Hydrozirconation of stannylacetylenes: A novel and highly efficient synthesis of 1,1-diiodo-, 1,1-dibromo-, and mixed (Z)- or (E)-1-iodo-1-bromo-1-alkenes using 1,1-hetero-bimetallic reagents [11]

Full text of DOI:10.1021/ja0114660

9694
J. Am. Chem. Soc. 2001, 123, 9694-9695
Scheme 1
Hydrozirconation of Stannylacetylenes: A Novel and
Highly Efficient Synthesis of 1,1-Diiodo-,
1,1-Dibromo-, and Mixed (Z)- or
(E)-1-Iodo-1-bromo-1-alkenes Using
1,1-Hetero-Bimetallic Reagents
Miguel J. Dabdoub,* Vaˆnia B. Dabdoub, and
Adriano C. M. Baroni
Laborato´rio de S´ıntese de Compostos Organocalcogeˆnios
Departamento de Qu´ımica - FFCLRP
UniVersidade de Sa˜o Paulo, AV. Bandeirantes, 3900
However, these routes are not efficient or general. Only specific
Ribeira˜o Preto, Sa˜o Paulo, Brazil
alkynes (oxygenated) were used because no general methods for
the regioespecific synthesis of the bimetallic starting materials
are known.11,12 Therefore, new, alternative and efficient processes
for the synthesis of 1,1-dihaloalkenes would be of considerable
value in organic chemistry.
ReceiVed June 14, 2001
In the past three decades 1,1-dibromo alkenes have been largely
employed as important intermediates in organic synthesis. Alkenyl
bromides of Z or E configuration and 1,1-dibromo-1-alkenes are
subunits present in the chemical structure of some natural products
isolated from marine sponges.1 Uenishi and co-workers2 described
the stereoselective transformation of 1,1-dibromo-1-alkenes 4 into
the (Z)-vinylbromides by hydrogenolysis using Bu3SnH and Pd-
(PPh3)4 as catalyst. Grandjean and Pale,3 obtained the E-isomers
as the major products by reaction of 4 with 1 equiv of
organolithium followed by hydrolysis. It is well established that
the stereospecific palladium-catalyzed cross-coupling of 1,1-
dibromo-1-alkenes 4 in a sequential manner provides access to
configurationally defined trisubstituted alkenes.4-6 In these pro-
cesses, monosubstitution of the bromide at the E-position occurs
exclusively as demonstrated by several authors employing
Negishi,4,5 Suzuki,6 and Stille7 reactions. Corey and Fuchs reported
in 1972 the use of dibromoalkene compounds as intermediates
in the transformation of aldehydes to terminal alkynes.8 Although
a wide series of 1,1-dibromo-1-alkenes or 1,1-diiodo-1-alkenes
are easily prepared,8,9 certain functionalized dibromides and
diiodides cannot be synthesized in an efficient manner while other
types of 1,1-dihalovinyl compounds such as mixed (Z)- or (E)-
1-iodo-1-bromo alkenes are not accessible at all. The most useful
procedures for the synthesis of compounds 3 and 4 are all
conceptually similar because they use Wittig or related ap-
proaches. The need for phosphorus reagents limits the appeal of
these methodologies as a result of toxicity, and the tedious
purification due to the voluminous waste streams particularly is
another drawback.10 Two other different routes that use homo-
bimetallic species of Sn11 or In12 obtained from alkynes have been
described for 3 and 4.
To solve all of these problems and inspired by the work of
Lipschutz13 who has shown that stannylacetylenes undergo the
regiocontrolled hydrozirconation with Cp2Zr(H)Cl, and also based
on our previous work,14 we would like to disclose in this report,
the first successful, seemingly general, halogenolysis of regio-
and stereochemically pure hetero 1,1-bimetallic species for the
synthesis of 1,1-diiodo, 1,1-dibromo, and the previously unknown
(E)- and (Z)-1-iodo-1-bromo-1-alkenes that can be difficult to
prepare in a stereospecific sense using existing methodologies.
The treatment of stannylacetylenes with 1.4 equiv of Cp2Zr(H)-
Cl generated the corresponding 1,1-heterobimetallic species of
tin and zirconium 2 that by iodinolysis (I2; 2.15 equiv) gave the
1,1-diiodoalkenes 3a-g in very good yields. The use of 2.5 equiv
of Br2 in CCl4 or 3.0 equiv of NBS gave the corresponding
dibromides 4a-g in 53-83% isolated yield (Scheme 1, Table 1).
