Efficient nitro-aldol reaction using SmI2: A new route to nitro alcohols under very mild conditions

Article abstract of DOI:10.1021/jo061465w

(Chemical Equation Presented) A novel method to obtain racemic 1-nitroalkan-2-ols by reaction of bromonitromethane with a variety of aldehydes and promoted by SmI₂ is reported. On the basis of these results, the chiral version has also been per

Full text of DOI:10.1021/jo061465w

these cases, enantiomeric excess of nitroaldol products, deter-
mined by chiral HPLC analysis, was reported.4a
Efficient Nitro-Aldol Reaction Using SmI2: A
New Route to Nitro Alcohols under Very Mild
Conditions
In view of its significance, there are several reviews concern-
ing the Henry reaction.5 The nitroaldol reaction is generally
performed in the presence of bases such as sodium methoxide,
sodium hydroxide, sodium carbonate, barium hydroxide, tet-
rabutylamonium hydroxide, triethylamine, LDA, or butyl-
lithium.2,5 Consequently, when the starting carbonyl compound
or the 1,2-nitro alcohol products are sensitive to the presence
of bases, other byproducts can contaminate the target 1,2-nitro
alcohols. For this reason, alternative procedures for the prepara-
tion of Henry-type adducts that obviate the use of bases would
be of great interest.6
Jose´ M. Concello´n,* Humberto Rodr´ıguez-Solla, and
Carmen Concello´n
Departamento de Qu´ımica Orga´nica e Inorga´nica, Facultad de
Qu´ımica, UniVersidad de OViedo, Julia´n ClaVer´ıa 8,
33071 OViedo, Spain
jmcg@fq.unioVi.es
Introduced by Kagan in 1977,7 samarium diiodide has been
used to perform various organic reactions, chiefly carbon-
carbon bond formation.8 However, to the best of our knowledge,
the synthesis of nitro alcohols (Henry adducts) by using
samarium diiodide has not been yet described.
ReceiVed July 14, 2006
In this paper, we describe a novel synthesis of racemic
1-nitroalkan-2-ols 3 by reaction of bromonitromethane9 with
various aldehydes promoted by SmI2, respectively. This process
take place under very mild reaction conditions. On the basis of
these results, the chiral version of this transformation has also
been performed on chiral N,N-dibenzylamino aldehydes derived
from alanine, phenylalanine, and leucine, affording the corre-
sponding 3-amino-1-nitroalkan-2-ols in high yield and good
stereoselectivity.
A novel method to obtain racemic 1-nitroalkan-2-ols by reac-
tion of bromonitromethane with a variety of aldehydes and
promoted by SmI2 is reported. On the basis of these results,
the chiral version has also been performed with chiral N,N-
dibenzyl amino aldehydes, affording the corresponding enanti-
opure 3-amino-1-nitroalkan-2-ols with good stereoselectivity.
Results and Discussion
Introduction
The initial studies on the preparation of racemic nitroalkan-
2-ols were performed using 2.5 equiv of SmI2.10 Thus, the
treatment of a solution of bromonitromethane (1.0 equiv) and
Since its introduction into organic synthesis, the nitro-aldol
reaction1 has become one of the most useful methodologies for
generating C-C bonds and obtaining polyfunctionalized mol-
ecules. The synthetic utility of the nitro-aldol reaction is based
on the versatility of the 1,2-nitro alcohols that are obtained,
which can be converted into 1,2-amino alcohols, amino sugars,
nitroketones, nitroalkenes, ketones (Nef reaction), and other
important compounds.2 Particularly, nitroaldol adducts of enan-
tiopure R-amino aldehydes can be readily converted into
pharmacologically important molecules such as the anti-HIV
drug amprenavir as well as R-hydroxy-â-amino acids, a valuable
backbone of peptide mimetics.3 However, to prepare nitroaldol
adducts from enantiopure R-amino aldehydes, chiral catalysts
or high pressures generally were necessary.4 Only in one of
(5) (a) Rosini, G.; Ballini, R. Synthesis 1988, 833-847. (b) Rosini, G.
