Structure elucidation of polyene systems with extensive charge delocalization - Carbocations from allylic carotenols

Article abstract of DOI:10.1021/ol034987w

(Matrix presented) The structures of two diastereomeric cations, readily prepared from β,β-caroten-4-ol (1) by treatment with trifluoroacetic acid, have been determined by NIR and NMR spectroscopy, resulting in the complete structure elucidation of the mo

Full text of DOI:10.1021/ol034987w

ORGANIC
LETTERS
2003
Vol. 5, No. 15
2675-2678
Structure Elucidation of Polyene
Systems with Extensive Charge
DelocalizationsCarbocations from
Allylic Carotenols
Geir Kildahl-Andersen, Bjart Frode Lutnaes, Jostein Krane, and
Synnøve Liaaen-Jensen*
Department of Chemistry, Norwegian UniVersity of Science and Technology (NTNU),
NO-7491 Trondheim, Norway
slje@chem.ntnu.no
Received June 3, 2003
ABSTRACT
The structures of two diastereomeric cations, readily prepared from â,â-caroten-4-ol (1) by treatment with trifluoroacetic acid, have been
determined by NIR and NMR spectroscopy, resulting in the complete structure elucidation of the most extensively delocalized carbocations
so far described. Higher partial charge was observed toward the center of the polyene chain (larger filled red circles). Bond reversion occurs
in the central region of the molecule.
In the carotenoid field the elimination of allylic hydroxy or
alkoxy groups in acidified chloroform, resulting in products
with prolonged chromophore, has become a useful diagnostic
reaction.1 This reaction, performed in 0.03 N HCl/CHCl3,
was first introduced in 1951 by Karrer’s school2 and later
standardized.3 The reaction was early employed for iso-
cryptoxanthin (1, â,â-caroten-4-ol), providing isocarotene (2,
4′,5′-didehydro-4,5′-retro-â,â-carotene).4 The reaction has
been considered to proceed via a hypothetic, rearranged
allylic carbocation, Scheme 1.1,5
A modern reinvestigation of the reaction referred to in
Scheme 1 has led to a complete structure elucidation of the
most charge delocalized carbocation (over 23 carbon atoms)
so far described.
(4RS)-Isocryptoxanthin (1) was prepared by NaBH4-
reduction of echinenone (â,â-caroten-4-one). The standard
reaction in 0.03 N HCl in CHCl3 was monitored by vis-
NIR spectroscopy, and the reaction mixture was analyzed
by HPLC. At room temperature, a weak absorption around
1010 nm was detected and assigned to the intermediate
carbocation. This cation intermediate was more pronounced
at -20 °C. However, the reaction proceeded to the elimina-
tion products isocarotene (2) and some 3,4-didehydro-â,â-
carotene. Strongly E/Z isomerized isocarotene (2), estab-
lished by HPLC analysis, was consistent with cationic
intermediates.
Recently we have characterized in detail a dication pre-
pared from â,â-carotene (3) by treatment with BF3-etherates.6
(1) Liaaen-Jensen, S. In Carotenoids; Isler, O., Ed.; Birkhau¨ser: Basel,
1971; pp 61-188.
(2) Karrer, P.; Leumann, E. HelV. Chim. Acta 1951, 34, 445-453.
(3) Entschel, R.; Karrer, P. HelV. Chim. Acta 1958, 41, 402-413.
(4) Wallcave, L.; Zechmeister, L. J. Am. Chem. Soc. 1953, 75, 4495-
4498.
(6) Lutnaes, B. F.; Bruås, L.; Krane, J.; Liaaen-Jensen, S. Tetrahedron
Lett. 2002, 43, 5149-5152.
(5) Pfander, H.; Leuenberger, U. Chimia (Aarau) 1976, 30, 71-73.
10.1021/ol034987w CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/03/2003

