A new strategy for the synthesis of γ-nitro alcohols from aliphatic nitro compounds

Article abstract of DOI:10.1055/s-2003-40203

A general method for the synthesis of γ-nitro alcohols 1 via C-C-cross-coupling of nitro compounds 3 with silyl derivatives of nitro compounds 4, deoximination of resulting substrates and selective reduction of carbonyl group of ketones 2 is elaborated.

Full text of DOI:10.1055/s-2003-40203

PAPER
1339
A New Strategy for the Synthesis of -Nitro Alcohols from Aliphatic Nitro
Compounds
R
-Nitro
A
lcohols
o
from
A
lipha
m
tic Nitro Compound
a
s
n A. Kunetsky, Alexander D. Dilman, Konstantin P. Tsvaygboym, Sema L. Ioffe,* Yury A. Strelenko,
Vladimir A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Moscow, Leninsky prosp. 47, Russian Federation
Fax +7(095)1355328; E-mail: iof@ioc.ac.ru
Received 7 March 2003
Herein we present a new strategy for the synthesis of -ni-
Abstract: A general method for the synthesis of -nitro alcohols 1
tro alcohols 1 by construction of nitro carbonyl deriva-
via C–C-cross-coupling of nitro compounds 3 with silyl derivatives
tives 2 from two molecules of aliphatic nitro compounds
(ANC) (Scheme 1).
of nitro compounds 4, deoximination of resulting substrates and se-
lective reduction of carbonyl group of ketones 2 is elaborated.
Key words: -nitro alcohols, aliphatic nitro compounds, new strat- ANC 3 can be primary, secondary, or nitro methane.
egy, N,N-bis(silyloxy)enamines, selective reduction
Compound 3 is used as nitro anion 5, and its nitro group
is preserved in the final nitro alcohol 1 (Scheme 2). ANC
4 must possess a methyl group at the -carbon atom,
which is eventually transformed into the methylene group
of 1. In the proposed method the ANC 4 is used as doubly
silylated derivatives – N,N-bis(silyloxy)enamines (BENA)
6.5 The nitro group of 4 is finally converted into the hy-
droxyl group of 1 (Scheme 2).
Aliphatic nitro alcohols constitute a class of useful inter-
mediates. Their utility in the total synthesis of natural
products,1 as well as their ability to serve as precursors to
aminoalcohols,2,3 may explain the growing interest in
these compounds. However, different types of nitro alco-
hols are investigated to varying degrees. Indeed, various
aspects of the chemistry of -nitro alcohols are very well
elaborated. At the same time, -nitro alcohols 1 are scant-
ily studied, and to date there are no general methods for
their synthesis. The occasional examples of the prepara-
tion of -nitro alcohols usually involve chemoselective re-
duction of their nearest precursors, corresponding
carbonyl compounds 2 obtained from either -haloke-
tones or , -enones (Scheme 1).4
The proposed strategy towards -nitro alcohols includes
three steps, namely, the C–C-cross-coupling of anions 5
with BENA 6 affording -nitrooxymes 7 followed by
deoxymination and carbonyl group reduction (Scheme 2,
Table 1).
We already studied in detail the first step.6 In general it
proceeds smoothly if N,N-bis(silyloxy)enamines 6 have a
terminal double bond (i.e. the starting ANC 3 has a methyl
substitutient).
However, this approach, which includes different manip-
ulations with functional groups on a fixed carbon skele-
ton, has quite limited scope owing to difficulties
associated with introduction of the nitro group.
For the deoximination of compounds 7 we tested several
– 8
known reagents such as HCl,7 [Et3NH]+CrClO3 ,
Bu4NMnO4,9 and levulinic acid,10 none of which turned
out to be generally applicable. For example, while treat-
Hal
O
O
NaNO2 or
AgNO2
NO2
O
NO2
R2
NO2
R3
R1
R1
R3
R3
R2
R1
R2
R3
R1
R2
HNO2
2
3
4
[H]
NO2 OH
R3
R1
R2
1
Scheme 1
Synthesis 2003, No. 9, Print: 03 07 2003.
Art Id.1437-210X,E;2003,0,09,1339,1346,ftx,en;P02403SS.pdf.
© Georg Thieme Verlag Stuttgart · New York

1340
R. A. Kunetsky et al.
PAPER
der these conditions aldoximes were smoothly oxidized to
carboxylic acids (for 2h–j R3 = OH).
The choice of procedure for selective reduction of keto or
carboxy group in compounds 2 depends on the type of
substrate. In the case of unfunctionalized -nitro ketones
and acids the BH3·THF worked well leading to desired
products without reduction of the nitro group in accor-
dance with literature data.12 It should be noted that the
common reducing agent for ketones – sodium borohy-
dride – is often not applicable to compound 2 owing to
facile elimination of HNO2.
We found that the presence of a nitro function at the -po-
sition to the carbonyl group significantly slows down the
reduction of the latter by BH3·THF. This phenomenon de-
creases the chemoselectivity of the reduction of corre-
sponding compounds 2. Thus, reaction of ketone 2e,
having an additional ester group, with BH3·THF gave rise
to desired alcohol 1e, along with diol 8b, which can be ob-
tained as the sole product when larger amounts of the re-
ducing agent are used. The reduction of ketones 2k,l with
BH3·THF was even less selective, with the yields of de-
sired alcohols being 31% and 44%, respectively. The re-
duction of acid 2j containing the ester function was also
non-selective. The latter observation was very surprising,
Scheme 2
ment of 7a,b with 6% HCl gave ketones 2a,b in 59% and
89% yields respectively, deoximination of derivative 7c
under the same conditions was accompanied by elimina-
tion of HNO2 from the desired product.
The most suitable reagent for the deoximinaton proved to
be CrO3/H2SO4 in aqueous acetone (Jones reagent),11
which neither caused elimination of HNO2 nor affected
other functional groups present in molecule 7. Though un-
Table 1 Synthesis of -Nitro Alcohols
Entry R1
R2
R3
ANC
3
BENA Oxime Yield of Ketone or Yield of 2 Alcohol or Diol, Yield of
6
7
7 (%)
72
72
90
90
81
71
71
64
40
47
55
62
76
55
Acid 2
(%)a
89
77
80
80
90
91
91
50
77
57
80
78
86
58
1 or 8
1a
1b
1c
1 or 8 (%)b,c
86 (43)
95 (58)
78d (51)
74 (48)
85 (45)
84d (47)
74 (48)
90
1
2
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
3a
3b
3c
3c
3d
3e
3e
3f
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6b
6b
6c
6c
7a
7b
7c
7c
7d
7e
7e
7f
7g
7h
7i
2a
Et
2b
2c
3
(CH2)2CO2Me
(CH2)2CO2Me
-(CH2)5-
H
4
H
2c
8a
1d
1e
5
2d
2e
6
(CH2)2CO2Me Me
(CH2)2CO2Me Me
7
2e
8b
1f
8
H
H
2f
9
Ph
Me
3g
3d
3a
3e
2g
1g
1h
1i
85
10
11
12
13
14
-(CH2)5-
2he
2ie
2je
2k
2l
62
Me
Me
H
68
(CH2)2CO2Me Me
H
7j
7k
7l
1j
54f
Et
H
H
H
(CH2)2CO2Me 3b
(CH2)2CO2Me 3f
1k
1l
31
44
a Deoximinaton with CrO3/H2O/H2SO4 in aqueous acetone.
b Reduction with BH3·THF if not mentioned otherwise.
c The yields in parentheses refer to the procedure [3 + 6] → 1 or 8 without purification of intermediate compounds and are given with respect
to ANC 3 or BENA 6 (for 1b).
d Reduction with NaBH3CN/HCl in MeOH.
e R3 = OH.
f Reduction conditions: 1) (PhO)2POCl/Et3N; 2) NaBH4/THF.
