On the stereospecific conversion of proximally-oxygenated trisubstituted vinyltriphenylstannanes into stereodefined trisubstituted alkenes

Article abstract of DOI:10.1021/ol051935t

(Chemical Equation Presented) Allylically oxygenated vinyl α-triphenylstannanes such as 22 can be readily converted into vinyl iodides and thereafter stereodefined trisubstituted alkenes with retention of configuration.

Full text of DOI:10.1021/ol051935t

ORGANIC
LETTERS
2005
Vol. 7, No. 24
5373-5376
On the Stereospecific Conversion of
Proximally-Oxygenated Trisubstituted
Vinyltriphenylstannanes into
Stereodefined Trisubstituted Alkenes
Paschalis Dimopoulos, Audrey Athlan, Soraya Manaviazar, and Karl J. Hale*
The Christopher Ingold Laboratories, The Chemistry Department, UniVersity College
London, 20 Gordon Street, London WC1H 0AJ, United Kingdom
k.j.hale@ucl.ac.uk
Received August 10, 2005
ABSTRACT
Allylically oxygenated vinyl
r-triphenylstannanes such as 22 can be readily converted into vinyl iodides and thereafter stereodefined trisubstituted
alkenes with retention of configuration.
For the O-directed, Ph3SnH-mediated, free-radical hydrostan-
nation of disubstituted acetylenes to emerge as a reaction of
true practical significance for the preparation of trisubstituted
olefins, its vinyltriphenylstannane products must be readily
transformable into stereodefined vinyl iodides to allow
transition-metal-catalyzed cross-coupling processes to com-
plete the final alkene elaboration step (Scheme 1).1
problematic. However, not long after we commenced our
studies on the O-directed hydrostannation reaction with Ph3-
SnH and cat. Et3B, we came across a report by Marco-
Contelles and Malacria2 in which they showed that the
iododemetalation of vinyltriphenylstannanes could take a
most unexpected course when an allylic O-substituent was
in close proximity to the Ph3Sn moiety. Specifically, they
demonstrated that when the vinyltriphenylstannanes 5 and
6 were reacted with molecular I2 in CH2Cl2, a separable
mixture of the chloro(diphenyl)stannylidenes 7 and 8 was
obtained, as opposed to the two vinylic iodides that were
expected (see Scheme 2).
Scheme 1 O-Directed Alkyne Hydrostannation and the
Subsequent Elaboration into Target Trisubstituted Alkenes
In light of their results, we conducted an exhaustive search
of the literature to find examples of other allylically
oxygenated â- and R-vinyl triarylstannanes that had been
successfully converted to vinyl halides by the action of
electrophilic halogen sources. To our surprise, virtually all
of the work that had previously been published had focused
(1) (a) Part 1: Dimopoulos, P.; Athlan, A.; Manaviazar, S.; George, J.;
Walters, M.; Lazarides, L.; Aliev, A. E.; Hale, K. J. Org. Lett. 2005, 7,
5369. (b) Part 3: Dimopoulos, P.; George, J.; Tocher, D. A.; Manaviazar,
S.; Hale, K. J. Org. Lett. 2005, 7, 5377.
(2) Marco-Contelles, J.; Mainetti, E.; Fensterbank, L.; Malacria, M. Eur.
J. Org. Chem. 2003, 1759.
At the outset of our studies on the aforesaid sequence, we
did not anticipate that the conversion of our vinyltriphenyl-
stannane products into vinyl iodides would be especially
10.1021/ol051935t CCC: $30.25
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Scheme 2. Unexpected Course to Iododestannylation
Scheme 5. Tin-Iodine Exchange of Vinyltriphenylstannane
16 and the Stille Coupling of 17
on (Z)-disubstituted â-triarylstannyl allyl alcohols,3 which
invariably react with halogens (Scheme 3) to give vinyl
nor its spectroscopic or analytical data ever reported, it
remained unclear as to whether a vinyl iodide had ever
actually been produced in this process.
Because the propargylic-O atom of an alkylacetylene is
capable of coordinating to a Ph3Sn radical during its addition
