Rearrangement of chiral 1-bromo-N-nitrobicyclo[2.2.1]heptan-2-imines

Article abstract of DOI:10.1016/j.tetasy.2013.06.001

The regio- and diastereospecific Wagner-Meerwein-type rearrangements of the potassium cyanide adducts of camphor-derived substituted 1-bromo-N- nitrobicyclo[2.2.1]heptan-2-imines under acidic conditions have been investigated. The selective formation of bromonorbornene derivatives has been demonstrated in the case of rearrangements involving intermediate α-bromocarbocations containing vicinal hydrogen atoms. In all other cases, hydrolysis of the intermediates resulted in the formation of a carbonyl group. The simplicity of this transformation opens up a novel and straightforward synthetic pathway to enantiopure derivatives of bridgehead-substituted norbornane carboxamides in just three steps, starting from 1-bromonorbornanones.

Full text of DOI:10.1016/j.tetasy.2013.06.001

Tetrahedron: Asymmetry 24 (2013) 817–821
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Rearrangement of chiral 1-bromo-N-nitrobicyclo[2.2.1]
heptan-2-imines
b,
Oleksandr V. Grytsai a, Marian V. Gorichko a, , Vladimir B. Golovko
⇑
⇑
a Department of Chemistry, Taras Shevchenko National University of Kyiv, 01601, Ukraine
b Department of Chemistry, University of Canterbury, P.B. 4800, Christchurch 8140, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 April 2013
Accepted 13 June 2013
The regio- and diastereospecific Wagner-Meerwein-type rearrangements of the potassium cyanide
adducts of camphor-derived substituted 1-bromo-N-nitrobicyclo[2.2.1]heptan-2-imines under acidic
conditions have been investigated. The selective formation of bromonorbornene derivatives has been
demonstrated in the case of rearrangements involving intermediate
a-bromocarbocations containing
vicinal hydrogen atoms. In all other cases, hydrolysis of the intermediates resulted in the formation of
a carbonyl group. The simplicity of this transformation opens up a novel and straightforward synthetic
pathway to enantiopure derivatives of bridgehead-substituted norbornane carboxamides in just three
steps, starting from 1-bromonorbornanones.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
(R1R2C=S) via substitution of the =N-NO2 moiety by reaction with
a primary amine, hydrazine, or hydrogen sulfide, which takes place
Nitroimines constitute a relatively unexplored class of com-
pounds due to the carbon atom of the nitroimine group having
high electrophilicity, which is significantly greater than that of
the carbon atom of the carbonyl group. Such high electrophilicity
leads to high reactivity of the nitroimine functional group. Hydro-
lysis to the parent carbonyl compounds is the simplest example of
this phenomenon.1a–e Moreover, compounds containing a hydro-
under much milder conditions compared to reactions involving the
carbonyl analogues as starting compounds. The synthesis of con-
formationally restricted ligands for catalytic asymmetric addition
to aldehydes was recently achieved using this synthetic pathway
starting from naturally occurring chiral compounds with a norbor-
nyl skeleton.6 The use of this synthetic methodology enabled the
synthesis of enantiopure imidazoline carbene ligands,7 enantiome-
rically enriched vic-amino alcohols,8 bornane-derived push-pull
butadienes,9 and the first ever synthesis of stable enantiopure
chiral N-H oxaziridines.10 The syntheses of compounds with anti-
arrhythmic, local anesthetic, and hypotensive activities11,12 were
recently reported by starting from norbornane nitroimine-deriva-
tives using this approach. High yields and excellent selectivities
are common for most of the reactions mentioned above because
water and nitrous oxide are the only significant by-products.
Sometimes, the loss of the N2O moiety leads to formation of the
carbocationic intermediates, which could react further depending
on their structure.13
gen atom at the
a-position relative to the nitroimine functional
group have a strong propensity to undergo a range of condensation
reactions.
