 ppm. IR (film): ν = 3283, 1739,
˜
6
3
2
1645 cm–1. MS (ESI): m/z = 212 [M – K]. C6H10BF3KNO3
(251.03): calcd. C 28.70, H 4.01, N 5.58; found C 28.48, H 3.93, N
5.52.
N-Benzyloxycarbonyl Potassium β-Trifluoroborate Alanine Methyl
Ester (3b): Following the general procedure for the synthesis of
potassium β-trifluoroborate alanine methyl esters, compound 3b
(45 mg, 65% over two steps) was obtained as a white solid. 1H
NMR (200 MHz, CD3OD): δ = 7.24 (s, 6 H), 4.96 (s, 2 H), 4.02 (t,
J = 7.0 Hz, 1 H), 3.57 (s, 3 H), 0.65–0.53 (m, 2 H) ppm. 13C NMR
(50 MHz, CD3OD): δ = 176.5, 156.9, 136.8, 128.0, 127.5, 127.3,
66.0, 52.6, 50.9 (carbon adjacent to boron was not observed) ppm.
11B NMR (64 MHz, CD3OD, BF3·OEt2): δ = 4.2 ppm. IR (film):
ν = 3340, 1749, 1720 cm–1. MS (ESI): m/z = 304 [M – K].
˜
C12H14BF3KNO4 (343.06): calcd. C 42.00, H 4.11, N 4.08; found
C 42.18, H 4.16, N 4.15.
N-tert-Butoxycarbonyl Potassium β-Trifluoroborate Alanine Methyl
Ester (3c): Following the general procedure for the synthesis of
potassium β-trifluoroborate alanine methyl esters, compound 3c
(42 mg, 68% over two steps) was obtained as a white solid. 1H
NMR (200 MHz, [D6]acetone): δ = 5.66 (br. s, 1 H), 3.89 (dd, J =
13.0, 6.5 Hz, 1 H), 3.46 (s, 3 H), 1.25 (s, 9 H), 0.48–0.42 (m, 2 H)
ppm. 13C NMR (50 MHz, [D6]acetone): δ = 176.0, 155.4, 77.7,
52.4, 50.6, 27.7 (carbon adjacent to boron was not observed) ppm.
BF ·OEt ): δ = 32.9 ppm. IR (film): ν = 3334, 1740, 1716,
˜
3
2
1686 cm–1. MS (ESI): m/z = 477 [M + 1]. C24H37BN2O7 (476.27):
calcd. C 60.51, H 7.83, N 5.88; found C 60.73, H 7.90, N 5.93.
(5S,8R,11S)-Methyl 11-Benzyl-5-isopropyl-3,6,9-trioxo-1-phenyl-8-
[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-2-oxa-4,7,10-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O50362
/KAP1
Date: 15-04-15 11:32:13
Pages: 10
F. Bartoccini, S. Bartolucci, S. Lucarini, G. Piersanti
FULL PAPER
11B NMR (64 MHz, [D6]acetone, BF3·OEt2): δ = 4.0 ppm. IR
5.14 (d, J = 7.0 Hz, 1 H), 5.07 (s, 2 H), 4.49–4.37 (m, 1 H), 3.57
(film): ν = 3332, 1735, 1715 cm–1. MS (ESI): m/z = 270 [M – K]. (s, 3 H), 1.43 (dd, J = 15.0, 6.5 Hz, 1 H), 1.24 (dd, J = 15.0, 9.0 Hz,
˜
C9H16BF3KNO4 (309.08): calcd. C 34.97, H 5.22, N 4.53; found C 1 H), 0.37 (s, 3 H), 0.36 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
35.16, H 5.31, N 4.45.
δ = 173.8, 155.4, 137.8, 136.3, 133.5, 129.2, 128.5, 128.1, 128.0,
127.9, 66.8, 52.1, 51.1, 20.6, –2.8, –2.9 ppm. IR (film): ν = 3346,
˜
N-[(9H-Fluoren-9-yl)methoxy]carbonylamino Potassium β-Trifluoro-
borate Alanine Methyl Ester (3d): Following the general procedure
for the synthesis of potassium β-trifluoroborate alanine methyl es-
ters, compound 3d (65 mg, 76% over two steps) was obtained as a
white solid. 1H NMR (400 MHz, [D6]DMSO): δ = 7.89 (d, J =
7.5 Hz, 2 H), 7.69 (d, J = 7.5 Hz, 2 H), 7.42 (t, J = 7.5 Hz, 2 H),
7.34 (t, J = 7.5 Hz, 2 H), 6.44 (br. d, J = 2.5 Hz, 1 H), 4.22 (s, 3
H), 3.91–3.86 (m, 1 H), 3.54 (s, 3 H), 0.51–0.39 (m, 2 H) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 175.7, 156.0, 144.4, 144.3,
141.1, 129.4, 128.1, 127.7, 127.5, 125.7, 121.8, 120.5, 66.1, 53.1,
51.5, 47.1 (carbon adjacent to boron was not observed) ppm. 11B
NMR (128 MHz, [D6]DMSO, BF3·OEt2): δ = 4.4 ppm. IR (film):
1748, 1724 cm–1. MS (ESI): m/z = 372 [M + 1], 294 [M – 77].
C20H25NO4Si (371.16): calcd. C 64.66, H 6.78, N 3.77; found C
64.89, H 6.71, N 3.83.
