Unusual conformational effect in alpha-aminoorganostannanes.

Article abstract of DOI:10.1021/ol990737x

[formula: see text] Dynamic NMR analysis of conformationally mobile and rigid 2-tributylstannyl-N-methylpiperidines revealed an unexpected conformational effect that is manifested in a small energy difference between conformers in which the tin is equatorial and axial. The major reason appears to be a distortion of the conformer in which the C-2-Sn bond is synclinal to the nitrogen lone pair.

Full text of DOI:10.1021/ol990737x

ORGANIC
LETTERS
1999
Vol. 1, No. 4
653-655
Unusual Conformational Effect in
r-Aminoorganostannanes
Robert E. Gawley,* Eddy Low, and Gilles Chambournier
Department of Chemistry, UniVersity of Miami, P.O. Box 249118,
Coral Gables, Florida 33124-0431
rgawley@miami.edu
Received June 15, 1999
ABSTRACT
Dynamic NMR analysis of conformationally mobile and rigid 2-tributylstannyl-N-methylpiperidines revealed an unexpected conformational
effect that is manifested in a small energy difference between conformers in which the tin is equatorial and axial. The major reason appears
to be a distortion of the conformer in which the C-2−Sn bond is synclinal to the nitrogen lone pair.
In the last 20 years, R-aminoorganolithiums have become
important reagents in organic synthesis because of their
versatility and configurational stability.1-7 From a stereo-
chemical standpoint, two of the more useful methods used
to access R-aminoorganolithiums are deprotonation and
transmetalation by tin-lithium exchange. The two methods
are complementary: deprotonation can be stereoselective,
whereas tin-lithium exchange provides access to compounds
that are not accessible by deprotonation due to a kinetic
barrier. Furthermore, since metal exchange usually proceeds
with retention of configuration at a stereogenic metal-bearing
carbon, tin-lithium exchange can afford organolithiums of
known absolute configuration.
transmetalation attempts have been reported are shown
below.9-16 In particular, note the effects of rings on the
success or failure of the transmetalation reaction. At a
position where the metal-bearing carbon is secondary, tin-
lithium exchange fails when the metal-bearing carbon is
acyclic, unless there is a chelating atom available. Clearly,
there are very subtle factors at work here, and structural
studies of R-aminoorganostannanes are warranted.
Unfortunately, metal exchange in R-aminoorganostannanes
is characterized by anomalies. Although R-aminoorganostan-
nanes first became precursors to R-aminoorganolithiums
nearly 30 years ago,8 transmetalation can be capricious.
Several examples of R-aminoorganostannanes for which
(1) Beak, P.; Reitz, D. B. Chem. ReV. 1978, 78, 275.
(2) Beak, P.; Zajdel, W. J.; Reitz, D. B. Chem. ReV. 1984, 84, 471.
(3) Gawley, R. E.; Rein, K. In ComprehensiVe Organic Synthesis.
SelectiVity, Strategy, and Efficiency in Modern Organic Chemistry; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, p 65.
(4) Gawley, R. E.; Rein, K. S. In ComprehensiVe Organic Synthesis;
Schreiber, S., Ed.; Pergamon: Oxford, 1991; Vol. 1, p 459.
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Acc. Chem. Res. 1996, 29, 552.
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Ed.; JAI: Greenwich, CT, 1998; Vol. 3, p 77.
(8) Peterson, D. J. J. Organomet. Chem. 1970, 21, P63.
10.1021/ol990737x CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/24/1999

