About the Leuckart reaction of chiral 2-norbornanones bearing electron-withdrawing groups: Reaction of bridgehead triflates and triflamides

Article abstract of DOI:10.1016/S0040-4020(03)00037-1

The mechanism of the Leuckart reaction of 3,3- and 7,7-dimethyl-2-oxo-1-norbornyl triflates and triflamides, synthesised by us starting from (1R)-camphor and (1R)-fenchone, has been studied. Strikingly, the electron-withdrawing capacity of the bridgehead substituents has demonstrated not to be enough to control the Wagner-Meerwein rearrangement during the course of the reaction, so that only both enantiomers of a 3,3-dimethylnorbornanediamine derivative have been obtained as final products. As a result, the total synthesis of these interesting chiral compounds has been optimised and shortened until three overall steps starting from (1R)-fenchone.

Full text of DOI:10.1016/S0040-4020(03)00037-1

Tetrahedron 59 (2003) 1565–1569
About the Leuckart reaction of chiral 2-norbornanones
bearing electron-withdrawing groups: reaction of bridgehead
triflates and triflamides
a
Antonio Garcıa Martınez, Enrique Teso Vilar, Amelia Garcıa Fraile
b
b
,
,
*
*
´
´
´
a
´
and Paloma Martınez-Ruiz
a
´ ´ ´
Departamento de Quımica Organica I, Facultad de Ciencias Quımicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n,
E-28040, Madrid, Spain
Departamento de Quımica Organica y Biologıa, Facultad de Ciencias, UNED, c/Senda del Rey 9, E-28040, Madrid, Spain
b
´
´
´
Received 5 July 2002; revised 20 November 2002; accepted 3 January 2003
Abstract—The mechanism of the Leuckart reaction of 3,3- and 7,7-dimethyl-2-oxo-1-norbornyl triflates and triflamides, synthesised by us
starting from (1R)-camphor and (1R)-fenchone, has been studied. Strikingly, the electron-withdrawing capacity of the bridgehead
substituents has demonstrated not to be enough to control the Wagner–Meerwein rearrangement during the course of the reaction, so that
only both enantiomers of a 3,3-dimethylnorbornanediamine derivative have been obtained as final products. As a result, the total synthesis of
these interesting chiral compounds has been optimised and shortened until three overall steps starting from (1R)-fenchone. q 2003 Elsevier
Science Ltd. All rights reserved.
1. Introduction
or a 2-acylamino carbocation 4 (Scheme 1).6b According to
it, an alternative way to obtain 7,7-dimethyl-1,2-
norbornanediamine derivatives with structural retention
could be the Leuckart reaction of substrates bearing
electron-withdrawing bridgehead substituents that
destabilise the rearranged 2-norbornyl cation 4.
The synthesis of chiral, vicinal diamines is a topic of interest
because of their potential applications in medicinal
chemistry as antitumour agents1,2 or as chiral ligands in
asymmetric synthesis.1,3 In the course of our research work
about the chemistry of chiral norbornane derivatives, we
have attempted the preparation of 1,2-norbornanediamines
through different approaches.4,5 Nevertheless, standard
procedures such as the synthesis and reduction of
2-norbornanoximes, or the reductive amination of
2-norbornanones with ammonia or amines, have failed
when applied to bridgehead amine derivatives.4 Finally, the
Leuckart reaction of different 7,7- or 3,3-dimethyl-2-
norbornanones has allowed us to obtain for the first time
both enantiomers of 3,3-dimethyl-1,2-norbornane-
diamines.6 However, we have not been able to synthesise
or even detect 7,7-dimethyl diamine precursors in any of the
reactions essayed.
The trifluoromethanesulphonamido (triflamido) and
trifluoromethanesulphonyloxy (trifliloxy) groups are well
known by their high overall electron-withdrawing effect;7
thus, it could be expected the Leuckart reaction of 2-oxo-1-
norbornyltriflamides or triflates to take place without
skeleton rearrangement. This would lead to the synthesis
of amino alcohol or diamine precursors with structural
retention, which is the main condition to obtain the desired
7,7-dimethylnorbornanediamine derivatives.