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

PAPER
-Nitro Alcohols from Aliphatic Nitro Compounds
1341
4-Nitro-4-phenylpentan-2-one Oxime (7g)
since acids are known to be much more reactive then es-
ters with respect to BH3·THF.12
To a solution of DBU (0.14 mL, 0.95 mmol) in CH2Cl2 (5 mL) at 5
°C was added -nitroethylbenzene (151 mg, 1 mmol), the reaction
mixture was stirred at 5 °C for 5 min, a solution of BENA 6a (243
mg, 1.05 mmol) in CH2Cl2 (3 mL) was added dropwise at 5 °C for
5 min. The reaction mixture was stirred at 5 °C for 1 h. A mixture
of NH4F (39 mg, 1.05 mmol), HOAc (0.07 mL, 1.3 mmol), and
MeOH (2.7 mL) was added over 5 min and the reaction mixture was
poured into H2O–Et2O (1:1, 20 mL). The aqueous layer was extract-
ed with Et2O (3 × 10 mL). The combined organic layers were
washed with brine, dried (Na2SO4) and evaporated. The residue was
recrystallized from petroleum ether–toluene (5:1) to give 88 mg of
7g (40%, anti-isomer); mp 100–105 °C.
The problems outlined above prompted us to find another
reducing agents for functionalized substrates 2. Since
there is no general solution, it was necessary to find spe-
cial conditions for each species. Thus, compounds 2c,e
were cleanly reduced by NaBH3CN in methanol in the
presence of HCl13 (Scheme 3). However, no reduction of
ketone 2l took place with NaBH3CN.
For reduction of acid 2j we used (PhO)2POCl to give
mixed anhydride which was treated with NaBH4 accord-
ing to a known procedure14 (Scheme 4).
1H NMR (CDCl3): = 1.44 (s, 3 H, MeCNO2), 1.81 (s, 3 H,
2
CH3C=NOH), 2.94 (d, 1 H, CHAHB, J = 14.8 Hz), 3.27 (d, 1 H,
-Nitro alcohols 1b,c,e,g,k were obtained as a diastereo-
meric ratio (1:2–1:2.7).
2
CHAHB, J = 14.8 Hz), 7.10–7.32 (m, 5 H, C6H5), 9.26 (br, 1 H,
OH).
13C NMR (CDCl3): = 14.2 (CH3C=N), 23.4 (CH3CNO2), 45.0
(CH2), 91.4 (CNO2), 125.0, 128.6 (o,m-CHPh), 128.8 (p-CHPh),
139.6 (i-CPh), 152.2 (C=N).
It is of special note that in most cases the whole three-step
sequence, [3 + 6]→7→2→1 (or 8), can be performed
without purification of intermediate compounds in about
50% yield with respect to ANC 3 (see Table 1).
Anal. Calcd for C11H14N2O3: C, 59.45; H, 6.35; N, 12.61. Found: C,
59.80; H, 6.37; N, 12.58.
In conclusion, we have demonstrated that -nitro alcohols
1 can be assembled simply in a facile manner from two
molecules of aliphatic nitro compounds. Our future stud-
ies will be aimed at the development of diastereo- and
enantioselective approaches toward -nitro and -ami-
noalcohols.
3-Methyl-3-nitrobutanal Oxime (7i)
To a solution of 2-nitropropane (1.35 mL, 15 mmol) in Et2O (120
mL) at 5 °C was added DBU (2.24 mL, 15 mmol), the reaction mix-
ture was stirred at 5 °C for 5 min, a solution of BENA 5b (3.285 g,
15 mmol) in mixture of Et2O–benzene (1:1, 60 mL) was added
dropwise at 5 °C over 1 h. The reaction mixture was stirred at 5 °C
for 2 h. A mixture of NH4F (0.555 g, 15 mmol), HOAc (1.29 mL,
22.5 mmol), and MeOH (24 mL) was added and after stirring for 20
min the reaction mixture was poured into H2O (150 mL). The aque-
ous layer was extracted with Et2O (4 × 40 mL), the combined organ-
ic layers were washed with brine, dried (Na2SO4), and evaporated to
give 1.20 g of 7i (55%, syn:anti, 1:1), purity >95% (1H NMR); oil.
NMR spectra were recorded on a Bruker AM-300, WM-250, and
AC-200 instruments. Chemical shifts were measured relative to the
residual solvent peak (1H, 13C)15 or external reference (MeNO2, 0
ppm, for 14N). Starting reagents were preparated by literature proce-
dures: TBAF,6 (PhO)2POCl,14 BH3·THF,12 ANC 3c,e,16 3g,17
BENA 5a–c,5 and oximes 7a–f,h,j,k,6 Reductions with BH3·THF
were performed in the atmosphere of dry argon in freshly distilled
solvents. Commercially available DBU was distilled from CaH2 in
vacuum and stored under argon.
1H NMR (CDCl3): = 1.62, 1.65 (s, 6 H, Me2C, syn and anti), 2.78
(d, 2 H, syn-CH2, 3J = 6.6 Hz,), 3.01 (d, 2 H, anti-CH2, 3J = 5.4 Hz,),
3
6.72 (t, 1 H, anti-CH=N, J = 5.4 Hz,), 7.35 (t, 1 H, syn-CH=N,
3J = 6.6 Hz,), 8.1–9.1 (br, 1 H, OH).
O
O
NaBH3CN/HCl
O
OH
MeO
MeO
MeOH
R
NO2
R NO2
R = H, 2c
Me, 2e
R = H, 1c, 78 %
Me, 1e, 84 %
Scheme 3
OPCl(OPh)2
Et3N
O
MeO2C
MeO2C
O
P
CO2H
Me NO2
Me NO2
OPh
PhO
O
2j
9j
NaBH4
MeO2C
OH
Me NO2
1j
54 %
Scheme 4
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

1342
R. A. Kunetsky et al.
PAPER
13C NMR (CDCl3): = 25.9, 26.1 (Me, syn and anti), 35.1 (CH2,
syn), 39.8 (CH2, anti), 86.2, 86.6 (CNO2, syn and anti), 146.1, 146.7
(C=N, syn and anti).