In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, pp 321-340. (c) Shvekhgeimer,
M. A. Russ. Chem. ReV. 1998, 67, 35-68. (d) Luzzio, F. A. Tetrahedron
2001, 57, 915-945 and ref 2.
(6) (a) Li, G.; Wei, H.-X.; Wills, S. Tetrahedron Lett. 1998, 39, 4607-
4610. (b) Ramachandran, P. V.; Reddy, M. V. R.; Rudd, M. T. Tetrahedron
Lett. 1999, 40, 627-630. (c) Ramachandran, P. V.; Reddy, M. V. R.; Rudd,
M. T. Chem. Commun. 1999, 1979-1980.
(7) Namy, J.-L.; Girard, P.; Kagan, H. B. New J. Chem. 1977, 1, 5-7.
(8) Reviews of synthetic applications of SmI2: (a) Soderquist, J. A.
Aldrichimica Acta 1991, 24, 15-23. (b) Molander, G. A. Chem. ReV. 1992,
92, 29-68. (c) Molander, G. A. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 1, pp 251-
282. (d) Molander, G. A. In Organic Reactions; Paquette, L. A., Ed.; John
Wiley: New York, 1994; pp 211-367. (e) Molander, G. A.; Harris, C. R.
Chem. ReV. 1996, 96, 307-338. (f) Molander, G. A.; Harris, C. R. Tetra-
hedron 1998, 54, 3321-3354. (g) Krief, A.; Laval, A. M. Chem. ReV. 1999,
99, 745-777. (h) Steel, P. G. J. Chem. Soc., Perkin Trans. 1 2001, 2727-
2751. (i) Kagan, H. B. Tetrahedron 2003, 59, 10351-10372. (j) Concello´n,
J. M.; Rodr´ıguez-Solla, H. Chem. Soc. ReV. 2004, 33, 599-609.
(9) gem-Halo nitro derivatives could be important starting materials in
organic chemistry. However, scarce examples of their synthetic applications
have been reported: (a) Ballini, R.; Fiorini, D.; Palmieri, A. Synlett 2003,
1704-1706. (b) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.;
Rossi, M. Tetrahedron 1999, 55, 6211-6218. (c) Attanasi, O. A.; Ballini,
R.; De Crescentini, L.; Filippone, P.; Mantellini, F. J. Org. Chem. 1999,
64, 9653-9657. (d) Ballini, R.; Bosica, G.; Parrini, M. Tetrahedron Lett.
1998, 39, 7963-7964. (e) Archibald, T. G.; Baum, K. J. Org. Chem. 1988,
53, 4645-4649. (f) Marchand, A. P.; Arney, B. E.; Dave, P. R. J. Org.
Chem. 1988, 53, 443-446. (g) Marchand, A. P.; Reddy, D. S. J. Org. Chem.
1984, 49, 4078-4080. (h) Marchand, A. P.; Suri, S. C. J. Org. Chem. 1984,
49, 2041-2043.
(1) Henry, L. Bull. Soc. Chim. Fr. 1895, 13, 999.
(2) Ono, N. In The Nitro Group in Organic Synthesis; Wiley-VCH: New
York, 2001; pp 30-69.
(3) (a) Norman, B. H.; Morris, M. L. Tetrahedron Lett. 1992, 33, 6803-
6807. (b) Kawabata, T.; Kiryu, Y.; Sugiure, Y.; Fuji, K. Tetrahedron Lett.
1993, 34, 5127-5130. (c) Sasai, H.; Kim, W.-S.; Suzuki, T.; Shibasaki,
M. Tetrahedron Lett. 1994, 35, 6123-6126. (d) Corey, E. J.; Zhang, F.-
Y.; Angew. Chem., Int. Ed. 1999, 38, 1931-1934. (e) Grembecka, J.;
Kafarski, P. Mini ReV. Med. Chem. 2001, 1, 133-144.
