Organocatalyzed enantioselective synthesis of nitroalkanes bearing all-carbon quaternary stereogenic centers through conjugate addition of acetone cyanohydrin

Article abstract of DOI:10.1055/s-2008-1078496

The first organocatalyzed phase-transfer enantioselective conjugate addition of cyanide ion derived from acetone cyanohydrin to β, β′-disubstituted nitroolefins is reported. The reaction leads to the efficient formation of nitroalkanes bearing an all-carb

Full text of DOI:10.1055/s-2008-1078496

LETTER
1857
Organocatalyzed Enantioselective Synthesis of Nitroalkanes Bearing
All-Carbon Quaternary Stereogenic Centers through Conjugate Addition of
Acetone Cyanohydrin
Synthesis of
Nit
u
roalkanes Be
c
aring
A
ll-C
a
arbonQuaternar
B
enters rnardi, Francesco Fini, Mariafrancesca Fochi,* Alfredo Ricci*
Dipartimento di Chimica Organica ‘A. Mangini’, Facoltà di Chimica Industriale, Università di Bologna, Viale Risorgimento 4,
40136 Bologna, Italy
Fax +39(051)2093654; E-mail: ricci@ms.fci.unibo.it
Received 7 April 2008
Abstract: The first organocatalyzed phase-transfer enantioselec-
tive conjugate addition of cyanide ion derived from acetone cyano-
R2O
R2O
N+
H
hydrin to b,b¢-disubstituted nitroolefins is reported. The reaction
leads to the efficient formation of nitroalkanes bearing an all-carbon
quaternary stereogenic center in up to 72% ee.
N+
R1
Br–
H
R1 Br–
Key words: asymmetric synthesis, conjugate addition, cyanohy-
N
N
drins, organocatalysis, quaternary stereogenic center
1a–c
2a–c
2a: R1 = Ph, R2 = H
1a: R1 = Ph, R2 = H
2b: R1 = Ph, R2 = PhCH2
2c: R1 = 3,5-CF3C6H3,
1b: R1 = Ph, R2 = PhCH2
1c: R1 = 3,5-CF3C6H3,
The discovery of methods for catalytic asymmetric conju-
gate additions involving C-nucleophiles is an important
target in synthesis1 and nitroalkenes, being strong Michael
acceptors, represent a suitable class of substrates for this
reaction. Moreover the resulting nitroalkanes can be con-
verted into highly functionalized and enantiomerically en-
riched organic molecules2 that contain stereogenic centers
relevant for the synthesis of biologically active com-
pounds. To the best of our knowledge there is only one
report3 of a conjugate addition that leads to the efficient
formation of an all-carbon quaternary stereogenic center
by addition of an alkyl metal to a nitroalkene under metal-
mediated catalysis.
2 = 3,5-CF3C6H3CH2
R
2 = 3,5-CF3C6H3CH2
R
Figure 1 Structure of organocatalysts
There are a number of potentially useful methods for hy-
drocyanation using various cyanating agents such as hy-
drogen cyanide,7 alkali or alkaline earth metal cyanides8
and TMSCN.9 Acetone cyanohydrin is one of the sim-
plest, most soluble, cheap and on large scale commercial-
ly available cyanide sources.10 Its use has been described
for regiospecific epoxide opening,11 as a Mitsunobu re-
agent in the cyanation of alcohols,12 and more recently in
the Strecker reaction.13 In evaluating the various alterna-
tives among the cyanation reagents, we were attracted to
a report by Armstrong14 that diastereoselective conjugate
addition of cyanide to a,b-unsaturated oxazolidinones
templates could be effected using acetone cyanohydrin
and a Lewis Acid such as samarium(III) isopropoxide.
The asymmetric conjugate addition of cyanide to a,b-un-
saturated carbonyl derivatives, leading to very important
chiral building blocks for pharmaceuticals, has been re-
cently reported by Jacobsen4 using a chiral aluminum
salen complexes and by Shibasaki5 and co-workers using
a chiral gadolinium catalyst. Both systems employ a rela-
tively expensive cyanide source, trimethylsilyl cyanide
(TMSCN).
Taking into consideration the hydrogen-bond activation
between the nitro group of nitroalkenes and protons of H-
bond donors such as ureas and thioureas,6 we first as-
sumed that these derivatives15 were probably suitable to
catalyze the reaction in an enantioselective manner. Pre-
liminary screening suggested however that these catalysts
proved to be essentially inactive for the reaction, no con-
version at all being typically observed after prolonged re-
action time.