13C NMR (CDCl3): = 28.3, 29.8 (CH2CH2), 29.7 (CH3CO), 45.3
(CH2CO), 51.9 (OMe), 81.3 (CNO2), 172.1 (CO2), 203.3 (CO).
1-(1-nitrocyclohexyl)propan-2-one (2d)
Methyl 6-Nitro-4-oxyiminohexanoate (7l)
Yield: 90%; oil.
To a solution of MeNO2 (0.81 mL, 15.0 mmol) in CH2Cl2 (100 mL)
at 5 °C was added DBU (2.23 mL, 15.0 mmol), the reaction mixture
was stirred at 5 °C for 5 min and then cooled down to –78 °C. A so-
lution of BENA 6c (4.54 g, 14.9 mmol) in CH2Cl2 (30 mL) and
Bu4NF in THF (4.08 mL 0.73 M, 2.97 mmol) were successively
added dropwise at –78 °C. The reaction mixture was stirred at –78
°C for 1 h, then a solution of HOAc (1.8 mL, 30.0 mmol) in Et2O
(10 mL) was added at –78 °C, and stirred for an additional 10 min.
The reaction mixture was poured into Et2O–H2O (2:1, 300 mL). The
aqueous layer was extracted with Et2O (3 × 30 mL), the combined
organic layers were washed with H2O (20 mL), brine, dried
(Na2SO4), and evaporated. The residue was subjected to column
chromatography (silica gel, CHCl3–Et2O 3:1) to give 1.67 g of 7l
(55%, syn:anti, 1:7); oil; Rf (syn and anti) 0.38 (CHCl3–Et2O, 2:1).
1H NMR (CDCl3): = 1.33–1.77 (m, 6 H, CH2-3 c-hex, CH2-4 c-hex),
1.84–2.04 and 2.19–2.34 (m, 4 H, CH2-2 c-hex), 2.14 (s, 3 H, Me),
3.07 (s, 2 H, CH2CO).
13C NMR (CDCl3): = 22.4 (CH2-3 c-hex), 24.7 (CH2-4 c-hex), 31.0
(Me), 34.4 (CH2-2 c-hex), 49.4 (CH2CO), 88.7 (CNO2), 203.7 (CO).
Methyl 4-Methyl-4-nitro-6-oxoheptanoate (2e)
Yield: 91%; oil.
1H NMR (CDCl3): = 1.67 (s, 3 H, MeCNO2), 2.17 (s, 3 H, MeCO),
2.20–2.39 (m, 4 H, CH2CH2), 2.93 (d, 1 H, CHHCO, 2J = 17.7 Hz),
3.28 (d, 1 H, CHHCO, 2J = 17.7 Hz), 3.67 (s, 3 H, OMe).
13C NMR (CDCl3): = 22.6 (CH3CNO2), 28.6 (CH2CO2Me), 30.6
(CH3CO), 34.5 (CH2CNO2), 49.9 (CH2CO), 51.8 (OMe), 87.0
(CNO2), 172.0 (CO2), 202.3 (CO).
1H NMR (CDCl3,): anti-7l: = 2.50–2.70 (m, 4 H, CH2CH2CO),
2.93 (t, 2 H, CH2CH2NO2, 3J = 6.7 Hz), 3.67 (s, 3 H, MeO), 4.59 (t,
2 H, CH2NO2, 3J = 6.7 Hz); syn-7l: δ = 4.65 (t, 2 H, CH2NO2,
3J = 7.4 Hz).
4-Nitrobutan-2-one (2f)
Yield: 50%; oil.
13C NMR (CDCl3): anti-7l: = 29.7 (CH2CH2CO), 24.0, 31.3
(CH2CNCH2), 52.0 (OMe), 71.0 (CH2NO2), 155.4 (C=N), 173.3
(COOMe); syn-7l: δ = 29.8 (CH2CH2CO), 27.1, 29.9 (CH2CNCH2),
52.0 (OMe), 70.8 (CH2NO2), 154.7 (C=N), 173.2 (COOMe).
1H NMR spectrum is identical to lit. data.20
4-Nitro-4-phenylpentan-2-one (2g)
Yield: 77%; oil.
1H NMR (CDCl3): = 2.10, 2.14 (s, 6 H, MeCNO2, MeCO), 3.25
(d, 1 H, CHAHB, 2J = 17.7 Hz), 3.77 (d, 1 H, CHAHB, 2J = 17.7 Hz),
7.34 (br, 5 H, C6H5).
13C NMR (CDCl3): = 23.8 (CH3CNO2), 30.7 (CH3CO), 51.6
(CH2), 89.9 (CNO2), 124.7, 129.0 (o-, m-, p-CHPh), 139.5 (i-CPh),
203.3 (CO).
Anal. Calcd for C17H12N2O5: C, 41.18; H, 5.92; N, 13.72. Found: C,
41.39; H, 5.84; N, 13.81.
Preparation of Jones’ Reagent11
To a solution of CrO3 (26.67 g, 0.266 mol) in H2O (27 mL) were
added concd H2SO4 (22.1 mL) with vigorous stirring and then H2O
up to a total volume of 100 mL.
(1-Nitrocyclohexyl)-acetic Acid (2h)
Yield: 57%; mp 100–104 °C (petroleum ether–toluene, 6:1).
1H NMR (CDCl3): = 1.39–1.75 (m, 6 H, 3 -CH2, 4 -CH2), 1.84–
2.01 and 2.24–2.41 (m, 4 H, 2 -CH2), 3.01 (s, 2 H, CH2CO), 10.30–
10.71 (br, 1 H, OH).
13C NMR (CDCl3): = 22.3 (3 -CH2), 24.6 (4 -CH2), 34.3 (2 -CH2),
41.8 (CH2CO), 88.2 (CNO2), 175.3 (CO).
Deoximination of 7a-l; General Procedure
To a solution of nitrooxime 7a–l (15 mmol) in acetone (70 mL) was
added Jones’ reagent (7a–g: 2.66 M, 5.6 mL, 15 mmol; 7h–l: 2.66
M, 11.2 mL, 30 mmol) with vigorous stirring at 20 °C. Two more
portions of Jones’ reagent (15 mmol each) were added after 1 and 2
h. After additional stirring for 2 h the reaction mixture was poured
into Et2O–H2O (1:1, 150 mL). The aqueous layer was extracted with
Et2O (4 × 25 mL), the combined organic layers were washed with
H2O (5 × 10 mL), brine (15 mL), dried (MgSO4), and evaporated to
give carbonyl compounds 2.18
Anal. Calcd for C8H13NO4: C, 51.33; H, 7.00; N, 7.48. Found: C,
51.57; H, 6.94; N, 7.36.
4-Methyl-4-nitropentan-2-one (2a)19
Yield: 89%; oil.
1H NMR (CDCl3): = 1.59 (s, 6 H, Me2C), 2.11 (s, 3 H, MeCO),
3.09 (s, 2 H, CH2CO).