to the acetylenic system, we became concerned that this very
same O-atom might strongly coordinate internally to the tin
center in our product R-vinyltriphenylstannanes. If this were
the case, then by analogy, one could expect the halogen-
tin exhange process to be potentially troublesome and
possibly yield vinyldiarylhalostannane products rather than
the desired vinylic halides.
Scheme 3. Attempted Halodemetalation of Various
â-Triphenylstannyl Allyl Alcohol Systems
In view of the enormous importance of this transformation
to the overall success of our new trisubstituted olefin
synthesis, we thought it essential that we unambiguously
determine the outcome of iododestannylation in R-triphenyl-
stannylalkene systems with an allylic O-substituent. The
present paper documents our findings in this respect and
provides, for the very first time, unambiguous proof that vinyl
iodides are indeed the favored products of iododestannylation
in such systems. We would also like to record here the
successful elaboration of these vinyl iodides into a range of
target trisubstituted alkenes by an assortment of Pd(0)-
catalyzed cross coupling techniques. As a result of the present
work, we can now claim to have successfully demonstrated
the great scope and worth of the O-directed, Ph3SnH-
mediated, alkyne hydrostannation reaction.
diarylhalostannyl alcohols as the preferred reaction products.
X-ray crystallographic studies on a significant number of
(Z)-disubstituted â-triarylstannylated allyl alcohols have
given valuable insights into this observed pattern of reactiv-
ity. It appears that in such systems, the central tin atom
always adopts a distorted trigonal bipyramidal geometry due
to strong internal coordination between the allylic OH and
the tin. Apparently, the latter greatly weakens the C-Sn bond
to the apical phenyl substituent, enabling it to be preferen-
tially cleaved by the halogen.
Our iododestannylation studies began with the vinylstan-
nane 16 (Scheme 5), which was dissolved in CH2Cl2, cooled
to -78 °C, and treated with 1.2 equiv of solid I2. After the
reaction mixture was warmed to rt and stirred for a further
40 min, TLC analysis revealed that a single faster moving
product had formed. After extractive workup and purification
by SiO2 flash chromatography, the alkene product was
isolated in 85% yield and was shown to be 17 by detailed
spectroscopic analysis. To confirm that 17 could be suc-
Surprisingly, only one R-triarylstannylated allylic alcohol
has ever been examined in the halodemetalation process viz.
(Z)-2-methyl-3-triphenylstannyl-3-penten-2-ol (15) with I2 in
CHCl3 (Scheme 4).4 Unfortunately, a structure was never
Scheme 4. Iododemetalation of Vinylstannane 15
(3) (a) Pan, H.; Willem, Meunier-Piret, J.; Gielen, M. Organometallics
1990, 9, 2199. (b) Gielen, M.; Lelieveld, P.; de Vos, D.; Pan, H.; Willem,
R.; Biesemans, M.; Fiebig, H. H. Inorg. Chim. Acta 1992, 196, 115. (c)
Kayser, F.; Biesemans, M.; Pan, H.; Gielen, M.; Willem, R. J. Chem. Soc.,
Perkin Trans. 2 1994, 297. (d) Kayser, F.; Biesemans, M.; Delmotte, A.;
Verbruggen, I.; De Borger, I.; Gielen, M.; Willem, R.; Tiekink, E. R. T.
Organometallics 1994, 13, 4026. (e) Dai, H. C.; Ying, Q. H.; Wang, X.
H.; Yue, S. M.; Pan, H. D.; Chen, X. Polyhedron 1998, 17, 2503.
(4) Willem, R.; Delmotte, A.; De Borger, I.; Biesemans, M.; Gielen, M.;
Kayser, F.; Tietink, E. R. T. J. Organomet. Chem. 1994, 480, 255.
assigned to the major alkene product of this reaction,
notwithstanding a claim being made that its triphenyltin
substituent had been successfully cleaved. Given that this
product was never isolated from the crude reaction mixture,
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Org. Lett., Vol. 7, No. 24, 2005