More than 100 years ago Angeli and Rimini reported on the
preparation of ‘pernitrosocamphor’, probably the first example of
a nitroimine described in the literature.2 Impressively, it took 65
years to elucidate its structure as that of 1,7,7-trimethyl-N-nitrobi-
cyclo[2.2.1]heptane-2-imine, another indirect indication of the
very high reactivity of this class of compounds.3 The vast majority
of relatively stable nitroimines are stabilized either by the pres-
ence of nearby substituents with substantial steric demands lead-
ing to efficient shielding4 or the influence of functional groups with
pronounced positive mesomeric effects5a,5b capable of reducing the
reactivity of the C=N-NO2 group.
2. Results and discussion
Nitroimines are often used in the synthesis of azomethines
Herein we have selected three chiral norbornanones: (1R,4R)-
1-bromo-3,3,4-trimethylbicyclo[2.2.1]heptan-2-one 1a;14a,14b
(1R,4R)-1-bromo-3,3-dimethylbicyclo[2.2.1]heptan-2-one
(R1R2C=NR3), hydrazones (R1R2C=NNR3R4), and thiocarbonyls
1b;15
and
(1R,4S)-1-bromo-7,7-dimethylbicyclo[2.2.1]heptan-2-one
1c16 (Scheme 1), with an
a-bromine atom in a bridgehead position
⇑
Corresponding authors. Tel.: +6433642442; fax: +44 1223336033.
E-mail addresses: fenchone@gmail.com (O.V. Grytsai), gorichko@chem.univ.kie-
which could be easily prepared in both enantiomeric forms starting
from a readily accessible naturally occurring material, camphor.
v.ua (M.V. Gorichko), vladimir.golovko@canterbury.ac.nz (V.B. Golovko).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.06.001

818
O. V. Grytsai et al. / Tetrahedron: Asymmetry 24 (2013) 817–821
CH3
R2
H3C
O
Br
R
R
R
R
R
R
NH2
Br
Br
Br
NaNO2,
O
N
OH
N
NO2 1. KCN
2. HCl
NH2OH
aq. H2SO4
4a R2 = CH3
2 = H
b
R
R1
propan-2-ol,
reflux 4-16 h
Et2O
R1
R1
R2
R2
R2
R1
R1
R1
H
CH3
CH3
1
2
3
R = H; R1 = R2 = CH3
1-3a
b R = H; R1 = CH3; R2 = H
c R = CH3; R1 = R2 = H
O
O
NH2
5
Scheme 1. Synthesis of bromonitroimines 3a-c and rearrangements of the corresponding a-cyanonitroamine salts under acidic conditions.
We synthesized stable nitroimine-derivatives 3a-c of the
bromonorbornanones 1a-c as model starting materials in order
to study the acid-induced rearrangement processes of the corre-
introduced onto the norbornane skeleton, which should affect
the stability of the corresponding intermediates. In the case of
the nitroimines 3a-c reported here, the Wagner-Meervein rear-
rangement yields the formation of the analogous intermediates
12 in which the bromo-substituent is located exactly at the cat-
ionic carbon atom (Scheme 3).
sponding
a-cyanonitroamines. We recently reported on a de-
tailed study of intramolecular cyclization reactions of 8-bromo
substituted camphor nitroimines under similar reaction condi-
tions.17 However, in the case of our selected compounds, we ex-
pected to observe the formation of both products of the
rearrangements of carbocationic intermediates as well as prod-
ucts of the intramolecular nucleophilic substitution of a bromine
atom.
Despite the significant steric hindrance, the carbonyl groups in
compounds 1a-c could be converted into the corresponding oxi-
mes in good yields by heating the starting ketones with hydroxyl-
amine in pyridine. However, in the case of tri-methyl-substituted
compound 1a, this transformation required a longer reaction time
(16 hours). Oximes 2a-c readily yielded the corresponding nitroi-
mine-derivatives 3a-c upon treatment with nitrous acid generated
in situ in a mixture of water and ether.
The reactivity of such intermediates appears to be defined by
the nature of the other substituents, particularly the R-groups at
the nearby vic-carbon atom. The presence of a hydrogen at the
carbon atom in a vicinal position relative to the carbocation en-
ables its elimination (as a proton) to yield the corresponding
bromo-substituted endocyclic alkenes (Scheme 3, Pathway A).
