A new regioselective Heck vinylation with enamides. Synthesis and investigation of fluorous-tagged bidentate ligands for fast separation

Article abstract of DOI:10.1021/jo034265i

Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation accelerated the palladium-catalyzed reactions, and full conv

Full text of DOI:10.1021/jo034265i

A New Regioselective Heck Vin yla tion w ith En a m id es. Syn th esis
a n d In vestiga tion of F lu or ou s-Ta gged Bid en ta te Liga n d s for F a st
Sep a r a tion
Karl S. A. Vallin,† Qisheng Zhang,‡ Mats Larhed,*,† Dennis P. Curran,*,‡ and
Anders Hallberg†
Department of Organic Pharmaceutical Chemistry, Uppsala University, BMC, Box-574,
SE-751 23 Uppsala, Sweden, and Department of Chemistry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15260
mats.larhed@orgfarm.uu.se
Received February 28, 2003
Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity
and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation
accelerated the palladium-catalyzed reactions, and full conversions were achieved after reaction
times of only 15-30 min. New bidentate fluorous-tagged 1,3-bis(diphenylphosphino)propane ligands
(F-dppp’s) were synthesized and examined. The cationic vinylations of the enamides with F-dppp
ligands rendered essentially the same R-selectivity and catalytic activity as in those vinylations
where nonfluorous ligands were employed. After reaction, the fluorous-tagged ligand material was
easily removed by convenient solid fluorous phase separation. The high selectivity, simplicity, and
generality of the experimental procedure should make this approach to 2-acylamino-1,3-butadienes
attractive.
In tr od u ction
sidering the fact that enamides are electron-rich, the
obvious question arose whether a protocol that enabled
also selective preparation of useful 2-acylamino-1,3-
butadienes could be developed.
The palladium-catalyzed Heck coupling is a powerful
tool in both organic and medicinal chemistry, and new
applications and protocols are reported continuously.1-6
Specifically, the coupling of vinyl halides (or pseudoha-
lides) with olefins to provide 1,3-dienes constitutes an
important subtype of the Heck reaction. In contrast to
the wide range of available vinyl palladium precursors
for this transformation, the olefinic substrates have so
far mostly been limited to electron-deficient olefins.1,3,5,6
Thus, there are only a few examples reported of success-
ful preparations of the synthetically very useful electron-
rich 1,3-dienes, despite the fact that electron-rich olefins
have been extensively exploited in the related Heck
arylation reaction.4,7,8 We recently reported highly selec-
tive internal Heck vinylations of alkyl vinyl ethers where
bidentate ligands controlled the regioselectivity.9,10 Con-
In modern synthetic chemistry laboratories protocols
for high reaction speed and rapid purification are highly
desired. To meet the first demand, controlled microwave
synthesizers have been developed.11-14 These heating
devices can accelerate palladium-catalyzed transforma-
tions and reduce the reaction times from many hours
down to a few minutes.15 Among the variety of methods
that have been used for improving the workup procedures
of chemical reactions, fluorous techniques have attracted
an increasing amount of attention due to quick liquid-
liquid and solid-liquid extractions.16,17 Recent investiga-
tions have showed that by shifting from liquid-liquid to
solid-liquid extractions, the fluorine content on the
tagged reagent or reactant can drastically be decreased
without affecting the efficiency of the fluorous separa-
tion.18
† Uppsala University.
‡ University of Pittsburgh.
(1) Heck, R. F. Org React. 1982, 27, 345-390.
(2) Daves, G. D., J r.; Hallberg, A. Chem. Rev. 1989, 89, 1433-1445.
(3) De Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994,
33, 2379-2411.
(10) Vallin, K. S. A.; Larhed, M.; J ohansson, K.; Hallberg, A. J . Org.
Chem. 2000, 65, 4537-4542.
(11) Strauss, C. R.; Trainor, R. W. Aust. J . Chem. 1995, 48, 1665-
(4) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2-7.
(5) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009-
3066.
1692.
(12) Lidstro¨m, P.; Tierney, J .; Wathey, B.; Westman, J . Tetrahedron
2001, 57, 9225-9283.
(13) Stadler, A.; Kappe, C. O. J . Comb. Chem. 2001, 3, 624-630.
(14) Loupy, A. Microwaves in Organic Synthesis; Wiley-VCH: Wein-
heim, 2002.
(15) Larhed, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res. 2002, 35,
717-727.
(16) Curran, D. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 1175-
1196.
(6) Larhed, M.; Hallberg, A. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-I., Ed.; Wiley-Inter-
science: New York, 2002; Vol. 1, pp 1133-1178.
(7) Ziegler, C. B., J r.; Heck, R. F. J . Org. Chem. 1978, 43, 2949-
2952.
(8) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J . Org. Chem.
1992, 57, 3558-3563.
(9) Andersson, C. M.; Hallberg, A. J . Org. Chem. 1989, 54, 1502-
1505.
(17) Tzschucke, C. C.; Markert, C.; Bannwarth, W.; Roller, S.; Hebel,
A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41, 3964-4000.
10.1021/jo034265i CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/24/2003
J . Org. Chem. 2003, 68, 6639-6645
6639

Vallin et al.
CHART 1
mainly to competing homocoupling of 1a (the formation
of bis-cyclohexenyls and oxidized derivatives). This com-
peting side reaction was favored at low temperature, but
by using microwave flash heating to 150 °C for 5 min
nearly all homocoupling product formation was quelled.
Unfortunately, the high reaction temperature was ac-
companied with a loss of R-selectivity (R/â ) 80/20).15
However, the isolated yield of branched 3a in the 15 min
microwave-heated reaction at 90 °C (51%, entry 2) was
similar to entry 1 (53%) due to the counteracting effects
of the temperature-suppressed homocoupling and the
reduced R-selectivity. By application of exactly the same
transformation with conventional heating at 90 °C, full
conversion of 1a was achieved after 1 h with a product
pattern very similar to that encountered in the micro-
wave reaction.24
This report is addressing the synthesis of dienamides
and the impact of a set of catalytic palladium systems
on the selective vinylic substitution of the R-hydrogen of
three different N-alkylated enamides. We report herein
(1) a new bidentate ligand-controlled, regioselective
synthesis of 2-acylamino-1,3-butadienes, (2) the synthesis
and examination of three fluorous-tagged dppp (F-dppp)
derivatives, and (3) the effect of microwave heating
(Mw∆).
