Novel Coupling Reactions of Dithioacetals with Organocuprate Reagents. Propargylic Dithioacetal as an Allene-1,3-Zwitterion Synthon

Full text of DOI:10.1021/jo970700v

4568
J . Org. Chem. 1997, 62, 4568-4569
Novel Cou p lin g Rea ction s of Dith ioa ceta ls
w ith Or ga n ocu p r a te Rea gen ts.
P r op a r gylic Dith ioa ceta l a s a n
Allen e-1,3-Zw itter ion Syn th on
Hsian-Rong Tseng and Tien-Yau Luh*
Department of Chemistry, National Taiwan University,
Taipei, Taiwan 106, Republic of China
Received April 18, 1997
The carbon-sulfur bond is known to be ambiphilic
toward nucleophiles because the electronegativities for
carbon and sulfur atoms are similar. Accordingly, dif-
ferent kinds of reagents or conditions may alter the
selectivity of the reaction. It is well documented that the
nickel-catalyzed cross-coupling reactions of organosulfur
compounds with Grignard reagents provide a useful entry
to convert a carbon-sulfur bond into a carbon-carbon
bond.1,2 The carbon-sulfur bond in these reactions can
be considered as a carbocation synthon. On the other
hand, the production of a carbanionic leaving group from
the corresponding thioether is rare unless a stabilized
anionic species is produced. For example, the reaction
of an (R-thioalkoxy)carbonyl compound with methyl
mercaptide affords the corresponding desulfurized prod-
uct.3 More recently, treatment of benzylic dithioacetals
with organolithium reagents has led to the formation of
the corresponding carbanions (eq 1).4
results in the sequential transformation of 1 into sub-
stituted allenes 5 or 6 (eqs 3-5).
In the beginning of this work, we tested the reactivity
of benzylic dithioacetals 7 toward organocopper reagents,
Thus, each of 7a and 7b was treated with 0.6 equiv of
tBu2CuLi at -78 °C for 30 min followed by quenching
with MeOH to give 8a and 8b in 95 and 90% yields,
respectively (eq 6). These promising preliminary results
demonstrated the first examples of ring-opening reactions
of dithiolanes with organocopper reagents.
Whereas propargylic acetals react readily with orga-
nocopper reagents to give the corresponding ring-opening
products,5 the corresponding reaction with sulfur analogs
has not been explored. We recently reported that the
propargylic dithioacetal 1 can serve as an allene-1,3-
dication synthon 2 upon treatment with the Grignard
reagent in the presence of a nickel catalyst (eq 2).2,6 In
this regard, the displacement of the two carbon-sulfur
bonds by two carbon-carbon bonds can be achieved in
one pot. However, the reaction would be more versatile
if the two carbon-sulfur bonds in 1 could be substituted
by different moieties. In this paper, we report an
unprecedented organocopper-induced C-S bond-cleavage
reaction of propargylic dithioacetals leading to the cor-
responding thioethers 3 or 4. The combination of this
process with the nickel-catalyzed cross coupling reaction
An extension of this procedure to the reaction of 1a
with the same copper reagent at -78 °C followed by
quenching with MeOH at -78 °C gave the corresponding
allenyl thioether 3a in 88% yield. When D2O was
employed to scavenge the reaction, deuterium incorpora-
tion at allenyl carbon (C3) was observed (Table 1, entry
2). On the other hand, when 3 equiv of MeI and 2 equiv
of HMPA7 were introduced at -78 °C instead of adding
D2O, methylation at the propargylic carbon occured to
give 4a (Table 1, entry 7). Representative results are
summarized in Table 1. Apparently, allenyl/propargyl
organocopper intermediates 9 or 10 are involved in these
reactions. It is noteworthy that neither 3 nor 4 reacted
further with the organocopper reagent under these
conditions.
(1) For reviews, see: (a) Naso, F. Pure Appl. Chem. 1988, 60, 79.
(b) Fiandanese, V. Pure Appl. Chem. 1990, 62, 1987. (c) Luh, T.-Y.;
Ni, Z.-J . Synthesis 1990, 89.
(2) For reviews, see: (a) Luh, T.-Y. Acc. Chem. Res. 1991, 24, 257.
(b) Luh, T.-Y.; Leung, M.-K. In Advances in the Use of Synthons in
Organic Chemistry; Dondoni, A., Ed.; J AI: London, 1995; Vol. 2, 129.
(c) Luh, T.-Y. Pure Appl. Chem. 1996, 68, 105.
(3) For example, see: Gassman, P. G.; Gilbert, D. P.; Luh, T.-Y. J .
Org. Chem. 1977, 42, 1340.
(4) Krief, A.; Kenda, B.; Barbeaux, P. Tetrahedron Lett. 1991, 32,
2509.
As can be seen from Table 1, a number of allenyl/
parpogylic thioethers 3/4 can be easily obtained from the
reactions of 1 with organocopper reagents. Sequential
(5) (a) Normant, J . F.; Alexakis, A. J . Organomet. Chem. 1973, 57,
C99. (b) Alexakis, A.; Mangeney, P.; Normant, J . F. Tetrahedron Lett.