Herein we disclose the first method for enantioselective
synthesis of nitroalkanes bearing an all-carbon quaternary
stereogenic center through conjugate addition of cyanide
(Scheme 1) to b,b¢-disubstituted nitroolefins. Asymmetric
organocatalysis, of great interest due to the conceptual im-
portance and its environmentally benign features,6 has
been used throughout.
These results along with subsequent investigations led us
to the significant conclusion that no cyanide was generat-
ed under these homogeneous conditions. Inspired by our
previous findings regarding the effectiveness of acetone
cyanohydrin as cyanide donor under phase-transfer
conditions13 we then turned our efforts to develop the cy-
anation in a biphasic system (inorganic base/organic sol-
vent). We began our screening by examining the ability of
quaternary ammonium salts derived from different cin-
NO2
NO2
organocatalysis
+
XCN
R2
CN
R1
R2
R1
Scheme 1 Hydrocyanation reaction
SYNLETT 2008, No. 12, pp 1857–1861
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1078496; Art ID: G08308ST
x
x
.x
x
.2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

1858
L. Bernardi et al.
LETTER
Table 1 Initial Screening and Optimization of the Reaction Conditionsa
NO2
NO2
NO2
catalyst (10 mol%)
NC
OH
+
+
solvent
base (s)
CN
r.t.
4
5
3
Entry
Catalyst
1a
Solvent
Base
Conversion (%)b
Yield of 4 (%)c
ee (%)d
10
1
2
toluene
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
85
80
95
95
95
94
93
95
97
95
94
65
70
60
70
58
70
75
70
72
75
72
2a
toluene
16
3
1b
toluene
32
4
2b
toluene
40
5
1c
toluene
43
6
2c
toluene
52
7
2b
toluene–CH2Cl2
(i-Pr)2O
toluene
29
8
2b
13
9
2b
41
10
11
2c
toluene
53
2c
toluene
67e
a Reactions were carried out with 3 (0.1 mmol), acetone cyanohydrin (18 mL, 0.2 mmol), catalyst (10 mol%) and solid base (0.2 mmol) in sol-
vent (1 mL) at r.t. for 18 h.
b Determined by 1H NMR spectroscopy; 8–15% of product 5 was present.
c Yields refer to isolated and chromatographically purified products.
d Determined by chiral stationary phase HPLC on an AD-H column with hexane–i-PrOH (80:20) as eluent, flow rate: 0.75 mL min–1, tR = 9.37
min (major), tR = 10.40 min (minor), l = 220 nm.
e Reaction was performed at –30 °C for 72 h.
chona alkaloids (Figure 1) to be effective in promoting alent and almost the same using five equivalents. With the
additions to b,b¢-disubstituted nitroolefins. Compound 316 aforementioned observations in hand, we set out to estab-
was employed as the test substrate.
lish the scope18 of the conjugated addition using 2c19 as
the catalyst of choice. The observed beneficial effect of
lowering the temperature on the enantioselectivity
(Table 1, entry 11) prompted us to perform the reaction at
–30 °C.
Whereas quinine and quinidine derivatives gave only ra-
cemic mixtures, more promising results were obtained
(Table 1) by using cinchonidinium (1a–c) and cinchonin-
ium (2a–c) salts, the latter leading to slightly better enan-
tioselection (compare in Table 1 entries 1, 3 and 5 with As shown in Table 2 the reactions proceeded smoothly to
entries 2, 4 and 6). Key elements for the success of the re- give the expected compounds 4 and 6–1120 in fairly good
action were the protection in the organocatalyst of the free isolated yields and with substantial enantioselectivities.
hydroxyl group at the position 9 by benzylation and the re- The electronic properties of the substituents on aromatic
placement of the meta hydrogens in these moieties by CF3 ring had a limited effect on the stereoselection of conju-
groups.
gate additions (entries 4–6). The size of the aliphatic
group on the other hand appeared to dictate the level of
enantioselectivity (entry 2) with larger groups being dele-
terious, whereas the opposite effect could be noticed (en-
try 3) on increasing the size of the aromatic moiety.