Use of the identical reaction system with the cyclic
enamides (2b and 2c) improved yields but afforded a
decreased selectivity for the branched 3b and 3c (entries
5, 7, and 8).25
Resu lts
In ter n a l Vin yla tion s. The preparative results of the
Heck reactions of three different vinyl triflates 1a -c with
the electron-rich enamides 2a -c (Chart 1) are presented
in eq 1 and Table 1. The triflates 1a -c (1.0 equiv) were
With the objective to suppress the products derived
from hydrogenolysis followed by aromatization (2-meth-
oxynaphthalene formation) and homocoupling in the
Heck vinylations of the more reactive 1b and the enam-
ides 2a -c, the dppp ligand was displaced with rac-
binap (entries 9-13).10,26 The change in catalytic sys-
tem reduced the byproduct formations and improved
the yields of 4a -c but resulted in a slightly slower
vinylation. However, increasing the temperature to
70-90 °C did not adversely affect the desired R-selectivity
(the R/â-ratio was constantly a very impressive >99/1).
The low isolated yield of 4a with microwave heating
(45%, entry 10) was a consequence of a higher degree of
hydrogenolysis followed by aromatization at the elevated
temperature.
The progesterone dienyl triflate 1c exhibited a similar
reactivity as the vinyl triflate 1a , but with a lower
tendency to form the corresponding homocoupled byprod-
uct. Compared to 1a , the triflate 1c was also less prone
to form the terminal coupling products, and the use of
the previously more demanding cyclic enamides 2b-c did
not reduce the regioselectivity.
F lu or ou s Cou p lin gs. When the fluorous F-dppp
ligand 6a was used in the vinylations of 1a and 1c, two
conclusions become apparent. First, the performance was
very similar to nonfluorous dppp, although the selectivity
was slightly lower (Table 1, entries 3, 4, 6, and 16).
Second, all free 6a , palladium-complexed 6a , and oxidized
6a were easily removed from the reaction medium by
direct solid fluorous phase separation using a 90%
methanol-10% water eluting system.27 The methanol
was thereafter removed under reduced pressure and the
salts were withdrawn by a water/ether extraction. Reso-
mixed with 3 mol % Pd(OAc)2 as palladium source, 9 mol
% bidentate ligand,19,20 1.2 equiv triethylamine, and 2.5
equiv of the olefins 2a -c in dry DMSO to give the
dienamides 3-5. Three different bidentate ligands were
used in the reactions, dppp,21 6a (F-dppp, p-C4F9), and
rac-binap21 (Table 1). The reactions were conducted under
nitrogen at 60-70 °C with classic oil-bath heating (C∆)
overnight22 or at 90 °C with 15-30 min of controlled
microwave heating. Employing standard heating and
dppp, high regioselectivity (R/â ) 96/4) was obtained with
triflate 1a and olefin 2a (entry 1). The enamide 2a
afforded a less selective mixture of regioisomers when
the reaction time was reduced by heating to 90 °C (entry
2).23 The relatively moderate yield (53%) of the diene-
amide 3a at 60 °C reaction temperature were attributed
(18) Curran, D. P.; Luo, Z. J . Am. Chem. Soc. 1999, 121, 9069-
9072.
(19) Amatore and J utand have recently demonstrated that 3 equiv
of dppp react with 1 equiv Pd(OAc)2 to afford Pd(0)(dppp)2 and dppp
monoxide in DMF. Thus, 1 equiv or (3 mol % dppp) is consumed in
the generation of the active Pd(0) catalyst.
(20) Amatore, C.; J utand, A.; Thuilliez, A. Organometallics 2001,
20, 3241-3249.
(21) dppp ) 1,3-bis(diphenylphosphino) propane, rac-binap ) race-
mic-2, 2′-bis(diphenylphosphino)-1,1′-binaphthyl.
(24) When monitoring the reaction mixture at 0, 15, 30, 45, and 60
min, the product 3a /homocoupling byproduct ratio increased signifi-
cantly according to GC/MS.
(22) Noncomplete consumption of the vinyl triflates (1a -c) was
observed after 6 h by GC/MS.
(25) Employing 18.0 mol % instead of 9.0 mol % dppp at 60 °C
(23) In an attempt to optimize the reaction further, we investigated
1,2,2,6,6-pentamethylpiperidine (PMP), diisopropylethylamine, dicy-
clohexane methylamine, proton sponge, or potassium carbonate as
different bases, but with no significant effect on selectivity and rate.
Exchanging Pd(OAc)2 with Pd2dba3 as palladium source retarded the
reaction rate drastically. The ligand 1,1′-bis(diphenylphosphino)-
ferrocene (dppf) performed similar to dppp, but binap decreased the
reaction rate with no effect on the selectivity. Applying the ionic liquid
bmimPF6 solvent retarded the reaction rate strongly.
resulted in a much slower (44 h) but equally selective internal
vinylation of vinyl triflate 1a (R/â ) 92/8). Unfortunately, massive
homocoupling reduced the yield of product 3b (36% isolated yield).
(26) The use of dppp with 1b under standard conditions (3 mol %
Pd(OAc)2, 9 mol % dppp) with classic heating afforded lower GC/MS
yields of dienamide 4 due to competing hydrogenolysis followed by
aromatization and homocoupling (44% yield of 4b at 60 °C and 48%
yield of 4c at 60 °C). The R/â regioselectivities were in all cases >99/1.
(27) Curran, D. P. Synlett 2001, 1488-1496.
6640 J . Org. Chem., Vol. 68, No. 17, 2003

Regioselective Heck Vinylation with Enamides
TABLE 1. In ter n a l Heck Vin yla tion of En a m id es w ith Vin yl Tr ifla tesa
a
Reaction conditions: The reactions were performed in 1.0 mmol scale with 1.0 equiv of 1a -c, 2.5 equiv of 2a -c, 3 mol % of Pd(OAc)2,
b
9 mol % of the bidentate ligand, and 1.2 equiv of Et3N in DMSO under N2. The regioselectivity (R/â ) internal/terminal) was determined
with 1H NMR and GC/MS of the crude product mixture. c >95% pure of the internal product (3-5) according to GC/MS or LC/MS.
nances from the phosphine-based ligand could not be
Selection of F -d p p p Liga n d s. To improve the sepa-
ration of the phosphine ligand from the reaction mixture,
we initially studied three new fluorous-tagged dppp
derivatives (6a -c, Table 2). These fluorous diphenylphos-
phinopropanes, with different fluorous content and tag-
ging position on the phenyl groups, were initially inves-
tigated in both an internal arylation and in the herein
reported Heck vinylation reaction (Tables 2 and 3). In
the coupling between the electron-rich butyl vinyl ether
(2d ) with 1-naphthyl triflate (1d ), 6a (F-dppp p-C4F9)
behaved similarly to the nonfluorous dppp (Table 2, entry
2). The arylation occurred smoothly in DMF with full
conversion and excellent regiocontrol. Applying the phos-
phine ligands with heavier fluorous tails, 6b,c, reduced
the reaction rate and decreased the selectivity (entries 3
1
detected in neither 31P nor H NMR spectra of the crude
product. Subsequent elution of the fluorous solid-phase
cartridge with THF provided a complicated phosphine
mixture according to 31P NMR analysis. Attempts to
reuse the isolated phosphine mixture as the catalytic
system in a second vinylation with 1a and 2b furnished
no Heck addition product under standard conditions.