2:1 ratio. 1H and 13C NMR chemical shifts of 4a and of â,â-
carotene (3)8 and isocarotene (2a)8 used as models are given
in Table 1, as well as shift differences between the cation
4a and the relevant model.
Scheme 1
Table 1. 1H and 13C Chemical Shifts for Monocation 4a and
Shift Changes Relative to 2 or 3 in CD2Cl2 Solution
δH (ppm)
δC (ppm)
4a
refa
∆
4a
refa
∆
1
2
3
4
5
6
7
8
36.5
40.1
23.6
35.1
40.8
23.0
1.4
-0.7
0.6
9.7
1.5
14.2
2.3
17.3
3.9
19.8
3.1
24.4
4.7
1.58d
2.24d
6.20
1.50
2.12
5.78
0.08
0.12
0.42
138.3
135.6
160.3
122.6
147.7
139.4
158.7
127.4
161.7
141.1
158.4
132.4
29.5
128.6
134.1
146.1
120.3
130.4
135.5
138.9
124.3
137.3
136.4
132.4
130.0
29.0?
29.0?
21.7
6.60
7.56
6.39
6.79
0.21
0.77
9
10
11
12
13
14
15
16
17
18
19
20
1′
7.29
7.00
7.41
6.44
6.63b
6.35
0.85
0.37
1.06
When isocryptoxanthin (1) was reacted with 13 mM
trifluoroacetic acid in CH2Cl2 at -20 °C, a fast and
quantitative conversion of 1 to a colorless (black at high
concentration) solution of cation 4 was observed, with λmax
1028 nm in the same region as carotenoid radical cations,7
Figure 1. The small differences in λmax for 4 in CH2Cl2 and
7.27
7.00
1.35
1.35
1.96
2.07
2.13
6.25
6.63
1.31
1.31
1.92
1.97
1.97
1.02
0.37
0.04
0.04
0.04
0.10
0.16
26.0
2.4
0.5
29.5
21.6
12.0
12.7
0.5
-0.1
-0.1
-0.1
0.3
12.1
12.8
34.4
34.7
2′
3′
4′
1.48d
1.61d
2.12d
1.46
1.62
2.02
0.02
-0.01
0.10
39.9
19.0
34.4
39.8
19.4
33.2
0.1
-0.4
1.2
5′
6′
7′
8′
139.9
138.7
138.2
137.0
154.6
133.6
143.5
137.8
163.9
136.8
154.3
29.0
129.3
138.0
126.7
137.8
136.0
130.8
125.1
137.3
136.4
132.4
130.0
29.0
10.6
0.7
11.5
-0.8
18.6
2.8
18.4
0.5
27.5
4.4
24.3
0.0
0.0
0.5
1.0
6.90
6.49
6.16
6.15
0.74
0.34
9′
10′
11′
12′
13′
14′
15′
16′
17′
18′
19′
20′
Σ
6.54
7.70
6.74
6.15
6.65
6.35
0.39
1.05
0.39
6.82
7.75
1.08
1.08
1.82
2.21
2.34
6.25
6.63
1.03
1.03
1.72
1.97
1.97
0.57
1.12
0.05
0.05
0.10
0.24
0.37
12.42c
Figure 1. Absorption spectra of isocryptoxanthin (1) and the
monocation 4 in CH2Cl2.
29.0
22.2
13.8
14.5
29.0
21.7
12.8
12.8
1.7
254.2
CHCl3 are ascribed to different solvents and counterions. The
stability of the cation 4 was monitored by its NIR absorption
at -20 °C, demonstrating a decrease in intensity at λmax of
<10% during 3 h.
Detailed NMR analysis (400 and 500 MHz, CD2Cl2, -10
°C) using CF3COOD as acid was carried out, including 1H,
1H-1H COSY, ROESY, 1H-13C HSQC, and 1H-13C HMBC
spectra.
a 2a used as reference for positions 1-11 and 16-19; 3 used for the
rest of the molecule. Data from ref 8, except H-11. b From ref 11. c Counting
methylene protons twice and methyl protons three times. d Methylene
protons pairwise same chemical shifts.
1
The total H (12.42 ppm) and 13C (254.2 ppm) shift
It was evident that the cation 4 had an unsymmetrical
structure and consisted of two isomers 4a and 4b in a ca.
difference of 4a relative to 2a (C-1-C-11 and C-16,17,18,-
(8) Englert, G. In Carotenoids Vol. 1B: Spectroscopy; Britton, G.,
Liaaen-Jensen, S., Pfander, H., Eds.; Birkha¨user: Basel, 1995; pp 147-
260.
(7) Konovalov, V. V.; Kispert, L. D. J. Chem. Soc., Perkin Trans. 2
1999, 4, 901-910.
2676
Org. Lett., Vol. 5, No. 15, 2003

