Allylation of Unactivated and/or Functionalized Alkynes with Allylindiums

Full text of DOI:10.1021/jo9701041

2318
J . Org. Chem. 1997, 62, 2318-2319
Allyla tion of Un a ctiva ted a n d /or
Ta ble 1. Allyla tion of Alk yn es w ith Allylin d iu m s
F u n ction a lized Alk yn es w ith Allylin d iu m s
Naoya Fujiwara and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-77, J apan
Received J anuary 22, 1997
Since the first carbometalation discovered by Ziegler
and Ba¨hr in 1927,1 a number of additions of organo-
metallics to carbon-carbon multiple bonds have been
reported.2 Although the allylmetalation of activated
alkynes, such as alkynyl ketones (Michael acceptor) and
alkynols (functional group substituted alkynes), and/or
the intramolecular allylmetalation proceed smoothly with
various other allylmetals,2 allylmetalation of simple
unactivated alkynes 1 is not so easy and only a limited
number of allylmetals are available for this purpose.3
More recently, Araki and his co-workers reported that
the reaction of allylindium4 with terminal alkynols5a and
allenols5b in DMF at 100-140 °C gave the corresponding
allylation products in good to high yields. However, the
presence of a hydroxy group was essential for facilitating
the addition, and the allylation of simple unactivated
alkynes was sluggish even at higher temperatures (150-
180 °C), giving the allylation products in low yields (12-
28%).5a
a
b
Isolated yield. Bromides were used as starting materials
instead of iodide.5
We wish to report that allylindium reagents react with
both unactivated alkynes and functionalized alkynes very
readily in THF6 to give the corresponding allylation
products in good to high yields (eq 1). Perhaps, the
allylindium addition to alkynes is the most widely
applicable procedure among a variety of allylmetalation
methods.3
The results are summarized in Table 1. The reaction
of phenylacetylene (1a ) with 0.6 equiv of allylindium,7
generated in situ by mixing In powder (1.2 equiv) with
allyl iodide (1.8 equiv) in THF, gave the allylation product
2a regioselectively in 94% yield (Table 1, entry 1). The
reactions of para-substituted arylalkynes 1b and 1c and
of benzylacetylene 1d proceeded smoothly to give 2b-d ,
respectively, in high to good yields (Table 1, entries 2-4).
The reactions shown in entries 1-4 (Table 1) were
complete with 2 h at 70 °C. The reactions of 1-octyne 1e
and 1-dodecyne 1f gave 2e and 2f, respectively, in good
yields (Table 1, entries 5 and 6). The allylation of the
enyne 1g also proceeded smoothly to give the correspond-
ing allylation product 2g in excellent yield (Table 1, entry
7). The allylations in entries 5-7 were complete within
1 h at 70 °C. The amino-substituted alkyne 1h , which
was inert to the Lewis acid-catalyzed allylsilylation3j due
to the coordination of Lewis acid to the nitrogen atom,8
reacted with allylindium at 70 °C for 2 h, giving the
corresponding allylation product 2h in 75% yield (Table
1, entry 8). It should be noted that the regioselectivity
of the allylation of 1h is opposite to that of propargyl
alcohol and related hydroxy-substituted alkynes;5a che-
lation-promoted allylation5 is not involved in the allyla-
tion of 1h .
(1) Ziegler, K.; Ba¨hr, K. Chem. Ber. 1928, 61, 253.
(2) For reviews, see: (a) Normant, J . F.; Alexakis, A. Synthesis 1981,
841 (organo-Li, -Mg, -Zn, -B, -Al, and -Cu compounds). (b) Oppolzer,
W. Angew. Chem., Int. Ed. Engl. 1989, 28, 38 (stoichiometric organo-
Li, -Mg, and -Zn and catalytic Ni, Pd, and Pt compounds). (c) Negishi,
E. Pure Appl. Chem. 1981, 53, 2333 (organo-Al/Ti and -Al/Zr system).
(d) Knochel, P. Comprehensive Organometallic Chemistry II; Able, E.
W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, 1995;
Vol. 11, p 159 (organo-Li, -Mg, -Zn, -B, -Al, -Cu, -Hg/Pd, -Ni, -Mn
compounds). (e) Knochel, P. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4,
p 865. (f) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207 (organo-
Li, -Mg, -Zn, -B, -Al compounds).
(3) (a) Takai, K.; Yamada, M.; Odaka, H.; Utimoto, K.; Fujii, T.;
Furukawa, I. Chem. Lett. 1995, 315 (allyl-Ta). (b) Takahashi, T.;
Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron Lett. 1994, 35, 5685
(allyl-Zr). (c) Chatani, N.; Amishiro, N.; Morii, T.; Yamashita, T.;
Murai, S. J . Org. Chem. 1995, 60, 1834 (allyl-Zn). (d) Molander, G. A.
J . Org. Chem. 1983, 48, 5409 (allyl-Zn). (e) Miller, J . A.; Negishi, E.
Tetrahedron Lett. 1984, 25, 5863 (allyl-Al). (f) Negishi, E.; Miller, J .
A. J . Am. Chem. Soc. 1983, 105, 6761 (allyl-Zn). (g) Eishi, J . J .;
Boleslawski, M. P. J . Organomet. Chem. 1987, 334, C1 (allyl-Ti). (h)
Yeon, S. H.; Han, J . S.; Hong, E.; Do, Y.; J ung, I. N. J . Organomet.
