Concise Synthesis of Potassium Acyltrifluoroborates from Aldehydes through Copper(I)-Catalyzed Borylation/Oxidation

Article abstract of DOI:10.1002/anie.201901748

Potassium acyltrifluoroborates (KATs) were prepared through copper(I)-catalyzed borylation of aldehydes and subsequent oxidation. This synthetic route is characterized by the wide range of aldehydes accessible, favorable step economy, mild reaction conditions, and tolerance of various functional groups, and it enables the facile generation of a range of KATs, for example, bearing halide, sulfide, acetal, or ester moieties. Moreover, this method was applied to the three-step synthesis of various α-amino acid analogues that bear a KAT moiety on the C-terminus by using naturally occurring amino acids as the starting material.

Full text of DOI:10.1002/anie.201901748

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Accepted Article
Title: Concise Synthesis of Potassium Acyltrifluoroborates from
Aldehydes by a Cu(I)-catalyzed Borylation/Oxidation Protocol
Authors: Jumpei Taguchi, Takumi Takeuchi, Rina Takahashi, Fabio
Masero, and Hajime Ito
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201901748
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10.1002/anie.201901748
Angewandte Chemie International Edition
COMMUNICATION
Concise Synthesis of Potassium Acyltrifluoroborates from
Aldehydes by a Cu(I)-catalyzed Borylation/Oxidation Protocol
Jumpei Taguchi,[a] Takumi Takeuchi,[a] Rina Takahashi,[a] Fabio Masero,[b] Hajime Ito*[a,c]
Abstract: Potassium acyltrifluoroborates (KATs) were prepared by a
copper(I)-catalyzed borylation of aldehydes and subsequent
Recently, our group and that of Perrin have reported the
ozonolysis and the dihydroxylation/oxidative cleavage of alkenyl
MIDA boronates, respectively, which afford acyl MIDA boronates
(Scheme 1Ba).2j,k These approaches are conducted under
relatively mild conditions and are suitable for the preparation of
highly functionalized acylboronates including the first examples of
enantioenriched α-amino acylboron compounds. In 2012, Yudin
and co-workers reported another mild synthetic route: the Dess-
Martin oxidation of α-hydroxy MIDA boronates, which affords acyl
MIDA boronates. Despite the mild conditions of this reaction, the
tolerance toward functional groups was not explored (Scheme
1Bb).2l,5 In any case, these three milder methods still require
multiple steps from easily available materials such as
alkenylboronates, and protection of the boronate moiety by MIDA
against oxidative conditions, which equates to additional steps.
α-Hydroxy boronates can be directly prepared from
aldehydes by Cu(I)-catalyzed borylation, followed by a treatment
with KHF2, which generates α-hydroxy trifluoroborates in a one-
pot fashion.6 Although the oxidation of α-hydroxy trifluoroborates
seems to be one of the most straightforward methods to
synthesize KATs, this avenue has not yet been reported. We
found that KATs can be synthesized by oxidation of potassium α-
hydroxy trifluoroborates using 9-azanoradamantane-N-oxyl (nor-
a
oxidation. This synthetic route is characterized by the wide range of
aldehydes accessible, a favorable step-economy, mild reaction
conditions, and the tolerance of various functional groups, enabling
the facile generation of KATs that bear e.g. halide, sulfide, acetal, or
ester moieties. Moreover, this method was applied to the three-step
synthesis of various α-amino acid analogues that bear a KAT moiety
on the C-terminus, using naturally occurring amino acids as the
starting material.
