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NMR study of the effect of nitrogen-borane coordination on the conformational equilibrium of six membered ring heterocycles.
Teahdrm Vol. 47. tio.34. pp 69036914.1991 Rmted m Great Bntarn
Nl4R STUDY OF THE EFFECT
oo4o4020/91 $3 oo+ 00 Presspk @ 1991 Pergamon
OF NITROGEN-BORANE COORDINATION ON THE CQNFORl4ATIOBALEQUILIBRIUM
OF SIX m Angelina
Flores-Parra*,
RING BElERCNZTCLES
Norberto
Farfan,
Fernandes-Sanchez Departamento
de
Quimica,
Politecnico
Centro
Nacionsl
de
Albert0
InvestlgacMn
Apartado
I
and Rosallnda
Postal
Hernindez-Bautista,
y de Estudios
14-740,
Lilia
Contreras*
Mexico,
D
Avanzados F
de1
Instltuto
07000, Mexico
(Received m USA 24 May 1991)
Summary The syntheses, conformational and spectroscopic studies of N-borane adducts of 14 It was found that borane nitrogen containing six-membered ring heterocycles are reported In addition, it can be very can act as a conformational and configurational locking agent helpful for the assignment of the chemical shifts of other atoms or groups in the molecule as well as to ascertain the configuration at substituted carbons
Introduction’ The
analysis
important
of
neighboring
carbon
sensitive
to
to
the
space,
identification
at
of
N-borane
the in
means
chemical
was not
of
‘H.
of
organic
“B
fixes
shifts
it
has a more stable
may become important
and
shifts
are
through
as a chiral
its very
bonds
probe2-4
the configuration
on the application
preferred
conformation
of
figure
giving
In turn
of
1
and coupling
is
adducts
results
configurations
N-borane
Borane
N-borane
these
of
at
at
of
of
ring
atoms including
in
the
tools
is
important
configuration for
structural
to
notice
that
than in the salts analyses
6903
the
of
the
the
ring
detailed
conformational
nitrogen
NMR spectra
nitrogen
shifts
six-membered
fixing
enough to allow
the study
ring
chemical
adducts
capable
stable
allow
constants
13C, ‘H and “B
and plperazlnes were reported before but a careful 5-s Although ammonium salts present spectra undertaken
adductsg-“,
provides
nitrogen
interactions
can be used
group
at
chemical
by borane
addltion
the borane
heterocycles
assignment
13C and
produced
borane
solution,
the establishment
piperidines
adducts
focused
room temperature
assignment
analysis
effects
and hence,
is of
adducts
of
adducts
configurational
shown that
the presence
1-14
by spectroscopic
equilibrium.
N-borane the
atom2-’
attention
heterocycles
conformation study
of
allows We have
adducts,
nitrogen
paper
that
and electronic
through
In amine-borane quaternized
ring
NMR data
atoms
steric
and directly
In this
the
information
and the
Some N-borane and detailed very
atom
and In consequence,
in
similar the
NMR to
borane
such adducts
6904
A FLORES-PARRA~~al
_~ 1 2 4 5
RRRR-
8 R- H, X- 0 9 R- H, X- NH 10 R- CH,, X- 0 11 R- CH,, X- NCH,
3 R- CH,, R,- H 6 R- OH, R,-H 7 R- H, R,- OH
R,- R,- R,- H CH,, R,- R,- R,- H R,- CH,, R,- R,- H R,- R,- R,- CH,
i2 .B
N-CH,
+=P
R3
0
0
R,
12
13 R- R2- H, R,- CH,, R,- C,H, 14 R- CH,, R,- R,- H, R,-C,H, figure 1 RESULTS AND DISCUSSION. N-H SIX-DRMBERED RING HETERDCYCLES. Piperidine, 1 Borane addition to piperidine 1 produces an equatorial N-borane adduct (lBe, "B
chemical
shift b= -15 5 ppm, JB-H = 97 Hz), which shows a predominant chair conformation at room temperature, as established by the 'H NMFI spectrum coupled to the neighboring protons
The N-H appears at 6 = 3 68 ppm
The equatorlal and axial protons of 1Be appear as
separate signals shifted to low field compared to those of the free piperidine 1, the equatorial protons of 1Be belng more shifted than the corresponding axial ones (B[b~-&~l = 0 74 ppm for the C-2 and C-6 protons, 0 25 ppm for those of C-3 and C-5 and 0 18 ppmfor C-41 The 13C NMFIof 18e is similar to that of N-methylpiperidine159 and even more to its salt 15H9 (figure 21
This is explained in terms of the fact that 13C NMFt is especially
sensitive to steric effects and 18e is sterically similar to 15H With the difference that
0 25a*N-H
24
Jq+:
0
159
1 i NtH
,,w+'(=
hi++
22?%zY 53 41 1H9 ('1
llB NHR
1Be
21 8
55 2
15H9 figure 2
6905
SIX membered rmg heterocycles
the substitution
effect
of
nitrogen
at
C-2 and C-6
is
stronger
(Aa 9 5 ppm) when compared to compound 1Be (Aa 6 1 ppm) to
the
“C
longer
NMFtdata
interactions that
bond distance Indicates and from
the equatorial
2 exists with
room temperature, kinetic
at
Compound 2Be has
shifts
of
free
92
has
an
equatorial
of
Another 6 = -
C-methyl
figure
at C-3 and C-5
in B13
both and
effects
31,
in
shows
a 60-40
upfleld
69
4
2Ba
produced
rqurllbrlum
(') llB H,,R (J
Heating
ratio
that
shift
the
the
to 80/20
borane
at C-3 and C-5
at
gives
group
1s
(< 0 7 ppm)
63
5
li132
and
16He’O an
axial is
by the axial-borane
argument
and
borane
H
The latter
in favor
18 1 ppm LJ = 110 Hz),
conformers
solution
of
the ZBe/PBa ratio
2Be
equillbrlum,
6 of the
the
32 4
(6 = -15 5 ppm, J = 97 Hz)
A6(16Ra-16Rc).
of
no 1.3-diaxial
chloroform
34 37 59 301q309
23'20
2
2Be
Analysis is
Addition
and an evidence
small
23 ~':;(94)~2~~;H~
of
1.3-diaxlal
(figure
substltuents by the very
in
position
amine increases
46
an equatorial ratio
of
2S/-&H 26 40 52
borane
XI
there
The ‘H NMFI spectrum
conformation
54
produced
equal
chair
31
conformational
(1 47
since
and C-6
In equatorlal
47
Compound 2Ba
of
on C-2
2Be and 2Ba
in an excess
is provided
..
shift
equatorial
derivative
to low field
a preferred
two equatorial
34
methyl group
in
N-epimers
60°C
equatorial
effects
effect
shifted
the methyl group
products,
7 hours
largely
are
compared to C-N
in 1Be is
the substitution
in the N-methyl
phenomenon can be attributed
2.
2-Methylplperldlne
the
(1 66 fi)”
the borane
protons
2-Hethylpiperidine,
mixture
in B-N
that
This
may be
between
group by the
the equilibrium
that
and an axial
16Ha and
16He
group
. (2) Value. of
AH' RI)
figure
4
and
may display
a
r3C NMR 1,3-diaxial
in A and at C-4 and C-6 by the axial comes from the chemical
seems to be an average borane
(6 = -
assumed from comparison
by the 2-methyl
mlxturc
of
borane
supported
(figure
19 5 ppm15)
between 4)
value
that
in the B conformers
the
“C
clearly
between A near
chemical shows
and by N-methyl
the or
2Ba 1,3-diaxl.1
Interactlone,
A6(2Ba-2Ac)
0,.
6906
A FLORES-PARRAet al
N-borane
in
conformers
means that group
vicinal
is
interactions
indicate Je-H
It
lnteresting on comparison 2B, proved
is
of
“C
with
respect
with
to 21
a very
strong
2Be and at
only
This
with
to 21,
antiperlplanar
is
those
of
and
an
and
a
the
weaker
in conformational
of
Analysis
at
borane
and
effect
at
of
showing
are based of
identification
of
2 63 ppm in 2Be (A6 = 0 07
the C-6 axial
borane
that
The
‘H NM8 spectrum
3 25 ppm in 2Ba (Aa = 0 69 ppm to also
(a
idHe”
equilibrium
the
which allowed
appears
coupling
coordination)
16Ha is
proton
borane methyl
B-H
axial
16Ha
of
axial
equatorial ln
in
ammonium salts
28a
the
differences atom
the mixture
and at
inductive
angle
of
observed
1 27 ppm in 2Ba,
borane
nitrogen
the
The C-2 axial
effect
proton,
The C-2 methyl
an equatorial
borane
low field
which evidences is
found
has
at
1 36
a deshielding
on the methyl protons
3-Nethylpiperidine,
3.
