Highly regioselective introduction of aryl substituents via asymmetric 1,4-addition of boronic acids to linear α,β,γ,δ-unsaturated ketones

Article abstract of DOI:10.1055/s-0035-1560513

An efficient palladium(II)-catalyzed regioselective asymmetric 1,4-conjugate addition of arylboronic acids to linear α,β,γ,δ-unsaturated ketones is developed using phosphapalladacycle catalysts. The relevant 1,4-products were obtained exclusively with per

Full text of DOI:10.1055/s-0035-1560513

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, 254–258
letter
254
K. Gan et al.
Letter
Synlett
Highly Regioselective Introduction of Aryl Substituents via
Asymmetric 1,4-Addition of Boronic Acids to Linear α,β,γ,δ-
Unsaturated Ketones
Ar
O
O
Kennard Gan
∗
Pd cat. (3 mol%)
Jia Sheng Ng
ArB(OH)2
K3PO4 (1 equiv)
toluene, r.t., 48 h
Abdul Sadeer
R
R
Sumod A. Pullarkat*
18 examples
up to 94 % yield
up to >99 % ee
R = aryl, hetaryl
Division of Chemistry and Biological Chemistry, School of Physical
and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, 637371, Singapore
sumod@ntu.edu.sg
Received: 09.07.2015
Accepted after revison: 23.09.2015
Published online: 22.10.2015
When compared to the aforementioned, a highly regio-
selective methodology for the selective 1,4-addition of alkyl
or aryl substituents on conjugated α,β,γ,δ-unsaturated
enones is rare. Zhang et al. have recently reported a copper-
catalyzed methodology using Grignard reagents which pro-
ceeds at –70 °C utilizing a ferrocenyl monophosphinooxaz-
oline ligand.7 However, the attempted addition of a benzyl
moiety using the methodology led to poor yields and enan-
tiomeric excesses.
Therefore, a protocol which allows the simultaneous
control of both regio- and stereoselectivity during the
course of the 1,4-addition of aryl substituents onto linear
α,β,γ,δ-unsaturated enones when employing air- and mois-
ture-stable reagents under facile conditions is highly desir-
able.
DOI: 10.1055/s-0035-1560513; Art ID: st-2015-b0523-l
Abstract An efficient palladium(II)-catalyzed regioselective asymmet-
ric 1,4-conjugate addition of arylboronic acids to linear α,β,γ,δ-unsatu-
rated ketones is developed using phosphapalladacycle catalysts. The
relevant 1,4-products were obtained exclusively with perfect regiose-
lectivity, appreciable yields, and enantioselectivities. A wide range of di-
enone substrates as well as substituted arylboronic acids are tolerated
in this protocol which proceeds at room temperature.
Key words asymmetric catalysis, regioselectivity, phosphapallada-
cycle, boronic acid, conjugate addition
Enantioselective 1,4-addition of C-nucleophiles to α,β-
unsaturated enones serves as a powerful synthetic tool to-
ward asymmetric C–C bond formation.1–3 Despite the sub-
stantial progress achieved in this area, reports on the analo-
gous asymmetric addition of C-nucleophiles to polyconju-
gated substrates such as α,β,γ,δ-unsaturated enones have
been relatively limited due to the difficulty in simultane-
ously controlling both the regioselectivity (1,2- vs. 1,4- vs.
1,6-addition) as well as the enantioselectivity of the reac-
tion. For α,β,γ,δ-unsaturated cyclic enones, highly efficient
protocols relying on copper-based catalysts have been re-
ported by Alexakis et al., employing Grignard reagents
which can selectively yield 1,4-adducts4a as well as a regio-
divergent method employing trialkylaluminium reagents
which provides access to 1,6-adducts.4c For linear α,β,γ,δ-
unsaturated enones, selective 1,6-additions of Grignard, tri-
alkylaluminium, and zinc-based C-nucleophiles have been
reported with copper-, rhodium-, and iridium-based cata-
lytic systems.5 Furthermore, reports by Hayashi et al. have
established iridium–chiral diene catalyzed protocols that
selectively yield 1,6-adducts in an enantioselective manner
when employing boroxines.6
We have recently disclosed the efficacy of phosphapal-
ladacycles as catalysts toward the addition of arylboronic
acids to linear and cyclic α,β-unsaturated enones, thus pro-
viding a viable alternative to existing rhodium(I) and cop-
per(I)/(II) catalysts for the preparation of synthetically rele-
vant C-chiral skeletons.8 These results prompted us to fur-
ther explore the potential of chiral palladacycles as
catalysts for a regioselective addition protocol involving lin-
ear polyconjugated enones using cheap and easily accessi-
ble arylboronic acids. Of particular interest would be the re-
gioselectivity pattern exhibited by these catalysts in the
case of a conjugated substrate.
