Direct fluorination of coumarin, 6-methyl-coumarin and 7-alkoxy-coumarins

Article abstract of DOI:10.1016/j.jfluchem.2005.07.007

Direct fluorination of coumarin in acid media led to complex mixtures of products arising from electrophilic substitution processes. Fluorination of 6-methyl- and 7-alkoxy-coumarins was, however, more selective and preparatively useful quantities of various fluorinated systems were obtained.

Full text of DOI:10.1016/j.jfluchem.2005.07.007

Journal of Fluorine Chemistry 126 (2005) 1377–1383
www.elsevier.com/locate/fluor
Direct fluorination of coumarin, 6-methyl-coumarin
and 7-alkoxy-coumarins
b
Darren Holling a, Graham Sandford a, , Andrei S. Batsanov ,
*
Dmitrii S. Yufit b, Judith A.K. Howard b
a Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK
b Chemical Crystallography Group, Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK
Received 29 June 2005; received in revised form 21 July 2005; accepted 22 July 2005
Available online 24 August 2005
Abstract
Direct fluorination of coumarin in acid media led to complex mixtures of products arising from electrophilic substitution processes.
Fluorination of 6-methyl- and 7-alkoxy-coumarins was, however, more selective and preparatively useful quantities of various fluorinated
systems were obtained.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Selective fluorination; Fluorine; Heterocycles; Coumarin; Electrophilic substitution
1. Introduction
At Durham [7,8], we are developing the use of elemental
fluorine as a viable reagent for organic synthesis and, in the
context of synthesizing fluorinated heteroaromatic deriva-
tives, we have reported direct fluorination reactions of
quinoline derivatives [9] and halogen mediated direct
fluorination of various pyridine and quinoxaline systems
[10].
Efficient methodology for the synthesis of selectively
fluorinated heteroaromatic systems is a high research
priority in organofluorine chemistry [1,2], partly because
of the increasing number of valuable, biologically active life
science products that contain fluorinated heteroaromatic
moieties [3].
Various papers describing the synthesis of fluorinated
coumarins (2H-chromen-2-ones), involving Balz–Schie-
mann [11], halogen exchange [12] and cyclisation
approaches [13–16] (Pechmann, Knoevenagel, etc.) have
been published. Electrophilic fluorination of coumarin by
acetyl hypofluorite, giving 3-fluoro-coumarin, was
described by Rozen et al. [17] and reaction of various
substituted coumarin systems with SelectfluorTM also
yielded appropriate 3-fluoro derivatives [18]. Rozen also
demonstrated [19] that reaction of coumarin with fluorine in
a mixture of chloroform, trichlorofluoromethane and ethanol
at low temperature gave a difluorinated product which, after
dehydrofluorination during purification, yielded 3-fluoro-
coumarin in overall good yield.
Synthetic procedures for the preparation of fluorinated
heterocycles include substitution of diazo groups (Balz–
Schiemann reaction) or chlorine (halogen exchange) by
fluorine or cyclisation strategies involving acyclic fluori-
nated ‘building blocks’ [1,2,4–6]. However, synthesis of the
necessary functionalised precursors can sometimes be very
complex and time consuming and, therefore, a more
convenient approach to the synthesis of fluorinated
heteroaromatic derivatives is, potentially, the selective
transformation of carbon–hydrogen bonds to carbon–
fluorine bonds in reactions involving electrophilic fluorinat-
ing agents.
Acids, such as formic and sulfuric acid, are effective
reaction media for fluorination processes [7] and, here, we
extend our studies on direct fluorination of heteroaromatic
* Corresponding author. Tel.: +44 191 334 2039; fax: +44 191 384 4737.
E-mail address: graham.sandford@durham.ac.uk (G. Sandford).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.07.007

1378
D. Holling et al. / Journal of Fluorine Chemistry 126 (2005) 1377–1383
fluoride to the carbon-carbon double bond of the hetero-
cyclic ring were observed.