Thus, starting from nitroimines 3a and 3b, we obtained the
corresponding amides (1R,4R)-2-bromo-4,7,7-trimethylbicyclo-
[2.2.1]hept-2-ene-1-carboxamide 4a and (1R,4R)-2-bromo-7,7-
dimethylbicyclo[2.2.1]hept-2-ene-1-carboxamide 4b with high
yields and selectivity. Only in cases when such elimination is
impossible (R = CH3) does the resulting intermediate carbocation
react with solvent (H2O) and, after elimination of HBr, form a
carbonyl group (Scheme 3, Pathway B). This pathway is illus-
trated by the reaction of nitroimine 3c, which under similar con-
ditions, yields (1S,4S)-3,3-dimethyl-2-oxobicyclo[2.2.1]heptane-
1-carboxamide 5.
The reaction of unsubstituted camphor-N-nitroimine 6 with the
cyanide anion resulted in the formation of camphene-1-carboxam-
ide 10 via the mechanism illustrated in Scheme 2, according to an
earlier report by Kocienski and Kirkup.13
First, the cyanonitramine 7 is generated in virtually quantitative
yield via the endo-addition of the cyanide anion. It is unstable
under acidic conditions, and gradually decomposes with the evolu-
tion of N2O from intermediate 8, which, upon Wagner-Meervein
rearrangement, yields a relatively stable tertiary carbocation 9.
Decomposition of the carbocation 9 by the loss of a proton from
the nearby methyl group results in formation of the corresponding
exocyclic alkene 10.
The structure of bromo-substituted alkene 4b was confirmed by
using single-crystal X-ray diffraction in order to remove any doubt
about potential simultaneous skeletal rearrangements during its
formation (Fig. 1).
Compound 5 was prepared independently via an alternative
pathway starting from the corresponding keto-acid18 in order
to confirm that our assignment of the structure of the rearrange-
ment product of nitroimine 3c was correct. Compound 5 was
prepared by starting from the corresponding keto-acid18 via
treatment with thionyl chloride followed by reaction with aque-
ous ammonia at 0 °C.
The reactivity of brominated derivatives of camphor in this
rearrangement could be somewhat different due to the geometric
and electronic effects imposed by the bromo-substituents
CH3
H3C
CH3
H
CH3
H
H3C
H3C
H3C
H
H
H3C
H3C
H3C
H3C
H2C
H
N
NHNO2
CN
-N2O
-H
N
O
H3C
HN
NH2
NH2
NNO2
O
H3C
H3C
O
O
H
6
7
8
9
10
Scheme 2. Synthesis of camphene-1-carboxamide via a Wagner-Meervein rearrangement of cyan nitroamine.

O. V. Grytsai et al. / Tetrahedron: Asymmetry 24 (2013) 817–821
Pathway A (R = H)
819
4a,b
R1
O
R1
O
R
R
Br
N
-H
N
Br
NH2
1. KCN
2. H
O
3a-c
R
-N2O
R1
R2
R
R2
H2O
R1
NH
H
-HBr
11
12
5
Pathway B (R = CH3)
Scheme 3. Proposed mechanism of formation of 4a,b and 5.
spectra were obtained on a Perkin Elmer BX II spectrometer. k max
(cm-1) values in IR spectra are given for the main absorption bands.
Mass spectra were recorded on an R 10-10 C Nermag (70 eV) quad-
rupolar spectrometer using desorption chemical ionization (DCI),
electrospray (ES), or fast atomic bombardment (FAB) techniques.
Optical rotations were measured using a sodium D line on
P-2000 series Jasco, PTC-262 polarimeter. Melting points are
uncorrected. All crystallographic measurements were performed
at room temperature on a Bruker Smart Apex II diffractometer
operating in the
x and u scans mode. The structure was solved
by direct methods and refined by the full-matrix least-squares
technique in the anisotropic approximation for non-hydrogen
atoms using the Bruker SHELXTL program package.19 Full crystallo-
graphic data for the structure of 4b have been deposited with the
Cambridge Crystallographic Data Centre under registration num-
ber 927999. Copy of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: +44 1223336033 or e-mail: deposit@ccdc.cam.ac.uk).