Chem. 1995, 499, 159 (Lewis acid-catalyzed allyl-Si). (i) Asao, N.;
Matsukawa, Y.; Yamamoto, Y. J . Chem. Soc., Chem. Commun. 1996,
1513 (Lewis acid-catalyzed allyl-Sn). (j) Asao, N.; Yoshikawa, E.;
Yamamoto, Y. J . Org. Chem. 1996, 4874 (Lewis acid-catalyzed allyl-
Si).
(5) (a) Araki, S.; Imai, A.; Shimizu, K.; Yamada, M.; Mori, A.;
Butsugan, Y. J . Org. Chem. 1995, 60, 1841. (b) Araki, S.; Usui, H.;
Kato, M.; Butsugan, Y. J . Am. Chem. Soc. 1996, 118, 4699.
(6) The reactions of R- and/or â-oxy aldehydes with allylindiums in
H2O and aqueous/dry THF have been studied: (a) Paquette, L. A.;
Mitzel, T. M. Tetrahedron Lett. 1995, 36, 6863. (b) Paquette, L. A.;
Mitzel, T. M. J . Am. Chem. Soc. 1996, 118, 1931. (c) Paquette, L. A.;
Mitzel, T. M. J . Org. Chem. 1996, 61, 8799.
(7) Two allyl groups among (allyl)3In2I3 are used for the allylation
reaction, and the third allyl group acts as a ligand of the In complex
(ref 4). Accordingly, 0.6 equiv of allylindium corresponds to 1.2 equiv
of allylating agent in the ordinary sense.
(4) Araki, S.; Ito, H.; Butsugan, Y. J . Org. Chem. 1988, 53, 1831.
(8) Yamamoto, Y.; Yoshikawa, E. Unpublished results.
S0022-3263(97)00104-7 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 8, 1997 2319
Sch em e 1
In addition, the reaction of 1a with crotylindium,
prepared from In powder and crotyl bromide in THF,
gave the γ-adduct 3 in 88% yield (Table 1, entry 9); the
straight chain R-adduct was not detected. The reaction
of 1a with methallylindium gave 4 in 90% yield (Table
1, entry 10).
Interestingly, the use of silyl-substituted alkynes
brought a regioselectivity different from the cases shown
above. The allylation of (trimethylsilyl)acetylene (1i)
occurred on the terminal carbon,9 giving the (Z)-allylation
product 5a stereoselectivity in 75% yield. The reaction
of silyl-substituted internal alkyne, 1-(trimethylsilyl)-1-
propyne (1j), gave a mixture of trans- and cis-allylation
products 5b in 50% yield. In the case of the silyl-
substituted acetylenes, an exceptionally longer reaction
time (∼36 h) was necessary to complete the allylation
reaction.
(20 wt % solution in D2O), giving the d2-allylation product
2a -d2 (95% d-content) in which two deuteriums were
incorporated at the C-1 position. The allylation reaction
of phenylacetylene-d 1a -d followed by the usual workup
using HCl-H2O afforded 2a , in which no deuterium was
incorporated, in 91% yield. Furthermore, the allylation
of 1a followed by treatment with I2 (5.0 equiv) at room
temperature gave the diiodinated product 6 in 74% yield.
These results suggest that the allylation of terminal
alkynes 1 would proceed through the double-indation
intermediate 7 (Scheme 1),11 which still has a reactive
allyl group. Another allyl group of 7 would react further
with 1: a possible intermediate is shown in 8, although
it is highly speculative.
Preparation of 2a from 1a is representative. Allylin-
dium was prepared by mixing In powder (0.069 g, 0.6
mmol) with allyl iodide (0.82 mL, 0.9 mmol) in THF (1.0
mL) at room temperature for 1 h.10 To a THF solution
of allylindium was added phenylacetylene (1a ) (0.55 mL,
0.5 mmol) at room temperature. The reaction mixture
was heated to 70 °C and stirred for 2 h. The reaction
was quenched with dilute hydrochloric acid (15 v/v %,
2.0 mL) at room temperature. The reaction product was
extracted with ether, washed with brine, dried with
anhyd Mg2SO4, concentrated under reduced pressure,
and purified by silica gel column chromatography using
hexane as an eluent, giving 2a (0.068 g) in 94% yield.
Although further study is needed to settle the mech-
anism of allyation, we are now in a position to carry out
the allylindation of unactivated and functionalized alkynes
in good to high yields and to synthesize various 2-sub-
stituted 1,4-pentadiene derivatives in a regio- and ste-
reocontrolled manner.
Su ppor tin g In for m ation Available: Characterization data
for reaction products (16 pages).
J O9701041
(10) The allylindium reagent was prepared originally in DMF (ref
4). Since then, the allylindation reactions of acetylenes have been
carried out in this solvent. Now, it is clear that the reagent can be
prepared in THF, and this finding expands the scope of this reagent
to the carboindation.
(11) A double-zincation intermediate was proposed in the allylzin-
cation of terminal alkynes: Frangin, Y.; Gaudemar, M. J . Organomet.
Chem. 1977, 142, 9. See also: Knochel, P. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 4, p 883.
To help clarify the mechanism of the allylindation, the
reaction of 1a with allylindium was quenched with DCl
(9) The allylation of TMS-substituted alkynes with allylzinc bromide
gives the same regioselectivity as the present allylindation: Molander,
G. A. J . Org. Chem. 1983, 48, 5409.