Methyl 2-(tert-Butoxycarbonylamino)-3-[dimethyl(phenyl)silyl]-
propanoate (4c):[6d] The residue obtained from the general pro-
cedure for CuI-catalysed silylation was purified by flash chromatog-
raphy (gradient, cyclohexane/CH2Cl2, 1:9 to CH2Cl2) to give 4c
(50 mg, 74 %) as a colourless oil. TLC (CH2Cl2): Rf = 0.5
1
(KMnO4). H NMR (200 MHz, CDCl3): δ = 7.54–7.49 (m, 2 H),
7.40–7.28 (m, 3 H), 4.86 (br. d, J = 8.0 Hz, 1 H), 4.41–4.29 (m, 1
H), 3.57 (s, 3 H), 1.43 (s, 9 H), 1.38 (dd, J = 15.0, 6.5 Hz, 1 H),
1.19 (dd, J = 15.0, 9.0 Hz, 1 H), 0.37 (s, 3 H), 0.36 (s, 3 H) ppm.
13C NMR (50 MHz, CDCl3): δ = 174.3, 154.9, 138.1, 133.5, 129.2,
ν = 3305, 1740, 1722 cm–1. MS (ESI): m/z = 392 [M – K].
˜
C19H18BF3KNO4 (431.09): calcd. C 52.92, H 4.21, N 3.25; found
C 52.81, H 4.16, N 3.32.
127.9, 79.73, 52.0, 50.5, 28.3, 20.6, –2.7, –2.9 ppm. IR (film): ν =
˜
3358, 1740, 1720 cm–1. MS (ESI): m/z = 338 [M + 1], 204 [M –
134]. C17H27NO4Si (337.17): calcd. C 60.50, H 8.06, N 4.15; found
C 60.26, H 8.12, N 4.11.
N-Phthalimido Potassium β-Trifluoroborate Alanine Methyl Ester
(3e): Following the general procedure for the synthesis of potas-
sium β-trifluoroborate alanine methyl esters, compound 3e (51 mg,
75 % over two steps) was obtained as a white solid. 1H NMR
(200 MHz, [D6]DMSO): δ = 7.82 (s, 1 H), 4.77 (dd, J = 13.0,
3.5 Hz, 1 H), 3.59 (s, 3 H), 1.20–1.01 (m, 1 H), 0.77–0.65 (m, 1 H)
ppm. 13C NMR (50 MHz, [D6]DMSO): δ = 173.2, 167.6, 134.6,
132.3, 123.2, 52.4, 51.2 (carbon adjacent to boron was not ob-
served) ppm. 11B NMR (64 MHz, [D6]DMSO, BF3·OEt2): δ =
Methyl 2-{[(9H-Fluoren-9-yl)methoxy]carbonylamino}-3-[dimeth-
yl(phenyl)silyl]propanoate (4d): The residue obtained from the gene-
ral procedure for CuI-catalysed silylation was purified by flash
chromatography (cyclohexane/EtOAc, 8:2) to give 4d (76 mg, 83%)
as a colourless oil. TLC (cyclohexane/EtOAc, 8:2): Rf = 0.5
1
(CAM). H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.5 Hz, 2
4.8 ppm. IR (film): ν = 1742, 1722 cm–1. MS (ESI): m/z = 300 [M –
˜
H), 7.42 (t, J = 8.0 Hz, 2 H), 7.37–7.36 (m, 2 H), 7.30–7.16 (m, 7
H), 5.00 (br. d, J = 8.5 Hz, 1 H), 4.32–4.25 (m, 1 H), 4.22–4.19 (m,
2 H), 4.04 (t, J = 7.0 Hz, 1 H), 3.45 (s, 1 H), 1.31–1.26 (m, 1 H),
1.13 (dd, J = 15.0, 9.0 Hz, 1 H), 0.22 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 174.0, 155.5, 143.9, 143.8, 141.3, 137.8,
133.5, 129.3, 128.0, 127.7, 127.0, 125.1, 120.0, 66.9, 52.2, 51.1, 47.1,
K]. C12H10BF3KNO4 (339.03): calcd. C 42.50, H 2.97, N 4.13;
found C 42.28, H 2.89, N 4.06.
General Procedure for the Copper(I)-Catalysed Silylation of De-
hydroalanine (1a–1f) and Dehydropeptides (1g–1i): A mixture of
CuCl (1 mg, 0.01 mmol), KOtBu (3.5 mg, 0.03 mmol), and dppbz
(5 mg, 0.01 mmol) in anhydrous THF (0.18 mL) was stirred for
30 min in a sealed tube. Me2PhSi-Bpin (71 μL, 0.26 mmol) was
added. The reaction mixture was stirred for 10 min, and then the
appropriate dehydroalanine (1a–1f) or dehydropeptide (1g–1i)
(0.2 mmol) in THF (0.18 mL) was added to the reaction mixture,
followed by MeOH (16 μL, 0.4 mmol). The reaction mixture was
then stirred at 50 °C for 20 h. The solvent was evaporated under
reduced pressure, and the residue was purified by flash chromatog-
raphy.
20.4, –2.80, –2.83 ppm. IR (film): ν = 3323, 1725, 1712 cm–1. MS
˜
(ESI): m/z = 460 [M + 1], 382 [M – 77]. C27H29NO4Si (459.19):
calcd. C 70.56, H 6.36, N 3.05; found C 70.68, H 6.27, N 2.96.
