Enantioselective γ-C(sp3)-H activation of alkyl amines via Pd(II)/Pd(0) catalysis

Article abstract of DOI:10.1021/jacs.8b01094

Pd(II)-catalyzed enantioselective γ-C(sp³)-H cross-coupling of alkyl amines via desymmetrization and kinetic resolution has been realized for the first time using chiral acetyl-protected aminomethyl oxazoline ligands (APAO). A diverse range of aryl- and vinyl-boron reagents can be used as coupling partners. The chiral γ-arylated alkylamine products are further transformed into chiral 2-substituted 1,2,3,4-tetra-hydroquinolines and spiro-pyrrolidines as important structural motifs in natural products and biologically active molecules.

Full text of DOI:10.1021/jacs.8b01094

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Enantioselective #-C(sp3)–H Activation
of Alkyl Amines via Pd(II)/Pd(0) Catalysis
Qian Shao, Qing-Feng Wu, Jian He, and Jin-Quan Yu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b01094 • Publication Date (Web): 09 Apr 2018
Downloaded from http://pubs.acs.org on April 9, 2018
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Enantioselective -C(sp3)–H Activation of Alkyl Amines via Pd(II)/Pd(0) Catalysis
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Qian Shao,† Qing-Feng Wu,† Jian He,† and Jin-Quan Yu*,†
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†Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037,
United States
RECEIVED DATE (automatically inserted by publisher); yu200@scripps.edu
Scheme 1. Enantioselective γ-C(sp3)–H Activation of Alkyl
Abstract: Pd(II)-catalyzed enantioselective γ-C(sp3)–H
Amines
cross-coupling of alkyl amines via desymmetrization and
kinetic resolution has been realized for the first time using
chiral acetyl-protected aminomethyl oxazoline ligands
(APAO). A diverse range of aryl- and vinyl-boron reagents
can be used as coupling partners. The chiral γ-arylated
alkylamine products are further transformed into chiral
2-substituted
1,2,3,4-tetra-hydroquinolines
and
spiro-pyrrolidines as important structural motifs in natural
products and biologically active molecules.
While Pd(OAc)2 has been long known to activate both sp2 and
sp3 C–H bonds,1 such reactivity driven by strong coordination
from substrates can also lead to persistent background reactions,
which presents
Pd(II)-catalyzed
a
fundamental challenge for rendering
racemic C–H activation
reactions2
enantioselective. Despite recent development of chiral Pd(II)
catalysts for enantioselective intermolecular C–H activation
reactions through weak coordination and ligand acceleration,3-6 as
well as Pd(0)-catalyzed intramolecular enantioselective C–H
arylation,7 scope and efficiency remains limited. For example,
protocols for enantioselective C–H activation reactions of
carboxylic acids and amide substrates are not applicable to alkyl
amine substrates. To date, there are only two examples of
enantioselective intermolecular γ-C(sp3)–H activation of amine
substrates involving cyclopropyl and benzylic C–H bonds
(Scheme 1).6a, 8 In addition, only arylation via a Pd(II)/Pd(IV)
catalytic cycle is compatible with these chiral catalysts.
Considering the broad utility of chiral amines in organic synthesis
and drug discovery,9 it is of great importance to develop
enantioselective C–H activation reactions of simple alkyl amines
using other catalytic cycles. Herein, we report the first chiral
catalyst for enantioselective γ-C(sp3)–H cross-coupling of
aliphatic amines with both aryl and vinyl boron reagents through
desymmetrization. Kinetic resolution10 of alkyl amines bearing
various α-substituents via γ-C(sp3)–H cross-coupling is also made
possible through catalyst modification, allowing the access to a
broader range of chiral amines.
the fact that acetyl protected amino oxazoline (APAO) chiral
ligands can facilitate carboxylic amide-directed enantioselective
C(sp3)–H
arylation
(Pd(II)/Pd(IV))
and
borylation
(Pd(II)/Pd(0)),5d, 5e we began to test this ligand for alkyl amine
derived substrates 1a. Encouragingly, the use of (S,S)-L3
furnished the cross-coupling product in 54% yield with 98% ee.