1985, 26, 4197. (c) Alexakis, A.; Mangeney, P.; Ghribi, A.; Marek, I.;
Sedrani, R.; Normant, J . F. Pure Appl. Chem. 1988, 60, 49. (d) Alexakis,
A.; Mangeney, P. Tetrahedron: Asymmetry 1990, 1, 477. (e) Marek,
I.; Mangeney, P.; Alexakis, A.; Normant, J . F. Tetrahedron Lett. 1986,
27, 5499. (f) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J . F. J .
Am. Chem. Soc. 1990, 112, 8042.
(7) HMPA was essential for the alkylation with MeI or allyl bromide
under these conditions (Table 1, entries 7 and 8). The yield was
otherwise much lower. (Cf. Lipshutz, B. H. In Organometallics in
Synthesis; Schlosser, M., Ed.; Wiley: Chichester, 1994; Chapter 4.)
(6) Tseng, H.-R.; Luh, T.-Y. J . Org. Chem. 1996, 61, 8685.
S0022-3263(97)00700-7 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 14, 1997 4569
Ta ble 1. Rea ction of 1 w ith R32Cu Li F ollow ed by
Tr ea tm en t w ith Electr op h ile (E+)
uct 11 was obtained in 52% yield (Table 2, entry 15). The
stereochemistry of 11 was determined by the NOE
experiments. Dimerization of 5a was also achieved in
59% yield upon treatment with MeMgI in the presence
of NiCl2(dppe).
product
(% yield)
entry substrate
R1
Ph
R2
R3
E
1
2
3
4
5
6
7
8
1a
1b
Me tBu
tBu
H
D
H
H
H
H
3a (88)
3b (81)
3c (95)
3d (93)
3e (82)
4c (94)
4a (81)
Ph
Bu
Ph tBu
nBu
1c
1d
1a
Me tBu
TMS Me tBu
Ph
Me tBu Me
tBu CH2dCHCH2 4b (80)a
a
Crude yield. The product was used directly for the next
In summary, we have demonstrated for the first time
the use of propargylic dithioacetals as allene-1,3-zwit-
terion synthons 12. By employing this procedure, di-, tri-,
as well as tetra-substituted allenes are thus synthesized
conveniently.
reaction.
Ta ble 2. NiCl2(d p p f)-Ca ta lyzed Cr oss-Cou p lin g
Rea ction s of 2 or 6 w ith Gr ign a r d Rea gen ts
product
(% yield)
entry
substrate
R4MgX
MeMgI
Ack n ow led gm en t. This work was supported by the
National Science Council of the Republic of China. We
thank Professor Bruce H. Lipshutz for helpful discus-
sions.
9
10
11
12
13
14
15
3a
3e
3c
4a
4b
4c
3a
5a (81)
5b (67)
5c (50)
6a (72)
6b (62)
6c (67)
11 (52)
PhMgBr
iPrMgBra
TMSCH2MgCl
nBuMgBr
PhMgBr
Su p p or tin g In for m a tion Ava ila ble: NMR spectra for
3a -e, 4a ,c, 5b, and 6a -c, 8a ,b, and 11 (14 pages).
MeMgIa
J O970700V
a
NiCl2(dppe) was employed as the catalyst.
(8) (a) Wenkert, E.; Hanna, J . M., J r.; Leftin, M. H.; Michelotti, E.
L.; Potts, K. T.; Usifer, D. J . Org. Chem. 1985, 50, 1125. (b) Wenkert,
E.; Ferreira, T. W. J . Chem. Soc., Chem. Commun. 1982, 840. (c) Trost,
B. M.; Lavoie A. C. J . Am. Chem. Soc. 1983, 105, 5075. (d) Trost, B.
M.; Ornstein, P. L. J . Org. Chem. 1982 47, 748. (e) Shen, G.-Y.; Tapia,
R.; Okamura, W. H. J . Am. Chem. Soc. 1987, 109, 7499. (f) Fabre, J .-
L.; J ulia, M. Tetrahedron Lett. 1983, 24, 4311. (g) Cuvigny, T.; Fabre,
J .-L.; Herve´ du Penhoat, C.; J ulia, M. Tetrahedron Lett. 1983, 24, 4319.
(h) Fabre, J .-L.; J ulia, M.; Verpeaux, J .-L. Bull. Soc. Chim. Fr. 1985,
772. (i) Capet, M, Cuvigny, T.; Herve´ du Penhoat, C.; J ulia, M.; Loomis,
G. Tetrahedron Lett. 1987, 28, 6273.
treatment of these thioethers with the Grignard reagent
in the presence of 5 mol% of NiCl2(dppf) resulted in a
convenient synthesis of substituted allenes 5/6. Table 2
summarizes representative examples. As expected,8
reduction of the C-S bond in 3c was observed when -
PrMgBr was employed (Table 2, entry 11).
i
When NiCl2(dppe) was employed as the catalyst in the
coupling reaction of 3a , the corresponding dimeric prod-