Organocatalytic Enantioselective Transfer Hydrogenation of β-Amino Nitroolefins

Article abstract of DOI:10.1002/adsc.201600061

The asymmetric organocatalytic transfer hydrogenation of β-acylamino and β-tert-butyloxycarbonylamino nitroolefins has been successfully realised in excellent enantioselectivities and yields (up to >99% ee, 97% yield) with a simple thiourea catalyst and a Hantzsch ester as hydrogen source, giving a direct access to enantiomerically pure β-amino nitroalkanes. (Figure presented.).

Full text of DOI:10.1002/adsc.201600061

COMMUNICATIONS
DOI: 10.1002/adsc.201600061
Organocatalytic Enantioselective Transfer Hydrogenation of
b-Amino Nitroolefins
Antonino Ferraro,a Luca Bernardi,a and Mariafrancesca Fochia,*
a
Department of Industrial Chemistry “Toso Montanari”, University of Bologna, V. Risorgimento 4, 40136 Bologna, Italy
E-mail: mariafrancesca.fochi@unibo.it
Received: January 15, 2016; Revised: February 12, 2016; Published online: April 19, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600061.
Abstract: The asymmetric organocatalytic transfer
hydrogenation of b-acylamino and b-tert-butyloxy-
carbonylamino nitroolefins has been successfully re-
alised in excellent enantioselectivities and yields
(up to >99% ee, 97% yield) with a simple thiourea
catalyst and a Hantzsch ester as hydrogen source,
giving a direct access to enantiomerically pure b-
amino nitroalkanes.
Scheme 1. Asymmetric hydrosilylation of b-p-methoxyphe-
nylamino nitroolefins
Keywords: alkenes; asymmetric synthesis; hydrogen
bonds; organocatalysis; reduction
kanes with good to high enantioselectivities (79–97%
ee) were obtained.
More recently, enantioselective metal-catalysed
asymmetric hydrogenations[13] of b-acylamino nitroo-
lefins have been developed. In 2013, Wang and Zhang
Enantiomerically pure b-amino nitroalkanes are ver- used a Rh-Tangphos complex achieving high enantio-
satile intermediates in organic synthesis, owing to selectivities for b-aryl b-amino nitroalkenes (up to
their easy conversion into a variety of useful com- 93% ee) but rather poor enantioselectivities for alkyl
pounds[1] such as a-amino acids,[2] 1,2-diamines,[3] substrates (only 8–22% ee) [Scheme 2, (i)].[14] After-
monoamines,[4] a-amino carbonyls and to various moi- ward, a highly efficient enantioselective hydrogena-
eties present in biologically active molecules[5] and tion of b-acylamino nitroolefins has been successfully
pharmaceuticals such as clopidogrel,[6] oseltamivir,[7] accomplished employing an Ir-spiroPhos complex and
and asimadoline.[8]
20 atm H2 as reported by Hou[15] [Scheme 2, (ii)] and
Traditionally, the preparation of chiral b-amino ni- by a rhodium/bifunctional bisphosphine-thiourea li-
troalkanes mainly counts on asymmetric aza-Henry
(nitro-Mannich) reactions,[9] in which chiral metal
complexes and organocatalysts were utilised to afford
moderate to high enantio-/diastereoselectivities. Suita-
ble alternative approaches are represented by the
asymmetric aza-Michael addition of amines to nitroal-
kenes,[10] and by the addition of aldehydes to b-amino
nitroalkenes proceeding via enamine catalysis.[11]
The asymmetric catalytic reduction of b-amino ni-
troolefins constitutes a complementary straightfor-
ward pathway to form chiral b-amino nitroalkanes,
owing to the easy availability of starting materials. In
this context, in 2012 the asymmetric hydrosilylation of
Scheme 2. Asymmetric hydrogenation of b-acylamino nitro-
alkenes: (i) [Rh(COD)TangPhos]BF4 (1 mol%), H2 (5 atm),
b-p-methoxyphenylamino nitroolefins using 10 to
TFE, room temperature, 20 h. (ii) [Ir(COD)Cl]2/(R,R)-f-spi-
20 mol% of a simple N-sulfinylurea as a bifunctional
roPhos (0.5 mol%), H2 (20 atm), CH2Cl2, 808C, 12 h. (iii)
(Rh(NBD)2BF4/ligand/substrate ratio 1:1.1:100, CH2Cl2, H2
(50 atm)/room temperature, 24 h.