13C NMR (CDCl3): = 26.2 [(CH3)2C], 30.3 (CH3CO), 51.2 (CH2),
3-Methyl-3-nitrobutanoic Acid (2i)
Yield: 80%; mp 95–100 °C (petroleum ether–toluene, 7:1)
1H NMR (Acetone-d6): = 1.68 (s, 6 H, Me2C), 3.08 (s, 2 H, CH2),
3.69–7.40 (br, 1 H, OH).
13C NMR (Acetone-d6): = 26.5 [(CH3)2C], 43.5 (CH2), 85.7
(CNO2), 170.9 (CO).
84.5 (CNO2), 203.6 (CO).
Anal. Calcd for C5H9NO4: C, 40.82; H, 6.17; N, 9.52. Found: C,
40.79; H, 6.18; N, 9.49.
4-Nitrohexan-2-one (2b)
Yield: 77%; oil.
1H NMR spectrum is identical to lit. data.7
5-Methoxycarbonyl-3-methyl-3-nitropentanoic Acid (2j)
Purified by column chromatography (silica gel, petroleum ether–
EtOAc, 1:1); yield 78%; mp 62–65 °C (petroleum ether–toluene,
3:2); Rf 0.48 (CHCl3–Et2O, 1:1).
Methyl 4-Nitro-6-oxoheptanoate (2c)
Yield: 80%; oil.
1H NMR (CDCl3): = 1.71 (s, 3 H, MeCN), 2.21–2.50 (s, 4 H,
1H NMR (CDCl3): = 2.05–2.20 (m, 2 H, CH2CH2CO2), 2.14 (s, 3
H, MeCO), 2.33–2.43 (m, 2 H, CH2 CH2CO2), 2.74 (dd, 1 H,
2
CH2CH2), 2.87 (d, 1 H, CHAHBCO2, J = 17.1 Hz), 3.22 (d, 1 H,
CHAHBCO2, 2J = 17.1 Hz), 3.68 (s, 3 H, OMe), 8.48–9.17 (br, 1 H,
2
3
CHAHBCO, J = 18.8, J = 4.7 Hz), 3.27 (dd, 1 H, CHAHBC=O,
2J = 18.8, J = 9.4 Hz), 3.63 (s, 3 H, OMe), 4.85–4.96 (m, 1 H,
3
OH).
13C NMR (CDCl3): = 22.6 (Me), 28.6, 34.5 (CH2CH2), 42.1
CHNO2).
(CH2CO2H), 52.2 (OMe), 87.0 (CNO2), 172.5, 174.1 (CO2).
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

PAPER
-Nitro Alcohols from Aliphatic Nitro Compounds
Minor Isomer:
1H NMR (DMSO-d6): = 0.97 (t, 3 H, CH3CH2, 3J = 7.4 Hz), 3.68–
3.80 (m, 1 H, CHOH), 4.69–4.76 (m, 1 H, CHNO2).
13C NMR (CDCl3): = 10.2 (CH3CH2), 23.8 (CH3CH), 27.8
(MeCH2), 42.2 (CHOH2), 64.2 (CHOH), 87.2 (CHNO2).
14N NMR (CDCl3): = 14.9 (NO2 for two diastereomers, 1/2 = 270
Hz).
1343
Anal. Calcd for C8H13NO6: C, 43.84; H, 5.98; N, 6.39. Found: C,
44.03; H, 5.89; N, 6.21.
Methyl 6-nitro-4-Oxooctanoate (2k)
Yield: 86%; oil.
1H NMR (CDCl3): = 0.86 (t, 3 H, CH3CH2, J = 7.4 Hz), 1.74–
3
1.88 (m, 2 H, MeCH2), 2.36–2.79 (m, 5 H, CH2CH2CO2 and
CHAHBCO), 3.25 (dd, 1 H, CHAHBCO, 2J = 18.4, 3J = 9.5 Hz), 3.54
3
3
3
(s, 3 H, OMe), 4.77 (ddt, 1 H, CHNO2, J = 6.5, J = 4.0, J = 9.5
Hz).
Anal. Calcd for C6H13NO3: C, 48.97; H, 8.90; N, 9.52. Found: C,
49.15; H, 8.76; N, 9.51.
13C NMR (CDCl3): = 9.7 (CH3C), 26.9, 27.5 (CH2CO2, CH2Me),
36.9 (CH2CH2CO2), 44.0 (CH2CO), 51.7 (OMe), 83.5 (CNO2),
172.8 (CO2), 204.6 (CO).
1-(1-Nitrocyclohexyl)-propan-2-ol (1d)
The reaction was carried out with BH3·THF (1.4 mmol, 1.86 mL
1.33 M solution THF) at 20 °C for 3.5 h; Yield: 85%; bp 89–90 °C
(0.2 Torr).
Methyl 6-Nitro-4-oxohexanoate (2l)
1H NMR (CDCl3): = 1.13 (d, 3 H, Me, 3J = 6.1 Hz), 1.20–1.75 [m,
9 H, OH, 4 × CH2-c-Hex except 2 H at -CH(2′)], 1.81 (dd, 1 H,
CHAHBCHOH, 2J = 15.0, 3J = 2.8 Hz), 2.02 (dd, 1 H, CHAHB-
CHOH, J = 15.0, J = 9.2 Hz), 2.30–2.47 (m, 2 H, -CH2-2 c-Hex),
3.83–3.98 (m, 1 H, CHOH).
Yield: 58%; oil
1H NMR spectrum is identical to lit. data.21
13C NMR (CDCl3): = 27.7 (CH2CO2), 37.0, 38.5 (CH2COCH2),
51.9 (MeO), 69.0 (CH2NO2), 173.0 (CO2), 204.4 (CO).
2
3
13C NMR (CDCl3): = 22.2, 22.3 (CH2-3 -c-Hex), 24.7 (CH2-4 -c-Hex),
24.9 (Me), 34.0, 34.9 (CH2-2 -c-Hex), 48.3 (CH2CHOH), 63.7
(CHOH), 90.3 (CNO2).
Reduction of Nitrocarbonyl Compounds 2a,b,d,f–i,k,l with
BH3·THF; General Procedure
To a solution of nitrocarbonyl compound 2 (1 mmol) in THF (1.5
mL) was added the specified amount of BH3·THF at the specified
temperature. The mixture was stirred for the specified time, then
MeOH (3.5 mmol for 1 mmol BH3·THF) was added dropwise, in 5
min the reaction mixture was poured into a mixture of H2O (4 mL)
and concd HCl (0.15 mL). The aqueous layer was extracted with
Et2O (6 × 3 mL), the combined organic layers were washed with
brine, dried (Na2SO4) and evaporated (for the isolation of nitrodiols
8a,b from the aqueous layer its continuous extraction with Et2O
over 18 h was required). For some alcohols 1 the reaction mixture
was quenched with MeOH (9 mmol per 1 mmol of BH3·THF) fol-
lowed by evaporation of the solvent in vacuum and column chroma-
tography.