Methyl 3-[Dimethyl(phenyl)silyl]-2-(1,3-dioxoisoindolin-2-yl)-
propanoate (4e): The residue obtained from the general procedure
for CuI-catalysed silylation was purified by flash chromatography
(gradient, cyclohexane/CH2Cl2, 1:1 to 2:8) to give 4e (54 mg, 73%)
as a colourless oil. TLC (CH2Cl2): Rf = 0.5 (KMnO4). 1H NMR
(200 MHz, CDCl3): δ = 7.62 (s, 4 H), 7.33–7.28 (m, 2 H), 7.02–
6.89 (m, 3 H), 4.95 (dd, J = 12.5, 3.5 Hz, 1 H), 3.69 (s, 3 H), 2.08
(dd, J = 15.0, 12.5 Hz, 1 H), 1.69 (dd, J = 15.0, 3.5 Hz, 1 H), 0.39
(s, 3 H), 0.26 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 171.0,
167.3, 137.0, 133.6, 133.23, 131.6, 128.5, 127.5, 123.1, 52.8, 48.7,
Methyl 2-Acetamido-3-[dimethyl(phenyl)silyl]propanoate (4a): The
residue obtained from the general procedure for CuI-catalysed sil-
ylation was purified by flash chromatography (CH2Cl2/acetone,
9:1) to give 4a (29 mg, 52%) as a colourless oil. TLC (CH2Cl2/
16.3, –2.3, –4.4 ppm. IR (film): ν = 1744, 1716 cm–1. MS (ESI): m/z
1
˜
acetone, 9:1): Rf = 0.3 (KMnO4). H NMR (200 MHz, CDCl3): δ
= 368 [M + 1], 290 [M – 77]. C20H21NO4Si (367.12): calcd. C 65.37,
H 5.76, N 3.81; found C 65.14, H 5.69, N 3.87.
= 7.53–7.46 (m, 2 H), 7.41–7.35 (m, 3 H), 5.64 (br. d, J = 7.5 Hz,
1 H), 4.61 (ddd, J = 15.0, J = 9.0, 6.0 Hz, 1 H), 3.58 (s, 3 H), 1.73
(s, 3 H), 1.41 (dd, J = 15.0, 6.0 Hz, 1 H), 1.23 (dd, J = 15.0, 9.0 Hz,
1 H), 0.36 (s, 3 H), 0.34 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 174.0, 169.4, 138.1, 133.5, 129.3, 128.0, 52.1, 49.2, 22.8, 20.2,
Methyl 3-[Dimethyl(phenyl)silyl]-2-(diphenylmethyleneamino)-
propanoate (4f): The residue obtained from the general procedure
for CuI-catalysed silylation was purified by flash chromatography
(cyclohexane/EtOAc, 95:5) to give 4f (56 mg, 70%) as a colourless
–2.8, –3.2 ppm. IR (film): ν = 3285, 1744, 1650 cm–1. MS (ESI):
˜
m/z = 280 [M + 1], 202 [M – 77]. C14H21NO3Si (279.13): calcd. C
60.18, H 7.58, N 5.01; found C 60.39, H 7.63, N 5.06.
1
oil. TLC (cyclohexane/EtOAc, 9:1): Rf = 0.5 (KMnO4). H NMR
(200 MHz, CDCl3): δ = 7.64–7.60 (m, 2 H), 7.47–7.30 (m, 11 H),
Methyl 2-(Benzyloxycarbonylamino)-3-[dimethyl(phenyl)silyl]- 7.09–7.05 (m, 2 H), 4.27 (dd, J = J = 7.0 Hz, 1 H), 3.63 (s, 3 H),
propanoate (4b): The residue obtained from the general procedure
for CuI-catalysed silylation was purified by flash chromatography
(gradient, cyclohexane/CH2Cl2, 1:1 to 2:8) to give 4b (50 mg, 67%)
as a colourless oil. TLC (CH2Cl2): Rf = 0.52 (CAM). 1H NMR
1.65 (dd, J = 14.5, 7.0 Hz, 1 H), 1.45 (dd, J = 14.5, 7.0 Hz, 1 H),
0.28 (s, 3 H), 0.27 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ =
173.8, 169.3, 139.3, 138.8, 136.2, 133.6, 130.3, 130.1, 128.9, 128.6,
128.5, 128.0, 127.7, 127.6, 62.4, 52.0, 21.6, –2.1, –2.3 ppm. IR
(200 MHz, CDCl3): δ = 7.51–7.42 (m, 2 H), 7.38–7.27 (m, 8 H), (film): ν = 1739, 1661 cm–1. MS (ESI): m/z = 402 [M + 1], 324 [M –
˜
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50362
/KAP1
Date: 15-04-15 11:32:13
Pages: 10
Copper-Catalysed Conjugate Additions
77]. C25H27NO2Si (401.18): calcd. C 74.77, H 6.78, N 3.49; found
C 74.98, H 6.69, N 3.42.
