Preparation of intermediates for fluorinated lignans by conjugated and tandem additions on 3-fluorofuran-2(5H)-one

Article abstract of DOI:10.1135/cccc20000772

Two syntheses of 3-fluorofuran-2(5H)-one (1) based on Wittig-Horner reaction of ethyl (diethoxyphosphoryl)fluoroacetate (15) with 2-oxoethyl acetate (16) or on transformation of D-erythronolactone (10) are given. 3-Fluorofuran-2(5H)-one (1) and ethyl 2-fluorobut-2-enoate (2) undergo conjugate addition with soft nucleophiles based on arenecarboxaldehyde dithioacetals 7 to form 2-fluorolactones 3 and 2-fluoroalkanoates 4. Intermediate enolates can be trapped in the sense of tandem addition with arenecarboxaldehydes 8 or (arylmethyl)bromides 9 to form intermediates 5 and 6 for fluorolignans. Although the conjugate addition proceeds with low stereoselectivity yielding mixture of both diastereoisomers, the electrophile in tandem addition attacks the intermediary fluoroenolate exclusively anti to its bulky β-substituent in good accord with non-fluorinated furan-2(5H)-ones.

Full text of DOI:10.1135/cccc20000772

7
72
Kvíčala et al.:
PREPARATION OF INTERMEDIATES FOR FLUORINATED LIGNANS
BY CONJUGATED AND TANDEM ADDITIONS
ON 3-FLUOROFURAN-2(5H)-ONE
Jaroslav KVÍČALAa1,*, Růžena VLASÁKOVÁ , Jakub PLOCAR , Oldřich PALETA
a
a
a2
b
and Andrew PELTER
a
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technická 5,
66 28Prague 6, Czech Republic; e-mail: kvicalaj@vscht.cz, paletao@vscht.cz
Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, U.K.;
e-mail: a.pelter@swansea.ac.uk
1
2
1
b
Received February 18, 2000
Accepted April 4, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday.
Two syn th eses of 3-fluorofuran -2(5H)-on e (1) based on Wittig–Horn er reaction of eth yl
(
dieth oxyph osph oryl)fluoroacetate (15) with 2-oxoeth yl acetate (16) or on tran sform ation of
D-eryth ron olacton e (10) are given . 3-Fluorofuran -2(5H)-on e (1) an d eth yl 2-fluorobut-
-en oate (2) un dergo con jugate addition with soft n ucleoph iles based on aren e-
2
carboxaldeh yde dith ioacetals 7 to form 2-fluorolacton es 3 an d 2-fluoroalkan oates 4. In ter-
m ediate en olates can be trapped in th e sen se of tan dem addition with aren ecarboxaldeh ydes
8
or (arylm eth yl)brom ides 9 to form in term ediates 5 an d 6 for fluorolign an s. Alth ough th e
con jugate addition proceeds with low stereoselectivity yieldin g m ixture of both
diastereoisom ers, th e electroph ile in tan dem addition attacks th e in term ediary fluoroen olate
exclusively anti to its bulky β-substituen t in good accord with n on -fluorin ated furan -
2
(5H)-on es.
Key w ord s: Con jugate addition s; Tan dem addition s; 2-Fluorobut-2-en oate; 2-Fluorobut-
-en -4-olide; Buten olides; Lign an s; Lacton es; Dith ioacetals; Fluorin ated com poun ds.
2
Th e butan olide or buten olide rin g system is frequen tly presen t in biologi-
cally active com poun ds. Podoph yllotoxin an d som e its derivatives possess
an tin eoplastic or an tiviral activity1 an d h en ce becam e th e ch allen ge for
syn th etic ch em ists. Tan dem addition of um poled aren ecarboxaldeh ydes on
2
3
furan -2(5H)-on e or its ch iral 5-substituted derivatives an d trappin g of in -
term ediated en olates with arom atic electroph iles belon gs to m ost frequen t
an d straigh tforward procedures leadin g to lign an in term ediates.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
773
Little is kn own about con jugate addition on 2-fluoroalken oates with th e
4
exception of 2-fluoroprop-2-en oates , as well as about th e ch em istry of
en olates of 2-fluoroalkan oates5 with th e exception of 2-fluoroacetates .
From th e results, two m ain drawbacks of α-fluoroen olates in com parison
with n on -fluorin ated on es can be recogn ized, viz. lower stability of
α-fluoroen olates resultin g in decom position an d in creased h ardn ess of th e
fluorin ated α-carbon with en h an ced ten den cy to O-alkylation of th e
6
7
en olate. Except for our prelim in ary report , n o tan dem addition on fluori-
n ated alken oates h ave been reported.
In troduction of fluorin e in to biologically active m olecules often results in
8
distin ctive m odification of th eir biological properties . Th e tradition al ap-
proach to preparation of fluorin ated com poun ds relies on n ucleoph ilic or
9
electroph ilic fluorin ation . On th e oth er h an d, th e role of easily accessible
fluorinated building blocks form in g a fam ily, wh ich could be called fluorine
pool in an alogy to chiral pool for ch iral com poun ds, is still m ore ackn owl-
1
0
edged
.
Various substituted fluorofuran on es h ave been syn th esized an d eith er
1
1
used as in term ediates or directly studied for biological activity . We re-
7
cen tly reported th e preparation of a n ew fluorin ated buildin g block,
3
-fluorofuran -2(5H)-on e (1) an d som e of its reaction s in cludin g pilot exper-
im en ts with con jugate an d tan dem addition . As products of th ese reaction s
are im portan t in term ediates for fluorin ated lign an s, we wish to report h ere
th e syn th esis of fluorolacton e 1 an d results of exten ded study of its beh av-
iour in con jugate an d tan dem addition s in full detail. For com parison , we
also studied th e above reaction with an open -ch ain fluoroalken oate, eth yl
2
-fluorobut-2-en oate (2).
Recen tly, preparation of fluorin ated podoph yllotoxin by direct
1
2
electroph ilic fluorin ation h as been publish ed with th e aim to preven t
racem ization at th e C3 carbon of th e furan on e rin g accom pan ied by loss of
biological activity. Th is work un derlin es th e im portan ce of fluorin ated
lign an s.
EXPERIMENTAL
Gen eral Com m en ts
Tem perature data are un corrected. 1H NMR 1D an d 2D spectra were recorded with a Varian
1
3
Gem in i 300 HC spectrom eter at 300.1 MHz usin g TMS as in tern al stan dard, C NMR spec-
tra were recorded with a Bruker AM 400 spectrom eter at 100.6 MHz usin g TMS as in tern al
1
9
standard, and F NMR spectra were recorded with a Bruker WP-80 SY spectrom eter at 76.5 MHz
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
74
Kvíčala et al.:
usin g CFCl3 as in tern al stan dard with upfield values design ed n egative. FTIR spectra were re-
corded with a Nicolet 740 in strum en t in KBr.
All m an ipulation s an d reaction s in cludin g organ om etallic reagen ts were perform ed with
exclusion of m oisture an d atm osph eric oxygen in oven -dried apparatuses. 2-O-Tosyl-
D-eryth ron o-1,4-lacton e (11) was prepared from easily available D-eryth ron o-1,4-lacton e (10)
1
3
accordin g to ref. . 2-Deoxy-2-fluoro-L-th reon o-1,4-lacton e (13, (3S,4R)-3-fluoro-4-h ydroxy-
,4-dih ydrofuran -2(3H)-on e) was form ed by fluorin ation of 2,3-an h ydro-D-eryth ron olacton e
3
1
4
(
12, (1R,5R)-3,6-dioxabicyclo[3.1.0]h exan -2-on e) . Eth yl fluoroiodoacetate (14) was pre-
pared from eth yl ch lorofluoroacetate by th e Fin kelstein reaction 16. 2-Oxoeth yl acetate (16)
1
5
was syn th esized from 1-eth oxyeth ylen e diacetate18. Eth yl 2-fluorobut-2-en oate (2, E/Z ra-
1
7
1
9
tio 89 : 11) was prepared by th e Wittig–Horn er reaction accordin g to ref. . A series of sub-
stituted [bis(ph en ylsulfan yl)m eth yl]ben zen es 7a–7d , viz. [bis(ph en ylsulfan yl)m eth yl]ben zen e
(
1
7a), 1-[bis(ph en ylsulfan yl)m eth yl]-4-m eth oxyben zen e (7b), 4-[bis(ph en ylsulfan yl)m eth yl]-
,2-dim eth oxyben zen e (7c), an d 5-[bis(ph en ylsulfan yl)m eth yl]-1,3-ben zodioxole (7d ), was
prepared from correspon din g com m ercially available aldeh ydes 8a–8d by reaction with
3
a
ben zen eth iol un der AlCl3 catalysis accordin g to ref. . 5-(Brom om eth yl)-1,2,3-trim eth oxy-
ben zen e (9b) was prepared from 3,4,5-trim eth oxyben zaldeh yde (8e) by NaBH reduction fol-
4
3
a
lowed by brom in ation
.
2
,3-An h ydro-D-eryth ron olacton e (12)
A 250 m l flask equipped with a m agn etic stirbar, reflux con den ser an d dryin g adapter (an h y-
drous CaCl ) was ch arged with dried KF (11.62 g, 200 m m ol), tosylated lacton e 11 (13.61 g,
2
5
0.0 m m ol), an d MeCN (120 m l). Th e m ixture was refluxed wh ile stirrin g for 4 h , cooled,
MeCN was added (150 m l) an d solids rem oved by ch rom atograph y over a sh ort colum n
SiO ). Evaporation of solven ts followed by distillation afforded epoxylacton e 12 as viscous
(
2
1
4
oil (3.39 g, 67.8%, b.p. 62–65 °C/250 Pa, ref. 79 °C/100 Pa).