We initiated our study by choosing the reaction of
(2E,4E)-1,5-diphenylpenta-2,4-dien-1-one (1a) with two
equivalents of phenylboronic acid (2a) as our model
(Scheme 1). We proceeded to screen a range of palladacy-
cles, C1–5 to analyze their catalytic efficacy. While the C–N-
type palladacycles C1 and C2 were ineffective toward the
addition reaction (Table 1, entries 1 and 2), their phospha-
palladacycle analogues C3–5 provided more encouraging
results. This is in agreement with previous observations
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 26, 254–258

255
K. Gan et al.
Letter
Synlett
Ph
∗
O
O
Pd cat. (3 mol%)
PhB(OH)2
K3PO4 (1 equiv)
toluene, r.t, 48 h
1a
2a
3a
PPh2
Pd
NH2
Pd
NMe2
Cl
2
Cl
2
Cl
Pd
2
C1
C2
C3
Cl
2
PPh2
Pd
Pd
Ph2P
Cl
2
O
R
Fe
C5
C4
Scheme 1 Optimization of conditions for the 1,4-addition phenylboronic acid (2a) to linear polyconjugated enone 1a
that N–C palladacycles are typically inactive in this scenario
due to their innate tendency to preferentially undergo re-
ductive elimination.9 A preliminary analysis of the results
obtained revealed that phosphapalladacycle C5 was the
most effective, furnishing the desired 1,4-adduct in a highly
regioselective manner with a 40% nonoptimized yield and
53% enantiomeric excess with no 1,2- or 1,6-addition prod-
ucts observed on the crude 1H NMR spectrum (Table 1, en-
try 5). The structural attributes of this catalyst, which al-
lows it to effectively relay stereocontrol to the reaction cen-
ters on palladium(II), has been previously described.10 The
influence of the boron source was subsequently analyzed.
Use of both phenylboroxine (PhBO)3 and phenyl potassium
tionalized conjugated ketone was employed. The reaction
proved robust when relatively bulky naphthyl and substi-
tuted benzyl substrates were used (3d–f). Furthermore, the
electronic influence of the para substituent on reactivity
was clearly evident when results obtained with 3g and 3h
were compared. With an electron-donating group (4-MeO),
a moderate yield of 60% with 66% enantiomeric excess was
obtained. However, with an electron-withdrawing group
(4-F3C), high yield of 86% and 79% enantiomeric excess was
achieved. This addition procedure can also be extended to
4-halogenated aromatic substrates 3i–k. In these cases,
–
trifluoroborate salt (K+PhBF3 ), however, did not result in a
Table 1 Optimization of Conditions for the 1,4-Addition of Phenylbo-
ronic Acid (2a) to Linear Polyconjugated Enone 1aa
substantial increase in yield and enantiomeric excess (Table
1, entries 6 and 7). We then proceeded to study the impact
of the tandem increase in boronic acid concentration and
catalyst loading (5 equiv and 3 mol% vs. 2 equiv and 2.5
mol%). These modifications led to an appreciable increase
in yield to 87% and selectivity to 76% when the addition was
conducted over 48 hours at room temperature. Lowering
the reaction temperature to 0 °C did not provide consider-
able improvement in selectivity but the yield deteriorated
significantly (Table 1, entry 8 vs. 9).
Using the chosen phosphapalladacycle C5 and adopting
the optimized conditions as in Table 1, entry 8, we proceed-
ed to screen the addition of 2a to various derivatives of die-
none 1a obtained by variation of the R moiety at the car-
bonyl carbon. This yielded the addition products 3a–k
(Scheme 2) in satisfactory yields (60–94%), perfect regiose-
lectivity, and moderate enantiomeric excess (66–80%).13 In-
terestingly, although the phenylation of 2-furyl- and 2-thie-
nyl-functionalized ketones proceeded smoothly yielding 3b
and 3c, no product was observed when the 2-pyridyl-func-
Entry
Cat. (mol%)
2a (equiv)
Temp
Yield (%)b ee (%)c
1
2
3
4
5
6
7
8
9
C1 (2.5)
C2 (2.5)
C3 (2.5)
C4 (2.5)
C5 (2.5)
C5 (2.5)
C5 (2.5)
C5 (3)
2
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0 °C
0
0
n.d.
n.d.
