New allene synthesis via carbocupration - Zinc carbenoid homologation and β-elimination sequence

Article abstract of DOI:10.1021/ol006276t

Polysubstituted propadienes are obtained in good to excellent yields by the consecutive carbocupration - homologation - β-elimination reactions on the easily accessible alkynyl sulfoxides or sulfones. This one-pot reaction also allows the preparation of f

Full text of DOI:10.1021/ol006276t

ORGANIC
LETTERS
2000
Vol. 2, No. 18
2849-2852
New Allene Synthesis via
Carbocupration−Zinc Carbenoid
Homologation and â-Elimination
Sequence
,†
Jos P. Varghese,† Paul Knochel,‡ and Ilan Marek*
Department of Chemistry and Institute of Catalysis Science and Technology,
Technion-Israel Institute of Technology, Technion City, 32000 Haifa, Israel, and
Institut fuer Organische Chemie der UniVersitae, Butenandtstrasse 5-13,
D-81377 Muenchen, Germany
chilanm@tx.technion.ac.il
Received June 29, 2000
ABSTRACT
Polysubstituted propadienes are obtained in good to excellent yields by the consecutive carbocupration−homologation−â-elimination reactions
on the easily accessible alkynyl sulfoxides or sulfones. This one-pot reaction also allows the preparation of functionalized allenes.
One of the most popular methods for the synthesis of allenes
is the reaction of propargylic derivatives with organometallic
reagents, especially organocopper reagents.1 Since the first
report by Crabbe et al.,2 many authors have used modified
organocopper reagents, with stoichiometric or catalytic
amounts of copper salt.3 The propargylic substrate itself
varies from ethers4 and epoxides5 to various esters of more
or less reactivity.6 The stereochemistry of the formal 1,3-
substitution reaction depends on the organometallic reagent
(and also on its halide),7 on the solvent, and on the type of
leaving group.8 However, in many cases, the synthesis of
substituted allenes has proven difficult and these previously
cited methods can lead to mixtures of desired allenes
(7) Marek, I.; Mangeney, P.; Alexakis, A.; Normant, J. F. Tetrahedron
Lett. 1986, 27, 5499.
(8) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. J. Am. Chem.
Soc. 1990, 112, 8042.
(9) (a) Nantz, M. H.; Bender, D. M.; Janaki, S. Synthesis 1993, 577. (b)
Doyle, M. P.; Bagheri, V.; Claxton, E. E J. Chem., Soc. Chem. Commun.
1990, 46. (c) Crabbe, P.; Barreiro, E.; Dollat, J. M.; Luche, J. L. J. Chem.
Soc., Chem. Commun. 1976, 183. (e) Tsuji, J.; Sugiura, T.; Minami, I.
Synthesis 1987, 603. (f) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996,
118, 4492. (g) Satoh, T.; Kuramochi, Y.; Inoue, Y. Tetrahedron Lett. 1999,
40, 8815.
† Technion-Israel Institute of Technology.
‡ Institut fuer Organische Chemie der Universitae, Butenandtstrasse.
(1) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley-
Interscience: New York, 1984.
(2) 2) Rona, P.; Crabbe, P. J. Am. Chem. Soc. 1968, 90, 4733.
(3) (a) Moreau, J. L.; Gaudemar, M. J. Organomet. Chem. 1976, 108,
159. (b) Alexakis, A.; Commercon, A.; Villieras, J.; Normant, J. F.
Tetrahedron Lett. 1976, 2313.
(4) Alexakis, A.; Normant, J. F.; Villieras, J. J. Mol. Catal. 1975, 76, 1.
(5) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. Tetrahedron
1991, 47, 1677.
(10) Brinkmeyer, R. S.; MacDonald, T. J. Chem. Soc., Chem. Commun.
1978, 876.
(11) MacDonald, T. L.; Reagan, D. R.; Brinkmeyer, R. S. J. Org. Chem.
1980, 45, 4740.
(12) (a) Vermeer, P.; Meijer, J.; Eylander, C. Recl. TraV. Chim. Pays-
Bas 1974, 93, 240. (b) Truce, W. E.; Lusch, M. J. J. Org. Chem. 1974, 39,
3174. (c) Truce, W. E.; Lusch, M. J. J. Org. Chem. 1978, 43, 2252. (d)
Fiandanese, V.; Marchese, G.; Naso, F. Tetrahedron Lett. 1978, 5131. (e)
Meijer, J.; Vermeer, P. Recl. TraV. Chim. Pays-Bas 1975, 94, 14.
(6) Landor, S. R. The chemistry of the allenes; Academic Press: New
York, 1982.
10.1021/ol006276t CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/09/2000