Eth yl (Dieth oxyph osph oryl)fluoroacetate (15)
A flask equipped with a m agn etic stirbar, reflux con den ser an d vacuum source was ch arged
with fluoroiodoacetate 14 (6.39 g, 27.5 m m ol) an d trieth yl ph osph ite (5.5 g, 33 m m ol). Vac-
uum was set to 4 kPa an d th e reaction m ixture was h eated to reflux for 19 h wh ile stirred.
2
0
Fluoroph osph on oacetate 15 (4.94 g, 74.2%, b.p. 104–107 °C/7 Pa, ref.
107–109 °C/40 Pa)
was obtain ed by distillation of th e reaction m ixture.
Eth yl 4-Acetoxy-2-fluorobut-2-en oate (17)
A 1 000 m l flask equipped with m agn etic stirbar, septum an d extern al coolin g bath was
ch arged with fluoroph osph on oacetate 15 (43.39 g, 179.2 m m ol) an d THF (360 m l). Th e m ix-
ture was cooled to –80 °C wh ile stirred an d BuLi solution (2.5 M in h exan es, 80 m l, 200
m m ol) was dropwise syrin ged to it, followed after 15 m in by addition of 2-oxoeth yl acetate
1
6 (17.32 g, 169.8 m m ol). Th e resultin g m ixture was stirred for 2 h at –80 °C an d h eated to
room tem perature. THF was rem oved on a vacuum rotary evaporator an d dieth yl eth er (200
m l) followed by water (200 m l) was added to th e crude reaction product. Th e water layer
was rem oved an d extracted with dieth yl eth er (3 × 300 m l), organ ic ph ases were collected,
dried with an h ydrous MgSO , th e dryin g agen t was filtered off an d dieth yl eth er was re-
4
m oved on a vacuum rotary evaporator to afford crude fluoroester 17 (30.7 g, 95.0%), wh ich
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
775
was directly used in th e n ext step. Distillation of a represen tative sam ple of th e crude prod-
uct (1.00 g, 5.26 m m ol) afforded pure product 17 as colourless liquid (659 m g, 62.6%, b.p.
5
0–51 °C/130 Pa, E/Z ratio 90 : 10). 1H NMR (300.1 MHz, CDCl ): (E)-isom er 1.36 t, 3 H,
3
3
3
JH,H = 7.1 (CH CH ); 2.06 s, 3 H, (CH CO); 4.30 q, 2 H,
3J
J
= 7.1 (CH CH ); 5.04 dd, 2 H,
3
2
3
H,H 3 2
4
3
3
= 6.5, JH,F = 3.2 (CH CH=); 5.96 dt, 1 H, JH,H = 6.5, JH,F = 18.6 (CH=CF); (Z)-isom er
H,H
.36 t, 3 H,
2
3
3
1
4
(
J
= 7.1 (CH CH ); 2.06 s, 3 H, (CH CO); 4.30 q, 2 H, JH,H = 7.1 (CH CH );
H,H 3 2 3 3 2
.80 dd, 2 H, JH,H = 6.7, JH,F = 2.6 (CH CH=); 6.21 dt, 1 H, JH,H = 6.8, 3JH,F = 31.9
3
4
3
2
CH=CF). 13C NMR (100.6 MHz,CDCl ): (E)-isom er 13.9 s (CH CH ); 20.4 s (CH CO); 58.9 d,
3 3 2 3
3
2
1
JC,F = 8 (CH CH=); 62.0 s (CH CH ); 118.2 d, JC,F = 21 (CH=CF); 147.9 d, JC,F = 260
2
3
2
2
(
CH=CF); 160.3 d, JC,F = 35, (CF=CO); 170.4 s (CH CO); (Z)-isom er sign als are too weak for
3
1
9
3
4
assign m en t. F NMR (76.5 MHz, CDCl ): (E)-isom er –119.8 dt, 1 F, JH,F = 19, JH,F = 3
3
3
4
(
=CF); (Z)-isom er –124.5 dt, 1 F, JH,F = 31, JH,F = 3 (=CF). IR (CHCl ): 1 740 s, 1 875 w,
3
3
9
026 w. For C H11FO4 (190.2) calculated: 50.5% C, 5.8% H, 10.0% F; foun d: 49.5% C, 6.0% H,
.6% F.
8
3
-Fluorofuran -2(5H)-on e (1)
Method A. A 10 m l flask equipped with Hückm an n adapter an d a source of vacuum was
ch arged with P O (4.25 g, 1.50 m m ol) an d fluorolacton e 13 (898 m g, 7.48 m m ol). Vacuum
2
5
was set to 2 kPa an d th e m ixture was h eated to 200 °C for 4 h wh ile distillin g th e product
off con tin un ously. Wash in g th e Hückm an n adapter with CHCl3 an d rem ovin g solven t in
vacuo yielded pure furan on e 1 (238 m g, 31.0%).
Method B. A 1 000 m l flask equipped with m agn etic stirbar was ch arged with crude
fluoroester 17 (29.63 g, 155.9 m m ol), dioxan e (250 m l), an d aqueous NaOH solution (10%,
2
50 m l). Th e resultin g two-ph ase system was stirred overn igh t at room tem perature Th e re-
sultin g h om ogen eous solution was extracted with CH Cl (2 × 200 m l) to rem ove organ ic
2
2
adm ixtures (m ain ly various acetals from preparation of oxoester 16) an d th en acidified with
HCl (1 : 1) to pH 1. Th e two-ph ase system form ed was con tin uously extracted with CHCl3
for 12 h . Th e organ ic ph ase was dried with an h ydrous MgSO , th e dryin g agen t was filtered
4
off an d solven ts were rem oved on a rotary vacuum evaporator. Fin al vacuum distillation af-
1
forded product 1 as colourless liquid (8.61 g, 56.0%, b.p. 98–99 °C/2 kPa). H NMR (300.1
MHz, CDCl ): 4.90 dd, 2 H, JH,H = 1.8, JH,F = 5.9 (CH CH=); 6.90 q, 1 H, 3J
3
4
=
3
JH,F = 2.0
= 8 (CH ); 123.2 d, JC,F = 8 (CH=);
3
2
H,H
1
3
3
2
(
1
1
CH CH=). C NMR (100.6 MHz, CDCl ): 66.8 d,
48.9 d, JC,F = 277 (=CF); 165.6 d, JC,F = 32 (CO). F NMR (76.5 MHz, CDCl ): –142.2 dt,
F, JH,F = 2, JH,F = 6 (=CF). IR (CHCl ): 1 682 m , 1 785 s, 3 025 w, 3 116 w. For C H FO
2
J
2
3
C,F
19
2
1
2
3
3
4
3
4
3
(
102.1) calculated: 47.1% C, 3.0% H, 18.6% F; foun d: 46.9% C, 3.4% H, 18.3% F.
Con jugate Addition s. Gen eral Procedure
A flask equipped with m agn etic stirbar, rubber septum an d coolin g bath was ch arged with
aren ecarboxaldeh yde dith ioacetal 7 an d THF, cooled to –80 °C, an d a sm all excess of BuLi
(
105%, given con cen tration in h exan es) was added dropwise to it. After 1 h , an equivalen t
of un saturated fluorolacton e 1 or fluoroester 2 was added dropwise an d th e resultin g m ix-
ture was stirred for 3 h at –80 °C. Th e reaction was stopped by quen ch in g with HCl (10% so-
lution in THF) at –80 °C. Th e reaction m ixture was allowed to reach room tem perature an d
solven ts were rem oved on a rotary vacuum evaporator. Th e product was isolated by repeated
colum n ch rom atograph y.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
76
Kvíčala et al.:
3
-Fluoro-4-[phenylbis(phenylsulfanyl)methyl]-4,5-dihydrofuran-2(3H)-one (3a). Reaction of
–
1
dith ioacetal 7a (685 m g, 2.22 m m ol), BuLi solution (1.40 m l, 1.89 m ol l , 2.50 m m ol), an d
fluorolacton e 1 (202 m g, 1.98 m m ol) in THF (6 m l) afforded after purification by colum n
ch rom atograph y (SiO , 20 × 3 cm , gradien t elution first with petroleum eth er–CH Cl 4 : 1,
2
2
2
th en with CH Cl ) fluorolacton e 3a (wh ite crystals, 352 m g, 41.4%, m .p. 46–52 °C) as a
2
2
1
m ixture of diastereoisom ers ((3R*,4R*)/(3R*,4S*) = 57 : 43). H NMR (300.1 MHz, CDCl ):
3R*,4R*)-3a 3.50 ddt, 1 H, JH,H = 8.2, JH,H = 6.6 (t),
3
3
3
3
(
J
= 25.8 (CH-CHF); 4.41 dd, 1 H,
= JH,H = 9.3 (OCH H -CH); 5.31 dd,
H,F
2
3
2
3
JH,H = 9.9, JH,H = 7.1 (OCH H -CH); 4.58 t, 1 H, JH,H
a
b
a
b
H, 3J
= 6.1, 2J
= 49.5 (CHF); 7.23–7.35 m , 13 H (Ar-H); 7.68 d, 2 H, JH,H = 8.2 (Ar-H);
H,F
3
1
H,H
3
3
3
(
2
3R*,4S*)-3a 3.20 ddt, 1 H, JH,H = 7.1 (t), JH,H = 6.6, JH,F = 20.3 (CH-CHF); 4.54 dd, 1 H,
3
= 7.1 (OCH H -CH); 4.90 dd, 1 H, 2J
3
JH,H = 9.9,
J
3
= 9.9, JH,H = 6.6 (OCH H -CH);
H,H a b
H,H
a
b
2
13
5
.17 dd, 1 H, JH,H = 7.2, JH,F = 50.6 (CHF); 7.10–7.80 m , 15 H (Ar-H). C NMR (100.6 MHz,
CDCl ): (3R*,4R*)-3a 50.3 d, JC,F = 19 (CH-CHF); 67.8 d,
C(SPh ) ); 88.4 d,
3R*,4S*)-3a 48.3 d, JC,F = 17 (CH-CHF); 68.5 s (OCH -CH); 69.8 s (C(SPh ) ); 86.7 d, JC,F
99 (CHF); 128.8–136.8 all s, 18 C (CAr); 171.3 d, JC,F = 16 (CO). F NMR (76.5 MHz,
CDCl ): (3R*,4R*)-3a –187.1 dd, 1 F, JH,F = 50, JH,F = 26 (CHF); (3R*,4S*)-3a –202.4 dd, 1 F,
JH,F = 51, JH,F = 21 (CHF). IR (CHCl ): 1 026 m , 1 219 s, 1 440 m , 1 478 w, 1 799 s, 3 025
3
4
J
= 5 (OCH -CH); 69.3 s
3
C,F 2
1
= 190 (CHF); 128.8–136.8 all s, 18 C (CAr); 171.1 d, 2JC,F = 16 (CO);
(
(
1
J
2
C,F
3
1
=
2
2
2
19
2
3
3
2
3
3
w. For C23H19FO2S2 (410.5) calculated: 67.3% C, 4.6% H; foun d: 65.5% C, 4.78% H.