NMR (400 MHz, CDCl3): δ = 7.48–7.46 (m, 2 H), 7.36–7.33 (m, 3
H), 7.25–7.18 (m, 3 H), 7.08–7.06 (m, 2 H), 6.62 (br. d, J = 3.5 Hz,
1 H), 4.78 (dd, J = 7.0, 3.0 Hz, 1 H), 4.58 (br. d, J = 3.5 Hz, 1 H),
4.13 (br. s, 1 H), 3.68 (s, 3 H), 3.10–3.00 (m, 2 H), 1.38 (s, 9 H),
1.37 (dd, J = 7.5, 2.5 Hz, 1 H), 1.06 (dd, J = 7.5, 5.0 Hz, 1 H), 0.31
(s, 3 H), 0.29 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
172.9, 171.8, 155.2, 138.2, 135.8, 133.5, 129.2, 128.6, 128.0, 127.1,
80.0, 53.1 52.2, 51.6, 37.9, 28.2, 19.6, –2.6, –3.3 ppm. IR (film):
(S)-Methyl 2-[(S)-2-(Benzyloxycarbonylamino)-3-methylbutan-
amido]-3-[dimethyl(phenyl)silyl]propanoate and (R)-Methyl 2-[(S)-2-
(Benzyloxycarbonylamino)-3-methylbutanamido]-3-[dimethyl(phen-
yl)silyl]propanoate (4g): The residue obtained from the general pro-
cedure for CuI-catalysed silylation using Z-l-Val-ΔAla-OMe (1 g)
was purified by flash chromatography (Et2O/petroleum ether, 1:1)
to give the less polar diastereoisomer of 4g (26 mg) as a white solid,
and the more polar distereoisomer of 4g (22 mg) as a white solid.
Total yield: 51%.
ν = 3382, 1750, 1706, 1642 cm–1. MS (ESI): m/z = 485 [M + 1].
˜
C26H36N2O5Si (484.24): calcd. C 64.43, H 7.49, N 5.78; found C
64.67, H 7.56, N 5.85.
General Procedure for the Hydrolysis of Esters 2d and 4d: Carb-
oxylic ester 2d or 4d (0.15 mmol) was dissolved in 1,2-dichloroe-
thane (0.7 mL), and trimethyltin hydroxide (54 mg, 0.3 mmol) was
added. The mixture was heated at 80 °C for 6 h. When the reaction
was complete, the mixture was concentrated in vacuo, and the resi-
due was dissolved in ethyl acetate (1 mL). The organic layer was
washed with KHSO4 (0.01 n aq.; 3ϫ 10 mL) and brine (10 mL),
and dried with Na2SO4. Removal of the solvent in vacuo gave the
carboxylic acid in sufficiently pure form, often with Ͼ98% purity
Data for 4g (less polar diastereoisomer): TLC (Et2O/petroleum
ether, 1:1): Rf = 0.39 (CAM), m.p. 122 °C. [α]2D5 = +14.6 (c = 0.48,
CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 7.52–7.47 (m, 2 H),
7.38–7.37 (m, 8 H), 5.97 (br. d, J = 7.0 Hz, 1 H), 5.24 (br. d, J =
9.0 Hz, 1 H), 5.12 (s, 2 H), 4.57 (dd, J = 15.0, 7.0 Hz, 1 H), 3.84–
3.77 (m, 1 H), 3.55 (s, 3 H), 2.04–1.88 (m, 1 H), 1.37–1.17 (m, 2
H), 0.89 (d, J = 6.5 Hz, 3 H), 0.83 (d, J = 6.5 Hz, 3 H), 0.34 (s, 3
H), 0.33 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 173.3,
170.6, 156.2, 137.8, 136.3, 133.5, 129.5, 128.5, 128.2, 128.13,
128.06, 67.0, 59.8, 52.1, 49.5, 31.3, 19.9, 18.9, 17.6, –3.0, –3.1 ppm.
1
(by H NMR spectroscopy).
IR (film): ν = 3269, 1747, 1715, 1662 cm–1. MS (ESI): m/z = 471
2-{[(9H-Fluoren-9-yl)methoxy]carbonylamino}-3-(4,4,5,5-tetrameth-
yl-1,3,2-dioxaborolan-2-yl)propanoic Acid (2l): Following the gene-
ral procedure for the hydrolysis of esters, compound 2l (54 mg,
˜
[M + 1], 393 [M – 77]. C25H34N2O5Si (470.22): calcd. C 63.80, H
7.28, N 5.95; found C 63.62, H 7.19, N 6.02.
1
83%) was obtained as a white solid. H NMR (400 MHz, CDCl3):
Data for 4g (more polar distereoisomer): TLC (Et2O/petroleum
ether, 1:1): Rf = 0.37 (CAM), m.p. 121 °C. [α]2D5 = –13.6 (c = 0.51,
CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 7.52–7.48 (m, 2 H),
7.40–7.33 (m, 8 H), 6.32 (br. d, J = 7.5 Hz, 1 H), 5.25 (br. d, J =
8.5 Hz, 1 H), 5.12 (s, 2 H), 4.54 (dd, J = 15.0, 7.5 Hz, 1 H), 4.01–
3.94 (m, 1 H), 3.51 (s, 3 H), 2.09–1.96 (m, 1 H), 1.36–1.27 (m, 2
H), 0.92 (d, J = 7.0 Hz, 3 H), 0.84 (d, J = 7.0 Hz, 3 H), 0.35 (s, 3
H), 0.33 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 173.3,
170.9, 156.4, 137.7, 136.1, 133.5, 129.4, 128.5, 128.2, 128.12,
128.07, 67.2, 60.0, 52.1, 49.6, 30.6, 19.9, 19.4, 17.1, –2.6, –3.0 ppm.
