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Scheme 1 Metalation of 7 followed by trapping with aromatic aldehydes.
adds smoothly to 4-bromobenzaldehyde (5c) and the trifluoro-
methyl ketone (5f) providing the quinolyl alcohols 4f–g in 65%
yield (Table 1, entries 6 and 7).
Fig. 1 Structure of N-heterocycles metalated by TMPMgClÁBF3 (1) and BF3
complexes.
The pyrazine 6 can also be metalated under these conditions
and the addition to various benzaldehydes gives the desired
carbinols 7a–c in 63–67% yield (Scheme 1).
Then, we examined various 3-substituted pyridines (8a–d)
and found that their treatment with TMPMgClÁBF3 (1) at À40 1C
or À78 1C affords metalated species of type 9 which react
smoothly with several aromatic aldehydes (Table 2). Thus, the
treatment of ethyl nicotinate (8a) with the Lewis pair 1
(1.1 equiv., À40 1C, 30 min) provides after the addition to
4-bromobenzaldehyde (5c, 0.8 equiv. À40 1C to 25 1C, 4 h) and
cyclization the lactone 10a in 72% yield (Table 2, entry 1).
Similarly, the 3-chloro and 3-fluoro substituted pyridines 8b
and 8c are readily metalated by TMPMgClÁBF3 (1, 1.1 equiv.)
at À78 1C within 10 min and give after quenching with the
aldehydes 5c and 5b, respectively, the alcohols 10b and 10c
in 71–81% yield (Table 2, entries 2 and 3). Finally diethyl-
nicotinamide (8d) is metalated under the same conditions
providing after addition to 3,4-dichlorobenzaldehyde (5d) the
desired carbinol 10d in 81% yield (Table 2, entry 4).
Table 2 Metalation of 3-substituted pyridines followed by trapping with aro-
matic aldehydes
In order to provide structural information on the 4-meta-
lated pyridines obtained by treatment of 8a–d with the Lewis
pair 1, we have performed low temperature 1H-, 13C- 11B-and
19F-NMR studies. In contrast to the 2-metalated species (3a and
3b) where a 2J19F–13C between C2 and the fluorine atoms can be
observed,4 such couplings could not be found for the 4-meta-
lated species 9a,7 thus excluding the formation of an arylic
Carbonyl
compound
3
trifluoroborate of structure 9aa (Fig. 1). Also no J19F–13C cou-
Entry
1
N-Heterocycle
Product
pling between C2 or C6 and fluorine could be observed,
suggesting that no, or only a very weak, complexation of BF3
by the pyridyl nitrogen occurs (see complex 9ab, Fig. 1).
In a control experiment we treated 8a with BF3ÁOEt2 in THF-d8
and found the expected 3J19F–13C coupling between C2, C6 and the
fluorine atoms (see complex 11, Fig. 1). Also a coordination of
TMPH to the BF3-group resulting in a structure like 12 could not be
observed. Control experiments showed that coordination of the
BF3-group to the solvent THF or the ester group of 8a does not take
place.8 Thus, we propose that the structure of intermediates of type
9 is a pyridylmagnesium derivative like 9ac (Fig. 1).
In conclusion, we have reported that the frustrated Lewis
pair 1 can be used to prepare either 2-pyridyl trifluoroborates or
4-pyridylmagnesium derivatives which can be trapped with
various aromatic aldehydes. Further extension of this research
is currently underway.
5c
2
3
5c
5b
5d
Notes and references
1 (a) G. Bentabed-Ababsa, S. C. S. Ely, S. Hesse, E. Nassar, F. Chevallier,
T. T. Nguyen, A. Derdour and F. Mongin, J. Org. Chem., 2010, 75, 839;
(b) M. Schlosser and F. Mongin, Chem. Soc. Rev., 2007, 36, 1161;
4
´
(c) F. Mongin and G. Queguiner, Tetrahedron, 2001, 57, 4059.
¨
2 (a) T. Voss, T. Mahdi, E. Otten, R. Frohlich, G. Kehr, D. W. Stephan
and G. Erker, Organometallics, 2012, 31, 2367; (b) G. Eros, K. Nagy,
+
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 2124--2126 2125
Manolikakes, Sophia M.
