Copper-Catalyzed Regio- and Enantioselective Aminoboration of Unactivated Terminal Alkenes

Article abstract of DOI:10.1002/chem.201801070

A CuCl/(R,R)-PTBP-BDPP-catalyzed regioselective and enantioselective aminoboration of simple and unactivated terminal alkenes with bis(pinacolato)diboron (pinB-Bpin) and hydroxylamines has been developed. The amino group and boryl group were incorporated

Full text of DOI:10.1002/chem.201801070

A Journal of
Accepted Article
Title: Copper-Catalyzed Regio- and Enantioselective Aminoboration of
Unactivated Terminal Alkenes
Authors: Kodai Kato, Koji Hirano, and Masahiro Miura
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Copper-Catalyzed Regio- and Enantioselective Aminoboration of
Unactivated Terminal Alkenes
Kodai Kato,[a] Koji Hirano,*[a] and Masahiro Miura*[a]
Dedication ((optional))
Abstract: A CuCl/(R,R)-PTBP-BDPP-catalyzed regioselective and
enantioselective aminoboration of simple and unactivated terminal
alkenes with bis(pinacolato)diboron (pinB–Bpin) and hydroxylamines
has been developed. The amino group and boryl group are
incorporated at the internal position and terminal position,
respectively, and the corresponding chiral b-borylalkylamines are
obtained with good to high enantiomeric ratios. The asymmetric
copper catalysis allows for rapid and concise transformation of
readily available olefinic feedstock-like materials into functionalized
chiral alkylamines of high potential in medicinal and pharmaceutical
chemistry.
PTBP-BDPP-catalyzed
regio-
and
enantioselective
aminoboration[8] of unactivated terminal alkenes with
bis(pinacolato)diboron (pinB–Bpin) and hydroxylamines.[9] The
asymmetric copper catalysis guides the amino group and boryl
group to the internal position and terminal position, respectively,
and the corresponding chiral b-borylalkylamines are obtained
with good to high enantiomeric ratios. The boron moiety can be
a
useful synthetic handle for further manipulations, thus
providing versatile chiral alkylamines, of great value in medicinal
and pharmaceutical applications, from the simple and abundant
terminal alkenes.
Our optimization studies commenced with vinylcyclohexane
(1a), pinB–Bpin, and O-benzoyl-N,N-dibenzylhydroxylamine (2a)
as model substrates. Given our recent findings[8] and literature
information,[10] the plausible catalytic cycle includes 1) s-bond
metathesis of L*CuOtBu with pinB–Bpin, forming the active boryl
copper species L*Cu-Bpin, 2) insertion of 1a into the Cu-B bond
of L*Cu-Bpin, 3) stereoretentive C–N bond formation with the
hydroxylamine 2a, and 4) regeneration of starting copper
alkoxide L*CuOtBu by salt metathesis with MOtBu (Scheme 1).
Both the regioselectivity and enantioselectivity can be
determined in the insertion step, and the optimization of
electronic and steric nature of ancillary ligand is thus a key to
success.
Catalytic asymmetric reactions of simple and abundant aliphatic
terminal alkenes have been longstanding research subjects in
synthetic
organic
chemistry.[1]
Among
them,
the
enantioselective difunctionalization in
a
fully intermolecular
manner has particularly received significant attention because
abundant olefinic feedstock-like materials can be readily
transformed into highly functionalized chiral molecules, which
are invaluable building blocks in the synthesis of complex
natural products and biologically active compounds. The most
reliable and well-known process is the Os-catalyzed
dihydroxylation originally developed by Sharpless.[2]
More
recently, the asymmetric diboration with chiral Pt and Rh
catalysts has been developed by Morken[3] and Nishiyama,[4] in
which the incorporated boryl group can participate in various
post functionalization reactions in stereospecific and site-
selective manners.[5] The former research group also reported
the asymmetric organocatalytic diboration.[6] On the other hand,
the unsymmetrical difunctionalization is much more challenging
because not only enantioselectivity but also regioselectivity
should be catalytically controlled. In 1995, Negishi developed
the Zr-catalyzed asymmetric carboalumination (ZACA) of simple
terminal alkenes with high regioselectivity as well as
pinB OtBu
L*Cu-Bpin
1a
pinB Bpin
L*Cu
*
Bpin
*
Bpin
CuL*
or
L*CuOtBu
(terminal borylation)
(internal borylation)
BzO NBn2
MOBz
2a
L*CuOBz
enantioselectivity.