The mechanism proposed by us for the Leuckart reaction of
7,7-dimethyl-1-substituted-2-norbornanones 16 implies an
intermediate 2-formylamino-2-norbornyl cation 2, which
can either suffer a reduction by the formate ion to give a
formamide 3, or a W-M rearrangement to give a 2-acyloxy-
Keywords: Leuckart reaction; triflate; triflamide.
*
Corresponding author. Tel.: þ913944236; fax: þ913944103;
e-mail: palmarti@quim.ucm.es
Scheme 1.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00037-1

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A. G. Martınez et al. / Tetrahedron 59 (2003) 1565–1569
1566
Scheme 2.
2. Results
Scheme 4.
2.1. Leuckart reaction of N-(2-oxo-1-norbornyl)-
triflamides
The GC/MS monitoring of the Leuckart reaction of 7,7-
dimethyl triflamide 11 (Scheme 4) indicates that the first
step is the transacylation at the bridgehead position, leading
to the 7,7-dimethyl-2-norbornyl formamide 15 as first
intermediate. The reactivity of this formamide has been
studied by us,6c and explains the appearance of 3,3-dimethyl
formamide ent-12 as intermediate as well as the isolation of
diformamide ent-13 as only final product (59% yield). None
intermediate similar to compound 14 (see Scheme 3) was
detected in the course of the reaction, which means that the
formamide addition to the carbonyl group to give a
2-formylamino-2-norbornyl cation is slower than the
transamidation at the bridgehead position. Consequently,
we were not able to study the effect of the triflamide group
on the stability of adjacent 7,7- or 3,3-dimethyl-2-norbornyl
cations. This fact prompted us to study the process starting
from 2-oxo-1-norbornyl triflates, whose bridgehead group is
not expected to suffer transacylation reactions in this
medium.
The triflamide moiety is well known as protecting group of
primary and secondary amines,8 mainly as a variant of the
Gabriel synthesis,9 but its reactivity as bridgehead sub-
stituent in rigid frameworks has not been studied to date.
The synthesis of the new N-(2-oxo-1-norbornyl)triflamides
10 and 11, starting from 2-methyliden-1-norbornylamines 6
and 7,10 is depicted in Scheme 2. The first step is the
reaction of the primary amino group with triflic anhydride in
the presence of triethylamine, at 2788C. The ozonolysis of
8 and 9 in CH2Cl2 at 2788C, followed by treatment with
dimethyl sulphide, gives the desired enantiopure 2-oxo-1-
norbornyltriflamides 10 and 11 with high yields.
The reaction of 10 with the formamide/formic acid couple
was carried out following the standard procedure described
in the literature.6,11 According to the GC/MS monitoring,
two different intermediates have been detected, that yield
the same 3,3-dimethyl formamide as the only final product
at the end of the process. The evolution of the reaction
mixture is summarised in Scheme 3. By one side, the
triflamide moiety suffers a N–S bond fission followed by
N-formylation, to give the (1R)-N-(3,3-dimethyl-2-oxo-1-
norbornyl)formamide 12.6c On the other side, the other
intermediate compound was also observed, which was
identified as N-(3,3-dimethyl-2-formylamino-1-norbornyl)-
triflamide 14 according to its mass spectrum fragmentation
pattern.12 However, all the attempts to isolate pure
compound 14 from the reaction medium by means of
column chromatography or recrystallisation were
unsuccessful. Through a transacylation process at the
bridgehead position, this triflamide also affords the
(1R,2R)-N-(3,3-dimethyl-2-formylamino-1-norbornyl)-
formamide 13 as final product (68% overall yield).
2.2. Leuckart reaction of 2-oxo-1-norbornyl triflates
We have described in previous papers the synthesis and
reactivity in solvolytic media of chiral 2-oxo-1-norbornyl
triflates starting from naturally occurring 2-norborna-
nones,13 as well as their application to the synthesis of
b-amino alcohols10 and diols.14 To study the behaviour of
these substrates with the HCOOH/HCONH2 couple, the
Leuckart reaction of (1R)-3,3-dimethyl-2-oxo-1-norbornyl
triflate 1913 was carried out. The results are shown in
Scheme 5: two different final products 18 and 13 were
obtained, resulting from two competitive reaction pathways.