Fluorination of coumarin 1 in sulfuric acid gave five
major products, as observed by 19F NMR, but, in this case,
no tarry material was obtained (Scheme 2). In this reaction
medium, only trace quantities of products arising from
fluorination of the hetero-ring were observed, indicating that
protonation of the oxygen atom by the strongly acidic
medium is sufficient to deactivate the hetero-ring towards
electrophilic attack by fluorine.
Isolation of pure fluorocoumarin products from the
complex product mixture was extremely difficult but column
chromatography, followed by preparative HPLC, allowed
the isolation of trace quantities of 3 and 7, which were both
identified unambiguously by X-ray crystallography (Fig. 1).
Other products were identified by 19F NMR, by comparison
to literature data [11,17,19,20], although pure samples could
not be obtained.
Scheme 1.
systems and report our investigations concerning the
fluorination of various coumarin derivatives in acidic
reaction media.
It has previously been established that electrophilic
substitution on coumarin under highly acidic conditions
occurs preferentially at the 6- and 8-positions, although
substitution at other sites can compete effectively [11,21]. A
consideration of the natures of the carbocationic inter-
mediates, in which charge is located on carbon sites adjacent
to ring oxygen providing significant enhanced stabilisation,
explains this preferred regiochemistry (for substitution at
position 6, for example, see Scheme 2). On the other hand,
electrophilic attack at the 5 and 7 positions would result in
some charge delocalisation on heterocyclic ring oxygen and
2. Results and discussion
Fluorination of coumarin 1 in formic acid gave a very
complex mixture consisting of many products from which
four major products 2–5 could be identified and their yields
estimated by 19F NMR, by comparison with literature data
[17,19] (Scheme 1). Whilst products arising from fluorina-
tion on the aryl ring predominate, significant quantities of
products from electrophilic addition of fluorine or formyl
Scheme 2.

D. Holling et al. / Journal of Fluorine Chemistry 126 (2005) 1377–1383
1379
Fig. 2. X-ray structures of 10 (left) and 11 (right).
Fig. 1. X-ray structures of 3 (left) and 7 (right), showing thermal ellipsoids
at the 50% probability level.
Similarly, fluorination of 6-ethoxy coumarin 15 gave
products 16 and 14 (Scheme 4 and Fig. 3).
further stabilisation of the protonated intermediate (for
example, Scheme 2, substitution at position 5). Conse-
quently, mixtures of all isomers are possible upon reactions
with electrophilic species, depending upon which of these
effects are dominant for each specific reaction. Here,
fluorination of coumarin (Scheme 2) occurs predominantly
at the 6- and 8-sites, although significant quantities of
7-fluorocoumarin are obtained.
In summary, fluorination of coumarin in sulfuric acid
gives a mixture of products from which no useful quantities
of fluorinated material can be obtained. However, fluorina-
tion of methyl and methoxy coumarins give various
fluorinated systems arising from electrophilic processes in
synthetically useful quantities.
Sulfuric acid, is therefore, the preferred reaction medium
for direct fluorination in this case because tar formation is
minimised and so the following reactions concerning
fluorination of various coumarin derivatives bearing electron
donating substituents on the carbocyclic ring were carried
out in this medium.
3. Experimental
3.1. General
All starting materials were obtained commercially
(Aldrich) and all solvents were dried using literature
procedures. NMR spectra were recorded in deuteriochloro-
form, unless otherwise stated, on a Varian VXR 400S NMR
spectrometer with tetramethylsilane and trichlorofluoro-
methane as internal standards. Spectral assignments were
Fluorination of 6-methyl coumarin 9 gave 10 and 11
(Scheme 3) which were both identified by X-ray crystal-
lography (Fig. 2). In this case, fluorination occurs selectively
at the 5-position, ortho to the methyl group, again consistent
with an electrophilic process. A mechanism for the
formation of 11, is given in Scheme 3 and this pathway
is reminiscent of the formation of hydrolysed products
obtained from the fluorination of methyl-quinoline that we
reported earlier [9].
made with the aid of data collected by H-1H COSY and
1
1H-13C HETCOR experiments and coupling constants are
given in Hz. Mass spectra were recorded on either a VG
7070E spectrometer or a Fisons VG Trio 1000 spectrometer
coupled with a Hewlett Packard 5890 series II gas
chromatograph. Accurate mass measurements were per-
formed by the EPSRC National Mass Spectrometry service,
Swansea, U.K. Elemental analyses were obtained on either a
Perkin-Elmer 240 or a Carlo Erba Elemental Analyser.