contaminated with the corresponding acetylenes. For ex-
ample, the unequivocal preparation of 1,1-disubstituted
propadienes9 (terminal allenes) still remains difficult since
the reaction of organocopper species can proceed either via
an SN2 (Scheme 1, path B) or an SN2′ process (Scheme 1,
would undergo a further reaction with the carbenoid leading
to a doubly homologated product. Interestingly, the corre-
sponding reaction with secondary zinc carbenoid is not
known, and except for the cyclopropanation of alkenes,16
the use of secondary zinc carbenoid in organic synthesis is
still in its infancy.
Therefore, we reasoned that the combined reactions
carbocupration of alkynyl sulfoxide and then homologation
of the resulting vinyl copper with zinc carbenoidscan result
in the formation of an allyl zinc derivative which will
undergo â-elimination17 to furnish a substituted allene as
described in Scheme 3. We first tested this new strategy by
Scheme 1
Scheme 3
path A).10 Several factors can influence this distribution,11
and as a consequence, a mixture of isomers is generally
formed, which leads to some tedious separations.
In this Letter, we would like to report a fundamentally
different approach for the synthesis of polysubstituted allenes
(including terminal allenes) which avoids the possible
formation of alkynes (via the SN2 process, path B, Scheme
1).
When monoalkylcopper reagents are added to R,â-acet-
ylenic sulfoxides, the â-alkylated R,â-ethylenic sulfoxides
are formed with an exclusive cis stereoselectivity and in
quantitative yields (Scheme 2).12 It is also known that the
using the well-known bis(iodomethyl)zinc derivative 1 for
the synthesis of 1,1-disubstituted propadienes.
We indeed found that organocopper reagent (generated by
the addition of 1 equiv of RMgBr to 1 equiv of CuBr in
THF) added quantitatively to the alkynyl sulfoxide (n ) 1,
Scheme 3) to give the vinyl organocopper derivative 2. Upon
addition of bis(iodomethyl)zinc derivative 1, prepared by the
treatment of Et2Zn with CH2I2 in THF at 0 °C for 0.5 h,
vinyl copper derivative 2 underwent homologation followed
by spontaneous â-elimination18 in less than 10 min at room
temperature. The scope of this reaction is broad as described
in Table 1. Primary (Me, Bu, and Oct, entries 1, 2, and 6)
Scheme 2
Table 1. Synthesis of 1,1-Disubstituted Propadienes
entries
R1
R2
n
allenes
yield,a
%
homologation reactions of alkenyl copper with (iodomethyl)-
zinc iodide13 ((ICH2)ZnI) or bis(iodomethyl)zinc ((ICH2)2-
Zn, 1)14 represent a powerful tool for the conversion of
alkenyl copper derivatives into allylic-zinc or -copper
compounds (Scheme 2).15
1
2
3
4
5
6
7
Hex
Hex
Hex
Hex
Hex
Bu
Me
Bu
i-Pr
t-Bu
Ph
1
1
1
1
1
1
2
4
5
6
7
8
9
9
75
80
65
50
95
80
85
Oct
Oct
However, this reaction has to be performed in the presence
of an electrophile such as an aldehyde since the allylic species
Bu
a Isolated yield after purification on silica gel.
(13) For a review on zinc carbenoids, see: Motherwell, W. B.; Nutley,
C. J. Contemp. Org. Synth. 1994, 1, 219.
(14) 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.
(15) (a) Knochel, P.; Jeong, N.; Rozema, M. J.; Yeh, M. C. P. J. Am.
Chem. Soc. 1989, 111, 6474. (b) Knochel, P.; Chou, T. S.; Chen, H. G.;
Yeh, M. C. P.; Rozema, M. J. J. Org. Chem. 1989, 54, 5202. (c) Knochel,
P.; Achyutha Rao, S. J. Am. Chem. Soc. 1990, 112, 6146. (d) Achyutha
Rao, S.; Knochel, P. J. Am. Chem. Soc. 1992, 114, 7579. (e) Achyutha
Rao, S.; Rozema, M. J.; Knochel, P. J. Org. Chem. 1993, 58, 2694.
as well as secondary (entry 3) and even tertiary alkyl groups
(entry 4) add cleanly to alkynyl sulfoxides and then lead to
(16) Charette, A. B.; Lemay, J. Angew. Chem., Int. Ed. Engl. 1997, 36,
1090.
(17) Organosulfur Chemistry, Synthetic and Stereochemical Aspects;
Page, P., Ed.; Academic Press: San Dieg, 1998.
(18) A novel radical â-elimination of vinyl sulfoxide was recently
published for the synthesis of substituted allenes: Delouvrie, B.; Lacote,
E.; Fensterbank, L.; Malacria, M. Tetrahedron Lett. 1999, 40, 3565.
2850
Org. Lett., Vol. 2, No. 18, 2000