The free
3 exists
plperidine
equatorial ratio,
position
comparison
molecule
is
while
to higher
epimers
piperidine
distinguishable
in
without as
3,
the
spectra
corresponding
chair
produces
as
conformation,
two N-eplmers
figure
steric
well
5
effects those
protons
axial
at
protons
near
of
C-2
331;@~; 26
33
are 51
30 19320 94@!:':* HC 29
45
91
observed,
(‘1
“B
figure
70
5
the nitrogen more
are
atom
abundant
shifted
in 14
to allow
In iH NMR, all
N-epimer
as
group
an 86 to
those
of
3Be,
are
lBe,
the
0 06 ppm to
higher
0 10 and 0 31 ppm, respectively,
H
29 H3C 36+j5;;o 29 18 17
A NMR
the 3-methyl
has the advantage
the same trends
shifted
17Ha’6 (11 not
the
and C-6
field 46
with
3Be and 3Ba in
This molecule
Compound 3Be shows
equatorial
anchored, the
addition
from the NM8 spectra,
between
of
in a preferred
Borane
as deduced
protons
field
H-B-H and
proportion
The
the
to assume that
respect
important
equatorial
of
due to the complexity
ppm in effect
an
larger
NM8 data
the C-2 and C-6 protons
an
equlllbrium
adducts
reasonable
difficult
low field
a
borane
its
the
coordination
indicates
between
of
between
favoring
a weaker
value
similarities
ppm to
The existence
destabilizing,
constants larger
A
63
l7 73H3C 3Ba
g
H
6907
SIX membered nng heterccycles
Compound 33a assumptlon around
seems to be
1s based
In a conformatlonal
shiftsI
of
shifted
also
1s that
that
“C
the
33 ppm) and also
Ii’He and 17Ha,
with
on
the similarity
supports
towards “B
the
NMR spectra
4
1s
positlon
Borane
N-epimers
(4Be
borane
in
shows only
a preferred
a steric
are
field
5 8 ppm whereas shifted
an axial
methyl groups
in
a 60
effect
the to
that
effect
of
and the axial an axial
which
A strong
the C-6
that
important
a sharp
largely axlal
(an
chemical
N-substltuent
of
at
the
compounds
13C chemical
equlllbrlum
in favor
of
this
-14 6 ppm which
This
1s expected
ln both
conformatlonal
argument
B
towards N-Cl43
shlfts
Comparison
the
signal
conformation case
of
40 ratio is
borane
one 1s at field
evidences
in
1,3-diaxial
“B
larger
methyl
of
3Ba
equilibrium
1s compatible
groups
2.
of
two
chemical
The axial borane
0 3 ppm to lower
4 9 ppm
effect
the 4Ba)
the equatorial
field
sterlc
in
gives
equatorial
a mixture
equatorial shift
shifts
the borane
at C-2 and C-6
these
An equatorial
protons
N-H appears
borane
and 2 4 ppm to higher
field
of
over
1s observed
axial
in C-3 and C-5
0 2
the methyl groups
effect
the
of
C-methyl
of
protons
In the 13C NMR spectrum
by an equatorial a
the
The presence
evident
borane,
with
2-methylplperldlne
4Be and 8 = -25 4 ppm for
1 3 ppm to higher borane
N-Cl43
from 3Be and 3Ba
chair
as in
shoti the antlperiplanar ppm to higher
Another
groups
addition, and 4Ba)
produces
B
shlfted
of
4.
groups___@ = -17 2 ppm for
at
between
an equatorial
conformer
Cis-2.6~Dlmethylplperidine,
groups
shlft
compounds 3Ba and l?lSa evidences
two equatorial
Piperldlne
equlllbrlum
chemical
NW
borane
by the
(8 ppm) in 4Ba -25 4(100)=
4 (‘1
“B
NMR
2.2,6.6-Tetramethylpiperidine, Piperldlne
5 1s in
lt
-losOc,
4Ba figure
equilibrlum
between
18 (2) may
6
5
conformational
5 (1)
4Be (JBH,Hz)
be Interchan.9cd.
the
two equivalent
5Be (3) not
flgure
observed.
7
chair
5Ba (') "B
NHR .t -105~~
forms
at
A FLORES-PARRAet al
27’C.
both methyl groups
appear
67 94 MHz. coalescence molecule
is
equatorial
of
“frozen”
0 3 Kcal/mol
the
at
Borane
a borane
the presence
of
The protonated
addition
adduct,
boric salt
3-Hydroxypiperidine.
in
data
The
bonds and
the
signal
largely
borane
with
NM8 spectrum measured at
Tc = -95
groups
at
(58~
effect
the
ppm and
the
AC*= 78:
and 58a in a 90 to
10 ratio)
inversion
NM8 chemical
The N-methyl
18 is
z 0 5’ C and 28 56
is
the ring
The “B
strong
with
shift
of
derivative
sterlc
obtained
5Be is
of 5 does
effect
However,
the B(OH)r-
in
as anion
of 58e
6H have a preferred
OH-axial
chair
conformation
for
6H is
borohydride
as
gives
a
6Be and 6Ba in
a 70 to
( 13C and ‘HI allows
in
conformer
13C data
6Ba
As
A appears
for
in
30 ratio
compound 3Ba. The “B
evident
stabilized
mixture
of
axial
from
the hydroxy the
13C NM8
by
hydrogen
6H shows two N-H signals
Analysis
the NM8 data
with
deduced
probably
the hydrochloride
lithium
conformation
respectively,
adducts
of
the
position,
(DMSO) of
with
remains
on the side
similarity
for
two N-epimers
salt
at
methyl
due to an extremely
and axial
Reaction
group
observed
energy
sterlc
the “C
6.
at -14 9 ppm
hydroxyl
for
conformation
a piperidlnium
hydrochloride
unexpected
N-equatorial
axial
strong
an analogue
equatorial
ppm
is
the
to
chair
a very
The ‘H NM8 spectrum 9 35
leads
presumably
acid, is
Compound 6 and its group
groups
with
in a predominant
at d = -22 2 ppm evidencing not give
methyl
-1OS’C
35 21 ppm, the calculated
ones at
Compound 5Be is
at 31 6 ppm However,
compound 3Ba and with
a
of
which
epimers
give
only
one to conclude
conformational
chemical
shift.
calculated
at
8 99
of
the
one
“8
that
the
equilibrium as well
values
as the
confirm
this
proposition -14
9.
%BH,
6
(=)
"B
6H
NHR
4-Hydroxypiperidine, 4-Hydroxypiperidine the
equatorial
borane-THF N-borane. borate,
two kinds
and a sharp similar
figure
8
A
B
6Ba
7. 7 exists position
showed
6Be
H
Ho
signal
in a preferred The of at
‘lB
chair
conformation
NMR spectrum
boron
atoms,
of
the
a signal
d +2 0 ppm which suggests
to a system studied
by us in borates
of
at
with
the hydroxyl
reaction 6 -15
product
group
of
7
1 ppm, expected
the presence ethanolamine
of
in
with
for
an
a N-coordinated
derivatives
Is
Since
6909
SIX membered nng heterocycles
water
addition dld not hydrolyze
a careful
examinatlon after
IBe(borate), one
recorded,
and
intramolecular
to
sharp
was
presents rings
another
one
to
at
only
+
to
cleanly
a
6
of
+18
ppm in
the It
an
a
boat
“B
thls
presence was
9
we decided
that
the
since
A
to undertake
compound obtained
two
substituted
conformation
complex
kinds
of
rings
piperidlne
with
the
in
is were
a
chair
plperidine
coordination
slmllar
of
a
In “C
performed
in
in
a
an boat
of
that
trimethyl that
NMR spectrum
coordinated
evidencing
addition
a fast
to
Arguments
borate,
7
which
exchange between
the
resulting
6(borate) in
or
favor
of
frozen
of
at
a
molecule the three
N-borate
system
7(borate)
gives
an intramolecular a “B
gives
characteristic
with
shows
The
borate
4-hydroxypiperidlne
compound 7 was
In
4-hydroxyplperldine
I’B
on compound 6,
on the fact
reported
the
nitrogen
Borane
1 4 ppm
we reacted
recorded
and 7Be(borate)
based
function,
NMR data, N-borane
and
signal
was
= +
borate
We propose
figure
boron,
of
rlng
complex are
N-coordination
‘“C
to
7(borate)
compounds 6Be(borate)
coordination
the
ppm lndlcative
1 6
stable
product
1.2,2,6,6,-pentamethyl-4-hydroxy-4-phenylplper~dine17
structure
produce
one kind
shows
very
to
for
The same experiment
L(borate)
at
attributed
the
borate
of
was
reported
confirm
signal
this
reaction
coordination
conformation
trlmethyl
the
examination
that
conformation
order
of
a
NMR signal
borate
room temperature
without
using
18 nitrogen coordination to a cobalt reagent 4b
Ring A
60
30 70 Ring C b.
