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Steric control in the base catalysed H-D exchange of an α,β-unsaturated ketone
Tetrahedron Letters No. 24, pp 2261 - 2262. @Pergamon Press Ltd. 1979. Printed in Great Britain.
STERIC CONTROL
IN THE BASE CATALYSED
H-D EXCHANGE
OF AN &B-UNSATURATED
KETONE
of Chemistry,
For the base catalysed
Monash
H-D exchange
4-t-butyl-1-acetylcyclohex-l-ene is clearly
a result of steric
A recent publication the base catalysed
University,
of the equatorial
have been shown to give the products
of androst-4-end-3,17-dione
reaction
the five potentially Reaction
keq/kax
is 3.8:1.
factors.
and the addition
at the axial 63-position
that in contrast
When
exchangeable
protons
the stereochemistry
of base catalysed
(11, is dominated in dioxan
in the products.
7 days led to essentially
COCD3
complete COCD
NaOD/D20 dioxan, '>. $
H-e),
as in (31.
exchange
3 H .D ,..'
7 days
'H and 2H spectra were recorded
of (1) was assigned
(s, 9H, But), 2.30 1.73-1.92
NaOD/D20
'_I_.. H !a H t BU (2)
(1)
6, 0.90
.D (...
15h '
H-D exchange
at 90' for 15h four of
I
The 1H spectrum
attack on
by steric rather than
had been replaced by deuterium
for a further
coCH3
of the five protons
in
of DC1 to 3-ethoxycholesta2 control. Each of these
even though this involves
(1) was reacted with NaOD/D20
under the same conditions
6 But
in
This
of the steroid molecule.
We wish to report
factors.
and the axial hydrogen
CH30Na,
of stereoelectronic
in the cyclic enone 4-t-butyl-1-acetylcyclohex-l-ene stereoelectronic
3168.
that stereoelectronic control predominates 1 Similarly, the base of the o-protons in twistan-4-one.
3,5-diene
@-face
Australia,
has demonstrated
H-D exchange
involves
Victoria,
hydrogen
rather than stereoelectronic
enolisation
latter examples
Clayton,
(1) in CH30D containing
catalysed
the more hindered
and Jlrqen U.G. Strauss,
Anna Straqalinou
Bruce A.W. Coller, W. Roy Jackson, Department
3
0 But
(3) for the products
as follows on the basis of extensive
(s, 3H, CH3CO),
(m, 3H. H-3~1, H-38, H-a),
6.02 2.40
(dd, lH, H-21, (dd, H, H-6@.
F= D H
(21 and
decoupling
1.0 (m, 2H, H-~'S), The coupling
(3).
experiments, 1.14
constants
(m, lH, J6o 68
I
11.5H2, J 14.5H2, J5o 6cL 4.5Hz, J 11.5Hz, J%,* 5.OHz, J2,3a 3.1Hz and J2,% 1.4Hz I 43,5o 3o,rY3 were assigned. The significant differences between J are consistent with a 3o,48 and JB8,43 fairly rigid cyclohexene chair conformation (4). The tetradeuterio subsituted compound (2)
COCH I3
2261
showed the olefinic
proton
as a doublet
Retention
of the pseudo-axial-axial
B-proton
had been preferentially
with J3.1Hz
and H as a triplet with J=11.4Hz. B of 11.4Hz suggested that the pseudo-equatorial
coupling exchanged.
The multiplet
centred
on 1.8 p.p.m.
had decreased
in intensity
by the equivalent of one proton and confirmation of this chemical shift was 2 from a H spectrum which showed a peak at 1.85 p.p_m. in addition to that due to the
obtained
COCD3 group.
of the pentadeuterio
The 'H n.m.r.
as a doublet
with J e
further agreement
5a 11.4Hz together
hydrogen
exchange
results
for exchange
that quoted B-protons enone
example2
for axial exchange
were made to measure
for a solution
at 35.6 04 .
of
The rate
and the axial hydrogen
It thus appears exchange
in CH30D
in terms of simple H-D exchange
and ButOK in ButOD.
that although
of equatorial
hydrogen
in the cyclic strong
exists and is only just overcome.
the relative
interpreted
rates of exchange
Unfortunately
the kinetic
of (1) with the bulkier
data could not be
reactions.
and Footnotes
1.