Melting points were recorded at atmospheric pressure and
are uncorrected. Column chromatography was carried out on
silica gel (Merck No. 1–09385, 230–400 mesh) and t.l.c.
Fluorination of 6-methoxy coumarin 12 gave two
products, 13 and 14, in ratios depending on reaction
conditions. The yield of 14 increases upon increasing the
amount of fluorine that is passed through the reaction
mixture (Scheme 4). Again, product identification was by
X-ray crystallography (Fig. 3) and a mechanism for the
formation of 14, by a process analogous to the fluorination of
methoxy quinoline systems [9], is shown in Scheme 4.
Scheme 3.

1380
D. Holling et al. / Journal of Fluorine Chemistry 126 (2005) 1377–1383
Scheme 4.
analysis was performed on silica gel t.l.c. plates using
dichloromethane as eluant.
the appropriate 19F NMR resonances gave the yield of
fluorinated derivative, based upon the conversion obtained
above. Analytical samples of fluorinated products were
obtained by either preparative scale GC or column
chromatography where possible. Yields of fluorinated
products are quoted as yields based on the conversion of
starting material.
3.2. Reactions with elemental fluorine
3.2.1. General procedure
Elemental fluorine, as a 10% (v/v) mixture with nitrogen,
was passed at a rate of ca. 50 ml minꢀ1 through a stirred,
cooled (0–5 8C) mixture which consisted of the substrate
and the reaction medium (formic or sulfuric acid). After
addition of the fluorine, the reaction mixture was poured into
water (1500 ml), neutralised (NaHCO3) and extracted with
dichloromethane (3 ꢁ 100 ml). The combined, dried
(MgSO4), organic extracts were evaporated to give a crude
product. The composition of a weighed crude reaction
mixture was determined by GCMS analysis and the
conversion of starting material was calculated from GC
peak intensities. The amount of fluorinated product in the
crude product was determined by adding a known amount of
a,a,a-trifluorotoluene to a weighed amount of the crude
product mixture. Comparison of the relative intensities of
3.2.2. Fluorination of 2H-chromen-2-one 1 in
formic acid
2H-Chromen-2-one 1 (5.0 g, 34 mmol), formic acid
(100 ml) and fluorine (68 mmol, 2 equivalents) gave an
orange solid (49% conv.) that contained 6-fluoro-2H-
3
chromen-2-one 2 [11,20] (20%), dF –119.9 (dd, JHF 8,
3JHF 7); 8-fluoro-2H-chromen-2-one 3 (8%); 3,4-difluor-
ochroman-2-one 4 [19]: dF –177.0 (1F, ddd, 2JHF 54, 3JFF 29,
3JHF 15, F-3), –206.8 (1F, ddd, 2JHF 44, 3JFF 15, 3JHF 6, F-4);
3-fluoro-2-oxochroman-4-yl methanoate 5 [17]: dF –205.2
2
3
(dd, JHF 46, JHF 5, F-3); small quantities of many other
products that could not be identified and tarry material. No
further purification was carried out.
