Proline-Mediated Baylis-Hillman Reaction of Methyl Vinyl Ketone without a Co-catalyst under Solvent-Free Conditions

Article abstract of DOI:10.1055/s-0036-1588320

A proline-mediated Baylis-Hillman reaction of methyl vinyl ketone with aromatic aldehydes has been carried out without using any co-catalyst, under solvent-free conditions. The reaction works efficiently at 60 °C in the presence of a small amount of water

Full text of DOI:10.1055/s-0036-1588320

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
H. Inani et al.
Letter
Synlett
Proline-Mediated Baylis–Hillman Reaction of Methyl Vinyl Ketone
without a Co-catalyst under Solvent-Free Conditions
Heena Inani
O
OH
O
Ajit Kumar Jha
L-proline
ArCHO
Ar
Srinivasan Easwar*
H2O (1.4 equiv)
60 °C
15 derivatives
up to 97% yield
Department of Chemistry, School of Chemical Sciences and
Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri,
Distt. Ajmer, Rajasthan 305817, India
Stand-alone proline-catalysed
No co-catalyst/additive required
Solvent-free conditions
easwar.srinivasan@curaj.ac.in
Possible trifunctional role of proline
Received: 23.06.2016
Accepted after revision: 30.08.2016
Published online: 27.09.2016
served that the reaction did not proceed in the absence of
either of the two catalysts. Similarly, Guo et al. more recent-
ly reported an L-proline and L-histidine co-catalysed Bay-
lis–Hillman reaction, in which the imidazole moiety, pres-
ent in the side chain of the latter, presumably plays the role
of the Lewis base.6 In a deviation from the use of Lewis base
as co-catalysts, Gruttadauria et al. reported a proline-cata-
lysed Baylis–Hillman reaction of methyl vinyl ketone with
aryl aldehydes carried out in the presence of NaHCO3 as an
additive in DMF–H2O (9:1).7 This was reported to be the
first evidence of proline acting as a bifunctional catalyst in
the Baylis–Hillman reaction between alkyl vinyl ketones
and aryl aldehydes. However, in this case also, the additive
NaHCO3 was an essential requirement as a co-catalyst for
the success of the reaction.
DOI: 10.1055/s-0036-1588320; Art ID: st-2016-b0406-l
Abstract A proline-mediated Baylis–Hillman reaction of methyl vinyl
ketone with aromatic aldehydes has been carried out without using any
co-catalyst, under solvent-free conditions. The reaction works efficient-
ly at 60 °C in the presence of a small amount of water to afford the Bay-
lis–Hillman adducts in reasonable to very good yields over 8–48 h. The
absence of a co-catalyst suggests that proline plays a role in the proton-
transfer step of the reaction mechanism, in addition to its proposed in-
volvement in the iminium ion formation and conjugate addition. This
would, in principle, imply that proline acts as a trifunctional catalyst in
the reaction, and mechanistic studies to gain a deeper understanding
of this aspect should provide further insights in the future.
Key words Baylis–Hillman, proline, methyl vinyl ketone, solvent-free,
co-catalyst, organocatalysis
Notably, in the reports discussed above, a co-cata-
lyst/additive was essential for the success of the intermo-
lecular Baylis–Hillman reaction; the use of proline in isola-
tion proved largely unsuccessful [Scheme 1, Eq. (1)].8 Fur-
thermore, the adducts obtained under these conditions
were racemic, although enantioselectivity was observed
when proline was used in combination with a peptide9a or a
chiral tertiary amine.9b–d Additionally, most of the above
studies used a DMF–H2O mixture as the reaction medium
to maximise the efficiency,10 although a rate acceleration of
both imidazole and other azole promoted Baylis–Hillman
reactions was reported in mildly basic water solution.11,12
Carrying out reactions under solvent-free conditions or in
solely aqueous media, while avoiding the use of toxic sol-
vents, is very much sought after as an approach towards
green and sustainable chemistry. Thus, in a continuation of
our efforts towards the development of environment
friendly methodologies to achieve important C–C bond for-
mations, and in light of the above reports, we herein report
a proline-catalysed Baylis–Hillman reaction between meth-
The Baylis–Hillman reaction is one of the most versatile
and atom-economic carbon–carbon bond-forming reac-
tions, and it has fascinated the synthetic community with
its tremendous potential ever since its discovery.1,2 Few
other C–C bond-forming reactions have the power to deliv-
er such densely functionalised adducts, which can be fur-
ther transformed in a myriad of ways, leading to innumera-
ble applications.3 With the advent and remarkable growth
of organocatalysis since the turn of the century, a variety of
methods for the asymmetric version of the reaction has
emerged, offering excellent enantiocontrol.4 This has been
accompanied by a parallel development of dual-catalysed
reactions, and several such protocols involving proline in
combination with a co-catalyst to bring about the reaction
through an enamine-aldol pathway have been successful. In
one such example, Shi et al. reported that a combination of
proline and imidazole could be used to catalyse the Baylis–
Hillman reaction between methyl vinyl ketone and several
substituted benzaldehydes.5 Interestingly, the authors ob-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