4.1.1. Materials
All starting materials were purchased from Acros, Merck,
Aldrich and Fluka chemicals. All solvents were distilled before
use.20 Ketones 1a-c were synthesized by starting from camphor
following literature procedures and completely characterized
using 1H and13C NMR, MS, and C,H,N analysis etc. with all obtained
results fitting previously reported literature data (details are not
reported here).14–16
Fig. 1. X-Ray crystal structure of (1R,4R)-2-bromo-7,7-dimethylbicyclo[2.2.1]hept-
2-ene-1-carboxamide 4b showing 50% probability displacement ellipsoids.
The availability of two alternative, highly selective, and high
yielding pathways for the rearrangement of intermediate carboca-
tions precisely controlled by the choice of substituents makes the
synthetic strategy reported herein particularly attractive for the
development of libraries of chiral building blocks for wide ranging
applications.
4.2. Synthesis of 1-bromo-bicyclo[2.2.1]heptan-2-one oximes
(general procedure)
3. Conclusion
A single-necked, round-bottomed flask equipped with a mag-
netic stirring bar was charged with 1 mmol of ketone 1a-c, 2 mmol
(0.139 g) of pyridine and 1.5 mmol (0.119 g) of hydroxylamine
hydrochloride in 50 mL of dry isopropanol. The mixture was stirred
for 4 hours at reflux (in the case of 1a, 16 hours), and the solvent
was removed under reduced pressure at 40 °C. Dichloromethane
(100 mL) and 0.1M hydrochloric acid (50 mL) were added to the
resulting solid and the organic phase was separated and washed
with 3 ꢀ 50 mL of distilled water. The organic phase was dried over
magnesium sulfate, filtered, and concentrated by rotary evapora-
tion. The product can be used in the next step without additional
purification. An analytical sample can be prepared by recrystalliza-
tion from isopropanol.
Precise control over the rearrangement of derivatives of chiral
1-bromo-N-nitroiminonorbornanes can be achieved via the choice
of substituents within a norboranone skeleton. The simplicity of
these transformations opens up a novel and straightforward
synthetic pathway to enantiopure derivatives of bridgehead
norbornane carboxamides in just three steps, starting from
1-bromonorbornanones. The described route constitutes a model
procedure for the preparation of a library of norbornane-based
functionalized compounds for a wide range of applications.
4. Experimental
4.1. General
4.2.1. (1R,4R)-1-Bromo-3,3,4-trimethylbicyclo[2.2.1]heptan-2-
one oxime 2a
This compound was obtained from (1R,4R)-1-bromo-3,3,4-trim-
ethylbicyclo[2.2.1]heptan-2-one 1a in 86% yield. Mp: 201ꢁ203 °C.
All experiments, unless otherwise stated, were carried under an
argon atmosphere. The 1H and13C NMR spectra were recorded on
‘Mercury 400’ Varian and Bruker AM 400 (400 MHz) spectrome-
ters. Tetramethylsilane was used as the internal standard. IR
½
a 2D0
ꢂ
¼ ꢁ38:0 (c 0.88, CHCl3). 1H NMR (400.45 MHz, [D6]DMSO): d =
1.01 (s, 3H); 1.20 (s, 3H); 1.22 (s, 3H); 1.53 (td, J = 12.6, 5.2 Hz, 1H);

820
O. V. Grytsai et al. / Tetrahedron: Asymmetry 24 (2013) 817–821
1.79ꢁ1.97 (m, 3H); 2.09 (d, J = 9.9 Hz, 1H); 2.19 (td, J = 12.6, 3.2 Hz,
1H); 10.37 (s, 1H). 13C {1H} NMR (75 MHz, CDCl3): d = 15.12, 19.30,
19.65, 33.87, 39.69, 45.85, 48.08, 51.27, 60.80, 167.17. IR (KBr,
cm-1): 3272, 3154, 2872, 2929, 2949, 2974, 1549. HRMS (CI,
CH4): calculated: 246.0494; found: 246.0505
CDCl3): d = 1.24 (s, 3H); 1.36 (s, 3H); 1.81ꢁ1.88 (m, 2H);
2.01ꢁ2.14 (m, 3H); 2.24ꢁ2.34 (m,1H); 2.37ꢁ2.42 (m, 1H). 13C
{1H} NMR (75 MHz, CDCl3): d = 22.69, 25.32, 25.60, 37.67, 45.49,
47.45, 48.42, 60.18, 184.64. IR (KBr, cm-1): 1307, 1314, 1560,
1647, 2876, 2936, 2974, 2988. MS (CI): m/z 261.1 (M+H).