-Fluoro-4-[(4-methoxyphenyl)bis(phenylsulfanyl)methyl]-4,5-dihydrofuran-2(3H)-one (3b). Re-
3
–
1
action of dith ioacetal 7b (708 m g, 2.09 m m ol), BuLi solution (1.32 m l, 1.89 m ol l , 2.25
m m ol), an d fluorolacton e 1 (205 m g, 2.01 m m ol) in THF (6 m l) afforded after purification
by repeated colum n ch rom atograph y (first SiO , 30 × 3 cm , eluen t petroleum eth er–CH Cl
2
2
2
1
: 1, th en SiO , 15 × 3 cm , eluen t CH Cl ) fluorolacton e 3b (wh ite crystals, 462 m g, 52.4%)
2 2 2
1
as a m ixture of diastereoisom ers ((3R*,4R*)/(3R*,4S*) 44 : 56). H NMR (300.1 MHz, CDCl ):
3
3
3
3
(
3R*,4R*)-3b 3.44 ddt, 1 H, JH,H = 8.2, JH,H = 6.6 (t), JH,F = 25.8 (CH-CHF); 3.82 s, 3 H
2
3
2
3
(
CH O); 4.29 dd, 1 H, JH,H = 10.0, JH,H = 7.2 (OCH H -CH); 4.55 dd, 1 H, JH,H = 9.9, JH,H
3 a b
3
2
3
=
(
8.8 (OCH H -CH); 5.27 dd, 1 H, JH,H = 6.1, JH,F = 50.0 (CHF); 6.85 d, 2 H, JH,H = 8.8
a b
Ar-H); 7.23–7.35 m , 10 H (Ar-H); 7.60 d, 2 H, 3J
= 8.2 (Ar-H); (3R*,4S*)-3b 3.11 dq, 1 H,
H,H
3
3
2
3
JH,H = 7.1 (q), JH,F = 22.9 (CH-CHF); 3.81 s, 3 H (CH O); 4.53 dd, 1 H, JH,H = 9.3, JH,H
=
=
3
2
3
3
7
.1 (OCH H -CH); 4.85 dd, 1 H,
J
= 9.3, JH,H = 6.6 (OCH H -CH); 5.14 dd, 1 H, JH,H
a
b
H,H a b
2
3
6
.6, JH,F = 50.6 (CHF); 6.83 d, 2 H, JH,H = 9.3 (Ar-H); 7.08–7.38 m , 10 H (Ar-H); 7.52 d, 2 H,
3
JH,H = 8.9 (Ar-H). 13C NMR (100.6 MHz, CDCl ): (3R*,4R*)-3b 50.3 d, JC,F = 19 (CH-CHF);
2
3
3
1
5
5.9 s (OCH ); 67.8 d, JC,F = 8 (OCH -CH); 67.6 s (C(SPh ) ); 88.2 d, JC,F = 190 (CHF); 114.5
3 2 2
2
s, 2 C (CAr); 129.4–135.9 all s, 15 C (CAr); 160.2 s (CAr-OCH ); 171.3 d, JC,F = 22 (CO);
3
(
3R*,4S*)-3b – th is diastereoisom er was n ot sufficien tly separated from th e form er on e to en -
1
9
2
able un equivocal assign m en t. F NMR (76.5 MHz, CDCl ): (3R*,4R*)-3b –187.5 dd, 1 F, JH,F
=
1
3
50, JH,F = 26 (CHF); (3R*,4S*)-3b –202.9 dd, 1 F, 2JH,F = 51, JH,F = 22 (CHF). IR (CHCl ):
3
3
3
027 m , 1 091 w, 1 257 s, 1 440 w, 1 509 m , 1 793 s, 3 012 w. Microan alysis was n ot ac-
com plish ed due to low stability of th e product.
-[(3,4-Dimethoxyphenyl)bis(phenylsulfanyl)methyl]-3-fluoro-4,5-dihydrofuran-2(3H)-one (3c).
4
–
1
Reaction of dith ioacetal 7c (733 m g, 1.99 m m ol), BuLi solution (0.90 m l, 2.19 m ol l , 1.99
m m ol), an d fluorolacton e 1 (204 m g, 2.00 m m ol) in THF (6 m l) afforded after purification
by repeated colum n ch rom atograph y (first SiO , 30 × 3 cm , eluen t petroleum eth er–CH Cl
2
2
2
1
: 1, th en SiO , 15 × 3 cm , eluen t CH Cl ) fluorolacton e 3c (wh ite crystals, 538 m g, 57.2%,
2 2 2
1
m .p. 48–51 °C) as a m ixture of diastereoisom ers ((3R*,4R*)/(3R*,4S*) 63 : 37). H NMR (300.1
MHz, CDCl ): (3R*,4R*)-3c 3.44 ddt, 1 H, JH,H = 8.8, JH,H = 6.6 (t), JH,F = 25.8 (CH-CHF);
3
3
3
3
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
777
3
4
.77 s, 3 H (CH O); 3.89 s, 3 H (CH O); 4.48 dd, 1 H, 2J
= 9.9, 3
J
= 7.1 (OCH H -CH);
3
3
H,H
H,H
a
b
.58 dd, 1 H, 2JH,H = 9.9, JH,H = 8.8 (OCH H -CH); 5.30 dd, 1 H, JH,H = 6.1, JH,F = 49.5
3
3
2
a
b
3
(CHF); 6.77 d, 2 H, JH,H = 8.8 (Ar-H); 7.22–7.35 m , 11 H (Ar-H); (3R*,4S*)-3c 3.10 ddt, 1 H,
3
JH,H = 7.1 (t), JH,H = 6.6, 3JH,F = 21.4 (CH-CHF); 3.79 s, 3 H (CH O); 3.89 s, 3 H (CH O);
3
3
3
.50 dd, 1 H, 2J
= 9.9, 3J
= 7.1 (OCH H -CH); 4.85 dd, 1 H, JH,H = 9.9, JH,H = 6.6
H,H a b
2
3
4
H,H
OCH H -CH); 5.16 dd, 1 H, 3J
= 6.6, JH,F = 50.5 (CHF); 6.74–7.52 m , 13 H (Ar-H).
H,H
2
(
a
b
1
3
2
C NMR (100.6 MHz, CDCl ): (3R*,4R*)-3c 50.3 d, JC,F = 18 (CH-CHF); 56.6 s, 2 C (OCH );
3
3
3
3
1
6
1
7.9 d, JC,F = 5 (OCH -CH); 69.3 d, JC,F = 14 (C(SPh ) ); 88.4 d, JC,F = 190 (CHF);
2 2
11.0–121.7 all s, 3C (CAr); 129.7–131.3 all s, 13 C (CAr); 149.4 s (CAr-OCH ); 149.8 s
3
2
(
CAr-OCH ); 171.3 d, JC,F = 22 (CO); (3R*,4S*)-3c – th is diastereoisom er was n ot sufficien tly
3
1
9
separated from th e form er on e to en able un equivocal assign m en t.
F NMR (76.5 MHz,
2
3
CDCl ): (3R*,4R*)-3c –186.8 dd, 1 F, JH,F = 50, JH,F = 26 (CHF); (3R*,4S*)-3c –202.3 dd, 1 F,
3
2
3
JH,F = 51, JH,F = 22 (CHF). IR (CHCl ): 1 025 s, 1 145 m , 1 259 s, 1 515 s, 1 797 s, 3 027 w.
