Stereoselective Synthesis of Stannyl Enones via Palladium-Catalyzed and Free Radical Hydrostannation of Alkynyl Ketones with Trineophyltin Hydride

Article abstract of DOI:10.1021/jo035396m

A study on the addition of trineophyltin hydride (1) to alkynones under free radical (AIBN and Et3B) and palladium-catalyzed [(PPh₃) ₂PdCl₂] conditions is reported. The results obtained indicate that the addition of 1 to eight ynones catalyzed by bis(triphenylphosphine)palladium(II) chloride led in all cases to addition products in very high yields (80-96%). These additions take place with excellent regio- and stereochemistry, leading to the α adducts as major products in seven out of the eight cases studied. Also the E adducts, resulting from a syn attack, were the only (seven cases) or the predominant (one case) products. The radical hydrostannations initiated by AIBN of ynones 2-5 with 1 led to addition products in good yields (60-88%); with the more hindered ketones 6 and 7-9 the yields obtained were lower. The radical additions initiated by triethylboron to ynones 2-6 follow a similar pattern but with lower yields; no addition products in the hydrostannation of ynones 7-9 were detected. The new acyl-substituted vinylstannanes, owing to their greater stability compared with that of their tributyl- and trimethylstannyl analogues, can be purified by column chromatography using neutral alumina (in all cases) or silica gel 60 (in most cases) as adsorbents. Full ¹H, ¹³C, and ¹¹⁹Sn NMR data are given.

Full text of DOI:10.1021/jo035396m

Ster eoselective Syn th esis of Sta n n yl En on es via
P a lla d iu m -Ca ta lyzed a n d F r ee Ra d ica l Hyd r osta n n a tion of
Alk yn yl Keton es w ith Tr in eop h yltin Hyd r id e
Ver o´ nica I. Dodero,†,‡ Liliana C. Koll,†,‡ M. Bel e´ n Faraoni, Terence N. Mitchell,* and
†
,§
J ulio C. Podest a´ *,
†,‡
Departamento de Qu ´ı mica, Universidad Nacional del Sur, Avenida Alem 1253, 8000 Bah ´ı a Blanca, and
CONICET Buenos Aires, Argentina, and Fachbereich Chemie Universit a¨ t Dortmund,
D-44221 Dortmund, Germany
jpodesta@uns.edu.ar
Received September 24, 2003
A study on the addition of trineophyltin hydride (1) to alkynones under free radical (AIBN and
Et B) and palladium-catalyzed [(PPh ) PdCl ] conditions is reported. The results obtained indicate
3 3 2 2
that the addition of 1 to eight ynones catalyzed by bis(triphenylphosphine)palladium(II) chloride
led in all cases to addition products in very high yields (80-96%). These additions take place with
excellent regio- and stereochemistry, leading to the R adducts as major products in seven out of
the eight cases studied. Also the E adducts, resulting from a syn attack, were the only (seven cases)
or the predominant (one case) products. The radical hydrostannations initiated by AIBN of ynones
2
-5 with 1 led to addition products in good yields (60-88%); with the more hindered ketones 6
and 7-9 the yields obtained were lower. The radical additions initiated by triethylboron to ynones
-6 follow a similar pattern but with lower yields; no addition products in the hydrostannation of
2
ynones 7-9 were detected. The new acyl-substituted vinylstannanes, owing to their greater stability
compared with that of their tributyl- and trimethylstannyl analogues, can be purified by column
chromatography using neutral alumina (in all cases) or silica gel 60 (in most cases) as adsorbents.
1
13
119
Full H, C, and Sn NMR data are given.
In tr od u ction
thesis of R- and â-stannyl enones has been carried out,
mostly in more than one step, by hydrostannation of
propargyl alcohols followed by oxidation of the vinyltin
Stannyl enones are compounds of importance in or-
ganic synthesis, for example, in the synthesis of natural
products of pharmacological interest. R-Stannyl enones
4
adducts, the photooxygenation of vinyl stannanes fol-
1
5
lowed by dehydration of the resulting hydroperoxides,
are considered synthetic equivalents of the anions of R,â-
enones. Hydrostannation of alkynyl ketones is the short-
est route to stannyl enones. Thus, the synthesis of
R-stannyl enones has been carried out by palladium(0)-
and palladium(II)-catalyzed hydrostannation of alkynones
with trimethyl- and tributyltin hydride.2 It should be
pointed out that the synthesis of these compounds
presents difficulties because of their instability; thus it
has been reported that some R-stannyl enones are
temperature-labile and so sensitive to acid conditions
that during the workup they tend to decompose and could
not be isolated pure.2 Among other methods, the syn-
the conjugate addition of the cuprate derived from copper-
1a
(I) thiophenoxide and Bu
3
SnLi to an ynone, and the
coupling of (E)-1,2-bis(tributylstannyl)ethene with acid
6
chlorides in the presence of palladium catalysts. We
could not find any reference to radical addition of
organotin hydrides to alkynones in the literature.