catalyst was reported (Scheme 1).[12] b-Amino nitroal-
Adv. Synth. Catal. 2016, 358, 1561 – 1565
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1561

COMMUNICATIONS
Antonino Ferraro et al.
Table 1. Selected optimisation results.[a]
gands complex employing 50 atm H2 as very recently
reported by Hu, Dong and Zhang [Scheme 2, (iii)].[16]
While direct hydrogenation uses a pressure of H2
gas, transfer hydrogenation refers to the addition of
hydrogen to a molecule from a non-H2 hydrogen
source. This synthetic technique is an attractive alter-
native to direct hydrogenation, since it does not re-
quire pressurised H2 gas nor elaborate experimental
set-ups.
Recently, many organocatalysts were extensively
used in asymmetric transfer hydrogenation processes,
especially using Hantzsch esters as readily available
and easy to handle hydrogen donors.[17] Chiral phos-
phoric acids[18] are the most used organocatalysts for
this type of reaction, even if the NH-containing orga-
nocatalysts have recently emerged in the asymmetric
catalytic transfer hydrogenation of nitroolefins (C=C
bond),[19] a,b-unsaturated aldehydes,[20] and conjugat-
ed olefins of steroids.[21]
Entry
2
Solvent
(M)
T
3
Conv. ee [%][c]
[8C] (mol%) [%][b]
1
2
3
4
5
6
7
8
a
b
b
b
b
b
b
b
b
b
b
b
p-xylene (0.1) 60
p-xylene (0.1) 60
p-xylene (0.3) 60
toluene (0.3) 60
PhCF3 (0.3)
DCM (0.3)
toluene (0.3) 60
toluene (0.3) 60
toluene (0.3) 40
toluene (0.3) 20
toluene (0.3) 40
toluene (0.3) 40
3a (10) 99
3a (10) 85
3a (5)
3a (5)
3a (5)
94
98
>99
97
>99
>99
97
98
96
96
60
40[d] 3a (5)
3a (2.5) 96
90
Following our recent study in this field,[19c] herein
we report on the catalytic asymmetric transfer hydro-
genation reaction of readily accessible b-amino nitro-
olefins 1 with Hantzsch esters 2, using a simple and
commercially available Jacobsen thiourea catalyst 3
(Scheme 3). Compared to previous work (Scheme 1
3a (1)
3a (5)
3a (5)
3b (5)
3c (5)
94
90
9
>99
97
99
>99
>99
94
10
11
12
99
96
[a]
Reaction conditions: 1a (0.05 mmol), cat. 3 (x mol%), sol-
vent, 2 (0.06 mmol), 14 h.
[b]
[c]
[d]
Determined on the crude mixture by 1H NMR analysis.
Determined by chiral stationary phase HPLC.
Reaction performed at 208C: conv. 97%, ee=97%
ble solvent. A lower catalyst loading (compare en-
tries 4, 7 and 8) gave a slight decrease in the enantio-
selectivity of the product 4a. We observed that when
the reaction temperature was decreased from 60 to
408C, the conversion remained excellent while enan-
tioselectivity reached perfect values (compare en-
tries 4 and 9). A further lowering to 208C gave
a small decrease in the conversion of 1a (compare en-
Scheme 3. Catalytic asymmetric transfer hydrogenation of b-
amino nitroolefins 1 with Hantzsch esters 2.
and Scheme 2), this protocol furnishes with a metal- tries 9 and 10).