The formed chiral alkylaluminum
MOtBu
Bpin
NBn2
intermediates underwent subsequent oxygenation and Pd-
catalyzed cross-coupling reaction, giving the corresponding
difunctionalized chiral molecules.[7] However, there still remains
a large demand for further development of enantioselective and
regioselective difunctionalization catalysis with more versatile
functional group incorporation. Herein, we report a CuCl/(R,R)-
NBn2
Bpin
*
*
or
3aa
3aa’
regioselectivity?
enantioselectivity?
Scheme 1. Working hypothesis of regio- and enantioselective copper-
catalyzed aminoboration of vinylcyclohexane (1a) with pinB–Bpin and and O-
benzoyl-N,N-dibenzylhydroxylamine (2a). Bz = benzoyl, Bn = benzyl, L* =
chiral ligand.
[a]
K. Kato, Prof. Dr. K. Hirano, Prof. Dr. M. Miura
Department of Applied Chemistry
Graduate School of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Fax: (+81) 6-6879-7362
E-mail: k_hirano@chem.eng.osaka-u.ac.jp;
miura@chem.eng.osaka-u.ac.jp
After extensive screening of chiral bisphosphine ligands on
the basis of reported Cu-catalyzed borylation with diboron
reagents,[11] we pleasingly found that a combination of CuCl
catalyst, (R,R)-PTBP-BDPP ligand, and NaOtBu base promoted
regio- and enantioselective aminoboration of 1a to form the
terminally borylated b-borylalkylamine 3aa in 76% yield with 24:1
Supporting information for this article is available on the WWW
under http://www.xxx.
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CuCl (10 mol%)
(R,R)-PTBP-BDPP (10 mol%)
R1
R2
regioisomeric ratio (r.r.) and 96:4 enantiomeric ratio (e.r.)
(Scheme 2; 0.25 mmol scale). The reaction could also be
scaled up to 1 mmol with the maintenance of regio- and
enantioselectivity. The formed aminoborated product 3aa was
easily oxidized with aq. H2O2 into the corresponding chiral
aminoalcohol 3aa-O without erosion of enantiomeric ratio.
Notably, the tert-butyl group at the para-position in the benzene
ring of (R,R)-PTBP-BDPP was critical for the high
regioselectivity and enantioselectivity; analogous (S,S)-BDPP,
(S,S)-Xyl-BDPP, and (S,S)-PMP-BDPP resulted in lower
regioisomeric ratio (6.7:1–9:1) and enantiomeric ratio (17:83–
10:90). Such a remote steric hindrance is particularly important
for the terminal borylation selectivity because the bisphosphine-
ligated copper moiety should be located at the more sterically
hindered internal position (Scheme 1).[12,13]
+
+
BzO
N
pinB Bpin
NaOtBu
THF, RT, 4 h
2
1a
R1 R2
N
R1 R2
N
NaBO3•OH2
Bpin
OH
3-O
THF/H2O
overnight
3
nC6H13
NMeBn
OH
NBn2
NEt2
N
Bpin
OH
OH
3ac-O, 32%[a] (48%)
3ab-O, 67%[a]
11.5:1 r.r, 96:4 e.r.
3aa, 76%
24:1 r.r, 96:4 e.r.
3ad-O, 40% (50%)
13:1 r.r, 95:5 e.r.
11.5:1 r.r, 95:5 e.r.
S
O
N
N
N
N
OH
OH
OH
OH
3ae-O, 66%[a]
3ah-O, 60%[a] (65%)
3ag-O, 37% (63%)
3af-O, 32% (40%)
>25:1 r.r, 95:5 e.r.
8:1 r.r, 95:5 e.r.
9:1 r.r, 96:4 e.r.
24:1 r.r, 96:4 e.r.
CuCl (10 mol%)
(R,R)-PTBP-BDPP (10 mol%)
pinB Bpin
+
tBu
tBu
NaOtBu
THF, RT, 4 h
BzO NBn2
Scheme 3. Copper-catalyzed regio- and enantioselective aminoboration of
vinylcyclohexane (1a) with bis(pinacolato)diboron and various hydroxylamines
2. Conditions: CuCl (0.025 mmol), (R,R)-PTBP-BDPP (0.025 mmol), 1a (0.75
mmol for 3aa–3ac, 1.25 mmol for 3ad–3ah), pinB–Bpin (0.38 mmol), 2 (0.25
mmol), NaOtBu (0.38 mmol), THF (1.5 mL), RT, 4 h, N2, then NaBO3•OH2 (2.5
mmol), THF/H2O (1:1), RT, overnight, open flask. Isolated yields based on 2
are given. 1H NMR yield in the Bpin form is in parentheses. Regioisomeric
ratio (r.r.) and enantiomeric ratio (e.r.) were determined by 1H NMR and HPLC
analysis on a chiral stationary phase, respectively. [a] Combined isolated yield
of 3-O and regioisomeric 3’-O.