Similar observations were made in the previous work
applying monodentate fluorous-tagged ligands, and the
results suggest that the catalyst degrades during the
course of the reaction.28
(28) Zhang, Q.; Luo, Z.; Curran, D. P. J . Org. Chem. 2000, 65, 8866-
8873.
J . Org. Chem, Vol. 68, No. 17, 2003 6641

Vallin et al.
TABLE 2. In flu en ce of Differ en t F -d p p p Liga n d s on th e
Ar yla tion of Bu tyl Vin yl Eth er a
TABLE 4. Syn th esis of F lu or ou s
Dip h en ylp h osp h in op r op a n es (F -d p p p ’s)
entry
ligand
time (h)
R/âb
conv (%)c
1
2
3
4
5
dppp
5
5
84
20
20
>99/1
>99/1
60/40
79/21
>99/1
100
100
83
100
100
F-dppp p-C4F9, 6a
F-dppp m-C6F13, 6b
F-dppp p-C6F13, 6c
F-dppp p-C6F13, 6cd
a
The reactions were performed in 0.1 mmol scale with 3 mol %
of Pd(OAc)2 and 6 mol % of the bidentate ligand in DMF at 80 °C.
The regioselectivity was determined with GC/MS. c Conversion
Rf
product yield (%)a
product yield (%)b
b
of 1d was determined with 2,3-dimethylnaphthalene as internal
standard and GC/MS. 9 mol % of 6c.
p-CH2CH2C4F9
m-CH2CH2C6F13
p-CH2CH2C6F13
8a (72%)
8b (61%)
8c (58%)
6a (56%)
6b (57%)
6c (62%)
d
TABLE 3. In flu en ce of Differ en t F -d p p p Liga n d s on th e
Vin yla tion of 2a w ith 1a a
a
b
Isolated yield of 8a -c, calculated from 7a -c. Isolated yield
of 6a -c, calculated from 8a -c.
entry
ligand
time (h)
R/âb
conv (%)c
1
2
3
4
dppp
20
20
20
20
96/4
96/4
96/4
96/4
100
100
99
1,3-dibromopropane and reduction with trichlorosilane
then provided the fluorous dppp’s 6a -c in 56-62%
isolated yields.
F-dppp p-C4F9, 6a
F-dppp m-C6F13, 6b
F-dppp p-C6F13, 6c
100
a
The reactions were performed on 0.2 mmol scale with 3 mol
% of Pd(OAc)2 and 9 mol % of the bidentate ligand in DMSO at 60
Discu ssion
b
°C. The regioselectivity was determined with GC/MS. c Conver-
sion of 2a was determined with o-xylene as internal standard and
GC/MS.
A few reports on metal-catalyzed synthesis of alkoxy-
dienes and dienamides, primarily prepared for subse-
quent evaluation in Diels-Alder reactions, have ap-
peared in the literature.32-35 In view of the known
difficulties in preparing the 2-acylamino-1,3-butadienes,36
the reported direct Heck route from vinyl triflates and
enamides constitutes a valuable new method.
We believe that this bidentate ligand-controlled viny-
lation is subject to strong electronic control.2,4,6 Thus, in
the presence of a strongly coordinating bidentate ligand,
ionization occurs by dissociation of the weakly coordinat-
ing triflate counterion and a cationic π-complex is formed.4
Internal vinylation then occurs by insertion of the pal-
ladium atom to the electron-rich â-carbon with subse-
quent generation of the internal carbon-carbon bond.
The diene products 3-5 are thereafter liberated by
â-elimination. The slightly lower regioselectivity with
microwave heating is probably a consequence of the
higher reaction temperature that destabilizes the ligand
coordination to the palladium complex.15
and 4). Thus, the regiocontrol and catalytic activity were
lost when the C6F13 tail was attached in the meta position
to the phosphorus atom (ligand 6b, entry 3).29,30 Notably,
in the case of para-substituted 6c, full conversion of 1d
and higher R-selectivity could be achieved by increasing
the ligand/palladium ratio (entry 5).
The internal vinylation with 1a and 2a in DMSO
provided high regioselectivty and reactivity with both the
nonfluorous and fluorous ligands 6a -c (Table 3), but the
competing vinyl triflate homocoupling process increased
in the following order: dppp < 6a < 6b < 6c. Thus, the
lightly fluorinated ligand 6a was selected for continued
investigation due to this trend, but also because of
preparative convenience, high activity, and good regio-
control in the test reactions (Tables 2 and 3). The results
from the 1.0 mmol scale vinylation of enamides 2a ,b are
reported in Table 1.
Syn th eses of F -d p p p ’s. The preparation of fluorous
diphenylphosphinopropanes started with the reaction of
fluorinated aryllithium reagents derived from the corre-
sponding fluorinated aryl bromides 7a -c28 with dieth-
ylphosphoramidous dichloride (Table 4). The reaction
mixture was directly hydrolyzed with concentrated hy-
drogen chloride to give the fluorinated diarylphosphine
oxides 8a -c as white solids.31 Alkylation of 8a -c with
The higher reaction rate in the vinylation of 2a with
1a under microwave heating at 90 °C, compared to the
results of the classic heating method at the same tem-
perature, is difficult to interpret. We speculate that the
technical difficulties in correct temperature monitoring
have contributed to this inconsistency.11
(31) Compound 8b was previously reported by Francio and Leit-
ner: Francio, G.; Leitner, W. Chem. Commun. 1999, 1663-1664.
(32) Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1991,
32, 1579-1582.
