α-Sulfinyl Carbanions as a New Source of Olefins

Article abstract of DOI:10.1021/ol036450o

(Matrix presented) Secondary α-lithiosulfinyl carbanions react either intermolecularly, after transmetalation into an organocopper derivative in an S_N2-type process with zinc carbenoid, or intramolecularly via higher-order zincate to give, through a tandem zinc homologation-β- elimination reaction the corresponding alkenes. α,α-Disubstituted alkenes are only formed from tertiary α-lithiosulfinyl carbanions via the 1,2-metalate rearrangement.

Full text of DOI:10.1021/ol036450o

ORGANIC
LETTERS
2
004
Vol. 6, No. 4
21-623
r-Sulfinyl Carbanions as A New Source
of Olefins
6
Adi Abramovitch, Jos P. Varghese, and Ilan Marek*
Department of Chemistry and Institute of Catalysis Science and Technology,
TechnionsIsrael Institute of Technology, Technion City, Haifa 32000, Israel
chilanm@tx.technion.ac.il
Received December 17, 2003
ABSTRACT
N
Secondary r-lithiosulfinyl carbanions react either intermolecularly, after transmetalation into an organocopper derivative in an S 2-type process
with zinc carbenoid, or intramolecularly via higher-order zincate to give, through a tandem zinc homologation−â-elimination reaction the
corresponding alkenes. r,r-Disubstituted alkenes are only formed from tertiary r-lithiosulfinyl carbanions via the 1,2-metalate rearrangement.
5
Chiral sulfoxides are very efficient chiral auxiliaries that are
inducing important asymmetric transformations. Therefore,
the past decades have witnessed an exponential use of these
chiral auxiliaries in asymmetric synthesis, establishing the
chiral sulfinyl group as one of the most efficient and versatile
route to chiral alkenes. Similarly, the â-elimination reaction
of sulfinyl radicals (estimated to be a very fast process, ca.
10 s ) for arylsulfoxide borne by a Csp center or a Csp
center was recently used. In parallel, we have also shown
that vinylic sulfoxides can be easily eliminated when
9
-1
3
6
2
7
1
8
chiral controllers in carbon-carbon bond formations. In this
context, we have recently reported the use of chiral sulfoxides
organometallics are situated in a â-position to lead to the
9
corresponding allenes. Therefore, in this three-component
in a four-component condensation reaction for the creation
of chiral quaternary centers. However, in most of the appli-
condensation reaction, namely, the carbocupration reaction
of alkynyl sulfoxides with the organocopper 1 followed first
by a zinc homologation reaction of the resulting vinylic
organometallic 2 with the primary zinc carbenoid 3 and
finally by a spontaneous syn-â-elimination, the corresponding
allene 5 is obtained in a single-pot operation and in excellent
overall yields (see Scheme 1). This strategy was recently
2
cations, sulfoxides are only chiral synthetic tools and must
3
be disposed of at the end of the sequence. As a potentially
very interesting transformation, we have reported the first
preparation of organometallic derivatives from vinyl sulfox-
ides and it was found to be synthetically very useful since
further functionalization easily increases the complexity of
1
0
applied to the preparation of chiral allenes.
4
the carbon skeleton. On the other hand, the thermal syn-â-
(
5) Goldberg, S. I.; Sahli, M. S. J. Org. Chem. 1967, 32, 2059.
elimination reaction between hydrogen and sulfoxide is a
(6) (a) Wagner, P. J.; Sedon, J. H.; Lindstrom, M. J. J. Am. Chem. Soc.
well-known process and has been found to be a powerful
1978, 100, 2579 (b) Lacote, E.; Delouvrie, B.; Fensterbank, L.; Malacria,
M. Angew. Chem., Int. Ed. 1998, 37, 2116.
(7) (a) Delouvrie, B.; Lacote, E.; Fensterbank, L.; Malacria, M. Tetra-
hedron Lett. 1999, 40, 3565 (b) Mouries, B.; Delouvrie, B.; Lacote, E.;
Fensterbank, L.; Malacria, M. Eur. J. Org. Chem. 2002, 1776.
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3995.
(9) Varghese, J. P.; Knochel, P.; Marek, I. Org. Lett. 2000, 2, 2849
(10) Varghese, J. P. Zouev, I.; Aufauvre, L.; Knochel, P.; Marek, I. Eur.
J. Org. Chem. 2002, 4151
(
1) Posner, G. H. The Chemistry of Sulphones and Sulphoxides; Patai,
S., Rappoport, Z., Stirling, C. J. M., Eds.; Wiley: Chichester, 1988.
2) Sklute, G.; Amsallem, D.; Shibli, A.; Varghese, J. P.; Marek, I. J.
Am. Chem. Soc. 2003, 125, 11776.
3) Holton, R. A.; Crouse, D. J.; Williams, A. D.; Kennedy, R. M. J.
Org. Chem. 1987, 52, 2317.
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Farhat, S.; Zouev, I., Marek, I. Tetrahedron 2003, In press.
(
(
(
1
0.1021/ol036450o CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/17/2004