(4) To see other reported syntheses of Henry adducts from chiral
aminoaldehydes: (a) Sohtome, Y.; Takemura, N.; Iguchi, T.; Hashimoto,
Y.; Nagasawa, K. Synlett 2006, 144-146. (b) Klein, G.; Pandiaraju, S.;
Reiser, O. Tetrahedron Lett. 2002, 43, 7503-7506. (c) Ma, D.; Pan, Q.;
Han, F. Tetrahedron Lett. 2002, 43, 9401-9403. (d) Misumi, Y.; Matsu-
moto, K. Angew. Chem., Int. Ed. 2002, 41, 1031-1033. (e) Hanessian, S.;
Devasthale, P. V. Tetrahedron Lett. 1996, 37, 987-990 and refs 3c,d. (f)
For a recent example of an enantioselective Henry reaction, see: Palomo,
C.; Oiarbide, M.; Laso, A. Angew. Chem., Int. Ed. 2005, 44, 3881-3884.
10.1021/jo061465w CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/31/2006
J. Org. Chem. 2006, 71, 7919-7922
7919

SCHEME 1. Synthesis of Nitro Alcohols 3
TABLE 1. Synthesis of Nitro Alcohols 3
SCHEME 2. Mechanistic Proposal
entry
3
R
yield (%)a
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
n-C7H15
Cy
i-Bu
>99
90
95
93
91
50
92
55
69
54
51
s-Bu
t-Bu
C9H17
b
c
PhCH2
Phc,d
-(CH2)5-
o-NO2C6H4
m-ClC6H4
c,e
10
11
3j
3k
c,e
SmI3 traces, which are present in the THF solutions of samarium
diiodide, as suggested by other works previously published.11
To prove the latest hypothesis, the reaction of octanal 1a and
bromonitromethane 2 was carried out with SmI3 (1.0 equiv)
instead of SmI2, the corresponding 1-nitrononan-2-ol 3a being
isolated in 89% yield.12 Moreover, nitro alcohols that could not
be obtained with SmI2 (phenylacetaldehyde, benzaldehyde,
o-nitrobenzaldehyde, and m-chlorobenzaldehyde) were prepared
using SmI3. So, the use of SmI3 could be a valuable alternative
to the use of SmI2.
Taking into account that reactions performed with SmI2
afforded cleaner crudes than those when SmI3 was used, all
reactions were carried out using SmI2. When compounds 3 were
not obtained using SmI2, they were performed with SmI3 (see
Table 1, entries 7, 8, 10, and 11).
a Yield of the corresponding isolated pure products 3 based on compounds
1. b Me2CdCH(CH2)2CH(Me)CH2. c The reaction was performed using
SmI3 instead of SmI2. In this case, a longer reaction time (18 h) was required.
d Compound purified by distillation. e Compounds purified by flash column
chromatography.
various aldehydes (1.0 equiv) in THF, with SmI2, at room
temperature afforded the corresponding nitro alcohol 3 in high
yield (Scheme 1).
Surprisingly, comparable yields of compounds 3 were
obtained when the reaction was carried out with sub-stoichio-
metric amounts (1.0, 0.5, or 0.35 equiv) of samarium diiodide
under the same reaction conditions. When this reaction was
carried out using lower amounts of SmI2 (0.1 equiv), a mixture
of 3, aldehyde, and bromonitromethane was obtained. This latest
result served to discard a samarium-promoted catalytic process.
Generally, cleaner reaction crudes were obtained when 1.0
equiv of SmI2 was employed rather than 0.5 or 0.35 equiv. Conse-
quently, the reactions were carried out with 1.0 equiv of SmI2,
and the results are shown in Table 1. The crude reaction products
were obtained with high purity after solvent removal under vac-
uum and filtration through a pad of Celite (Table 1, entries 1-7
and 9). Only column chromatography purification was necessary
when the reaction was performed with 0.5 or 0.35 equiv of SmI2.