free procedure not only b-amino nitroalkanes bearing
Using these conditions, catalysts 3b and 3c, closely
an acyl moiety at the amine, but also the correspond- related to 3a but varying in the amide N-substitu-
ing compounds with a synthetically more useful ents,[24] were applied to the reaction. Both the N,N-di-
Boc[22] protecting group. Furthermore, the products 4 ethyl derivative 3b and the N-methyl-N-benzhydryl
bearing both b-aryl and b-alkyl substituents are ob- amide 3c did not give any improvement compared to
tained with very high enantioselectivities in all cases. 3a (compare entries 9, 11 and 12).
We started our studies by testing the transfer hy-
These conditions were taken as optimal to study
drogenation reaction between (Z)-N-(2-nitro-1-phe- the scope of the reaction (Table 2). Similar to deriva-
nylvinyl)acetamide 1a[23] with ethyl Hantzsch ester 2a tive 1a, the reactions with different substrates 1b–
as hydrogen donor in p-xylene at 608C. Screening of e bearing aromatic rings substituted with either elec-
a few different thiourea catalysts immediately pointed tron-donating or electron-withdrawing groups and
to the Jacobsen derivative 3a[24] since the desired b- a 2-naphthyl substituent afforded a series of b-acyl-
amino nitroalkanes 4a was obtained in quantitative amino nitroalkanes 4b–e with excellent results (90–
conversion and 94% ee (Table 1, entry 1). Moving to 94% yield and 97 to >99% ee, entries 2–5). Notably,
the tert-butyl Hantzsch ester 2b the ee increased to under the optimised reaction conditions tert-butyl
98% (entry 2).[25] Then, a short solvent screening (en- (Z)-(2-nitro-1-phenylvinyl)carbamate 1f led to the
tries 4–6) indicated toluene (0.3M) as the most suita- corresponding b-amino nitroalkane 4f bearing the
1562
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 1561 – 1565

COMMUNICATIONS
Organocatalytic Enantioselective Transfer Hydrogenation
Table 2. Scope of the reaction.[a]
kanes 1o–q with a methyl group placed in each posi-
tion on the aromatic ring, were tested. Derivatives
4o–q could be obtained in 86–40% yields and with
very good enantioselectivities (entries 16–18). Yields
followed the order para>meta>ortho, indicating
a (not dramatic) sensitivity of the reaction to steric
factors. Enantioselectivities remained always very
high.
The absolute configuration of products 4 was deter-
mined to be S by comparison with literature data
(CSP-HPLC retention time and optical rotation [a]D
value) for compounds 4a,[15] 4f,[26,10c] 4i,[26,10c] 4h,[26]
4k[27] and 4q[28] (for details, see the Supporting Infor-
mation).
tert-Butyl (Z)-(2-nitro-1-phenylprop-1-en-1-yl)car-
bamate 1r was subjected to the optimised reaction
conditions affording a mixture of two nearly enantio-
pure diasteroisomers (1S,2R)-4r and (1S,2S)-4r in
a 2:1 ratio in 88% yield (Scheme 4).[29]
Entry
1
R1
Ph
R2
4
Yield[b] [%] ee[c] [%]
1
2
3
4
5
6
a
b
c
d
e
f
CH3
a
b
c
d
e
f
97
91
90
94
91
90
86
91
60
88
91
92
71
86
93
86
75
40
>99
>99
97
97
99
>99
>99
98
96
98
93
97
>99
>99
96
97
>99
98
4-MeOC6H4 CH3
4-ClC6H4
4-FC6H4
2-naphthyl
Ph
Ph
n-Pent
i-Bu
c-Hex
i-Pr
Et
2-furyl
4-CF3C6H4
4-NO2C6H4 t-BuO
CH3
CH3
CH3
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
t-BuO
7[d]
8[e]
9[e]
10[e]
11[e]
12[e]
13
14
15[f]
16
17
18
f
f
g
h
i
j
k
l
m
n
o
p
q
g
h
i
j
k
l
m
n
o
p
q
4-MeC6H4
3-MeC6H4
2-MeC6H4
t-BuO
t-BuO
t-BuO
[a]
Reaction conditions: 1 (0.15 mmol), cat. 3a (0.075 mmol,
5 mol%), 2b (0.18 mmol), 408C, 14 h.