the expected allenes in good yields (the yield is slightly
decreasing when the substitution of the organocopper is
increasing). When the homologation described in entry 6 was
performed with iodomethylzinc iodide instead of bis(iodo-
methyl)zinc, 1, the yield of 9 is slightly lower (70%).
Arylcopper also reacted to give the corresponding allene in
excellent yield (entry 5).
reaction with copper salt, the organocopper was formed and
added to the alkynyl sulfoxide as described in Scheme 5.
Scheme 5
It is interesting to note that although methyl and phenyl
copper are known to be sluggish in the carbocupration
reaction of alkyne, the activation of the sulfoxide moiety
allowed these additions in excellent yields.
In all cases, no trace of any isomeric product was detected
(no other nonpolar products), which leads to a very easy final
purification. Even alkynyl sulfones furnished allenes in
excellent yield by the carbocupration-homologation-â-
elimination sequence (entry 7, Table 1). Although alkynyl
sulfides19 and alkynyl phosphonates20 also underwent the
carbocupration reaction, no homologatedsor allenesproducts
were detected.
The homologation step (2 to 3, Scheme 3) has to be
performed at room temperature since at lower temperature
the allylic organometallic 3 underwent a second homologa-
tion reaction with the carbenoid 1 according to Scheme 4.21
This is the first example of a carbocupration reaction of an
alkyne with a functionalized aryl derivative, which occurred
quantitatively.23
Then, by addition of 1 at room temperature to the
functionalized organocopper reagent 12, the homologation-
â-elimination occurred to give the expected allene 13 in 85%
isolated yield (yield based on the starting ethyl 4-iodoben-
zoate after five consecutive steps, Scheme 5). Then, we
wanted to apply our new strategy to the synthesis of 1,1,3-
trisubstituted propadiene.24 To do so, it was necessary to
perform the homologation reaction with a secondary zinc
carbenoid. However, as discussed previously, their uses in
organic synthesis are mainly limited25 to their in situ
preparations for cyclopropanation reactions. Therefore, our
strategy was designed in such a way that as soon as the
secondary zinc carbenoid is formed in situ, it should react
with the vinyl copper 2. Indeed, we found that the successive
Scheme 4
n
addition of dibutylzincsprepared by the reaction of BuLi
with ZnBr2sfollowed by the addition of bisiodo alkane 1426
into the vinyl copper solution 2 at 20 °C gave the expected
1,1,3-trisubstituted allenes in excellent yield within 30 min
as described in Scheme 6 , and the results are reported in
Table 2.
The presence of an organometallic derivative was proved
by the isolation of 10 after the reaction was quenched with
MeOD. The recently reported iodine-magnesium exchange
reaction for the preparation of functionalized magnesium