(29) In contrast to ligand 6c, the regioselectivity in the reaction
between 1d and 2d in DMF did not improve at higher concentrations
of ligand 6b (9 mol %). We speculate that the poor R/â-ratio in the
arylation of 2d with 6b is a result of faster oxidation of 6b to the
corresponding dioxide in DMF than in DMSO (used in the vinylation
reactions). Rapid oxidation of 6b in CDCl3 at room temperature
furnished pure dioxide 9; see the Experimental Section.
(33) Occhiato, E. G.; Trabocchi, A.; Guarna, A. J . Org. Chem. 2001,
66, 2459-2465.
(34) Miniere, S.; Cintrat, J .-C. J . Org. Chem. 2001, 66, 7385-7388.
(35) Tanaka, R.; Hirano, S.; Urabe, H.; Sato, F. Org. Lett. 2003, 5,
67-70.
(30) Berners-Price, S. J .; Norman, R. E.; Sadler, P. J . J . Inorg.
Biochem. 1987, 31, 197-209.
(36) Overman, L. E.; Clizbe, L. A.; Freerks, R. L.; Marlowe, C. K. J .
Am. Chem. Soc. 1981, 103, 2807-2815.
6642 J . Org. Chem., Vol. 68, No. 17, 2003

Regioselective Heck Vinylation with Enamides
hydroxide. The fluorinated aryl bromides 7a -c were prepared
according to the previously described method.28 All Heck
vinylation reactions were performed using the appropriate
choice of classic heating time and temperature, or microwave
heating temperature and irradiation time, until the complete
consumption of the starting vinyl triflates. The bis-vinyl and
the oxidized bis-vinyl byproducts were detected by GC/MS and
LC/MS.
Gen er a l P r oced u r e for Cla ssic Syn t h esis of 2-Acyl-
a m in o-1,3-bu ta d ien es (3-5, Ta ble 1). A mixture of the vinyl
triflate (1.0 mmol), enamide (2.5 mmol), triethylamine (0.121
g, 1.2 mmol), Pd(OAc)2 (0.0067 g, 0.030 mmol), and bidentate
ligand (0.090 mmol) was stirred in 4.0 mL of dry DMSO under
N2 in a sealed 2.0-5.0 mL Smith process vial (for reaction time
and temperature, see Table 1). After complete conversion of
the starting vinyl triflate as analyzed by GC/MS or LC/MS,
the reaction mixture was allowed to cool.
The preparative vinylations at 60 °C provided signifi-
cantly larger amounts of homocoupled bis-vinyl byprod-
ucts than experiments at higher temperature. These
byproducts may be formed not only by direct homocoup-
ling but also after hydrogenolysis of the vinyl triflate,
producing the cyclic alkene, followed by a subsequent
Heck coupling with an intact triflate 1. The larger diene/
homocoupled byproduct ratio observed at higher temper-
atures may thus originate from a predominance of
enamide vinylation, as compared to the competing vinyl
triflate reduction.
Con clu sion
In summary, we have presented a novel palladium-
catalyzed procedure for synthesis of 2-acylamino-1,3-
butadienes from vinyl triflates and enamides. Although
only a limited number of examples are provided here, we
believe that the ease of operation and the high regiose-
lectivity will prove to be useful in synthetic work. The
fact that vinylations with fluorous ligands delivered
branched products in useful yields proves that the
cationic Heck cycle apparently can selectively operate
also with this new catalytic system. The use of rapid
microwave in-situ heating and fluorous solid phase
purification combines strategic features for reducing both
time and effort at both the reaction and separation
stages. Employing fluorous solid-phase purification is a
rapid and efficient method to completely remove the
fluorous-tagged phosphine ligand before subsequent prod-
uct isolation. We theorize that future work will also
deliver protocols for recycling of new catalytic systems
using microwave heating and fluorous technologies.
Wor k u p Meth od a . The reaction mixture containing dppp
or rac-binap was poured into 0.1 M NaOH and extracted with
diethyl ether. The combined organic layers were washed with
brine and dried over potassium carbonate.
Wor k u p Meth od b. When using fluorous-tagged 6a , the
reaction mixture was charged directly on to the fluorous
reverse phase silica gel and the organic mixture was eluated
with 200 mL, 90% methanol-10% water, to give an organic
fraction. The methanol was then removed under reduced
pressure and the salts were removed by ether extraction. The
combined ether layers were washed with brine, dried over
potassium carbonate, and concentrated. Subsequent elution
of the fluorous silica gel with 50 mL of 100% methanol
provided some of the homocoupled byproducts.
The product (3-5) was finally purified by column chroma-
tography (hexane:ethyl acetate).
Gen er a l P r oced u r e for Micr ow a ve Hea ted Syn th esis
of 2-Acyla m in o-1,3-bu ta d ien es (3a -c, 4a ,c, a n d 5a ) (Ta ble
1, En tr ies 2, 4, 6, 8, 10, 13, 15). The microwave-assisted
vinylation was performed as described under General Proce-
dure for Classic Synthesis of 2-Acylamino-1,3-butadienes, but
with controlled microwave heating in a single-mode synthe-
sizer. The products were purified as described for the conven-
tionally heated products.
Exp er im en ta l Section
Gen er a l. All Heck coupling reactions were conducted in
sealed process vials under nitrogen with magnetic stirring. The
1H NMR and 13C NMR spectra of the Heck coupling products
were recorded at 270 and 68 MHz or at 400 and 100 MHz,
respectively. The 1H, 13C, 19F, and 31P NMR of the fluorous
diphenylphosphinopropane compounds were recorded at 300,
75, 282.5, and 121.5 MHz, respectively. Chemical shifts are
reported as δ values (ppm) referenced to the following sol-
vent signals: CHCl3, δ 7.26; CDCl3, δ 77.0; CH3CN, δ 1.94;
CD3CN, δ 118.3. Mass spectra were recorded on a GC/MS,
equipped with a 25 m × 0.20 mm or a 30 m × 0.25 mm
capillary column, utilizing electron impact (EI) at an ionizing
energy of 70 eV. RP/HPLC/MS was performed in ESI mode,
on a C8 column (4.6 × 50 mm) using an CH3CN/H2O gradient
with 0.05% HCOOH, employing UV (214, 255 nm) and MS
detection. Fluorous solid-phase extractions were performed
with fluorous SPE Cartridges (5 g, 10 cm3) from Fluorous
Technologies Inc. Column chromatography was performed
using commercially available silica gel 60 (particle size 40-
63 µm) or prepacked silica columns (average particle size 53
µm). The microwave heating was performed in a single-mode
cavity producing controlled irradiation at 2450 MHz. Reaction
temperature and pressure were determined using the built-
in, on-line IR and pressure sensors.
r-Ar yla tion of Vin yl Eth er 2d w ith Na p h th yl Tr ifla te
1d (Ta ble 2). A mixture of 1d (0.028 g, 0.10 mmol), 2d (0.025
g, 0.25 mmol), triethylamine (0.012 g, 0.12 mmol), Pd(OAc)2
(0.0007 g, 0.003 mmol), and bidentate ligand (0.006 mmol) was
stirred at 80 °C, in 1.5 mL of dry DMF under N2 in a sealed
process vial (for reaction time and temperature see Table 2).