Pure product 4, isolated by chromatography on silica gel.
Determined by chiral stationary phase HPLC.
On a 2.0 mmol scale.
[b]
[c]
[d]
[e]
[f]
Scheme 4.
Reaction performed at 608C.
Reaction performed at 208C.
Extensive mechanistic studies of the role of chiral
thiourea catalysts related to 3a, using kinetic, spectro-
Boc protecting group in 90% yield, and with complete scopic and computational work, have previously been
enantioselectivity (entry 6). The transfer hydrogena- performed, establishing its more stable conformations
tion of 1f could also be performed on a larger scale and mode of action.[24a] Building upon these studies
(2 mmol, Table 1, entry 7) although with a small ero- and in line with our previous hypothesis[19c] and relat-
sion in the yield (compare entries 6 and 7). It was also ed calculation results,[19d] a tentative reaction model
very pleasing to observe that the reaction could be for the transfer hydrogenation reaction of b-amino ni-
applied successfully to substrates 1g–k bearing ali- troalkenes can be reasonably put forward (Scheme 5).
phatic chain groups, which furnished the expected N- This model implies the stabilisation of the transition
Boc protected products 4g–k with excellent results state of the reaction by coordination of the nitro
(entries 8–12).
group of nitroalkenes by the thiourea moiety, while
A heteroaromatic substituent in substrate 1l was the amide oxygen coordinates the Hantzsch ester at
also well tolerated by the catalytic system, as well as its NH proton, positively charged during the hydride-
substrates 1m–o bearing aromatic rings substituted transfer step. A subsequent irreversible proton trans-
with either electron-donating or electron-withdrawing fer step leads to the (S)-adducts 4 and the pyridine
groups, the corresponding N-Boc adducts 4l–o being derivative with concomitant catalyst release.
produced with very good yields and enantioselectivi-
ties (96 to >99% ee, entries 13–16).
The very high enantioselectivities obtained with the
catalyst 3a with both the previously reported[19c] b-tri-
To evaluate the influence of the substitution pattern fluoromethyl and the present b-amino nitroolefins re-
on the benzene ring, Boc-protected b-amino nitroal- marks the reliability of this model and the good geo-
Adv. Synth. Catal. 2016, 358, 1561 – 1565
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1563

COMMUNICATIONS
Antonino Ferraro et al.
[2] a) E. Forestim, G. Palmieri, M. Petrini, R. Profeta, Org.
Biomol. Chem. 2003, 1, 4275–4281; b) R. Ballini, M.
Petrini, Tetrahedron 2004, 60, 1017–1047.
[3] a) D. Lucet, T. Le Gall, C. Mioskowski, Angew. Chem.
1998, 110, 2724–2772; Angew. Chem. Int. Ed. 1998, 37,
2580–2627; b) J. Wu, D. Wang, F. Wu, B. Wan, J. Org.
Chem. 2013, 78, 5611–5617; c) C. A. Sandoval, T.
Ohkuma, K. Muniz, R. Noyori, J. Am. Chem. Soc.
2003, 125, 13490–13503; d) H. Ooka, N. Arai, K.
Azuma, N. Kurono, T. Ohkuma, J. Org. Chem. 2008,
73, 9084–9093.
[4] B. Shen, J. N. Johnston, Org. Lett. 2008, 10, 4397–4400.
[5] a) F. A. Davis, Y. Zhang, D. Li, Tetrahedron Lett. 2007,
48, 7838–7840; b) M. E. Flanagan, T. A. Blumenkopf,
W. H. Brissette, M. F. Brown, J. M. Casavant, C. Shang-
Poa, J. L. Doty, E. A. Elliott, M. B. Fisher, M. Hines, C.