After purification by column chromatography (silica gel,
AcOEt/MeOH), these compounds were characterised as
(1R)-5,5-dimethyl-1-bicyclo[2.1.1]hexanecarboxamide 18
(44% yield), and (1R,2R)-N-(3,3-dimethyl-2-formylamino-
1-norbornyl)formamide 13 (35% yield). According to our
experience about the reactivity of ketotriflate 19 in
solvolytic media,13b,15 we can conclude that a ring
contraction process favoured by the nucleofugacity of the
triflate group and the s-participation of the C2–C3 bond
originates the formation of carboxamide 18. The other
reaction pathway constitutes the proper Leuckart reaction of
the 2-oxo-1-norbornyl triflate that yields again diformamide
13 at the end of the process. As intermediates in this route,
we have detected the 7,7-dimethyl-2-oxo-1-norbornyl tri-
flamide ent-11 (less than 10%), and the bridgehead
formamides ent-15 and 12 (Scheme 5).
Scheme 3.

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A. G. Martınez et al. / Tetrahedron 59 (2003) 1565–1569
1567
Scheme 6.
The first intermediate detected is the (1S)-N-(3,3-dimethyl-
2-oxo-1-norbornyl)triflamide ent-10, together with a little
amount of (1S)-N-(3,3-dimethyl-2-oxo-1-norbornyl)forma-
mide ent-12. The appearance of the intermediate (1S)-N-
(3,3-dimethyl-2-formylamino-1-norbornyl)triflamide ent-
14 was also observed, coming from the formamide addition
to ketone ent-10. All the intermediates give finally
diformamide ent-13 as the only final product with an
overall yield of 72%. Consequently, this route is the shortest
way (three overall steps starting from (1R)-fenchone) to
access to the synthesis of 1,2-norbanediamine derivatives.
The mechanism proposed in Scheme 6 involves a Wagner–
Meerwein rearrangement of carbocation 24 to give a
triflyloxycarbenium ion 25. In a similar way to cation 21
(see Scheme 5), it suffers an intramolecular transacylation to
give 26. The N–C bond hydrolysis in 26 gives triflamide
ent-10, which reacts with formamide and formic acid to
yield finally diformamide ent-13 through the triflamide ent-
14 or the formamide ent-12 (see Scheme 3). This last
compound can also be originated through the N–S bond
hydrolysis in the intermediate 26. None ring contraction
product was detected in the crude reaction, in agreement
with the different behaviour of triflates 19 and 23 observed
in solvolytic media.13b
Scheme 5.
As shown in Scheme 5, the mechanism proposed implies the
formamide addition to the carbonyl group of 19 to give the
2-formylamino-2-norbornylcation 20. Owing to the
electron-withdrawing effect of the trifluoromethanesul-
phonyl group, this cation should be more stable than the
triflyloxycarbenium ion 21, originated after a Wagner–
Meerwein rearrangement. Nevertheless, by monitoring the
process we have not detected in the reaction medium any
2-formylamino-1-norbornyl triflate resulting from the
reduction of cation 20. It means that carbocation 21 suffers
an intramolecular transamidation that shifts the equilibrium
to the right, in a similar way to the Leuckart reaction of
2-oxo-1-norbornyl acetates or propionates.6b The com-
petitive hydrolysis of the N–S or N–C bond in the
intermediate 22 explains both formamide ent-15 and
triflamide ent-11 to appear simultaneously in the reaction
medium. The later evolution of the intermediates follows
the mechanism described before (see Schemes 2–4), and
finally diformamide 13 is obtained as the only product of
this reaction pathway.
3. Conclusions
In summary, we have shown that a cascade of Wagner–
Meerwein transpositions and intramolecular transacylations
dominates the Leuckart reaction of 7,7-dimethyl-2-nor-
bornanones bearing N- or O-trifluoromethanesulphonyl
substituents at the bridgehead position. These rearrange-
ments that had been previously described by us for the
analogous amides and esters, cannot be avoided by
increasing the electron-withdrawing capacity of the
bridgehead groups, and the only products of the process
The last substrate tested for the Leuckart reaction was the
(1R)-7,7-dimethyl-2-oxo-1-norbornyltriflate2314(Scheme6).