14N NMR (CDCl3): = 19.4 (NO2, 1/2 = 280 Hz).
Anal. Calcd C9H17NO3: C, 57.73; H, 9.15; N, 7.48. Found: C, 57.44;
H, 9.10; N, 7.68.
4-Nitrobutan-2-ol (1f)
The reaction was carried out with BH3·THF (1.2 mmol, 1.60 mL
1.33 M solution in THF) at 20 °C for 1 h; yield: 90%; bp 100–110
°C (7–8 Torr, short-path apparatus), nd20 1.4448 (lit.22 nd19 1.4445).
1H NMR (CDCl3): δ = 1.21 (d, 3 H, Me, 3J = 5.9 Hz), 1.86–2.25 (m,
2 H, CH2), 2.31 (br, 1 H, OH), 3.79–3.99 (m, 1 H, CHOH), 4.38–
4.64 (m, 2 H, CHNO2).
13C NMR (CDCl3): δ = 23.6 (Me), 35.9 (CH2), 64.8 (CHOH), 72.6
(CH2NO2).
4-Methyl-4-nitropentan-2-ol (1a)
The reaction was carried out with BH3·THF (1.4 mmol, 1.86 mL
1.33 M solution in THF) at 20 °C for 3.5 h; yield: 86%; bp 65–67
°C (0.2 Torr).
1H NMR (CDCl3): = 1.22 (d, 3 H, Me, 3J = 6.1 Hz), 1.63, 1.66 [s,
6 H, (CH3)2C], 1.96 (dd, 1 H, CHAHB, 2J = 15.3, 3J = 3.1 Hz), 2.23–
2.32 (br, 1 H, OH), 2.22 (dd, 1 H, CHAHB, 2J = 15.3, 3J = 9.8 Hz),
3.88–4.02 (m, 1 H, CHOH).
13C NMR (CDCl3): = 24.6, 25.5 and 26.7 (3 × Me), 48.2 (CH2),
64.2 (CH), 86.9 (CNO2).
14N NMR (CDCl3): = 23.4 (NO2, 1/2 = 250 Hz).
4-Nitro-4-phenylpentan-2-ol (1g)
The reaction was carried out with BH3·THF (1.4 mmol, 1.86 mL
1.33 M solution in THF) at 20 °C for 3.5 h; yield: 85%, minor:major
ca. 1:2.5 (1H NMR); bp 130–145 °C (0.2 Torr, short-path appara-
tus).
Major Isomer:
3
1H NMR (CDCl3): = 1.23 (d, 3 H, CH3COH, J = 5.9 Hz), 1.59
(br, 1 H, OH), 2.10 (s, 1 H, MeCNO2), 2.32–2.47 (m, 1 H, CHAHB),
2.75 (dd, 1 H, CHAHb, 2J = 14.7, 3J = 10.3 Hz), 3.78–3.97 (m, 1 H,
CHOH), 7.31–7.49 (m, 5 H, C6H5).
13C NMR (CDCl3): = 23.7, 25.2 (CH3CNO2 and CH3CHOH), 47.6
(CH2), 64.6 (CHOH), 92.2 (CNO2), 125.3 (p-CHPh), 128.8 (o-, m-
CHPh), 139.9 (i- CPh).
Anal. Calcd C6H13NO3: C, 48.97; H, 8.90; N, 9.52. Found: C, 49.08;
H, 8.88; N, 9.48.
4-Nitrohexan-2-ol (1b)7
The reaction was carried out with BH3·THF (1.4 mmol, 1.86 mL
1.33 M solution in THF) at 20 °C, for 3.5 h; yield: 95%, minor:ma-
jor ca. 1:2.7 (1H NMR); bp 66–67 °C (0.15 Torr).
Minor Isomer:
1H NMR (CDCl3): = 1.25 (d, 3 H, CH3COH, 3J = 6.6 Hz), 2.07 (s,
1 H, MeCNO2), 2.65 (dd, 1 H, CHAHB, 2J = 15.5, 3J = 2.2 Hz).
Major Isomer:
13C NMR (CDCl3): = 24.6, 25.3 (CH3CNO2 and CH3CHOH), 48.4
(CH2), 65.1 (CHOH), 93.3 (CNO2), 125.1 (p- CHPh), 128.8 (o-, m-
CHPh), 140.4 (i-CPh).
14N NMR (CDCl3): δ = 18.9 (NO2 for two diastereomers, 1/2 = 275
Hz).
1H NMR (DMSO-d6): = 0.96 (t, 3 H, CH3CH2, 3J = 7.4 Hz), 1.23
(d, 3 H, CH3CH, 3J = 7.0 Hz), 1.62–2.28 (m, 4 H, 2 × CH2), 2.42–
2.84 (br, 1 H, OH), 3.81–3.92 (m, 1 H, CHOH), 4.51–4.73 (m, 1 H,
CHNO2).
13C NMR (CDCl3): = 10.1 (CH3CH2), 23.6 (CH3CH), 27.3
(MeCH2), 42.1 (CH2), 65.3 (CHOH), 87.8 (CHNO2).
Anal. Calcd for C11H13NO3: C, 63.14; H, 7.23; N, 6.69. Found: C,
63.28; H, 7.23; N, 6.54.
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

1344
R. A. Kunetsky et al.
PAPER
2-(1-Nitrocyclohexyl)-ethanol (1h)
2.66 (br, 1 H, OH), 3.68 (s, 3 H, OMe), 3.66–3.83 (m, 1 H, CHOH),
The reaction was carried out with BH3·THF (2 mmol, 2.66 mL 1.33
M solution in THF) at 20 °C for 2 h; yield: 62%; bp 100–105 °C (0.2
Torr, short-path apparatus).
1H NMR (CDCl3): = 1.20–1.72 (m, 8 H, 4 × CH2-c-Hex except
CH2-2 -c-Hex), 2.04 (t, 2 H, CH2CH2OH, 3J = 6.8 Hz), 2.28–2.43 (m,
2 H, CH2-2 -c-Hex), 2.52–2.71 (br, 1 H, OH), 3.59 (t, 2 H, CH2OH,
3J = 6.8 Hz).
4.47–4.68 (m, 2 H, CH2NO2).
13C NMR (CDCl3): = 30.8, 32.6 and 34.9 (3 × CH2 except
CH2NO2), 52.4 (MeO), 68.5 (CHOH), 73.0 (CH2NO2), 175.1
(CO2).
14N NMR (CDCl3): = 4.5 (NO2, 1/2 = 140 Hz).
Anal. Calcd for C7H13NO5: C, 43.98; H, 6.85; N, 7.33. Found: C,
43.74; H, 6.74; N, 7.23.
13C NMR (CDCl3): δ = 22.3 (CH2-3 -c-Hex), 24.7 (CH2-4 -c-Hex), 34.3
(CH2-2 -c-Hex), 42.1 (CH2), 57.6 (CH2OH), 90.2 (CNO2).