The reaction is general as shown by the results compiled in
Table 1. Linear, branched, cyclic, and aromatic aldehydes were
successfully used as starting materials. This process can also
be carried out using readily enolizable aldehydes (Table 1, entry
7), and some other functionalities were compatible with this
transformation, such as the nitro group, chlorine atom, and C-C
double bonds (Table 1, entries 6, 10, and 11). When electron-
rich substituted aryl aldehydes such as p-anisaldehyde (p-MeO-
C6H4CHdO) or p-NMe2-C6H4CHdO were utilized, no reac-
tion took place. Finally, it is noteworthy that, in contrast to other
previously described methods, the reaction can be performed
with both hindered aldehydes and cyclic ketones such as
pivaldehyde 1e and cyclohexanone 1i (Table 1, entries 5 and
9, respectively).
Based on these observations we disclose the following
mechanism to explain the synthesis of nitro alcohols 3. The
reaction could be triggered by traces of the SmI3 present in the
solution of SmI2 in THF. So, SmI3 could release iodide, which
might attack the bromine atom of the bromonitromethane,
generating IBr and promoting the addition of the nitronate anion
4 to the corresponding carbonyl compound (Scheme 2). The
IBr generated could transform the SmI2 into SmI3 or SmI2Br,
which would continue the reaction. Moreover, the generated
samarium alcoholate “ROSmI2” or “ROSmIBr” 5, could also
act (similarly to SmI3 or SmI2Br) as source of iodide, and after
two successive iodide-releases would generate species such as
“(RO)3Sm” that would afford compounds 3 after hydrolysis.
This proposed mechanism is in agreement with the use of sub-
stoichiometric amounts of SmI2 or SmI3 (0.5 or 0.35 equiv).
The obtained results in the synthesis of racemic nitro alcohols
3 prompted us to test the possible application of this method
for synthesizing enantiopure 3-amino-1-nitroalkan-2-ols. When
this transformation was performed on chiral N,N-dibenzylamino
aldehydes 6, under the same reaction conditions, the correspond-
ing 3-amino-1-nitroalkan-2-ols 7 were obtained in high yields and
with a good diastereoisomeric ratio (dr) (Scheme 3, Table 2).
1
The stereoselectivity of the reaction was determined by H
NMR spectroscopy (300 MHz) on the crude products 7. The
mixture of diastereoisomers obtained was easily separated. After
The synthesis of nitro alcohols 3 using an amount <2.0 equiv
of SmI2 is inconsistent with the typical SmI2 role as monoelec-
tronic reducing agent in Barbier-type processes. Alternatively,
the reaction might be promoted by the iodide released by the
(11) (a) Kwon, D. W.; Kim, Y. H.; Lee, K. J. Org. Chem. 2002, 67,
9488-9491. (b) Concello´n, J. M.; Bernad, P. L.; Bardales, E. Chem. Eur.
J. 2004, 10, 2445-2450. (c) Concello´n, J. M.; Bardales, E.; Concello´n, C.;
Garc´ıa-Granda, S.; D´ıaz, M. R. J. Org. Chem. 2004, 69, 6923-6926.
(12) When this process was performed with 1.0, 0.5, and 0.35 equiv of
SmI3, 3a was similarly obtained with a yield ranging between 72% and
89%.
(10) The solution of SmI2 in THF was rapidly obtained by reaction of
diiodomethane with samarium powder in the presence of sonic waves:
Concello´n, J. M.; Rodr´ıguez-Solla, H.; Bardales, E.; Huerta, M. Eur. J.
Org. Chem. 2003, 1775-1778.
7920 J. Org. Chem., Vol. 71, No. 20, 2006

SCHEME 3. Synthesis of
(2R,3S)-3-Amino-1-nitroalkan-2-ols 7
H), 3.29 (br s, 1 H), 1.56-1.19 (m, 12 H), 0.82 (t, J ) 6.2 Hz, 3
H). 13C NMR (75 MHz, CDCl3): δ 80.5 (CH2), 68.6 (CH), 33.6
(CH2), 31.55 (CH2), 29.1 (CH2), 28.9 (CH2), 25.0 (CH2), 22.4 (CH2),
13.8 (CH3). HRMS: calcd for [C9H19NO3 - OH] 172.1338, found
172.1335. IR (neat): 3409, 2902, 1555, 1466, 1380 cm-1. Rf 0.3
(hexane/EtOAc 5/1).