The chemistry of acylboron compounds represents a rapidly
growing research theme in organic synthesis.1 In 2007, Nozaki,
Yamashita, and co-workers achieved the first isolation of
acylboron by the reaction between boryl lithium species and
benzoyl chloride.2a Since this seminal work, the preparation and
reactivity of acylborons have been studied enthusiastically.2 – 4
Among these acylboron species, potassium acyltrifluoroborates
(KATs) are of particular interest due to their unique reactivity and
remarkable stability toward air and moisture.3,4d,e In 2012, Dumas,
Bode, and Molander reported the highly chemoselective and rapid
amide-bond-forming reaction between KATs and hydroxylamines,
i.e., KAT ligation.3a Although other acylboron species such as acyl
N-methyliminodiacetyl (MIDA) boronates and monofluoro
acylborates have also been used in this amide-bond-formation
reaction, all these reagents can be derived from KATs; in other
words: strategic importance should be attributed to KATs as
precursors to a wide variety of acylboron species.3c,d
In 2012, Dumas and Bode reported that KATs can be
synthesized by lithiation of benzotriazole-based N,O-acetals,
followed by a trapping using a boron electrophile, and quenching
with aqueous KHF2 (Scheme 1Aa).2e,f Bode and co-workers also
developed a thioformamide-derived reagent that enables a one-
pot KAT synthesis from aryl lithium or alkyl cuprate compounds
(Scheme 1Ab).2g,h Although these two approaches are practical,
given that various N,O-acetals or organometallic reagents are
accessible from the corresponding aldehydes or halides, the
requirement for highly reactive organolithium reagents leaves still
room for the improvement of the functional-group tolerance.
(A) Previous synthetic routes to KATs
a) Molander (2010), Bode (2012)
b) Bode (2014)
SEt
BF3
O
Li
Bt
R M +
then
KF
B(OMe)3
+
N
R
BF3K
then
KHF2
R
OR'
Potassium
acyltrifluoroborate (KAT)
M = Li or Cu
(B) Reported preparation of acyl MIDA boronate by oxidation
a) Ito, Bode, Perrin (2017)
b) Yudin (2012)
Me
Dess-Martin
periodinane
O
R’
N
OH
B(MIDA)
O3 or
B
R
O
OsO4
NaIO4
R
R
B(MIDA)
O
O
O
Acyl MIDA boronate
Multiple steps from easily
accessible compounds
(C) Oxidation of potassium α-hydroxy trifluoroborate (This work)
Cu(I)-catalyzed
borylation
OH
BF3K
O
O
Oxidation
BF3K
KAT
R
R
R
H
then KHF2 aq.
[a]
J. Taguchi, T. Takumi, R. Takahashi, and Prof. Dr. H. Ito
Division of Applied Chemistry, Graduate School of Engineering
Hokkaido University
Widely available
α-Hydroxy trifluoroborate
Kita 13 Nishi 8 Kita-ku, Sapporo, Hokkaido 060-8628 (Japan)
E-mail: hajito@eng.hokudai.ac.jp
F. Masero
Laboratorium für Organische Chemie, Department of Chemistry and
Applied Bioscience, ETH Zürich 8093 Zürich (Switzerland)
Prof. Dr. H. Ito
Scheme 1. (A) Previous synthetic routes to KATs. (B) Reported preparation of
acyl MIDA boronate by oxidation. (C) Oxidation of potassium α-hydroxy
trifluoroborates (Bt = benzotriazole).
[b]
[c]
Institute for Chemical Reaction Design and Discovery (WPI-
ICReDD), Hokkaido University
Kita 13 Nishi 8 Kita-ku, Sapporo, Hokkaido 060-8628 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/xx.
AZADO) or DMSO/Ac2O under optimized conditions (Scheme 1C).
This MIDA-free approach reduces the number of synthetic steps
and provides a short and scalable route to KATs that is compatible
with a wide variety of functional groups. The important features of
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10.1002/anie.201901748
Angewandte Chemie International Edition
COMMUNICATION
this approach are the commercial availability of a wide variety of
aldehydes, its step-economy, and a wide product scope including
KATs derived from biologically-related molecules including
carbohydrate, steroid, and α-amino acids.
oxidants such as NaOCl or PhI(OAc)2 generated complex
mixtures (entries 6, 7).9 The oxidation with Tetrapropyl ammonium
perruthenate (TPAP)/NMO afforded 2a in lower yield (38%, entry
8).