3
For C25H23FO4S2 (470.6) calculated: 63.8% C, 4.9% H; foun d: 63.9% C, 5.1% H.
-[(1,3-Benzodioxol-5-yl)bis(phenylsulfanyl)methyl]-3-fluoro-4,5-dihydrofuran-2(3H)-one (3d ).
4
–
1
Reaction of dith ioacetal 7d (702 m g, 1.99 m m ol), BuLi solution (0.90 m l, 2.19 m ol l , 1.99
m m ol), an d fluorolacton e 1 (207 m g, 2.03 m m ol) in THF (6 m l) afforded after purification
by repeated colum n ch rom atograph y (first SiO , 15 × 3 cm , eluen t CHCl , th en SiO , 15 × 3 cm ,
2
3
2
eluen t petroleum eth er–CH Cl 1 : 1) fluorolacton e 3d (wh ite crystals, 127 m g, 13.8%, m .p.
2
2
1
9
5–106 °C) as a m ixture of diastereoisom ers ((3R*,4R*)/(3R*,4S*) 72 : 28). H NMR (300.1
3
3
3
MHz, CDCl ): (3R*,4R*)-3d 3.39 ddt, 1 H, JH,H = 8.2, JH,H = 6.8 (t), JH,F = 25.8 (CH-CHF);
3
2
3
= 7.1 (OCH H -CH); 4.54 dd, 1 H, 2J
3
4
(
1
(
9
1
1
.40 dd, 1 H, JH,H = 9.9,
J
= 9.9, JH,H = 8.8
H,H
H,H
a
b
3
2
OCH H -CH); 5.28 dd, 1 H, JH,H = 6.0, JH,F = 50.0 (CHF); 6.02 s, 2 H (OCH O); 6.71 d,
a
b
2
3
3
H, JH,H = 8.2 (Ar-H); 7.03 d, 1 H, JH,H = 8.2 (Ar-H); 7.38 s, 1 H (Ar-H); 7.24–7.37 m , 10 H
Ar-H); (3R*,4S*)-3d 3.09 dq, 1 H, 3J
= 6.6 (q), JH,F = 20.3 (CH-CHF); 4.48 dd, 1 H, JH,H =
H,H
3
2
.9, JH,H = 7.1 (OCH H -CH); 4.87 dd, 1 H, JH,H = 9.9, 3JH,H = 6.0 (OCH H -CH); 5.15 dd,
3
2
a
b
a
b
H, 3
J
= 6.6, JH,F = 50.5 (CHF); 5.97 s, 2 H (OCH O); 6.67 d, 1 H, JH,H = 8.2 (Ar-H); 7.08 d,
8.2 (Ar-H); 7.17–7.39 m , 11 H (Ar-H).
3R*,4R*)-3d 50.5 d, JC,F = 19 (CH-CHF); 67.7 d, 3J = 5 (OCH -CH); 70.2 s (C(SPh ) ); 88.3 d,
2
3
H,H
2
3
13
H, JH,H
=
C NMR (100.6 MHz, CDCl ):
3
2
(
1
C,F 2 2
JC,F = 190 (CHF); 102.4 s (OCH O); 108.4 s (CAr); 110.8 s (CAr); 123.3 s (CAr); 129.7–136.0
2
all s, 13 C (CAr); 148.5 s (CAr-OCH ); 149.0 s (C -OCH ); (3R*,4S*)-3d – th is diastereoisom er
2
Ar
2
was n ot sufficien tly separated from th e form er on e to en able un equivocal assign m en t.
1
9
2
3
F NMR (76.5 MHz, CDCl ): (3R*,4R*)-3d –187.2 dd, 1 F, JH,F = 50, JH,F = 26 (CHF);
3
2
3
(
3R*,4S*)-3d –202.6 dd, 1 F, JH,F = 50, JH,F = 20 (CHF). IR (CHCl ): 1 041 s, 1 103 w, 1 240 s,
3
1
4
431 m , 1 466 s, 1 505 s, 1 795 s, 3 028 w. For C24H19FO4S2 (454.5) calculated: 63.4% C,
.2% H; foun d: 62.9% C, 4.5% H.
Ethyl 3-[(3,4-dimethoxyphenyl)bis(phenylsulfanyl)methyl]-2-fluorobutanoate (4). Reaction of
–
1
dith ioacetal 7c (770 m g, 2.09 m m ol), BuLi solution (1.32 m l, 1.89 m ol l , 2.25 m m ol), an d
fluoroester 2 (261 m g, 1.98 m m ol) in THF (6 m l) afforded after purification by repeated col-
um n ch rom atograph y (first SiO , 20 × 3 cm , eluen t CH Cl , th en SiO , 15 × 3 cm , eluen t pe-
2
2
2
2
troleum eth er–EtOAc 3 : 2) fluoroester 4 (wh ite crystals, 787 m g, 79.6%) as a m ixture of
1
diastereoisom ers ((2R*,3R*)/(2R*,3S*) 69 : 31). H NMR (300.1 MHz, CDCl ): (2R*,3R*)-4 1.16 d,
3
3
3
3
3
3
3
5
(
(
H, JH,H = 7.1 (CH CH); 1.26 t, JH,H = 7.1 (CH CH O); 2.80 dq, 1 H, JH,H = 7.1, JH,F =
3 3 2
3
0.0 (CH-CHF); 3.77 s, 3 H (OCH ); 3.87 s, 3 H (OCH ); 4.12 q, 2 H, JH,H = 7.2 (OCH CH );
3
3
2
3
.95 d, 1 H, 2JH,F = 49.5 (CHF); 6.78–7.42 m , 13 H (Ar-H); (2R*,3S*)-4 1.15 d, 3 H, JH,H = 7.1
3
CH CH); 1.18 t, JH,H = 7.1 (CH CH O); 2.88 d of quin tet, 1 H, JH,H = 6.5, 3J
3
3
= 21.0
H,F
3
3
2
3
CH-CHF); 3.77 s, 3 H (OCH ); 3.88 s, 3 H (OCH ); 4.09 q, 2 H, JH,H = 7.2 (OCH CH ); 5.13 dd,
3
3
2
3
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
78
Kvíčala et al.:
1
H, 3JH,H = 6.0, 2J
= 47.8 (CHF). 13C NMR spectra were n ot recorded due to low stability
H,F
1
9
2
3
of th e product. F NMR (76.5 MHz, CDCl ): (2R*,3R*)-4 –200.5 dd, 1 F, JH,F = 49, JH,F = 29
3
CHF); (2R*,3S*)-4 –177.4 dd, 1 F, 2JH,F = 48, JH,F = 21 (CHF). IR (CHCl ): 1 026 s, 1 140 m ,
3
(
3
1
261 s, 1 440 m , 1 465 m , 1 511 s, 1 583 s, 1 728 s, 3 026 w. Microanalysis was not accom -
plished due to low stability of the product.
Tan dem Addition s. Gen eral Procedure
A flask equipped with a m agn etic stirbar, rubber septum an d coolin g bath was ch arged with
aren ecarboxaldeh yde dith ioacetal 7, THF, cooled to –80 °C an d a sm all excess of BuLi
(
105%, given con cen tration in h exan es) was added dropwise. After 1 h , on e equivalen t of
un saturated fluorolacton e 1 was added dropwise an d th e resultin g m ixture was stirred at –80 °C
for 3 h . Th e solution of fluoroen olate th us form ed was tran sferred with a cooled (solid CO2)
Teflon capillary in to a stirred aren ecarboxaldeh yde 8 or (arylm eth yl)brom ide 9 (ca 0.8
equivalen t with respect to fluorocom poun d) cooled to –80 °C. Th e resultin g m ixture was
stirred at –80 °C for 0.5 h an d at –30 °C for 2 h . Th e reaction was stopped by quen ch in g
with HCl (10% solution in THF) at –80 °C. Th e reaction m ixture was allowed to reach room
tem perature an d solven ts were rem oved by rotary vacuum evaporator. Th e product was iso-
lated by repeated colum n ch rom atograph y. Attem pts to perform an alogous tan dem addi-
tion s with fluoroester 2 were on ly m argin ally successful due to low stability of th e
2
1
products
-Fluoro-3-[hydroxy(3,4,5-trimethoxyphenyl)methyl]-4-[phenylbis(phenylsulfanyl)methyl]-
,5-dihydrofuran-2(3H)-one (5a). Th e reaction of dith ioacetal 7a (682 m g, 2.21 m m ol), BuLi
.