Scheme 6. Tin-Iodine Exchange of Vinyltriphenylstannane
19 and the Sonogashira Coupling of 20
Scheme 7. Tin-Iodine Exchange of Vinyltriphenylstannane
22 and 25 and Their Subsequent Stille Couplings To Give 24
and 27
cessfully converted into a representative target alkene, with
retention of olefin geometry, we examined its Stille coupling5
with vinyltri-n-butylstannane and catalytic (MeCN)2PdCl2 in
DMF at rt and observed that 18 was formed very cleanly in
77% yield.
We next addressed the iododestannylation of vinylstannane
19, whose sterically more encumbered 1,3-dioxolane system
was now derived from cyclohexanone (Scheme 6). As
previously, the desired tin-iodine exchange reaction with
I2 proceeded efficiently and with complete retention of
configuration; vinyl iodide 20 being isolated in 82% yield.
The latter was coupled to trimethylsilylacetylene, under
Pd(0)/Cu(I)-mediated Sonogashira conditions,6 using Et3N
as the base in DMF at 100 °C for 16 h. A single cross-
coupling product 21 emerged in 80% yield.
bromide that is generated after metal-halogen exchange
between 29 and 30.
Encouraged by these successes, we extended our iodode-
metalation studies to vinyl-R-triphenylstannanes in which the
1,3-dioxolane system was branched. With the methyl- and
phenyl-substituted vinyltriphenylstannanes 22 and 25 (Scheme
7), the expected vinyl iodides 23 and 26 were again formed
after I2 treatment and alkene geometry was preserved. We
also found that 22 could equally well be converted into 23
by the action of N-iodosuccinimide (NIS) in CH2Cl2 at 0 °C
(98%), although clearly this is a more expensive option than
I2. Happily, reasonable results were later obtained in the
Pd(0)-mediated sp3/sp2-Stille cross couplings that were
performed on 23 and 26 with Me4Sn, so long as both
reactions were effected in the presence of copper(I) iodide
and triphenylarsine in DMF at 100 °C.7
Scheme 8. Iododestannylation of Vinyltriphenylstannane 28
and the Negishi Coupling of 29
Given the present very high level of interest in sp3/sp2
cross couplings between vinyl halides and alkylzinc halides,
we iododestannylated 28 to obtain 29 and examined its
Negishi coupling8 with 30 (Scheme 8). Apart from obtaining
the desired cross-coupling product 31 in 37% yield, the
dehalogenated product 32 was also coproduced in 24% yield.
Presumably, 32 arises from protonation of the vinylzinc
Having confirmed that 1,3-dioxolane-containing vinyl
R-triphenylstannanes could successfully be converted into
representative trisubstituted alkenes in reasonable yield, we
(8) (a) Negishi, E.; Zhang, Y.; Cederbaum, F. E.; Webb, M. B. J. Org.
Chem. 1986, 51, 4080. (b) Negishi, E.; Ay, M.; Gulevich, Y. V.; Noda, Y.
Tetrahedron Lett. 1993, 34, 1437. (c) McMurry, J. E.; Bosch, G. K. J. Org.
Chem. 1987, 52, 4885. (d) Asao, K.; Iio, H.; Tokoroyama, T. Tetrahedron
Lett. 1989, 30, 6401. (e) Nakamura, E.; Sekiya, K.; Kuwajima, I.
Tetrahedron Lett. 1987, 28, 337. (f) Jackson, R. F. W.; Turner, D.; Block,
M. H. J. Chem. Soc., Chem. Commun. 1995, 2207. (g) Zhu, L.; Wehmeyer,
R. M.; Rieke, R. D. J. Org. Chem. 1991, 56, 1445. (h) Negishi, E.; Liu, F.
In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J.,
Eds.; VCH: Weinheim, 1998; p 1.
(5) Farina, V.; Krishnamurthy, V.; Scott, W. J. The Stille Reaction; John
Wiley & Sons: New York, 1998; p 1.
(6) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4465. (b) Sonogashira, K. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, p 521.
(7) For a previous example of the Ph3As/CuI/(MeCN)2PdCl2 being used
to mediate a Stille coupling, see; Gibbs, R. A.; Krishnan, U.; Dolence, J.
M.; Poulter, C. D. J. Org. Chem. 1995, 60, 7821.
Org. Lett., Vol. 7, No. 24, 2005
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Scheme 9. Conversion of Vinylstannane 33 into 36
Scheme 11. Conversion of 42 into 43, 45, and 47
next examined the iodinolysis of R-triphenylstannyl alkenes
with an allylic OH. The first system we investigated was
the vinyltriphenylstannane 33; it smoothly iododestannylated
in 86% yield (Scheme 9). Vinyl iodide 34 was subsequently
employed for a Suzuki coupling9 with 35, which furnished
36 in 78% yield.
with 30 also occurred cleanly (37%) but was slow due to
steric hindrance.
Finally, the iododemetalation of a vinyl R-triphenylstan-
nane with an allylic OPMB (PMB ) p-methoxybenzyl)
group was studied (Scheme 11). As expected, 42 reacted
readily. The resulting vinyl iodide 43 also successfully
engaged in Suzuki reactions9 to give 45 and 47, respectively,
in 70% and 90% yield.
In like fashion, the branched allylic alcohol 37 (Scheme
10) could be readily iododestannylated (91% yield), O-
Scheme 10. Iododestannylation of Vinyltriphenylstannane 37
In conclusion, we have demonstrated for the first time that
vinyl triphenylstannanes, with an allylic O-substituent R to
the tin residue, can successfully be converted into vinyl
iodides in good yield with retention of configuration by two
methods. We have also shown that the iodoalkene products
can be readily transformed into a variety of trisubstituted
alkenes through a range of Pd (0) catalyzed cross-coupling
techniques. As a result of our work, we have now demon-
strated the great synthetic worth of the O-directed, Ph3SnH-
mediated, free-radical hydrostannation process for stereode-
fined trisubstituted olefin construction.
and the Pd(0)-Mediated Carbonylation and Negishi Coupling of
39
Acknowledgment. We thank the EPSRC (Project Grants
GR/N20959/01 and GR/S27733/01), The University of
London Central Research Fund, Novartis Pharma AG, Merck
Sharp & Dohme (Harlow), and Pfizer (Sandwich) for their
generous financial support.
Supporting Information Available: Full experimental
1
procedures, 500 MHz H and 125 MHz 13C spectra, and
silylated (91% yield), and carbonylated (55% yield) to obtain
the enoate 40 as a single product. Negishi coupling9 of 39
HRMS spectra for all new compounds are provided. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(9) Reviews: (a) Suzuki, A. In Metal-Catalyzed Cross-Coupling Reac-
tions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; p
49. (b) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
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