3.2.3. Fluorination of 2H-chromen-2-one 1 in
sulfuric acid
2H-Chromen-2-one 1 (2.5 g, 17 mmol), sulfuric acid
(100 ml) and fluorine (204 mmol, 12 equivalents) gave a
crude product (69% conv.) that contained 6-fluoro-2H-
chromen-2-one 2 [20] (20%), 7-fluoro-2H-chromen-2-one 6
3
4
[20] (22%); dF –117.9 (td, JHF 8, JHF 5); 8-fluoro-2H-
chromen-2-one 3 (8%); 5,6-difluoro-2H-chromen-2-one 7
(15%); and 6,8-difluoro-2H-chromen-2-one 8 (17%); dF –
124.6 (1F, ddd, 4JFF 18, 3JHF 8, 3JHF 4, F-6), –138.3 (1F, ddd,
3
5
4JFF 17, JHF 12, JHF 2, F-8); and trace quantities of other
products. Column chromatography on silica gel using
diethyl ether/hexane (2:1) as elutant and further purification
by preparative HPLC (using a 21.4 cm Hypersil (semi)
preparative column, water/methanol (3:2) as elutant,
10 ml minꢀ1 flow rate) gave analytical samples of 8-
fluoro-2H-chromen-2-one 3; dF –134.0 (dd, 3JHF 9, 4JHF 4, F-
8); and, 5,6-difluoro-2H-chromen-2-one 7 as white crystals;
3
3
dH 6.52 (1 H, d, JHH 10.0, H-3), 7.10 (1 H, ddd, JHH 9.5,
4JHF 3.5, 5JHF 2.0, H-8), 7.35 (1 H, dt, 4JHF 8.5, 3JHH = 3JHF
Fig. 3. X-ray structures of 13 (top), 14 (middle) and 16 (bottom). Molecules
13 and 14 lie in the mirror planes; primed atoms are generated thereby.

D. Holling et al. / Journal of Fluorine Chemistry 126 (2005) 1377–1383
1381
3
3
9.5, H-7), 7.95 (1 H, dd, 3JHH 10.0, H-4); dF –142.6 (1 F, ddd,
3JFF 21, 3JHF 10, 4JHF 4, F-6), –143.5 (1 F, ddd, 3JFF 21, 4JHF
8, 5JHF 1, F-5); dC 110.2 (d, 2JCF 16, C-4a), 112.5 (s, C-8),
117.8 (s, C-3), 120.0 (d, 2JCF 20, C-7), 135.4 (s, C-4), 145.6
(dd, 1JCF 257, 2JCF 14, C-6), 146.2 (dd, 1JCF 246, 2JCF 11, C-
5), 149.7 (s, C-8a), 159.4 (s, C-2); m/z (EI+) 182 (M+, 85%),
154 (100), 125 (54); M+, 182.017612. C9H4F2O2 requires
M+, 182.017936.
(1 H, dm, JHH 10.0, H-3), 7.21 (1 H, d, JHH 10.4, H-5),
7.37 (1 H, dm, 3JHH 9.6, H-4); dF ꢀ112.3 (s); dC 100.1 (d,
1JCF 248, C-8), 112.7 (t, JCF 6, C-4a), 119.9 (s, C-3),
122.1 (t, 3JCF 3, C-6), 140.0 (s, C-5), 141.5 (s, C-4), 152.1
3
2
2
(t, JCF 22, C-8a), 157.3 (s, C-2), 184.4 (t, JCF 22, C-7);
m/z (EI+) 198 (M+, 21%), 63 (100); M+, 198.012302.
C9H4F2O3 requires M+, 198.012851.
3.2.6. Fluorination of 7-methoxy-2H-chromen-2-one 12
(10 equivalents of F2)
3.2.4. Fluorination of 6-methyl-2H-chromen-2-one 9
6-Methyl-2H-chromen-2-one 9 (5.0 g, 34 mmol) and
fluorine (170 mmol, 5 equivalents), sulfuric acid (>98%)
(90 ml) and water (10 ml) gave a yellow oil (52% conv.).