The conversion was determined with 2,3-dimethyl naphthalene
as internal standard.
r-Vin yla tion of En a m id e 2a w ith Vin yl Tr ifla te 1a
(Ta ble 3). The reaction of 1a and 2a was performed as
described under General Procedure for Classic Synthesis of
2-Acylamino-1,3-butadienes but on a 0.2 mmol scale (for
reaction time and temperature, see Table 3). The conversion
was determined with o-xylene as internal standard.
4-ter t-Bu tylcycloh ex-1-en yl tr iflu or om eth an esu lfon ate
(1a ): 1H NMR (CDCl3, 400 MHz) δ 5.73-5.75 (m, 1H), 2.27-
2.46 (m, 2H), 2.15-2.25 (m, 1H), 1.89-2.00 (m, 2H), 1.25-
1
1.42 (m, 2H), 0.88 (s, 9H). The H NMR data were confirmed
with COSY and HETCOR.
N-[1-(4-ter t-Bu t yl-1-cycloh exen -1-yl)vin yl]-N-m et h yl-
a ceta m id e (3a ): colorless oil; eluent hexane/ethyl acetate (8/2
v/v) with silica gel; 1H NMR (CDCl3) δ 5.80-5.85 (m, 1H), 5.17
(s, 1H), 4.96 (s, 1H), 3.01 (s, 3H), 3.06 (s, 3H), 2.26-2.32 (m,
1H), 2.07-2.20 (m, 2H), 1.94 (s, 3H), 1.83-1.98 (m, 2H), 1.12-
1.31 (m, 2H), 0.87 (s, 9H); 13C NMR (CDCl3) δ 170.8, 150.4,
131.5, 127.8, 110.2, 43.7, 35.9, 32.1, 27.2, 27.1, 26.6, 23.8, 21.2;
Ma ter ia ls. All reagents were obtained from commercial
sources and used without further purification. DMSO (H2O <
0.01%) was used as received, but tetrahydrofuran (THF) and
diethyl ether were freshly distilled from sodium benzophenone
ketyl under nitrogen. The vinyl triflates 1a -c are known
compounds and were prepared by literature procedures.37,38
The 1H NMR data obtained for 1a did not correspond to the
literature data.39 Triethylamine was distilled over potassium
(37) Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.;
Pietroni, B. R. J . Org. Chem. 1992, 57, 976-982.
(38) Pal, K. Synthesis 1995, 12, 1485-1487.
(39) Scott, W. J .; Crisp, G. T.; Stille, J . K. Org. Synth. 1990, 68,
116-129.
J . Org. Chem, Vol. 68, No. 17, 2003 6643

Vallin et al.
MS m/z (relative intensity 70 eV) 235 (49, M+), 220 (95), 56
(100). Anal. Calcd for C15H25NO: C, 76.55; H, 10.71; N, 5.95.
Found: C, 76.37; H, 10.51; N, 5.69.
1-[1-(20-Oxop r egn a -3,5-d ien -3-yl)vin yl]-2-p yr r olid in o-
n e (5b): pale yellow solid; eluent hexane/ethyl acetate (4/6,
v/v) with silica gel; 1H NMR (CDCl3) δ 5.93 (s, 1H), 5.52-5.55
(m, 1H), 5.30 (s, 1H), 5.02 (s, 1H), 3.49-3.61 (m, 2H), 2.49-
2.57 (m, 3H), 2.13 (s, 3H), 0.93 (s, 3H), 0.64 (s, 3H); 13C NMR
(CDCl3) δ 209.5, 174.6, 144.8, 141.4, 128.8, 127.0, 126.6, 110.0,
63.3, 57.0, 50.6, 48.0, 44.1, 38.8, 34.8, 33.6, 31.9, 31.7, 31.54,
31.46, 24.3, 23.0, 22.8, 21.1, 19.2, 18.7, 13.3. Anal. Calcd for
1-[1-(4-ter t-Bu tyl-1-cycloh exen -1-yl)vin yl]-2-p yr r olid i-
n on e (3b): colorless oil; eluent hexane/ethyl acetate (8/2 v/v)
with silica gel: 1H NMR (CDCl3) δ 5.74-5.76 (m, 1H), 5.18 (s,
1H), 4.93 (s, 1H), 3.46-3.56 (m, 2H), 2.47 (t, 2H, J ) 8.1 Hz),
2.22-2,30 (m, 1H), 1.98-2.18 (m, 4H), 1.81-1.92 (m, 2H),
1.08-1.30 (m, 2H), 0.83 (s, 9H); 13C NMR (CDCl3) δ 174.4,
144.9, 131.3, 126.5, 108.9, 50.4, 43.5, 32.1, 31.4, 27.1, 27.0, 26.7,
23.7, 18.6; MS m/z (relative intensity 70 eV) 247 (18, M+), 190
(37), 86 (100). Anal. Calcd for C16H25NO: C, 77.68; H, 10.19;
N, 5.66. Found: C, 77.43; H, 9.97; N, 5.76.
C
27H37NO2: C, 79.56; H, 9.15; N, 3.44. Found: C, 79.44; H,
9.03; N, 3.47.