Dimethyl sulfoxide (DMSO) can also be used in this
reaction as a source of terminal olefin as described in
Scheme 2.
Scheme 1
Scheme 2
3
The question of the fate of sp R-sulfinyl carbanions for
the zinc homologation followed by â-elimination reactions
11
as a new source of olefins was then logically raised, because
this conversion (alkyl sulfoxides into polysubstituted olefins)
would be an interesting synthetic transformation. To answer
this appealing question, 6a-e were first metalated with
12
LDA and transmetalated with CuBr to lead to the R-sulfinyl
organocopper derivatives 7a-e (Table 1). Primary zinc
After metalation-transmetalation, the formed dimsyl cop-
1
4
per 10 is treated with the in situ-prepared secondary zinc
1
5
16
carbenoid 11 (formed by treatment of 1,1-bisiodoalkane
Table 1. R-Sulfinyl Carbanions into Monosubstituted Alkenes
1
2
2 with Bu Zn, 2 LiBr) to give the zinc homologated product
13, which spontaneously undergoes a â-elimination reaction
to lead to the corresponding allylbenzene 14 in 70% overall
yield.
However, this olefination reaction from R-sulfinyl car-
banion does not proceed in satisfactory yield when the
tertiary metalated sulfoxide 15 is used. Indeed, the resulting
organocopper was found to be thermally unstable17 and
therefore no homologated product was obtained (Scheme 3).
entry
compounds
R
products
yield (%)a
1
2
3
4
5
6a
6b
6c
6d
6e
C11H23
9a
9b
9c
9d
9e
77
70
50b
65
65
PhCH2CH2CH2
C6H5
p-MeOC6H4
p-MeC6H4
a
Scheme 3
Yield of isolated pure products after purification on column chroma-
b
tography. Styrene 9c is a volatile product, and therefore this yield is lower.
carbenoid, namely, bis(iodomethyl)zinc carbenoid13 3 (pre-
pared by treatment of Et Zn with CH I in THF) was then
2 2 2
added, and via the tandem intermolecular nucleophilic
substitution followed by â-elimination reaction, olefins 9a-e
were obtained in good overall yields as described in Table
1. Aliphatic as well as aromatic olefins can be easily prepared
(Table 1, entries 1-5).
With the idea to solve this problem, we turned our attention
to the intramolecular zinc homologation reaction via the 1,2-
zincate rearrangement. We first tested the behavior of
primary sulfoxides such as 6a in this new experimental
condition. When 6a was successively metalated with LDA,
followed by the addition of a second equivalent of n-BuLi
(
11) Transformation of alkyl sulfones into olefins is known and suc-
cessfully used in natural product synthesis, see: (a) De Lima, C.; Julia,
M.; Verpeaux, J.-N. Synlett 1992, 133. (b) Smith, A. B., III; Minbiole, K.
P.; Verhoest, P. R.; Beauchamp, T. J. Org. Lett. 1999, 1, 913. (c) Romo,
D,; Meyer, S. D.; Johnson, D. D.; Schreiber, S. L. J. Am. Chem. Soc. 1993,
15, 7906. (d) Charreau, P.; Julia, M.; Verpeaux, J.-N. J. Organomet. Chem.
989, 379, 201. (e) Smith, A. B., III.; Zhuang, L.; Brook, C. S.; Boldi, A.
M.; McBriar, M. D.; Moser, W. H.; Murase, N.; Nakayama, K.; Verhoest,
P. R.; Lin, Q. Tetrahedron Lett. 1997, 38, 8667. (f) Alonso, D. A.; Falvello,
L. R.; Mancheno, B.; Najera, C.; Tomas, M. J. Org. Chem. 1996, 61, 5004.
1
8
1
1
(14) Lipshutz, B. H. Synlett 1990, 119.
(
g) Alonso, D. A.; Alonso, E.; Najera, C.; Ramon, D. J.; Yus, M.
(15) For preparation of secondary zinc carbenoid via bismetalated species,
see: Chemla, F.; Marek, I.; Normant, J. F. Synlett 1993, 665. For the
preparation from 1,1-bisiodoalkanes, see: (b) Shibli, A.; Varghese, J. P.;
Knochel, P.; Marek, I. Synlett 2001, 818. (c) Charette, A. B.; Lemay, J.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1090.
(16) Aufauvre, L.; Knochel, P.; Marek, I. Chem. Commun. 1999, 2207.
(17) Tertiary organocopper 15 already decomposes at -50 °C.
(18) (a) Marek, I. Tetrahedron 2002, 58, 9463. (b) Harada, T.; Katsuhira,
T.; Hara, D.; Kotani, Y.; Maejima, K.; Kaji, R.; Oku, A. J. Org. Chem.
1993, 58, 4897. (c) Harada, T.; Chiba, M.; Oku, A. J. Org. Chem. 1999,
64, 8210.
Tetrahedron 1997, 53, 4835 (h) Alonso, D. A.; Costa, A.; Mancheno, B.;
Najera, C. Tetrahedron 1997, 53, 4791.
12) Corey, E. J.; Weigel, L. O.; Chamberlin, A. R.; Cho, H.; Hua, H.
C. J. Am. Chem. Soc. 1980, 102, 6613.
13) For a detailed study on the structure of halomethylzinc reagents,
see: (a) Charette, A. B.; Marcoux, J. F.; Molinaro, C.; Beauchemin, A.;
Brochu, C.; Isabel, E. J. Am. Chem. Soc. 2000, 122, 4508. (b) Denmark, S.
E.; Edwards, J. P.; Wilson, S. R. J. Am. Chem. Soc. 1992, 114, 2592. (c)
Denmark, S. E.; O’Connor, S. P. J. Org. Chem. 1997, 62, 3390. (d)
Denmark, S. E.; Edwards, J. P. J. Org. Chem. 1991, 56, 6974.
(
(
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Org. Lett., Vol. 6, No. 4, 2004