,3
7
In previous work, we have shown that hydrostanna-
tion of substituted alkynes with trineophyltin hydride (1)
leads stereoselectively and in high yields to vinylstan-
nanes that showed enhanced stability in comparison with
that of vinylstannanes resulting from the additions of the
more common triorganotin hydrides (Me, Bu, and Ph).
We thus considered it of interest to carry out a study on
the free radical and palladium-catalyzed addition of
trineophyltin hydride (1) to various alkynyl ketones. It
should be noted that, taking into account both the regio-
,3
†
Universidad Nacional del Sur.
CONICET (National Research Council).
University of Dortmund.
‡
§
(1) (a) Wipf, P.; Lim, S. J . Am. Chem. Soc. 1995, 117, 558. (b) Spino,
C.; Barriault, N. J . Org. Chem. 1999, 64, 5292. (c) Corey, E. J .;
Guzman-Perez, A.; Lazerwith, S. E. J . Am. Chem. Soc. 1997, 119,
1
(
1769. (d) Peel, M. R.; J ohnson, C. R. Tetrahedron Lett. 1986, 27, 5947.
e) Keck, G. E.; Burnett, D. A. J . Org. Chem. 1987, 52, 2958.
2) (a) Cochran, J . C.; Bronk, B. S.; Terrence, K. M.; Phillips, H. K.
(4) Konoike, T.; Araki, Y. Tetrahedron Lett. 1992, 33, 5093.
(5) Adam, W.; Klug, P. Synthesis 1994, 557.
(6) (a) Renaldo, A. F.; Labadie, J . W.; Stille, J . K. Org. Synth. 1988,
67, 86. (b) Echavarren, A. M.; P e´ rez, M.; Casta n˜ o, A. M.; Cuerva, J .
M. J . Org. Chem. 1994, 59, 4179.
(7) (a) Dodero, V. I.; Koll, L. C.; Mandolesi, S. D.; Podest a´ , J . C. J .
Organomet. Chem. 2002, 650, 173. (b) Dodero, V. I.; Mitchell, T. N.;
Podest a´ , J . C. Organometallics 2003, 22, 856.
(
Tetrahedron Lett. 1990, 31, 6621. (b) Zhang, H. X.; Guib e´ , F.; Balavoine,
G. J . Org. Chem. 1990, 55, 1857. (c) Smith, N. D.; Mancuso, J .; Lautens,
M. Chem. Rev. 2000, 100, 3257.
(3) Bellina, F.; Carpita, A.; Ciucci, D.; De Santis, M.; Rossi, R.
Tetrahedron 1993, 49, 4677.
1
0.1021/jo035396m CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/03/2003
J . Org. Chem. 2003, 68, 10087-10091
10087

Dodero et al.
F IGURE 1. Hydrostannation of 3-butyn-2-one under radical conditions. 119Sn NMR spectra: (A) addition of Nph
addition of Bu SnH.
SnH (1), (B)
3
3
SCHEME 1. syn a n d a n ti Ad d ition s of
Tr in eop h yltin Hyd r id e to Alk yn yl Keton es
additions (Figure 1) clearly show that the hydrostanna-
tion using hydride 1 (spectrum A) is more efficient and
selective than the addition of tributyltin hydride (spec-
trum B).
These spectra show that whereas the addition of
hydride 1 is very selective, giving a mixture of two
products in a ratio 96/4 (later we determined that they
were the Z-addition products), the addition of tributyltin
hydride leads to a mixture of various vinylstannanes: not
only vinyl ketones but also allyl alcohols, tin alkoxides,
and hexabutylditin (-81.7 ppm).
We then carried out a study on the addition of trine-
ophyltin hydride (1) to the following ynones: 3-butyn-2-
one (2), 3-pentyn-2-one (3), 3-octyn-2-one (4), 4-phenyl-
and stereochemistry of the addition of tin hydride 1, these
reactions could lead to four stereoisomers as shown in
Scheme 1.
3
2
-butyn-2-one (5), 1-phenyl-2-propyn-1-one (6), 1-phenyl-
-butyn-1-one (7), 1-phenyl-2-heptyn-1-one (8), and 1,3-
diphenyl-2-propyn-1-one (9). First we studied the additions
under radical conditions (Table 1, Methods A and B) of
Resu lts a n d Discu ssion
1
to the above-mentioned alkynes; the results obtained
are summarized in Table 1.