We then systematically modified APAO ligands at both the side
chain and the oxazoline ring to further optimize this
transformation (L4-L13). We found that the reactivity of this
cross-coupling reaction is highly sensitive to the steric hindrance
of the ligand side chain (L4-L7). Reaction with ligand bearing a
bulky t-Bu group improved the yield from 54% to 65% (L7). Fine
tuning of other substituents on the side chain did not provide
better results. The use of (S,R)-L7, the other diastereomer of the
optimal ligand, provided the enantiomer of product with 32%
yield and 98% ee. Para-trifluoromethyl substitution on the phenyl
ring gave slightly lower yield (L8). Increasing the steric hindrance
on the oxazoline ring was detrimental to the reaction, presumably
due to the ineffective binding of APAO ligand to Pd(II) species
(L9-L11). The chiral oxazoline ligands lacking a stereocenter on
either the side chain or the oxazoline moiety gave poor yields and
enantioselectivities (L12 and L13), which speaks to the
importance of both chiral centers on the APAO ligand backbones
for chiral induction. In all cases, material balances are
approximately 90%. Lack of the diarylation product also suggests
Based on our previously developed γ-C(sp3)–H arylation6a and
cross coupling11 of alkyl amines, we initiated our investigation to
develop γ-C(sp3)–H cross-coupling of amine 1a using various
types of bidentate chiral ligands (Table 1). While no C(sp3)–H
arylation occurred in the absence of ligand, we were delighted to
observe that the acetyl-protected aminoethyl quinoline (APAQ)
ligand (L1) provided the desired product in 30% yield with 97%
ee, and Ac-L-Val-OH (L2) provided product in 38% yield with
26% ee. However, the efforts to further improve the yield and
enantioselectivity failed after an extensive screening of APAQ
and mono-N-protected amino acid (MPAA) ligands. Considering
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Table 1. Ligand Developmenta, b
Table 2. Enantioselective Cross-Coupling with Arylboron
Reagents a, b
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a Reaction conditions: substrate 1a (0.1 mmol), 2a (2.0 equiv.), Pd(OAc)2 (10 mol%),
ligand (15 mol%), Ag2CO3 (2.0 equiv.), Na2CO3 (2.0 equiv.), 1,4-benzoquinone (BQ)
(0.5 equiv.), H2O (5.5 equiv.), t-AmylOH (1.0 mL), 80 °C, 12 h, N2. b The yields
were determined by 1H NMR analysis of the crude product using CH2Br2 as the
internal standard. The ee values were determined by HPLC analysis on a chiral
stationary phase.
a Reaction conditions: substrate 1a (0.1 mmol), 2 (2.0 equiv.), Pd(OAc)2 (10 mol%),
(S,S)-L7 (15 mol%), Ag2CO3 (2.0 equiv.), Na2CO3 (2.0 equiv.), 1,4-benzoquinone
(BQ) (0.5 equiv.), H2O (5.5 equiv.), t-AmylOH (1.0 mL), 80 °C, 12 h, N2. b Isolated
yields. The ee values were determined by HPLC analysis on a chiral stationary
phase.
that the high enantioselectivity originates from the high-level
enantio-control in the mono-arylation reaction instead of partial
kinetic resolution. Finally, control experiments revealed that the
Pd catalyst, silver source, BQ, base, and H2O were all crucial for
the C(sp3)–H cross-coupling reaction (see Supporting Information
for the detail optimization of these parameters).
groups at the para position also performed well (3i and 3j).
Reactions with biphenyl, 1-naphthyl, and 2-naphthyl boronic acid
pinacol ester furnished the desired products in good yields with
excellent
enantioselectivities
(3k-3m).
Furthermore,
meta-substituted and disubstituted arylboron reagents were all
well tolerated (3n-3r). Heteroaryl boronate ester was also
compatible with this reaction, albeit giving lower yield (3p). The
Tf group of 3b was removed in a two-step procedure to yield free
amine without loss of optical activity (see Supporting
Information). The free amine can also direct γ-C(sp3)−H arylation
of the remaining ethyl group using our transient directing group to
access a wider range of amines.12
Extending this enantioselective C−H activation method to
-C(sp3)–H coupling with vinylboron reagents will allow the
access to a broader range of chiral amines. Hence, we next
investigated the coupling of Tf-protected amines with various
vinylboron reagents, which has not been reported to date.