1
1-Cyclohexyl-2-nitroethanol (3b). H NMR (300 MHz, CD-
Cl3): δ 4.47 (dd, J ) 3.4, 13.1 Hz, 1H), 4.40 (dd, J ) 8.5, 13.1
Hz, 1H), 4.10-4.04 (m, 1H), 2.5 (s, 1H), 1.83-0.99 (m, 11H).
13C NMR (75 MHz, CDCl3): δ 79.2 (CH2), 72.7 (CH), 41.3 (CH),
28.6 (CH2), 27.8 (CH2), 25.9 (CH2), 25.7 (CH2), 25.6 (CH2). MS
(70 eV) m/z (%): 127 (<1) [M - NO2]+, 83 (75), 55 (100), 41
(52). IR (neat): 3422, 2927, 1555, 1450, 1385 cm-1. Rf 0.3 (hexane/
EtOAc 5/1). Anal. Calcd for C8H15NO3: C, 55.47; H, 8.73; N, 8.09.
Found: C, 55.50; H, 8.67; N, 8.15
TABLE 2. Synthesis of Products 7
dr (%)b
yield (%)c
entry
7a
R
crude
purifiedd
crude
purifiedd
1
2
3
7a
7b
7c
Me
Bn
i-Bu
85
77
62
>95
>95
>95
quant
quant
quant
70
68
61
a Enantiomeric excess (ee) >98% was determined by chiral HPLC
(Chiracel OD-H) analysis. b Diastereoisomeric ratio (dr) determined by 300
MHz 1H NMR analysis. c Yield of the corresponding isolated pure products
based on compounds 6. d Purified by flash column chromatography.
1
4-Methyl-1-nitropentan-2-ol (3c). H NMR (300 MHz, CD-
Cl3): δ 4.40-4.31 (m, 3H), 2.94 (s, 1H), 1.88-1.72 (m, 1H) 1.51-
1.39 (m, 2H), 0.93 (d, J ) 6.3 Hz, 3H), 0.91 (d, J ) 6.3 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 80.9 (CH2), 66.8 (CH), 42.3 (CH2),
24.1 (CH), 22.9 (CH3), 21.5 (CH3). HRMS calcd for [C6H13NO3
- OH] 130.0868, found 130.0865. IR (neat): 3417, 2960, 1557,
1469, 1386 cm-1. Rf 0.3 (hexane/EtOAc 10/1).
conventional column chromatography, pure compounds 7 were
obtained with a diastereoisomeric ratio >95%.
3-Methyl-1-nitropentan-2-ol (3d). Mixture of diastereoisomers.
1H NMR (300 MHz, CDCl3): δ 4.50-4.18 (m, 4H), 2.71-2.45
(m, 2H), 2.10-2.33 (m, 2H), 1.45-1.62 (m, 4H), 1.12-1.35 (m,
6H), 0.76-0.99 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 79.5
(CH2), 78.9 (CH2), 72.3 (CH), 71.5 (CH), 38.3 (CH), 38.1 (CH),
25.4 (CH2), 24.6 (CH2), 14.4 (CH3), 13.5 (CH3), 11.4 (CH3), 11.1
(CH3). IR (neat): 3412, 2928, 1557, 1463, 1383 cm-1. Rf 0.3
(hexane/EtOAc 5/1). Anal. Calcd for C6H13NO3: C, 48.97; H, 8.90;
N, 9.52. Found: C, 48.83; H, 9.01; N, 9.50.