Aryl substituted α-hydroxy trifluoroborate 1a was prepared
from o-tolualdehyde according to the procedure reported by
Molander.6b Our initial attempt to synthesize α-hydroxy MIDA
boronates via the reaction between 1a and (TMS)2MIDA/BF3·Et2O
was unsuccessful.3c Therefore, we investigated the direct
oxidation of 1a.7 When 1a was subjected to a Dess-Martin
oxidation under reaction conditions similar to those for the
oxidation of α-hydroxy MIDA boronates reported by Yudin, the
reaction afforded a complex mixture, in which the desired KAT 2a
was not detected (Table 1, entry 1). Subsequently, we
investigated standard Swern oxidation conditions using
DMSO/(COCl)2; alas, the low solubility of 1a hampered the
reaction (entry 2). However, we found that Albright-Goldman
oxidation conditions using DMSO/Ac2O at room temperature
furnished 2a in good yield (85%, entry 3).8 Oxidation using
catalytic amounts of nor-AZADO or AZADOL and a stoichiometric
amount of the co-oxidant NaNO2 with acetic acid also afforded 2a
in 92% and 66% yield (entries 4, 5), respectively, while other co-
Then, we investigated the scope of this reaction using two
favorable procedures: oxidation with i) DMSO/Ac2O and ii) nor-
AZADO catalyst (Scheme 2). The reaction exhibited high
functional-group tolerance and afforded KATs containing methoxy
(2b), halide (2c–2e), trifluoromethyl (2f), and sulfide (2g) moieties
in good to high yield (63–93%). Sterically hindered aryl acylboron
2h was also prepared in good yield (44%). This method can also
be applied to the preparation of an acylboron bearing thiophene
(2i: 56%). In addition to aryl or heteroaryl KATs, this method was
also effective for the preparation of alkyl KATs. α-Hydroxy
trifluoroborates bearing primary (2j), secondary (2k), and tertiary
alkyl groups (2l) can also be used in this method and afford the
corresponding KATs in good to high yield (69–78%).
Conditions A:
Ac2O/DMSO, rt
OH
BF3K
1b—1q
O
Conditions A or B
R
R
BF3K
Conditions B:
nor-AZADO/NaNO2
AcOH, CH3CN, rt
2b—2q
Table 1. Optimization of the oxidation conditions.
O
O
O
OH
BF3K
O
BF3K
BF3K
BF3K
oxidation
BF3K
Cl
MeO
F
2b: 80% (B)
2c: 93% (A)
2d: 87% (A)
1a
2a
O
O
O
entry
oxidation conditions
yield (%)[a]
BF3K
BF3K
BF3K
F3C
1b
2c
3d
4e
5f
Dess-Martin periodinane, CH2Cl2, rt, 1.5 h
DMSO, (COCl)2, Et3N, THF, –78 ºC, 0.25 h
DMSO, Ac2O, rt, 4 h
<5
<5
85
92
66
<5
<5
38
Br
MeS
Ph
2e: 79% (B)
2f: 63% (B)[a]
2g: 82% (B)
O
O
S
O
BF3K
BF3K
BF3K
nor-AZADO, NaNO2, AcOH, rt, 0.5 h
AZADOL, NaNO2, AcOH, rt, 17 h
AZADOL, NaClO, rt, 0.5 h
2i: 56% (B)[a]
2h: 44% (B)
2j: 69% (A)
58% (B)
O
6g
7h
8i
O
O
BF3K
BF3K
AZADOL, PhI(OAc)2, rt, 1 h
BF3K
7
TPAP, NMO, MS 3A, rt, 2 h
2l: 72% (B)
2m: 33% (A)
67% (B)
2k: 77% (A)
78% (B)
[a] Isolated product yield are reported. [b] 1a (0.3 mmol), Dess-Martin
periodinane (2.0 equiv), CH2Cl2, rt, 1.5 h. [c] 1a (0.5 mmol), DMSO (2.2
equiv), (COCl)2 (1.1 equiv), Et3N (excess), THF, –78 ºC, 15 min. [d] 1a (0.5
mmol), Ac2O (20 equiv), DMSO, rt, 4 h. [e] 1a (0.5 mmol), nor-AZADO (10
mol%), NaNO2 (1.5 equiv), AcOH (2.0 equiv), CH3CN, rt, 18 h. [f] 1a (0.5
mmol), AZADOL (10 mol%), NaNO2 (1.5 equiv), AcOH (2.0 equiv), 17 h. [g]
1a (0.5 mmol), AZADOL (5 mol%), NaClO (1.5 equiv), CH3CN, rt, 0.5 h. [h]
1a (0.5 mmol), AZADO (10 mol%), PhI(OAc)2 (1.5 equiv), CH3CN, rt, 1 h.
CH3CN, rt, 17 h. [i] 1a (0.5 mmol), TPAP (10 mol%), NMO (6.0 equiv), MS
3A, CH3CN, rt, 2 h.