δ = 7.77 (d, J = 7.5 Hz, 2 H), 7.61 (t, J = 7.5 Hz, 2 H), 7.41 (t, J
= 7.5 Hz, 2 H), 7.31 (t, J = 7.5 Hz, 2 H), 5.71 (br. d, J = 8.0 Hz,
1 H), 4.59 (dd, J = 14.0, 6.5 Hz, 1 H), 4.44–4.35 (m, 2 H), 4.25 (t,
J = 7.0 Hz, 1 H), 1.40 (d, J = 6.5 Hz, 2 H), 1.26 (d, J = 4.0 Hz, 12
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 177.4, 156.1, 143.9,
143.7, 141.3, 127.7, 127.0, 125.2, 125.1, 120.0, 84.0, 67.2, 50.6, 47.1,
24.8, 24.6 (carbon adjacent to boron was not observed) ppm. 11B
NMR (128 MHz, CDCl , BF ·OEt ): δ = 7.16 ppm. IR (film): ν =
˜
3
3
2
3415, 3321, 1729, 1721 cm–1. MS (ESI): m/z = 438 [M + 1], 436
[M – 1].
IR (film): ν = 3270, 1749, 1714, 1662 cm–1. MS (ESI): m/z = 471
˜
2-{[(9H-Fluoren-9-yl)methoxy]carbonylamino}-3-[dimethyl(phenyl)-
silyl]propanoic Acid (4l): Following the general procedure for the
hydrolysis of esters, compound 4l (53 mg, 79%) was obtained as a
white solid. 1H NMR (400 MHz, CDCl3): δ = 8.73 (br. s, 1 H),
7.76 (d, J = 7.5 Hz, 2 H) 7.55–7.29 (m, 11 H), 5.09 (br. s, 1 H),
4.36–4.29 (m, 2 H), 4.15–4.12 (m, 1 H), 1.46–1.43 (m, 1 H), 1.28–
1.25 (m, 1 H), 0.35 (s, 3 H), 0.33 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 178.9, 155.8, 143.8, 143.7, 141.3, 137.8,
133.5, 129.3, 128.0, 127.7, 127.0, 125.1, 120.0, 67.0, 51.2, 47.1, 20.0,
[M + 1], 393 [M – 77]. C25H34N2O5Si (470.22): calcd. C 63.80, H
7.28, N 5.95; found C 63.59, H 7.36, N 5.87.
(S)-Methyl 2-{(S)-2-(tert-Butoxycarbonylamino)-3-[dimethyl(phenyl)-
silyl]propanamido}-3-phenylpropanoate and (S)-Methyl 2-{(R)-2-
(tert-Butoxycarbonylamino)-3-[dimethyl(phenyl)silyl]propanamido}-
3-phenylpropanoate (4h): The residue obtained from the general
procedure for CuI-catalysed silylation using N-Boc-ΔAla-l-Phe-
OMe (1h) was purified by flash chromatography (gradient, Et2O/
petroleum ether, 4:6 to 1:1) to give the less polar diastereoisomer
of 4h (18 mg) as a yellowish oil, and the more polar diastereoisomer
of 4h (14 mg) as a yellowish oil. Total yield: 33%.
–2.7, –3.1 ppm. IR (film): ν = 3411, 3313, 1723 cm–1. MS (ESI):
˜
m/z = 444 [M – 1].
β-Boronoaspartic Acid (5):[5f] The crude 2c obtained from methyl 2-
(tert-butoxycarbonylamino)acrylate (1c; 0.2 mmol) by following the
general procedure for copper(I)-catalysed borylation was heated at
70 °C for 16 h in the presence of HCl (6 n aq.; 4 mL). The organic
by-products were removed by washing the aqueous layer repeatedly
with CH2Cl2 (3ϫ 20 mL). The aqueous layer was concentrated in
vacuo at 40 °C to give a brownish powder. Trituration with acetone
Data for 4h (less polar diastereoisomer): TLC (Et2O/petroleum
1
ether, 1:1): Rf = 0.27 (CAM). [α]2D5 = +31.1 (c = 0.77, CH2Cl2). H
NMR (400 MHz, CDCl3): δ = 7.50–7.48 (m, 2 H), 7.37–7.35 (m, 3
H), 7.25–7.23 (m, 3 H), 7.09–7.07 (m, 2 H), 6.49 (br. d, J = 3.5 Hz,
1 H), 4.75–4.70 (m, 1 H), 4.65 (br. d, J = 3.5 Hz, 1 H), 4.14–4.10
(m, 1 H), 3.70 (s, 3 H), 3.12 (dd, J = 7.0, 3.0 Hz, 1 H), 3.03 (dd, J
= 7.0, 3.0 Hz, 1 H), 1.40 (s, 9 H), 1.40–1.35 (m, 1 H), 1.14–1.08
(m, 1 H), 0.33 (s, 3 H), 0.32 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 172.6, 171.6, 155.1, 138.1, 135.8, 133.5, 129.3, 129.2,
128.5, 128.0, 127.0, 80.0, 53.2, 52.2, 51.8, 37.9, 28.2, 19.6, –2.6,
1
and CH2Cl2 gave pure β-boronoaspartic acid (5; 24 mg, 70%). H
NMR (200 MHz, D2O): δ = 4.10 (dd, J = 10.0, 8.0 Hz, 1 H), 1.30
(dd, J = 14.0, 8.0 Hz, 1 H), 1.05 (dd, J = 14.0, 10.0 Hz, 1 H) ppm.