As in the case of 3,3-dimethyl triflate 19, the reaction
pathway is consistent with consecutive Wagner–Meerwein
rearrangements and intramolecular transacylations.

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A. G. Martınez et al. / Tetrahedron 59 (2003) 1565–1569
1568
are 1,2-diamides having a gem-dimethyl group attached to
the C3 centre. Therefore, the 2I effect of both triflamide and
trifliloxy groups seems to be compensated by their electron
donating þM effect7b,16 towards an adjacent cationic centre.
Besides the mechanistic relevance of the process, the
employment of 2-oxo-1-norbornyl triflates as substrates for
the Leuckart reaction has resulted in an optimisation of the
stereoselective synthesis of enantiopure 1,2-norbornanedia-
mine precursors, that can be obtained in three steps, with an
overall yield of 53%, starting from (1R)-fenchone.
1.00 g of (1R)-7,7-dimethyl-2-methyliden-1-norbornyl-
amine 7 gave 1.63 g of triflamide 9 (87% yield, white
crystals). Mp: 115.9–118.08C. [a]2D0¼þ2.8 (c 1.03,
CH2Cl2). IR (KBr) n 3270, 2960, 1440, 1370, 1240, 1210,
1
1200, 1150 cm21. H NMR (300 MHz, CDCl3) d 5.06 (t,
J¼2.6 Hz, 1H), 4.89 (t, J¼2.0 Hz, 1H), 4.77 (br. s, 1H), 2.50
(m, 2H), 2.06 (dt, J¼16.5, 2.0 Hz, 1H), 1.97 (m, 1H), 1.78
(m, 2H), 1.39 (m, 1H), 1.02 (s, 3H), 0.88 (s, 3H) ppm. 13C
NMR (75 MHz, CDCl3) d 153.4, 119.5 (q, J¼318.0 Hz),
104.4, 73.5, 48.4, 41.1, 35.7, 28.2, 27.2, 18.7, 18.3 ppm. MS
(%B): 283 (Mþz, 3), 268 (2), 254 (4), 240 (10), 228 (22), 214
(4), 150 (41), 134 (8), 106 (30), 94 (39), 81 (21), 69 (50), 53
(30), 41 (100). Exact mass calcd: 283.0854; found:
283.0863.
4. Experimental
4.1. General
4.3. Synthesis of N-(2-oxo-1-norbornyl)triflamides
1H and 13C NMR spectra: Varian VXR 300S and Brucker
AC250 spectrometers, with tetramethylsilane as internal
standard. Capillary GC/MS: Shimadzu QP-17A (column
type: TRB-1, 30 m) coupled to a Shimadzu QP-5000 Mass-
spectrometer (EI, 60 eV). Exact mass: VG AutoSpec mass
spectrometer. Melting points: Gallenkamp apparatus; values
are uncorrected. Molecular rotations: Perkin–Elmer 241
spectropolarimeter. For the preparation of 6 and 7 from
(1R)-camphor and (1R)-fenchone, respectively, see Ref. 10.
For the synthesis of compounds 19 and 23, see Ref. 13.
In a typical procedure, a solution of 2-methyliden-1-
norbornylamine (1.00 g, 3.5 mmol) in 40 mL of CH2Cl2 at
2788C was submitted to ozonolysis and monitored by GC
until disappearance of the starting material. After treatment
with SMe2, water (30 mL) was added, and the organic phase
separated. The aqueous layer was extracted again with
CH2Cl2 (3£20 mL), and the combined organic extracts
dried with MgSO4. After filtration and solvent elimination,
the obtained ketones were very pure; nevertheless, purifi-
cation can be made through recrystallisation in hexane at
2258C.