γ-Styrenylation of amine 1a using chiral ligand (S,S)-L7 afforded
the product in 50% yield and 96% ee. The use of (S,S,S)-L14,
containing an additional chiral center at C-5, improved the yield
to 56% and enantioselectivity to 99% ee (Table 3). A number of
disubstituted (Z)-vinylboron reagents (4a-4e), as well as
With the optimal reaction conditions established, we set out
to explore this enantioselective γ-C(sp3)−H cross-coupling
reaction of amine derivative 1a with a wide range of arylboron
reagents in the presence of (S,S)-L7 as ligand (Table 2). Reaction
with simple phenylboronic acid pinacol ester provided 3b in good
yield and excellent enantioselectivity (64%, 97% ee). Arylboron
reagents with both electron-donating and electron-withdrawing
substituents at the para and meta positions are well tolerated,
affording the desired products in good yields with excellent
enantioselectivities (>96% ee in all cases). Coupling partners
bearing electron-withdrawing ester, acetyl, trifluoromethyl, fluoro,
formyl, and nitro groups at the para position gave moderate to
good yields (41%-65%) with excellent enantioselectivities (3a,
3c-3g). No product was observed, using bromophenyl boronic
acid pinacol ester (3h). Coupling partners bearing
electron-donating substituents such as methyl and methoxyl
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trisubstituted vinylboron reagent (4f) were compatible with this
Table 4. Kinetic Resolution of Cross-Coupling with Arylboron
Reagents a, b
reaction. Coupling partners bearing 1-aryl-2-alkyl, diaryl, dialkyl,
and trialkyl groups gave moderate yields and excellent
enantioselectivities. 1-Cyclohexenyl-Bpin and 1-cyclopentyl-Bpin
were both well tolerated as coupling partners in this reaction (5g,
5h). Hetero-cyclohexenyl boronate esters also afforded desired
products in good enantioselectivities, albeit in lower yields (5i,
5j). These heterocycle-containing chiral amines are useful
intermediates in drug discovery.
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Table 3. Enantioselective Cross-Coupling with Vinylboron
Reagents a, b
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a
Reaction conditions: substrate 1 (0.1 mmol), 2 (2.0 equiv.), Pd(OAc)2 (10 mol%),
ligand (15 mol%), Ag2CO3 (2.0 equiv.), Na2CO3 (2.0 equiv.), 1,4-benzoquinone (BQ)
(0.5 equiv.), H2O (5.5 equiv.), t-AmylOH (1.0 mL), 80 °C, 24 h, N2. b Isolated yields.
The ee values were determined by HPLC analysis on a chiral stationary phase.
acid and β-substituted substrates also afforded desired products in
excellent enantioselectivity, albeit in lower yields (6e, 6f).
To showcase the synthetic utility of this enantioselective C−H
activation reaction, the cross-coupling products were further
transformed into chiral 2-substituted 1,2,3,4-tetra-hydroquinolines
without loss of optical activity (Table 5).13 Various substituents
such as 2-naphthyl, para- and meta-substituted arylated products
were well tolerated in the condition. Treatment of the vinylated
product 5j with concentrated sulfuric acid in DCM gave the
spiro-pyrrolidine derivative 7g in 79% yield.14 Deprotection was
readily accomplished by treating the cyclization product with
Red-Al in toluene at 50 °C, affording chiral 2-methyl-1,2,3,4-
a Reaction conditions: substrate 1a (0.1 mmol), 4 (3.0 equiv.), Pd(OAc)2 (10 mol%),
ligand (15 mol%), Ag2CO3 (2.0 equiv.), Na2CO3 (2.0 equiv.), 1,4-benzoquinone (BQ)
(0.5 equiv.), H2O (5.5 equiv.), THF (1.0 mL), 70 °C, 24 h, N2. b Isolated yields. The
ee values were determined by HPLC analysis on a chiral stationary phase.