2-Amino-3-(hydroxydimethylsilyl)propanoic Acid Hydrochloride
(6):[5e] The crude 4c obtained from methyl 2-(tert-butoxycarbonyl-
amino)acrylate (1c; 0.2 mmol) by following the general procedure
for copper(I)-catalysed silylation was heated at 70 °C for 16 h in
the presence of HCl (6 n aq.; 4 mL). The organic by-products were
removed by washing the aqueous layer repeatedly with CH2Cl2 (3ϫ
–3.1 ppm. IR (film): ν = 3309, 1746, 1724, 1663 cm–1. MS (ESI):
˜
m/z = 485 [M + 1]. C26H36N2O5Si (484.24): calcd. C 64.43, H 7.49,
N 5.78; found C 64.65, H 7.41, N 5.86.
Data for 4h (more polar diastereoisomer): TLC (Et2O/petroleum
1
ether, 1:1): Rf = 0.25 (CAM). [α]2D5 = +35.9 (c = 0.32, CH2Cl2). H
Eur. J. Org. Chem. 0000, 0–0
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Date: 15-04-15 11:32:13
Pages: 10
F. Bartoccini, S. Bartolucci, S. Lucarini, G. Piersanti
FULL PAPER
[7]
a) E. Angelini, C. Balsamini, F. Bartoccini, S. Lucarini, G. Pier-
santi, J. Org. Chem. 2008, 73, 5654–5657; b) S. Lucarini, F.
Bartoccini, F. Battistoni, G. Diamantini, G. Piersanti, M.
Righi, G. Spadoni, Org. Lett. 2010, 12, 3844–3847; c) M. Righi,
F. Bartoccini, S. Lucarini, G. Piersanti, Tetrahedron 2011, 67,
7923–7928; d) S. Bartolucci, F. Bartoccini, M. Righi, G. Pier-
santi, Org. Lett. 2012, 14, 600–603; e) S. Lucarini, M. Mari, G.
Piersanti, G. Spadoni, RSC Adv. 2013, 3, 19135–19143; f) M.
Mari, F. Bartoccini, G. Piersanti, J. Org. Chem. 2013, 78, 7727–
7734; g) F. Bartoccini, M. Casoli, M. Mari, G. Piersanti, J.
Org. Chem. 2014, 79, 3255–3259; h) M. Mari, S. Lucarini, F.
Bartoccini, G. Piersanti, G. Spadoni, Beilstein J. Org. Chem.
2014, 10, 1991–1998.
20 mL). The aqueous layer was concentrated in vacuo at 40 °C to
give pure 2-amino-3-(hydroxydimethylsilyl)propanoic acid hydro-
chloride (6; 32 mg, 81%) as a yellowish powder. 1H NMR
(400 MHz, D2O): δ = 4.10 (dd, J = 10.0, 6.0 Hz, 1 H), 1.28 (dd, J
= 14.5, 10.0 Hz, 1 H), 1.19 (dd, J = 14.5, 6.0 Hz, 1 H) ppm.
Acknowledgments
The authors thank Prof. Gilberto Spadoni for useful discussions.
[1] a) W. Bains, R. Tacke, Curr. Opin. Drug Discovery Dev. 2003,
6, 526–543; b) F. Issa, M. Kassiou, L. M. Rendina, Chem. Rev.
2011, 111, 5701–5722; c) J. Liu, J. J. Lavigne, Boronic Acids:
Preparation and Applications in Organic Synthesis Medicine
and Materials, vol. 1 and 2, 2nd ed. (Ed.: D. G. Hall), Wiley-
VCH, Weinheim, Germany, 2011; d) A. K. Franz, S. O. Wilson,
J. Med. Chem. 2013, 56, 388–405; e) A. R. Martin, J. J. Vasseur,
M. Smietana, Chem. Soc. Rev. 2013, 42, 5684–5713; f) C.
Cheng, J. F. Hartwig, Science 2014, 343, 853–857; g) A. A. Tou-
tov, W.-B. Liu, K. N. Betz, A. Fedorov, B. M. Stoltz, R. H.
Grubbs, Nature 2015, 518, 80–84.
[2] a) W. Yang, X. Gao, B. Wang, Med. Res. Rev. 2003, 23, 346–
368; b) S. J. Baker, J. W. Tomsho, S. J. Benkovic, Chem. Soc.
Rev. 2011, 40, 4279–4285; c) B. C. Das, P. Thapa, R. Karki, C.
Schinke, S. Das, S. Kambhampati, S. K. Banerjee, P. V. Veldhu-
izen, A. Verma, L. M. Weiss, T. Evans, Future Med. Chem.
2013, 5, 653–676.
[8]
[9]
Z.-T. He, Y.-S. Zhao, P. Tian, C.-C. Wang, H.-Q. Dong, G.-Q.
Lin, Org. Lett. 2014, 16, 1426–1429.
a) S. Mun, J.-E. Lee, J. Yun, Org. Lett. 2006, 8, 4887–4889; b)
G. A. Molander, D. E. Petrillo, Org. Lett. 2008, 10, 1795–1798;
c) M. Gao, S. B. Thorpe, W. L. Santos, Org. Lett. 2009, 11,
3478–3481; d) H. Chea, H.-S. Sim, J. Yun, Adv. Synth. Catal.
2009, 351, 855–858; e) H. Chea, H.-S. Sim, J. Yun, Bull. Korean
Chem. Soc. 2010, 31, 551–552; f) K. Knott, J. Fishovitz, S. B.