OAc
O
AcO
AcO
O
O
O
O
AcO
BF3K
BF3K
O
2n: 30% (A)
2o: 70% (B)
Scheme 2. Substrate scope. Reaction conditions A: 1 (0.3 mmol), Ac2O (20
equiv), DMSO, rt, 12 h–17 h. Reaction conditions B: 1 (0.3 mmol), nor-AZADO
(10 mol%), NaNO2 (1.5 equiv), AcOH (2.0 equiv), CH3CN, rt, 12 h–24 h. Isolated
product yields are reported. [a] NMR yields are reported.
OAc
AcO
AcO
I
O
–
O
n-Pr4N+ · RuO4
N O
N OH
AZADOL
Dess-Martin
preiodinane
nor-AZADO
TPAP
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10.1002/anie.201901748
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COMMUNICATION
Table 2. Preparation of KAT-containing α-amino-acid analogues.[a]
be prepared from commercially available α-amino acids in one
step.10b
phenylalanine-derived
Cu(I)-catalyzed
borylation
aldehyde
of
N-Boc-protected
α-hydroxy
CbzHN
OH
O
O
afforded
i) borylation
2-Aminoethanol
PGHN
PGHN
trifluoroborate 3b in 61% (entry 2). The oxidation of 3b furnished
N-Boc-protected phenylalanine type KAT 4b in high yield with
high enantiomeric purity (80%, 99% ee). This method can also be
applied to the preparation of N-Fmoc-protected leucine-type KAT
(4c), and N-Cbz-protected valine-type KAT (4d) in high yields
excellent enantiopurities (entries 3, 4, borylation: 62% (3c), 50%
(3d); oxidation: 71%, 99% ee (4c), 77%, 99% ee (4d)).12 These
KATs, especially for leucine-type KATs, has significant
importance for peptide–peptide ligation due to their frequent
appearance in natural proteins compared with serine residue,
which is required in native chemical ligation (NCL).11 Considering
the accessibility of α-amino aldehydes from α-amino acids, this
chiral-pool-based synthetic strategy provides a general, and
scalable approach to α-amino KATs that is advantageous relative
to the reported oxidative cleavage of alkenyl MIDA boronates,
which requires enantioenriched propargyl amine as starting
materials.2j, 10
H
BF3K
ii) oxidation
O
R
α-Amino aldehyde
R
PGHN
4a—4d
OH
R
α-Amino acid
>99% ee
borylation
yield (%)[b]
oxidation
yield (%)[b]
ee (%)
entry
product
O
1
52
61
76[c]
–
CbzHN
BF3K
4a
O
BocHN
2
3
4
80
71
77
99
99
99
BF3K
Ph
4b
O
FmocHN
a) Gram-scale synthesis of 2c
BF3K
62
50
B2(pin)2 (1.0 equiv)
1.5 mol% (ICy)CuCl
3.0 mol% K(O-t-Bu)
THF, rt, 2.5 h
5.0 mol%
nor-AZADO
NaNO2
4c
O
O
(1.5 equiv)
O
H
BF3K
AcOH
(2.0 equiv)
CH3CN
CbzHN
then KHF2 aq.
(8.0 equiv)
99%
BF3K
F
F
rt, 5 days
4d
10 mmol
2c, 62% (2.1 g)
isolated by filtration
[a] Borylation conditions: aldehyde, B2pin2 (1.1 equiv), (ICy)CuCl (3–10
mol%), K(Ot-Bu) (6–20 mol%), MeOH (2.0 equiv), THF, rt, 2–7 h. Oxidation
conditions: 3, nor-AZADO (10 mol%), NaNO2 (1.5 equiv), AcOH (2.0 equiv),
CH3CN, rt, 4–12 h. [b] Isolated product yields are reported. [c] Reaction was
performed with 2.0 mol% TBABr. (Cbz = benzyloxycarbonyl, Boc = tert-
b) Gram-scale synthesis of 4b from N-Boc-protected phenylalanine
B2(pin)2 (1.1 equiv)
1.5 mol% (ICy)CuCl
3.0 mol% K(O-t-Bu)
1) CDI
CH2Cl2
O
OH
BF3K
THF, rt, 3 h
BocHN
Ph
BocHN
Ph
butoxy carbonyl; Fmoc
=
fuorenylmethyloxycarbonyl; [B]
= potassium
OH
trifluoroborate; (ICy)CuCl
=
1,3-dicyclohexylimidazol-2-ylidene-copper(I)
2) DIBAL
–78 ºC
85%
then KHF2 aq.