14N NMR (CDCl3): = 18.7 (NO2, 1/2 = 200 Hz).
4-Nitroheptan-1,6-diol (8a)
The reaction was carried out with BH3·THF (5 mmol, 6.65 mL 1.33
M solution in THF) at 20 °C for 4 h; yield: 74%; minor:major ca.
1:2.7 (1H NMR); bp 135–137 °C (0.15 Torr).
Anal. Calcd for C8H15NO3: C, 55.47; H, 8.73; N, 8.09. Found: C,
55.50; H, 8.66; N, 8.12.
Major Isomer:
3-Methyl-3-nitrobutanol (1i)
1H NMR (CDCl3): = 1.26 (d, 3 H, CH3CHOH, 3J = 6.0 Hz), 1.54–
2.27 (m, 8 H, CH2CH2, CH2CHOH, 2 × OH), 3.63–3.82 (m, 2 H,
CH2OH), 3.87–3.96 (m, 1 H, CHOH), 4.67–4.77 (m, 1 H, CHNO2).
13C NMR (CDCl3): δ = 23.6 (CH3CHOH), 28.3 and 29.9 (CH2CH2),
42.4 (CH2CHOH), 61.2, 65.0 (CH2OH, CHOH), 85.9 (CHNO2).
The reaction was carried out with BH3·THF (2 mmol, 2.66 mL 1.33
M solution in THF) at 20 °C for 2 h; yield: 62%; bp 46–52 °C (0.2
Torr, short-path apparatus).
1H NMR (CDCl3): = 1.52 [s, 6 H, (CH3)2C], 2.09 (t, 2 H, CH2,
3J = 6.6 Hz), 2.95–3.14 (br, 1 H, OH), 3.57 (t, 2 H, CH2OH, 3J = 6.6
Hz).
Minor Isomer:
1H NMR (CDCl3): = 1.23 (d, 3 H, CH3CHOH, 3J = 6.4 Hz), 3.63–
3.82 (m, 1 H, CHOH), 4.83–4.93 (m, 1 H, CHNO2).
13C NMR (CDCl3):
= 21.7 [(CH3)2C)], 38.0 (CH2), 53.6
(CH2OH), 82.6 (CNO2).
13C NMR (CDCl3): = 23.8 (CH3CHOH), 28.5, 30.8 (CH2CH2),
42.5 (CH2CHOH), 61.2, 64.2 (CH2OH and CHOH), 85.5 (CHNO2).
14N NMR (CDCl3): = 16.0, (NO2 for two diastereomers, 1/2 = 620
Hz).
14N NMR (CDCl3): = 17.5 (NO2, 1/2 = 200 Hz).
Anal. Calcd for C5H11NO3: C, 45.10; H, 8.33; N, 10.52. Found: C,
44.98; H, 8.84; N, 10.64.
Methyl 6-Nitro-4-oxyoctanoate (1k)
Anal. Calcd for C7H15NO4: C, 47.45; H, 8.53; N, 7.90. Found: C,
47.51; H, 8.48; N, 7.91.
The reaction was carried out with BH3·THF (1.2 mmol, 1.6 mL 1.33
M solution in THF) at 0 °C for 2 h, the crude product was purified
by column chromatography (silica gel, CHCl3→CHCl3–Et2O, 3:1);
yield: 31%, minor:major ca. 1:2 (1H NMR), bp 121–128 °C (0.2
Torr, short-path apparatus); Rf 0.31 (CHCl3–Et2O, 2:1).
4-Methyl-4-nitroheptan-1,6-diol (8b)
The reaction was carried out with BH3·THF (5 mmol, 6.65 mL 1.33
M solution in THF) at 20 °C for 4 h; yield: 74%; minor:major ca.
1:2 (1H NMR); bp 124–135 °C (0.2 Torr).
Major Isomer:
1H NMR (CDCl3): = 0.94 (s, 3 H, CH3CH2), 1.60–2.27 (m, 6 H,
CH2CH2, MeCH2), 2.37–2.60 (m, 2 H, CH2CHOH), 2.65–2.85 (br,
1 H, OH), 3.49–3.78 (m, 1 H, HCOH),3.66 (s, 3 H, OMe), 4.51–
4.66 (m, 1 H, CHNO2).
13C NMR (CDCl3): = 10.0 (CH3C), 27.1, 30.3 and 32.2 (CH2CH2
and MeC), 40.6 (CH2CHOH), 51.9 (OMe), 68.7 (HCOH), 87.5
(CNO2), 174.4 (CO2).
Major Isomer:
1H NMR (CDCl3): = 1.19 (d, 3 H, CH3COH, 3J = 5.9 Hz), 1.26–
1.70, 1.80–2.20 (m, 5 H, CH2CH2 and CHAHBCHOH), 1.60 (s, 3 H,
MeCNO2), 2.30 (dd, 1 H, CHAHBCHOH, J = 15.1, J = 9.8 Hz),
2.38–2.60 (br, 2 H, 2 × OH), 3.54–3.66 (m, 2 H, CH2OH), 3.93–4.04
(m, 1 H, CHOH).
13C NMR (CDCl3): = 21.8, 24.9 (CH3CNO2, CH3CHOH), 26.8,
36.6 (CH2CH2), 47.5 (CH2CHOH), 61.9, 64.1 (CH2OH and
CHOH), 89.9 (CNO2).
2
3
Minor Isomer:
1H NMR (CDCl3): = 0.95 (s, 3 H, CH3CH2), 4.70–4.83 (m, 1 H,
CHNO2).
13C NMR (CDCl3): = 10.2 CH3C), 27.7, 30.4 and 32.4 (CH2CH2
and MeC), 40.7 (CH2CHOH), 51.9 (OMe), 67.5 (HCOH), 86.9
(CNO2), 174.4 (CO2).
14N NMR (CDCl3): = 13.6 (NO2 for two diastereomers, 1/2 = 260
Hz).
Minor Isomer:
1H NMR (CDCl3): = 1.26–1.70 and 1.80–2.20 (m, 2 H, CH2),
3.81–3.93 (m, 1 H, CHOH).
13C NMR (CDCl3): = 23.0, 25.1 (CH3CNO2 and CH3CHOH),
27.0, 36.0 (CH2CH2), 47.1 (CH2CHOH), 61.9, 64.4 (CH2OH and
CHOH), 90.8 (CHNO2).
14N NMR (CDCl3): = 18.6, (NO2 for two diastereomers, 1/2 = 640
Hz).
Anal. Calcd C9H17NO5: C, 49.30; H, 7.82; N, 6.39. Found: C, 49.37;
H, 7.63; N, 6.42.
Anal. Calcd for C8H17NO4: C, 50.25; H, 8.96; N, 7.32. Found: C,
50.17; H, 8.95; N, 7.41.