Because of the lack of information on the radical
additions of other organotin hydrides to alkynones, we
initially compared the addition of tributyltin hydride and
of trineophyltin hydride (1) to 3-butyn-2-one. The 1 Sn
NMR spectra of the crude products resulting from these
The Z geometry was assigned on the basis of the large
J (Sn,H) coupling constants, all of them over 112 Hz (see
3
19
Experimental Section, Table 2), which indicate the exist-
ence of trans H-C-C-Sn linkages in these compounds.
1
0088 J . Org. Chem., Vol. 68, No. 26, 2003

Stereoselective Synthesis of Stannyl Enones
TABLE 1. Tr in eop h yltin Hyd r id e (1) Ad d ition s to Alk yn yl Keton es
a
The reactions were carried out under a nitrogen atmosphere; ratio 1/alkyne ) 1. Method A: AIBN 0.01 equiv, without solvent. Method
b
B: triethylboron 0.1 equiv, in ethyl ether. Method C: (PPh3)2PdCl2 2% in THF. Yields of products isolated from chromatography except
when otherwise stated. In CDCl3; in ppm with respect to Me4Sn. In these cases Z(R) ) E(R). e From the H and/or
c
d
1
119
Sn NMR spectra
of the crude products. f No adduct formation was detected. g From the spectra of the mixture.
On the other hand, the E stereochemistry was assigned
taking into account that the observed J (Sn,H) coupling
constants were mostly around 65 Hz and, in one case,
of the vinyl carbons and the trineophyltin moiety at-
tached to the other vinyl carbon of these adducts. These
structures were confirmed by a detailed analyses of the
H and C NMR data (Supporting Information, Tables
2 and 3).
3
1
13
8
2.6 Hz (Supporting Information, Table 2), clearly indi-
cating a cis arrangement of the proton attached to one
J . Org. Chem, Vol. 68, No. 26, 2003 10089

Dodero et al.
SCHEME 2. Iod od esta n n yla tion s a n d Stille Rea ction s of Som e Acyl-Su bstitu ted Vin ylsta n n a n es
In Table 1, it can be seen that whereas the radical
hydrostannations initiated by AIBN (Method A) of ynones
On the other hand, the results obtained in the radical
additions initiated by triethylboron (Method B), although
disappointing from the point of view of the yields, showed
that in those cases where the addition took place (Table
1, ynones 2-6) in four out of five cases the predominant
products were those with the Z configuration. Also, in
four out of five cases the products of â regiochemistry
were obtained in higher proportion.
2
-5 with the organotin hydride 1 lead to addition
products in good to very good yields (60-88%), the yields
obtained with the more hindered ketones 6 (43%) and
7
-9 (6-25%) are lower. In Table 1 it can also be seen
that the radical additions initiated by triethylboron
Method B) to ynones 2-6 follow a similar pattern with,
(
in general, substantially lower yields. We could not detect
addition products in the hydrostannations of ynones 7-9
with hydride 1 using Method B.
As shown in Table 1, the palladium-catalyzed reactions
took place with excellent regio- and stereochemistry.
Thus, the R adducts were the major products in seven
out of the eight cases studied, and the E adducts,
resulting from a syn attack, were the only (seven cases)
or the predominant (one case) products of the hydrostan-
nations using trineophyltin hydride (1).
It should be mentioned that although these radical
additions led in most cases to mixtures of trineophyltin
adducts, we were able to separate and purify these by
column chromatography. This suggests that trineophyltin
adducts are more stable than their trimethyl- and tribu-
tyltin analogues, which have been reported to decompose
To test the chemical reactivity of the new trineophyl-
stannylenones, we carried out iododestannylations and
Stille reactions with some of them (Scheme 2). We found
that the reactions between iodine and adducts 21 and
24 lead selectively and almost quantitatively to the
2
8
during chromatographic purification or to isomerize.
The addition of 1 catalyzed by bis(triphenylphosphine)-
palladium(II) chloride to the same ynones 2-9 (Table 1,
Method C) led in all cases to addition products in very
high yields (80-96%). It should be noted that the yields
obtained in the palladium-catalyzed hydrostannations of
9
corresponding iodovinyl ketones 30 and 31, respectively.