(8.0 equiv)
62%
chloride; B2(pin)2 = bis(pinacolato)diboron).
15 mmol
OH
BF3K
3b
2.0 mol% nor-AZADO
NaNO2 (1.5 equiv)
O
BocHN
BocHN
Ph
Acylboron species bearing alkene (2m) and acetal moieties (2n)
were also obtained in 30–67% yield. KATs 2g, 2m, and 2n are
particularly important as their synthesis via the oxidative cleavage
of alkenyl MIDA boronates is nontrivial.2j,k Based on the versatility
of this method, we applied it to the preparation of KATs bearing
biological molecules, which afforded glucose-bearing KAT 2o in
70% yield. This late-stage modification of bio-active molecules to
the corresponding KATs has significant potential for the
preparation of glycopeptide and antibody-drug conjugates.
BF3K
AcOH (2.0 equiv)
CH3CN, rt, 6.5 h
Ph
3b, 5.0 mmol
4b
82% (1.5 g), 99% ee
Scheme 3. Gram-scale synthesis of 2c and 4b.
This borylation/oxidation protocol is especially amenable to
a gram-scale synthesis of KATs (Scheme 3). Borylation of 10
mmols of 4-fluoro benzaldehyde with 1.5 mol% of (ICy)CuCl
catalyst followed by oxidation with 5.0 mol% nor-AZADO afforded
KAT 2c in 62% yield (2.1 g). It is the simplicity of the synthetic
protocol that renders it suitable for upscaling: the oxidation does
not require an inert atmosphere and the products in each step can
be easily isolated by filtration. Furthermore, phenylalanine-
derived α-hydroxy trifluoroborate 3b was obtained in 53% yield
from commercially available N-Boc-protected phenylalanine in
two steps (Scheme 3b). The oxidation of 3b (5.0 mmol) with 2.0
Subsequently, we investigated the synthesis of α-amino
acid-derived KATs (Table 2). This class of compounds is very
attractive due to its potential use as a building block in peptide
conjugation using KAT ligation.1b,2j,k N-Cbz glycinal can be
synthesized by the oxidation of N-Cbz-protected 2-aminoethanol.
Cu(I)-catalyzed borylation afforded α-hydroxy trifluoroborate 3a in
52% and followed by nor-AZADO oxidation afforded N-Cbz
glycine type KAT 4a in 76% (entry 1). Next, we investigated the
synthesis of enantioenriched amino acid analogues. The
corresponding starting materials, i.e., the α-amino aldehydes, can
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10.1002/anie.201901748
Angewandte Chemie International Edition
COMMUNICATION
15257; Angew. Chem. 2017, 129, 15459; l) Z. He, P. Trinchera, S.
Adachi, J. D. St. Denis, A. K. Yudin, Angew. Chem., Int. Ed. 2012, 51,
11092; Angew. Chem. 2012, 124, 11254.
mol% nor-AZADO affords the corresponding phenylalanine-type
KAT 4b in 82% yield (1.5 g) without any loss of enantiopurity.
In summary, we have developed an operationally simple
protocol for the preparation of KATs in two steps from aldehydes.
This borylation/oxidation proceeds under mild conditions and
exhibits high functional-group tolerance toward e.g. halide, acetal,
sulfide, and ester moieties. The oxidation can be accomplished
with i) DMSO/Ac2O or ii) nor-AZADO catalyst, and the conditions
for either oxidation are practical as the use of expensive
stoichiometric oxidants is not required. Importantly, various α-
[3]
[4]
a) A. M. Dumas, G. A. Molander, J. W. Bode, Angew. Chem., Int. Ed.
2012, 51, 5683; Angew. Chem. 2012, 124, 5781. b) H. Noda, G. Erős, J.
W. Bode, J. Am. Chem. Soc. 2014, 136, 5611; c) H. Noda, J. W. Bode,
Chem. Sci. 2014, 5, 4328; d) H. Noda,; J. W. Bode, J. Am. Chem. Soc.