Table 5. Cyclization of Cross-Coupling Products a, b
Next, we began to develop chiral ligands for enantioselective
γ-C(sp3)–H coupling of unsymmetric amines through kinetic
resolution (Table 4). Guided by the established enantioselective
desymmetrization C–H coupling (Table 1), the reaction of
racemic 1b with para-methoxycarbonyl-phenylboronic acid
pinacol ester was carried out in the presence of 10 mol%
Pd(OAc)2, 15 mol% (S,S)-L7, 2.0 equiv. of Ag2CO3, 2.0 equiv. of
Na2CO3, 0.5 equiv. of BQ, and 5.5 equiv. of H2O in t-AmylOH at
80 °C. We were pleased to find that the desired cross-coupling
product 6a was obtained with 40% yield and 84% ee. Encouraged
by this result, a variety of APAO ligands with different side
chains were screened and (S,S)-L15 was found to give the best
s-factor of 167 (6a, 34% yield, 98% ee) (see Supporting
Information for detail optimization of the reaction). With the
optimized reaction conditions in hand, we next investigated
different amines and arylboron coupling partners. Notably,
differentiation of a hydrogen atom and a relatively small methyl
group in 2-butylamine is highly challenging. We were pleased to
find that cross-coupling of 2-butylamine derived substrate gave
the arylated product in 32% yield and 96% ee (6b). This
enantioselective C−H activation protocol is compatible with
amino alcohol derived substrates (6c, s = 67; 6d, s = 233). Amino
a Reaction conditions: substrate 3 or 6 (0.1 mmol), 1,3-diiodo-5,5-dimethylhydantoin
(DIH) (2.0 equiv.), DCE (5.0 mL), hv, 60 °C, 6 h, N2. b Isolated yields. The ee values
were determined by HPLC analysis on a chiral stationary phase.
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Scheme 2. The Removal of Auxiliary a, b
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139, 12398. (h) Zhu, C.; Wang, D.; Zhao, Y.; Sun, W.-Y.; Shi, Z. J. Am.
Chem. Soc. 2017, 139, 16486. (i) Yang, L.; Neuburger, M.; Baudoin, O.
Angew. Chem., Int. Ed. 2018, 57, 1394.
(8) Wang, H.; Tong, H.-R.; He, G.; Chen, G. Angew. Chem., Int. Ed. 2016, 55,
15387.
(9) (a) Zhi, L.; Tegley, C. M.; Marschke, K. B.; Jones, T. K. Bioorg. Med.
Chem. Lett. 1999, 9, 1009. (b) Bohl, C. E.; Chang, C.; Mohler, M. L.;
Chen, J.; Miller, D. D.; Swaan, P. W.; Dalton, J. T. J. Med. Chem. 2004,
47, 3765. (c) Lindsley, S. R.; Moore, K. P.; Rajapakse, H. A.; Selnick, H.
G.; Young, M. B.; Zhu, H.; Munshi, S.; Kuo, L.; McGaughey, G. B.;
Colussi, D.; Crouthamel, M.-C.; Lai, M.-T.; Pietrak, B.; Price, E. A.;
Sankaranarayanan, S.; Simon, A. J.; Seabrook, G. R.; Hazuda, D. J.;
Pudvah, N. T.; Hochman, J. H.; Graham, S. L.; Vacca, J. P.; Nantermet, P.
G. Bioorg. Med. Chem. Lett. 2007, 17, 4057.
(10) For a single example of kinetic resolution through a intramolecular
C(sp3)–H arylation see: Katayev, D.; Larionov, E.; Nakanishi, M.;
Besnard, C.; Kꢀndig, E. P. Chem. - Eur. J. 2014, 20, 15021.
(11) Shao, Q.; He, J.; Wu, Q.; Yu, J.-Q. ACS Catal. 2017, 7, 7777.
(12) Wu, Y.; Chen, Y.-Q.; Liu, T.; Eastgate, M.-D.; Yu, J.-Q. J. Am. Chem. Soc.
2016, 138, 14554.
a Reaction conditions: 7a (0.1 mmol), Red-Al (10.0 equiv.), toluene (1.0 mL), 50 oC,
N2, 10 h. b Isolated yield.
tetra-hydroquinoline in 99% yield and 96% ee (Scheme 2). It
should be noted that 2-substituted 1,2,3,4-tetra-hydroquinolines
and spiro-pyrrolidines are important structural motifs in
biologically active molecules and natural products.
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In summary, we have developed Pd(II)-catalyzed
enantioselective γ-C(sp3)–H cross-coupling of alkyl amines
protected by a removable Tf group. C–H arylation and vinylation
via desymmetrization or kinetic resolution provide an access to a
broad range of chiral alkyl amines.
(13) Moroda, A.; Furuyama, S.; Togo, H. Synlett 2009, 8, 1336.
(14) Henderson, L.; Knight, D. W.; Williams, A. C. Synlett 2012, 23, 1667.
Acknowledgements. We gratefully acknowledge The Scripps
Research Institute and the NIH (NIGMS, 2R01GM084019) for
financial support. We thank David Hill for chiral separation of
compound 7g.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Constable, A. G.; McDonald, W. S.; Sawkins, L. C.; Shaw, B. L. J.