19
2
2
<10
30
40
20
0
2
44
2
53
1 (PhBO)3
43
2 (K+PhBF3
)
n.d.
76
–
5
5
87
60
C5 (3)
79
a All reactions were performed in the presence of 0.5 mmol 2a, 0.1 mmol
1a, 2.5 or 3 mol% catalyst, 0.1 mmol K3PO4 in 0.5 mL of toluene at the stat-
ed temperature for 48 h. The structure of 3a was determined via compari-
son of 1H NMR and 13C NMR spectra with known dossiers.11
b Isolated yield after column purification
c The ee were determined via HPLC using a chiral column, chirality of 3a
was determined via comparison of optical rotation values with known dos-
siers.12
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 26, 254–258

256
K. Gan et al.
Letter
Synlett
yields obtained were consistently high (90%), with fluori-
nated and brominated substrates providing 72% enantio-
meric excess while the chlorinated derivative afforded 76%
enantiomeric excess.
Subsequently, we studied the tolerance of this protocol
to the use of other aryl boronic acids when used in conjunc-
tion with various linear dienones. Trace conversions were
observed when bulky groups (1-naphthyl and 2-naphthyl
boronic acids) were used. Tolyl boronic acids (Scheme 3, 3l–
n,q,r) in general gave comparatively low yields (60–66%)
when the methyl substituent of the incoming aryl boronic
acid moiety is aligned closer to the β carbon of the enone
substrate. In other instances, the yields were appreciably
higher (74–80%).
On the other hand, the enantiomeric excesses showed
an opposite trend, with high enantiomeric excesses ob-
tained (94–99%) when substituents on the aryl boronic acid
moiety were in the 2-position while those where the sub-
stituents are in the 3- and 4-positions gave lower enanti-
oselectivity values (60–76%). It was also noted that the ad-
dition of o-tolylboronic acids to conjugated enone sub-
strates where the R group at the carbonyl carbon were
substituted phenyls gave higher enantioselectivity values
(Scheme 3, 3l vs. 3q vs. 3r).
O
Ph
O
∗
C5 (3 mol%)
PhB(OH)2
R
R
K3PO4 (1 equiv)
toluene, r.t, 48 h
3a–k
1a–k
2a
O
O
O
∗
∗
∗
O
S
(+)-3a
85%
(–)-3b
94%
(+)-3c
80%
(76%)
(68%)
(70%)
O
O
O
∗
∗
∗
(+)-3e
86%
(72%)
(–)-3f
84%
(80%)
(–)-3d
80%
(70%)
O
O
∗
∗
OMe
CF3
(–)-3g
60%
(+)-3h
86%
(66%)
(78%)
O
O
O
∗
∗
∗
F
Cl
Br
(+)-3j
90%
(+)-3i
90%
(+)-3k
90%
(72%)
(76%)
(72%)
Scheme 2 1,4-Addition of phenylboronic acid 2a to polyconjugated enones 1a–k. All reactions were performed in the presence of 0.5 mmol 2a, 0.1
mmol 1a–k, 3 mol% catalyst, 0.1 mmol K3PO4 in 0.5 mL of toluene at the stated temperature. Isolated yields are followed by enantiomeric excesses in
brackets. The enantiomeric excess was determined by HPLC using a chiral column.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 26, 254–258

257
K. Gan et al.
Letter
Synlett
Ar
O
O
∗
Pd cat. (3 mol%)
ArB(OH)2
R
R
K3PO4 (1 equiv)
toluene, r.t, 48 h
3l–r
1a,f,j
2a–e
O
O
O
∗
∗
∗
(+)-3n
78%
(68%)
(+)-3l
66%
(94%)
(+)-3m
74%
(60%)
F
OMe
O
O
∗
∗
(+)-3p
80%
(+)-3o
80%
(76%)
(76%)
O
O
∗
∗
(+)-3q
60%
(+)-3r
62%
Cl
(>99%)
(92%)
Scheme 3 1,4-Addition of functionalized boronic acids to 1a All reactions were performed in the presence of 0.5 mmol 2a, 0.1 mmol 1a–k, 3 mol%
catalyst, 0.1 mmol K3PO4 in 0.5 mL of toluene at the stated temperature. Isolated yields are followed by enantiomeric excesses in brackets. The enantio-
meric excess was determined by HPLC using a chiral column.