Methyl 6-Nitro-4-oxyhexanoate (1l)
The reaction was carried out with BH3·THF (1.2 mmol, 1.6 mL 1.33
M solution in THF) at 0 °C for 2 h; the crude product was purified
by column chromatography (silica gel, CHCl3–Et2O, 2:1); yield:
44%; bp 105–115 °C (0.2 Torr, short-path apparatus); Rf 0.17
(CHCl3–Et2O, 2:1)
1H NMR (CDCl3): = 1.68–1.93, 1.94–2.12 and 2.16–2.30 [m, 4 H,
CH2(CHOH)CH2], 2.49 (t, 2 H, CH2CO2Me, J = 7.2 Hz), 2.53–
Methyl 4-Methyl-4-nitro-6-oxyhexanoate (1j)
To a solution of nitro acid 2j (205 mg, 1 mmol) in THF (7.5 mL)
was added Et3N (0.14 mL, 1 mmol) followed by (PhO)2POCl (268.5
mg, 1 mmol) in THF (3.5 mL). The reaction mixture was stirred for
2 h, filtered. Powdered NaBH4 (76 mg, 2 mmol) was added to the
filtrate, and after stirring for 2 h the mixture was quenched with
AcCl (0.14 mL) in MeOH (4 mL), the solvent was evaporated, and
3
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

PAPER
-Nitro Alcohols from Aliphatic Nitro Compounds
1345
the residue was subjected to column chromatography (silica gel, pe-
troleum ether–EtOAc, 1:3) to give 110 mg of 1j; yield: 54%; bp
125–135 °C (0.06 Torr, short-path apparatus); Rf 0.48 (petroleum
ether–EtOAc, 1:3)
1H NMR (CDCl3): = 1.57 (s, 3 H, MeCNO2), 2.03–2.48 (m, 7 H,
CH2CH2 and CH2CH2OH), 3.65 (s, 3 H, MeO), 3.62–3.80 (m, 2 H,
CH2OH).
13C NMR (CDCl3): = 22.1 (MeCNO2), 28.8, 34.5 (CH2CH2), 41.2
(CH2COH), 52.1 (CH2OH), 58.1 (MeO), 89.3 (CNO2), 172.9 (CO2).
14N NMR (CDCl3): = 18.0 (NO2, 1/2 = 165 Hz).
13C NMR (CDCl3): = 22.7, 25.2 (CH3CNO2 and CH3CHOH),
28.9, 34.4 (CH2CH2), 47.2 (CH2CHOH), 51.9 (OMe), 64.4
(CHOH), 90.0 (CNO2), 172.9 (CO).
14N NMR (CDCl3): = 18.5 (NO2 for two diastereomers, 1/2 = 600
Hz).
Anal. Calcd for C9H17NO5: C, 49.31; H, 7.82; N, 6.39. Found: C,
49.71; H, 7.60; N, 6.48.
Preparation of γ-Nitroalcohols 1a–e and Nitrodiols 9a,b without
Purification of Intermediate Compounds
Preparation of 1a,d,e; General Procedure for Secondary ANC
To a solution of DBU (2.78 mL, 18.6 mmol) in Et2O (180 mL) at 5
°C was added nitrocyclohexane (3d) (2.26 mL, 18.6 mmol), the
mixture was stirred at 5 °C for 5 min, then a solution of BENA 6a
(4.77 g, 20.46 mmol) in Et2O (180 mL) was added dropwise at 5 °C
for 2 h, the reaction mixture was stirred at 0 °C for 1 h, the mixture
of NH4F (0.69 g, 18.6 mmol), HOAc (1.60 mL, 27.9 mmol), and
MeOH (30 mL) was added, the reaction mixture was stirred for an
extra 20 min, and poured into H2O (150 mL). The aqueous layer was
extracted with Et2O (4 × 80 mL), the combined organic layers were
washed with brine, dried (Na2SO4) and concentrated to give 7d
(3.00 g). To a solution of 7d in acetone (70 mL) Jones’ reagent (5.62
mL 2.67 M solution, 15 mmol) was added at 20 °C. Two more por-
tions of Jones’ reagent (15 mmol each) were added after 1 and 2
hours. After additional stirring for 2 h the reaction mixture was
poured into H2O–Et2O (1:1, 150 mL), the aqueous layer was ex-
tracted with Et2O (4 × 25 mL), the combined organic layers were
washed with H2O (4 × 10 mL), brine, dried (MgSO4) and the solvent
evaporated, the residue was azeotropically dried with toluene to
give 2.59 g of 2d. To a solution of 2d in THF (20 mL) at 20 °C was
added BH3·THF (12.5 mL 1.33 M solution in THF, 16.55 mmol).
MeOH (2.4 mL, 59 mmol) was added in 3 h, the mixture was poured
into HCl (1.7 mL concd HCl and 50 mL H2O), and extracted with
Et2O (5 × 20 mL). The combined organic layers were washed with
brine, dried (Na2SO4), and the solvent evaporated, the residue was
distilled to give 1.57 g of 1c (8.4 mmol, yield 45% refers to ANC
without purification of intermediate compounds 3d). Nitroalcohols
1a and 1e were obtained analogously (yields are given in Table 1).
Anal. Calcd for C8H15NO5: C, 46.82; H, 7.37; N, 6.83. Found: C,
46.58; H, 7.09; N, 6.89.
Methyl 4-Nitro-6-oxyheptanoate (1c)
To a solution of ketone 2c (203 mg, 1 mmol) and NaBH3CN (94.5
mg, 1.5 mmol) in MeOH (1.7 mL) a solution of AcCl (106 L, 1.5
mmol) in MeOH (5 mL) was added dropwise over 3 h. To achieve
complete conversion (TLC control) the addition of NaBH3CN and
AcCl/MeOH could be repeated, in 24 h the reaction mixture was
evaporated and residue was poured into H2O–Et2O (1:1, 40 mL), the
aqueous layer was extracted with Et2O (3 × 5 mL). The combined
organic layers were washed with brine (5 mL), dried (Na2SO4), the
solvent evaporated and distilled in a short-path apparatus, to give
160 mg of 1c; yield: 78%; minor:major ca. 1:2.5 (1H NMR); bp
100–107 °C (0.05 Torr).
Major Isomer:
1H NMR (CDCl3): = 1.22 (d, 3 H, CH3CHOH, 3J = 6.0 Hz), 1.82
2
3
3
(ddd, 1 H, CHAHBCHOH, J = 14.8, J = 4.7, J = 6.7 Hz), 2.03–
2.45 (m, 6 H, CH2CH2, CHAHBCHOH), 3.67 (s, 3 H, OMe), 3.85–
3.97 (m, 1 H, CHOH), 4.69 (q, 1 H, CHNO2, 3J = 6.7 Hz).
13C NMR (CDCl3): δ = 23.6 (CH3C), 28.2, 29.8 (CH2CH2), 42.2
(CH2), 51.8 (OMe), 64.9 (CHOH), 85.0 (CHNO2), 172.6 (CO).