li
*o Q”
$;..o&H
<;O&Q8H3 O-B +2
65
51
55
0 * $
/H
7L
7Be(borate) “B
s BH;15
Lb
O-B +lb
Ring B
(‘)
Q”
00
.\
9b
YL 1*
43
93
0
NH
7(borate)
NMR
figure 9 Morpholine.
8.
the equator-la1 adduct 8Be
in a
preferred chair
Morpholine 8
adds borane to give
conformation
Assignment of all carbon and proton absorptions was done using ‘H/‘H and
W3C
correlation
spectra
The ‘H NMR spectrum
of
compound 8Be at room temperature 1s
similar to the spectrum of methylmorpholinelg "frozen" at -6O'C
The anchored molecule
allows one to observe the electronic effect of the oxygen lone pairs on the neighboring protons
Comparison of the ‘H NMR spectra of N-borane substituted piperidine and N-borane
substituted morpholine shows that substitution of a methylene group by an oxygen atom has a sizeable deshielding effect on the C-2 and C-6 axial protons and a shielding effect on
A FLORES-PARRAeta1
the equatorlal protons at the same carbons, figure 10 2
H 52
3
1
H 37
2b
2 1
H"
55
0
5
HH 1 80
H?hB
Ie
79
HaB:~+
H
H 3 69
1
Oc, H
J
I
3
7b
H 55
4
1Be
50
3
60
8Be flgure 10
Piperazlne. 9 Borane monoaddition to plperazlne gives a mixture of compounds, in which monoborane 9Be can be detected and its 13C and "B NMB chemical shifts asslgned Borane dladdiation grves in some cases only compound 9BaBe and in others a mixture with less than 5 % of 9BaBe (6 13C = 46 29 ppm)
The methylene protons in 9BeBe dlsplay an AB signal, the equatorial
hydrogen atoms appearing at 2 90 ppm (JAB = 9 3 Hz) and the axial ones at 2 53 ppm, the latter are coupled with the axial N-H (J = 9 7 Hz) conformation, and 6 "B
= -14 1 ppm 44
HNeNH
i
49
HNeN=BH312 49
-15
b*
I
29
9
li
9Be
9BeBe
flgure 11
(Jas, x2)
NNR
93
H3B~NL&y3,..,* 52
46
(') "B
The molecule is in a predominant chair
N-BETBYLBETEBOCYCLES. N-Bethylmorphollne. 10 This heterocycle is in a conformational equilibrium between the two equivalent chair conformations (in 'H NMB its Tc is -3l'C in CLlzClzat 100 MBz'~) also a complex in conformational equilibrium which shows a "B = 98 7 Hz)
Borane addition affords
NMFtsignal at -10 2 ppm (J
Application of Eliel's equation"" using the 6 B"
values for an equatorial
(-8 0 ppm) or an axial borane (-14 5 ppm)20b gives a 40 to 60 ratio of 10Be to 1OBa favoring the equatorial methyl over the borane and a
singlet for
lnsolublllty of
the N-methyl group
the
complex has
The 'H NMB showed four broad multlplets
lndlcatlve of
precluded variable
an
equilibrium, unfortunately
temperature experiments
1,3-dlaxlal interactions and substitution effects are observed in the 13C NM8 spectrum
BH3 f owN\CH3
=
'sN+H3
I CH3 1OBa
figure 12
1OBe
The
6911
SIX membered nng heterocycles
N,N-Dimethylpiperazinc, 11 Plperazlne 11 1s in ring conformational equillbrlum wlth the methyl groups In equatorial positions at room temperature, as deduced from the 13C NM8 data, Tc is reported to be - 8 5 OC in CDZC~~'~ Borane dladditlon glves two different N-eplmers 1lBaBa and 118aBe In a 60 to 40 ratio At room temperature, the "B NM8 spectrum shows two signals at -13 6 ppm attributed to the axlal boranes of 118a8a and another one at -11 0 ppm assigned to compound 118aBe
The latter is In conformational equilibrium since at low temperature the
-11 0 ppm signal gives rise to two absorptions. one at d = -13 6 ppm for an axial borane and the other
one
at -8 0 ppm for the equatorial one
"C NMR low temperature experiments
allow one to obtain the chemical shifts of "frozen" 118aI#e,and "B
NMR low temperature
experlments to calculate the AG* for the ;ing inversion of 118aBe (AGO= 13 4 KcaVmol)
-13
44
6=
B"3
0 5
21
CH3 I
"3C_N~-CH, 53 44
H3C\ 'w\CH,
72
71
55
:3;;K5&K$ JI_
66 JI N
13
11 (‘)
llB
53 6.
H,Bd
BH,
66
-a
n/H,
o=
RH
BH,
ti
---3
1lBaBa
a
NHR
p'
2
9
1lBaBe
figure 13
B”3
Dihydrodithiazine, 12. This molecule was previously studied by Katritzky"
who found that the ring 1s in
conformational equilibrium between the two chair forms (Tc -4l'C in CDC13 and CFC13, AG' 11 Kcal/mol for the ring inversion) with the N-methyl In a preferred axial position, as confirmed by examination of the 13C chemical shift of the methyl group (6 = 37 5 ppm)
At
- 80°C the molecule is "frozen" and all protons in the 90 MHz 'H NM8 spectrum can be assigned
37
501 4
CH3 I
I
281
12 4
42
452
H
I
2
592
H
4
062
,,
?^
P
12 (-80'~)
OH
g5E, t ‘2d 62
1911
12Be
NMR,
(2)
‘H
602
H
c*3
2 -91L
(1) 13c
4
\gsS$ 3g&s7$~562 s
Rss”* CH3
952
H
NMR,
(*)
llg
NHR
figure 14
A FLORESPARRA et al
In contrast axial
to morphollne,
position
(6
compound 19” equatorlal
=
where
borane
protons
give
an
1 4 Hz1 with
the
system
NM8 coupling
by
methyl
is
is
similar
12 and 12Be,
shifted
to
high
is
supported
of electronic
to that
of
13,
(0 54
density
at
allow
C-4
small
solely
as
a
fixed
atoms
C-methyl
in
borane of
axial
groups
The “B
value
methyl
of
equatorial
(‘1
downfield
alpha to it
protons
indicating
a
are
the presence
which “frozen”
This shifted
values
to
is
low
also
field
of an equatorial
an
those
(A6
0 4
C-4 (J =
as an ABX The
‘H
between
the
adduct
are
and
the
the
borane
C-2
protons)
ephedrine], the
by a decrease
13
morpholone
13Be with with
for
similar
to
and
and
phenyl
and
0 5
by comparison
both that
of
by
an
compound 20”
methylene
N-methyl
an syn-axial
for
13 exists
the
the
was deduced
calculated
borane
in
also
Comparison
(50 60 ppml produced found
the
conformation
AB system
molecule
with
the
atoms
the conformation
effect
conformers 12Be
The
anti-axial
The C-2
ppm respectively)
and C-6 also
borane
13 “B
NNR
figure N-Nethyl-S-methyl-6-phenyl-1.4-oxazin-Z-one The free in
shows
for
a W coupling
observed
of
of
herezob
where
can be explained
from f-1
an equatorial
effect
showing
ppm for
conformation
cases
shifting
0 76
room temperature
a
shift
protons
the sulfur
14,
In both
-7 8 ppm supports
has
at
The alternative
unlikely
proton
behavior
[derived that
NMR spectrum
low temperature
and
NMR value
values reported
which are
in the
group
13C NM8 values
“B
The
proton
axial
lone pairs
gives
i3C NM8 chemical of
group group
very
the
protons
figure
addition
positlons
is
the observed
N-methyl
conformer,
Borane
the
with
one to deduce a chair
This
reveals
the N-methyl
the other
atoms,
effect
N-klethyl-5-methyl-6-phenyl-l,4-oxazin-Z-one
hydrogen
by
compound 12 at
the axial
The 278--MHz ‘H NMFt spectrum
41 8 ppm
the equatorial
shows that
for
show a very
at
hydrogen
and pattern
figure
field
protons
found
12Be with comparison
In agreement with
(JAB = 14 Hz).