Recently, as part of an NMR investigation of heterocyclic
R-aminoorganometallics, we examined the carbon-13 NMR
spectra of N-methyl-2-tributylstannylpiperidine (1) at low
temperature. We were surprised to find evidence of two
nearly equally populated conformers, suggesting that there
is a stereoelectronic effect that influences the solution
structure of R-aminoorganostannaes.
for N-methyl-2-tributylstannylpiperidine, as shown in Scheme
1, resulting from ring inversion (RI, vertical arrows) and
Scheme 1a
Partial 13C spectra (C-2, C-6, and the N-methyl region) of
N-methyl-2-tributylstannylpiperidine and the same region
(now including C-4) of cis-N-methyl-4-tert-butyl-2-tributyl-
stannylpiperidine, 2, at various temperatures, are shown in
Figure 1. The absence of any dynamic phenomena in the
a NI ) nitrogen inversion; RI ) ring inversion. N&RI )
simultaneous nitrogen and ring inversion.
nitrogen inversion (NI, horizontal arrows). From the Meeq-
Sneq conformer, RI gives the high-energy MeaxSnax conformer
and then NI affords the MeeqSnax conformer. The latter is
more easily accessed via the MeaxSneq conformer by a
sequential NI-RI sequence from the MeeqSneq conformer.
It has also been suggested that these individual motions could
be coupled such that conversion of the MeeqSneq to the Meeq-
Snax conformer takes place directly (N&RI).18 The energetic
preference for the N-methyl of N-methylpiperidine for the
equatorial orientation is 2.41 kcal/mol (chloroform solu-
tion),19 so the two Meax conformers are unlikely contributors,
leaving the MeeqSneq and MeeqSnax as the two species
observed by NMR.
Figure 1. Partial 13C NMR spectra (100 MHz, THF-d8) of
N-methyl-2-tributylstannylpiperidine and cis-N-methyl-4-tert-butyl-
2-tributylstannylpiperidine.
The free energy difference for a methyl in the 2-position
of N-methylpiperidine is 1.7 kcal/mol,20 the same as its A
value in methylcyclohexane. The A values for several
trialkylstannyl groups (Me3Sn, i-Pr3Sn, Me2PhSn) range from
1 to 1.1 kcal/mol in substituted cyclohexanes,21 and those
for tributylstannyl should be similar. Since the free energy
differences for a methyl in cyclohexane and N-methyl-
piperidine are the same, it is reasonable to assume similar
energy differences for stannyl groups in cyclohexanes and
N-methylpiperidine. Therefore, one might expect ∆G° )
1.0-1.1 kcal/mol for the MeeqSneq a MeeqSnax equilibrium
at low temperature (the Me3Sn value was determined at low
temperature). This would correspond to an equilibrium
constant of ∼1/14, reflecting an 7:93 mixture. The ratio of
peaks in the low-temperature NMR of 1 is 55:45 favoring
the diequatorial isomer (vide infra), corresponding to ∆G°
) 73 cal/mol at -70 °C. To compensate for the expected
spectra of 2 fix the dynamic phenomena of 1 as ring
inversions. The coalescence temperature for the N-methyl
signal of 1 is near -30° and corresponds to an energy of
activation of approximately 11 kcal/mol. In comparison, the
barrier to ring inversion for N-methylpiperidine (in methanol)
is 14.4 kcal/mol.17
Only two species are observed in the DNMR spectra at
slow exchange. There are four possible chair conformations
(9) Pearson, W. H.; Lindbeck, A. C. J. Am. Chem. Soc. 1991, 113, 8546.
(10) Burchat, A. F.; Chong, J. M.; Park, S. B. Tetrahedron Lett. 1993,
34, 51.
(11) Gawley, R. E.; Zhang, Q. J. Am. Chem. Soc. 1993, 115, 7515.
(12) Gawley, R. E.; Zhang, Q. Tetrahedron 1994, 50, 6077.
(13) Gawley, R. E.; Zhang, Q.; Campagna, S. J. Am. Chem. Soc. 1995,
117, 11817.
(14) Gawley, R. E.; Campagna, S. In ECHET96. Electronic Conference
on Heterocyclic Chemistry; Rzepa, H., Snyder, J., Eds.; Royal Society of
Chemistry: London, 1997 (CD-ROM).
(15) Tsunoda, T.; Fujiwara, K.; Yamamoto, Y.; Itoˆ, S. Tetrahedron Lett.
1991, 32, 1975.
(16) Gawley, R. E.; Evanseck, J. D.; Pearson, W. H.; Stevens, E. P. In
ECHET96. Electronic Conference on Heterocyclic Chemistry; Rzepa, H.,
Snyder, J., Eds.; Royal Society of Chemistry: London, 1997 (CD-ROM).
(17) Lambert, J. B.; Keske, R. G.; Carhart, R. E.; Jovanovich, A. P. J.
Am. Chem. Soc. 1967, 89, 3761.
(18) Delpuech, J.-J. In Cyclic Organonitrogen Stereodynamics; Lambert,
J. B., Taieuchi, Y., Eds.; VCH: New York, 1992; p 169.
(19) Crowley, P. J.; Robinson, M. J. T.; Ward, M. G. Tetrahedron 1977,
33, 915.
(20) Eliel, E. L.; Kandasamy, D.; Yen, C.; Hargrave, K. D. J. Am. Chem.
Soc. 1980, 102, 3698.
(21) Kitching, W.; Olszowy, H. A.; Harvey, K. J. Org. Chem. 1982, 47,
1893.
654
Org. Lett., Vol. 1, No. 4, 1999