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O. Gálvez, C. P. Schaack, H. Noda, J. W. Bode, J. Am. Chem. Soc. 2017,
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Poda, A. K. Yudin, Org. Lett. 2015, 17, 5594; b) C. F. Lee, A. Holownia,
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Diaz, C. C. G. Scully, S. K. Liew, S. Adachi, P. Trinchera, J. D. St Denis,
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W. Bode, Org. Lett. 2018, 20, 4044.
amino-acid analogues containing
a KAT moiety, which is
expected to be essential for peptide-peptide conjugation, can be
prepared from naturally occurring α-amino aldehydes without
racemization. The utility of this method was demonstrated by the
synthesis of a KAT-containing carbohydrate, and a column-
chromatography-free gram-scale synthesis. This general method
is expected to broaden the range of applications of KAT not only
in the context of bioconjugation, but also in organic synthesis and
material science.
[5]
Z. He; A. K. Yudin, J. Am. Chem. Soc. 2011, 133, 13770. The preparation
of α-hydroxy MIDA boronates is shown below ([B] = MIDA boronate).
Me
Pinnick
N
BF3·Et2O
CHO
oxidation
mCPBA
R
O
B
R
O
[B]
R
[B]
Acknowledgements
O
O
O
Alkenyl MIDA boronate
Me
O
N
Barton
decarboxylation
This study was financially supported by the Institute for Chemical
Reaction Design and Discovery (WPI-ICReDD), which was
established by the World Premier International Research Initiative
(WPI), MEXT, Japan, as well as KAKENHI grants 17H06370
(JSPS) and JP18H03907. J.T. would like to thank the JSPS for a
scholarship (KAKENHI grant 16J01384).
Dess-Martin
oxidation
CO2H
OH
B
R
O
O
O
R
[B]
R
[B]
O
α-Hydroxy MIDA boronate
Acyl MIDA boronate
[6]
[7]
a) D. S. Laitar, E. Y. Tsui, J. P. Sadighi, J. Am. Chem. Soc. 2006, 128,
11036; b) G. A. Molander, S. R. Wisniewski, J. Am. Chem. Soc. 2012,
134, 16856; c) K. Kubota, E. Yamamoto, H. Ito, J. Am. Chem. Soc. 2015,
137, 420; d) B. Carry, L. Zhang, M. Nishiura, Z. Hou, Angew. Chem., Int.
Ed. 2016, 55, 6257; Angew. Chem. 2016, 128, 6365.
Keywords: amino acid • boron • copper • oxidation • acylboron
a) G. A. Molander, M. Ribagorda, J. Am. Chem. Soc. 2003, 125, 11148;
b) G. A. Molander, R. Figueroa, Org. Lett. 2006, 8, 75; c) G. A. Molander,
D. E. Petrillo, J. Am. Chem. Soc. 2006, 128, 9634; d) G. A. Molander, D.
J. Cooper J. Org. Chem. 2007, 72, 3558; e) D.-S. Kim, K. Bolla, S. Lee,
J. Ham, Tetrahedron 2011, 67, 1062.
[1]
For reviews on acylboron compounds, see: a) F. K. Scharnagl, S. K.
Bose, T. B. Marder, Org. Biomol. Chem. 2017, 15, 1738; b) H. Noda, J.
W. Bode, Org. Biomol. Chem. 2016, 14, 16; c) J. D. St. Denis, Z. He, A.
K. Yudin, ACS Catal. 2015, 5, 5373.
[2]
a) M. Yamashita, Y. Suzuki, Y. Segawa, K. Nozaki, J. Am. Chem. Soc.
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10.1002/anie.201901748
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Potassium acyltrifluoroborates
(KATs) can be prepared in two
steps from the corresponding
aldehydes by a sequential Cu(I)-
catalyzed borylation and an
oxidation with either nor-AZADO
catalyst or Ac2O/DMSO. This
method is step-economical,
scalable, and exhibits high
Jumpei Taguchi, Takumi Takeuchi,
Rina Takahashi, Fabio Masero,
Hajime Ito*
Page No. – Page No.
Concise Synthesis of Potassium
Acyltrifluoroborates from
Aldehydes by a Cu(I)-catalyzed
Borylation/Oxidation Protocol
functional-group tolerance. In
addition, a-amino KATs, which are
expected to be essential for peptide
ligations, were prepared using
naturally occurring α-amino acid as
starting materials.
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