Indium-mediated regioselective Markovnikov allylation of unactivated terminal
alkynes
Brindaban C. Ranu* and Adinath Majee
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India
Allylation of unactivated terminal alkynes by a simple
treatment with allyl bromide and indium metal in THF at
room temperature produces 1,4-dienes via regioselective
Marknovnikov addition.
aqueous THF are not successful. At lower temperature (0–5 °C),
no efficient coupling is also observed.
In conclusion, the present procedure provides an efficient and
general methodology for indium-mediated allylation of un-
activated terminal alkynes. The notable advantages are the mild
conditions (room temperature), operational simplicity (one-pot
reaction), high yield (75–90%) and excellent regioselectivity
(Markovnikov addition). To the best of our knowledge, this is
the first report of indium-mediated Markovnikov allylation of
uncativated alkynes. We believe this procedure will find useful
application in organic synthesis. Further investigations to gain a
better understanding of the criteria for selectivity and to broaden
the scope of this reaction are in progress.
Metal-mediated reactions play a significant role in organic
synthesis. Of all the metals, indium has emerged in recent years
as the one with most potential because of its advantages with
regard to handling, toxicity, reactivity and selectivity.1 Al-
though indium-mediated carbonyl addition reactions have
experienced tremendous growth in recent times,2 its other
interesting domains, including carboindation, still remain less
well-explored.3 Recently, a procedure for allylation of carbon–
carbon triple bonds, using indium powder and allylic bromides
in DMF at elevated temperature to produce allylalkenols
predominantly via anti-Markovnikov addition, has been demon-
strated.3a One serious limitation of this procedure is that the
presence of a hydroxyl functionality near the triple bond is
essential, and thus nonfunctionalised† or hydroxy-protected
alkynes are not susceptible to allylation.3a We have observed a
very significant effect on the course of the indium-mediated
allylation reaction with a change of solvent and modification of
the experimental conditions. Thus, unactivated (nonfunction-
alised and hydroxy-protected) alkynes underwent efficient
allylation via Markovnikov addition by simple treatment with
allyl bromide and indium metal in THF at room temperature
(Scheme 1).
Table 1 Allylation of alkynes with allyl bromide and indium metal in
THF
Entry
Alkyne
t/h
3
Product
Yield (%)a
Bu
1
2
3
Bu
86
85
90
C6H13
C6H13
3
Ph
Ph
3
80b
85
CH2OH
4
5
3
5
i
OH
R
C CH
R
CH2OC5H11
CH2OPh
OC5H11
Scheme 1 Reagents and conditions: i, In, THF, room temp.
6
7
8
6
6
86
85
OPh
OBn
The experimental procedure is very simple. A mixture of
alkyne (1 mmol), allyl bromide (8 mmol)‡ and indium metal (1
mmol, cut into small pieces) in THF (2 cm3) was stirred at room
temperature until completion of the reaction (TLC). The
reaction mixture was quenched with a few drops of dilute HCl
and extracted with diethyl ether. Evaporation of the solvent
followed by purification via silica gel chromatography fur-
nished the pure product.§
Several structurally varied terminal alkynes underwent
allylation by this procedure to provide the corresponding
1,4-dienes. The results are summarised in Table 1. Nonfunc-
tionalised alkynes such as hex-1-yne, oct-1-yne and phenyl-
acetylene (entries 1–3) produced Markovnikov addition prod-
ucts as the sole isolable compounds in high yields. Very
interestingly, although the alkynols (entries 4, 9 and 11)
furnished almost exclusively or predominantly the anti-Mar-
kovnikov addition products, the corresponding ethers (entries
5–8, 10 and 12) underwent Markovnikov coupling exclusively.
This reversal of regioselectivity with protection of the hydroxy
group is very significant from a mechanistic as well as a
synthetic point of view.
O
Ph
O
Ph
CH2OBn
OH
24
75
OH
83b
8
8
9
MeO
MeO
OMe
OMe
10
11
12
90
MeO
MeO
OH
OH
Ph
+
85
(55:45)
6
7
Ph
OH
Ph
O
O
86
Ph
Ph
Yields refer to pure isolated products fully characterised by 1H and 13C
NMR spectroscopy. b The corresponding Markovnikov product is formed in
less than 5%.
In general, the reactions are very clean, and no side products
were found. No reaction occurred with internal alkynes. THF is
found to be the best choice as solvent. Reactions in water and in
a
Chem. Commun., 1997
1225
Ranu, Brindaban C.