2 3 2
On the other hand, whereas the PdCl (PPh ) -catalyzed
Stille reaction between adduct 10 and bromobenzene led
2
10
ynones using trimethyl- and tributyltin hydrides were
to (Z)-benzylideneacetone (32) in 83% yield, the reaction
between 30% and 37% lower than the yields obtained in
the additions of hydride 1.
of adduct 21 with bromobenzene gave (Z)-3,4-diphenyl-
3
-buten-2-one (33) (75%).11 These results clearly indicate
that the reactivity of the new trineophylstannylenones
is similar to that of the tributyl- and trimethylstannyle-
nones reported previously by other authors.
In the case of the radical additions initiated by AIBN,
in only three cases (Table 1, ynones 2, 3, 6) do the Z
adducts, resulting from an anti addition, predominate
over the E adducts. As in previous studies we have
demonstrated that the stereochemistry of these additions
The major advantages of the hydrostannation of ynones
with trineophyltin hydride are not only the higher yields
but the greater stability of the resulting adducts com-
pared with that of their tributyl- and trimethylstannyl
analogues. The stability of the trineophylstannylenones
enable their separation and purification by column
chromatography either using neutral alumina (in all
cases) or silica gel 60 (in most cases) as adsorbents, this
resulting in a dramatic improvement of the yields of pure
isolated compounds.
7
is anti; the mixtures of E and Z isomers obtained in the
additions to some of these carbonyl conjugated alkynes
probably arise from configurational instability of the
principally formed Z isomers. As for the regiochemistry,
a clear predominance of the R adducts (six out of eight
cases) over the â adducts is observed. The fact that the
1
2
bulk of the substituents R and R do not apparently have
any influence on the orientation of the addition suggests
that the predominance of the R adducts could be con-
nected with electronic factors.
(9) Huang, Y.-Z.; Shi, L.-L.; Li, S.-W.; Huang, R. Synth. Commun.
1
989, 19, 2639.
10) Xu, J .-H.; Wang, L.-Ch.; Xu, J .-W.; Yan, B. J . Chem. Soc., Perkin
(
(
8) Cochran, J . C.; Prindle, V.; Young, H. A.; Kumar, M. H.; Tom,
Trans. 1 1994, 571.
(11) J ohnson, C. R.; Adams, J . P.; Braun, M. P.; Senanayake, C. B.
W.; Wovkulich, P.; Uskokovic, M. R. Tetrahedron Lett. 1992, 33, 917.
S.; Petraco, N. D. K.; Mohoro, C.; Kelley, B. Synth. React. Inorg. Met.-
Org. Chem. 2002, 32, 885.
1
0090 J . Org. Chem., Vol. 68, No. 26, 2003

Stereoselective Synthesis of Stannyl Enones
Exp er im en ta l Section
g, 0.02 mmol) in dry THF (4 mL) under nitrogen was added
hydride 1 (0.519 g, 1 mmol), and the mixture was stirred at
room temperature for 1 h. The solution was diluted with
hexane (5 mL) and cooled in the refrigerator, and then the
residual Pd(0) was filtered through a porous plate. The solvent
NMR spectra were recorded on a 300-MHz instrument,
using CDCl
3
as solvent; chemical shifts (δ) are reported in ppm
1 13
with respect to TMS ( H and C) and with respect to Me
4
Sn
1
19
in the case of Sn NMR spectra. IR spectra were recorded on
a FT spectrometer. Mass spectra were obtained using a 70-eV
mass spectrometer. Irradiations were conducted in a reactor
equipped with four 250-W lamps with peak emition at 350 nm.
All the solvents and reagents used were analytical reagent
grade. Trineophyltin hydride (1) was prepared as described
119
was then distilled off under reduced pressure, and the Sn
NMR spectrum of the product showed that it consisted of only
one compound, (E)-3-(trineophylstannyl)-3-octen-2-one (17),
peak at -66.5 ppm. Column chromatography (silica gel 60) of
the crude product gave compound 17 pure (0.580 g, 0,9 mmol,
9
0%) in the fraction eluted with hexanes-ethyl ether (98:2).
1
2
previously. 3-Butyn-2-one (2) was purchased, and 3-pentyn-
Rep r esen ta tive Stille Cou p lin g Rea ction : Syn th esis
2
2
-one (3), 3-octyn-2-one (4), 4-phenyl-3-butyn-2-one (5), 1-phenyl-
-propyn-1-one (6), 1-phenyl-2-butyn-1-one (7), 1-phenyl-2-
14
of (Z)-4-P h en yl-3-bu ten -2-on e (32). To a mixture of bro-
2 3 2
mobenzene (0.083 g, 0.53 mmol), PdCl (PPh ) (0.014 g, 2%),
heptyn-1-one (8), and 1,3-diphenyl-2-propyn-1-one (9) were
prepared following known techniques.
and some crystals of 2,6-di-tert-butyl-4-methylphenol under
nitrogen was added a solution of 10 (0.340 g, 0.58 mmol) in
dry toluene (1.3 mL) at room temperature, and the mixture
was stirred for 30 h under reflux, with monitoring by TLC.