H. Inani et al.
Letter
Synlett
yl vinyl ketone (2) and aryl aldehydes carried out without
any co-catalyst/additive under solvent-free conditions
[Scheme 1, Eq. (2)].
Table 1 Optimisation of L-Proline-Mediated Baylis–Hillman Reaction
of Methyl Vinyl Ketone (2) with p-Nitrobenzaldehyde (1a)a
OH
O
O
CHO
L-proline
O
L-proline
O2N
ArCHO
no reaction
Refs 5–7
O2N
(1)
(2)
DMF–H2O/
MeOH–H2O
1a
2
3a
Entry
2 (equiv) H2O (μL)
Proline
(equiv)
Temp. (°C)
Time
(h)
Yield
O
(%)b
OH
Ar
O
L-proline
This work
ArCHO
1
2
5
3
3
5
5
5
5
5
3
5
3
5
3
–
–
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.3
1.0
60
60
40
60
60
60
60
60
60
40
40
60
60
10
10
16
8
83
82
81
91
87
76
67
60
88
91
65
70
99
solvent-free
Scheme 1
3
–
4
25
50
100
250
500
25
25
25
25
25
Our endeavours started with an attempt to utilise pro-
line in the absence of a co-catalyst/additive for carrying out
a Baylis–Hillman reaction. To our pleasant surprise, under
solvent-free conditions, the reaction of 2 with p-nitrobenz-
aldehyde (1a) using 50 mol% proline at 60 °C proceeded
smoothly and cleanly to afford 83% yield of the Baylis–Hill-
man adduct 3a in just 10 h (Table 1, entry 1). Unfortunately,
as was the case with most other dual-catalysed reactions
discussed above,5–7 no induction of asymmetry in the prod-
uct was observed under these conditions.13 Similar yields of
the same adduct could be achieved with a slightly lower
stoichiometry of the ketone or upon running the reaction at
a lower temperature for a longer duration (entries 2 and 3).
We then studied the effect of water on the reaction, follow-
ing earlier reports and studies on the favourable role of wa-
ter in accelerating the Baylis–Hillman reaction.14,15 Indeed,
performing the reaction in a micro-aqueous environment
of 25 or 50 μL of H2O led to an increase in the efficiency (en-
tries 4 and 5), the former conditions affording the adduct in
91% yield in just 8 h; however, to our disappointment, the
addition of water did not produce any change in the stereo-
selectivity of the reaction. Upon increasing the amount of
water, a steady decrease in the efficiency of the reaction en-
sued (entries 6–8); the yields in these cases fell below that
for the reaction carried out in the absence of water, thus al-
luding to an intriguing role of a micro-aqueous environ-
ment. Reducing the ketone stoichiometry or lowering the
temperature of the reaction in the presence of water to
40 °C had little or no impact on the efficiency (entries 9 and
10), although lowering both the parameters together
proved unfavourable (entry 11). Finally, variation in the cat-
alyst loading led to interesting results: a drop in the yield
was observed with only 30 mol% of the catalyst, but with
stoichiometric L-proline a near quantitative yield of the
product was obtained in just 5.5 h (entries 12 and 13).
