6
714
J . Org. Chem. 1997, 62, 6714-6715
Ta ble 1. Th er m a l Allyla tion s of Ald eh yd es w ith
Th er m a l Allyla tion s of Ald eh yd es w ith a
F lu or ou s Allylsta n n a n e. Sep a r a tion of
Or ga n ic a n d F lu or ou s P r od u cts by Solid
(
C6F 13CH2CH2)3Sn CH2CHdCH2
liquid-liquid
extraction
fluorous solid
phase extraction
P h a se Extr a ction w ith F lu or ou s Rever se
P h a se Silica Gel†
aldehyde
crude purity, crude purity, isolated
entry
(R)
yield, %
%
yield, %
%
yield, %
a
b
c
d
e
f
pOMeC6H4
1-Naphthyl
PhCH2CH2
PhCH(CH3)
c-C6H11
61
92
82
83
85
88
93
94
94
93
98
95
80
60
100
98
76
84
100
79
100
91
93
70
70
71
Dennis P. Curran,* Sabine Hadida, and Mu He
a
a
a
Department of Chemistry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15260
55
40
62
90
98
80
85
88
pNO2C6H4
oNO2C6H4
g
94
Received J une 12, 1997
a
Mixture of syn/anti-isomers 1.6/1.
Successful methods for combinatorial or parallel syn-
thesis must couple efficient reaction chemistry with
simple purification methods. In the ideal scenario (which
is still difficult to reach for many kinds of reactions), the
product of the reaction should be in a different phase from
dendridic substrates from small organic molecules in
processes that resemble filtrations more than chromatog-
raphies.10
In this communication, we describe the synthesis of a
new fluorous allylstannane, (C F CH CH ) SnCH -
1
everything else remaining in the final reaction mixture.
6
13
2
2
3
2
When this goal is reached, the processing of a crude
reaction mixture through one or more simple phase
separation techniques (evaporation, extraction, filtration)
provides a pure product. The traditional use of organic
substrates, reactants, reagents, and catalysts is now
being augmented by analogous reaction components that
CHdCH (1) and show that its thermal reactions with
2
aldehydes are roughly comparable to the reactions with
1
1
the standard reagent Bu SnCH CHdCH 2 (eq 1a,b).
3
2
2
The fluorous and organic products of these reactions can
be separated by fluorous-organic liquid-liquid extrac-
tion or, more conveniently, by the new technique of
fluorous solid phase extraction (FSPE). This new sepa-
ration technique should dramatically expand the utility
and accelerate the development of fluorous synthesis
methods.
2
,3
3,4
are water soluble or are attached to insoluble or
5
soluble polymers. Each of these strategic modifications
is allied with a simple phase separation technique for
purification (for example, acid-base extraction or filtra-
tion).
6
The fluorous phase is emerging as a complement and
(1a)
supplement to the standard phases, and fluorous syn-
thesis techniques show promise for broader applica-
tions.1
,7,8
To date, the only separation technique allied
with fluorous synthesis has been organic-fluorous liquid-
liquid extraction. Recently, traditional acid-base liquid-
liquid extraction methods have been supplemented by
solid phase extraction (SPE) techniques.9 In these
techniques, ion exchange resins are used to “extract”
complementary functionalities out of the eluent and onto
the column. Erstwhile chromatographies are turned into
(
1b)
The fluorous allylstannane 1 was readily synthesized
by the reaction of allyl magnesium bromide with readily
available tris[2-(perfluorohexyl)ethyl]tin bromide ((C
CH CH SnBr). Preliminary attempts to conduct Lewis
6 13
F -
2
2 3
)
filtrations where the R
f
of a given subset of molecules is
acid promoted reactions with 1 gave mixed results;
however, we discovered that thermal allylations with 1
were roughly comparable to those with allyltributyltin.