A range of solvents was examined and toluene emerged as
superior medium (better enantioselection) (compare
entries 6–8). The reaction proceeded with high conver-
sions and the expected product was isolated in fairly good
yields using various mild inorganic bases such as K2CO3 To shed some light onto the mechanism of this conjugate
and Cs2CO3. However in line with the inherent property of addition a few ancillary experiments were performed by
most b,b¢-disubstituted nitroalkenes to isomerize under changing also the cyanide source (Table 3). As expected
basic conditions or upon prolonged reaction times,17 no reaction occurred using KCN in the absence of catalyst
amounts varying up to 15% of the nonconjugated nitroalk- (entry 1) and with acetone cyanohydrin and catalysts in
ene 5, untouched under the reaction conditions, were the absence of base (entry 2). Interestingly (entry 3) the re-
found in the reaction mixture. The enantiomeric excess action with acetone cyanohydrin in the presence of the
was not influenced by the amount of acetone cyanohydrin, base led even after prolonged reaction times to very low
whereas the chemical yields were lower using one equiv- conversion (5% ca) whereas (entry 4) by using KCN in the
Synlett 2008, No. 12, 1857–1861 © Thieme Stuttgart · New York

LETTER
Synthesis of Nitroalkanes Bearing All-Carbon Quaternary Stereogenic Centers
1859
Table 2 Substrate Scope for the Organocatalytic Asymmetric Hydrocyanation of b,b¢-Disubstituted Nitroolefinsa
CF3
Br–
F3C
N+
CF3
O
H
CF3
NO2
R2
NO2
R2
NO2
R2
N
2c (10 mol%)
NC
OH
+
+
R1
R1
R1
toluene
CN
K2CO3 (s)
4, 6–11
–30 °C, 72 h
Entry
R1
Ph
Ph
R2
H
Et
H
H
H
H
H
Product
Yield (%)b
ee (%)c
67
1
2
3
4
5
6
7
4
72
60
68
75
62
64
52
6
33
2-naphthyl
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2-furyl
7
72
8
64
9
58
10
11
56
65
a Reactions were carried out with substrate (0.1 mmol), acetone cyanohydrin (18 mL, 0.2 mmol), catalyst 2c (10 mol%) and K2CO3 (28 mg, 0.2
mmol) in toluene (1 mL) at –30 °C for 72 h.
b Yields refer to isolated and chromatographically purified products.
c Determined by chiral stationary phase HPLC.
Table 3 Supplementary Experiments with Different Cyanide
presence of catalyst 2c, high conversion and substantial
enantioselectivity could be observed (entry 4). Finally re-
placing acetone cyanohydrin with more sterically hin-
dered benzophenone and fluorenone cyanohydrins, led
(entries 6 and 7) to sizeable erosion of the enantioselectiv-
ity as compared to the reaction performed under the opti-
mized conditions (entry 5).
Sourcesa
Entry
Cyanide source Base
Catalyst Conversion ee
(%)b
(%)c
1
2
KCN
–
–
–
–
–
–
NC
OH
OH
2c
–
On these grounds a preliminary mechanistic proposal for
this phase-transfer organocatalyzed conjugated addition
can be envisaged which highlights the key role played by
the organocatalyst in the formation of a chiral ion pair in
the organic medium, with the CN ion generated by inter-
action of the base with the cyanohydrin. The transfer of
the C-nucleophile at the conjugated position of the elec-
trophilic nitroolefin then follows. To date any prediction
regarding the nature of the chiral ion pair is highly specu-
lative. However, the deleterious effect on the enantio-
selectivity caused by an increase of the steric bulk in the
cyanohydrins, suggests the possibility that the catalysts
might accommodate in its chiral pocket an anionic species
more complex than a CN ion. Finally, considering the
moderate enantioselectivities in Table 2, undoubtedly in
these reactions the workability of other pathways, such as
an equilibrium occurring at level of chiral ion pair leading
to the conjugate addition product formation without rec-
ognition of the chiral organocatalytic species, appears
likely.
NC
3
4
5
K2CO3
–
–
5
KCN
2c
95
95
37
53
NC
OH
K2CO3 2c
K2CO3 2c
NC
Ph
OH
Ph
6
7
90
93
32
24
NC
OH
K2CO3 2c
a Reactions were carried out with substrate (0.1 mmol), catalyst 2c (10
mol%) and K2CO3 (28 mg, 0.2 mmol) in toluene (1 mL) at –30 °C for
72 h.
b Determined by 1H NMR spectroscopy.
c Determined by chiral stationary phase HPLC.