The reaction at 60 °C using 25 μL of water and 5 equiva-
lents of ketone was selected as the optimised conditions16
for generating Baylis–Hillman adducts with various aro-
matic aldehydes. As expected, reactions using electron-de-
ficient aromatic aldehydes progressed with high efficiency
5
10
18
18
18
8
6
7
8
9
10
11
12
13
8
8
8
5.5
a All reactions were performed on 1 mmol of the aldehyde.
b Isolated yield after column chromatographic purification.
to afford the adducts in very good yields in shorter reaction
times, with nicotinaldehyde (1d) needing only 3 h to afford
90% yield of the product (Table 2, entries 1–3). The reac-
tions with 4-bromo and 2-chlorobenzaldehydes also
worked well to deliver the corresponding adducts in excel-
lent yields, albeit requiring longer reaction times (entries 4
and 5). Reactions with a variety of other aldehydes, includ-
ing o-, m-, and p-substituted, disubstituted and penta-
substituted benzaldehydes, also gave reasonable yields of
the corresponding Baylis–Hillman products (entries 6–12).
The electron-neutral benzaldehyde was also examined, and
it was found to display moderate efficiency in yielding the
desired product (entry 13). Only the reaction with the
strongly electron-donating p-anisaldehyde was rather low
yielding, affording just 18% of the product even after five
days (entry 14). All the above adducts, except 3m,18 are
known compounds and showed spectroscopic data that
were consistent with their structures.
Having demonstrated the generality of the method, our
attention turned to the mechanism of this unique proline-
catalysed reaction, which proceeds without a co-catalyst or
additive [it might be argued that H2O, present in a micro
quantity in the reaction, might in itself be considered as an
additive, but it must be reiterated that the reaction works
reasonably well even in the absence of water (as shown in
Table 1)]. The mechanism of the Baylis–Hillman reaction
has always been the subject of much scrutiny. Recent re-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
H. Inani et al.
Letter
Synlett
Table 2 Baylis–Hillman Reaction between Methyl Vinyl Ketone and Ar-
methyl vinyl ketone with 4-nitrobenzaldehyde using only
proline, in the absence of NaHCO3, was unsuccessful even
after 16 h at 40 °C.
omatic Aldehydes under the Optimised Conditions17
O
OH
O
In the context of the present work, in the absence of a
co-catalyst and under solvent-free conditions, an alterna-
tive mechanism to the enaminolactone pathway proposed
by Gruttadauria might also be envisaged. Thus, it might be
possible that proline functions as the Lewis base under the
present reaction conditions, adding to the enone or to the
ene-iminium ion, if one were to take into account the likely
initial interaction of proline with the carbonyl group, in
conjugate fashion. The enamine intermediate generated by
conjugate addition to the latter, depicted by 4a in Scheme 2,
may then be expected to react with the aldehyde. The other
aspect to be stressed upon in the mechanistic pathway, in
our opinion, would be the key proton transfer step. The effi-
ciency of the present reaction, even in the absence of an ad-
ditive and under solvent-free conditions, rationally alludes
to the involvement of proline in the proton-transfer step.
This possibility is highlighted in the proposed mechanism,
illustrating the participation of proline in the proton-trans-
fer step by a H-bonding interaction, which is similar to the
role that was outlined for the bicarbonate in Gruttadauria’s
report. Thus overall, as depicted in Scheme 2, the proposed
pathway involves initial addition of enamine 4a to aldehyde
1, forming the intermediate adduct 4b. Interaction of pro-
line with 4b by H-bonding (encircled for illustration) ought
to result in the key transfer of proton, leading to intermedi-
ate adduct 4c after elimination of proline (one could also
envisage an intramolecular H-bonding interaction involv-
ing the proline that is already present at the β-position).
The pathway is then completed by a reversal of the first
step of the reaction; namely, hydrolysis of the iminium ion,
to deliver the desired product and regenerate the catalyst.
An alternative pathway, also involving participation of pro-
line in the proton-transfer step by H-bonding interaction, is
possible if proline is considered to be additionally involved
in activating the aldehyde. The corresponding iminium spe-
cies generated would then react with enamine 4a and lead
to the formation of the product. The central feature in ei-
ther case though is the proposed additional responsibility
borne by proline in delivering the product in the absence of
a co-catalyst / additive.