4.2. Synthesis of N-(2-methyliden-1-norbornyl)-
triflamides
4.3.1. (1R)-N-(3,3-Dimethyl-2-oxo-1-norbornyl)tri-
flamide 10. According to the procedure described above,
1.00 g of (1R)-N-(3,3-dimethyl-2-methyliden-1-norbornyl)-
triflamide 8 gave 0.95 g of ketone 10. Yield: 94% (colour-
less syrup), [a]D20¼þ19.5 (c 0.88, CH2Cl2). IR (CCl4) n
3150, 2970, 1750, 1715, 1420, 1380, 1355, 1230, 1200,
1150, 1030 cm21. 1H NMR (250 MHz, CDCl3) d 5.75 (br. s,
1H), 2.35–1.80 (m, 6H), 1.55 (m, 1H), 1.10 (s, 3H), 1.09 (s,
3H) ppm. 13C NMR (62.5 MHz, CDCl3) d 215.3, 118.9 (q,
J¼319 Hz), 70.6, 46.2, 42.6, 38.6, 29.1, 23.7, 23.4,
21.3 ppm. MS (%B): 257 (Mþz2C2H4, 1), 242 (1), 214
(64), 136 (1), 124 (11), 108 (8), 83 (13), 69 (100), 55 (28),
41 (65). Exact mass calcd: 285.0646; found: 285.0644.
In a typical procedure, a solution of trifluoromethanesul-
phonic anhydride (1.1 mL, 6.6 mmol) in 10 mL of CH2Cl2
was added at 2788C over a solution of the corresponding
2-methylyden-1-norbornylamine (1.00 g, 6.6 mmol) and
triethylamine (2.7 mL, 19.7 mmol) in 20 mL of CH2Cl2.
When the hydrochloride of the amine was used as starting
compound, 26.5 mmol of triethylamine were added, with
similar final yield. The reaction was maintained under
stirring 30 min at 2788C, and 30 min at room temperature.
Then the mixture was hydrolysed with 30 mL of water, and
extracted with CH2Cl2 (2£30 mL). The organic layer was
washed with 10% HCl solution (2£20 mL) and brine
(2£30 mL), and dried over MgSO4. After solvent elimin-
ation, the obtained triflamides were very pure; nevertheless,
purification can be made through recrystallisation in hexane
at 2258C.
4.3.2. (1R)-N-(7,7-Dimethyl-2-oxo-1-norbornyl)tri-
flamide 11. According to the procedure described above,
1.00 g of (1R)-N-(3,3-dimethyl-2-methyliden-1-norbornyl)-
triflamide 9 gave 0.82 g of ketone 11. Yield: 81% (white
crystals), mp: 95.7–98.28C, [a]2D0¼246.8 (c 0.80, CH2Cl2).
IR (CCl4) n 3100, 2960, 2900, 1750, 1420, 1380, 1370,
1220, 1200, 1140, 1070 cm21. 1H NMR (300 MHz, CDCl3)
d 5.60 (br. s, 1H), 2.66 (m, 1H), 2.48 (dt, J¼18.6, 3.9 Hz,
1H), 2.20–2.02 (m, 3H), 1.68–1.46 (m, 2H), 1.19 (s, 3H),
0.90 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3) d 211.3,
119.3 (q, J¼319.1 Hz), 75.9, 47.5, 40.9, 39.8, 26.3, 23.1,
19.5, 18.6 ppm. MS (%B): 257 (Mþz2C2H4, 14), 241 (23),
228 (1), 216 (23), 201 (3), 188 (3), 146 (1), 136 (3), 124
(51), 108 (21), 97 (19), 83 (23), 69 (46), 55 (61), 41 (100).
Exact mass calcd: 285.0646; found: 285.0638.
4.2.1. (1R)-N-(3,3-Dimethyl-2-methyliden-1-norbornyl)-
triflamide 8. According to the procedure described above,
1.00 g of (1R)-3,3-dimethyl-2-methyliden-1-norbornyl-
amine 6 gave 1.65 g of triflamide 8. Yield: 88% (colourless
syrup), [a]2D0¼þ9.7 (c 1.01, CH2Cl2). IR (CCl4) n 3385,
2980, 1430, 1380, 1230, 1200, 1150 cm21 1H NMR
.
(300 MHz, CDCl3) d 5.51 (br. s, 1H), 4.90 (s, 1H), 4.78
(s, 1H), 2.20–1.50 (m, 7H), 1.11 (s, 3H), 1.09 (s, 3H) ppm.