R.R. Fraser
2.
K. Henderson
and P.J. Champagne,
Spectra
J.Amer.Chem.Soc.,
were recorded
and his colleagues Rate constants recorded
natural
are reported
shown to be virtually
constant versus
was monitored
a graphical
previously ",
mode.
described
in UK 2 April 1979)
aliquots Average
1978, 15; S.K. Malhotra
was calculated
and
for 2H by Dr. Alan Jones
Canberra,
A.C.T.
order rate constants. using a VG-Micromass
Mass spectra were
spectrometer
values were taken after correction of a d
derivative,
3 in less than one minute
by the diminution
integral
1087.
Centre,
The formation
complete
for d5 formation
N.M.R.
as pseudo-first
abundances.
1978, 100, 657.
1965, 87, 3228. 1 for H and at 41.44MHz
from quenched
in the unfocussed
isotopic
derivative
at 290MHz
J.C.S.Chem.Comm.,
at the National
on samples
operating
J.Amer.Chem.Soc.,
and F.J. McQuillin,
H.J. Ringold,
(Received
for
k
(krel = 64).
bases NaOPh
4.
of exchange
(0.485M) were measured
hydrogen
lead to a preferential
preference
preference
0.333h-1 and were k eq = 3.8 is dramatically less than rel = keq'kax 1 or for the of the two cl-protons in twistan-4-one (krel - 290)
for the exchange
Attempts
3.
48 in
to attack of base on the axial
The kinetics
sodium methoxide
of the equatorial
in the steroidal
stereoelectronic
for H
due to long range coupling
that the stereoelectronic
resistance
group.
The ratio of these rate constants
(1) steric effects
References
suggest
the steric
-cis-t-butyl
(1) (0.07M) in CH30D containing
k ax O.O86h-'.
strongly
cannot overcome
atom by the adjacent,
constants
(3) now showed the absorption
with these proposals.
The stereochemical pseudo-axial
compound
with some fine splitting
in intensity
i.e. COCD
and the formation of the d3peak.
for
was
3' of d4
The rate
by means of a graph of d5 peak height
of the d4 peak height,
by R.P. Bell and B.A.W.
[d51 = k/[d41dt,
Caller,
Trans.Faraday
a procedure Sot.,
1964,
STERIC CONTROL
IN THE BASE CATALYSED
H-D EXCHANGE
OF AN &B-UNSATURATED
KETONE
of Chemistry,
For the base catalysed
Monash
H-D exchange
4-t-butyl-1-acetylcyclohex-l-ene is clearly
a result of steric
A recent publication the base catalysed
University,
of the equatorial
have been shown to give the products
of androst-4-end-3,17-dione
reaction
the five potentially Reaction
keq/kax
is 3.8:1.
factors.
and the addition
at the axial 63-position
that in contrast
When
exchangeable
protons
the stereochemistry
of base catalysed
(11, is dominated in dioxan
in the products.
7 days led to essentially
COCD3
complete COCD
NaOD/D20 dioxan, '>. $
H-e),
as in (31.
exchange
3 H .D ,..'
7 days
'H and 2H spectra were recorded
of (1) was assigned
(s, 9H, But), 2.30 1.73-1.92
NaOD/D20
'_I_.. H !a H t BU (2)
(1)
6, 0.90
.D (...
15h '
H-D exchange
at 90' for 15h four of
I
The 1H spectrum
attack on
by steric rather than
had been replaced by deuterium
for a further
coCH3
of the five protons
in
of DC1 to 3-ethoxycholesta2 control. Each of these
even though this involves
(1) was reacted with NaOD/D20
under the same conditions
6 But
in
This
of the steroid molecule.
We wish to report
factors.
and the axial hydrogen
CH30Na,
of stereoelectronic
in the cyclic enone 4-t-butyl-1-acetylcyclohex-l-ene stereoelectronic
3168.
that stereoelectronic control predominates 1 Similarly, the base of the o-protons in twistan-4-one.
3,5-diene
@-face
Australia,
has demonstrated
H-D exchange
involves
Victoria,
hydrogen
rather than stereoelectronic
enolisation
latter examples
Clayton,
(1) in CH30D containing
catalysed
the more hindered
and Jlrqen U.G. Strauss,
Anna Straqalinou
Bruce A.W. Coller, W. Roy Jackson, Department
3
0 But
(3) for the products
as follows on the basis of extensive
(s, 3H, CH3CO),
(m, 3H. H-3~1, H-38, H-a),
6.02 2.40
(dd, lH, H-21, (dd, H, H-6@.