reagent22 also enhances the scope of the synthesis of 1,1-
disubstituted propadiene. Indeed, treatment of ethyl 4-iodo-
benzoate with i-PrMgBr leads to the corresponding func-
tionalized arylmagnesium halide 11. By a transmetalation
Scheme 6
(19) Vermeer, P.; de Graaf, C.; Meijer, J. Recl. TraV. Chim. Pays-Bas
1974, 93, 24.
(20) Cristau, H.-J.; Gasc, M.-B.; Mbianda, X. Y. J. Organomet. Chem.
1994, 474, C14.
(21) No further homologation was observed since the chelated homoallyl
zinc is less reactive than the parent allylzinc.
(22) Rottlander, M.; Boymond, L.; Berillon, L.; Leprete, A.; Varchi, G.;
Avolio, S.; Laaziri, H.; Quequiner, G.; Ricci, A.; Cahiez, G.; Knochel, P.
Chem. Eur. J. 2000, 6, 767 and references cited therein.
(23) The carbocupration reaction of functionalized alkyl groups was
already reported: Achyutha Rao, S.; Knochel, P. J. Am. Chem. Soc. 1991,
113, 5735.
(24) (a) Ruitenberg, K.; Kleijn, H.; Meijer, J.; Oostveen, E. A.; Vermeer,
P. J. Organomet. Chem. 1982, 224, 399. (b) de Graaf, W.; Boersma, J.;
van Koten, G.; Elsevier: C. J. J. Organomet. Chem. 1989, 378, 115. (c)
Ma, S.; Zhang, A. J. Org. Chem. 1998, 63, 9601.
The plausible mechanism for this reaction is shown in
Scheme 6. The in situ formed secondary carbenoid 15s
generated by the reaction between Bu2Zn, 2LiBr, and 14s
reacted with the vinyl copper 2 to give the homologated
(25) For in situ preparation from sp3 bismetallic derivatives, see: Chemla,
F.; Marek, I.; Normant, J. F. Synlett 1993, 665.
(26) Aufauvre, L.; Knochel, P.; Marek, I. Chem. Commun. 1999, 2207.
Org. Lett., Vol. 2, No. 18, 2000
2851

This strategy also allowed for the preparation of function-
alized allenes in a one-pot procedure.
Table 2. Synthesis of 1,1,3-Trisubstituted Propadienes
Synthetic applications of the present methodology as well
as new developments are in progress in our laboratory.
entries
R1
R2
allenes
yield,a %
1
2
3
4
Hex
Hex
Hex
Bu
Et
Ph
Bu
Et
17
18
19
20
90
84
85
80
Acknowledgment. I.M. is a Ygal Alon fellow. This
research was supported by a grant from the G.I.F., the
German-Israeli Foundation for Scientific Research and
Development (I-535-083.05/97), and by the fund for the
promotion of research at the Technion.
a Isolated yield after purification on silica gel.
product 16, as an unstable intermediate, which underwent
an instantaneous â-elimination to furnish the corresponding
allenes.
In conclusion, polysubstituted allenes were obtained in
good to excellent yield by the consecutive carbocupration-
zinc carbenoid homologation and finally â-elimination reac-
tions on the easily accessible alkynyl sulfoxides or sulfones.
Supporting Information Available: Experimental details
1
and H NMR and 13C NMR spectra for compounds 4-10,
13, and 17-20. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL006276T
2852
Org. Lett., Vol. 2, No. 18, 2000