Synlett 2008, No. 12, 1857–1861 © Thieme Stuttgart · New York

1860
L. Bernardi et al.
LETTER
(12) Tsunoda, T.; Uemoto, K.; Nagino, C.; Kawamura, M.; Kaku,
H.; Ito, S. Tetrahedron Lett. 1999, 40, 7355.
(13) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Fini, F.; Pettersen,
D.; Ricci, A. J. Org. Chem. 2006, 71, 9869.
(14) Armstrong, A.; Convine, N. J.; Popkin, M. E. Synlett 2006,
1589.
(15) 1,3-Bis[3,5-bis(trifluoromethyl)diphenyl]thiourea and the
chiral mixed thiourea-cinchona organocatalyst discovered
by Soós were used in these experiments. See: (a) Schreiner,
P. R.; Wittkopp, A. Org. Lett. 2002, 4, 217. (b) Vakulya,
B.; Varga, S.; Csámpai, A.; Soós, T. Org. Lett. 2005, 7,
1967.
In conclusion, we have accomplished the first organocat-
alyzed phase-transfer enantioselective conjugate addition
of cyanide ion derived from acetone cyanohydrin to b,b¢-
disubstituted nitroolefins that leads to the efficient forma-
tion of an all-carbon quaternary stereogenic center. On-
going studies will include the screening of other
organocatalytic species aimed at improving the enantio-
selectivity of these reactions and their further extension to
other polysubstituted Michael acceptors.
(16) For a practical synthesis of this substrate, see: Ohta, H.;
Kobayashi, N.; Ozaki, K. J. Org. Chem. 1989, 54, 1802.
(17) Czekelius, C.; Carreira, E. M. Org. Process Res. Dev. 2007,
11, 633.
Acknowledgment
We are thankful for the funding from the National Project (PRIN)
‘Stereoselezione in sintesi Organica: Metodologie ed Applicazioni
2007’ and the ‘ex-60% MUR Funding 2007’. The financial support
of the Merck-ADP Grant 2007 is also gratefully acknowledged.
(18) Nitroalkenes were prepared according to the following
published procedures: (a) See ref. 3. (b) Martin, N. J. A.;
Ozores, L.; List, B. J. Am. Chem. Soc. 2007, 127, 8976.
(19) N,O-Di[3,5-bis(trifluoromethyl)benzyl]cinchoninium
bromide (2c): 3,5-Bis(trifluoromethyl)benzyl bromide
(0.48 mL, 2.6 mmol) was added to a suspension of
cinchonine (0.59 g, 2.0 mmol) in toluene (6 mL). The
mixture was vigorously stirred at 90 °C for 18 h and then
cooled to r.t. and filtered. The white solid obtained (0.82 g,
68%) was washed with toluene (2 × 25 mL), dried under
reduced pressure and used without further purification. 3,5-
Bis(trifluoromethyl)benzyl bromide (0.37 mL, 2.0 mmol)
and 50% aq NaOH (53 mg, 1.33 mmol) were added to a
solution of N-3,5-bis(trifluoromethyl)benzylcinchoninium
bromide (0.4 g, 0.66 mmol) in CH2Cl2 (7 mL). The reaction
mixture was stirred for 6 h at r.t. and then quenched by
addition of H2O. The aqueous layer was extracted with
CH2Cl2 (2 × 5 mL) and the combined organic layers were
dried (MgSO4), filtered and evaporated in vacuo. The crude
product was purified by chromatography on silica gel
column with hexane–EtOAc–MeOH–CH2Cl2 (5:4:2:1) as
eluent to give the title product as a pale yellow solid (0.32 g,
58%); mp 162–165 °C; [a]D20 +48.3 (c = 0.94, CHCl3). 1H
NMR (400 MHz, CDCl3): d = 8.93 (br s, 1 H), 8.74 (d, J =