Thorpe, I. Lee, W. L. Santos, Org. Biomol. Chem. 2010, 8,
3451–3456; g) S. B. Thorpe, X. Guo, W. L. Santos, Chem. Com-
mun. 2011, 47, 424–426; h) M. Gao, S. B. Thorpe, C. Kleeberg,
C. Slebodnick, T. B. Marder, W. L. Santos, J. Org. Chem. 2011,
76, 3997–4007; i) J. C. H. Lee, R. McDonald, D. G. Hall, Nat.
Chem. 2011, 3, 894–899; j) S. B. Thorpe, J. A. Calderone, W. L.
Santos, Org. Lett. 2012, 14, 1918–1921; k) C. Pubill-Ulldemol-
ins, A. Bonet, C. Bo, H. Gulyas, E. Fernandez, Chem. Eur. J.
2012, 18, 1121–1126; l) A. Welle, V. Cirriez, O. Riant, Tetrahe-
dron 2012, 68, 3435–3443; for leading reviews, see: m) E. Hart-
mann, D. J. Vyas, M. Oestreich, Chem. Commun. 2011, 47,
7917–7932; n) A. D. J. Calow, A. Whiting, Org. Biomol. Chem.
2012, 10, 5485–5497; o) Synthesis and Application of Or-
ganoboron Compounds: S. Lee, J. Yun, Top. Organomet. Chem.
2015, 49, 73–92.
In contrast, boronate esters are usually purified by distillation
at high temperatures. However, one valuable aspect of this cata-
lytic process is the ability to use the boronate esters in situ,
because the reaction gives only volatile/inert side-products.
a) M. Suginome, Y. Ito, Chem. Rev. 2000, 100, 3221–3256; b)
H. E. Burks, J. P. Morken, Chem. Commun. 2007, 4717–4725;
c) T. Ohmura, M. Suginome, Bull. Chem. Soc. Jpn. 2009, 82,
29–49; d) E. Hartmann, D. J. Vyas, M. Oestreich, Chem. Com-
mun. 2011, 47, 7917–7932; e) M. Oestreich, E. Hartmann, M.
Mewald, Chem. Rev. 2013, 113, 402–441.
For selected examples, see: a) A. Welle, J. Petrignet, B. Tinant,
J. Wouters, O. Riant, Chem. Eur. J. 2010, 16, 10980–10983; b)
K.-S. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132, 2898–
2900; c) D. J. Vyas, R. Fröhlich, M. Oestreich, Org. Lett. 2011,
13, 2094–2097; d) D. J. Vyas, C. K. Hazra, M. Oestreich, Org.
Lett. 2011, 13, 4462–4465; e) J. A. Calderone, W. L. Santos,
Org. Lett. 2012, 14, 2090–2093; f) C. K. Hazra, M. Oestreich,
Org. Lett. 2012, 14, 4010–4013; g) K.-S. Lee, H. Wu, F.
Haeffner, A. H. Hoveyda, Organometallics 2012, 31, 7823–
7826; h) V. Cirriez, C. Rasson, T. Hermant, J. Petrignet, J. D.
Álvarez, K. Robeyns, O. Riant, Angew. Chem. Int. Ed. 2013,
52, 1785–1788; Angew. Chem. 2013, 125, 1829–1832; i) L. B.
Delvos, D. J. Vyas, M. Oestreich, Angew. Chem. Int. Ed. 2013,
52, 4650–4653; Angew. Chem. 2013, 125, 4748–4751; j) A. Hen-
sel, K. Nagura, L. B. Delvos, M. Oestreich, Angew. Chem. Int.
Ed. 2014, 53, 4964–4967; Angew. Chem. 2014, 126, 5064–5067;
k) C. K. Hazra, C. Fopp, M. Oestreich, Chem. Asian J. 2014,
9, 3005–3010; l) L. B. Delvos, A. Hensel, M. Oestreich, Synthe-
sis 2014, 46, 2957–2964; m) V. Pace, J. P. Rae, D. J. Procter,
Org. Lett. 2014, 16, 476–479; n) J. A. Calderone, W. L. Santos,
Angew. Chem. Int. Ed. 2014, 53, 4154–4158; Angew. Chem.
2014, 126, 4238–4244; o) R. T. H. Linstadt, C. A. Peterson,
D. J. Lippincott, C. I. Jette, B. H. Lipshutz, Angew. Chem. Int.
Ed. 2014, 53, 4159–4163; Angew. Chem. 2014, 126, 4243–4247.
[3] For leading references, see: H. Einsele, Rec. Results Cancer Res.
2010, 184, 173–187.
[4] a) M. F. Hawthorne, A. Maderna, Chem. Rev. 1999, 99, 3421–
3434; b) R. F. Barth, J. F. Coderre, M. G. H. Vicente, T. E.
Blue, Clin. Cancer Res. 2005, 11, 3987–4002; c) G. W. Kabalka,
M.-L. Yao, Anti-Cancer Agents Med. Chem. 2006, 6, 111–125;
d) G. W. Kabalka, M.-L. Yao, S. R. Marepally, S. Chandra,
Appl. Radiat. Isot. 2009, 67, 374–379; e) G. W. Kabalka, A. L.
Shaikh, R. F. Barth, T. Huo, W. Yang, P. M. Gordnier, S.
Chandra, Appl. Radiat. Isot. 2011, 69, 1778–1781; f) L. Kan-
kaanranta, T. Seppälä, H. Koivunoro, K. Saarilahti, T. Atula,
J. Collan, E. Salli, M. Kortesniemi, J. Uusi-Simola, P.
Välimäki, A. Mäkitie, M. Seppänen, H. Minn, H. Revitzer, M.