L-proline (0.5 equiv)
H2O (25 µL), 60 °C
ArCHO
Ar
1b–o
2 (5 equiv)
3b–o
Entry
Aldehyde
Ar
Product Time (h) Yield (%)
1
2
1b
1c
1d
1e
1f
o-NO2C6H4
p-CNC6H4
3-pyridyl
p-BrC6H4
o-ClC6H4
o-BrC6H4
p-ClC6H4
m-ClC6H4
p-FC6H4
3b
3c
3d
3e
3f
13
14
3
87
92
90
93
97
65
36
51
55
58
40
72
42
18
3
4
48
48
48
21
48
48
24
15
20
48
120
5
6
1g
1h
1i
3g
3h
3i
7
8
9
1j
3j
10
11
12
13
14
1k
1l
C6F5
3k
3l
p-CF3C6H4
4-Cl-3-NO2C6H3
Ph
1m
1n
1o
3m
3n
3o
p-OCH3C6H4
search efforts involving kinetic and theoretical studies have
resulted in a deeper understanding of the reaction from dif-
ferent perspectives, especially with regard to the rate-de-
termining step and the key proton transfer.19–23 The dual
catalyst mechanism has added an extra dimension to such
studies, with extra emphasis on proline-mediated reac-
tions. For example, for the Baylis–Hillman reaction using
proline and imidazole, Shi et al. proposed an enamine-aldol
pathway; the former being generated by the Michael addi-
tion of the co-catalyst onto the corresponding iminium spe-
cies formed from the parent ketone.5 Barbas and co-work-
ers, on the other hand, postulated a Mannich type reaction
involving a dienamine mechanism for the proline-imidaz-
ole co-catalysed aza-Baylis–Hillman reaction of β-substi-
tuted α,β-unsaturated aldehydes with α-imino esters.24 For
their proline-bicarbonate co-catalysed Baylis–Hillman re-
action of methyl vinyl ketone with aromatic aldehydes,
Gruttadauria and co-workers postulated an interesting
mechanistic pathway involving an enaminolactone.7 The
role of the bicarbonate was explained in terms of activation
of the aldehyde partner in the C–C bond formation and,
more importantly, in the proton transfer step (by many ac-
counts the rate-limiting step of the reaction), which is evi-
dent in their proposed mechanism. These postulates were
corroborated with detailed kinetic and computational stud-
ies. Pertinently, the authors reported that the reaction of
As noted above, the proton-transfer step has been the
focus of much research related to mechanistic studies of the
Baylis–Hillman reaction. The proposed H-bonding role of
proline in this key step is both intriguing and exciting from
a mechanistic perspective; it would imply that proline per-
forms a third function in the reaction, in addition to the al-
ready proposed roles in the iminium formation/conjugate
addition and aldehyde activation. The present reaction
could thus be the first time that proline is seen to act as a
trifunctional catalyst in the Baylis–Hillman reaction be-
tween methyl vinyl ketone and aldehydes. Further experi-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
H. Inani et al.
Letter
Synlett
Ar
H
O
N
O
N
OH
O
:
H
N
OH
N
+ H2O
L-proline
H
Ar
O
Ar
3
2
HN
[4b]
O
NH
[4a]
[4c]
COOH
N
H
O
Ar
1
' } ' has been used to represent the rest of a proline unit
Scheme 2 Proposed mechanistic pathway highlighting the involvement of proline in the proton-transfer step of the Baylis–Hillman reaction in the
absence of a co-catalyst
ments coupled with parallel computational studies need to
be taken up in this regard to gain a deeper insight into the
mechanism and substantiate our hypothesis.
(3) (a) Bharadwaj, K. C. RSC Adv. 2015, 5, 75923. (b) Xie, P.; Huang,
Y. Org. Biomol. Chem. 2015, 13, 8578. (c) Bhowmik, S.; Batra, S.
Curr. Org. Chem. 2014, 18, 3078. (d) Liu, T.-Y.; Xie, M.; Chen, Y.-C.
Chem. Soc. Rev. 2012, 41, 4101. (e) Rios, R. Catal. Sci. Technol.
2012, 2, 267. (f) Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Chem.
Commun. 2009, 5496.