F= D H
(21 and
decoupling
1.0 (m, 2H, H-~'S), The coupling
(3).
experiments, 1.14
constants
(m, lH, J6o 68
I
11.5H2, J 14.5H2, J5o 6cL 4.5Hz, J 11.5Hz, J%,* 5.OHz, J2,3a 3.1Hz and J2,% 1.4Hz I 43,5o 3o,rY3 were assigned. The significant differences between J are consistent with a 3o,48 and JB8,43 fairly rigid cyclohexene chair conformation (4). The tetradeuterio subsituted compound (2)
COCH I3
2261
showed the olefinic
proton
as a doublet
Retention
of the pseudo-axial-axial
B-proton
had been preferentially
with J3.1Hz
and H as a triplet with J=11.4Hz. B of 11.4Hz suggested that the pseudo-equatorial
coupling exchanged.
The multiplet
centred
on 1.8 p.p.m.
had decreased
in intensity
by the equivalent of one proton and confirmation of this chemical shift was 2 from a H spectrum which showed a peak at 1.85 p.p_m. in addition to that due to the
obtained
COCD3 group.
of the pentadeuterio
The 'H n.m.r.
as a doublet
with J e
further agreement
5a 11.4Hz together
hydrogen
exchange
results
for exchange
that quoted B-protons enone
example2
for axial exchange
were made to measure
for a solution
at 35.6 04 .
of
The rate
and the axial hydrogen
It thus appears exchange
in CH30D
in terms of simple H-D exchange
and ButOK in ButOD.
that although
of equatorial
hydrogen
in the cyclic strong
exists and is only just overcome.
the relative
interpreted
rates of exchange
Unfortunately
the kinetic
of (1) with the bulkier
data could not be
reactions.
and Footnotes
1.
R.R. Fraser
2.
K. Henderson
and P.J. Champagne,
Spectra
J.Amer.Chem.Soc.,
were recorded
and his colleagues Rate constants recorded
natural
are reported
shown to be virtually
constant versus
was monitored
a graphical
previously ",
mode.
described
in UK 2 April 1979)
aliquots Average
1978, 15; S.K. Malhotra
was calculated
and
for 2H by Dr. Alan Jones
Canberra,
A.C.T.
order rate constants. using a VG-Micromass
Mass spectra were
spectrometer
values were taken after correction of a d
derivative,
3 in less than one minute
by the diminution
integral
1087.
Centre,
The formation
complete
for d5 formation
N.M.R.
as pseudo-first
abundances.
1978, 100, 657.
1965, 87, 3228. 1 for H and at 41.44MHz
from quenched
in the unfocussed
isotopic
derivative
at 290MHz
J.C.S.Chem.Comm.,
at the National
on samples
operating
J.Amer.Chem.Soc.,
and F.J. McQuillin,
H.J. Ringold,
(Received
for
k
(krel = 64).
bases NaOPh
4.
of exchange
(0.485M) were measured
hydrogen
lead to a preferential
preference
preference
0.333h-1 and were k eq = 3.8 is dramatically less than rel = keq'kax 1 or for the of the two cl-protons in twistan-4-one (krel - 290)
for the exchange
Attempts
3.
48 in
to attack of base on the axial
The kinetics
sodium methoxide
of the equatorial
in the steroidal
stereoelectronic
for H
due to long range coupling
that the stereoelectronic
resistance
group.
The ratio of these rate constants
(1) steric effects
References
suggest
the steric
-cis-t-butyl
(1) (0.07M) in CH30D containing
k ax O.O86h-'.
strongly
cannot overcome
atom by the adjacent,
constants
(3) now showed the absorption
with these proposals.
The stereochemical pseudo-axial
compound
with some fine splitting
in intensity
i.e. COCD
and the formation of the d3peak.
for
was
3' of d4
The rate
by means of a graph of d5 peak height
of the d4 peak height,
by R.P. Bell and B.A.W.
[d51 = k/[d41dt,
Caller,
Trans.Faraday
a procedure Sot.,
1964,