Minor Isomer:
1H NMR (CDCl3): = 1.19 (d, 3 H, CH3CHOH, 3J = 6.0 Hz), 1.72
(ddd, 1 H, CHAHBHOH, 2J = 14.8, 3J = 3.4, 3J = 9.4 Hz), 3.70–3.82
(m, 1 H, CHOH), 4.79–4.89 (m, 1 H, CHNO2).
13C NMR (CDCl3): = 23.7 (CH3C), 29.0, 29.9 (CH2CH2), 42.3
(CH2), 51.8 (OMe), 64.0 (CHOH), 84.6 (CHNO2), 172.3 (CO).
Preparation of 1b,c; General Procedure for Primary Nitro
Compounds
To a solution of 1-nitropropane 3b (2 mL, 22.5 mmol) in CH2Cl2
(150 mL) at 5 °C was added DBU (3.32 mL, 22.5 mmol), the reac-
tion mixture was stirred at 5 °C for 5 min and then cooled down to
–78 °C. A solution of BENA 6a (5.0 g, 21.4 mmol) in CH2Cl2 (49
mL) was added followed by Bu4NF (5.35 mL 0.8 M solution in
THF, 4.28 mmol). The mixture was stirred at –78 °C for 1 h, a so-
lution of HOAc (2.57 mL, 45.0 mmol) in Et2O (27 mL) was added,
kept for additional 10 min, and poured into Et2O–H2O (5:3, 400
mL). The aqueous layer was extracted with Et2O (3 × 50 mL), the
combined organic layers were washed with H2O (30 mL), brine (30
mL), dried (Na2SO4) and evaporated to give 7b (3.25 g). Jones’ re-
agent (6.80 mL 2.66 M solution, 18.0 mmol) was added at 20 °C to
a solution of 7b in acetone (60 mL). Two more portions of Jones’
reagent (18 mmol each) were added after 1 and 2 hours. After addi-
tional stirring for 2 h the reaction mixture was poured into Et2O–
H2O (1:1, 130 mL), the aqueous layer was extracted with Et2O (4 ×
40 mL), the combined organic layers were washed with H2O (4 × 8
mL), brine (10 mL), dried (MgSO4) and the solvent evaporated, the
residue was azeotropycally dried with toluene to give 2d (2.43 g).
To a solution of 2d in THF (22 mL) at 20 °C was added BH3·THF
(14.7 mL, 1.33 M solution in THF, 19.6 mmol), after 3 h MeOH
(2.48 mL, 61mmol). The mixture was poured into HCl (from 1.6
mL concd HCl and 47 mL H2O), the aqueous layer was extracted
with Et2O (5 × 30 mL). The combined organic layers were washed
with brine (20 mL), dried (Na2SO4) and evaporated, the residue was
distilled to give 1b (1.81 g, yield 58% refers to BENA 6a).
14N NMR (CDCl3): = 13.0 (NO2 for two diastereomers, 1/2 = 380
Hz).
Anal. Calcd for C8H15NO5: C, 46.82; H, 7.36; N, 6.82. Found: C,
46.89; H, 7.22; N, 6.86.
Methyl 4-Methyl-4-nitro-6-oxyheptanoate (1e)
Nitro ketone 2e was reduced to 1e analogously. After concentration
of the organic phase the residue was subjected to column chroma-
tography (silica gel, CHCl3–Et2O, 3:1) to give ester 1e; yield: 84%,
minor:major ca. 1:2 (1H NMR); bp 137–142 °C (0.7 Torr); Rf 0.31
(CHCl3–Et2O, 3:1)
Major Isomer:
1H NMR (CDCl3): = 1.23 (d, 3 H, CH3CHOH, 3J = 6.4 Hz), 1.62
(s, 3 H, MeCNO2), 1.85 (dd, 1 H2J = 15.1,3J = 2.7 Hz, OH), 2.30–
2.45 (6 H, 3 × CH2), 3.67 (s, 3 H, OMe), 3.98–4.06 (m, 1 H,
CHNO2).
13C NMR (CDCl3): = 21.6, 25.0 (CH3CNO2 and CH3CHOH),
28.7, 35.0 (CH2CH2), 47.4 (CH2CHOH), 51.9 (OMe), 64.0
(CHOH), 89.1 (CNO2), 172.7 (CO).
Minor Isomer:
1H NMR (CDCl3): = 1.22 (d, 3 H, CH3CHOH, 3J = 6.4 Hz), 1.63
(s, 3 H, MeCNO2), 3.89–3.98 (m, 1 H, CHNO2).
Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York

1346
R. A. Kunetsky et al.
PAPER
Nitroalcohol 1c was obtained analogously (yield 51% refers to
ANC without purification of intermediate compounds 3c).
(5) (a) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S.
L.; Strelenko, Yu. A.; Tartakovsky, V. A. Synthesis 1998,
181. (b) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.;
Ioffe, S. L.; Kachala, V. V.; Strelenko, Yu. A.; Tartakovsky,
V. A. J. Chem. Soc., Perkin Trans. 1 2000, 2926.
(6) Dilman, A. D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu.
A.; Tartakovsky, V. A. Synthesis 1999, 1767.
(7) Kadentsev, V. I.; Kolotyrkina, N. G.; Stomakhin, A. A.;
Chizhov, O. S.; Ioffe, S. L.; Lyapkalo, I. M.; Dilman, A. D.;
Tishkov, A. A. Russ. Chem. Bull. (Engl. Trans.) 1998, 47,
1225.
Preparation of Diols 8a,b without Purification
This was performed analogously to that described above using
BH3·THF (3.2 mmol per 1 mmol of ANC 3, 2.4 mL, 1.33 M solu-
tion in THF) at 20 °C for 4 h. Yields of target diols are given in
Table 1.
Acknowledgment
(8) Rao, C. G.; Radnakrishna, A. S.; Singh, B. B.; Bhanagar, S.
P. Synthesis 1983, 808.
(9) Vankar, P.; Rathore, R.; Chandrasekan, S. J. Org. Chem.
1986, 51, 3063.
(10) DePuy, C. H.; Ponder, B. W. J. Am. Chem. Soc. 1959, 81,
4629.
This work was performed at the Scientific Educational Center for
young chemists and supported by Russian Foundation for Basic Re-
search (grants ## 99-03-32015 and 00-15-97455) and by The Feder-
al Target Program ‘Integration’ (projects ## A0082 and B0062).
(11) Kleinfelter, D. C.; Schleyer, P. R. Org. Synth. 1962, 42, 79.
(12) Brown, H. C.; Heim, P.; Yoon, N. M. J. Am. Chem. Soc.
1970, 92, 1637.
(13) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem.
Soc. 1971, 93, 2897.
(14) Koizumi, T.; Yamamoto, N.; Yosh, E. Chem. Pharm. Bull.
1973, 21, 312.
(15) Gottlieb, H. E.; Katlyar, V.; Nudelman, A. J. Org. Chem.
1997, 62, 7512.
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Synthesis 2003, No. 9, 1339–1346 ISSN 1234-567-89 © Thieme Stuttgart · New York