values
‘H 6 of
equatorial
only
the C-2 and C-6 equatorial
The coupling
system
as
8 ppm) is
homogenlclty
ABX2
glves
established
addition
ppml
axial
fb = -
The conformational
borane
42 95
morpholone
equatorial
protons
Borane
14 is
positions, addition
anchored figure gives
[derived
in a chair 15,
15
as
evidenced
two N-epimers
from f-1
conformer by
pseudoephedrinel,
with
the three
the
AB system
14Ba and 14Be in
14.
substituent of
a 90 to
the
groups methylene
10 ratio
The
6913
SIX membered nng heterocycles
equatorial
N-methyl
absorptlons
are
important
to
appears
A = 52 04 ppm and
at
at A = -14 5 ppm (axial
notice
the
compared to the other
deshielding
boranel effect
and at
of
the
axial
one
at
is
borane
on
attrlbuted
l’B
41 47 ppm
-8 0 ppm (equatorial
axial
(AA= 0 5 ppml, uhlch
N-eplmer
boranel
the
It
hydrogen
to a fleld
NMB
at
is C-6
effect
41 47
14 (') "8
the
14Be
14Ba 16
NHR
figure Conclusions. Borane
addition
temperature observation N-borane would
be
It
expected of
in the presence groups
higher
field
interest
the
carbons
that
antiperiplanar allows
in 13Be,
effect of
shifts
in
effects
one to assign
adducts
This
is
of
of
boranes
steric
effect
the “B
signal
are
a
kinetic
related
borane
an alternative as
borane
is
to
to quarternary
ratio
N-H borane
the
“B
group
products
favoring
to higher
than axial
fleld
the axial
predominant by heating
ones
shifts
Axial
what
concerning
involves
can be approached
chemical
for
somewhat over
observations
which
more stable
on the
to variable
locking
favored
salts
adducts
adducts
are
independent
14Ba and 14Be the nitrogen
lone The
analogues pairs
on
information
the position
atoms in more complex heterocycles borane
used
, the methyl
boranes
appear
at
It
is
ones of
piperidine
anchored
be
approach
Equatorial
shifting
than equatorial
effect
axial
piperidlnes
amine
constitutes
can
Borane additiongives
that
The thermodynamic
The ‘H NMR chemical
The locking
borane
thermodynamically
of free
in viclnal
N-heterocycles
that
conformers clear
show a systematic
groups
of
is
in
N-substituted
approach22
Methyl
membered ring
of preferred
adducts
alkylations axial
to six
NMB spectroscopy
in stereochemical
of
bearing the
provided
the borane,
such as,
of
concentration
atoms become stable another
heteroatom
neighboring
hydrogen
by
the
as well
13 and 14,
study as
of the
thus pointing
chiral
allows
these
atoms,
centers
one to
see
including
model molecules
configuration
of
other
to the importance
of
analyses
EXPEBIUENTAL. ‘II
and 13C NMR spectra were recorded on Varian XL-BOOGS. Jeol GSX-270 or Jeol FX-90 ctrometers Chemical shifts are reported in parts per million relative to Me&i (61 We B NMB spectra were recorded on a Jeol GSX-270 or a Jeol FX-90 using BFs-etherate as the external standard Tetrahydrofuran was distilled under dry nitrogen from sodium using bezzophenone as Reactions Indicator. the borane-THF complex was prepared uslng a published procedure were carried out under a nitrogen atmosphere The piperidlnes were commercially available,
6914
A FLGRES-PARRAet al
24
and morpholones tetrahydrodlthlazlne was prepared as were prepared by reported dehvdratlon in drv toluene from the N-~2-hydroxy-l-methyl-~~phenylethyl~-N-methylamlno aceilc acid derived from (ephedrine 13 and pseudoephedrlne 141d” of Preparation of the adducts was carried out by addition of 1 2 or 2 4 equivalents borane-THF to compounds 1 to I4 to obtain monoborane and dlborane addition, respectively, To a stirred solution containing 10 mmol of the following the general procedure below heterocycle In 4 ml of THF was added dropwlse a solution of 2 0 M BHa-THF in THF (12 mmol for monoaddltlon and 24 mm01 for diaddltlon, respectively) The solvent was evaporated immediately and the products were examined by NMR
Acknowledgements We are grateful to Conacyt-Mexico and Cosnet for financial support and Dr P Ariza-Castolo, G Paredes-Tepox for Joseph-Nathan, Chemists A Uribe and C recording the spectra and to Dr Rosa Santillan for reading the manuscript and for her helpful comments, and to one of the referees for a stimulating criticism of the paper
References 1 A preliminary communication of this work was presented at the Boron USA Workshop, Research Triangle Park, NC USA, June 6-9, 1990 2 R Contreras, F Santiesteban, M A Paz-Sandoval and B Wrackmeyer. Tetrahedron, 40, 3829 (19841 Reson 3 M A Paz-Sandoval, F Santiesteban and R Contreras, Mag Chem , 23, 428 (19851 4 R Contreras, H R Morales, M L Mendoza and C Domlnguez. Spectrochlm Acta, 43A, 43 (19871 5 A R Gatti and T Wartlk, Inorg Chem , 5. 2075 (19661 6 R Lyle and E W Southwick and J J Kaminskl, J Am Chem Sot , 94, 1413 (1972) 7 H Noth and B Wrackmeyer, Cl-rem Ber , 107, 3070 (19741 33, 915 (19771 8 P J Crowley, M J T Robinson and M G Ward, Tetrahedron, Mag Reson , 11, 418 9 C G Beguin, M N Deschamps, V Boubel and J J Delpuech, Org (19781 10 E L Eliel, D Kandasamy, C Yen and K D Hargrave, J Am Chem Sot, 102, 3698 (19801 11 A F Casy and F 0 Ogungbamila, Org Mag Reson , 18, 171 (19821 12 Our results from a crystallografic X-ray diffraction study of an amine-borane adduct 13 These effects were evaluated by comparison of calculated 8 of conformers A and Blrsing the data of 1Be and the empirical values for an axial and an equatorial methyl group and also using the experimental values of 8 of 2 and the effects of an axial borane 4Ba or an equatorial borane 4Be 14 F W Wehrll, T Wlrthlln, Interpretation of Carbon-13 NMR Spectra, Heyden, Lonafn, 45 by extrapolation of d (19801 15 The expected value of -19 5 ppm was calculated B NNR of 14Ba by adding 5 ppm for substitution of the N-methyl by a H, T Mantilla, F Santlesteban, R Contreras and A Kla&be, Tetrahedron Lett 23, 1561(19821 16 Our results. the chemical shifts of 17Ba and 17Be were assigned by INEPT esperiments 17 R E Lyle,. J Org Chem , 22, 1280 (19571 18 R J Abraham and C J Medforth. J Chem Sot , Chem Commun , 1637 (19871 19 R K Harris and R A Spragg, J- Chem Sot , Chem Conunun, 314 (19661 bl The equatorial borane values were 20 al E Eliel. Chem Ind (London) 568 (19591 and axial borane obtained from compounds 12Be. 13Be, 14Be and 1lBaBe at low temperature values from 14Ba and 14BaBe at low temperature J Chem Sot , Perkln II, 21 L Angiollnl. R P Duke, R A Y Jones and R Katritzky, 674 (19721 22 J HcKenna, Topics Stereochem , 5. 275 (19701 23 H C Brown, Organic Synthesis via Borane Wiley, New York (19751 24 S A Hughes and E B McCall, Chem Abs 60, 5528a (19641 25 N Farfan, L Cuellar, J M Aceves and R Contreras, Synthesis. 927 (19871
Nl4R STUDY OF THE EFFECT
oo4o4020/91 $3 oo+ 00 Presspk @ 1991 Pergamon
OF NITROGEN-BORANE COORDINATION ON THE CQNFORl4ATIOBALEQUILIBRIUM
OF SIX m Angelina
Flores-Parra*,
RING BElERCNZTCLES
Norberto
Farfan,
Fernandes-Sanchez Departamento
de
Quimica,
Politecnico
Centro
Nacionsl
de
Albert0
InvestlgacMn
Apartado
I
and Rosallnda
Postal
Hernindez-Bautista,
y de Estudios
14-740,
Lilia
Contreras*
Mexico,
D
Avanzados F
de1
Instltuto
07000, Mexico
(Received m USA 24 May 1991)
Summary The syntheses, conformational and spectroscopic studies of N-borane adducts of 14 It was found that borane nitrogen containing six-membered ring heterocycles are reported In addition, it can be very can act as a conformational and configurational locking agent helpful for the assignment of the chemical shifts of other atoms or groups in the molecule as well as to ascertain the configuration at substituted carbons
Introduction’ The
analysis
important
of
neighboring
carbon
sensitive
to
to
the
space,
identification
at
of
N-borane
the in
means
chemical
was not
of
‘H.