4.2.2. (1R,4R)-1-Bromo-3,3-dimethylbicyclo[2.2.1]heptan-2-one
oxime 2b
4.3.3. (1R,4S)-1-Bromo-7,7-dimethyl-N-nitrobicyclo[2.2.1]hep-
tan-2-imine 3c
This compound was obtained from (1R,4R)-1-bromo-3,3-dim-
ethylbicyclo[2.2.1]heptan-2-one 1b in 94% yield. Mp: 222ꢁ223
This compound was obtained from (1R,4S)-1-bromo-7,7-dim-
ethylbicyclo[2.2.1]heptan-2-one oxime 2c in 85% yield. Mp:
°C. ½a 2D0
ꢂ
¼ ꢁ59:6 (c 0.87, CHCl3). 1H NMR (400.45 MHz, [D6]DMSO):
42ꢁ43 °C. ½a 2D0
ꢂ
¼ ꢁ41:25 (c 0.91, CHCl3). 1H NMR (300 MHz,
d = 1.29 (s, 6H), 1.705ꢁ1.94 (m, 5H), 2.10 (td, J = 12.1, 3.4 Hz, 1H),
2.19 (d, J = 9.6 Hz, 1H), 10.34 (s, 1H). 13C {1H} NMR (75 MHz,
CDCl3): d = 22.14, 23.06, 38.10, 26.13, 44.08, 46.23, 47.07, 61.35,
166.30. IR (KBr, cm-1): 3275, 3165, 2890, 2949, 2989, 1452. HRMS
(CI, CH4): calculated: 232.0337; found: 232.0344.
CDCl3): d = 0.97 (s, 3H); 1.09 (s, 3H); 1.42ꢁ1.51 (m, 1H);
2.03ꢁ2.19 (m, 3H); 2.27 (d, J = 18.6 Hz, 1H); 2.31ꢁ2.42 (m, 1H);
2.77ꢁ2.85 (m, 1H). 13C {1H} NMR (75 MHz, CDCl3): d = 183.80,
69.12, 51.33, 40.34, 35.18, 34.92, 27.82, 19.62, 18.91. IR (KBr, cm-1):
1295, 1313, 1575, 1647, 1654, 2879, 2941, 2972, 3429. HRMS (CI,
CH4): calculated: 261.0239; found: 261.0228.
4.2.3. (1R,4S)-1-Bromo-7,7-dimethylbicyclo[2.2.1]heptan-2-one
oxime 2c
4.4. Reaction of N-nitroimines 3a-c with a cyanide ion (general
This compound was obtained from (1R,4S)-1-bromo-7,7-dim-
ethylbicyclo[2.2.1]heptan-2-one 1c in 91% yield. Mp: 190ꢁ191
procedure)
°C. ½a 2D0
ꢂ
¼ ꢁ49:3 (c 0.85, CHCl3). 1H NMR (400.45 MHz, [D6]DMSO):
A solution of nitrimine (1 mmol) in methanol (10 mL) was
added to the mixture of acetone cyanohydrin (2 mmol, 0.170 g)
and potassium hydroxide (1.5 mmol, b0.084 g) in distilled water
(10 mL). The resulting mixture was stirred magnetically and
refluxed for 20 min. After cooling in ice, an excess of 3 M aqueous
hydrochloric acid was added over 5 min with vigorous stirring.
