Synthesis and structure of highly polarised double-bond compounds derived from S-proline

Article abstract of DOI:10.1016/S0040-4039(00)01372-1

Reaction of the chiral iminium salt 3 with stabilised carbanions gives the compounds 4-9 containing a highly polarised double bond. The extent of this polarisation is determined by variable temperature ¹H NMR studies, comparison of ¹³C NMR chemical shifts and an X-ray structure determination. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01372-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7965–7968
Synthesis and structure of highly polarised double-bond
compounds derived from S-proline
R. Alan Aitken,* Karamat Ali, Noem´ı de Elena and Philip Lightfoot
School of Chemistry, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK
Received 18 July 2000; accepted 10 August 2000
Abstract
Reaction of the chiral iminium salt 3 with stabilised carbanions gives the compounds 4–9 containing a
1
highly polarised double bond. The extent of this polarisation is determined by variable temperature H
NMR studies, comparison of 13C NMR chemical shifts and an X-ray structure determination. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: iminium salts; enamino esters; thiazolidines; X-ray crystal structures.
Some time ago we described the use of the chiral iminium salt 3 derived from (S)-proline for
the kinetic resolution of secondary alcohols.1 While this work was in progress, Yadav and
co-workers briefly reported that the salt 3 reacted with the anions of dimethyl malonate and
malononitrile to give 4 and the corresponding dinitrile2, but the structure and reactivity of these
products was not examined in detail. In view of the high degree of polarisation expected for the
double bond of such compounds, their structure is of some interest and their chirality may
potentially be exploited in developing new methods in asymmetric synthesis. We report here the
synthesis of a wider range of such compounds, an examination of their structure using NMR
methods and in one case an X-ray diffraction study, and a preliminary survey of their reactivity.
The salt 3 was readily prepared by treatment of (S)-prolinol 1 with CS2 and aqueous sodium
hydroxide to give the thiazolidinethione 2 followed by quaternisation with methyl iodide.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01372-1

7966
Addition of this to a THF solution of the appropriate acidic methylene compound and
sodium hydride followed by aqueous work-up and chromatographic purification gave the
desired compounds in moderate to good yield. Starting from dimethyl malonate, methyl
phenylacetate and ethyl acetoacetate gave the products 4, 5 and 6, respectively.3 The corre-
sponding reaction of dibenzoylmethane proved to be more complex. Unexpectedly the prod-
ucts included 1,1-dibenzoylethane and 2,2-dibenzoylpropane presumably from methylation of
the anion by 3, and the desired product 7 was only formed in low yield and was accompanied
by the monobenzoyl product 8. As shown this probably results from attack of MeS− on a
benzoyl group in the intermediate rather than the deprotonation required to give 7. Confirma-
tion of the structure of 8 was obtained by its more rational synthesis by treatment of
acetophenone with LDA followed by the salt 3, and by starting from propiophenone the
compound 9 was obtained similarly.
The imidazolidine-based salt 12 also reacted with the anion of dimethyl malonate to give the
product 13. Formation of salt 12 was achieved by treatment of the known diamine 104 with
thiophosgene and triethylamine to give 11 followed by quaternisation with methyl iodide.
There has been considerable interest in compounds containing a double bond with electron
donors on one end and acceptors on the other.5 The bond may become so highly polarised
that it is more accurately viewed in the fully charge-separated form with a single bond
connecting delocalised anion and cation fragments. One consequence of this is that there is
free rotation about the bond and this feature was immediately apparent in the spectra of 4, 7
and 13, which at room temperature showed only a single set of signals for the ester and
ketone groups. In the cases of 4 and 13 this was quantified by means of a variable tempera-
1
ture H NMR study, which gave coalescence temperatures and free energy barriers to rotation
indicating a high contribution from the charge-separated forms 4a and 13a as shown. The
values obtained for DGc are comparable to those reported for the model compounds 146 and
15.7 It should be noted that all the compounds with R1"R2 showed a single set of NMR
signals at room temperature. In the case of 6 this probably also implies that there is essentially

7967
free rotation about the double bond, while for 5, 8 and 9 with only a single strong electron
withdrawing group present, the compounds exist as a single geometrical isomer, most likely the
ones shown with the most powerful donor and acceptor groups E to one another as previously
found.5
A further measure of the extent of bond-polarisation in such compounds is the difference in
chemical shift of the two carbons observed by 13C NMR.5 As shown in Table 1, the signal for
the effectively cationic carbon adjacent to N comes in the range 160–170 ppm, while the
effectively anionic carbon between the acceptor groups is greatly shielded and appears around
90–100 ppm or in the case of 13 at 75.5 ppm. Although there are few good models for
compounds 4–9, the value of Dl for 13 may be compared with 85.3 for 16.8
Table 1
Some properties of compounds 4–9 and 13
Compound
Yield (%)
Mp (°C)
[h]D
lC (CꢀC)
Dl
4
5
6
7
8
81
59
56
ꢀ10
78
80
79–80
81–82
(oil)
−311.5
−147.5
–
166.7
161.9
168.2
168.8
162.6
166.6
165.0
90.8
98.2
101.8
108.9
88.2
75.9
63.7
66.4
59.9
74.4
64.9
89.5
–
–
122–124
130–132
135–137
−368.9
−217.2
−19.4
9
13
101.7
75.5
84
A further insight into the structure of these compounds was provided by a single-crystal X-ray
diffraction study of 5 (Fig. 1).9 This showed two inequivalent, but closely similar, molecules to
be present in the unit cell. Besides confirming the relative E configuration of the nitrogen and
ester groups about the double bond, this allowed assessment of the extent of polarisation of the
,
double bond. The length of 1.37 A for the C(1)ꢁC(7) bond is indicative of about 80% double
bond character and may be compared to the values shown for the model compounds 17–19.10
,
As expected there is also significant shortening of the C(1)ꢁS(1) (1.778 A) and C(1)ꢁN(1) (1.346
,
A) bonds, but there is no evidence for pyramidalisation at either C(1) or C(7).