The hydrozirconation and the halogenolysis steps were carried
out at room temperature in THF, under a nitrogen atmosphere. It
is noteworthy that the developed route is compatible with various
functionalities such as hydroxylic groups or alkyl halides which
cannot be present when phosphorus ylides are used. For the
unprotected hydroxylic compounds 3f and 4f it was necessary
the use of 2.8 equiv of the Schwartz’s reagent15 (Cp2Zr(H)Cl).
The reactions were clean, and no alkynyl halides nor over-
halogenated products, for example, RCHICI3 or RCHBrCBr3,
were detected.
The results summarized in Table 1 and Scheme 1 show the
generality of the new route to trisubstituted 1,1-dihalo-alkenes,
in which the two carbon-halogen bonds are formed in a one-pot
reaction, yet expected to be stepwise (Schemes 1 and 2), because
the reactions of the C-Zr bond with electrophiles,13,14 are
normally much faster than the reactions of the C-Sn bond. In
accordance with these previous results, we isolated the new
compounds 5a-c as exclusive products by the iodinolysis of the
C-Zr bond using I2 (1.07 equiv) in THF at room temperature.
By contrast, our attempts to induce similar reactions of zirconated
vinylstannane intermediates with Br2 did not produce clean and
useful results. Reactions of 2 with 1.1 equiv of Br2/CCl4 show
no chemospecificity, with the halogenolysis of the C-Zr (in 2)
and C-Sn (in 6) bonds being competitive in their respective
reactions with Br2. Even the treatment of intermediates 2 with
0.9 equiv of Br2 in CCl4 at -78 °C afforded a mixture of products
* To whom correspondence should be addressed. Fax: 55-16-633-8151.
E-mail: migjodab@usp.br.
(1) (a) Hirsh, S.; Carmely, S.; Kashman, Y. Tetrahedron 1987, 43, 3257.
(b) Quiin, R. J.; Tucker, D. J. Tetrahedron Lett. 1985, 26, 1671.
(2) Uenishi, J.; Kawahama, R.; Yonemitsu, O. J. Org. Chem. 1998, 63, 3,
8975.
(3) Grandjean, D.; Pale, P. Tetrahedron Lett. 1993, 34, 1155.
(4) (a) Minato, A.; Suzuki, K.; Tamao, K. J. Am. Chem. Soc. 1987, 109,
1257. (b) Minato, A. J. Org. Chem. 1991, 56, 4052. (c) Panek, J. S.; Hu, T.
J. Org. Chem. 1997, 62, 4912.
(5) Xu, C.; Negishi, E. Tetrahedron Lett. 1999, 40, 431.
(6) (a) Roush, W. R.; Moriarty, K. J.; Brown, B. B. Tetrahedron Lett. 1990,
31, 6509. (b) Roush, W. R.; Koyama, K.; Curtin, M. L.; Moriarty, K. J. J.
Am. Chem. Soc. 1996, 118, 7502. (c) Baldwin, J. E.; Chesworth, R.; Paker, J.
S.; Russell, A. T. Tetrahedron Lett. 1995, 36, 9551.
(7) Shen, W.; Wang, L. J. Org. Chem. 1999, 64, 8873.
(8) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(9) (a) Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc. 1962,
84, 1745. (b) Michel, P.; Gennet, D.; Rassat, A. Tetrahedron Lett. 1999, 40,
8575. (c) Michel. P.; Rassat, A. Tetrahedron Lett. 1999, 40, 8579. (d) Bonnet,
B.; Le Gallic, Y.; Ple´, G.; Duhamel, L. Synthesis 1993, 1071.
(10) Wang, Z.; Campagna, S.; Yang, K.; Xu, G.; Pierce, M. E.; Fortunak,
J. M.; Confalone, P. N. J. Org. Chem. 2000, 65, 1889.
(11) Quayle, P.; Wang, J.; Xu, J.; Urch, C. J. Tetrahedron Lett. 1998, 39,
481.