of
organic
“B
fixes
shifts
it
has a more stable
may become important
and
shifts
are
through
as a chiral
its very
bonds
probe2-4
the configuration
on the application
preferred
conformation
of
figure
giving
In turn
of
1
and coupling
is
adducts
results
configurations
N-borane
Borane
N-borane
these
of
at
at
of
of
ring
atoms including
in
the
tools
is
important
configuration for
structural
to
notice
that
than in the salts analyses
6903
the
of
the
the
ring
detailed
conformational
nitrogen
NMR spectra
nitrogen
shifts
six-membered
fixing
enough to allow
the study
ring
chemical
adducts
capable
stable
allow
constants
13C, ‘H and “B
and plperazlnes were reported before but a careful 5-s Although ammonium salts present spectra undertaken
adductsg-“,
provides
nitrogen
interactions
can be used
group
at
chemical
by borane
addltion
the borane
heterocycles
assignment
13C and
produced
borane
solution,
the establishment
piperidines
adducts
focused
room temperature
assignment
analysis
effects
and hence,
is of
adducts
of
adducts
configurational
shown that
the presence
1-14
by spectroscopic
equilibrium.
N-borane the
atom2-’
attention
heterocycles
conformation study
of
allows We have
adducts,
nitrogen
paper
that
and electronic
through
In amine-borane quaternized
ring
NMR data
atoms
steric
and directly
In this
the
information
and the
Some N-borane and detailed very
atom
and In consequence,
in
similar the
NMR to
borane
such adducts
6904
A FLORES-PARRA~~al
_~ 1 2 4 5
RRRR-
8 R- H, X- 0 9 R- H, X- NH 10 R- CH,, X- 0 11 R- CH,, X- NCH,
3 R- CH,, R,- H 6 R- OH, R,-H 7 R- H, R,- OH
R,- R,- R,- H CH,, R,- R,- R,- H R,- CH,, R,- R,- H R,- R,- R,- CH,
i2 .B
N-CH,
+=P
R3
0
0
R,
12
13 R- R2- H, R,- CH,, R,- C,H, 14 R- CH,, R,- R,- H, R,-C,H, figure 1 RESULTS AND DISCUSSION. N-H SIX-DRMBERED RING HETERDCYCLES. Piperidine, 1 Borane addition to piperidine 1 produces an equatorial N-borane adduct (lBe, "B
chemical
shift b= -15 5 ppm, JB-H = 97 Hz), which shows a predominant chair conformation at room temperature, as established by the 'H NMFI spectrum coupled to the neighboring protons
The N-H appears at 6 = 3 68 ppm
The equatorlal and axial protons of 1Be appear as
separate signals shifted to low field compared to those of the free piperidine 1, the equatorial protons of 1Be belng more shifted than the corresponding axial ones (B[b~-&~l = 0 74 ppm for the C-2 and C-6 protons, 0 25 ppm for those of C-3 and C-5 and 0 18 ppmfor C-41 The 13C NMFIof 18e is similar to that of N-methylpiperidine159 and even more to its salt 15H9 (figure 21
This is explained in terms of the fact that 13C NMFt is especially
sensitive to steric effects and 18e is sterically similar to 15H With the difference that
0 25a*N-H
24
Jq+:
0
159
1 i NtH
,,w+'(=
hi++
22?%zY 53 41 1H9 ('1
llB NHR
1Be
21 8
55 2
15H9 figure 2
6905
SIX membered rmg heterocycles
the substitution
effect
of
nitrogen
at
C-2 and C-6
is
stronger
(Aa 9 5 ppm) when compared to compound 1Be (Aa 6 1 ppm) to
the
“C
longer
NMFtdata
interactions that
bond distance Indicates and from
the equatorial
2 exists with
room temperature, kinetic
at
Compound 2Be has
shifts
of
free
92
has
an
equatorial
of
Another 6 = -
C-methyl
figure
at C-3 and C-5
in B13
both and
effects
31,
in
shows
a 60-40
upfleld
69
4
2Ba
produced
rqurllbrlum
(') llB H,,R (J
Heating
ratio
that
shift
the
the
to 80/20
borane
at C-3 and C-5
at
gives
group
1s
(< 0 7 ppm)
63
5
li132
and
16He’O an
axial is
by the axial-borane
argument
and
borane
H
The latter
in favor
18 1 ppm LJ = 110 Hz),
conformers
solution
of
the ZBe/PBa ratio
2Be
equillbrlum,
6 of the
the
32 4
(6 = -15 5 ppm, J = 97 Hz)
A6(16Ra-16Rc).
of
no 1.3-diaxial
chloroform
34 37 59 301q309
23'20
2
2Be
Analysis is
Addition
and an evidence
small
23 ~':;(94)~2~~;H~
of
1.3-diaxlal
(figure
substltuents by the very
in
position
amine increases
46
an equatorial ratio
of
2S/-&H 26 40 52
borane
XI
there
The ‘H NMFI spectrum
conformation
54
produced
equal
chair
31
conformational
(1 47
since
and C-6
In equatorlal
47
Compound 2Ba
of
on C-2
2Be and 2Ba
in an excess
is provided
..
shift
equatorial
derivative
to low field
a preferred
two equatorial
34
methyl group
in
N-epimers
60°C
equatorial
effects
effect
shifted
the methyl group
products,
7 hours
largely
are
compared to C-N
in 1Be is
the substitution
in the N-methyl
phenomenon can be attributed
2.
2-Methylplperldlne
the
(1 66 fi)”
the borane
protons
2-Hethylpiperidine,
mixture
in B-N
that
This
may be
between
group by the
the equilibrium
that
and an axial
16Ha and
16He
group
. (2) Value. of
AH' RI)
figure
4
and
may display
a
r3C NMR 1,3-diaxial
in A and at C-4 and C-6 by the axial comes from the chemical
seems to be an average borane
(6 = -
assumed from comparison
by the 2-methyl
mlxturc
of
borane
supported
(figure
19 5 ppm15)
between 4)
value
that
in the B conformers
the
“C
clearly
between A near
chemical shows
and by N-methyl
the or
2Ba 1,3-diaxl.1
Interactlone,
A6(2Ba-2Ac)
0,.
6906
A FLORES-PARRAet al
N-borane
in
conformers
means that group
vicinal
is
interactions
indicate Je-H
It
lnteresting on comparison 2B, proved
is
of
“C
with
respect
with
to 21
a very
strong
2Be and at
only
This
with
to 21,
antiperlplanar
is
those
of
and
an
and
a
the
weaker
in conformational
of
Analysis
at
borane
and
effect
at
of
showing
are based of
identification
of
2 63 ppm in 2Be (A6 = 0 07
the C-6 axial
borane
that
The
‘H NM8 spectrum
3 25 ppm in 2Ba (Aa = 0 69 ppm to also
(a
idHe”
equilibrium
the
which allowed
appears
coupling
coordination)
16Ha is
proton
borane methyl
B-H
axial
16Ha
of
axial
equatorial ln
in
ammonium salts
28a
the
differences atom
the mixture
and at
inductive
angle
of
observed
1 27 ppm in 2Ba,
borane
nitrogen
the
The C-2 axial
effect
proton,
The C-2 methyl
an equatorial
borane
low field
which evidences is
found
has
at
1 36
a deshielding
on the methyl protons
3-Nethylpiperidine,
3.