Column chromatography with silica gel 70-230 of the product
1
3
Ad d ition of Tr in eop h yltin Hyd r id e (1) to Yn on es
u n d er Ra d ica l Con d ition s. Typ ica l P r oced u r es. Meth od
A. A mixture of 1-phenyl-2-propyn-1-one (6) (0.130 g, 1 mmol),
hydride 1 (0.519 g, 1 mmol), and AIBN as a catalyst, under
nitrogen, was heated at 65 °C during 2.5 h. (This optimal time
of reaction and temperature was indicated in earlier experi-
ments in which the reaction was monitored by taking samples
at intervals and observing the disappearance of the Sn-H
9
gave compound 32 (0.064 g, 0.44 mmol, 83%) in the fraction
eluted with hexanes-ethyl ether (94:6).
Rep r esen ta tive Iod od esta n n yla tion Rea ction : Syn -
3
th esis of 1-Iod ovin ylp h en yl Keton e (31). To a solution of
2
0
-(trineophylstannyl)-1-phenyl-2-propen-1-one (24) (0.085 g,
.13 mmol) in dry CH Cl (1.5 mL) under nitrogen was added
1
absorption by IR and products formation by H NMR.) The
2
2
1
19
Sn NMR spectrum of the crude product showed that it
iodine (1.1 equiv, 0.04 g, 0.144 mmol). The mixture was stirred
consisted of two compounds: (Z)-3-(trineophylstannyl)-1-phen-
yl-2-propen-1-one (23), peak at -91.1 ppm (17%), and 2-(tri-
neophylstannyl)-1-phenyl-2-propen-1-one (24), peak at -66.3
ppm (83%). Column chromatography (silica gel 60) of the
mixture afforded compounds 23 (0.043 g, 0.07 mmol, 7%) and
at room temperature for 30 min, with monitoring of the
reaction by TLC. The iodovinyl ketone 318 was purified by
column chromatography with silica gel 70-230 eluting with
hexane (0.032 g, 0.12 mmol, 95%).
2
4 (0.234 g, 0.36 mmol, 36%) in the fractions eluted with
Ack n ow led gm en t. This work was supported by
CONICET (Capital Federal, Argentina), CIC (Buenos
Aires Province, Argentina), and Universidad Nacional
del Sur (Bah ´ı a Blanca, Argentina). We acknowledge a
research grant from Fundaci o´ n Antorchas (Argentina).
A travel grant to one of us (J .C.P.) from the Alexander
von Humboldt Foundation and fellowships from
CONICET and DAAD (Germany) to V.I.D. are also
gratefully acknowledged.
hexanes-ethyl ether (90:10).
Meth od B. To a solution of 3-butyn-2-one (2) (0.052 g, 0.77
mmol) and tin hydride 1 (0.400 g, 0.77 mmol) in dry ethyl ether
(3 mL) under nitrogen was added triethylboron (0.077 mmol,
0
.077 mL of a 1 M solution in hexane), and the mixture was
1
19
stirred for 3 h at room temperature. The Sn NMR spectrum
of the product showed that it consisted of only one compound,
(Z)-4-(trineophylstannyl)-3-buten-2-one (10), peak at -89.0
ppm. Column chromatography (neutral alumina) of the crude
product gave compound 10 pure (0.357 g, 0.608 mmol, 79%)
in the fraction eluted with hexanes-ethyl ether (95:5).
Ad d ition of Tr in eop h yltin Hyd r id e (1) to Yn on es
Catalyzed by Bis(tr iph en ylph osph in e)palladiu m (II) Ch lo-
r id e. Meth od C. To a solution of 3-octyn-2-one (4) (0.124 g, 1
mmol) and bis(triphenylphosphine)palladium(II) chloride (0.011
Su p p or tin g In for m a tion Ava ila ble: Characterization
1
13
data for the products including full H and C NMR spectra,
as well as mass spectra of the isolated pure compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O035396M
(
12) Chopa, A. B.; Z u´ n˜ iga, A. E.; Podest a´ , J . C. J . Chem. Res. (S)
989, 234.
13) Hanack, M., Hassdenteufel, J . R. Chem. Ber. 1982, 115, 764.
1
(14) McKean, D. R.; Parrinello, G.; Renaldo, A.; Stille, J . K. J . Org.
Chem. 1987, 52, 422.
(
J . Org. Chem, Vol. 68, No. 26, 2003 10091