Enantioselective copper-catalyzed reductive coupling of vinylazaarenes with n -boc aldimines

Article abstract of DOI:10.1055/s-0034-1379548

The diastereo- and enantioselective reductive coupling of vinylazaarenes with N-Boc aldimines is described. The reactions proceed using chiral copper-bisphosphine complexes in the presence of TMDS as a hydride source to give reductive coupling products in moderate to high enantioselectivities.

Full text of DOI:10.1055/s-0034-1379548

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 350–354
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Enantioselective Copper-Catalyzed Reductive Coupling of
Vinylazaarenes with N-Boc Aldimines
Bonnie Choia,b
N
Boc
Aakarsh Saxenaa
Joshua J. Smitha,b
Gwydion H. Churchillc
Hon Wai Lam*a,b
N
N
NHBoc
Cu (cat.)
(S)-DTBM-SEGPHOS (cat.)
N
+
N
Ph
TMDS, THF
27 examples
59–94% ee
H
Ph
Me
69%
>19:1 dr, 92% ee
a EaStCHEM, School of Chemistry, University of Edinburgh, Joseph
Black Building, The King’s Buildings, West Mains Road, Edinburgh
EH9 3JJ, UK
b School of Chemistry, University of Nottingham, University Park,
Nottingham, NG7 2RD, UK
+
4
4
1
(
1
5
9
)
5
1
3
5
5
5
hon.lam@nottingham.ac.uk
c AstraZeneca Process Research and Development, Charter Way,
Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK
Received: 16.09.2014
Accepted after revision: 22.10.2014
Published online: 21.11.2014
copper-catalyzed reductions of β,β-disubstituted alkenyl-
azaarenes2a and copper-catalyzed reductive couplings of
alkenylazaarenes with ketones (Scheme 1, a).2d This latter
process enables the synthesis of products containing an
azaarene and two stereogenic centers, including a tertiary
alcohol. The ability to employ other types of electrophiles
would be beneficial to expand the range of accessible prod-
ucts.
DOI: 10.1055/s-0034-1379548; Art ID: st-2014-r0773-c
Abstract The diastereo- and enantioselective reductive coupling of vi-
nylazaarenes with N-Boc aldimines is described. The reactions proceed
using chiral copper–bisphosphine complexes in the presence of TMDS
as a hydride source to give reductive coupling products in moderate to
high enantioselectivities.
Krische and co-workers have described the racemic rho-
dium-catalyzed hydrogenative coupling of vinylazines with
N-sulfonylaldimines (Scheme 1, b),3 and we envisaged that
a related enantioselective variant employing chiral copper
hydride chemistry4 could be developed. Although the inter-
molecular reductive aldol reaction5 of α,β-unsaturated car-
bonyl compounds, catalyzed by chiral copper–hydride
complexes, has been successful,6 the corresponding reduc-
tive Mannich reactions7 have been less well studied.8 To
date, the only report of enantioselective copper-catalyzed
Key words asymmetric catalysis, copper, enantioselectivity, imines,
vinylazaarenes
The broad significance of aromatic nitrogen heterocy-
cles (azaarenes) in chiral biologically active compounds and
other functional molecules has prompted our group to in-
vestigate the potential of C=N-containing azaarenes as acti-
vating groups in new catalytic enantioselective processes.1,2
During this program, we have reported enantioselective
a) enantioselective reductive coupling of alkenylazaarenes with ketones (ref. 2d)
Me2N
Ph2P
F
Ph2P
Fe
(5 mol%)
O
N
N
Cu(OAc)2•H2O (5 mol%)
+
OMe
PhSiH3 (1.5 equiv)
toluene, 0 °C to r.t.
N
N
F
OH
MeO
74%, >19:1 dr, >99% ee
(14 other examples)
b) racemic reductive coupling of vinylazines with N-sulfonylaldimines (ref. 3)
(2-Fur)3P (12 mol%)
[Rh(cod)2]BARF (5 mol%)
NHSO2Ar
ArO2S
R1
N
R1
+
N
R2
H2 (1 atm), Na2SO4 (2.0 equiv)
CH2Cl2, 25 °C
R2
N
H
Me
Scheme 1 Existing catalytic reductive coupling reactions of alkenylazaarenes
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 350–354

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B. Choi et al.