1-[1-(20-Oxop r egn a -3,5-d ien -3-yl)vin yl]-2-a zep a n on e
(5c): pale yellow solid; eluent hexane/ethyl acetate (4/6, v/v)
with silica gel; 1H NMR (CDCl3) δ 5.95 (s, 1H), 5.50-5.54 (m,
1H), 5.26 (s, 1H), 4.99 (s, 1H), 3.35-3.48 (m, 2H), 2.61-2.66
(m, 2H), 2.52-2.57 (m, 1H), 2.13 (s, 3H), 0.91 (s, 3H), 0.64 (s,
3H); 13C NMR (CDCl3) δ 209.7, 175.6, 150.3, 141.6, 128.8,
127.1, 126.6, 110.1, 63.8, 57.1, 52.2, 48.1, 44.2, 38.9, 37.6, 34.9,
33.7, 32.1, 31.8, 31.7, 30.2, 28.7, 24.5, 23.7, 22.88, 22.87, 21.2,
19.2, 13.4. Anal. Calcd for C29H41NO2: C, 79.95; H, 9.49; N,
3.22. Found: C, 79.75; H, 9.28; N, 3.18.
1-[1-(4-t er t -Bu t yl-1-cycloh e xe n -1-yl)vin yl]-2-a ze p a -
n on e (3c): colorless oil; eluent hexane/ethyl acetate (7/3 v/v)
with silica gel; 1H NMR (CDCl3) δ 5.77-5.82 (m, 1H), 5.15 (s,
1H) 4.90 (s, 1H), 3.36-3.42 (m, 2H), 2.57-2.63 (m, 2H), 2.27-
2,35 (m, 1H), 2.09-2.20 (m, 2H), 1.83-1.94 (m, 2H), 1.64-
1.83 (m, 6H), 1.13-1.31 (m, 2H), 0.85 (s, 9H); 13C NMR (CDCl3)
δ 175.5, 150.4, 131.2, 126.5, 108.8, 52.1, 43.6, 37.5, 32.1, 30.1,
28.7, 27.14, 27.13, 26.6, 23.8, 23.5; MS m/z (relative intensity
Bis[4-(3,3,4,4,5,5,6,6,7,7,8,8,8-Tr idecaflu or ooctyl)ph en yl]-
p h osp h in e Oxid e (8c). To a 250 mL, three-neck flask with
t-BuLi (17.7 mL, 1.7 M in pentane, 30.0 mmol) at -78 °C was
added dropwise a solution of 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tri-
decafluorooctyl)phenyl bromide (7c, 7.54 g, 15.0 mmol) in dry
diethyl ether (100 mL). After the addition was complete, the
mixture was warmed to 0 °C in 30 min. Diethylphosphor-
amidous dichloride (1.0 mL, 13.5 mmol) was then added
slowly to the reaction mixture at 0 °C. The resulting mix-
ture was further stirred at 0 °C overnight. Concentrated
aqueous hydrogen chloride (2.0 mL, 24.0 mmol) was then
added and the mixture was stirred at room temperature for
4 h. The reaction was quenched by adding H2O (50 mL). The
ether layer was separated and the aqueous layer was fur-
ther extracted with ether (50 mL) three times. The com-
bined ether layers were washed with brine and dried over
magnesium sulfate. After evaporation of the solvent under
vacuum, the residue was purified by column chromatography
on silica gel (hexane/EtOAc ) 10:1) and further purified by
recrystallization from pentane to give product 8c (4.68 g, 78%)
as a white solid: 1H NMR (300 MHz, CDCl3) δ 2.39 (tt, J )
18.0, 8.7 Hz, 4H), 2.96-3.02 (m, 4H), 7.38 (dd, J ) 8.1, 2.1
Hz, 4H), 7.67 (dd, J ) 13.8, 8.1 Hz, 4H), 8.08 (d, J ) 481.8
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 26.6, 32.5 (t, J FC ) 22.5
Hz), 105.2-121.3 (m, C6F13), 129.0 (d, J PC ) 12.0 Hz), 129.9
(d, J PC ) 105.0 Hz), 131.3 (d, J PC ) 11.5 Hz), 144.3; 19F NMR
(282.5 MHz, CDCl3) δ -125.0 (4F), -122.3 (4F), -121.7 (4F),
-120.7 (4F), -113.4 (4F), -79.6 (6F); 31P NMR (121.5 MHz,
CDCl3) δ 21.4 (s); FAB-MS m/z 895 (M + H)+; HRMS (FAB)
for C28H18F26OP (M + H)+ calcd 895.0680, found 895.0672.
Anal. Calcd for C28H18F26OP: C, 37.60; H, 1.92. Found: C,
37.67; H, 1.96.
70 eV) 275 (88, M+), 218 (56), 96 (100). Anal. Calcd for C18H29
-
NO: C, 78.49; H, 10.61; N, 5.09. Found: C, 78.17; H, 10.40;
N, 5.21.
N-[1-(6-Meth oxy-3,4-d ih yd r o-1-n a p h th a len yl)vin yl]-N-
m et h yla cet a m id e (4a ):40 colorless oil; eluent hexane/ethyl
acetate (8/2 v/v) with silica gel; 1H NMR (CDCl3) δ 7.29 (d,
1H, J ) 8.5 Hz), 6.77 (d, 1H, J ) 2.7), 6.72 (dd 1H, J ) 8.5,
2.7 Hz), 6.04 (t, 1H, J ) 4.9 Hz ), 5.35 (s, 1H), 5.18 (s, 1H),
3.81 (s, 3H), 3.06 (s, 3H), 2.71 (t, 2H, J ) 7.7 Hz), 2.25-2.31
(m, 2H), 2.15 (s, 3H); 13C NMR (CDCl3) δ 171.0, 158.7, 147.5,
139.2, 134.8, 126.7, 126.0, 125.9, 113.9, 112.4, 111.0, 55.2, 35.3,
28.5, 23.2, 21.9; MS m/z (relative intensity 70 eV) 257 (70, M+),
214 (48), 56 (100); HRMS (EI+) calcd for C16H19NO2 (M+)
257.1416, found 257.1416.
1-[1-(6-Meth oxy-3,4-d ih yd r o-1-n a p h th a len yl)vin yl]-2-
p yr r olid in on e (4b):40 colorless oil; eluent hexane/ethyl ac-
1
etate (8/2 v/v) with silica gel; H NMR (CDCl3) δ 7.29 (d, 1H,
J ) 8.4 Hz), 6.77 (d, 1H, J ) 2.6), 6.72 (dd 1H, J ) 8.4, 2.6
Hz), 6.04 (t, 1H, J ) 4.7 Hz ), 5.40 (s, 1H), 5.10 (s, 1H), 3.78
(s, 3H), 3.35 (t, 2H, J ) 7.0 Hz), 2.75 (t, 2H, J ) 7.8 Hz), 2.41
(t, 2H, J ) 8.1 Hz), 2.25-2.32 (m, 2H), 1.82-1.91 (m, 2H); 13
C
NMR (CD3CN) δ 174.4, 159.7, 144.6, 139.0, 137.5, 127.5, 127.0,
125.7, 114.4, 112.1, 104.9, 55.7, 49.0, 32.8, 28.8, 23.6, 18.6; MS
m/z (relative intensity 70 eV) 269 (100, M+), 254 (42), 184 (26).