Almost immediate precipitation of carboxamide 4a,b or 5 was
accompanied by gas (N2O) evolution. The amide was filtered off,
washed with distilled water (2 ꢀ 10 mL), dried in a vacuum desic-
cator overnight, and recrystallized from absolute 2-propanol.
d = 0.92 (s, 3H); 1.05 (s, PH); 1.34ꢁ1.43 (m, 1H); 1.95ꢁ2.07 (m,
3H); 2.18ꢁ2.30 (m, 2H); 2.63ꢁ2.71 (m, 1H); 9.7 (br s, 1H). 13C
{1H} NMR (75 MHz, CDCl3): d = 163.52, 70.17, 50.47, 40.44,
36.14, 33.32, 28.44, 19.80, 18.83. IR (KBr, cm-1): 3304, 2890,
2935, 2965, 2983,1437. HRMS (CI, CH4): calculated: 232.0337;
found: 232.0349.
4.3. Synthesis of N-nitroimines (general procedure)
To a solution of 1 mmol oxime 2a-c in dry ether was added a
concentrated aqueous solution of 2.4 mmol (0.166 g) of sodium
nitrite. Concentrated sulfuric acid (1 mmol, 0.096 g) diluted to a
20% aqueous solution was then added cautiously over 10 min with
vigorous swirling. The ether layer turned brown within 10 minutes
from the start of the addition of the acid. The ether layer was sep-
arated and solvent was removed on a rotary evaporator with the
water bath temperature not exceeding 40 °C. Complete removal
of the ether coincided with the disappearance of the brown color-
ation. Next, crude N-nitroimine was dissolved in dichloromethane
(50 mL) washed with distilled water three times, dried over mag-
nesium sulfate, and filtered. The solvent was removed by rotary
evaporation with the water bath temperature not exceeding 40
°C. The compounds obtained can be used in the next step without
further purification.
4.4.1. (1R,4R)-2-Bromo-4,7,7-trimethylbicyclo[2.2.1]hept-2-
ene-1-carboxamide 4a
This compound was obtained from (1R,4R)-1-bromo-3,3,4-
dimethyl-N-nitrobicyclo[2.2.1]heptan-2-imine 3a in 88% yield.
Mp: 146ꢁ148 °C. ½a D20
ꢂ
¼ þ73:35 (c 0.85, CHCl3). 1H NMR (300
MHz, CDCl3): d
= 0.83 (s, 3H); 0.97 (s, 3H); 1.07 (s, 3H);
1.18ꢁ1.37 (m, 2H); 1.73 (ddd, J = 11.7, 8.5, 3.3 Hz, 1H); 2.28
(ddd, J = 11.7, 8.6, 3.0 Hz, 1H); 5.63 (br s, 1H); 5,97 (s, 1H); 6,39
(br s, 1H). 13C {1H} NMR (75 MHz, CDCl3): d = 172.16, 141.95,
121.28, 70.21, 60.70, 57.25, 33.18, 27.61, 18.35, 17.77, 13.28. IR
(KBr, cm-1): 3503, 3371, 3199, 2957, 2929, 1664, 1606, 1439,
1389. HRMS (CI, CH4): calculated: 258.0494; found: 258.0497.
4.4.2. (1R,4R)-2-Bromo-7,7-dimethylbicyclo[2.2.1]hept-2-ene-1-
carboxamide 4b
4.3.1. (1R,4R)-1-Bromo-3,3,4-trimethyl-N-nitrobicyclo[2.2.1]hep-
tan-2-imine 3a
This compound was obtained from (1R,4R)-1-bromo-3,3-
dimethyl-N-nitrobicyclo[2.2.1]heptan-2-imine 3b in 82% yield.
This compound was obtained as a mixture of syn- and anti-iso-
mers (1: 1) from (1R,4R)-1-bromo-3,3,4-trimethylbicyclo[2.2.1]-
heptan-2-one oxime 2a in 90% yield. Mp: 144ꢁ146 °C.