Column chromatography on silica gel using diethyl ether/
hexane (1:1) as elutant, gave 5-fluoro-6-methyl-2H-chro-
men-2-one 10 (2.0 g, 69%) as a white solid; m.p. 78–79 8C;
dH 2.30 (3 H, d, 4JHF 2.0, Me), 6.42 (1 H, d, 3JHH 9.6, H-3),
7.02 (1 H, d, 3JHH 8.8, H-8), 7.32 (1 H, dd, 3JHH = 4JHF 8.4,
H-7), 7.93 (1 H, d, 3JHH 9.6, H-4); dF –123.8 (d, 4JHF 8); dC
13.8 (d, 3JCF 3, Me), 108.6 (d, 2JCF 20, C-6), 112.0 (d, 4JCF 4,
C-8), 116.5 (d, 4JCF 2, C-3), 119.7 (d, 2JCF 16, C-4a), 134.0
(d, 3JCF 7, C-7), 136.4 (d, 3JCF 5, C-4), 152.6 (d, 3JCF 5, C-
8a), 156.2 (d, 1JCF 252, C-5), 160.1 (s, C-2); m/z (EI+) 178
(M+, 82%), 150 (63), 149 (90); M+, 178.042877. C10H7FO2
requires M+, 178.043008; and, 6-fluoro-6-methyl-6-hydro-
2H-chromen-2,5-dione 11 (0.31 g, 10%) as a yellow solid;
m.p. 128–130 8C; dH 1.57 (3 H, d, 3JHF 22.0, Me), 6.23 (1 H,
7-Methoxy-2H-chromen-2-one 12 (4.1 g, 23 mmol),
sulfuric acid (100 ml) and fluorine (234 mmol, 10 equiva-
lents) gave a yellow solid (94% conv.). Recrystallisation of
the crude product from dichloromethane gave 8,8-difluoro-
8-hydro-2H-chromen-2,7-dione 14 (2.59 g, 72%) as a
yellow solid; spectral data as above.
3.2.7. Fluorination of 7-ethoxy-4-methyl-2H-chromen-
2-one 15
7-Ethoxy-4-methyl-2H-chromen-2-one
15
(3.3 g,
16 mmol), sulfuric acid (100 ml) and fluorine (80 mmol,
5 equivalents) gave a yellow solid (76% conv.). Washing the
crude product with diethyl ether and column chromato-
graphy on silica gel using dichloromethane as elutant gave
7-ethoxy-8-fluoro-4-methyl-2H-chromen-2-one 16 (1.64 g,
55%) as a white solid; m.p. 149–151 8C; (Found: C, 64.6; H,
5.0. C12H11FO3 requires C, 64.9; H, 5.0%); dH 1.42 (3 H, t,
3JHH 7.0, CH2CH3), 2.33 (3 H, s, 4-Me), 4.13 (2 H, q, 3JHH
7.0, OCH2CH3), 6.08 (1 H, s, H-3), 6.83 (1 H, m, H-5), 7.22 (1
3
d, 3JHH 9.6, H-3), 6.42 (1 H, d, JHH 10.4, H-8), 6.70 (1 H,
dd, 3JHH 10.4, 3JHF 7.6, H-7), 7.76 (1 H, d, 3JHH 9.6, H-4); dF
–158.6 (qd, 3JHF 23, 3JHF 7); dC 24.2 (d, 2JCF 27, Me), 90.4
3
H, d, JHH 8.5, H-6); dF –155.7 (d, 4JHF 7, F-8); dC 14.7 (s,
1
3
(d, JCF 180, C-6), 110.0 (d, JCF 4, C-4a), 114.4 (s, C-3),
120.6 (d, 3JCF 9, C-8), 138.9 (s, C-4), 143.7 (d, 2JCF 23, C-7),
158.6 (s, C-2), 165.2 (d, 4JCF 3, C-8a), 191.9 (d, 2JCF 16, C-
5); m/z (EI+) 194 (M+, 82%), 100 (100); M+, 194.038471.
C10H7FO3 requires M+, 194.037922.