19) or 3 (rest of the molecule) was consistent with a
monocarbocation.6,9,10 The 13C chemical shift differences,
Table 1, were used to identify the charge distribution in 4a.
The charge was mainly located in the central region; ∆δC >
18 ppm at C-10, 12, 14, 15′, 13′, 11′, and 9′; ∆δC > 9 ppm
also includes C-4, 6, 8, 5′, and 7′. Larger filled red circles
(structures 4a and 4b) indicate higher charge density. Judged
by the chemical shift and coupling pattern, 4a contained an
olefinic proton at C-4. A double bond at C-8,9 was concluded
from the long-range coupling of Me-19 to H-8 in the COSY
spectrum and the s-trans coupling of 13.4 Hz for H-7,8.
A common â-end group, extended from C-1′ to C-10′,
followed from the trans H-7′,8′ coupling constant (J ) 16.0
Hz) and long-range coupling of Me-19′ to H-10′. Conse-
quently, bond reversion (dotted bonds) must take place within
the C-10-C-11′ region in 4a.
the configuration of the exocyclic C-6,7 double bond caused
by restricted rotation of the ring. The effect of this E/Z
isomerization on the charge distribution in the two diaster-
eomeric cations 4a and 4b is reflected by the difference in
chemical shift data, Tables 1 and 2.
Rotation also of the C-6′,7′ single bond of the monocation
4 was observed by a sharp singlet at δH 1.38 ppm,
constituting 20% of the geminal dimethyl groups of the â-end
group. Support for this assignment was obtained from the
HMBC spectrum, giving the following carbon chemical
shifts: 30.3 ppm (C-16′,17′), 34.4 ppm (C-1′), and 135.9
ppm (C-6′).
Structures 4c and 4d for these less populated conformers
of the monocation 4 are shown. For 4c, all polyene single
bonds are in the s-trans configuration, giving the best overlap
of π orbitals. This would therefore be the structure expected
to provide maximum charge delocalization. It is interesting
to note that the C-6′,7′ s-trans conformation of the â-end
group has only been encountered in the ionized state.
The isomer 4b differed from 4a in chemical shifts mainly
in the C-1-C-10 region, as predicted for opposite configu-
The monocation 4 in CH2Cl2 solution was reacted with
water as a nucleophile in aqueous acetone at -10 °C,
pigment recovery 88%. The reaction mixture was analyzed
by HPLC/vis, revealing the formation of strongly E/Z
isomerized isocryptoxanthin (1, 89% of total recovered) and
isocarotene (2, ca. 5%). Both 4a and 4b will provide 1 with
a C-6,7 s-cis bond. All carotenoids with the common â-end
group exist in this preferred conformation.8,12
1
ration of the exocyclic C-6,7 double bond. H and 13C
chemical shifts for this isomer and shift changes relative to
relevant models are given in Table 2.
Table 2. 1H and 13C Chemical Shifts for Monocation 4b and
Shift Changes Relative to 2 or 3 in CD2Cl2 Solutiona
Isocarotene was originally assigned the structure 2. More
recent NMR studies including NOE experiments have
demonstrated that the C-6,7 E (trans) end group A dominated
over the C-6,7 Z (cis) end groups B in a 3:1 ratio in CDCl3.11
This means that 2 consisted of three diastereomers with end
groups A,A (2a, 56%), B,B (2b, 6%), and A,B (2c, 38%).
The formation of products 2 (as 2a, 2b, 2c) and 1 from the
cations 4a and 4b may readily be rationalized.
The smooth formation of the cations 4 by treatment of
the allylic carotenol isocryptoxanthin (1) with CF3COOH in
CH2Cl2 demonstrates a preferential and selective protonation
of the hydroxy group, followed by elimination of water to
produce the cations 4. No protonation of the polyene chain
was noted. It has been shown previously that treatment of
unsubstituted â,â-carotene (3) with CF3COOH at -20 °C
δH (ppm)
δC (ppm)
4b
refb
∆
4b
refb
∆
1
2
3
4
5
6
7
8
16
17
18
Σ
38.2
36.5
24.4
138.7
132.9
162.7
121.7
149.5
28.1
36.3
37.2
23.9
129.8
132.5
147.4
118.6
131.0
28.0
1.9
-0.7
0.5
8.9
0.4
15.3
3.1
18.5
0.1
0.1
0.5
1.57d
2.30d
6.04
1.49
2.12
5.64
0.08
0.18
0.40
6.65
7.49
1.16
1.16
2.15
6.38
6.69
1.12
1.12
2.09
0.27
0.80
0.04
0.04
0.06
28.1
26.0
28.0
25.5
12.66c
255.4
a Chemical shifts in positions not given in Table 2 are the same as for
4a given in Table 1. b 2b used as reference for positions 1-8 and 16-18;
data from ref 8. c Counting methylene protons twice and methyl protons
three times. d Methylene protons pairwise same chemical shifts.
(9) Sorensen, T. S. J. Am. Chem. Soc. 1965, 87, 5075-5084.
(10) Schleyer, P. v. R.; Lenoir, D.; Mison, P.; Liang, G.; Prakash, G. K.
S.; Olah, G. A. J. Am. Chem. Soc. 1980, 102, 683-691.
(11) Andrewes, A. G.; Englert, G.; Borch, G.; Strain, H. H.; Liaaen-
Jensen, S. Phytochemistry 1979, 18, 303-309
The total NMR evidence is thus accommodated with 4
being a mixture of the stereoisomers 4a and 4b differing in
(12) Mo, F. In Carotenoids Vol. 1B: Spectroscopy; Britton, G., Liaaen-
Jensen, S., Pfander, H., Eds.; Birkha¨user: Basel, 1995; pp 321-342.
Org. Lett., Vol. 5, No. 15, 2003
2677