The absolute configuration of 7 was established by compari-
son of the spectroscopic data of 7b with those previously
reported in the literature for the same compound.3d Structures
of 7a and 7c (Table 2) were assigned by analogy.13
The enantiomeric purity of compounds 7 was determined by
chiral HPLC chromatography of 7a, showing an enantiomeric
excess (ee) >98%. A racemic mixture of 7a was prepared from
racemic alaninal 6a to exclude the possibility of coelution of
both enantiomers in HPLC.14
3,3-Dimethyl-1-nitrobutan-2-ol (3e). 1H NMR (300 MHz,
CDCl3): δ 4.51 (dd, J ) 2.3, 13.1 Hz, 1H), 4.35 (dd, J ) 10.2,
13.1 Hz, 1H), 4.01 (dd, J ) 2.3, 10.2 Hz, 1H), 2.64 (s, 1H), 0.95
(s, 9H). 13C NMR (75 MHz, CDCl3): δ 78.1(CH2), 76.1 (CH),
34.1 (C), 25.4 (3 × CH3). MS (70 eV) m/z (%): 131 (<1) [M -
H2O]+, 87 (10), 57 (100), 41 (50), 29 (25). IR (neat): 3448, 2963,
1557, 1480, 1383 cm-1. Rf 0.3 (hexane/EtOAc 5/1). Anal. Calcd
for C6H13NO3: C, 48.97; H, 8.90; N, 9.52. Found: C, 48.79; H,
9.20; N, 9.35.
Conclusions
In conclusion, we have described a novel reaction of
bromonitromethane with a variety of aldehydes in very mild
conditions promoted by SmI2 to afford nitroalkan-2-ols. Starting
from chiral N,N-dibenzyl aminoaldehydes, the corresponding
enantiopure (2R,3S)-3-amino-1-nitroalkan-2-ols were obtained
with good stereoselectivity. Other synthetic applications of these
reactions, studies directed toward fully delineating the factors
involved in these transformations, and attempts to develop the
catalytic version of this process are currently under investigation
within our laboratory.
1
4,8-Dimethyl-1-nitronon-7-en-2-ol (3f). H NMR (300 MHz,
CDCl3): δ 5.06-5.01 (m, 2H), 4.42-4.23 (m, 4H), 4.13-3.92 (m,
2H), 2.04-1.82 (m, 4H), 1.63 (s, 6H), 1.55 (s, 6H), 1.43-1.04
(m, 10H), 0.91 (t, J ) 6.3 Hz, 6H). 13C NMR (75 MHz, CDCl3):
δ 131.3 (C), 131.2 (C), 124.1 (2 × CH), 81.7 (CH2), 80.7 (CH2),
66.8 (CH), 66.4 (CH), 40.8 (CH2), 40.5 (CH2), 37.3 (CH2), 36.1
(CH2), 28.7 (CH), 28.2 (CH), 25.3 (2 × CH3), 25.1 (CH2), 24.9
(CH2), 19.7 (CH3), 18.6 (CH3), 17.4 (2 × CH3). IR (neat): 3420,
2926, 1555, 1456, 1381 cm-1. Rf 0.3 (hexane/EtOAc 5/1). Anal.
Calcd for C11H21NO3: C, 61.37; H, 9.83; N, 6.51. Found: C, 61.50;
H, 9.71; N, 6.62
1-Nitro-3-phenylpropan-2-ol (3g). 1H NMR (300 MHz, CDCl3)
and 13C NMR (75 MHz, CDCl3) have been compared with the data
previously described in ref 15. IR (neat): 3422, 3014, 2975, 2921,
1561, 1425, 1382 cm-1. Rf 0.4 (hexane/EtOAc 5/1).
Experimental Section
General Procedure. SmI2 or SmI3 (0.8 mmol, 1 equiv) in THF
(8 mL) was added to a stirred solution of bromonitromethane 2
(0.8 mmol, 1 equiv) and the corresponding carbonyl compound 1
or 6 (0.8 mmol, 1 equiv) in THF (5 mL). After stirring the reaction
at room temperature for 2 h it was quenched with aqueous HCl
(10 mL, 0.1 M) before the organic material was extracted with
dichloromethane. The combined extracts were washed with an
aqueous saturated solution of Na2S2O3 and then dried over Na2-
SO4, and the solvent was removed under reduced pressure, affording
compounds 3 or 7.
