introduced by Husson et al.,11 and the produced ions were
reported to be conveniently reduced by zinc borohydride.
However, to our knowledge, the addition of an aliphatic
Grignard onto these iminium ions preformed by AgBF4 was
described only once11 and occurred with a low yield, together
with the formation of the corresponding enamine.
Scheme 1. Synthesis of R-Amino Nitriles 6 and 7
We verified that reaction of 4 or 5 with AgBF4 in CDCl3
followed by filtration of the precipitated AgCN produced
almost quantitatively the corresponding iminiums (appear-
ance of a signal in 1H NMR at 8.98 and 8.73 ppm
respectively for 4 and 5). Furthermore, the fact that similar
yields and selectivity were obtained in the case of substrates
6 and 7 (Table 1, entries 7-9) is also in agreement with the
production of an intermediate iminium ion.
During the reaction of these iminiums with an organo-
metallic reagent, an obvious side reaction is the deprotonation
of the iminium ion. The produced enamine can then add to
the starting iminium and oligomerization may follow. The
occurrence of this competing deprotonation depends both on
the basicity of the organometallic and on the structure of
the iminium substrate: while this is not possible in the case
of 4, it appears to be particularly easy in the case of the
strained indolizidinium ion derived from 6 or 7. The
deprotonation of these preformed iminiums is probably less
effective when acetylenic Grignard reagents are used since
they are less basic than vinylic Grignards. This might at least
partially explain why the use of AgBF4 is useless in these
cases.
In regard to the nature of the reacting vinyl organometallic
(Table 3), parameters governing this reaction remain un-
clear: though iminium ions are known to be soft electrophilic
species,12 the hard or soft character of the reacting vinyl
organometallic does not explain the obtained results: vinyl-
lithium (harder than vinylic Grignards) gave low yields, but
dilithiumpropenylcuprate, considered as a softer nucleophile
than vinylic Grignards, is ineffective. On the other hand, the
presence of silver(I) salt in the reaction mixture can also
induce undesired side reactions with the vinyl organometallic,
as evidenced in the case of alane 22 (vide supra).
readily at ca. -40 °C, while Grignard reagent alone required
protracted reaction time at rt to reach completion.
The beneficial outcome of the use of silver tetrafluorobo-
rate was much less pronounced when acetylenic Grignards
were used (Table 2). In these cases, similar or even better
yields of addition product were obtained in the absence of
additive.
The nature of the R-amino nitrile had also an influence
on the success of these reactions: while very good yields
were obtained under our standard conditions with substrates
4 and 5 (Table 1 entries 1-6), lower yields were observed
with cyano indolizidines 6 and 7 (entries 7-9) though in
these cases AgBF4 still had a beneficial influence on both
yield and diastereoselectivity. Using these substrates, byprod-
ucts were produced together with the vinylic indolizidines
which could not be obtained in pure form.
The behavior of other vinylic reagents in the presence of
AgBF4 was next examined: vinylzinc8 and vinyllithium
reagents gave much lower yields compared to vinylic
Grignards (Table 3, entries 1, 2, 5, and 6). Vinylic alane 22
and vinylic silanes9 25 and 27 (entries 4, 7, and 8) failed to
give any addition product, and in the former case, a clean
coupling of the vinylic alane was observed with the
concomitant reduction of Ag+.10 Finally, an organocuprate
gave unidentified products, but no addition was observed
(entry 3).
A standard procedure using 1.6 equiv of silver tetrafluo-
roborate (rt, THF, 10 mn) with respect to the starting R-amino
nitrile, followed by addition of 3-4 equiv of the vinylic
Grignard at -78 °C, soon emerged as the best operative
conditions.
In conclusion, this work shows that silver tetrafluoroborate
as an iminium promoter is a very efficient additive in the
Bruylants reaction involving vinylic Grignards. Owing to the
The use of silver tetrafluoroborate to promote the forma-
tion of an iminium ion from an R-amino nitrile was first
Table 3. Bruylants Reaction Performed on Amino Nitriles 4 and 5 with Other Vinyl Metals in the Presence of AgBF4 (1.6 equiv)
entry
substrate
organometallic
conditions
product
yield (%)
1
2
3
4
5
6
7
8
4
4
4
4
4
5
5
5
propenylLia (1.5)
propenylZnClb(1.5)
dipropenylCuLic (1.5)
22d (2)
-78 to 0 °C, 1 h
-78 to 0 °C, 1 h
-78 to 0 °C, 1 h
-78 to 0 °C, 1 h
-78 to 0 °C, 1 h
-78 to 0 °C, 1 h
reflux 12 h
10 (R4: Me)
10 (R4: Me)
10 (R4: Me)
23 (R4: C6H13
23 (R4: C6H13
13 (R4: H)
32
13
0
)
)
0
24e (3)
13
59
0
vinylZnClf (1.5)
25
27
26 (R4: C6H13
28 (R4: C8H15
)
)
reflux 12 h
0
a Obtained from Br/Li exchange (t-BuLi) from a (E/Z) 60/40 mixture of 1-bromoprop-1-ene. b Obtained from Br/Li exchange (t-BuLi) from a (E/Z) 60/40
mixture of 1-bromoprop-1-ene followed by transmetalation with zinc chloride. c Obtained from Br/Li exchange (t-BuLi) from a (E/Z) 60/40 mixture of
1-bromoprop-1-ene followed by transmetalation with copper iodide (0.5 equiv). d Obtained by reaction of DIBALH with prop-1-yne. e Obtained from Br/Li
f
exchange (t-BuLi) from (E)-1-bromooct-1-ene. Obtained by transmetalation of vinylmagnesium bromide with ZnCl2.
Org. Lett., Vol. 2, No. 14, 2000
2087