to regenerate the LDA, and then with the bis(iodomethyl)-
zinc carbenoid 3, the olefin 9a was isolated in 70% yield
metalate rearrangement of higher order zincate as described
in Table 2.
(Scheme 4).
Table 2. R-Lithiocarbanions into R,R-Disubstituted Alkenes
Scheme 4
entry
R1
R2
products
yield (%)a
1
2
3
4
C11H23
C4H9
C4H9
C6H5
C4H9
C6H5
CH2CHdCH2
CH2CHdCH2
23a
23b
23c
23d
65
68
66
67
a
Yield of isolated pure product after column chromatography.
By using these new conditions for the intramolecular 1,2-
metalate rearrangement, R,R-disubstituted olefins are ob-
tained in good overall yield from the corresponding R-sulfi-
nyl carbanions in an easy and straightforward manner. It
should be emphasized that the reaction does not require an
excess of reagents; 1 equiv of zinc carbenoid 3 for 1 equiv
of disubstituted sulfoxide 20 and 1 equiv of LDA are used.
Moreover, these mild conditions allow the exclusive prepara-
tion of nonconjugated dienes such as 23c,d (Table 2, entries
3 and 4).
The regeneration of LDA is fundamental for the reaction
to proceed (without adding this second equivalent of BuLi,
no transformation of alkyl sulfoxide into olefin was ob-
served). This result can be interpreted by the necessity to
reach the “higher order zincate” 18 as a reactive intermediate
In conclusion, R-mono- and R,R-disubstituted alkenes are
easily prepared from R-lithiosulfinyl carbanions via two dif-
19
20
21
(
Scheme 4). Higher order cuprate and zincate derivatives
have already been described for the 1,2-metalate rearrange-
ferent mechanisms: (1) an intermolecular S 2-type process
N
22
ment. Based on these observations, the preparation of R,R-
between an organocopper and the zinc carbenoid and (2)
disubstituted alkenes was reinvestigated through the 1,2-
intramolecular reaction via a higher order zincate and sub-
sequent 1,2-metalate rearrangement.
In both cases, the tandem zinc homologation-â-elimina-
tion reaction leads to the expected olefins in an easy and
straightforward manner.
(19) If the in situ-generated HN(i-Pr)2 protonates the organozincate 17,
two different carbon-carbon bonds of 17 can be cleaved. (a) The Zn-
CH2I bond leads to a new RCH(SOTol)ZnCH2I combined with CH3I and
LiN(i-Pr)2. The reaction between the first and the latter compounds may
+
lead to the new heterozincate RCH(SOTol)Zn(i-Pr)2NCH2I, Li . However,
no zinc homologation was observed. (b) If the Zn-CH(SOTol)R bond is
cleaved, Zn(CH2I)2, RCH2SOTol, and LiN(i-Pr)2 are formed. Heterozincate
Zn(CH2I)2N(i-Pr)2 can result from the combination of the two anionic
species, but no zinc homologation of alkyl sulfoxides RCH2(SOTol) can
be expected.
Acknowledgment. This research was supported by a
grant from the G.I.F., the German-Israeli Foundation for
Scientific Research and Development (I-693-7.5/2001), and
by the Fund for the Promotion of Research at Technion.
(20) (a) Kocienski, P.; Wadman, S. N.; Cooper, K. J. Am. Chem. Soc.
1
989, 111, 2363 (b) Barber, C.; Bury, P.; Kocienski, P.; O’Shea, M.; J.
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J.-L.; Normant, J. F. Tetrahedron Lett. 1994, 35, 6873.
1
13
cedures with a description of H and C NMR data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(
21) (a) Creton, I.; Marek, I.; Normant, J. F. Tetrahedron Lett. 1995,
6, 7451. (b) Creton, I.; Marek, I.; Normant, J. F. Synthesis 1996, 1499.
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3
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