1-Nitro-2-phenylethan-2-ol (3h).1H NMR (300 MHz, CDCl3)
and 13C NMR (75 MHz, CDCl3) have been compared with the data
previously described in ref 15. IR (neat): 3430, 3050, 2981, 2926,
1555, 1420, 1375 cm-1. Rf 0.4 (hexane/EtOAc 5/1).
1
1
1-Nitrononan-2-ol (3a). H NMR (300 MHz, CDCl3): δ 4.40
1-(Nitromethyl)cyclohexanol (3i). H NMR (300 MHz, CD-
Cl3): δ 4.47 (s, 2H), 2.93 (br s, 1H), 2.1-1.1 (m, 10H). 13C NMR
(75 MHz, CDCl3): δ 80.6 (CH2), 70.7 (C), 34.8 (2 × CH2), 25.1
(CH2), 21.4 (2 × CH2). HRMS calcd for [C7H13NO3 - NO2]
113.0966, found 113.0971. IR (neat): 3398, 2927, 1549, 1450, 1380
cm-1. Rf 0.2 (hexane/EtOAc 5/1).
(dd, J ) 3.4, 12.5 Hz, 1H), 4.37-4.30 (m, 1 H), 4.29-4.24 (m, 1
(13) The addition of the anion to 5 takes place under nonchelation control,
in agreement with other previously reported addition of nucleophiles to
N,N-dibenzyl R-aminoaldehydes: (a) Reetz, M. T. Angew. Chem., Int. Ed.
1991, 30, 1531-1546. (b) Reetz, M. T. Chem. ReV. 1999, 99, 1121-1162.
(14) Chiral HPLC analysis for 7a shows ee > 98%: Chiracel-OD, UV
detector 210 nm, 0.5 mL/min, 95/5 hexane/i-PrOH, tR 37.5 min; racemic
mixture tR 34.9 and 37.5 min.
(15) Sorgedrager, M. J.; Malpique, R.; van Rantwijk, F.; Sheldon, R. A.
Tetrahedron: Asymmetry 2004, 15, 1295-1299.
J. Org. Chem, Vol. 71, No. 20, 2006 7921

1-Nitro-2-(o-nitrophenyl)ethan-2-ol (3j). 1H NMR (300 MHz,
CDCl3): δ 8.10-7.49 (m, 4H), 6.02 (dd, J ) 2.3, 9.0 Hz, 1H),
4.85 (dd, J ) 2.3, 13.3 Hz, 1H), 4.55 (dd, J ) 9.0, 13.3 Hz, 1H),
3.60 (br s, 1H). 13C NMR (75 MHz, CDCl3): δ 147.0 (C), 134.3
(CH), 134.1 (C), 129.5 (CH), 128.6 (CH), 124.8 (CH), 80.0 (CH2),
66.7 (CH). MS (70 eV) m/z (%): 166 (<1) [M - NO2]+, 148 (55),
121 (50), 91 (64), 77 (95), 65 (100), 51 (63). IR (neat): 3585,
3015, 2986, 2927, 1558, 1529, 1418, 1377, 1348 cm-1. Rf 0.25
(hexane/EtOAc 3/1). Anal. Calcd for C8H8N2O5: C, 45.29; H, 3.80;
N, 13.20. Found: C, 45.15; H, 3.97; N, 13.18.
(2R,3S)-3-Dibenzylamine-1-nitro-4-phenylbutan-2-ol (7b).
1
[R]25D, H NMR, 13C NMR, and IR spectroscopical data were in
accordance with those previously reported in ref 3d.