Kent, E. M. Kudlacz, B. M. Lillie, K. S. Magnuson, S. P.
McCurdy, M. J. Munchhof, B. D. Perry, P. S. Sawyer,
T. J. Strelevitz, C. Subramanyam, J. Sun, D. A. Whipple,
P. S. Changelian, J. Med. Chem. 2010, 53, 8468–8484.
[6] G. Deray, C. Bagnis, R. Brouard, J. Necciari, A. F.
Leenhardt, F. Raymond, A. Baumelou, Clin. Drug In-
vestig. 1998, 16, 319–328.
[7] J.-J. Shie, J.-M. Fang, S.-Y. Wang, K.-C. Tsai, Y.-S. E.
Cheng, A.-S. Yang, S.-C. Hsiao, C.-Y. Su, C.-H. Wong,
J. Am. Chem. Soc. 2007, 129, 11892–11893.
[8] W. Binder, J. S. Walker, Br. J. Pharmacol. 1998, 124,
647–654.
[9] a) B. Westermann, Angew. Chem. 2003, 115, 161–163;
Angew. Chem. Int. Ed. 2003, 42, 151–153; b) E. Mar-
ques-Lopez, P. Merino, T. Tejero, R. P. Herrera, Eur. J.
Org. Chem. 2009, 2401–2420; c) A. Noble, J. C. Ander-
son, Chem. Rev. 2013, 113, 2887–2939; d) H. Pellissier,
Recent Developments in Asymmetric Organocatalysis,
RSC Catalysis Series, 2010, Chapter 3, pp 123–149;
e) A. M. F. Phillips, Recent Advances on the Organoca-
talytic Asymmetric Aza-Henry Reaction, in: Current Or-
ganocatalysis, 2016, Vol. 3, (Ed: B. K. Banik), DOI:
10.2174/2213337202666150908210627.
Scheme 5. Tentative reaction model.
metrical fit between the electrostatically complemen-
tary functionalities of the catalyst and a transition
state leading to (S)-products. Moreover, the results re-
ported in Scheme 4 suggest that while the stereo-
chemistry of the conjugate addition of the hydride is
controlled very efficiently by the catalyst, there is
little, if any, stereocontrol over the ensuing proton-
transfer step(s) to the prochiral carbon of the nitro-
nate.[30] The two diastereomers at the stereogenic
centre a to the nitro group are in fact generated in
nearly equimolar amounts.[31]
In summary, we have developed a highly enantiose-
lective organocatalytic transfer hydrogenation of b-
acylamino and b-tert-butyloxycarbonylamino nitroole-
fins 1 with a simple thiourea catalyst and Hantzsch
esters 2 as hydrogen source for the direct access to
enantiomerically pure b-amino nitroalkanes.
Experimental Section
General Procedure for the Asymmetric Transfer
Hydrogenation
[10] a) L. Wang, S. Shirakawa, K. Maruoka, Angew. Chem.
2011, 123, 5439–5442; Angew. Chem. Int. Ed. 2011, 50,
5327–5330; b) D. Uraguchi, D. Nakashima, T. Ooi, J.
Am. Chem. Soc. 2009, 131, 7242–7243; c) L. Lykke, D.
Monge, M. Nielsen, K. A. Jorgensen, Chem. Eur. J.
2010, 16, 13330–13334; d) J. Wang, H. Li, L. Zu, W.
Wang, Org. Lett. 2006, 8, 1391–1394.
In a screw-cap, round-bottom vial, catalyst 3a (3.9 mg,
0.0075 mmol, 0.05 equiv.) and Hantzsch ester 2b (56 mg,
0.18 mmol, 1.2 equiv.) were added to a stirred solution of
1 (0.15 mmol) in toluene (510 mL, 0.3M). The vial was satu-
rated with nitrogen and closed with the cap. The reaction
mixture was stirred for 14 h at 408C (Pg=Ac) or for 18 h at
408C (Pg=Boc, R1 =aromatic) or for 24 h at 608C (Pg=
Boc, R1 =aliphatic). The resulting mixture was purified by
column chromatography to afford product 4.