In conclusion, we have developed a facile palladium(II)-
catalyzed regioselective asymmetric 1,4-addition protocol
for the reaction between arylboronic acids and linear
α,β,γ,δ-unsaturated enones which can be conducted at
room temperature using easily accessible and stable boron-
ic acids. It needs to be noted that the previous reported
method for the installation of aryl moieties on linear
α,β,γ,δ-unsaturated enones required the use of Grignard re-
agents and had to be carried out at –70 °C. The ability of the
current protocol to tolerate a wide range of substituted
enone substrates as well as arylboronic acids makes it a ver-
satile method which fills the lacunae that currently exists
with regards to the lack of a regio- and enantioselective
method for the introduction of aryl groups while allowing
the use of cheap reagents under ambient conditions. Efforts
in our laboratory are currently focused on further catalyst
development and the application of this methodology to
other asymmetric synthesis scenarios.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560513.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
(1) For selected books, see: (a) Perlmutter, P. Conjugate Addition
Reactions in Organic Synthesis; Pergamon Press: Oxford, 1992.
(b) Tomioka, K.; Nagaoka, Y. Comprehensive Asymmetric Cataly-
sis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: New
York, 1999, Chap. 31.1. (c) Kanai, M.; Shibasaki, M. Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; Wiley: New York, 2000, 2nd
ed. 569–592. (d) Lipshutz, B. H. Organometallics in Organic Syn-
thesis. A Manual; Schlosser, M., Ed.; Wiley: Chichester, 2002,
2nd ed. 665–680. (e) Berthon, G.; Hayashi, T. Catalytic Asymmet-
ric Conjugate Reactions; Córdova, A., Ed.; Wiley: Weinheim,
2010, 1–70. (f) Modern Organocopper Chemistry; Krause, N., Ed.;
Wiley-VCH: Weinheim, 2002, ; and references cited therein. For
selected reviews, see: (g) Sibi, M.; Manyem, S. Tetrahedron 2000,
56, 8033. (h) Krause, N.; Hoffmann-Röder, A. Synthesis 2001,
171. (i) Christoffers, J.; Koripelly, G.; Rosiak, A.; Rössle, M. Syn-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 26, 254–258

258
K. Gan et al.
Letter
Synlett
thesis 2007, 1279. (j) He, Q.; Xie, F.; Fu, G.; Quan, M.; Shen, C.;
Yang, G.; Gridnev, I. D.; Zhang, W. Org. Lett. 2015, 17, 2250; and
references cited therein.
(6) (a) Nishimura, T.; Yasuhara, Y.; Sawano, T.; Hayashi, T. J. Am.
Chem. Soc. 2010, 132, 7872. (b) Nishimura, T.; Noishiki, A.;
Hayashi, T. Chem. Commun. 2012, 48, 973. (c) Nishimura, T.;
Yasuhara, Y.; Hayashi, T. Angew. Chem. Int. Ed. 2006, 45, 5164.
(7) Ma, Z.; Xie, F.; Yu, H.; Zhang, Y.; Wu, X.; Zhang, W. Chem.
Commun. 2013, 49, 5292.
(8) (a) Wong, J.; Gan, K.; Chen, H. J.; Pullarkat, S. A. Adv. Synth. Catal.
2014, 356, 3391. (b) Gan, K.; Sadeer, A.; Chang, X.; Li, Y.;
Pullarkat, S. A. Organometallics 2014, 33, 5074.
(9) (a) He, P.; Lu, Y.; Dong, C.-G.; Hu, Q.-S. Org. Lett. 2007, 9, 343.
(b) Bedfore, R. B.; Betham, M.; Charmant, J. P. H.; Haddow, M. F.;
Orpen, A. G.; Pilarski, L. T.; Coles, S. J.; Hursthouse, M. B. Organo-
metallics 2007, 26, 6346.
(2) For selected rhodium-/copper-catalyzed 1,4-boronic acid addi-
tions, see: (a) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103,
2829. (b) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
(c) Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2003, 22, 4313.
(d) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A.