Kouri, P. Kotiluoto, T. Seren, I. Auterinen, S. Savolainen, H.
Joensuu, Int. J. Radiat. Oncol. Biol. Phys. 2012, 82, e67–75.
[5] a) D. H. Kinder, M. M. Ames, J. Org. Chem. 1987, 52, 2452–
2454; b) G. K. Hsiao, D. G. Hangauer, Synthesis 1998, 1043–
1046; c) R. Tacke, M. Merget, R. Bertermann, M. Bernd, T.
Beckers, T. Reissmann, Organometallics 2000, 19, 3486–3497;
d) M. Merget, K. Gunther, M. Bernd, E. Gunther, R. Tacke,
J. Organomet. Chem. 2001, 628, 183–194; e) R. Tacke, T.
Schmid, M. Merget, Organometallics 2005, 24, 1780–1783: f)
V. J. Reddy, J. S. Chandra, M. V. R. Reddy, Org. Biomol. Chem.
2007, 5, 889–891; g) F. Cavelier, D. Marchand, J. Martinez,
Chem. Biodiversity 2008, 5, 1279–1287; h) J. T. Lee, D. Y. Chen,
Z. Yang, A. D. Ramos, J. J.-D. Hsieh, M. Bogyo, Bioorg. Med.
Chem. Lett. 2009, 19, 5086–5090; i) A. Rene, N. Vanthuyne, J.
Martinez, F. Cavelier, Amino Acids 2013, 45, 301–307.
[6] a) M. N. Kenworthy, J. P. Kilburn, R. J. K. Taylor, Org. Lett.
2004, 6, 19–22; b) C. W. Barfoot, J. E. Harvey, M. N. Kenwor-
thy, J. P. Kilburn, M. Ahmed, R. J. K. Taylor, Tetrahedron
2005, 61, 3403–3417; For other methods: c) R. D. Walkup,
D. C. Cole, B. R. Whittlesey, J. Org. Chem. 1995, 60, 2630–
2634; d) M. P. Sibi, B. J. Harris, J. J. Shay, S. Hajra, Tetrahedron
1998, 54, 7221–7228; e) B. M. Trost, C. Lee, J. Am. Chem. Soc.
2001, 123, 12191–12201; f) H. Audi, E. Rémond, M.-J. Eymin,
A. Tessier, R. Malacea-Kabbara, S. Jugé, Eur. J. Org. Chem.
2013, 7960–7972; g) attempts to synthesize alanine–organobor-
ane derivatives have been made previously, but hydroboration
with 9-BBN-H of the dehydro amino acid derivatives failed,
see: P. N. Collier, Ph. D. Thesis, University of York, 2001.
[10]
[11]
[12]
8
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Copper-Catalysed Conjugate Additions
[13] a) M. Jewgin´ski, J. Krzciuk-Gula, M. Makowski, R. Latajka,
P. Kafarski, Beilstein J. Org. Chem. 2014, 10, 660–666; b) C. D.
Spicer, B. G. Davis, Nat. Commun. 2014, 5, 4740.
[14] Tandem addition/enantioselective protonation of dehydroalan-
ines are rare. For examples, see: a) L. Navarre, S. Darses, J.-P.
Genet, Angew. Chem. Int. Ed. 2004, 43, 719–723; Angew. Chem.
2004, 116, 737–741; b) T. Jousseaume, N. E. Wurz, F. Glorius,
[15] The pinacolboronate moiety could also be considered to be a
masked form of a hydroxy group. In fact, upon treatment of
boronated dipeptides 2g and 2h with a mixture of Na3BO3 in
THF and H2O, the C–B bond was smoothly and selectively
oxidized to give protected dipetides Z-Val-Ser-OMe (7) and
Boc-Ser-Phe-OMe (8) in good yields (see Supporting Infor-
mation).
Angew. Chem. Int. Ed. 2011, 50, 1410–1414; Angew. Chem. [16] K. C. Nicolaou, A. A. Estrada, M. Zak, S. Hyup Lee, B. S. Saf-
2011, 123, 1446–1450; c) S.-W. Duan, J. An, J.-R. Chen, W.-J.
Xiao, Org. Lett. 2011, 13, 2290–2293; d) M. E. Kieffer, L. M.
Repka, S. E. Reisman, J. Am. Chem. Soc. 2012, 134, 5131–
5137.
ina, Angew. Chem. Int. Ed. 2005, 44, 1378–1382; Angew. Chem.
2005, 117, 1402–1406.
Received: March 18, 2015
Published Online: ᭿
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Job/Unit: O50362
/KAP1
Date: 15-04-15 11:32:13
Pages: 10
F. Bartoccini, S. Bartolucci, S. Lucarini, G. Piersanti
FULL PAPER
Conjugate Addition
F. Bartoccini, S. Bartolucci, S. Lucarini,
G. Piersanti* ................................... 1–10
Synthesis of Boron- and Silicon-Contain-
ing Amino Acids through Copper-Cata-
lysed Conjugate Additions to Dehydro-
alanine Derivatives
Copper mediated β-boration and β-silyl-
ation of a variety of dehydroalanine and
dehydropeptide compounds gives ready ac-
cess to orthogonally N- and C-protected
boron- and silicon-containing amino acids
and small peptides.
Keywords: Boron
/ Silicon / Copper /
Amino acids / Homogeneous catalysis /
Michael addition
10
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