The free
3 exists
plperidine
equatorial ratio,
position
comparison
molecule
is
while
to higher
epimers
piperidine
distinguishable
in
without as
3,
the
spectra
corresponding
chair
produces
as
conformation,
two N-eplmers
figure
steric
well
5
effects those
protons
axial
at
protons
near
of
C-2
331;@~; 26
33
are 51
30 19320 94@!:':* HC 29
45
91
observed,
(‘1
“B
figure
70
5
the nitrogen more
are
atom
abundant
shifted
in 14
to allow
In iH NMR, all
N-epimer
as
group
an 86 to
those
of
3Be,
are
lBe,
the
0 06 ppm to
higher
0 10 and 0 31 ppm, respectively,
H
29 H3C 36+j5;;o 29 18 17
A NMR
the 3-methyl
has the advantage
the same trends
shifted
17Ha’6 (11 not
the
and C-6
field 46
with
3Be and 3Ba in
This molecule
Compound 3Be shows
equatorial
anchored, the
addition
from the NM8 spectra,
between
of
in a preferred
Borane
as deduced
protons
field
H-B-H and
proportion
The
the
to assume that
respect
important
equatorial
of
due to the complexity
ppm in effect
an
larger
NM8 data
the C-2 and C-6 protons
an
equlllbrium
adducts
reasonable
difficult
low field
a
borane
its
the
coordination
indicates
between
of
between
favoring
a weaker
value
similarities
ppm to
The existence
destabilizing,
constants larger
A
63
l7 73H3C 3Ba
g
H
6907
SIX membered nng heterccycles
Compound 33a assumptlon around
seems to be
1s based
In a conformatlonal
shiftsI
of
shifted
also
1s that
that
“C
the
33 ppm) and also
Ii’He and 17Ha,
with
on
the similarity
supports
towards “B
the
NMR spectra
4
1s
positlon
Borane
N-epimers
(4Be
borane
in
shows only
a preferred
a steric
are
field
5 8 ppm whereas shifted
an axial
methyl groups
in
a 60
effect
the to
that
effect
of
and the axial an axial
which
A strong
the C-6
that
important
a sharp
largely axlal
(an
chemical
N-substltuent
of
at
the
compounds
13C chemical
equlllbrlum
in favor
of
this
-14 6 ppm which
This
1s expected
ln both
conformatlonal
argument
B
towards N-Cl43
shlfts
Comparison
the
signal
conformation case
of
40 ratio is
borane
one 1s at field
evidences
in
1,3-diaxial
“B
larger
methyl
of
3Ba
equilibrium
1s compatible
groups
2.
of
two
chemical
The axial borane
0 3 ppm to lower
4 9 ppm
effect
the 4Ba)
the equatorial
field
sterlc
in
gives
equatorial
a mixture
equatorial shift
shifts
the borane
at C-2 and C-6
these
An equatorial
protons
N-H appears
borane
and 2 4 ppm to higher
field
of
over
1s observed
axial
in C-3 and C-5
0 2
the methyl groups
effect
the
of
C-methyl
of
protons
In the 13C NMR spectrum
by an equatorial a
the
The presence
evident
borane,
with
2-methylplperldlne
4Be and 8 = -25 4 ppm for
1 3 ppm to higher borane
N-Cl43
from 3Be and 3Ba
chair
as in
shoti the antlperiplanar ppm to higher
Another
groups
addition, and 4Ba)
produces
B
shlfted
of
4.
groups___@ = -17 2 ppm for
at
between
an equatorial
conformer
Cis-2.6~Dlmethylplperidine,
groups
shlft
compounds 3Ba and l?lSa evidences
two equatorial
Piperldlne
equlllbrlum
chemical
NW
borane
by the
(8 ppm) in 4Ba -25 4(100)=
4 (‘1
“B
NMR
2.2,6.6-Tetramethylpiperidine, Piperldlne
5 1s in
lt
-losOc,
4Ba figure
equilibrlum
between
18 (2) may
6
5
conformational
5 (1)
4Be (JBH,Hz)
be Interchan.9cd.
the
two equivalent
5Be (3) not
flgure
observed.
7
chair
5Ba (') "B
NHR .t -105~~
forms
at
A FLORES-PARRAet al
27’C.
both methyl groups
appear
67 94 MHz. coalescence molecule
is
equatorial
of
“frozen”
0 3 Kcal/mol
the
at
Borane
a borane
the presence
of
The protonated
addition
adduct,
boric salt
3-Hydroxypiperidine.
in
data
The
bonds and
the
signal
largely
borane
with
NM8 spectrum measured at
Tc = -95
groups
at
(58~
effect
the
ppm and
the
AC*= 78:
and 58a in a 90 to
10 ratio)
inversion
NM8 chemical
The N-methyl
18 is
z 0 5’ C and 28 56
is
the ring
The “B
strong
with
shift
of
derivative
sterlc
obtained
5Be is
of 5 does
effect
However,
the B(OH)r-
in
as anion
of 58e
6H have a preferred
OH-axial
chair
conformation
for
6H is
borohydride
as
gives
a
6Be and 6Ba in
a 70 to
( 13C and ‘HI allows
in
conformer
13C data
6Ba
As
A appears
for
in
30 ratio
compound 3Ba. The “B
evident
stabilized
mixture
of
axial
from
the hydroxy the
13C NM8
by
hydrogen
6H shows two N-H signals
Analysis
the NM8 data
with
deduced
probably
the hydrochloride
lithium
conformation
respectively,
adducts
of
the
position,
(DMSO) of
with
remains
on the side
similarity
for
two N-epimers
salt
at
methyl
due to an extremely
and axial
Reaction
group
observed
energy
sterlc
the “C
6.
at -14 9 ppm
hydroxyl
for
conformation
a piperidlnium
hydrochloride
unexpected
N-equatorial
axial
strong
an analogue
equatorial
ppm
is
the
to
chair
a very
The ‘H NM8 spectrum 9 35
leads
presumably
acid, is
Compound 6 and its group
groups
with
in a predominant
at d = -22 2 ppm evidencing not give
methyl
-1OS’C
35 21 ppm, the calculated
ones at
Compound 5Be is
at 31 6 ppm However,
compound 3Ba and with
a
of
which
epimers
give
only
one to conclude
conformational
chemical
shift.
calculated
at
8 99
of
the
one
“8
that
the
equilibrium as well
values
as the
confirm
this
proposition -14
9.
%BH,
6
(=)
"B
6H
NHR
4-Hydroxypiperidine, 4-Hydroxypiperidine the
equatorial
borane-THF N-borane. borate,
two kinds
and a sharp similar
figure
8
A
B
6Ba
7. 7 exists position
showed
6Be
H
Ho
signal
in a preferred The of at
‘lB
chair
conformation
NMR spectrum
boron
atoms,
of
the
a signal
d +2 0 ppm which suggests
to a system studied
by us in borates
of
at
with
the hydroxyl
reaction 6 -15
product
group
of
7
1 ppm, expected
the presence ethanolamine
of
in
with
for
an
a N-coordinated
derivatives
Is
Since
6909
SIX membered nng heterocycles
water
addition dld not hydrolyze
a careful
examinatlon after
IBe(borate), one
recorded,
and
intramolecular
to
sharp
was
presents rings
another
one
to
at
only
+
to
cleanly
a
6
of
+18
ppm in
the It
an
a
boat
“B
thls
presence was
9
we decided
that
the
since
A
to undertake
compound obtained
two
substituted
conformation
complex
kinds
of
rings
piperidlne
with
the
in
is were
a
chair
plperidine
coordination
slmllar
of
a
In “C
performed
in
in
a
an boat
of
that
trimethyl that
NMR spectrum
coordinated
evidencing
addition
a fast
to
Arguments
borate,
7
which
exchange between
the
resulting
6(borate) in
or
favor
of
frozen
of
at
a
molecule the three
N-borate
system
7(borate)
gives
an intramolecular a “B
gives
characteristic
with
shows
The
borate
4-hydroxypiperidlne
compound 7 was
In
4-hydroxyplperldine
I’B
on compound 6,
on the fact
reported
the
nitrogen
Borane
1 4 ppm
we reacted
recorded
and 7Be(borate)
based
function,
NMR data, N-borane
and
signal
was
= +
borate
We propose
figure
boron,
of
rlng
complex are
N-coordination
‘“C
to
7(borate)
compounds 6Be(borate)
coordination
the
ppm lndlcative
1 6
stable
product
1.2,2,6,6,-pentamethyl-4-hydroxy-4-phenylplper~dine17
structure
produce
one kind
shows
very
to
for
The same experiment
L(borate)
at
attributed
the
borate
of
was
reported
confirm
signal
this
reaction
coordination
conformation
trlmethyl
the
examination
that
conformation
order
of
a
NMR signal
borate
room temperature
without
using
18 nitrogen coordination to a cobalt reagent 4b
Ring A
60
30 70 Ring C b.