[11] T. Mukaiyama, H. Ishikawa, H. Koshino, Y. Hayashi,
Chem. Eur. J. 2013, 19, 17789–17800.
[12] X.-W. Liu, Y. Yan, Y.-Q. Wang, C. Wang, J. Sun, Chem.
Eur. J. 2012, 18, 9204–9207.
[13] For the hydrogenation of nitroalkenes see: a) S. Li, K.
Huang, B. Cao, J. Zhang, W. Wu, X. Zhang, Angew.
Chem. 2012, 124, 8701–8704; Angew. Chem. Int. Ed.
2012, 51, 8573–8576; b) Q. Zhao, S. Li, K. Huang, R.
Wang, X. Zhang, Org. Lett. 2013, 15, 4014–4017; c) S.
Li, K. Huang, J. Zhang, W. Wu, X. Zhang, Chem. Eur.
J. 2013, 19, 10840–10844. For transfer hydrogenation
and conjugate addition, see: d) C. Czekelius, E. M. Car-
reira, Angew. Chem. 2003, 115, 4941–4943; Angew.
Chem. Int. Ed. 2003, 42, 4793–4795; e) C. Czekelius,
E. M. Carreira, Org. Lett. 2004, 6, 4575–4577; f) C. Cze-
kelius, E. M. Carreira, Org. Process Res. Dev. 2007, 11,
Acknowledgements
We acknowledge financial support from the University of Bo-
logna (RFO program).
References
[1] N. Ono, The Nitro Group in Organic Synthesis, John
Wiley & Sons, New York, 2001.
1564
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 1561 – 1565

COMMUNICATIONS
Organocatalytic Enantioselective Transfer Hydrogenation
633–636; g) O. Soltani, M. A. Ariger, E. M. Carreira,
Org. Lett. 2009, 11, 4196–4198.
[14] M. Zhou, D. Dong, B. Zhu, H. Geng, Y. Wang, X.
Zhang, Org. Lett. 2013, 15, 5524–5527.
[15] Q. Yan, M. Liu, D. Kong, G. Zi, G. Hou, Chem.
Commun. 2014, 50, 12870–12872.
[23] b-Acylamino nitroolefins were obtained by amination
of b-nitroolefins followed by protection of the obtained
b-nitroenamines following literature procedures, see: S.
Seko, I. Komoto, J. Chem. Soc. Perkin Trans. 1 1998,
2975–2976 and ref.[14]
[24] a) S. J. Zuend, E. N. Jacobsen, J. Am. Chem. Soc. 2009,
131, 15358–15374; b) S. J. Zuend, M. P. Coughlin, M. P.
Lalonde, E. N. Jacobsen, Nature 2009, 461, 968–970.
[25] For a tentative rationalisation of the superior behaviour
of tert-butyl Hantzsch ester 2b in organocatalytic asym-
metric reactions, see ref.[17b] It must also be noted that
tert-butyl ester 2b features improved solubility in
apolar solvents, compared to 2a.
[16] P. Li, M. Zhou, Q. Zhao, W. Wu, X. Hu, X.-Q. Dong,
X. Zhang, Org. Lett. 2016, 18, 40–43.
[17] a) D. Wang, D. Astruc, Chem. Rev. 2015, 115, 6621–
6686; b) S. G. Ouellet, A. M. Walji, D. W. C. MacMil-
lan, Acc. Chem. Res. 2007, 40, 1327–1339; c) S. L. You,
Chem. Asian J. 2007, 2, 820–827; d) S. J. Connon, Org.
Biomol. Chem. 2007, 5, 3407–3417; e) S. Rossi, M. Be-
naglia, E. Massolo, L. Raimondi, Catal. Sci. Technol.