equatorial preference of 1.0-1.1 kcal/mol, there must be a
compensating force reminiscent of the anomeric effect in
carbohydrates, and its value must be approximately 0.9-
1.0 kcal/mol. However, as explained below, this effect is
not due to a stabilization of the axial conformer.
Hz) coupling is evident in the N-methyl carbon, but it is
difficult to quantitate because of line broadening by the
nitrogen. Nevertheless, this value is near the minimum
possible coupling on the Karplus curve and corresponds to
a torsion angle of approximately 70°. Taken together, these
features are consistent with a half-chair conformation for 2,
with a nearly planar, sp2-hybridized nitrogen atom.
At the slow exchange limit, the two conformations of 1
can be analyzed independently, with the couplings sum-
marized in Table 1. The MeeqSneq conformer has couplings
to the N-methyl and C-6 that indicate a half-chair conforma-
tion similar to that observed for 1, while the MeeqSnax
conformation shows couplings indicative of a normal,
undistorted chair.
The Karplus relationship for couplings to the N-methyl
and C-6 go through a nitrogen atom and therefore may not
strictly adhere to the Karplus curve derived from carbocycles.
Nevertheless, there appear to be no inconsistencies in the
data, so we assume the relationship is valid for 119Sn-C-
N-13C.
3
A Karplus relationship has been observed for the JSn-C
couplings in a number of rigid bicyclic and tricyclic
organostannanes.22 Synclinal torsions afford 3JSn-C couplings
of 14 Hz, whereas antiperiplanar 3JSn-C couplings are 63 Hz.
Substituted cyclohexylstannanes, such as cis- and trans-4-
tert-butylcylohexyltrimethylstannane show couplings from
tin to the C-3 and C-5 ring carbons that are entirely consistent
with the Karplus relationship: in the cis isomer, the synclinal
coupling is 12.0 Hz, whereas the coupling is 67.1 Hz in the
trans isomer, which has an antiperiplanar torsion angle.23
The chemical shifts and coupling constants for 2 are listed
in Table 1. Couplings to C-4 and C-6 correspond to torsion
3
Table 1. Chemical Shifts and JSn-C Coupling Constants for 1
and 2a
The reasons for the conformational distortions in the
diequatorial isomers are not obvious. No such distortions are
evident in cis-2-methylcyclohexyltrimethylstannane, which
exhibits couplings to the C-3 and C-5 carbons consistent with
a 180° torsion angle,24 so it would seem that the nitrogen is
responsible for the ring distortion. Since the diequatorial
conformer is the one that is distorted, the small energy
difference between the MeeqSneq and MeeqSnax conformers
of 1 appears to be due to a destabilization of the conformer
in which the carbon-tin bond is synclinal to the nitrogen
lone pair.
It is not clear whether this conformational distortion is
relevant to the failure of certain R-aminostannanes to
transmetalate, since both 1 and 2 transmetalate in 15 minutes
or less at -80°. On the other hand, the effect observed here
may manifest itself differently in acyclic systems.
MeeqSneq
1
MeeqSnax
1
2
N-Me
C-2
49.9b(e8.8)c
59.6
48.2b (8.8)
64.2
(139, 145)d
49.1 (5.3)c
59.6
(204, 213)d
49.0 (25.5)
60.5 (27.5)
(202, 214)d
C-4
C-6
26.2e (20.3)
60.2 (24.6)
56.3 (11.8)
a Chemical shifts in ppm, relative to TMS; reference line THF-d8 at 67.4
ppm. Coupling constants in parentheses. All spectra recorded at 100 MHz,
at -70 °C, unless otherwise noted. b Conformational isomers assigned by
comparison of the chemical shifts and the coupling constants with 2.
c Coupling constant is approximate due to line broadening. The satellite
appeared as an unresolved shoulder. d Couplings to 117Sn and 119Sn nuclides.
e Room-temperature value. At -70 °C, the lines are obscured by the THF
signal.
Acknowledgment is made to the donors of the Petroleum
Research Fund, administered by the American Chemical
Society, for partial support of this work (PRF 32984-AC1).
We also thank the NIH for partial support (GM 56271).
angles of ∼125°. This anticlinal angle requires that the C-2-
Sn bond must nearly eclipse the C-3-H bond. A small (<9
(22) Doddrell, D.; Burfitt, I.; Kitching, W.; Bullpitt, M.; Lee, C.-H.;
Mynott, R. J.; Considine, J. L.; Kuivila, H. G.; Sarma, R. H. J. Am. Chem.
Soc. 1974, 96, 1640.
(23) Kitching, W.; Olszowy, H.; Waugh, J.; Doddrell, D. J. Org. Chem.
1978, 43, 898.
(24) Kitching, W.; Olszowy, H. A.; Harvey, K. J. Org. Chem. 1982, 47,
1893.
Supporting Information Available: Details of the syn-
thesis of stannane 2 from 4-tert-butylpyridine. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL990737X
Org. Lett., Vol. 1, No. 4, 1999
655