All the allylation results with 1 are summarized in Table
(ideally) either 1 or 0 as determined by whether the
molecules and the eluent bear an acid or base functional-
ity complementary to the column or not. Similarly, size
exclusion chromatography has been used to separate
1
1
1
.
†
In an initial series of experiments, 3 equiv of fluorous
Dedicated to Professor Dieter Seebach on the occasion of his 60th
birthday.
allylstannane 1 and 1 equiv of an aldehyde were heated
for 3 d at 140 °C without solvent. The crude reaction
mixture was then partitioned between acetonitrile and
FC-72 (fluorohexanes). The layers were separated, and
after washing two more times with FC-72, the acetoni-
trile layer was evaporated to give the crude organic
product. The crude yield of each reaction was determined
by weighing, and the purity of each alcohol product 4 was
determined by GC analysis against authentic samples.
Most of the products were formed in reasonable yields
and purities. That the impurities in these alcohols are
not fluorous was clear from both weight and spectroscopic
analysis. Given the high molecular weight of the fluorous
piece, even relatively small amounts of fluorous impuri-
ties would quickly push the crude weight yield to exceed
(
1) Curran, D. P. ChemtractssOrg. Chem. 1996, 9, 75.
(2) Balkenhohl, F.; von dem Bussche-H u¨ nnefeld, C.; Lansky, A.;
Zechel, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2289.
3) Cheng, S.; Comer, D. D.; Williams, J . P.; Myers, P. L.; Boger, D.
L. J . Am. Chem. Soc. 1996, 118, 2567.
(
(
(
(
(
4) Thompson, L. A.; Ellman, J . A. Chem. Rev. 1996, 96, 555.
5) Gravert, D. J .; J anda, K. D. Chem. Rev. 1997, 97, 489.
6) Horvath, I. T.; Rabai, J . Science 1994, 266, 72.
7) Studer, A.; Hadida, S.; Ferritto, R.; Kim, S. Y.; J eger, P.; Wipf,
P.; Curran, D. P. Science 1997, 275, 823.
8) (a) Curran, D. P.; Hadida, S. J . Am. Chem. Soc. 1996, 118, 2531.
b) Curran, D. P.; Hoshino, M. J . Org. Chem. 1996, 61, 6480. (c) Studer,
(
(
A.; J eger, P.; Wipf, P.; Curran, D. P. J . Org. Chem. 1997, 62, 2917. (d)
Studer, A.; Curran, D. P. Tetrahedron, in press. (e) Larhed, M.;
Hoshino, M.; Hadida, S.; Curran, D. P.; Anders, H. J . Org. Chem., in
press.
(9) (a) Gayo, L. M.; Suto, M. J . Tetrahedron Lett. 1997, 38, 513. (b)
Siegel, M. G.; Hahn, P. J .; Dressman, B. A.; Fritz, J . E.; Grunwell, J .
R.; Kaldor, S. W. Tetrahedron Lett. 1997, 38, 3357. (c) Flynn, D. L.;
Crich, J . Z.; Devraj, R. V.; Hockerman, S. L.; Parlow, J . J .; South, M.
S.; Woodard, S. J . Am. Chem. Soc. 1997, 119, 4874. For related
techniques of polymer quenching, see (d) Kaldor, S. W.; Siegel, M. G.;
Fritz, J . E.; Dressman, B. A.; Hahn, P. J . Tetrahedron Lett. 1996, 37,
(10) Kim, R. M.; Manna, M.; Hutchins, S. M.; Griffin, P. R.; Yates,
N. A.; Bernick, A. M.; Chapman, K. T. Proc. Natl. Acad. Sci. U.S.A.
1996, 93, 10012.
7
193. (e) Booth, R. J .; Hodges, J . C. J . Am. Chem. Soc. 1997, 119, 4882.
(11) Daud e´ , G.; Pereyre, M. J . Organomet. Chem. 1980, 190, 43.
S0022-3263(97)01059-1 CCC: $14.00 © 1997 American Chemical Society