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reductive Mannich reactions is from Kanai, Shibasaki,
and co-workers, who described the reductive coupling of
α,β-unsaturated esters with N-phosphinoyl ketimines.7f
Herein, we describe the enantioselective copper-cata-
lyzed reductive coupling of vinylazaarenes with N-Boc aldi-
mines. Both vinylazines and vinylazoles are effective
substrates, and the Boc protection in the products is advan-
tageous for subsequent deprotection.
High diastereoselectivities (≥10:1 dr) were observed with
vinylazaarenes containing benzannulation (3a, 3b, 3e, and
3f), while 2-bromo-6-vinylpyridine and 3-phenyl-6-vinyl-
pyridazine resulted in more modest diastereoselectivities
(3c and 3d). In the former case, the diastereomers were dif-
ficult to separate completely, and the minor isomer was
formed in a much lower enantiomeric excess (20% ee) com-
pared with the major isomer (80% ee).
Our investigations began with an evaluation of chiral bi-
sphosphines, reductants, and reaction conditions for the
copper-catalyzed reductive coupling of 2-vinylquinoline
(1a) with N-Boc aldimine 2a (1.1 equiv), which led to the
identification of (S)-DTBM-SEGPHOS (L1) as an effective
chiral ligand.
The reductive coupling of 4-phenyl-2-vinylthiazole (1g)
with imine 2a proceeded with low enantioselectivity using
ligand L1. Fortunately, (R,R)-Ph-BPE (L2) provided improved
results and gave 3g in 88% yield, >19:1 dr, and 87% ee
(Scheme 3).10
Ph
In the presence of Cu(OAc)2·H2O (5 mol%), L1 (5 mol%),
and 1,1,3,3-tetramethyldisiloxane (TMDS, 1.2 equiv), the
reaction proceeded smoothly in THF at room temperature
to give the reductive coupling product 3a as the anti diaste-
reomer in 63% yield, >19:1 dr, and 85% ee (Scheme 2).9,10
Under these conditions, various other vinylazaarenes 1b–f
were also effective in reactions with imine 2a, which gave
products 3b–f in 58–74% yield and 75–92% enantiomeric
excess. Besides quinoline (3a), azaarenes that were tolerat-
ed included quinoxaline (3b), a bromopyridine (3c), a phen-
ylpyridazine (3d), benzoxazole (3e), and benzothiazole (3f).
Ph
P
P
Ph
Ph
Ph
Ph
L2 (5 mol%)
Boc
H
N
NHBoc
Ph
N
Cu(OAc)2•H2O (5 mol%)
N
+
S
S
TMDS (1.2 equiv)
Ph
THF, 0 °C to r.t., 16 h
Me
3g 88%
>19:1 dr, 87% ee
1g
2a (1.1 equiv)
Scheme 3 Reductive coupling of 1g with 2a using ligand L2
O
O
O
PAr2
PAr2
L1 (5 mol%)
O
Ar = 3,5-(t-Bu)2-4-MeOC6H2
Cu(OAc)2•H2O (5 mol%)
Boc
H
N
NHBoc
Ph
N
N
Ar
X
Ar
X
+
Ph
TMDS (1.2 equiv)
THF, 0 °C to r.t., 16 h
Me
2a (1.1 equiv)
1a–f
3a–f
N
NHBoc
Ph
NHBoc
NHBoc
Ph
N
N
Ph
Br
N
Me
Me
Me
3ca 68%
3:1 dr, 80% ee (20% ee)
3b 69%
>19:1 dr, 92% ee
3a 63%
>19:1 dr, 85% ee
Ph
NHBoc
Ph
N
NHBoc
Ph
N
NHBoc
Ph
N
O
S
N
Me
3d 58%
5:1 dr, 82% ee
Me
3e 74%
14:1 dr, 75% ee
Me
3f 65%
10:1 dr, 88% ee
Scheme 2 Enantioselective reductive coupling of vinylazaarenes 1a–f with N-Boc imine 2a. Reactions were conducted using 0.30 mmol of 1a–f. Unless
stated otherwise, yields are of pure isolated major diastereomers. Diastereomeric ratios were determined by 1H NMR analysis of the unpurified reaction
mixtures. Enantiomeric excesses were determined by chiral HPLC analysis. a Yield of a 4.3:1 mixture of diastereomers. The enantiomeric excess of the
minor diastereomer is indicated in parentheses.