3
4
–
1
solution (1.40 m l, 1.89 m ol l , 2.50 m m ol), an d fluorolacton e 1 (206 m g, 2.02 m m ol) in
THF (6 m l) with 3,4,5-trim eth oxyben zaldeh yde (8e, 295 m g, 1.51 m m ol) in THF (2 m l) af-
forded after purification by colum n ch rom atograph y (SiO , 20 × 3 cm , gradien t elution first
2
with CH Cl , th en with EtOAc) fluorolacton e 5a (wh ite crystals, 787 m g, 64.3%, m .p. 76–86 °C)
2
2
1
as a m ixture of two diastereoisom ers (syn-(1′R*,3R*,4S*)/anti-(1′R*,3S*,4R*) 19 : 81). H NMR
300.1 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5a – th is diastereoisom er was n ot sufficien tly
(
3
separated from th e latter on e to en able un equivocal assign m en t; anti-(1′R*,3S*,4R*)-5a
3
3
3
.09 d, 1 H, JH,H = 4.4 (OH); 3.34 d, 1 H, JH,H = 7.7 (CH -CH-CF); 3.70 s, 6 H (CH O); 3.82 s,
2
3
H (CH O); 4.40 dd, 1 H, JH,H = 9.9, 3J
= 8.8 (CH-OH); 5.24 d, 1 H, JH,H = 9.9 (OCH H -CH); 6.47 s, 2 H (Ar-H); 6.92–7.99 m ,
5 H (Ar-H). 13C NMR (100.6 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5a – th is diastereoisom er was
2
= 7.7 (OCH H -CH); 5.08 dd, 1 H, JH,H = 3.9,
a b
3
3
3
H,H
3
2
J
H,F
a
b
1
3
n ot sufficien tly separated from th e latter on e to en able un equivocal assign m en t;
2
anti-(1′R*,3S*,4R*)-5a 46.3 d, JC,F = 16 (CH -CH-CF); 57.0 s, 2 C, (CH O); 61.6 s, 1 C,
(
2
3
2
1
CH O); 69.0 s (OCH -CH); 70.2 s (C(SPh ) ); 75.9 d, JC,F = 11 (CF-CH-OH); 95.8 d, JC,F =
3 2 2
2
1
1
1
09 (CF); 103.7–106.7 all s, 7 C (CAr); 127.8–138.5 all s, 14 C (CAr); 154.0 s, 2 C (CAr-OCH );
3
1
9
3
54.2 s (CAr-OCH ). F NMR (76.5 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5a –165.6 d, 1 F, JH,F
=
3
3
3
0 (CF); anti-(1′R*,3S*,4R*)-5a –168.4 d, 1 F, JH,F = 9 (CF). IR (CHCl ): 1 131 s, 1 230 m ,
3
333 w, 1 422 w, 1 464 m , 1 507 w, 1 599 w, 1 766 m , 3 022 w. For C33H31FO6S2 (606.7)
calculated: 65.4% C, 5.1% H; foun d: 64.9% C, 5.4% H.
-[(3,4-Dimethoxyphenyl)bis(phenylsulfanyl)methyl]-3-fluoro-3-[hydroxy(3,4,5-trimethoxyphenyl)-
methyl]-4,5-dihydrofuran-2(3H)-one (5b). Th e reaction of dith ioacetal 7c (772 m g, 2.10 m m ol),
4
–
1
BuLi solution (1.30 m l, 1.89 m ol l , 2.30 m m ol), an d fluorolacton e 1 (202 m g, 1.98 m m ol)
in THF (6 m l) with 3,4,5-trim eth oxyben zaldeh yde (8e, 310 m g, 1.58 m m ol) in THF (2 m l)
afforded after purification by colum n ch rom atograph y (first SiO , 30 × 3 cm , eluen t CH Cl ,
2
2
2
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
779
th en SiO , 20 × 3 cm , eluen t CH Cl –EtOAc 6 : 1) fluorolacton e 5b (wh ite crystals, 765 m g,
2
2
2
5
8.0%, m .p. 77–90 °C) as
a
m ixture of two diastereoisom ers (syn-(1′R*,3R*,4S*)/
1
anti-(1′R*,3S*,4R*) 27 : 73). H NMR (300.1 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5b 3.10 dd, 1 H,
3
2
3
3
JH,H = 9.9, JH,H = 7.8 (OCH H -CH); 3.48 d, 1 H, JH,H = 6.6 (CH -CH-CF); 3.63–3.88 m ,
a
b
2
3
2
1
6
3
5 H (CH O); 4.95 d, 1 H, JH,F = 9.9 (CH-OH); 5.05 d, 1 H, JH,H = 9.9 (OCH H -CH);
3 a b
3
.40–7.99 m , 15 H (Ar-H); anti-(1′R*,3S*,4R*)-5b 3.23 d, 1 H, JH,H = 7.8 (CH -CH-CF);
.63–3.88 m , 15 H (CH O); 4.32 dd, 1 H, JH,H = 9.9, JH,H = 8.7 (OCH H -CH); 5.05 d, 1 H,
3 a b
2
2
3
3
2
JH,F = 8.8 (CH-OH); 5.18 d, 1 H, JH,H = 9.3 (OCH H -CH); 6.40–7.99 m , 15 H (Ar-H).
a
b
1
3
C NMR (100.6 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5b – th is diastereoisom er was n ot sufficien tly
3
separated from th e latter on e to en able un equivocal assign m en t; anti-(1′R*,3S*,4R*)-5b
2
4
6.8 d, JC,F = 18 (CH -CH-CF); 56.4 s, 1 C (CH O); 56.6 s, 1 C (CH O); 56.9 s, 2 C (CH O);
2 3 3 3
2
5
1
7.0 s, 1 C (CH O); 61.7 d, JC,F = 15 (CF-CH-OH); 69.6 s (OCH -CH); 70.7 s (C(SPh ) ); 95.8 d,
3 2 2
JC,F = 206 (CF); 104.2–113.9 all s, 5 C (CAr); 129.2–138.2 all s, 14 C (CAr); 148.9–154.0 all s,
C (CAr-OCH ). F NMR (76.5 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5b –165.1 d, 1 F, JH,F = 10
3 3
CF); anti-(1′R*,3S*,4R*)-5b –168.0 d, 1 F, JH,F = 9 (CF). IR an d elem en tal an alyses were n ot
accom plish ed due to low stability of th e product.
-[(1,3-Benzodioxol-5-yl)bis(phenylsulfanyl)methyl]-3-fluoro-3-(hydroxyphenylmethyl)-4,5-dihydro-
furan-2(3H)-one (5c). Th e reaction of dith ioacetal 7d (703 m g, 2.00 m m ol), BuLi solution
0.90 m l, 2.19 m ol l–1, 2.00 m m ol), an d fluorolacton e 1 (210 m g, 2.06 m m ol) in THF (6 m l)
1
9
3
5
(
3
4
(
with ben zaldeh yde (8a, 190 m g, 1.79 m m ol) in THF (2 m l) afforded after purification by col-
um n ch rom atograph y (first SiO , 15 × 3 cm , eluen t EtOAc, th en SiO , 30 × 3 cm , eluen t
2
2
petroleum eth er–EtOAc 7 : 3) fluorolacton e 5c (wh ite crystals, 589 m g, 51.1%, m .p. 190–194 °C)
1
as a m ixture of diastereoisom ers (syn-(1′R*,3R*,4S*)/anti-(1′R*,3S*,4R*) 38 : 62). H NMR
2
3
(
(
300.1 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5c 2.86 dd, 1 H, JH,H
=
8.6, JH,H
=
6.9
=
3
OCH H -CH); 3.14 bs, 1 H (OH); 3.43 d, 1 H, 3J
= 5.1 (CH -CH-CF); 4.83 d, 1 H, 2J
a
b
H
,
H
2
H,H
3
1
1
4
5
1
0.3 (OCH H -CH); 5.09 d, 1 H, JH,F = 10.3 (CH-OH); 5.95 s, 2 H (OCH O); 6.56–7.70 m ,
a b 2
8 H (Ar-H); anti-(1′R*,3S*,4R*)-5c 2.61 s, 1 H (OH); 3.16 d, 1 H, JH,H = 8.2 (CH -CH-CF);
.04 dd, 1 H, JH,H = 9.3, JH,H = 8.2 (OCH H -CH); 5.06 d, 1 H, 2J
3
2
2
3
= 11.0 (OCH H -CH);
a b
a
b
H,H
.10 d, 1 H, 3J
= 10.4 (CH-OH); 5.94 s, 2 H (OCH ); 6.19 d, 1 H, JH,H = 8.2 (Ar-H); 6.25 d,
3
H,F
2
3
13
H, JH,H
=
8.2 (Ar-H); 6.75–7.67 m , 16 H (Ar-H).
C NMR (100.6 MHz, CDCl ):
3
syn-(1′R*,3R*,4S*)-5c – th is diastereoisom er was n ot sufficien tly separated from th e latter on e
2
to en able un equivocal assign m en t; anti-(1′R*,3S*,4R*)-5c 46.2 d, JC,F = 16 (CH -CH-CF); 69.6 s
2
2
1
(
(
(
OCH -CH); 72.0 s (C(SPh ) ); 74.3 d, JC,F = 25 (CF-CH-OH); 96.0 d, JC,F = 209 (CF); 101.1 s
2 2
OCH O); 106.4 s, 1 C (CAr); 109.7 s, 1 C (CAr); 125.3–139.6 all s, 19 C (CAr); 146.3 s, 1 C
2
CAr-OCH ); 146.5 s, 1 C (C -OCH ); 170.7 d, 2J
= 24 (CO). F NMR (76.5 MHz, CDCl ):
19
2
Ar
2
C,F
H,F
3
syn-(1′R*,3R*,4S*)-5c –165.7 dd, 1 F, JH,F = 10, 3J
3
= 2 (CF); anti-(1′R*,3S*,4R*)-5c –169.1 dd,
F, JH,F = 9, JH,F = 1 (CF). IR (CHCl ): 1 042 m , 1 142 w, 1 239 s, 1 408 m , 1 487 s, 1 505 m ,
786 s, 3 022 w. For C31H25FO5S2 (560.7) calculated: 66.4% C, 4.5% H; foun d: 65.3% C,
.8% H.