li
*o Q”
$;..o&H
<;O&Q8H3 O-B +2
65
51
55
0 * $
/H
7L
7Be(borate) “B
s BH;15
Lb
O-B +lb
Ring B
(‘)
Q”
00
.\
9b
YL 1*
43
93
0
NH
7(borate)
NMR
figure 9 Morpholine.
8.
the equator-la1 adduct 8Be
in a
preferred chair
Morpholine 8
adds borane to give
conformation
Assignment of all carbon and proton absorptions was done using ‘H/‘H and
W3C
correlation
spectra
The ‘H NMR spectrum
of
compound 8Be at room temperature 1s
similar to the spectrum of methylmorpholinelg "frozen" at -6O'C
The anchored molecule
allows one to observe the electronic effect of the oxygen lone pairs on the neighboring protons
Comparison of the ‘H NMR spectra of N-borane substituted piperidine and N-borane
substituted morpholine shows that substitution of a methylene group by an oxygen atom has a sizeable deshielding effect on the C-2 and C-6 axial protons and a shielding effect on
A FLORES-PARRAeta1
the equatorlal protons at the same carbons, figure 10 2
H 52
3
1
H 37
2b
2 1
H"
55
0
5
HH 1 80
H?hB
Ie
79
HaB:~+
H
H 3 69
1
Oc, H
J
I
3
7b
H 55
4
1Be
50
3
60
8Be flgure 10
Piperazlne. 9 Borane monoaddition to plperazlne gives a mixture of compounds, in which monoborane 9Be can be detected and its 13C and "B NMB chemical shifts asslgned Borane dladdiation grves in some cases only compound 9BaBe and in others a mixture with less than 5 % of 9BaBe (6 13C = 46 29 ppm)
The methylene protons in 9BeBe dlsplay an AB signal, the equatorial
hydrogen atoms appearing at 2 90 ppm (JAB = 9 3 Hz) and the axial ones at 2 53 ppm, the latter are coupled with the axial N-H (J = 9 7 Hz) conformation, and 6 "B
= -14 1 ppm 44
HNeNH
i
49
HNeN=BH312 49
-15
b*
I
29
9
li
9Be
9BeBe
flgure 11
(Jas, x2)
NNR
93
H3B~NL&y3,..,* 52
46
(') "B
The molecule is in a predominant chair
N-BETBYLBETEBOCYCLES. N-Bethylmorphollne. 10 This heterocycle is in a conformational equilibrium between the two equivalent chair conformations (in 'H NMB its Tc is -3l'C in CLlzClzat 100 MBz'~) also a complex in conformational equilibrium which shows a "B = 98 7 Hz)
Borane addition affords
NMFtsignal at -10 2 ppm (J
Application of Eliel's equation"" using the 6 B"
values for an equatorial
(-8 0 ppm) or an axial borane (-14 5 ppm)20b gives a 40 to 60 ratio of 10Be to 1OBa favoring the equatorial methyl over the borane and a
singlet for
lnsolublllty of
the N-methyl group
the
complex has
The 'H NMB showed four broad multlplets
lndlcatlve of
precluded variable
an
equilibrium, unfortunately
temperature experiments
1,3-dlaxlal interactions and substitution effects are observed in the 13C NM8 spectrum
BH3 f owN\CH3
=
'sN+H3
I CH3 1OBa
figure 12
1OBe
The
6911
SIX membered nng heterocycles
N,N-Dimethylpiperazinc, 11 Plperazlne 11 1s in ring conformational equillbrlum wlth the methyl groups In equatorial positions at room temperature, as deduced from the 13C NM8 data, Tc is reported to be - 8 5 OC in CDZC~~'~ Borane dladditlon glves two different N-eplmers 1lBaBa and 118aBe In a 60 to 40 ratio At room temperature, the "B NM8 spectrum shows two signals at -13 6 ppm attributed to the axlal boranes of 118a8a and another one at -11 0 ppm assigned to compound 118aBe
The latter is In conformational equilibrium since at low temperature the
-11 0 ppm signal gives rise to two absorptions. one at d = -13 6 ppm for an axial borane and the other
one
at -8 0 ppm for the equatorial one
"C NMR low temperature experiments
allow one to obtain the chemical shifts of "frozen" 118aI#e,and "B
NMR low temperature
experlments to calculate the AG* for the ;ing inversion of 118aBe (AGO= 13 4 KcaVmol)
-13
44
6=
B"3
0 5
21
CH3 I
"3C_N~-CH, 53 44
H3C\ 'w\CH,
72
71
55
:3;;K5&K$ JI_
66 JI N
13
11 (‘)
llB
53 6.
H,Bd
BH,
66
-a
n/H,
o=
RH
BH,
ti
---3
1lBaBa
a
NHR
p'
2
9
1lBaBe
figure 13
B”3
Dihydrodithiazine, 12. This molecule was previously studied by Katritzky"
who found that the ring 1s in
conformational equilibrium between the two chair forms (Tc -4l'C in CDC13 and CFC13, AG' 11 Kcal/mol for the ring inversion) with the N-methyl In a preferred axial position, as confirmed by examination of the 13C chemical shift of the methyl group (6 = 37 5 ppm)
At
- 80°C the molecule is "frozen" and all protons in the 90 MHz 'H NM8 spectrum can be assigned
37
501 4
CH3 I
I
281
12 4
42
452
H
I
2
592
H
4
062
,,
?^
P
12 (-80'~)
OH
g5E, t ‘2d 62
1911
12Be
NMR,
(2)
‘H
602
H
c*3
2 -91L
(1) 13c
4
\gsS$ 3g&s7$~562 s
Rss”* CH3
952
H
NMR,
(*)
llg
NHR
figure 14
A FLORESPARRA et al
In contrast axial
to morphollne,
position
(6
compound 19” equatorlal
=
where
borane
protons
give
an
1 4 Hz1 with
the
system
NM8 coupling
by
methyl
is
is
similar
12 and 12Be,
shifted
to
high
is
supported
of electronic
to that
of
13,
(0 54
density
at
allow
C-4
small
solely
as
a
fixed
atoms
C-methyl
in
borane of
axial
groups
The “B
value
methyl
of
equatorial
(‘1
downfield
alpha to it
protons
indicating
a
are
the presence
which “frozen”
This shifted
values
to
is
low
also
field
of an equatorial
an
those
(A6
0 4
C-4 (J =
as an ABX The
‘H
between
the
adduct
are
and
the
the
borane
C-2
protons)
ephedrine], the
by a decrease
13
morpholone
13Be with with
for
similar
to
and
and
phenyl
and
0 5
by comparison
both that
of
by
an
compound 20”
methylene
N-methyl
an syn-axial
for
13 exists
the
the
was deduced
calculated
borane
in
also
Comparison
(50 60 ppml produced found
the
conformation
AB system
molecule
with
the
atoms
the conformation
effect
conformers 12Be
The
anti-axial
The C-2
ppm respectively)
and C-6 also
borane
13 “B
NNR
figure N-Nethyl-S-methyl-6-phenyl-1.4-oxazin-Z-one The free in
shows
for
a W coupling
observed
of
of
herezob
where
can be explained
from f-1
an equatorial
effect
showing
ppm for
conformation
cases
shifting
0 76
room temperature
a
shift
protons
the sulfur
14,
In both
-7 8 ppm supports
has
at
The alternative
unlikely
proton
behavior
[derived that
NMR spectrum
low temperature
and
NMR value
values reported
which are
in the
group
13C NM8 values
“B
The
proton
axial
lone pairs
gives
i3C NM8 chemical of
group group
very
the
protons
figure
addition
positlons
is
the observed
N-methyl
conformer,
Borane
the
with
one to deduce a chair
This
reveals
the N-methyl
the other
atoms,
effect
N-klethyl-5-methyl-6-phenyl-l,4-oxazin-Z-one
hydrogen
by
compound 12 at
the axial
The 278--MHz ‘H NMFt spectrum
41 8 ppm
the equatorial
shows that
for
show a very
at
hydrogen
and pattern
figure
field
protons
found
12Be with comparison
In agreement with
(JAB = 14 Hz).