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Various other (hetero)aromatic N-Boc aldimines 2b–l
also underwent reductive coupling with vinylazaarenes 1a–
f, giving products 4a–s in 59–94% enantiomeric excess for
the major diastereomers (Scheme 4).10 The diastereoselec-
tivities of these reactions ranged from 1.3:1 (4i) to >19:1
(4a–c,e,f,r). Compared with the results shown in Scheme 2
and with similar reactions using ketones as electrophiles,2d
these reactions often provided lower yields of the reductive
coupling products due to more prevalent side reactions,
such as simple reduction of both reaction partners without
C–C bond formation. Although no definitive trends could be
deduced from the particular combinations of substrates
that resulted in the highest enantioselectivities, values of
85% enantiomeric excess or higher were observed in several
cases (4a,c,d,i,k,q–s). With respect to the imine, a range of
substituents (methyl, trifluoromethyl, chloro-, methoxy, di-
oxolane, or boronate esters) at various positions on the phe-
nyl ring were tolerated.
Furthermore, reactions of imines containing 1-naphthyl,
2-naphthyl, or 2-thienyl groups were also successful. As ob-
served previously (Scheme 1), the reactions of 2-bromo-6-
vinylpyridine and 3-phenyl-6-vinylpyridazine generally
gave lower diastereoselectivities (4g–l) compared with the
other vinylazaarenes. Lower diastereoselectivities were also
obtained with an imine containing a p-pinacol boronic es-
ter (4i and 4s). Interestingly, the minor diastereomers ob-
tained for products 4g and 4i were obtained in low or
nonexistent enantiomeric excesses.
O
O
O
PAr2
PAr2
L1 (5 mol%)
O
Ar = 3,5-(t-Bu)2-4-MeOC6H2
Cu(OAc)2•H2O (5 mol%)
Boc
H
N
NHBoc
R
N
N
Ar
X
Ar
X
+
TMDS (1.2 equiv)
THF, 0 °C to r.t., 16 h
R
Me
1a–f
2b–l (1.1 equiv)
4a–s
N
N
NHBoc
Ar
NHBoc
N
R
Me
Me
4a Ar = 2-naphthyl, 58%, >19:1 dr, 86% ee
4b Ar = 4-MeC6H4, 61%, >19:1 dr, 82% ee
4c Ar = 2-ClC6H4, 42%, >19:1 dr, 85% ee
4d R = 4-F3C, 46%, 5:1 dr, 93% ee
4e R = 3-MeO, 59%, >19:1 dr, 79% ee
4f R = 2-Me, 56%, >19:1 dr, 80% ee
Ph
NHBoc
NHBoc
N
Br
N
N
R
R
Me
Me
4ga R = 3-MeO, 71%, 3:1 dr, 80% (5% ee)
4hb R = 2-Me, 55%, 3:1 dr, 79% (57% ee)
4ic R = 4-B(pin), 56%, 1.3:1 dr, 85% (0% ee)
4j R = 2-MeC6H5, 51%, 5:1 dr, 74% ee
4k R = 1-naphthyl, 35%, 6:1 dr, 88% ee
4l R = piperonyl, 50%, 3:1 dr, 59% ee
N
NHBoc
R
N
NHBoc
O
S
R
Me
Me
4m R = 2-thienyl, 71%, 10:1 dr, 69% ee
4n R = 2-naphthyl, 63%, 8:1 dr, 81% ee
4o R = piperonyl, 78%, 10:1 dr, 79% ee
4p R = 3-Cl, 42%, 6:1 dr, 75% ee
4q R = 2-Me, 54%, 6:1 dr, 94% ee
4r R = 1-naphthyl, 71%,>19.1 dr, 94% ee
4s R = 4-B(pin), 40%, 3:1 dr, 86% ee
Scheme 4 Enantioselective reductive coupling of vinylazaarenes 1a–f with various N-Boc imines. Reactions were conducted using 0.30 mmol of 1a–f.