(2R,3S)-3-Dibenzylamine-5-methyl-1-nitrohexa-2-ol (7c). [R]25
D
1
) -2.4 (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 7.43-
7.25 (m, 10H), 4.74 (dd, J ) 1.4, 13.1 Hz, 1H), 4.47-4.41 (m,
1H), 4.16 (dd, J ) 9.6, 13.1 Hz, 1H), 3.71 (syst. AB, d, J ) 13.6
Hz, 2H), 3.61 (syst. AB, d, J ) 13.6 Hz, 2H), 2.90 (br s, 1H),
2.78-2.69 (m, 1H), 1.97-1.84 (m, 1H), 1.77-1.66 (m, 1H), 1.45-
1.31 (m, 1H), 0.99 (d, J ) 6.5 Hz, 3H), 0.91 (d, J ) 6.5 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 139.0 (2 × C), 128.8 (4 × CH),
128.4 (4 × CH), 127.2 (2 × CH), 79.9 (CH2), 70.0 (CH), 56.9
(CH), 54.5 (2 × CH2), 35.6 (CH2), 25.5 (CH), 22.9 (CH3), 22.7
(CH3). IR (neat): 3465, 3058, 2951, 2923, 2867, 1609, 1552, 1495,
1378 cm-1. Rf 0.45 (hexane/EtOAc 3/1). Anal. Calcd for
C21H28N2O3: C, 70.76; H, 7.92; N, 7.86. Found: C, 71.01; H, 8.10;
N, 7.99.
1-Nitro-2-(m-chlorophenyl)ethan-2-ol (3k). 1H NMR (300
MHz, CDCl3): δ 7.44-7.27 (m, 4H), 5.46 (dd, J ) 3.1, 7.8 Hz,
1H), 4.66-4.45 (m, 2H), 3.14 (br s, 1H). 13C NMR (75 MHz,
CDCl3): δ 140.0 (C), 134.9 (C), 130.2 (CH), 129.0 (CH), 126.1
(CH), 124.0 (CH), 80.8 (CH2), 70.2 (CH). MS (70 eV) m/z (%):
201 (10) [M]+, 154 (100), 139 (60), 91 (68), 77 (86). IR (neat):
3424, 3056, 2987, 2926, 1557, 1421, 1378 cm-1. Rf 0.2 (hexane/
EtOAc 3/1). Anal. Calcd for C8H8ClNO3: C, 47.66; H, 4.00; N,
6.95. Found: C, 47.81; H, 4.23; N, 7.06.
Acknowledgment. We thank the Ministerio de Educacio´n
y Ciencia (CTQ2004-1191/BQU) for financial support. J.M.C.
thanks Carmen Ferna´ndez-Flo´rez for her time. H.R.S. and C.C.
thank the Ministerio de Educacio´n y Ciencia for a Ramo´n y
Cajal Contract (Fondo Social Europeo) and a predoctoral FPI
fellowship, respectively. Our thanks to Vicente del Amo for
his revision of the English.
(2R,3S)-3-Dibenzylamine-1-nitrobutan-2-ol (7a). [R]25
)
D
+18.1 (c 1.1, CHCl3). 1H NMR (300 MHz, CDCl3): δ 7.41-7.27
(m, 10H), 4.87 (dd, J ) 1.8, 13.5 Hz, 1H), 4.17-4.11 (m, 1H),
3.95-3.87 (m, 1H), 3.65 (syst. AB, d, J ) 13.4 Hz, 2H), 3.28 (syst.
AB, d, J ) 13.4 Hz, 2H), 2.65-2.55 (m, 2H), 1.11 (d, J ) 6.6 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ 138.8 (2 × C), 128.8 (4 ×
CH), 128.5 (4 × CH), 127.3 (2 × CH), 79.7 (CH2), 70.9 (CH),
55.2 (CH), 54.3 (2 × CH2), 8.2 (CH3). HRMS calcd for [C18H22N2O3
- CH(OH)CH2NO2] 224.1439, found 224.1438. IR (neat): 3563,
3493, 3091, 2930, 1550, 1490, 1375 cm-1. Rf 0.4 (hexane/EtOAc
3/1).
Supporting Information Available: General procedures and
copies of 13C NMR spectra for compounds 3 and 7. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO061465W
7922 J. Org. Chem., Vol. 71, No. 20, 2006