1a
P
P
2a
NBn2
NBn2
aq. H2O2
aq. NaOH
Bpin
OH
tBu
(R,R)-PTBP-BDPP
tBu
THF/EtOH
RT, 30 min
3aa-O
3aa
76%, 24:1 r.r., 96:4 e.r. (0.25 mmol scale) 52% (from 1a), 96:4 e.r.
73%, 24:1 r.r., 95:5 e.r. (1.0 mmol scale) (0.25 mmol scale)
results with other BDPPs (1H NMR yield of 3aa and e.r. of 3aa-O)
MeO
OMe
P
P
P
P
P
P
MeO
OMe
We next tested several aliphatic terminal alkenes 1 for the
regio- and enantioselective aminoboration with 2a (Table 1).
Almost products could be isolated in the Bpin form by
purification with column chromatography, but determination of
enantiomeric ratio was conducted after the oxidation with aq.
H2O2 because of better stability and reproducibility of the
corresponding aminoalcohols for HPLC analysis. In addition to
vinylcyclohexane (1a), allylically substituted vinylcyclopentane
(1b) and 1,1-diphenyl-2-propene (1c) provided the high
regioselectivity (>25:1 r.r.) while the former gave better
enantioselectivity (94:6 e.r. for 3ba-O vs 80:20 e.r. for 3ca-O;
entries 1 and 2). Allylbenzene derivatives 1d–1f were also
viable substrates, and high regioselectivity (13:1–24:1 r.r.) and
acceptable enantioselectivity (80:20–95:5 e.r.) were observed
(entries 3–5). The homoallylbenzene 1g resulted in somewhat
lower regio- and enantioselectivity (5.3:1 r.r. and 77:23 e.r.; entry
6), but the introduction of additional substituent at the
homoallylic position increased the values of both r.r. and e.r.
(6.7:1 r.r. and 91:9 e.r. for 3ha-O, 8.1:1 r.r. and 83:17 e.r. for
3ia-O; entries 7 and 8). The simplest 1-octene (1j) could also be
converted to the corresponding chiral aminoborated product with
synthetically useful level of 5.3:1 r.r. and 82:18 e.r. (entry 9).
Moreover, the asymmetric Cu catalysis was tolerated with silyl
ether (1k), ester (1l), and imide (1m) groups to furnish the
functionality-enriched chiral alkylamines with 6.7:1–10:1 r.r. and
83:17–89:11 e.r. (3ka-O–3ma-O; entries 10–12).
(S,S)-BDPP
67%, 9:1 r.r., 11:89 e.r.
(S,S)-Xyl-BDPP
65%, 8:1 r.r., 17:83 e.r.
(S,S)-PMP-BDPP
68%, 6.7:1 r.r., 10:90 e.r.
Scheme 2. Optimal conditions for CuCl/(R,R)-PTBP-BDPP-catalyzed regio-
and enantioselective aminoboration of vinylcyclohexane (1a) and performance
of other BDPP-type ligands. Isolated yields are given for the reaction with
(R,R)-PTBP-BDPP. The e.r. refers to the enantiomeric ratio of major
regioisomer.
With conditions in Scheme 2, we first investigated the scope
of hydroxylamines 2 with 1a. The representative products are
shown in Scheme 3.
Except for 3aa, all aminoborated
compounds 3 were less stable for column chromatographic
purification, and thus the isolation and determination of
regioisomeric and enantiomeric ratios were performed after the
NaBO3-mediated
aminoalcohols 3-O.