(13) (a) Lipschutz, B. H.; Keil, R.; Barton, J. C. Tetrahedron Lett. 1992,
33, 5861. (b) Lipschutz, B. H.; Bhandari, A.; Lindsley, C.; Keil, R.; Wood,
M. R. Pure Appl. Chem. 1994, 66, 1493.
(14) We earlier reported the use 1,1-hetero-bimetallic species of tin and
zirconium that were selectively reacted with BuTeBr and PhSeBr to obtain
the corresponding 1-(tributylstannyl)-1-telluro (or seleno) alkenes in very good
yields: Dabdoub, M. J.; Baroni, A. C. M. J. Org. Chem. 2000, 65, 54.
(15) Buchwald, S. L.; LaMarie, S. J.; Nielsen, R. B.; Watson, B. T.; King,
S. M. Tetrahedron Lett. 1987, 28, 3895.
(12) Klaps, E.; Schmid, W. J. Org. Chem. 1999, 64, 7537.
10.1021/ja0114660 CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/07/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 39, 2001 9695
Table 2. 1-Halo-1-tributyltin-1-alkenes Obtained
Table 1. 1,1-Dihaloalkenes Obtained Using Bimetallic Species
Table 3. (Z)- or (E)-1-Iodo-1-bromo-1-alkenes Obtained
a Fully characterized by NMR, MS, HRMS, and IR data. b Isolated
yields. c I2/THF. d Br2/CCl4. e NBS/THF/CH2Cl2.
Scheme 2
a Isolated yield(column chromatography). b Isolated yield(PTLC).
trol. Performing the reactions of 6a-c with I2/THF 0 °C, it was
possible to obtain the isomerically pure (Z)-1-iodo-1-bromo
alkenes 8a-c in very high yields after column chromatography.
In our first attempts to prepare the isomers of E-configuration,
reactions of 5 with Br2/CCl4 at room temperature, 0 °C, or -78
°C were carried out. Mixtures of (E)-9 and (Z)-8 isomers and the
dibromo compound 4 were obtained under any of these conditions.
The observed results were rationalized on the basis of an
addition-elimination process in compound 9 initially formed. This
side reaction was completely suppressed by performing bromi-
nolysis with NBS in a mixture of THF/CH2Cl2. Under these
conditions, the isomers of E-configuration 9a-c were exclusively
obtained and were isolated by PTLC in the yields indicated in
Table 3. Independent of mechanistics assumptions about stereo-
chemistry of halogenations of alkenylmetal compounds, the
Scheme 3
1
stereochemistry of 5, 6, 8, and 9 could be assigned by H and
13C NMR (chemical shifts, NOESY and JHvinyl-Sn). For compounds
8a-b the vinylic hydrogen appears at 6.45 ppm, and for 8c, at
7.65 ppm, while for isomers 9a-b it appears at 6.79-6.81 ppm
and at 7.87 for 9c.
In conclusion, the first synthesis of potentially useful 1-iodo-
1-bromo-1-alkenes was developed with complete stereocontrol.
Our methods were proven also to be highly efficient for the
preparation of 1,1-diiodo-1-alkenes and 1,1-dibromo-1-alkenes,
which are highly useful synthetic intermediates. Further work
examining the selective reactivity of the halogen atoms in 3, 4,
8, and 9 and also between halogens and tributyltin group in 5
and 6 is in progress.
which contained the desired (Z)-6, their E-isomer, the 1,1-
dibromo-1-alkene 4, and the (Z)-vinyl stannane 7 (Scheme 2).
Compound 7 is formed by the proton trap during the aqueous
workup.
The observed results (Scheme 2) allowed us to conclude that
somehow the Sn/Br exchange in 6 is faster than the Zr/Br
exchange in 2 (k2>k1), while in 2 the Zr/halogen exchange is
always exclusive (the (Z)-vinyl bromide was never obtained).
Using NBS (1.05 equiv) in THF/CH2Cl2 at -78 °C to room
temperature, it was possible to overcome these problems, and
compounds 6a-c were isolated in excellent yields (Table 2,
Scheme 2).
Acknowledgement is due to FAPESP for financial support of this
work. Professor Joseph P. Marino (University of Michigan) is acknowl-
edged for high-resolution mass spectra.
Supporting Information Available: Experimental procedures, ana-
lytical data, and spectra for all prepared compounds (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
With compounds 5 and 6 in hand we decided to perform the
halogenolysis of the C-Sn bond using a halogenating agent
differing from that used in the first step so that we could
synthesize compounds of type 8 and 9 with complete stereocon-
JA0114660