Unless stated otherwise, yields are of pure isolated major diastereomers. Diastereomeric ratios were determined by 1H NMR analysis of the unpurified
reaction mixtures. Enantiomeric excesses were determined by chiral HPLC analysis. Where measured, the enantiomeric excess of the minor diastereo-
mer is indicated in parentheses. a Yield of a 4.7:1 mixture of diastereomers. b Yield of a 3:1 mixture of diastereomers. c Yield of a 1.6:1 mixture of
diastereomers.
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Ph
Ph
P
P
Ph
Ph
Boc
Ph
L2 (5 mol%)
N
N
NHBoc
Ph
Cu(OAc)2•H2O (5 mol%)
H
S
N
+
TMDS (1.2 equiv)
THF, 0 °C to r.t., 16 h
Me
S
OMe
2f (1.1 equiv)
OMe
>19:1 dr, 78% ee
1g
4t 83%
Scheme 5 Reductive coupling of 1g with 2f using ligand L2
Me
PCy2
PAr2
Fe
L3 (5 mol%)
Ar = 3,5-(F3C)2C6H3
Cu(OAc)2•H2O (5 mol%)
Boc
N
N
NHBoc
Cy
N
+
S
TMDS (1.2 equiv)
THF, 0 °C to r.t., 16 h
H
Cy
S
Me
4u 73% (16%)a
3:1 dr, 82% ee (75% ee)a
1f
2m (2.0 equiv)
Scheme 6 Reductive coupling of 1f with an aliphatic N-Boc imine 2m using ligand L3. a Values in parentheses refer to the yield and enantiomeric excess
of the minor diastereomer.
Once again, (R,R)-Ph-BPE (L2) was a superior ligand
compared with L1 in a reductive coupling involving 4-phe-
nyl-2-vinylthiazole (Scheme 5).10
azaarenes with (hetero)aryl N-Boc imines. The reactions
provide reductive coupling products with moderate to high
enantioselectivities (up to 94% ee).
The reaction of 2-vinylbenzothiazole (1f) with an imine
2m (2.0 equiv) containing an aliphatic substituent (cyclo-
hexyl) was also studied (Scheme 6). Although low stereose-
lectivities were obtained using ligands L1 or L2, the
Josiphos ligand SL-J006-1 (L3) gave improved results and
provided two diastereomers of 4u in 73% and 16% yields, in
82% and 75% enantiomeric excess for the major and minor
isomers, respectively.
Acknowledgment
We thank the EPSRC, University of Edinburgh, University of Notting-
ham, AstraZeneca, and GlaxoSmithKline for financial support of this
work. We are grateful to Dr. Gary S. Nichol (University of Edinburgh)
and Dr. William Lewis (University of Nottingham) for assistance with
X-ray crystallography.
Finally, removal of the Boc group from 4a was achieved
under acidic conditions (using HCl generated by the reac-
tion of TMSCl with MeOH), which provided amine 5 in 90%
yield with no loss of enantiopurity (Scheme 7).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379548.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
NHBoc
NH2
Ar
TMSCl, MeOH
50 °C, 30 min
References and Notes
N
Ar
N
Me
4a (86% ee)
Me
(1) For an overview of C=N-containing azaarenes as activating
groups in enantioselective catalysis, see: Best, D.; Lam, H. W.
J. Org. Chem. 2014, 79, 831.
(2) For reactions from our group describing the use of C=N-con-
taining azaarenes as activating groups in enantioselective catal-
ysis, see: (a) Rupnicki, L.; Saxena, A.; Lam, H. W. J. Am. Chem.
Soc. 2009, 131, 10386. (b) Pattison, G.; Piraux, G.; Lam, H. W.
J. Am. Chem. Soc. 2010, 132, 14373. (c) Saxena, A.; Lam, H. W.
Chem. Sci. 2011, 2, 2326. (d) Saxena, A.; Choi, B.; Lam, H. W.
J. Am. Chem. Soc. 2012, 134, 8428. (e) Fallan, C.; Lam, H. W.
Ar = 2-naphthyl
5 90%
(86% ee)
Scheme 7 Deprotection of 4a
In summary, the results presented herein demonstrate
the ability of chiral copper–bisphosphine complexes to cat-
alyze the enantioselective reductive coupling of vinyl-
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Chem. Eur. J. 2012, 18, 11214. (f) Best, D.; Kujawa, S.; Lam, H. W.