CH2CH3), 18.7 (s, 4-Me), 65.5 (s, OCH2CH3), 109.6 (s, C-5),
112.6 (s, C-3), 114.6 (s, C-4), 119.2 (d, 3JCF 5, C-6), 139.7 (d,
1JCF 251, C-8), 142.9 (d, 2JCF 9, C-8a), 149.6 (d, 2JCF 8, C-7),
3
152.3 (d, JCF 2, C-4a), 159.7 (s, C-2); m/z (EI+) 222 (M+,
52%), 194 (52), 166 (100). Dissolving the crude reaction
mixture in a minimum amount of hot dichloromethane,
followed by the addition of cold hexane and subsequent
isolation of the precipitate by filtration, gave 8,8-difluoro-4-
methyl-8-hydro-2H-chromen-2,7-dione 14 (0.68 g, 26%) as a
yellow solid; physical and specral data as above
3.2.5. Fluorination of 7-methoxy-2H-chromen-2-one 12
(5 equivalents of F2)
7-Methoxy-2H-chromen-2-one 12 (2.5 g, 14 mmol),
sulfuric acid (100 ml) and fluorine (70 mmol, 5 equiva-
lents) gave a yellow solid (65% conv.). Recrystallisation of
the crude product from acetonitrile gave 8-fluoro-7-
methoxy-2H-chromen-2-one 13 (1.18 g, 66%) as a white
solid; m.p. 190–192 8C; dH (DMSO-d6; 50 8C) 3.94 (3 H, s,
3.3. X-ray crystallography1
3
The X-ray single crystal data were collected on the
Bruker 3-circle diffractometers equipped with SMART 1K
(7 and 13) or SMART 6K CCD area detectors and Oxford
Cryostream cooling devices, using graphite monochromated
˚
Mo Ka-radiation (l = 0.71073 A). Crystal data and experi-
mental details are given in Table 1. For all crystals the
structure solutions and refinements on F2 were performed
OMe), 6.32 (1 H, d, JHH 9.5, H-3), 7.17 (1 H, t,
3JHH = 4JHF 8.0, H-6), 7.46 (1 H, d, 3JHH 8.5, H-5), 7.97 (1
H, d, 3JHH 9.5, H-4); dF (DMSO-d6; 50 8C) ꢀ158.0 (d, 4JHF
8); dC (DMSO-d6; 50 8C) 56.6 (s, OMe), 109.5 (s, C-6),
1
113.2 (s, C-3), 123.4 (s, C-5), 138.2 (d, JCF 248, C-8),
2
142.3 (d, JCF 9, C-7), 143.7 (s, C-4a), 144.0 (s, C-4),
149.8 (d, 2JCF 7, C-8a), 158.6 (s, C-2); m/z (EI+) 194 (M+,
82%), 166 (61), 151 (100); M+, 194.038008. C10H7FO3
requires M+, 194.037922; and recrystallisation of the
residue from dichloromethane gave 8,8-difluoro-8-hydro-
2H-chromen-2,7-dione 14 (0.42 g, 23%) as a yellow solid;
m.p. 133–135 8C; dH 6.25 (1 H, dm, 3JHH 10.0, H-6), 6.55
1
CCDC 275895 to 275902 contain the supplementary crystallographic
data for this paper. These data can be viewed free of charge via http://
www.ccdc.cam.ac.uk/cont/retrieving.html or from the CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK. Fax: +44 1223 336033. E-mail: depos-
it@ccdc.cam.ac.uk.

1382
D. Holling et al. / Journal of Fluorine Chemistry 126 (2005) 1377–1383
Table 1
Crystal data and experimental details
Compound
3
7
10
11
13
14
14a
16
CCDC dep. No.
Empirical formula
Formula weight
T (K)
275895
C9H5FO2
164.13
120
275896
C9H4F2O2
182.12
120
275897
C10H10FO2
178.16
120
275898
C10H7FO3
194.16
120
275899
C10H7FO3
194.16
150
275900
C9H4F2O3
198.12
293
275901
C9H4F2O3
198.12
120
275902
C12H11FO3
222.21
120
Crystal system
Space group (no.)