diethylamine,
oxidation[14]
into
Other acyclic amines including N,N-
N-benzyl-N-methylamine, N-hexyl-N-
the
corresponding
pentenylamine underwent the reaction to form the corresponding
chiral aminoalcohols 3ab-O, 3ac-O, and 3ad-O with high
regioselectivity (11.5:1–13:1 r.r.) and enantioselectivity (95:5–
96:4 e.r.). The CuCl/(R,R)-PTBP-BDPP catalyst was also
compatible with cyclic amines; piperidine, morpholine,
thiomorpholine, and azepane-containing aminoalcohols 3ae-O–
3ah-O were obtained with 8:1–>25:1 r.r. and 95:5–96:4 e.r. As
mentioned above, whereas the enantioselectivity was uniformly
high, the regioselectivity was somewhat dependent on the steric
and electronic nature of hydroxylamine.[15]
Table 1. Copper-catalyzed regio- and enantioselective aminoboration of
various simple terminal alkenes 1 with bis(pinacolato)diboron and O-benzoyl-
N,N-dibenzylhydroxylamine (2a).[a]
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with pinB–Bpin (d 30.6 ppm in 11B NMR), the original 31P{1H}
signal of (R,R)-PTBP-BDPP (d –6.8 ppm) was shifted to d –4.8
ppm. Concurrently, one new signal corresponding to pinB-OtBu
appeared at d 21.2 ppm in 11B NMR.[21] Theses spectra changes
suggest the formation of (R,R)-PTBP-BDPP-ligated Cu-Bpin
species, although the corresponding 11B signal was not detected,
same as reported analogous phosphine-supported borylcopper
complexes.[22] Additionally, pinB–Bpin seems to accelerate the
coordination of (R,R)-PTBP-BDPP to Cu center by promoting
the dissociation of aggregated CuOtBu or formation of Cu-Bpin
species. Subsequent addition of vinylcyclohexane (1a) form a
new but small signal at d 34.0 ppm in 11B NMR, which is
assigned to be an alkene-inserted b-boryl alkylcopper
CuCl (10 mol%)
pinB Bpin
aq. H2O2
aq. NaOH
NBn2
NBn2
(R,R)-PTBP-BDPP (10 mol%)
R
+
OH
Bpin
THF/EtOH
RT, 30 min
R
NaOtBu
THF, RT, 4 h
R
BzO NBn2
1
3
3-O
2a
Entry
1
1
3, Yield [%], r.r.[b]
3-O, Yield [%], e.r.[c]
3ba-O, 44, 96:4
3ba, 62 (74), >25:1
1b
Ph
3ca, 35 (42), >25:1
3da, (57), 24:1
3ca-O, 31, 80:20
3da-O, 36, 80:20
2
3
Ph
1c
Ph
1d
OMe
MeO
3ea, 60 (76), 24:1
3fa, 63 (80), 13:1
3ea-O, 51, 95:5
3fa-O, 43, 81:19
4
5
1e
complex.[10a]
However, any additional changes were not
observed even after 40 min at room temperature. On the other
hand, in the presence of NaOtBu an amount of b-boryl
alkylcopper complex was increased to be over that of the
1f
Ph
3ga-O, 38, 77:23
3ha-O, 48, 91:9
6
3ga, 55, 5.3:1
3ha, 65, 6.7:1
1g
Ph
starting pinB–Bpin after
1 h at room temperature, thus
7[d]
suggesting NaOtBu can accelerate the alkene insertion into the
borylcopper species as well as play roles in the CuOtBu
generation and regeneration steps.[23] Finally, we observed the
formation of aminoborated product 3aa (d 35.0 ppm in 11B NMR,
Ph
1h
3ia, 41 (57), 8.1:1
3ja, 67, 5.3:1
3ka, 64, 6.7:1
3la, 75, 9:1
3ia-O, 30, 83:17
3ja-O, 40, 82:18
3ka-O, 54, 83:17
3la-O, 56, 83:17
3ma-O, 31, 89:11
8
1i
1j
9
C6H13
1
also confirmed by H NMR) and complete consumption of pinB–
TBSO
Bpin by addition of O-benzoyl-N,N-dibenzylhydroxylamine (2a).
On the basis of the above findings, it is stated that the alkene
insertion step can be rate-limiting and greatly promoted by
external alkoxide base. Additionally, the following C–N forming
process is relatively facile and strongly drives the process to the
product formation.