3
3
1
1
4
3
4
-[(1,3-Benzodioxol-5-yl)bis(phenylsulfanyl)methyl]-3-fluoro-3-[hydroxy(3,4,5-trimethoxyphenyl)-
methyl)-4,5-dihydrofuran-2(3H)-one (5d ). Reaction of dith ioacetal 7d (706 m g, 2.01 m m ol),
–
1
BuLi solution (0.90 m l, 2.19 m ol l , 2.00 m m ol), an d fluorolacton e 1 (206 m g, 2.02 m m ol)
in THF (6 m l) with 3,4,5-trim eth oxyben zaldeh yde (8e, 296 m g, 1.51 m m ol) in THF (2 m l)
afforded after purification by colum n ch rom atograph y (first SiO , 15 × 3 cm , eluen t petro-
2
leum eth er–EtOAc 6 : 4, th en SiO , 30 × 3 cm , eluen t CHCl –EtOAc 9 : 1) fluorolacton e 5d
2
3
(
(
wh ite crystals, 767 m g, 58.4%, m .p. 188–195 °C) as a m ixture of two diastereoisom ers
1
syn-(1′R*,3R*,4S*)/anti-(1′R*,3S*,4R*) 45 : 55). H NMR (300.1 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5d
3
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
80
Kvíčala et al.:
3
7
.00 bs, 1 H (OH); 3.12 dd, 1 H, 2JH,H = 9.8, 3JH,H = 7.5 (OCH H -CH); 3.41 d, 1 H, 3J
=
H,H
a
b
2
.5 (CH -CH-CF); 3.81 s, 3 H (CH O); 3.86 s, 6 H (CH O); 4.95 d, 1 H, JH,H = 10.4
2
3
3
3
(
(
OCH H -CH); 5.06 d, 1 H, JH,F = 10.4 (CH-OH); 5.98 s, 2 H (OCH O); 6.51–7.76 m , 15 H
a b 2
Ar-H); anti-(1′R*,3S*,4R*)-5d 2.80 s, 1 H (OH); 3.22 d, 1 H, JH,H = 7.5 (CH -CH-CF); 3.72 s,
3
2
H (CH O); 3.84 s, 3 H (CH O); 4.29 dd, 1 H, JH,H = 9.9, 3J
2
= 7.7 (OCH H -CH); 5.07 d,
H,H a b
6
1
1
7
3
3
3
2
H, JH,F = 8.3 (CH-OH); 5.12 d, 1 H, JH,H = 9.9 (OCH H -CH); 5.93 s, 2 H (OCH ); 6.17 d,
= 8.7 (Ar-H); 6.29 d, 1 H JH,H = 8.7 (Ar-H); 6.46 s, 2 H (Ar-H); 6.76 d, 2 H, JH,H =
.5 (Ar-H); 7.02 s, 1 H (Ar-H); 7.12–7.42 m , 6 H (Ar-H); 7.71 d, 1 H, JH,H = 7.7. C NMR
a
b
2
H, 3J
3
3
H,H
3
13
2
(
(
(
100.6 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5d 47.6 d,
CH O); 60.2 s, 1 C (CH O); 61.2 s (OCH -CH); 76.3 d, JC,F = 3 (C(SPh ) ); 76.3 d, JC,F = 31
CF-CH-OH); 96.9 d, JC,F = 206 (CF); 102.8 s (OCH O); 106.1 s, 1 C (CAr); 106.3 s, 2 C (CAr);
J
= 16 (CH -CH-CF); 57.2 s, 2 C
3
C,F
2
3
2
3
3
2
2
1
2
1
11.4 s, 1 C (CAr); 123.5–140.3 all s, 15 C (CAr); 148.4 s, 1 C (CAr-OCH ); 148.6 s, 1 C
2
2
(
CAr-OCH ); 155.0 s, 3 C (C -OCH ); 175.1 d, JC,F = 23 (CO); anti-(1′R*,3S*,4R*)-5d – th is
2
Ar
3
diastereoisom er was n ot sufficien tly separated from th e form er on e to en able un equivocal
1
9
3
assign m en t. F NMR (76.5 MHz, CDCl ): syn-(1′R*,3R*,4S*)-5d –165.6 dd, 1 F, JH,F = 10,
3
3
JH,F = 2 (CF); anti-(1′R*,3S*,4R*)-5d –168.5 d, 1 F, 3JH,F = 9, JH,F = 1 (CF). IR (CHCl ): 1 026 m ,
3
3
1
138 m , 1 240 s, 1 465 s, 1 509 s, 1 594 s, 1 728 m , 1 786 m , 3 012 m . Microan alysis was
n ot accom plish ed due to low stability of th e product.
-[(3,4-Dimethoxyphenyl)bis(phenylsulfanyl)methyl]-3-fluoro-3-(phenylmethyl)-4,5-dihydrofuran-
4
2
1
(3H)-one (6a). Th e reaction of dith ioacetal 7c (768 m g, 2.09 m m ol), BuLi solution (1.32 m l,
.89 m ol l–1, 2.25 m m ol), an d fluorolacton e 1 (204 m g, 2.00 m m ol) in THF (6 m l) with
ben zyl brom ide (9a, 269 m g, 1.57 m m ol) in THF (2 m l) afforded after purification by col-
um n ch rom atograph y (SiO , 30 × 3 cm , gradien t elution first with petroleum eth er–CH Cl
2
2
2
1
4
: 1, th en with CH Cl ) sin gle diastereoisom er of fluorolacton e (3R*,4R*)-6a (wh ite crystals,
2 2
1
2
48 m g, 40.0%, m .p. 148–153 °C). H NMR (300.1 MHz, CDCl ): 3.19 dd, 1 H, JH,H = 13.5,
3
3
2
JH,F = 20.2 (Ar-CH H -CF); 3.24 m , 2 H (CH -CH-CF + Ar-CH H -CF); 3.60 dd, 1 H, JH,H
=
=
a
b
2
a
b
0.4, 3JH,H = 7.7 (OCH H -CH); 3.80 s, 3 H (CH O); 3.86 s, 3 H (CH O); 4.96 dd, 1 H, JH,H
2
1
1
4
a b 3 3
4
13
0.4,
J
2
= 2.2 (OCH H -CH); 6.50–7.64 m , 18 H (Ar-H). C NMR (100.6 MHz, CDCl ):
H
,
F
a
b
3
2
1.9 d, JC,F = 25 (Ar-CH -CF); 47.2 d, JC,F = 21 (CH -CH-CF); 56.2 s, 1 C (CH O); 56.8 s, 1 C
2
2
3
(
CH O); 67.0 s (OCH -CH); 95.3 d, 1J
= 211 (CF); th e rest of carbon sign als could n ot be
C,F
3
2
1
9
un equivocally assign ed due to partial decom position of th e m ixture. F NMR (76.5 MHz,
CDCl ): –161.3 ddd, 1 F, JH,F = 23, JH,F = 15, JH,F = 2 (CF). IR (CHCl ): 1 026 m , 1 146 m ,
3
3
4
3
3
1
258 s, 1 485 m , 1 514 s, 1 603 w, 1 791 s, 3 026 m . Microan alysis was n ot accom plish ed
due to low stability of th e product.
-[(3,4-Dimethoxyphenyl)bis(phenylsulfanyl)methyl]-3-fluoro-3-[(3,4,5-trimethoxyphenyl)methyl]-
,5-dihydrofuran-2(3H)-one (6b ). Reaction of dith ioacetal 7c (776 m g, 2.11 m m ol), BuLi
4
4
–
1
solution (1.32 m l, 1.89 m ol l , 2.25 m m ol), an d fluorolacton e 1 (202 m g, 1.98 m m ol) in THF
(
(
6 m l) with 5-(brom om eth yl)-1,2,3-trim eth oxyben zen e (9b, 408 m g, 1.56 m m ol) in THF
2 m l) afforded after purification by colum n ch rom atograph y (SiO , 40 × 3 cm , gradien t elu-
2
tion first with petroleum eth er–CH Cl 1 : 2, th en with CH Cl ) sin gle diastereoisom er of
2
2
2
2
1
fluorolacton e (3R*,4R*)-6b (wh ite crystals, 736 m g, 57.2%, m .p. 117–125 °C). H NMR (300.1
MHz, CDCl ): 2.99 dd, 1 H, JH,H = 13.7, JH,F = 24.2 (Ar-CH H -CF); 3.18 t, 1 H, JH,H
2
3
2
3
=
JH,F
=
3
a
b
1
3.8 (Ar-CH H -CF); 3.18 m , 1 H (CH -CH-CF); 3.74 s, 6 H (CH O); 3.82 s, 9 H (CH O); 3.93
a
b
2
3
3
2
3
4
2
ddd, 1 H, JH,H = 10.4, JH,H = 7.2, JH,F = 4.2 (OCH H -CH); 5.07 d, 1 H, JH,H = 9.9
a
b
3
3
(
(
(
OCH H -CH); 6.26 s, 2 H, (Ar-H); 6.44 d, 1 H, JH,H = 8.8 (Ar-H); 6.80 d, 1 H, JH,H = 8.8
a b
Ar-H); 6.80–7.64 m , 11 H (Ar-H).