J. Am. Chem. Soc. 2012, 134, 18193. (g) Roy, I. D.; Burns, A. R.;
Pattison, G.; Michel, B.; Parker, A. J.; Lam, H. W. Chem. Commun.
2014, 50, 2865.
17.7 mg, 0.015 mmol), and imine 2a (68 mg, 0.33 mmol) in THF
(1.5 mL) was stirred at 0 °C for 15 min. TMDS (64 μL, 0.36
mmol) was then added dropwise over 1 min. The mixture was
stirred at 0 °C for 1 h, then at r.t. for 15 h. The reaction was
quenched carefully with SiO2, and the resulting suspension was
stirred for 15 min before being filtered through a short plug of
SiO2 using EtOAc as eluent and concentrated in vacuo. Purifica-
tion of the residue by flash column chromatography gave the
reductive coupling product.
(3) Komanduri, V.; Grant, C. D.; Krische, M. J. J. Am. Chem. Soc. 2008,
130, 12592.
(4) For reviews of copper hydride chemistry, see: (a) Lipshutz, B. H.
Synlett 2009, 509. (b) Deutsch, C.; Krause, N.; Lipshutz, B. H.
Chem. Rev. 2008, 108, 2916. (c) Rendler, S.; Oestreich, M. Angew.
Chem. Int. Ed. 2007, 46, 498. (d) Lipshutz, B. H. In Modern
Organocopper Chemistry; Wiley-VCH: Weinheim, 2002, 167–
187.
(5) For selected reviews on reductive aldol reactions, see:
(a) Krische, M. J.; Jang, H. Y. In Comprehensive Chirality; Carreira,
E. M.; Yamamoto, H., Eds.; Elsevier: Amsterdam, 2012, 100–121.
(b) Nishiyama, H.; Ito, J.-i. Chem. Commun. 2010, 203. (c) Han, S.
B.; Hassan, A.; Krische, M. J. Synthesis 2008, 2669. (d) Garner, S.
A.; Han, S. B.; Krische, M. J. In Modern Reduction Methods;
Wiley-VCH: Weinheim, 2008, 387–417. (e) Nishiyama, H.;
Shiomi, T. Top. Curr. Chem. 2007, 279, 105. (f) Ngai, M.-Y.; Kong,
J.-R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063.
(6) For intermolecular copper-catalyzed reductive aldol reactions,
see: (a) Zhao, D.; Oisaki, K.; Kanai, M.; Shibasaki, M. Tetrahedron
Lett. 2006, 47, 1403. (b) Welle, A.; Diez-Gonzalez, S.; Tinant, B.;
Nolan, S. P.; Riant, O. Org. Lett. 2006, 8, 6059. (c) Chuzel, O.;
Deschamp, J.; Chausteur, C.; Riant, O. Org. Lett. 2006, 8, 5943.
(d) Deschamp, J.; Chuzel, O.; Hannedouche, J.; Riant, O. Angew.
Chem. Int. Ed. 2006, 45, 1292. (e) Zhao, D.; Oisaki, K.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 14440. (f) Li, Z.; Jiang,
L.; Li, Z.; Chen, H. Chin. J. Chem. 2013, 31, 539. (g) Li, Z.; Zhang,
Z.; Yuan, L.; Jiang, L.; Li, Z.; Li, Z. Synlett 2014, 25, 724.
(7) For examples of catalytic reductive Mannich reactions, see:
(a) Muraoka, T.; Kamiya, S.-i.; Matsuda, I.; Itoh, K. Chem.
Commun. 2002, 1284. (b) Townes, J. A.; Evans, M. A.; Queffelec,
J.; Taylor, S. J.; Morken, J. P. Org. Lett. 2002, 4, 2537.
(c) Nishiyama, H.; Ishikawa, J.; Shiomi, T. Tetrahedron Lett. 2007,
48, 7841. (d) Garner, S. A.; Krische, M. J. J. Org. Chem. 2007, 72,
5843. (e) Prieto, O.; Lam, H. W. Org. Biomol. Chem. 2008, 6, 55.