J.; Feringa, B. L. Chem. Rev. 2008, 108, 2824. (e) Alexakis, A.;
Benhaim, C. Eur. J. Org. Chem. 2002, 19, 3221. (f) Alexakis, A.;
Bäckvall, J. E.; Krause, N.; Pamies, O.; Dieguez, M. Chem. Rev.
2008, 108, 2796.
(3) For selected palladium-catalyzed 1,4-boronic acid additions,
see: (a) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Angew. Chem.
Int. Ed. 2003, 42, 2768. (b) Nishikata, T.; Yamamoto, Y.; Gridnev,
I. D.; Miyarau, N. Organometallics 2005, 24, 5025. (c) Nishikata,
T.; Yamamoto, Y.; Miyaura, N. Chem. Lett. 2005, 34, 720.
(d) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Chem. Lett. 2007,
36, 1442. (e) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Tetrahe-
dron. Lett. 2007, 48, 4007. (f) Nishikata, T.; Yamamoto, Y.;
Miyaura, N. Adv. Synth. Catal. 2007, 349, 1759. (g) Gini, F.;
Hessen, B.; Minnaard, A. Org. Lett. 2005, 7, 5309.
(h) Gottumukkala, A. L.; Matcha, K.; Lutz, M.; de Vries, J. G.;
Minnaard, A. Chem. Eur. J. 2012, 18, 6907. (i) Kikushima, K.;
Holder, J. C.; Gatti, M.; Stoltz, B. M. J. Am. Chem. Soc. 2011, 133,
6902. (j) Holder, J. C.; Marziale, A. N.; Gatti, M.; Mao, B.; Stoltz,
B. M. Chem. Eur. J. 2013, 19, 74. (k) Holder, J. C.; Goodman, E. D.;
Kikushima, K.; Gatti, M.; Marziale, A. N.; Stoltz, B. M. Tetrahe-
dron 2014, 71, 5781. (l) Jiang, C.; Lu, Y.; Hayashi, T. Angew. Chem.
Int. Ed. 2014, 53, 9936. (m) Liu, G.; Lu, X. J. Am. Chem. Soc. 2006,
128, 16504. (n) Song, J.; Shen, Q.; Xu, F.; Lu, X. Org. Lett. 2007, 9,
2947. (o) Zhou, F.; Yang, M.; Lu, X. Org. Lett. 2009, 11, 1405.
(p) Dai, H.; Yang, M.; Lu, X. Adv. Synth. Catal. 2008, 350, 249.
(q) Dai, H.; Lu, X. Tetrahedron. Lett. 2009, 50, 3478. (r) Tao, Z.;
Shi, M. Chem. Eur. J. 2008, 14, 3759. (s) Ma, G. N.; Zhang, T.; Shi,
M. Org. Lett. 2009, 11, 875. (t) Liu, Z.; Shi, M. Tetrahedron 2010,
66, 2619. (u) Zhang, T.; Xu, Q.; Zhang, R.; Zhang, T.; Shi, M. J. Org.
Chem. 2010, 75, 3935. (v) Wang, F.; Chen, F.; Qu, M.; Li, T.; Liu,
Y.; Shi, M. Chem. Commun. 2013, 49, 3360. (w) Gu, P.; Xu, Q.; Shi,
M. Organometallics 2013, 32, 7575. (x) Chen, J.; Lu, X.; Lou, W.;
Ye, Y.; Jiang, H.; Zeng, W. J. Org. Chem. 2012, 77, 8541. (y) Yang,
G.; Zhang, W. Angew. Chem. Int. Ed. 2013, 52, 7540. (z) Quan, M.;
Yang, G.; Xie, F.; Gridnev, I. D.; Zhang, W. Org. Chem. Front. 2015,
2, 398.
(4) (a) Hénon, H.; Mauduit, M.; Alexakis, A. Angew. Chem. Int. Ed.
2008, 47, 9122. (b) Thaler, T.; Knochel, P. Angew. Chem. Int. Ed.
2009, 48, 645. (c) Tissot, M.; Poggiali, D.; Hénon, H.; Müller, D.;
Guénée, L.; Mauduit, M.; Alexakis, A. Chem. Eur. J. 2012, 18,
8731.
(5) (a) Fillion, E.; Wilsily, A.; Liao, E. T. Tetrahedron: Asymmetry
2006, 17, 2957. (b) den Hartog, T.; Harutyunyan, S. R.; Font, D.;
Minnaard, A. J.; Feringa, B. L. Angew. Chem. Int. Ed. 2008, 47, 398.