˚
a (A)
˚
b (A)
˚
c (A)
Monoclinic
Pc (7)
3.7260(2)
8.2531(4)
11.3619(5)
96.227(2)
347.33(3)
2
Monoclinic
P21/c (14)
7.071(1)
8.522(1)
12.291(1)
105.54(1)
713.6(1)
4
Orthorhombic
Pna21 (33)
20.0846(5)
3.7945(1)
10.4322(3)
90
Monoclinic
P21/c (14)
9.4545(3)
10.7328(4)
8.2003(3)
94.737(2)
829.27(5)
4
Orthorhombic
Pnma (62)
6.908(1)
6.503(1)
18.576(2)
90
Monoclinic
P21/m (11)
7.020(1)
6.503(1)
8.748(1)
96.73(1)
396.6(1)
2
Monoclinic
P21/m (11)
7.013(2)
6.343(3)
8.738(3)
96.74(1)
386.0(3)
2
Monoclinic
P21/n (14)
4.8635(5)
18.235(2)
11.854(1)
92.82(3)
1050.0(2)
4
b (8)
3
˚
V (A )
795.05(4)
4
834.5(3)
4
Z
r (calc.) (g/cm3)
m (Mo Ka) (mmꢀ1
1.569
1.705
1.488
1.555
1.545
1.659
1.705
1.406
)
0.13
0.15
0.12
0.13
0.13
0.16
0.16
0.11
Reflections collected
Independent reflections
R (int)
3227
8529
6812
6474
9491
4942
2437
5700
1670
1869
2105
2408
2199
1257
1075
2529
0.019
0.048
0.022
0.017
0.044
0.026
0.016
0.033
Restraints/parameters
2/129
0/121
1/140
0/155
0/104
0/94
0/94
0/189
R [I > 2s(I)]
wRðF2Þ [all data]
0.034
0.050
0.031
0.037
0.043
0.046
0.036
0.046
0.095
0.131
0.089
0.112
0.122
0.163
0.105
0.138
a
Contains ca. 6% of 6,8,8-trifluoro-8-hydro-2H-chromen-2,7-dione.
Table 2
˚
Bond distances (A) in crystal structures
3
7
10
11
13
14a
16b
O(1)–C(2)
O(1)–C(9)
C(2)–O(2)
C(2)–C(3)
C(3)–C(4)
C(4)–C(10)
C(5)–C(10)
C(5)–C(6)
C(6)–C(7)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
C(5)–F/O
C(6)–F
1.382(2)
1.369(2)
1.207(2)
1.448(2)
1.346(2)
1.442(2)
1.403(2)
1.382(2)
1.392(2)
1.374(2)
1.388(2)
1.395(2)
1.388(2)
1.383(2)
1.211(2)
1.456(2)
1.348(3)
1.440(2)
1.399(2)
1.378(3)
1.384(3)
1.391(3)
1.392(3)
1.404(2)
1.347(2)
1.352(2)
1.387(2)
1.374(1)
1.203(2)
1.452(2)
1.340(2)
1.440(2)
1.403(2)
1.376(2)
1.403(2)
1.384(2)
1.386(2)
1.394(2)
1.359(2)
1.405(1)
1.393(2)
1.407(2)
1.355(2)
1.206(2)
1.453(2)
1.356(2)
1.445(2)
1.470(2)
1.344(3)
1.462(2)
1.557(3)
1.500(2)
1.353(2)
1.394(2)
1.377(2)
1.212(2)
1.451(2)
1.356(2)
1.451(2)
1.402(2)
1.387(2)
1.401(2)
1.394(2)
1.382(2)
1.405(2)
1.351(1)
1.210(2)
1.443(2)
1.350(1)
1.433(1)
1.462(2)
1.536(1)
1.498(1)
1.335(1)
1.451(1)
1.369(1)
1.218(1)
1.406(1)
1.527(1)
1.378(2)
1.212(2)
1.453(2)
1.350(3)
1.447(3)
1.402(3)
1.382(3)
1.407(3)
1.397(3)
1.386(3)
1.397(3)
C(6)–C(11)
C(7)–O
1.508(2)
1.357(2)
1.354(2)
1.217(2)
1.365(1)
1.357(2)
1.357(2)
C(8)–F
a
1.350(2)
At 120 K.
b
C(4)–C(13) 1.500(2).
with the SHELXTL 6.12 (Bruker AXS, Madison, WI, USA,
2001) program suite. Non-hydrogen atoms were refined
anisotropically. All hydrogen atoms were located in
difference Fourier syntheses and refined isotropically in
all structures except 7 and 10, where they were placed in
calculated positions and refined in ‘‘riding’’ mode. Bond
distances for all structures are listed in Table 2.
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We thank EPSRC for funding (Quota studentship to DH).

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