7.4 Hz, 1 H), 8.37 (s, 2 H), 8.06 (s, 2 H), 7.90 (s, 2 H), 7.81
(s, 1 H), 7.54 (t, J = 7.05 Hz, 2 H), 7.43 (m, 1 H), 6.76 (br s,
1 H), 6.60 (d, J = 12.3 Hz, 1 H), 5.80 (m, 1 H), 5.53 (d, J =
12.4 Hz, 1 H), 5.23 (d, J = 10.5 Hz, 2 H), 5.04 (d, J = 17.0
Hz, 2 H), 4.82 (d, J = 12.4 Hz, 1 H), 4.65 (br s, 1 H), 4.15 (t,
J = 10.0 Hz, 1 H), 3.29 (t, J = 11.0 Hz, 1 H), 2.65 (m, 1 H),
2.49 (m, 3 H), 1.84 (m, 2 H), 1.49 (m, 1 H). 13C NMR (100
MHz, CDCl3): d = 149.2, 148.5, 139.4, 139.3, 139.0, 134.5,
134.05, 132.4 (q, J = 34 Hz), 130.0, 129.9, 128.8, 127.8,
127.5, 123.05 (q, J = 273 Hz, CF3), 124.9, 124.4, 122.5 (q,
J = 273 Hz, CF3), 122.4, 118.4, 75.1, 69.9, 66.8, 60.9, 56.0,
55.0, 37.3, 26.8, 23.4, 22.1. 19F NMR (376 MHz, CDCl3):
d = 62.9 (s, 6 F), –63.0 (s, 6 F). IR (CHCl3): 3367, 3030,
2960, 1371, 1278, 1176, 1142, 903 cm–1. ESI–MS (+): m/z =
779 [M+]. ESI–MS (–): m/z = 81, 79 [M–]. Anal. Calcd for
C37H31BrF12N2O: C, 53.70; H, 3.78; N, 3.39. Found: C,
53.74; H, 3.72; N, 3.44.
References and Notes
(1) (a) Perlmutter, P. Conjugate Addition Reactions in Organic
Synthesis; Pergamon Press: Oxford, 1992. (b) Vicario, J. L.;
Badía, D.; Carrillo, L. Synthesis 2007, 2065. (c) Sulzer-
Mossé, S.; Alexakis, A. Chem. Commun. 2007, 3123.
(d) López, F.; Minnaard, A. J.; Feringa, B. L. Acc. Chem.
Res. 2007, 40, 179. (e) Tomioka, K.; Nagaoka, Y.
Conjugate Addition of Organometallic Reagents, In
Comprehensive Asymmetric Catalysis, Vol. 3; Jacobsen, E.
N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer-Verlag: New
York, 1999, 1105–1120.
(2) (a) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini,
M. Chem. Rev. 2005, 105, 933. (b) Ono, N. The Nitro
Group in Organic Synthesis; Wiley: New York, 2001.
(c) Perekalin, V. V.; Lipina, E. S.; Berestovitskaya, V. M.;
Efremov, D. A. Nitroalkenes; John Wiley & Sons:
Chichester, 1994. (d) Nitro Compounds, Recent Advances in
Synthesis and Chemistry: Organic Nitro Chemistry Series;
Feuer, H.; Nielsen, A. T., Eds.; Wiley-VCH: Weinheim,
1990.
(3) Wu, J.; Mampreian, D. M.; Hoveyda, A. H. J. Am. Chem.
Soc. 2005, 127, 4584.
(4) (a) Jacobsen, E. N.; Mazet, C. Angew. Chem. Int. Ed. 2008,
47, 1762. (b) Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J.
Am. Chem. Soc. 2004, 126, 9928. (c) Sammis, G. M.;
Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125, 4442.
(5) Mita, T.; Sasaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem.
Soc. 2005, 127, 514.
(6) Berkessel, A.; Gröger, H. In Asymmetric Organocatalysis:
From Biomimetic Concept to Applications in Asymmetric
Synthesis; Wiley-VCH: Weinheim, 2005.
(7) (a) Synoradzki, L.; Rowicki, T.; Wlostowski, M. Org.
Process Res. Dev. 2006, 10, 103. (b) Brunel, J. M.; Holmes,
I. P. Angew. Chem. Int. Ed. 2004, 43, 2752.
(8) Ooi, T.; Uematsu, Y.; Maruoka, K. J. Am. Chem. Soc. 2006,
128, 2548; and references therein.
(9) (a) Takamura, M.; Hamashima, Y.; Usuida, H.; Kanai, M.;
Shibasaki, M. Angew. Chem. Int. Ed. 2000, 39, 1650.
(b) Liu, X.; Qin, B.; Zhou, X.; He, B.; Feng, X. J. Am. Chem.