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found:
C, 75.64; H, 6.95; N, 5.29.
1-[1-(6-Meth oxy-3,4-d ih yd r o-1-n a p h th a len yl)vin yl]-2-
a zep a n on e (4c):40 colorless oil; eluent hexane/ethyl acetate
1
(6/4 v/v) with silica gel; H NMR (CD3CN) δ 7.20 (d, 1H, J )
8.5 Hz), 6.75 (d, 1H, J ) 2.7), 6.69 (dd 1H, J ) 8.5, 2.7 Hz),
6.05 (t, 1H, J ) 4.8 Hz ), 5.22 (s, 1H), 5.09 (s, 1H), 3.74 (s,
3H), 3.36-3.40 (m, 2H), 2.68 (t, 2H, J ) 7.8 Hz), 2.45-2.50
(m, 2H), 2.18-2.25 (m, 2H), 1.55-1.61 (m, 4H), 1.37-1.45 (m,
2H); 13C NMR (CD3CN) δ 175.7, 159.8, 148.2, 139.5, 137.6,
128.1, 127.4, 127.3, 114.3, 112.4, 112.0, 55.8, 50.3, 38.6, 29.1,
28.7, 24.1, 23.9; MS m/z (relative intensity 70 eV) 297 (100,
M+), 184 (24), 96 (41). Anal. Calcd for C19H23NO2: C, 76.73;
H, 7.80; N, 4.71. Found: C, 76.50; H, 7.99; N, 4.50.
Bis[4-(3,3,4,4,5,5,6,6,6-n on a flu or oh exyl)p h en yl]p h os-
p h in e Oxid e (8a ). This was synthesized in a manner similar
to 8c. Diethylphosphoramidous dichloride (1.0 mL, 6.87 mmol)
and 7a (5.60 g, 13.9 mmol) were used to yield 8a (3.43 g, 72%)
as a white solid: 1H NMR (300 MHz, CDCl3) δ 2.39 (tt, J )
18.1, 8.6 Hz, 4H), 2.96-3.02 (m, 4H), 7.37 (dd, J ) 8.1, 2.1
Hz, 4H), 8.08 (d, J ) 481.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 26.5, 32.3 (t, J FC ) 22.0 Hz), 104.7-123.5 (m, C4F9), 129.0
(d, J PC ) 13.0 Hz), 130.4, 131.3 (d, J PC ) 11.7 Hz), 144.2 (d,
J PC ) 2.4 Hz); 19F NMR (282.5 MHz, CDCl3) δ -124.8 (4F),
-123.2 (4F), -113.6 (4F), -79.8 (6F); 31P NMR (121.5 MHz,
CDCl3) δ 21.4 (s); EIMS m/z 694 (M+), 447, 371; HRMS for
N-Meth yl-N-[1-(20-oxop r egn a -3,5-d ien -3-yl)vin yl]a cet-
a m id e (5a ): pale yellow solid; eluent hexane/ethyl acetate (7/
3, v/v) with silica gel; 1H NMR (CD3CN) δ 5.96 (s, 1H), 5.59-
5.63 (m, 1H), 5.33 (s, 1H), 5.12 (s, 1H), 2.95 (s, 3H), 2.56-2.61
(m 1H), 2.07 (s, 3H), 1.84 (s, 3H), 0.92 (s, 3H), 0.66 (s, 3H); 13
C
NMR (CD3CN) δ 209.8, 170.6, 151.4, 142.6, 130.5, 128.4, 128.1,
112.4, 64.1, 57.7, 49.0, 44.6, 39.4, 36.2, 35.6, 34.4, 32.7, 32.5,
31.7, 25.0, 23.5, 23.4, 21.9, 21.4, 19.4, 13.6. Anal. Calcd for
C
24H17OF18P calcd 694.0730, found 694.0742.
Bis[3-(3,3,4,4,5,5,6,6,7,7,8,8,8-tr idecaflu or ooctyl)ph en yl]-
p h osp h in e Oxid e (8b).31 This was synthesized in a manner
similar to 8c. Diethylphosphoramidous dichloride (0.86 g, 4.92
mmol) and 7b (4.95 g, 9.84 mmol) were used to yield 8b (2.68
g, 61%) as white solid: 1H NMR (300 MHz, CDCl3) δ 2.25-
2.45 (m, 4H), 2.51-2.56 (m, 4H), 7.46-7.75 (m, 8H), 8.10 (d,
J ) 480.0 Hz, 1H).
C
26H37NO2: C, 78.94; H, 8.43; N, 3.54. Found: C, 78.77; H,
9.51; N, 3.65.
(40) The products 4a -c were unstable and oxidized easily to the
1-hydroxy-1,2-dihydronaphthalene analogues or to the aromatic naph-
thalene analogues, specially 4a .
6644 J . Org. Chem., Vol. 68, No. 17, 2003

Regioselective Heck Vinylation with Enamides
1,3-Bis{bis(4-[(3,3,4,4,5,5,6,6,7,7,8,8,8-tr idecaflu or ooctyl)-
p h en yl]p h osp h in o}p r op a n e (6c). Bis[4-(3,3,4,4,5,5,6,6,7,7,-
8,8,8-tridecafluoroocty)phenyl]phosphine oxide 8c (2.38 g, 2.66
mmol) was dissolved in dry THF (15 mL) in a 50 mL three-
neck flask. To this solution sodium hydride (0.106 g, 60% on
oil, 2.66 mmol) was added at room temperature under argon.
The resulting mixture was stirred at room temperature for
30 min. A solution of 1,3-dibromopropane (268.9 mg, 1.33
mmol) in THF (1 mL) was then added to the reaction solution
slowly. The resulting mixture was stirred at room temperature
for 4 h. The reaction was quenched by adding water. THF was
partially removed under vacuum. The residue was extracted
with ethyl acetate three times. The combined ethyl acetate
layers were dried over magnesium sulfate. The solvent was
then removed. The residue was dried under vacuum overnight
before it was mixed with freshly distilled xylene (35 mL). To
this mixture, trichlorosilane (1.1 mL) and triethylamine (1.5
mL) were added under argon. The mixture was stirred at 100
°C for 1 h, 110 °C for 1 h, and then refluxed for 6 h. The
reaction solution was then cooled to room temperature and
30% sodium hydroxide aqueous solution (30 mL) was added.