10
11
12[e]
1k
PivO
1l
PhthN
3ma, 45, 10:1
1m
[a] Conditions: CuCl (0.025 mmol), (R,R)-PTBP-BDPP (0.025 mmol), 1 (1.0
mmol), pinB–Bpin (0.38 mmol), 2a (0.25 mmol), NaOtBu (0.38 mmol), THF
(1.5 mL), RT, 4 h, N2, then aq. H2O2 (30%, 0.5 mL, 5 mmol), aq. NaOH (3 M,
0.5 mL, 1.5 mmol), THF/EtOH (1.0/0.50 mL), RT, open flask, 30 min. [b]
Combined isolated yields of 3 and regioisomeric 3’ are given. 1H NMR yields
are in parentheses. Regioisomeric ratio (r.r.) was determined by 1H NMR. [c]
Isolated yields of 3-O based on 2a are given. Enantiomeric ratio (e.r.) was
determined by HPLC analysis on a chiral stationary phase. [d] Under LiOtBu-
modified conditions: 1h (0.25 mmol), pinB–Bpin (0.38 mmol), 2a (0.38 mmol),
LiOtBu (0.75 mmol). [e] Oxidation was performed with NaBO3•OH2 (2.5 mmol)
In conclusion, we have developed a CuCl/(R,R)-PTBP-
BDPP-catalyzed
regioselective
and
enantioselective
aminoboration of simple terminal alkenes. The asymmetric
catalysis can convert the readily available and abundant olefinic
feedstock-like materials to chiral functionalized alkylamines of
great values in medicinal and pharmaceutical chemistry.
Additionally, preliminary mechanistic studies suggest the rate-
limiting alkene insertion to phosphine-ligated borylcoppers and
additional roles of alkoxide bases in the insertion step. Further
improvement of regio- and enantioselectivity, expansion of
substrate scope, and application to complex molecule synthesis
are ongoing in our laboratory.
in THF/H2O (1:1) at RT, overnight. PhthN
butyldimethylsilyl, Piv = tert-butylcarbonyl.
= phthalimidyl, TBS = tert-
Based on the rich chemistry of Bpin moiety, the obtained
aminoborated product 3aa can be readily derivatized into
several functionalized chiral alkylamines (Scheme 4). The
treatment with MeO-NHLi followed by Boc protection afforded
the corresponding optically active 1,2-diamine 4 with orthogonal
protecting groups.[16] The conversion of 3aa into the internal
ammonium trifluoroborate salt 5[17] was also possible by using a
KF/tartaric acid protocol, which was originally developed by
Lloyd-Jones.[18] Notably, in this case, 5 was purified by simple
filtration without any column chromatography. Additionally, one-
carbon homologation and successive Suzuki-Miyaura cross-
coupling furnished the arylated product 7 in an acceptable
overall yield. During the aforementioned transformations, the
enantiomeric ratio remained well.[19]
+NHBn2
NBn2
NBn2
1) MeO-NHLi
THF, 60 ˚C
aq. KF
(+)-tartaric acid
–
BF3
Bpin
NHBoc
2) (Boc)2O, RT
THF/MeCN
RT
4, 32%
>25:1 r.r.,96:4 e.r.
3aa
5, 52%
>25:1 r.r., 96:4 e.r.
24:1 r.r., 95:5 e.r.
BuLi
ClCH2Br
Ph Br
NBn2
NBn2
Pd(OAc)2/RuPhos
CsOH•OH2
Bpin
Ph
1,4-dioxane/H2O
100 ˚C
6, 34%
>25:1 r.r.
7, 42%
>25:1 r.r., 96:4 e.r.
To get insight into the mechanism proposed in Scheme 1,
we finally monitored the reaction mixture by 31P{1H} and 11B
NMR (Scheme 5). Initial simple mixing of (R,R)-PTBP-BDPP
and CuOtBu in [D8]THF at room temperature gave almost no
significant change in 31P{1H} NMR, probably because of
tetrameric structure of CuOtBu.[20] However, upon treatment
Scheme 4. Derivatization of optically active aminoborated product 3aa. Boc =
tert-butoxycarbonyl,
RuPhos
=
dicyclohexylphosphino-2’,6’-
diisopropoxybiphenyl.
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COMMUNICATION
pinB–Bpin
Gosmini, Synthesis 2014, 46, 2258; f) M. T. Pirnot, Y.-M. Wang, S. L.
Buchwald, Angew. Chem. Int. Ed. 2016, 55, 48; Angew. Chem. 2016,
128, 48; g) X. Dong, Q. Liu, Y. Dong, H. Liu, Chem. Eur. J. 2017, 23,
248. Selected examples: h) A. M. Berman, J. S. Johnson, J. Am. Chem.
Soc. 2004, 126, 5680; i) M. J. Campbell, J. S. Johnson, Org. Lett. 2007,
9, 1521; j) S. Liu, L. S. Liebeskind, J. Am. Chem. Soc. 2008, 130, 6918;
k) T. J. Barker, E. R. Jarvo, J. Am. Chem. Soc. 2009, 131, 15598; l) S.