values
‘H 6 of
equatorial
only
the C-2 and C-6 equatorial
The coupling
system
as
8 ppm) is
homogenlclty
ABX2
glves
established
addition
ppml
axial
fb = -
The conformational
borane
42 95
morpholone
equatorial
protons
Borane
14 is
positions, addition
anchored figure gives
[derived
in a chair 15,
15
as
evidenced
two N-epimers
from f-1
conformer by
pseudoephedrinel,
with
the three
the
AB system
14Ba and 14Be in
14.
substituent of
a 90 to
the
groups methylene
10 ratio
The
6913
SIX membered nng heterocycles
equatorial
N-methyl
absorptlons
are
important
to
appears
A = 52 04 ppm and
at
at A = -14 5 ppm (axial
notice
the
compared to the other
deshielding
boranel effect
and at
of
the
axial
one
at
is
borane
on
attrlbuted
l’B
41 47 ppm
-8 0 ppm (equatorial
axial
(AA= 0 5 ppml, uhlch
N-eplmer
boranel
the
It
hydrogen
to a fleld
NMB
at
is C-6
effect
41 47
14 (') "8
the
14Be
14Ba 16
NHR
figure Conclusions. Borane
addition
temperature observation N-borane would
be
It
expected of
in the presence groups
higher
field
interest
the
carbons
that
antiperiplanar allows
in 13Be,
effect of
shifts
in
effects
one to assign
adducts
This
is
of
of
boranes
steric
effect
the “B
signal
are
a
kinetic
related
borane
an alternative as
borane
is
to
to quarternary
ratio
N-H borane
the
“B
group
products
favoring
to higher
than axial
fleld
the axial
predominant by heating
ones
shifts
Axial
what
concerning
involves
can be approached
chemical
for
somewhat over
observations
which
more stable
on the
to variable
locking
favored
salts
adducts
adducts
are
independent
14Ba and 14Be the nitrogen
lone The
analogues pairs
on
information
the position
atoms in more complex heterocycles borane
used
, the methyl
boranes
appear
at
It
is
ones of
piperidine
anchored
be
approach
Equatorial
shifting
than equatorial
effect
axial
piperidlnes
amine
constitutes
can
Borane additiongives
that
The thermodynamic
The ‘H NMR chemical
The locking
borane
thermodynamically
of free
in viclnal
N-heterocycles
that
conformers clear
show a systematic
groups
of
is
in
N-substituted
approach22
Methyl
membered ring
of preferred
adducts
alkylations axial
to six
NMB spectroscopy
in stereochemical
of
bearing the
provided
the borane,
such as,
of
concentration
atoms become stable another
heteroatom
neighboring
hydrogen
by
the
as well
13 and 14,
study as
of the
thus pointing
chiral
allows
these
atoms,
centers
one to
see
including
model molecules
configuration
of
other
to the importance
of
analyses
EXPEBIUENTAL. ‘II
and 13C NMR spectra were recorded on Varian XL-BOOGS. Jeol GSX-270 or Jeol FX-90 ctrometers Chemical shifts are reported in parts per million relative to Me&i (61 We B NMB spectra were recorded on a Jeol GSX-270 or a Jeol FX-90 using BFs-etherate as the external standard Tetrahydrofuran was distilled under dry nitrogen from sodium using bezzophenone as Reactions Indicator. the borane-THF complex was prepared uslng a published procedure were carried out under a nitrogen atmosphere The piperidlnes were commercially available,
6914
A FLGRES-PARRAet al
24
and morpholones tetrahydrodlthlazlne was prepared as were prepared by reported dehvdratlon in drv toluene from the N-~2-hydroxy-l-methyl-~~phenylethyl~-N-methylamlno aceilc acid derived from (ephedrine 13 and pseudoephedrlne 141d” of Preparation of the adducts was carried out by addition of 1 2 or 2 4 equivalents borane-THF to compounds 1 to I4 to obtain monoborane and dlborane addition, respectively, To a stirred solution containing 10 mmol of the following the general procedure below heterocycle In 4 ml of THF was added dropwlse a solution of 2 0 M BHa-THF in THF (12 mmol for monoaddltlon and 24 mm01 for diaddltlon, respectively) The solvent was evaporated immediately and the products were examined by NMR
Acknowledgements We are grateful to Conacyt-Mexico and Cosnet for financial support and Dr P Ariza-Castolo, G Paredes-Tepox for Joseph-Nathan, Chemists A Uribe and C recording the spectra and to Dr Rosa Santillan for reading the manuscript and for her helpful comments, and to one of the referees for a stimulating criticism of the paper
References 1 A preliminary communication of this work was presented at the Boron USA Workshop, Research Triangle Park, NC USA, June 6-9, 1990 2 R Contreras, F Santiesteban, M A Paz-Sandoval and B Wrackmeyer. Tetrahedron, 40, 3829 (19841 Reson 3 M A Paz-Sandoval, F Santiesteban and R Contreras, Mag Chem , 23, 428 (19851 4 R Contreras, H R Morales, M L Mendoza and C Domlnguez. Spectrochlm Acta, 43A, 43 (19871 5 A R Gatti and T Wartlk, Inorg Chem , 5. 2075 (19661 6 R Lyle and E W Southwick and J J Kaminskl, J Am Chem Sot , 94, 1413 (1972) 7 H Noth and B Wrackmeyer, Cl-rem Ber , 107, 3070 (19741 33, 915 (19771 8 P J Crowley, M J T Robinson and M G Ward, Tetrahedron, Mag Reson , 11, 418 9 C G Beguin, M N Deschamps, V Boubel and J J Delpuech, Org (19781 10 E L Eliel, D Kandasamy, C Yen and K D Hargrave, J Am Chem Sot, 102, 3698 (19801 11 A F Casy and F 0 Ogungbamila, Org Mag Reson , 18, 171 (19821 12 Our results from a crystallografic X-ray diffraction study of an amine-borane adduct 13 These effects were evaluated by comparison of calculated 8 of conformers A and Blrsing the data of 1Be and the empirical values for an axial and an equatorial methyl group and also using the experimental values of 8 of 2 and the effects of an axial borane 4Ba or an equatorial borane 4Be 14 F W Wehrll, T Wlrthlln, Interpretation of Carbon-13 NMR Spectra, Heyden, Lonafn, 45 by extrapolation of d (19801 15 The expected value of -19 5 ppm was calculated B NNR of 14Ba by adding 5 ppm for substitution of the N-methyl by a H, T Mantilla, F Santlesteban, R Contreras and A Kla&be, Tetrahedron Lett 23, 1561(19821 16 Our results. the chemical shifts of 17Ba and 17Be were assigned by INEPT esperiments 17 R E Lyle,. J Org Chem , 22, 1280 (19571 18 R J Abraham and C J Medforth. J Chem Sot , Chem Commun , 1637 (19871 19 R K Harris and R A Spragg, J- Chem Sot , Chem Conunun, 314 (19661 bl The equatorial borane values were 20 al E Eliel. Chem Ind (London) 568 (19591 and axial borane obtained from compounds 12Be. 13Be, 14Be and 1lBaBe at low temperature values from 14Ba and 14BaBe at low temperature J Chem Sot , Perkln II, 21 L Angiollnl. R P Duke, R A Y Jones and R Katritzky, 674 (19721 22 J HcKenna, Topics Stereochem , 5. 275 (19701 23 H C Brown, Organic Synthesis via Borane Wiley, New York (19751 24 S A Hughes and E B McCall, Chem Abs 60, 5528a (19641 25 N Farfan, L Cuellar, J M Aceves and R Contreras, Synthesis. 927 (19871