results in protonation of the polyene chain,7,13 as determined
by 1H, 1H-1H COSY, and HSQC NMR (600 MHz, CDCl3,
-20 °C) analysis.13
constants should serve as reference data for extensive
empirical force-field and ab initio calculations of these large
polyenyl carbocations.
Work on the cation prepared from isozeaxanthin (â,â-
carotene-4,4′-diol) with suitable acids is in progress.
The charge distribution of the monocation 4, which is the
longest charged polyene system structurally elucidated, may
be of relevance for the understanding of conductivity
properties of doped carotenoids14 and conducting organic
polymers. The NMR chemical shifts and indirect coupling
Acknowledgment. We thank Hoffmann-La Roche, Basel,
for a sample of synthetic echinenone and for a research grant
to S.L.J.
Supporting Information Available: NMR spectra of
isocryptoxanthin and the monocations. This material is
available free of charge via the Internet at http://pubs.acs.org.
(13) Lutnaes, B. F.; Krane, J.; Liaaen-Jensen, S. In Book of Abstracts,
13th International Carotenoid Symposium, Honolulu, 2002, p 108.
(14) Sen, S.; Pal, P.; Misra, T. N. J. Mater. Sci. 1993, 28, 1367-1371.
OL034987W
2678
Org. Lett., Vol. 5, No. 15, 2003