1
3
C NMR (100.6 MHz, CDCl ): 43.7 d, 2J
= 26
C,F
3
2
Ar-CH -CF); 48.7 d, JC,F = 17 (CH -CH-CF); 56.5 s, 1 C (CH O); 56.6 s, 1 C (CH O); 56.9 s,
2
2
3
3
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
781
2
1
C (CH O); 61.6 s, 1 C (CH O); 68.2 s (OCH -CH); 69.5 s (C(SPh ) ); 94.9 d, 1J
= 209 (CF);
C,F
07.9 s, 2 C (CAr); 109.8 s, 1 C (CAr); 114.2 s, 1 C (CAr); 121.3 s, 1 C (CAr); 128.4–138.5 all s,
3
3
2
2
1
4 C (CAr); 148.9 s, 1 C (CAr-OCH ); 149.2 s, 1 C (C -OCH ); 154.0 s, 3 C (C -OCH ); 174.2 d,
3
Ar
3
Ar
3
2
JC,F = 25 (CO). 19F NMR (76.5 MHz, CDCl ): –162.0 ddd, 1 F, JH,F = 29, 3J
3
4
= 14, JH,F = 5
H,F
3
(
CF). IR (CHCl ): 1 026 m , 1 132 s, 1 257 s, 1 405 m , 1 513 s, 1 592 m , 1 791 m , 3 025 m .
3
For C35H35FO7S2 (650.8) calculated: 64.8% C, 5.1% H; foun d: 64.4% C, 5.9% H.
RESULTS AND DISCUSSION
Preparation of 3-Fluorofuran-2(5H)-one (1)
From retrosyn th etic an alysis, two approach es leadin g to fluorolacton e 1 were
form ulated, viz. transform ation of appropriately substituted non-fluorinated
butan olides or buten olides an d th e form ation of (E)-2-fluoroalken oate from
a pair of two-carbon fragm en ts followed by rin g closure.
Th e first approach uses fluorobutan olide 11, previously m ade from
1
4
2
-brom o-2-deoxy-D-th reon olacton e , as th e key in term ediate. We prepared
1
3
fluorolacton e 11 from easily accessible D-eryth ron olacton e 10 (Sch em e 1).
O
O
O
O
O
O
O
O
O
O
(i)
(ii)
(iii)
(iv)
HO
(
OH
HO
OTs
O
HO
F
F
10
11
12
13
1
o
o
i) TsCl, pyridine, -25 C, 72 h, 73%; (ii) KF, acetone, reflux, 12 h, 68%; (iii) Et3N.3HF, 70 C,
o
7
2 h, 41%; (iv) P2O5, 200 C, 2 h, 31%
SCHEME 1
Noteworth y is th e good yield of epoxide 12 form ed by overall
in tram olecular syn substitution of tosylate 11 alth ough in an an alogous
open -ch ain tosylate, th e attack of th e in tern al n ucleoph ile is exclusively
2
2
anti (ref. ). Th e probable in term ediate of th e reaction was fluorolacton e 13.
Th e sam e product in a lower yield was obtain ed wh en sodium carbon ate
was used in stead of potassium fluoride. As n ucleoph ilic substitution of
tosylate by carbon ate ion h as been observed23, we assum e again th at two
con secutive substitution s with double in version on th e C-2 carbon oc-
curred. Th e m ain drawback of th e syn th esis as depicted in Sch em e 1 is th e
m oderate yields of th e two last steps, viz. open in g of th e epoxide rin g by
fluoride ion an d deh ydration of fluorolacton e 13 to fluorobuten olide 1. We
th erefore turn ed our atten tion to th e oth er approach .
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
82
Kvíčala et al.:
Num erous ways can be used for th e preparation of 2-fluorobut-2-en oates,
2
4
but m ost of th em are eith er n on -stereoselective or lead to Z-con figuration
2
5
of th e double bon d . Th e on ly m eth od for con structin g (E)-2-fluoroalk-
-en oates em ploys th e Wittig–Horn er reaction of fluoroph osh on oacetate 15
2
1
1
with an appropriate aldeh yde an d we th erefore followed th is route. Th e
publish ed syn th esis of fluoroester 15 starts from relatively expen sive
1
1
brom otrifluoroeth en e . In stead, we used ch eap ch lorotrifluoroeth en e,
wh ich required on e m ore reaction step, viz. tran sform ation of eth yl
1
5
ch lorofluoroacetate to eth yl fluoroiodoacetate 14 by th e Fin kelstein reac-
1
6
tion . We were n ot able to prepare th e secon d key in term ediate,
1
7
2
-oxoeth yl acetate (16), in th e pure state by described procedure . How-
ever, th e reaction of 16 of low purity with ph osph on oacetate 15 afforded
-substituted fluorobuten oate 17 with th e desired (E)-con figuration , wh ich ,
4
after alkalin e h ydrolysis of both ester groups, afforded, after acidification
an d con tin uous extraction , th e target fluorolacton e 1 in an acceptable yield
(
Sch em e 2). Acid-base m an ipulation en abled to rem ove successively both
organ ic an d in organ ic adm ixtures leavin g pure product 1.
O
O
OEt
O
(i)
(ii)
O
AcO
OEt
F
P
OEt
OEt
O
F
F
15
17
1
o
(
i) 1. BuLi; 2. AcOCH2CHO (16), THF, -80 C, 2 h, 95%; (ii) 1. NaOH, dioxane, H2O,
o
o
2
0 C, 12 h; 2. HCl, H2O, 20 C, 12 h, 56%
SCHEME 2
Conjugate Additions
Soft carbon n ucleoph iles such as th e lith ium salts of dith ioacetals 7a–7d at-
tack fluorofuran on e 1, or fluoroester 2 by con jugate addition at C-3 as th e
softer electroph ilic cen tre (Sch em e 3).
Com poun ds 3 an d 4 were obtain ed by quen ch in g th e en olates with h y-
droch loric acid in poor to m oderate yields. Products 3 an d 4 suffer from
low stability an d th erefore, in som e cases, we were n ot to able to perform
com plete an alysis before decom position . Exten sive decom position is proba-
bly th e source of low yield of 3d , too. Th e ratios of in dividual diastereo-
isom ers were estim ated from NMR spectra of crude reaction m ixtures an d
are listed togeth er with yields in Table I.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
783
3
Hydrogen -fluorin e vicin al couplin g con stan ts J
in diastereoisom ers 3
H,F
*
form ed m ostly to a greater exten t (design ed 3R ,4R*) h ave a value of 26 Hz
com pared with 20 Hz in th e m ostly m in or diastereoisom ers (design ed
2
6
3
R*,4S*). From m olecular m ech an ics calculation s , com poun ds 3 with a
bulky substituen t on C-3 in pseudoequatorial position seem to prefer en ve-
lope con form ation an d th e dih edral an gle F–C–C–H ca 40° an d ca 170° for
th e trans an d cis isom ers, respectively (see Fig. 1). As th e couplin g con stan t
PhS SPh
PhS SPh
PhS SPh
R2
R1
R2
R1
R2
R1
(i), (ii), (iv)
O
O
F
F
O
O
7
(3R*,4R*)-3
(3R*,4S*)-3
(
i), (iii), (iv)
R1
R2
H
3
, 7
a
b
c
d
H
PhS SPh
F
PhS SPh
F
MeO
H
R2
R1
R2
R1
MeO MeO
OCH
O
O
2
O
OEt
OEt
COOEt
F
(
3R*,4R*)-4
(3R*,4S*)-4
1
R = R2 = MeO (4)
2
i) BuLi, THF, -80 C, 1 h; (ii) 1, -80 oC, 3 h; (iii) 2, -80 oC, 3 h; (iv) HCl, THF, -80 C
o
o
(
SCHEME 3
TABLE I
Con jugate addition s of dith ioacetal 7 based an ion s on fluoroesters 1 an d 2
Product diastereoisom er
ratio, %
Yield
%
Dith ioacetal
Fluoroester
Product
R1
R2
(
R*,R*)
(R*,S*)
4
1.4
7
7
7
7
7
a
b
c
d
c
1
1
1
1
2
3a
3b
3c
3d
4
H
H
H
57
44
63
72
69
43
56
37
28
31
MeO
52.4
MeO MeO 57.2
OCH O 13.8
MeO MeO 79.6
2
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
84
Kvíčala et al.:
sh ould be larger for anti com pared with gauche con form ation 27, m ajor
diastereoisom ers are m ost probably th e cis isom ers (wh ich correspon ds to
3
R*,4R*), form ed preferen tially due to steric h in dran ce by th e bulky
substituten t at C-3. A sim ilar relation sh ip can be observed for h ydrogen -
3
h ydrogen vicin al couplin g con stan t JH,H. We assum e th at diastereoisom ers
of open -ch ain fluoroester 4 beh ave sim ilarly.
Tandem Additions
We succeeded in perform in g tan dem addition s on fluorofuran on e 1 usin g
lith ium salts of dith ioacetals 7 as n ucleoph iles an d aren ecarboxaldeh ydes 8
or arylm eth yl brom ides 9 as electroph iles. Th e results in cludin g th e ratios
of diastereoisom ers form ed are listed in Table II. An alogous product form ed
from fluoroester 2 proved to be h igh ly un stable an d h en ce on ly brief
1
9
21
F NMR spectra could be recorded before decom position
.
To obtain acceptable yields, optim ized reaction con dition s h ad to be
m ain tain ed, viz. form ation of carban ion by th e action of butyllith ium , in -
verse addition of th e preform ed fluorin ated en olate to th e electroph ile at
low tem perature, an d settin g th e tem perature for th e secon d step of tan dem
addition to –30 °C (Sch em e 4).