Soc. 2005, 127, 12224. (c) Wang, J.; Hu, X.; Jiang, J.; Gou,
S.; Huang, X.; Liu, X.; Feng, X. Angew. Chem. Int. Ed. 2007,
46, 8468.
(10) Gregory, R. J. H. Chem. Rev. 1999, 99, 3649; and references
therein.
(11) Mitchell, D.; Koenig, T. M. Tetrahedron Lett. 1992, 33,
3281.
(20) General Procedure for the Hydrocyanation of b,b¢-
Disubstituted Nitroolefins: Catalyst (8.3 mg, 0.01 mmol)
was added to a screw-tapped test tube that contained a
mixture of nitroolefin (0.1 mmol), acetone cyanohydrin
(0.018 mL, 0.2 mmol) and toluene (1 mL). After the
resulting mixture had been cooled to –30 °C finely powdered
K2CO3 (28 mg, 0.2 mmol) was added in one portion. The
reaction mixture was then vigorously stirred at the same
temperature without any precaution to exclude moisture or
air. After 72 h, the reaction product was directly isolated by
Synlett 2008, No. 12, 1857–1861 © Thieme Stuttgart · New York

LETTER
Synthesis of Nitroalkanes Bearing All-Carbon Quaternary Stereogenic Centers
1861
column chromatography on silica gel with hexane–EtOAc
(5:1) as eluent.
8.03 (d, J = 2.2 Hz, 1 H), 7.94 (d, J = 8.7 Hz, 1 H), 7.87 (m,
2 H), 7.57 (m, 2 H), 7.51 (dd, J1 = 8.7 Hz, J2 = 2.2 Hz, 1 H),
4.89 (d, J = 13.0 Hz, 1 H), 4.81 (d, J = 13.0 Hz, 1 H), 1.99
(s, 3 H). 13C NMR (150 MHz, CDCl3): d = 133.13, 133.07,
132.1, 129.75, 128.3, 127.7, 127.4, 127.3, 125.6, 122.0,
120.0, 81.45, 41.5, 24.8. IR (CHCl3): 3036, 2927, 2248,
1563, 1373 cm–1. ESI–MS (+): m/z = 263 [M+ + Na].
2-(4-Chlorophenyl)-2-methyl-3-nitropropanenitrile:
HPLC on an AD-H column with hexane–i-PrOH (80:20) as
eluent, flow rate: 0.75 mL min–1, tR = 10.63 min (minor),
tR = 11.85 min (major), l = 220 nm; [a]D20 –16.7 (c = 0.65,
CHCl3). 1H NMR (400 MHz, CDCl3): d = 7.44 (s, 4 H), 4.74
(s, 2 H), 1.88 (s, 3 H). 13C NMR (100 MHz, CDCl3): d =
135.4, 133.5, 129.7, 126.9, 119.5, 81.2, 40.9, 24.9. IR
(CHCl3): 3054, 2927, 2248, 1564, 1495, 1374, 1103, 1014,
815 cm–1. ESI–MS (+): m/z = 247 [M+ + Na].
2-Methyl-3-nitro-2-phenylpropanenitrile: HPLC on an
AD-H column with hexane–i-PrOH (80:20) as eluent, flow
rate: 0.75 mL min–1, tR = 9.37 min (major), tR = 10.40 min
(minor), l = 220 nm; [a]D20 +12.4 (c = 0.45, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.38–7.53 (m, 5 H), 4.78
(d, J = 13.0 Hz, 1 H), 4.72 (d, J = 13.0 Hz, 1 H), 1.90 (s, 3
H). 13C NMR (150 MHz, CDCl3): d = 135.0, 129.6, 129.3,
125.5, 119.95, 81.6, 41.3, 24.8. IR (CHCl3): 3021, 2928,
2855, 2248, 1562, 1449, 1374, 780, 700 cm–1. ESI–MS
(+): m/z = 213 [M+ + Na].
2-Methyl-2-(naphthalen-2-yl)-3-nitropropanenitrile:
HPLC on an AD-H column with hexane–i-PrOH (95:5) as
eluent, flow rate: 0.50 mL min–1, tR = 52.59 min (minor),
tR = 54.75 min (major), l = 254 nm; [a]D20 +11.6 (c = 0.59,
CHCl3); mp 133–135 °C. 1H NMR (400 MHz, CDCl3): d =
Synlett 2008, No. 12, 1857–1861 © Thieme Stuttgart · New York

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