13C NMR (75 MHz, CDCl3)
d
163.1, 119.1 (q,
J¼318.0 Hz), 99.8, 69.4, 44.6, 42.1, 41.1, 33.6, 29.2, 25.8,
24.0 ppm. MS (%B): 283 (Mþz, 4), 254 (3), 240 (100), 214
(2), 150 (10), 134 (4), 121 (6), 106 (13), 91 (12), 69 (43), 41
(42). Exact mass calcd: 283.0854; found: 283.0844.
4.4. General procedure for the Leuckart reaction of
2-norbornanones
4.2.2. (1S)-N-(7,7-Dimethyl-2-methyliden-1-norbornyl)-
triflamide 9. According to the procedure described above,
A mixture of 2.0 mmol of the corresponding 2-norbornanone,

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A. G. Martınez et al. / Tetrahedron 59 (2003) 1565–1569
1569
formamide (32.2 mmol) and formic acid (17.9 mmol) was
Acknowledgements
heated to 1508C. The reaction progress was monitored by
GC/MS until total disappearance of starting ketone and
intermediate compounds. Lower yields were observed after
long reaction times due to formation of dark-coloured
polymeric products. After completion of the reaction,
20 mL of saturated aqueous solution of NaHCO3 were
added, and the mixture was extracted with CH2Cl2
(4£30 mL). The organic layer was washed with water
(30 mL) and brine (20 mL) and dried over anhydrous
MgSO4. After filtration, the solvent was evaporated in
vacuo. The residue was analysed by GC/MS and NMR
´
We wish to thank the Ministerio de Ciencia y Tecnologıa of
Spain (research project BQU2001-1347-C02-02) and
UNED (research project 2001V/PROYT/18) for the finan-
cial support of this work.
References
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1
(endo/exo¼95:5, H NMR 300 MHz, CDCl3). The crude
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reaction mixture was decolourised with charcoal and
recrystallised in MeOH/Et2O; this procedure gave in all
cases the pure endo-epimer.
4.4.1. Leuckart reaction of (1R)-N-(3,3-dimethyl-2-oxo-
1-norbornyl)triflamide 10. Following the procedure
described above, 0.30 g (1.05 mmol), of (1R)-N-(3,3-
dimethyl-2-oxo-1-norbornyl)triflamide 10 gave 0.15 g of
(1R,2R)-N-(3,3-dimethyl-2-formylamine-1-norbornyl)for-
mamide 13, 68% yield. [a]2D0¼258.5 (c 0.98, MeOH). As
intermediate of the reaction we detected by GC/MS the
(1R,2R)-N-(3,3-dimethyl-2-formylamine-1-norbornyl)tri-
flamide 14: MS (%B): 214 (Mþz2C5H11NO, 5), 181 (13),
163 (3), 136 (3), 100 (8), 82 (100), 55 (18), 46 (20), 41 (18).
´ ´
4. Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; de la Moya
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Cerero, S.; Dıaz Oliva, C.; Subramanian, L. R.; Maichle, C.
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´ ´
5. Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; de la Moya
´
Cerero, S.; Martıınez Ruiz, P. Tetrahedron: Asymmetry 1998,
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´ ´ ´
´ ´
6. (a) Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; Martınez
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4.4.2. Leuckart reaction of (1R)-N-(7,7-dimethyl-2-oxo-
1-norbornyl)triflamide 11. Following the procedure
described above, 0.30 g (1.05 mmol) of (1R)-N-(7,7-
dimethyl-2-oxo-1-norbornyl)triflamide 11 gave 0.13 g of
(1S,2S)-N-(3,3-dimethyl-2-formylamine-1-norbornyl)for-
mamide ent-13, 59% yield. [a]2D0¼þ57.6 (c 1.03, MeOH).
´ ´
A. G.; Teso Vilar, E.; Garcıa Fraile, A.; Martınez-Ruiz, P. Eur.
´
J. Org. Chem. 2001, 15, 2805–2808. (c) Martınez, A. G.; Teso
´ ´
Vilar, E.; Garcıa Fraile, A.; Martınez-Ruiz, P. Tetrahedron:
Asymmetry 2001, 12, 2153–2158.