Th e products 5 con tain th ree asym m etric cen tres, but on ly two diastereo-
isom ers, syn an d anti were isolated. Th is in dicates th at th e aren ecarbox-
aldeh yde attack proceeds exclusively anti to th e bulky β-substituen t of
fluoroen olate in accord with kn own tan dem addition s on n on -fluorin ated
2
,3
buten olides an d in lin e with proton ation , in wh ich th e effect is n ot so
m arked as expected with a less bulky electroph ile. Moreover, h ydro-
gen -fluorin e vicin al couplin g con stan t 3JH,F fell below an observable lim it
2
8
(
≈2 Hz) wh ich im plies th e trans con figuration accordin g to publish ed data
PhS
PhS
H
F
O
O
O
Ar
O
Ar
PhS
PhS
F H
H H
*
*
*
*
(3R ,4S )-3
3JHF ~ 20 Hz
3JHH ~ 7 Hz
(
3R ,4R )-3
3JHF ~ 26 Hz
3JHH ~ 6 Hz
FIG. 1
Most stable con form ers of both diastereoisom ers of fluorolacton e 3
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
785
PhS SPh
PhS SPh
R2
R1
R2
R1
PhS SPh
i), (ii), (iii), (v)
R2
R1
(
O
O
HO
F
HO
F
O
O
7
R3
R3
R3
R3
(i), (ii), (iv), (v)
R3
R3
syn-(1'R*,3R*,4S*)-5
anti-(1'R*,3S*,4R*)-5
PhS SPh
R2
R1
R1
R2
R3
5
a
b
c
d
O
H
H
MeO
F
MeO MeO MeO
O
OCH2O
OCH2O
H
R3
R3
MeO
R3
(
3R*,4R*)-6
CH
O
8
a
b
c
d
e
R1
H
R2
R3
H
H
H
H
H
H
R1
R2
R3
H
6
a
b
MeO
R1
R3
MeO MeO
MeO MeO
R2
MeO MeO MeO
OCH O
2
8
MeO MeO MeO
(
i) BuLi, THF, -80 oC, 1 h; (ii) 1, -80 oC, 3 h; (iii) inverse addition, PhCHO (8a) or
3
,4,5-(MeO)3PhCHO (8e), -80 oC, 0.5 h, then -30 oC, 2 h; (iv) inverse addition,
PhCH2Br (9a) or 3,4,5-(MeO)3PhCH2Br (9b), -80 oC, 0.5 h, then -30 C, 2 h;
o
(
v) HCl, THF, -80 o
C
SCHEME 4
TABLE II
Tan dem addition s of dith ioacetal 7 based an ion s on fluorolacton e 1
Relative diastereo-
isom er ratio, %
Dith io- Fluoro-
Yield
%
Electroph ile
Product
R1
R2
R3
acetal
ester
syn
anti
7
7
7
7
7
7
a
c
d
d
c
c
1
1
1
1
1
1
8e
8e
8a
8e
9a
9b
5a
5b
5c
5d
6a
6b
H
H
MeO 64.3
19
27
38
45
81
73
62
55
MeO MeO MeO 58.0
OCH O
H
51.1
MeO 58.4
40.0
2
OCH O
2
MeO MeO
H
–
–
MeO MeO MeO 57.2
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

7
86
Kvíčala et al.:
on substituted fluorobutan olides. Relative con figuration s were estim ated on
th e basis of gen erally accepted Zim m erm an –Traxler m odel of tran sition
2
9
state for aldol reaction , wh ich sh ould prefer form ation of anti
diastereoisom ers 5 (see Fig. 2).
An oth er in direct support for th e relative con figuration s of tan dem addi-
tion products com es from 1H NMR spectra. In th e syn adducts 5, th e NMR
sh ift of on e proton of th e CH O group of th e furan on e rin g h as a surpris-
2
in gly low value (2.8–3.2 ppm , con firm ed by 2D COSY NMR experim en ts)
relative to th e sam e proton sh ift of th e anti diastereoisom ers 5 (4.0–4.4 ppm )
an d also relative to th e oth er proton of th e CH O group (4.8–5.1 ppm ). Pro-
2
vided th at h ydrogen bon d in com poun ds 5 is form ed between th e h ydroxyl
group an d th e carbon yl oxygen or fluorin e, products 5 ten d to adopt con -
form ation sim ilar to th e tran sition state (Fig. 2). For assum ed syn diastereo-
isom ers, th is results in placin g on e of th e h ydrogen s of th e furan on e rin g
(
boldfaced in Fig. 2) above th e arom atic rin g. Th is h ydrogen is th en ob-
served at a h igh er local m agn etic field with a correspon din g upfield sh ift of
its sign al.
Sim ilarly to aldol products 5, trappin g of in term ediate fluoroen olate by
arylm eth yl brom ides 9 in tan dem addition s resulted in th e form ation of
sin gle diastereoisom er as a result of exclusive anti attack.
Com poun ds 3–6 are im portan t syn th etic in term ediates for th e syn th esis
of fluorin ated lign an s, an d un derlin e th e im portan ce of fluorofuran on e 1 as
a readily available startin g m aterial. In con trast to direct electroph ilic fluo-
rin ation of podoph yllotoxin 12, syn th etic approach allows for preparation of
un n atural an alogues of podoph yllotoxin lign an s. Th e m ain drawback of
th e tan dem addition approach is lim ited stability of th e products.
R3
F
O
O
Li
R3
SPh SPh
H
F
R2
H
R
O
O
O
Li
R3
R=
R1
H
H
H
R
O
R3
R3
H
R3
H
H
*
*
*
*
*
*
syn-(1'R ,3R ,4S )-5
anti-(1'R ,3S ,4R )-5
FIG. 2
Zim m erm an –Traxler m odels of tran sition states of th e secon d step of tan dem addition of
dith ioacetal 7 based an ion on fluorolacton e 1 with aren ecarboxaldeh yde 8
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Fluorinated Lignans
787
This project was supported by the Grant Agency of the Czech Republic (grant No. 203/96/1057)
and by the Ministry of Education, Youth and Sports of the Czech Republic (Project LB98233).
REFERENCES AND NOTES
1
2
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c) VanVliet D. S., Lee K.-H.: Tetrahedron Lett. 1999, 40, 2259.
. a) Ziegler F. E., Schwartz J. A.: J. Org. Chem. 1978, 43, 985; b) Pelter A., Ward R. S.,
Pritchard M. C., Kay I. T.: J. Chem. Soc., Perkin Trans. 1 1988, 1603; c) Ogiku T., Yoshida Sh.-I.,
Kuroda T., Takahashi M., Ohmizu H., Iwasaki T.: Bull. Chem. Soc. Jpn. 1992, 65, 3495.
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Pelter A., Abd-El-Ghani A.: Tetrahedron 1996, 52, 1303.
3
4
5
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1. Reaction of lithium salt of aryldithioacetal 7c, fluoroester 2 and 3,4,5-trimethoxy-
benzaldehyde (8e) afforded crude ethyl 3-[(3,4-dimethoxyphenyl)bis(phenylsulfanyl)-
methyl]-2-fluoro-2-[(3,4,5-trimethoxyphenyl)methyl]butanoate as the mixture of two
diastereoisomers A and B (44 : 56), which decomposed during column chromatography.
1
9
The yield estimated from F NMR spectra of the crude mixture was about 225 mg
(
1
13.6%). 19F NMR (76.5 MHz, CDCl ): diastereoisomer A –173.4 dd, 1 F, JH,F = 32, JH,F
0 (CF); diastereoisomer B –169.2 dd, 1 F, JH,F = 22, JH,F = 10 (CF).
3
3
=
3
3
3
2
2
2
2. Fleming P. R., Sharpless K. B.: J. Org. Chem. 1991, 56, 2869.
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J. Org. Chem. 1990, 55, 4639.
2
5. a) Allmendinger T.: Tetrahedron 1991, 47, 4905; b) Normant J. F., Foulon J. P., Masure D.,
Sauvetre R., Villieras J.: Synthesis 1975, 122; c) Ishihara T., Kuroboshi M.: Chem. Lett.
1
987, 1145; d) Kitazume T., Ishikawa N.: Chem. Lett. 1981, 1259; e) Usuki Y., Iwaoka M.,
Tomoda S.: J. Chem. Soc., Chem. Commun. 1992, 1148; f) Matsuo N., Kende A. S.: J. Org.
Chem. 1988, 53, 2304; g) Clemenceau D., Cousseau J.: Tetrahedron Lett. 1993, 6903.
6. Molecular modelling was performed by MM2 routine, program Hyperchem 2. Hypercube,
Inc. and Autodesk, Inc. 1991.
2
2
2
7. Williamson K. L., Hsu Y.-F. L., Hall F. H., Swager S., Coulter M. S.: J. Am. Chem. Soc.
1
968, 90, 6717.
8. a) Araki K., Yun W. Q., O′Toole J., Toscano P. J., Welch J. T.: Carbohydr. Res. 1993, 249,
1
39; b) Welch J. T., Plummer J. S., Chou T.-Sh.: J. Org. Chem. 1991, 56, 353; in this
a)
article the configuration assignment is erroneous .
2
9. Brown M. in: Houben–Weyl. Methods of Organic Chemistry (G. Helmchen, R. W. Hoffmann,
J. Mulzer and E. Schaumann, Eds), Vol. E21b, p. 1609. Thieme, Stuttgart 1995.
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