The resulting mixture was then stirred at 60 °C until both
layers were clear. The organic layer was separated and the
aqueous layer was further extracted with toluene three times.
The combined organic layers were dried over magnesium
sulfate. The solvent was removed under vacuum. The residue
was purified by column chromatography on silica gel (hexane/
EtOAc ) 50:1) to give product 6c (1.34 g, 56%) as white solid:
1H NMR (300 MHz, CDCl3) δ 1.63 (q, J ) 6.6 Hz, 2H), 2.23 (t,
J ) 7.5 Hz, 4H), 2.38 (tt, J ) 18.1, 9.3 Hz, 8H), 2.89-2.95 (m,
8H), 7.18 (d, J ) 7.5 Hz, 8H), 7.33-7.37 (m, 8H); 13C NMR
(75 MHz, CDCl3) δ 22.4 (t, J ) 16.5 Hz), 26.2, 29.6 (t, J ) 11.6
Hz), 32.8 (t, J ) 21.9 Hz), 104.7-123.0 (m, C6F13), 128.4 (d, J
) 6.5 Hz), 133.2 (d, J ) 18.5 Hz), 136.7 (d, J ) 11.6 Hz), 139.8;
19F NMR (282.5 MHz, CDCl3) δ -124.8 (8F), -121.8 (8F),
-121.5 (8F), -120.8 (8F), -113.7 (8F), -79.8 (12F); 31P NMR
(121.5 MHz, CDCl3) δ -18.2 (s); FAB-MS m/z 1797 (M + H)+.
Anal. Calcd for C59H38F52P2: C, 39.44; H, 2.13. Found: C,
39.63; H, 2.21.
7.8 Hz, 4H), 7.33-7.38 (m, 8H); 13C NMR (75 MHz, CDCl3) δ
22.4, 26.4, 29.5 (t, J ) 11.9 Hz), 32.8 (t, J ) 21.7 Hz), 107.2-
123.3 (m, C4F9), 128.7 (d, J ) 7.1 Hz), 133.3 (d, J ) 18.3 Hz),
136.1 (d, J ) 9.0 Hz), 140.2; 19F NMR (282.5 MHz, CDCl3) δ
-124.5 (8F), -123.3 (8F), -113.7 (8F), -79.9 (12F); 31P NMR
(121.5 MHz, CDCl3) δ -18.1 (s); EIMS m/z 1396 (M+), 1073.
Anal. Calcd for C51H38F36P2: C, 43.86; H, 2.74. Found: C,
43.80; H, 2.60.
1,3-Bis{bis[3-(3,3,4,4,5,5,6,6,7,7,8,8,8-tr idecaflu or ooctyl)-
p h en yl]p h osp h in o}p r op a n e (6b). This was synthesized in
a manner similar to 6c. Compound 8b (0.81 g, 0.90 mmol) was
used to yield 6b (0.46 g, 57%) as colorless oil: 1H NMR (300
MHz, CDCl3) δ 1.78-1.84 (m, 2H), 2.34-2.54 (m, 12H), 2.96-
3.01 (m, 8H), 7.27-7.39 (m, 16H); 13C NMR (75 MHz, CDCl3)
δ 22.8 (t, J FC ) 17.4 Hz), 26.6, 29.7 (d, J PC ) 12.2 Hz), 33.0 (t,
J FC ) 22.0 Hz), 105.0-121.6 (m, C6F13), 128.8, 129.1 (d, J PC
)
5.8 Hz), 131.1 (d, J PC ) 16.3 Hz), 133.1 (d, J PC ) 20.8 Hz),
139.4 (d, J PC ) 16.4 Hz), 139.7 (d, J PC ) 7.2 Hz); 19F NMR
(282.5 MHz, CDCl3) δ -122.2 (8F), -119.2 (8F), -118.7 (8F),
-117.7 (8F), -110.4 (8F), -77.4 (12F); 31P NMR (121.5 MHz,
CDCl3) δ -16.2 (s); FAB-MS m/z 1796 (M+), 1373, 919. Anal.
Calcd for C59H38F52P2: C, 39.44; H, 2.13. Found: C, 39.33; H,
2.32.
1,3-Bis{bis-[3-(3,3,4,4,5,5,6,6,7,7,8,8,8-tr idecaflu or oocty)-
p h en yl]p h osp h in oxid e}p r op a n e (9): dioxidized 6b, pale
red oil; 1H NMR (300 MHz, CDCl3) δ 1.91-2.10 (m, 2H), 2.21-
2.58 (m, 12H), 2.83-3.01 (m, 8H), 7.33-7.70 (m, 16H); 13C
NMR (75 MHz, CDCl3) δ 14.8, 26.4 (t, J FC ) 4.3 Hz), 30.0 (d,
J PC ) 71.0 Hz), 32.5 (t, J FC ) 22.0 Hz), 105.0-124.0 (m, C6F13),
128.8 (d, J PC ) 10.4 Hz), 129.1 (d, J PC ) 12.2 Hz), 130.6 (d,
J PC ) 8.5 Hz), 132.0 (d, J PC ) 2.4 Hz), 133.0 (d, J PC ) 98.3
Hz), 140.0 (d, J PC ) 11.0 Hz); 19F NMR (282.5 MHz, CDCl3) δ
-122.8 (8F), -120.0 (8F), -119.5 (8F), -118.5 (8F), -111.2
(8F), -77.4 (12F); 31P NMR (121.5 MHz, CDCl3) δ 38.7 (s);
HRMS (FAB) for C59H39F52O2P2 (M + H)+ calcd 1829.1595,
found 1829.1590.
Ack n ow led gm en t. We gratefully acknowledge the
support from the Swedish Natural Science Research
Council. We also thank PersonalChemistry AB for pro-
viding us with the SmithSynthesizer and Dr. Kristofer
Olofsson for creative discussions.
1,3-Bis{bis-[4-(3,3,4,4,5,5,6,6,6-n on a flu or oh exyl)p h en yl]-
p h osp h in o}p r op a n e (6a ). This was synthesized in a manner
similar to 6c. Compound 8a (1.25 g, 1.80 mmol) was used to
yield 8b (0.642 g, 51%) as colorless oil: 1H NMR (300 MHz,
CDCl3) δ 1.63 (q, J ) 6.9 Hz, 2H), 2.23 (t, J ) 7.2 Hz, 4H),
2.38 (tt, J ) 18.0, 9.0 Hz, 8H), 2.89-2.95 (m, 8H), 7.18 (d, J )
J O034265I
J . Org. Chem, Vol. 68, No. 17, 2003 6645