7968
Figure 1. X-Ray structure of 5. Selected bond lengths; C(1)ꢁS(1) 1.778(4), C(2)ꢁS(1) 1.803(5), C(1)ꢁN(1) 1.346(5),
,
C(1)ꢁC(7) 1.370(6), C(7)ꢁC(10) 1.497(6), C(7)ꢁC(8) 1.445(6), C(8)ꢁO(1) 1.217(5), C(8)ꢁO(2) 1.351(6) A; dihedral
angles S(1)ꢁC(1)ꢁC(7)ꢁC(8) 5.8(8), S(1)ꢁC(1)ꢁC(7)ꢁC(10) 167.5(4), C(1)ꢁC(7)ꢁC(8)ꢁO(1) 7.5(10), C(1)ꢁC(7)ꢁ
C(8)ꢁO(2) 173.3(5)°; angle sum at C(1) 360.0, C(7) 359.6°
A preliminary study of the reactivity of 4 with nucleophiles and electrophiles showed it to be
quite unreactive. Treatment with methyl iodide gave no reaction, while with methyl triflate the
only process observed was protonation by adventitious triflic acid. Compound 4 was also inert
to butyllithium and ethylmagnesium bromide. It appears that the charge in 4 is too delocalised
to permit reaction with either nucleophiles or electrophiles, but compounds such as 5, 8 and 9
where the extent of anion delocalisation is less may show useful reactivity and this is currently
being examined.
References
1. Aitken, R. A.; Ali, K.; Mesher, S. T. E. Tetrahedron Lett. 1997, 38, 4179–4182.
2. Yadav, L. D. S.; Sharma, S.; Vaish, A. Ind. J. Chem. 1992, 31B, 604–605.
3. Selected spectroscopic data 4: lH 4.39 (1H, m), 3.76 (6H, s), 3.37 (1H, m), 3.10 (2H, m), 2.82 (1H, t, J 11 Hz),
2.20–2.00 (3H, m) and 1.70 (1H, m); lC 167.4 (2×CO), 166.7 (4ry), 90.8 (4ry), 69.2 (CH), 51.6 (2×Me), 49.8 (CH2),
32.8 (CH2), 29.5 (CH2) and 27.3 (CH2). 13: lH 7.35–7.28 (2H, m), 7.25–7.15 (2H, m), 7.09 (1H, m), 4.38 (1H, m),
4.12 (1H, t, J 7 Hz), 3.90 (1H, t, J 7 Hz), 3.57 (1H, m), 3.34 (6H, s), 3.22 (1H, m), 2.30–2.00 (3H, m) and 1.75
(1H, m); lC 167.5 (2×CO), 165.0 (4ry), 142.2 (4ry), 129.1 (2 CH), 124.8 (CH), 121.1 (2 CH), 75.5 (4ry), 59.4 (CH),
56.2 (CH2), 50.5 (2×Me), 48.4 (CH2), 31.6 (CH2) and 26.7 (CH2).
4. Mukaiyama, T. Tetrahedron 1981, 37, 4111–4119.
5. Sandstro¨m, J. Top. Stereochem. 1983, 14, 83–181.
6. Shvo, Y.; Belsky, I. Tetrahedron 1969, 25, 4649–4665.
7. Wennerbeck, I.; Sandstro¨m, J. Org. Magn. Reson. 1972, 4, 783–809.
8. Wang, M.-X.; Liang, J.-M.; Huang, Z.-T. J. Chem. Res. (M) 1994, 1001–1019.
9. Crystal data for 5: C15H17NO2S, M=275.36, colourless plate, crystal dimensions 0.50×0.40×0.20 mm, monoclinic,
3
,
,
space group P21 (c4), a=8.555(3), b=15.555(3), c=10.663(2) A, i=91.23(2)°, V=1418.7(5) A , Z=4,
D
calcd=1.289 Mg m−3, T=293 K, R=0.037, Rw=0.030 for 1930 reflections with I>3|(I) and 342 variables. Data
were collected on a Rigaku AFC7S diffractometer with graphite-monochromated Mo Ka radiation (u=0.71069
,
A). The structure was solved by direct methods (SIR92) and refined using full-matrix least-squares methods.
CCDC 146743.
10. (a) Adhikesavalu, D.; Venkatesan, K. Acta Crystallogr., Sect. C 1983, 39, 589–592. (b) Kamath, N. U.;
Venkatesan, K. Acta Crystallogr., Sect. C 1984, 40, 559–562. (c) Adhikesavalu, D.; Venkatesan, K. Acta
Crystallogr., Sect. C 1983, 39, 1424–1426.
.