Chem. Soc., Chem. Commun. 1978, 1061. (b) Carr, K.; Sutherland, J. K. J.
Chem. Soc. Chem, Commun. 1984, 1227. (c) Baldwin, J. E.; Nájera, C.;
Yus, M. J. Chem. Soc. Chem, Commun. 1985, 126. (d) Balavoine, G.;
Clinet, J. C. J. Organomet. Chem. 1990, 390, C84.
(2) (a) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42,
1074. (b) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936.
(c) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. Chem. Rev. 2017,
117, 8754.
(3) For reviews on enantioselective C–H activation, see: (a) Giri, R.; Shi,
B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem. Soc. Rev. 2009, 38,
3242. (b) Herrmann, P.; Bach, T. Chem. Soc. Rev. 2011, 40, 2022. (c)
Newton, C. G.; Wang, S.-G.; Oliveira, C. C.; Cramer, N. Chem. Rev. 2017,
117, 8908. (d) Baudoin, O. Acc. Chem. Res. 2017, 50, 1114.
(4) For intermolecular enantioselective Pd(II)-catalyzed C(sp2)–H activation
reactions, see: (a) Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2008, 47, 4882. (b) Shi, B.-F.; Zhang, Y. H.; Lam, J. K.;
Wang, D. H.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 460. (c) Gao, D.-W.;
Shi, Y.-C.; Gu, Q.; Zhao, Z.-L.; You, S.-L. J. Am. Chem. Soc. 2013, 135,
86. (d) Pi, C.; Li, Y.; Cui, X., Zhang, H.; Han, Y. B.; Wu, Y. Chem. Sci.
2013, 4, 2675. (e) Chu, L.; Xiao, K.-J.; Yu, J.-Q. Science 2014, 346, 451.
(f) Du, Z. J.; Guan, J.; Wu, G. J.; Xu, P.; Gao, L. X.; Han, F. S. J. Am.
Chem. Soc. 2015, 137, 632.
(5) For intermolecular enantioselective Pd(II)-catalyzed C(sp3)–H activation
reactions, see: (a) Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu,
J.-Q. J. Am. Chem. Soc. 2011, 133, 19598. (b) Chen, G.; Gong, W.;
Zhuang, Z.; Andra, M. S.; Chen, Y.-Q.; Hong, ̈X.; Yang, Y.-F.; Liu, T.;
Houk, K. N.; Yu, J.-Q. Science 2016, 353, 1023. (c) Jain, P.; Verma, P.;
Xia, G.; Yu, J.-Q. Nat. Chem. 2016, 353, 1023. (d) Wu, Q.-F.; Shen, P.-X.;
He, J.; Wang, X.-B.; Zhang, F.; Shao, Q.; Zhu, R.-Y.; Mapelli, C.; Qiao, J.
X.; Poss, M. A.; Yu, J.-Q. Science 2017, 355, 499. (e) He, J.; Shao, Q.;
Wu, Q.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 3344.
(6) (a) Chan, K. S. L.; Fu, H.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 2042.
(b) Laforteza, B. N.; Chan, K. S. L.; Yu, J.-Q. Angew., Chem. Int. Ed.
2015, 54, 11143. (c) Smalley, A. P.; Cuthbertson, J. D.; Gaunt, M. J. J. Am.
Chem. Soc. 2017, 139, 1412.
(7) For intramolecular enantioselective Pd(0)-catalyzed C−H activation, see:
(a) Nakanishi, M.; Katayev, D.; Besnard, C.; Kꢀndig, E. P. Angew. Chem.,
Int. Ed. 2011, 50, 7438. (b) Anas, S.; Cordi, A.; Kagan, H. B. Chem.
Commun. 2011, 47, 11483. (c) Saget, T.; Cramer, N. Angew. Chem., Int.
Ed. 2012, 51, 12842. (d) Shintani, R.; Otomo, H.; Ota, K.; Hayashi, T. J.
Am. Chem. Soc. 2012, 134, 7305. (e) Ladd, C. L.; Charette, A. B. Org. Lett.
2016, 18, 6046. (f)Yang, L.; Melot, R.; Neuburger, M.; Baudoin, O. Chem.
Sci. 2017, 8, 1344. (g) Pedroni, J.; Cramer, N. J. Am. Chem. Soc. 2017,
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