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4.4.3. Leuckart reaction of (1R)-3,3-dimethyl-2-oxo-
norbornyl triflate 19. Following the procedure described
above, the reaction was carried out starting from 0.30 g
(1.04 mmol) of (1R)-3,3-dimethyl-2-oxo-norbornyl triflate.
The crude reaction was purified by column chromatography
(silica gel, AcOEt/MeOH, 4:1) gave a mixture of 0.08 g of
diformamide 13 (35% yield), [a]2D0¼256.8 (c 0.72, MeOH),
and 0.07 g (44% yield) of (1R)-5,5-dimethyl-1-bi-
cycle[2.1.1]hexanecarboxamide 18.
´ ´
10. Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; de la Moya
´
Cerero, S.; Martınez Ruiz, P.; Subramanian, L. R.
Tetrahedron: Asymmetry 1996, 7, 1257–1260.
11. Moore, M. L. Org. React. 1949, 5, 301–330.
12. MS (EI, 60 eV) (% B): 214 (Mþz2C5H11NO, 5), 181 (13), 163
(3), 136 (3), 100 (8), 82 (100), 55 (18), 46 (20), 41 (18). For
comparison with other 1,2-norbornane derivatives, see:
4.4.4. (1R)-5,5-Dimethyl-1-bicycle[2.1.1]hexanecarbox-
amide 18. [a]2D0¼þ6.45 (c 0.77 MeOH). Mp: 82.8–
84.68C. IR (CHCl3) n: 3420, 2980, 2970, 1680, 1590,
1400 cm21. 1H NMR (300 MHz, CDCl3) d 6.25 (br. s, 1H),
5.45 (br. s, 1H), 2.22 (m, 1H), 2.07 (m, 1H), 1.92 (m, 1H),
1.78 (m, 2H), 1.65 (m, 1H), 1.25 (s, 3H), 1.16 (d, J¼7.2 Hz,
1H), 0.93 (s, 3H) ppm. 13C NMR (62.5 MHz, CDCl3) d
176.2, 56.6, 48.6, 43.5, 37.5, 29.5, 26.0, 19.6, 19.3 ppm. MS
(%B): 153 (Mþ, 3), 138 (23), 124 (13), 112 (25), 109 (17),
85 (52), 69 (49), 67 (55), 58 (47), 41 (100). Exact mass
calcd: 153.1154; found: 153.1159.
´ ´
Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; de la
´
Moya Cerero, S.; Martınez Ruiz, P. Rapid Commun. Mass
Spectrom. 1999, 13, 1472–1476.
´ ´
13. (a) Martınez, A. G.; Teso Vilar, E.; Osıo Barcina, J.;
´
Rodrıguez Herrero, M. E.; Manrique, J.; Hanack, M.;
Subramanian, L. R. Tetrahedron Lett. 1992, 33, 607–608. (b)
´
´
´
Martınez, A. G.; Teso Vilar, E.; Osıo Barcina, J.; Rodrıguez
Herrero, M. E.;delaMoyaCerero, S.;Hanack, M.;Subramanian,
L. R. Tetrahedron: Asymmetry 1993, 4, 2333–2334.
´ ´
14. Martınez, A. G.; Teso Vilar, E.; Garcıa Fraile, A.; de la Moya
´
Cerero, S.; Gonzalez-Fleitas, J. M.; Subramanian, L. R.
Tetrahedron: Asymmetry 1994, 5, 1373–1376.
4.4.5. Leuckart reaction of (1R)-7,7-dimethyl-2-oxo-
norbornyl triflate 23. Following the procedure described
above, 0.30 g (1.04 mmol) of triflate 23 gave 0.16 g (72%
yield) of (1S,2S)-N-(3,3-dimethyl-2-formylamine-1-nor-
bornyl)formamide ent-13. [a]2D0¼þ58.1 (c 0.71, MeOH).
´
´
15. Martınez, A. G.; Teso Vilar, E.; Osıo Barcina, J.; de la Moya
Cerero, S. Tetrahedron 1996, 52, 14041–14048.
16. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91,
165–195.