N. Mlynarski, A. S. Karns, J. P. Morken, J. Am. Chem. Soc. 2012, 134,
16449; m) C. Zhu, G. Li, D. H. Ess, J. R. Falck, L. Kürti, J. Am. Chem.
Soc. 2012, 134, 18253; n) R. P. Rucker, A. M. Whittaker, H. Dang, G.
Lalic, J. Am. Chem. Soc. 2012, 134, 6571; o) J. He, T, Shigenari, J.-Q.
Yu, Angew. Chem. Int. Ed. 2015, 54, 6545; Angew. Chem. 2015, 127,
6645; p) Y. Yang, S.-L. Shi, D. Niu, P. Liu, S. L. Buchwald, Science
2015, 349, 62; q) D. Nishikawa, K. Hirano, M. Miura, J. Am. Chem. Soc.
2015, 137, 15620.
P
P
P
δ 30.6 (11B)
CuOtBu
pinB–Bpin
[D8]THF, RT
almost
no change
+
Cu-Bpin
[D8]THF, RT
pinB OtBu
δ 21.2 (11B)
P
δ –4.8 (31P{1H})
no signal (11B)
(R,R)-PTBP-BDPP
δ –6.8 (31P{1H})
pinB–Bpin
P
P
1a
NBn2
Cu
full consumption
2a
BzO NBn2
(NaOtBu)
Bpin
Bpin
+
[D8]THF, RT, 2 h
[D8]THF, RT
pinB OtBu
δ 21.2 (11B)
3aa
in case with NaOtBu
δ 34.0 (11B)
δ 35.0 (11B)
also confirmed by 1H NMR
trace w/o NaOtBu
major product w/NaOtBu
Scheme 5. NMR studies.
[10] For stoichiometric reactions of borylcopper species with alkenes, see:
a) D. S. Laitar, E. Y. Tsui, J. P. Sadighi, Organometallics 2006, 25,
2405; b) J. Lee, S. Radomkit, S. Torker, J. del Pozo, A. H. Hoveyda,
Nat. Chem. 2018, 10, 99. Recent computational studies: c) S. Tobisch,
Chem. Eur. J. 2017, 23, 17800.
Acknowledgements ((optional))
This work was supported by JSPS KAKENHI Grant Nos. JP
15H05485 (Grant-in-Aid for Young Scientists (A)) to K.H. and JP
17H06092 (Grant-in-Aid for Specially Promoted Research) to
M.M. We thank Dr. Mitsuhisa Yamano (SPERA PHARMA, Inc.)
for generous gift of (R,R)-PTBP-BDPP.
[11] Reviews: a) K. Semba, T. Fujihara, J. Terao, Y. Tsuji, Tetrahedron
2015, 71, 2183; b) H. Yoshida, ACS Catal. 2016, 6, 1799. Selected
recent examples of bisphosphine-based enantioselective catalysts: c) F.
Meng, F. Haeffner, A. H. Hoveyda, J. Am. Chem. Soc. 2014, 136,
11304; d) K. Kubota, K. Hayama, H. Iwamoto, H. Ito, Angew. Chem. Int.
Ed. 2015, 54, 8809; Angew. Chem. 2015, 127, 8933; e) K. Kubota, Y.
Watanabe, K. Hayama, H. Ito, J. Am. Chem. Soc. 2016, 138, 4338; f) N.
Kim, J. T. Han, D. H. Ryu, J. Yun, Org. Lett. 2017, 19, 6144.
[12] See the Supporting Information for more detailed optimization studies.
The absolute configuration of 3ja-O (Table 1, entry 9) was determined
to be S by comparison of specific rotation to the reported value. Others
were tentatively assigned by analogy.
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Published online on ((will be filled in by the editorial staff)
Keywords: asymmetric catalysis · boron· chiral amine · copper ·
electrophilic amination
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Copper-Catalyzed Regio- and
Enantioselective Aminoboration of
Unactivated Terminal Alkenes
Remote control:
A
copper-catalyzed regioselective and enantioselective
aminoboration of unactivated terminal alkenes with bis(pinacolato)diboron and
hydroxylamines has been developed to deliver the terminally borylated chiral b-
borylalkylamines in good yields.
The key to achieve the high regio- and
enantioselectivity is the use of (R,R)-PTBP-BDPP ligand of remote steric hindrance
with the para tert-butyl group. The asymmetric copper catalysis can readily
transform the abundant olefinic feedstock-like materials into functional chiral
alkylamines of great interest in medicinal and pharmaceutical applications.
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