(c) den Hartog, T.; van Dijken, D. J.; Minnaard, A. J.; Feringa, B. L.
Tetrahedron: Asymmetry 2010, 21, 1574. (d) Tissot, M.; Muller,
D.; Belot, S.; Alexakis, A. Org. Lett. 2010, 12, 2770. (e) Wencel-
Delord, J.; Alexakis, A.; Crevisy, C.; Mauduit, M. Org. Lett. 2010,
12, 4335.
(10) Pullarkat, S. A.; Leung, P. H. Top. Organomet. Chem. 2012, 43,
145.
(11) Roscales, S.; Rincón, Á.; Buxaderas, E.; Csákÿ, A. G. Tetrahedron
Lett. 2012, 53, 4721.
(12) See Supporting Information.
(13) Synthesis of Compound 3
Arylboronic acid (0.5 mmol, 5 equiv) and α,β,γ,δ-unsaturated
ketone (0.1 mmol, 1 equiv) were added to a solution of catalyst
(0.015 mmol, 3 mol%) in toluene (0.5 mL). K3PO4 (0.1 mmol, 1
equiv) was subsequently added, and the solution left to stir for
48 h. The crude adduct was then purified via silica gel chroma-
tography (n-hexanes–EtOAc = 10:1 or n-hexanes–CH2Cl2 = 1:1).
(R)-1,3,5-Triphenylpent-4-en-1-one (3a)
Light yellow oil. 1H NMR (300 MHz, CDCl3): δ = 3.51 (m, 2 H,
CH2), 4.31 (m, 1 H, CHAr), 6.40 (m, 2 H), 7.18–7.56 (m, 13 H),
7.94 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 44.0, 44.6, 126.3,
126.7, 127.3, 127.8, 128.1, 128.5, 128.7, 128.7, 130.1, 132.7,
133.1, 137.2, 137.2, 143.4, 198.2. ESI-HRMS: m/z calcd for
C
23H21O [M + H]+: 313.1592; found: 313.1591. [α]D 3.01 (c 0.7,
CHCl3). The er were determined via HPLC using a chiral column
(Daicel Chiralpak IC), n-hexanes–i-PrOH = 98:2, 0.5 mL/min,
254 nm: tR (major) = 22.1 min; tR (minor) = 25.3 min.
(+)-3,5-Diphenyl-1-(p-tolyl)pent-4-en-1-one (3e)
Light yellow oil. 1H NMR (500 MHz, CDCl3): δ = 2.39 (s, 3 H,
ArMe), 3.46 (m, 2 H, CH2), 4.29 (m, 1 H, CHAr), 6.39 (m, 2 H),
7.16–7.31 (m, 12 H), 7.84 (m, 2 H). 13C NMR (100 MHz, CDCl3):
δ = 21.7, 44.0, 44.4, 126.3, 126.6, 127.2, 127.8, 127.9, 128.3,
128.5, 128.5, 128.7, 129.3, 130.0, 132.7, 134.7, 137.3, 143.4,
143.9, 197.8. ESI-HRMS: m/z calcd for C24H23O [M + H]+:
327.1749; found: 327.1744. [α]D 0.8 (c 0.4, CH2Cl2). The er were
determined via HPLC using a chiral column (Daicel Chiralpak
IC), n-hexanes–i-PrOH = 98:2, 0.5 mL/min, 280 nm: tR (major) =
21.4 min; tR (minor) = 23.2 min.
(+)-1,5-Diphenyl-3-(p-tolyl)pent-4-en-1-one (3n)
Light yellow oil. 1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3 H,
ArMe), 3.47 (m, 2 H, CH2), 4.26 (m, 1 H, CHAr), 6.38 (m, 2 H),
7.10–7.56 (m, 12 H), 7.94 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ
= 21.2, 43.7, 44.7, 126.2, 127.6, 128.1, 128.4, 128.6, 129.4, 132.8,
133.0, 136.2, 137.3, 140.3, 198.4. ESI-HRMS: m/z calcd for
C
24H23O [M + H]+: 327.1749; found: 327.1750. [α]D 5.2 (c 0.2,
CH2Cl2). The er was determined via HPLC using a chiral column
(Daicel Chiralpak IC), n-hexanes–i-PrOH = 99:1, 0.5 mL/min,
210 nm: tR (major) = 26.5 min (major); tR (minor) = 29.9 min.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 26, 254–258