Mp: 163ꢁ164 °C. ½a D20
ꢂ
¼ þ75:65 (c 0.81, CHCl3). 1H NMR (300
MHz, CDCl3): d = 0.94 (s, 3H); 1.07ꢁ1.14 (m, 4H); 1.29 (ddd, J =
12.3, 9.2, 3.6 Hz, 1H); 1.92ꢁ2.01 (m, 1H); 2.24ꢁ2.32 (m, 1H);
2.46 (t, J = 3.4 Hz, 1H); 5.64 (br s, 1H); 6.20 (d, J = 3.3 Hz, 1H);
6.72 (br s, 1H). 13C {1H} NMR (75 MHz, CDCl3): d = 172.21,
138.01, 122.31, 68.55, 59.49, 54.19, 27.08, 25.54, 20.62, 20.51. IR
(KBr, cm-1): 1385, 1398, 1612, 1679, 2886, 2964, 3151, 3489,
3453, 3151. HRMS (CI, CH4): calculated: 244.0337; found:
244.0341.
½
a 2D0
ꢂ
¼ ꢁ65:3 (c 0.86, CHCl3). 1H NMR (300 MHz, CDCl3): d = 1.28
(s, 3H); 1.05 (s, 3H); 1.10 (s, 3H); 1.14 (s, 3H); 1.16 (s, 3H); 1.22
(s, 3H); 1.57ꢁ1.70 (m, 2H); 1.82ꢁ1.99 (m, 4H); 2.07ꢁ2.17 (m,
1H); 2.21ꢁ 2.43 (m, 5H). 13C {1H} NMR (75 MHz, CDCl3):
d = 184.99, 183.36, 59.51, 57.92, 53.44, 50.41, 49.54, 49.25, 49.19,
46.63, 39.16, 38.81, 33.25, 32.94, 24.19, 22.12, 21.41, 19.82,
14.95, 14.87. IR (KBr, cm-1): 1307, 1465, 1567, 1648, 2877, 2934,
2975, 3434. MS (CI): m/z 275.1 (M+H).
4.4.3. (1S,4S)-3,3-Dimethyl-2-oxobicyclo[2.2.1]heptane-1-carbox-
amide 5
4.3.2. (1R,4R)-1-Bromo-3,3-dimethyl-N-nitrobicyclo[2.2.1]hept-
an-2-imine 3b
This compound was obtained from (1R,4S)-1-bromo-7,7-
dimethyl-N-nitrobicyclo[2.2.1]heptan-2-imine 3c in 78% yield.
This compound was obtained from (1R,4R)-1-bromo-3,3-
dimethylbicyclo[2.2.1]heptan-2-one oxime 2b in 81% yield. Mp:
Mp: 158ꢁ159 °C. ½a D20
ꢂ
¼ ꢁ52:5 (c 1.30, CHCl3). 1H NMR (500
MHz, CDCl3): d = 1.06 (s, 3H); 1.07 (s, 3H); 1.61 (dt, J = 12.9, 6.9
Hz, 1H); 1.82 (m, 2H); 2.05ꢁ2.11 (m, 1H); 2.21ꢁ2.27 (m, 1H);
130ꢁ131 °C. ½a 2D0
ꢂ
¼ ꢁ73:2 (c 0.93, CHCl3). 1H NMR (300 MHz,

O. V. Grytsai et al. / Tetrahedron: Asymmetry 24 (2013) 817–821
821
6.02 (br s, 1H); 7.55 (br s, 1H). 13C {1H} NMR (125 MHz, CDCl3): d =
220.21, 172.77, 61.04, 49.00, 44.78, 38.67, 31.71, 24.39, 23.20,
21.68. Anal. Calcd: C, 66.27; H, 8.34; N, 7.73; Found: C, 66.24; H,
8.37; N, 7.75.
8. Squire, M. D.; Burwell, A.; Ferrence, G. M.; Hitchcock, S.
Asymmetry 2002, 17, 1849–1854.
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556.
R
Tetrahedron
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