2014, 4, 2708–2723; f) L. Bernardi, M. Fochi, M. Comes
Franchini, A. Ricci, Org. Biomol. Chem. 2012, 10,
2911–2922; g) C. Zheng, S.-L. You, Chem. Soc. Rev.
2012, 41, 2498–2518.
[26] C. Palomo, M. Oiarbide, A. Laso, R. López, J. Am.
Chem. Soc. 2005, 127, 17622–17623.
[27] F. Fini, V. Sgarzani, D. Pettersen, R. P. Herrera, L. Ber-
nardi, A. Ricci, Angew. Chem. 2005, 117, 8189–8192;
Angew. Chem. Int. Ed. 2005, 44, 7975–7978.
[28] C. Palomo, M. Oiarbide, R. Halder, A. Laso, R. López,
Angew. Chem. 2006, 118, 123–126; Angew. Chem. Int.
Ed. 2006, 45, 117–120.
[29] For enantioselective hydrogenation of a,b-disubstituted
nitroalkenes see: S. Li, K. Huangb, X. Zhang, Chem.
Commun. 2014, 50, 8878–8881.
[30] For our recent study on nitro-nitronate tautomerisation
processes in organocatalytic reactions, see: S. Romani-
ni, E. Galletti, L. Caruana, A. Mazzanti, F. Himo, S.
Santoro, M. Fochi, L. Bernardi, Chem. Eur. J. 2015, 21,
17578.
[31] As suggested by one of the referees (E)-(2-nitroprop-1-
en-1-yl)benzene was reacted under the optimised reac-
tion conditions obtaining the corresponding (2-nitro-
propyl)benzene in a racemic form confirming that
there is no stereocontrol over the proton transfer
step(s) to the prochiral carbon of the nitronate. The
two enantiomers at the stereogenic centre a-to the
nitro group of (2-nitropropyl)benzene are in fact gener-
ated in equimolar amounts.
[18] D. Parmar, E. Sugiono, S. Raja, M. Rueping, Chem.
Rev. 2014, 114, 9047–9153.
[19] a) N. J. A. Martin, X. Cheng, B. List, J. Am. Chem. Soc.
2008, 130, 13862–13863; b) N. J. A. Martin, L. Ozores,
B. List, J. Am. Chem. Soc. 2007, 129, 8976–8977; c) E.
Martinelli, A. C. Vicini, M. Mancinelli, A. Mazzanti, P.
Zani, L. Bernardi, M. Fochi, Chem. Commun. 2015, 51,
658–660; d) E. Massolo, M. Benaglia, M. Orlandi, S.
Rossi, G. Celentano, Chem. Eur. J. 2015, 21, 3589–3595;
e) J. F. Schneider, F. C. Falk, R. Frçhlich, J. Paradies,
Eur. J. Org. Chem. 2010, 2265–2269; f) J. F. Schneider,
M. B. Lauber, V. Muhr, D. Kratzer, J. Paradies, Org.
Biomol. Chem. 2011, 9, 4323–4327; g) J. C. Anderson,
P. J. Koovits, Chem. Sci. 2013, 4, 2897–2901; h) L.-A.
Chen, W. Xu, B. Huang, J. Ma, L. Wang, J. Xi, K.
Harms, L. Gong, E. Meggers, J. Am. Chem. Soc. 2013,
135, 10598–10601.
[20] C. Ebner, A. Pfaltz, Tetrahedron 2011, 67, 10287–10290.
[21] D. B. Ramachary, R. Sakthidevi, P. S. Reddy, RSC Adv.
2013, 3, 13497–13506.
[22] a) A. Isidro-Llobet, M. lvarez, F. Albericio, Chem.
Rev. 2009, 109, 2455–2504; b) G. Theodoridis, Tetrahe-
dron 2000, 56, 2339–2358.
Adv. Synth. Catal. 2016, 358, 1561 – 1565
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1565