(4) (a) Wei, Y.; Shi, M. Chem. Rev. 2013, 113, 6659. (b) Mansilla, J.;
Saa, J. M. Molecules 2010, 15, 709. (c) Masson, G.; Housseman,
C.; Zhu, J. Angew. Chem. Int. Ed. 2007, 46, 4614. (d) Shi, M.; Jiang,
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(5) Shi, M.; Jiang, J.-K.; Li, C.-Q. Tetrahedron Lett. 2002, 43, 127.
(6) Guo, P.-F.; Wei, Q.-Y.; Jiang, H.; Xie, P.-F. Res. Chem. Intermed.
2012, 38, 639.
(7) Gruttadauria, M.; Giacalone, F.; Lo Meo, P.; Marculescu, A. M.;
Riela, S.; Noto, R. Eur. J. Org. Chem. 2008, 1589.
(8) A proline-catalysed enantioselective intramolecular Baylis–
Hillman reaction in the absence of a co-catalyst has been
reported and studied, see: (a) Chen, S.-H.; Hong, B.-C.; Su, C.-F.;
Sarshar, S. Tetrahedron Lett. 2005, 46, 8899. (b) Duarte, F. J. S.;
Cabrita, E. J.; Frenking, G.; Santos, A. G. Chem. Eur. J. 2009, 15,
1734.
(9) (a) Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett. 2003,
5, 3741. (b) Tang, H.; Zhao, G.; Zhou, Z.; Zhou, Q.; Tang, C. Tetra-
hedron Lett. 2006, 47, 5717. (c) Tang, H.; Gao, P.; Zhao, G.; Zhou,
Z.; He, L.; Tang, C. Catal. Commun. 2007, 8, 1811. (d) Tang, H.;
Zhao, G.; Zhou, Z.; Gao, P.; He, L.; Tang, C. Eur. J. Org. Chem. 2008,
126.
In summary, we have reported a proline-mediated Bay-
lis–Hillman reaction of methyl vinyl ketone with aromatic
aldehydes under solvent-free conditions without the use of
any co-catalyst. To our knowledge, this is the first report of
an intermolecular Baylis–Hillman reaction that works satis-
factorily using proline in the absence of any co-catalyst. The
solvent-free conditions offer an added advantage from a
green perspective for this atom-economic C–C bond-form-
ing reaction. The role of proline in the proton-transfer step
needs to be further investigated to establish the trifunc-
tional role of proline in this reaction. Looking ahead, new
proline-based catalysts may be designed to carry out the
reaction even more efficiently under milder conditions,
while also expanding the scope to include other substrates.
In this regard, thoughtfully constructed dipeptides could
turn out to be more efficient catalysts and could potentially
offer mechanistic clues on this increasingly intriguing reac-
tion. Efforts in this direction are in progress in our group
and the results will be published in due course.
(10) Davies, H. J.; Ruda, A. M.; Tomkinson, N. C. O. Tetrahedron Lett.
2007, 48, 1461.
Acknowledgment
H.I. thanks UGC for a fellowship. S.E. thanks DST, India for research
funding. The authors thank the Central University of Rajasthan for
support.
(11) Luo, S.; Wang, P. G.; Cheng, J.-P. J. Org. Chem. 2004, 69, 555.
(12) Luo, S.; Mi, X.; Wang, P. G.; Cheng, J.-P. Tetrahedron Lett. 2004,
45, 5171.
(13) Determined by HPLC analysis on a chiral stationary phase: Chi-
ralcel OD-H column; hexane–i-PrOH, 95:5; 1 mL/min; 23.09
and 24.74 min.
References and Notes
(14) Cai, J.; Zhou, Z.; Zhao, G.; Tang, C. Org. Lett. 2002, 4, 4723.
(15) (a) Roy, D.; Patel, C.; Sunoj, R. B. J. Org. Chem. 2009, 74, 6936.
(b) Roy, D.; Sunoj, R. B. Chem. Eur. J. 2008, 14, 10530.
(16) Although a similar reaction at 40 °C gave an identical yield,
60 °C was chosen for the reactions with other aldehydes to
ensure better yields with less reactive substrates.