(f) Du, Y.; Xu, L.-W.; Shimizu, Y.; Oisaki, K.; Kanai, M.; Shibasaki,
M. J. Am. Chem. Soc. 2008, 130, 16146.
Data for 3a
24
Rf = 0.31 (20% EtOAc–PE); mp 128–131 °C (EtOAc–PE); [α]D
+98.6 (c 1.10, CHCl3). IR (film): 2970, 2934, 1709 (C=O), 1503,
1390, 1289, 827, 756, 700 cm–1. 1H NMR [500 MHz, (CD3)2CO]: δ
= 8.14 (d, J = 8.4 Hz, 1 H), 8.05 (d, J = 8.3 Hz, 1 H), 7.88 (d, J = 8.0
Hz, 1 H), 7.75 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H), 7.57–7.51 (m, 1 H),
7.33 (d, J = 7.3 Hz, 2 H), 7.24 (t, J = 8.0 Hz, 3 H), 7.16 (t, J = 7.0 Hz,
2 H), 5.09 (t, J = 7.7 Hz, 1 H), 3.63–3.54 (m, 1 H), 1.35 (d, J = 6.9
Hz, 3 H), 1.27 (s, 9 H). 13C NMR [125.8 MHz, (CD3)2CO]: δ =
165.1, 156.0, 148.5, 144.1, 137.0, 130.2, 129.7, 128.9, 128.6,
128.0, 127.7, 127.5, 126.8, 122.8, 78.5, 60.2, 48.1, 28.5, 19.6. ESI-
HRMS: m/z calcd for C23H27N2O2 [M + H]+: 363.2067; found:
363.2067. HPLC: Chiralcel OD-H column (i-hexane–i-PrOH,
90:10; 1.0 mL/min, 254 nm, 25 °C); tR (major) = 4.6 min, tR
(minor) = 5.9 min; 85% ee.
Data for 3f
24
Rf = 0.32 (20% EtOAc–PE); mp 142–145 °C (EtOAc–PE); [α]D
+55.0 (c 1.00, CHCl3). IR (film): 2979, 2928, 1713 (C=O), 1498,
1390, 1365, 1170, 1022, 759, 700 cm–1 1H NMR [400 MHz,
.
(CD3)2CO]: δ = 7.98 (t, J = 8.9 Hz, 2 H), 7.54–7.45 (m, 1 H), 7.45–
7.35 (m, 3 H), 7.30 (t, J = 7.4 Hz, 2 H), 7.23 (t, J = 7.5 Hz, 1 H),
6.80 (d, J = 7.5 Hz, 1 H), 5.15–4.90 (m, 1 H), 3.88–3.65 (m, 1 H),
1.37 (d, J = 6.8 Hz, 3 H), 1.28 (s, 9 H). 13C NMR [125.8 MHz,
(CD3)2CO]: δ = 174.7, 155.9, 154.1, 142.9, 135.6, 129.1, 128.0,
127.8, 126.8, 125.7, 123.4, 122.6, 78.9, 60.3, 45.1, 28.5, 19.5. ESI-
HRMS: m/z calcd for C21H25N2O2S [M + H]+: 369.1631; found:
369.1634. HPLC: Chiralpak IC column (hexane–i-PrOH, 98:2; 0.8
mL/min, 280 nm, 25 °C); tR (major) = 18.9 min, tR (minor) = 27.9
min; 88% ee.
(10) Where indicated, the relative and absolute stereochemistries of
the products were assigned by analogy with those of products
3f,g, 4d,k,q,t, which were determined by X-ray crystallography
(see Supporting Information for details). CCDC 1019731–
1019736 contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
(8) For related enantioselective copper-catalyzed reductive
hydroamination reactions, see: (a) Miki, Y.; Hirano, K.; Satoh, T.;
Miura, M. Angew. Chem. Int. Ed. 2013, 52, 10830. (b) Zhu, S.;
Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135,
15746. (c) Miki, Y.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2014, 16, 1498.
the Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif or by writing to the
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail:
deposit@ccdc.cam.ac.uk.
(9) General Procedure for the Reductive Coupling of
Vinylazaarenes with Imine 2a Using Ligand L1
A solution of the appropriate vinylazaarene (0.30 mmol),
Cu(OAc)2·H2O (3.0 mg, 0.01 mmol), (S)-DTBM-SEGPHOS (L1,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 350–354

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