(17) Proline-Catalysed Baylis–Hillman Reaction; Typical Proce-
dure: Methyl vinyl ketone (2; 5.0 mmol) and H2O (25 μL) were
added to L-proline (0.5 mmol) in a 5-mL vial and the solution
was stirred for 15 min at room temperature. p-Nitrobenzalde-
hyde (1a; 1.0 mmol) was then added and the reaction mixture
was stirred for 8 h and heated at 60 °C. Direct silica gel column
chromatographic purification of the reaction mixture (EtOAc–
petroleum ether, 1:4) afforded the pure product 3a (201 mg,
(1) (a) Baylis, A. B.; Hillman, M. E. D. Ger. Offen. 1972, 2, 155, 113;
Chem. Abstr. 1972, 77, 34174q; Hillman M. E. D., Baylis, A B. US
Patent 1973, 3,743,669. (b) Morita, K.; Suzuki, Z.; Hirose, H. Bull.
Chem. Soc. Jpn. 1968, 41, 2815.
(2) For reviews and books, see: (a) Basavaiah, D.; Veeraraghavaiah,
G. Chem. Soc. Rev. 2012, 41, 68. (b) Basavaiah, D.; Reddy, B. S.;
Badsara, S. S. Chem. Rev. 2010, 110, 5447. (c) Basavaiah, D.;
Venkateswara Rao, K.; Jannapu Reddy, R. Chem. Soc. Rev. 2007,
36, 1581. (d) Basavaiah, D.; Jaganmohan Rao, A.; Satyanarayana,
T. Chem. Rev. 2003, 103, 811. (e) The Chemistry of the Morita–
Baylis–Hillman Reaction; Shi, M.; Wang, F.; Zhao, M.-X.; Wei, Y.,
Eds.; RSC Publishing: London, 2011.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

E
H. Inani et al.
Letter
Synlett
91%) as a light-brown solid. 1H NMR (CDCl3, 500 MHz): δ = 8.19
(d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 6.28 (s, 1 H), 6.04 (s,
1 H), 5.68 (d, J = 5.0 Hz, 1 H), 3.38 (d, J = 5.0 Hz, 1 H), 2.36 (s,
3 H).
(19) (a) Price, K. E.; Broadwater, S. J.; Jung, H. M.; McQuade, D. T. Org.
Lett. 2005, 7, 147. (b) Price, K. E.; Broadwater, S. J.; Walker, B. J.;
McQuade, D. T. J. Org. Chem. 2005, 70, 3980.
(20) (a) Aggarwal, V. K.; Fulford, S. Y.; Lloyd-Jones, G. C. Angew.
Chem. Int. Ed. 2005, 44, 1706. (b) Robiette, R.; Aggarwal, V. K.;
Harvey, J. N. J. Am. Chem. Soc. 2007, 129, 15513.
(18) 3-[(4-Chloro-3-nitrophenyl)(hydroxy)methyl]but-3-en-2-
one (3m): Yellow semisolid; IR (KBr): 3427, 1668, 1537 cm–1
;
1H NMR (CDCl3, 500 MHz): δ = 7.90 (d, J = 1.9 Hz, 1 H), 7.56 (dd,
J = 8.4, 1.9 Hz, 1 H), 7.52 (d, J = 8.4 Hz, 1 H), 6.31 (s, 1 H), 6.12 (s,
1 H), 5.63 (d, J = 5.9 Hz, 1 H), 3.42 (d, J = 5.0 Hz, 1 H), 2.38 (s,
3 H); 13C NMR (CDCl3, 125 MHz): δ = 200.0, 148.6, 147.8, 142.4,
131.7, 131.2, 127.9, 125.9, 123.5, 71.5, 25.3; HRMS (ESI): m/z [M
+ H] calcd. for C11H10ClNO4: 256.0298; found: 255.9916.
(21) Amarante, G. W.; Milagre, H. M. S.; Vaz, B. G.; Ferreira, B. R. V.;
Eberlin, M. N.; Coelho, F. J. Org. Chem. 2009, 74, 3031.
(22) Xu, J. J. J. Mol. Struct. (Theochem) 2006, 767, 61.
(23) Roy, D.; Sunoj, R. B. Org. Lett. 2007, 9, 4873.
(24) Utsumi, N.; Zhang, H.; Tanaka, F.; Barbas, C. F. III. Angew. Chem.
Int. Ed. 2007, 46, 1878.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E