pioneering work of Binger that a tertiary amine complex of
trialkylalanes or dialkylaluminum hydrides 1 reacts with
alkynes to furnish solely the corresponding acetylide-tertiary
amine complexes 2 (Figure 1).7
Table 1. Effect of the Amount of Triethylamine in the
Alumination of Heptyne with DIBALH
entry
Et3N equiv (X)
yield (%)a
de (%)b
1
2
3
4
0.2
65
86
25
90
>97
>97
>97
>97
0.05
0.005
0.05c
a Yield of isolated pure compound based on 5. b Determined by 1H NMR
Figure 1. Catalytic cycle of terminal alumination in the presence
of triethylamine.
on the crude reaction mixture. c Metalation was performed at 0 °C for
2 h.
We have shown that this unreactive species can then react
with different electrophiles after decomplexation with
trimethylaluminum.4a We reasoned that this decomplexation
could in fact be performed by the metalating agent 3 itself,
leading to a process catalytic in triethylamine and affording
uncomplexed reactive mixed alkynylalanes 4.
First experiments were conducted with DIBALH as a
metalating agent and oxazolidine 5 as standard electrophile
(Table 1).
A fast metalation could be observed using 20% triethyl-
amine, evidenced by a rapid evolution of hydrogen gas at
room temperature (entry 1).8 This reaction occurred within
less than 1 h using only 5% triethylamine (entry 2), whereas
a smaller amount of catalyst led to a significantly lower
conversion (entry 3). The best results were obtained when
preparing the acetylide at 0 °C (entry 4).9 In all the cases,
compound 6a was obtained as a single diastereomer.10
In such conditions, the reaction becomes highly efficient
and general, as exemplified in Table 2. This procedure is
(2) Carbonyl groups: (a) Niwa, S.; Soai, K. J. Chem. Soc., Perkin Trans.
1 1990, 937. (b) Tombo, G. M. R.; Didier, E.; Loubinoux, B. Synlett 1990,
547. (c) Ishizaki, M.; Hoshino, O. Tetrahedron: Asymmetry 1994, 5, 1901.
(d) Corey, E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151. (e)
Tan, L.; Chen, C.-Y.; Tillyer, R. D.; Grabowski, E. J. J.; Reider, P. J. Angew.
Chem., Int. Ed. 1999, 38, 711. (f) Frantz, D. E.; Fa¨ssler, R.; Carreira, E.
M. J. Am. Chem. Soc. 2000, 122, 1806. (g) Boyall, D.; Lopez, F.; Sazaki,
H.; Frantz, D.; Carreira, E. M. Org. Lett. 2000, 2, 4233. (h) Sasaki, H.;
Boyall, D.; Carreira, E. M. HelV. Chim. Acta 2001, 84, 964. (i) Anand, N.
K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687. (j) Lu, G.; Li, X.;
Chan, W. L.; Chan, A. S. C. Chem. Commun. 2002, 172. (k) Moore, D.;
Pu, L. Org. Lett. 2002, 4, 1855. (l) Cozzi, P. G. Angew. Chem., Int. Ed.
2003, 42, 2895. (m) Lu, G.; Li, X.; Jia, X.; Chan, W. L.; Chan, A. S. C.
Angew. Chem., Int. Ed. 2003, 42, 5057. Imines or nitrones: (n) Frantz, D.
E.; Fa¨ssler, R.; Carreira, E. M. J. Am. Chem. Soc. 1999, 121, 11245. (o)
Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638. (p) Fa¨ssler, R.; Franz,
D. E.; Oetiker, J.; Carreira, E. M. Angew. Chem., Int. Ed. 2002, 41, 3054.
(q) Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2003, 5,
3273.
Table 2. Diastereoselective Alkynylation of Oxazolidines with
Mixed Alkynylorganoaluminum Reagents
entry
R
compound
yield (%)a
de (%)b
(3) (a) Frantz, D. E.; Fa¨ssler, R.; Tomooka, C. S.; Carreira, E. M. Acc.
Chem. Res. 2000, 33, 373. (b) Tzalis, D.; Knochel, P. Angew. Chem., Int.
Ed. 1999, 38, 1463. (c) Fischer, C.; Carreira, E. M. Org. Lett. 2001, 3,
4319. (d) Pinet, S.; Pandya, S. U.; Chavant, P. Y.; Ayling, A.; Valle´e, Y.
Org. Lett. 2002, 4, 1463. (e) Koradin, C.; Polborn, K.; Knochel, P. 2002,
41, 2535. (f) Koradin, C.; Polborn, K.; Gommermann, N.; Knochel, P. Chem.
Eur. J. 2003, 9, 2797.
1
2
3
4
pent
Ph
(CH2)3Cl
(CH2)6C≡CH
6a
6b
6c
6d
90
95
80
85
>97
>97
>97
>97
(4) (a) Blanchet, J.; Bonin, M.; Chiaroni, A.; Micouin, L.; Riche, C.;
Husson, H.-P. Tetrahedron Lett. 1999, 40, 2935. (b) Blanchet, J.; Bonin,
M.; Micouin, L.; Husson, H.-P. J. Org. Chem. 2000, 65, 6423. (c) Blanchet,
J.; Bonin, M.; Micouin, L.; Husson, H.-P. Tetrahedron Lett. 2001, 42, 3171.
(d) Blanchet, J.; Bonin, M.; Micouin, L.; Husson, H.-P. Eur. J. Org. Chem.
2002, 2598. For the use of alkynyl alanes and alanates in the racemic
synthesis of propargylamines, see: (e) Ahn, J. H.; Joung, M. J.; Yoon, N.
M.; Oniciu, D. C.; Katritsky, A. R. J. Org. Chem. 1999, 64, 488.
(5) (a) Powell, N. A.; Rychnovsky, S. D. Tetrahedron Lett. 1998, 39,
3103. (b) Sasaki, M.; Tanino, K.; Miyashita, M. J. Org. Chem. 2001, 66,
5388. (c) Shanmugam, P.; Miyashita, M. Org. Lett. 2003, 5, 3265.
(6) (a) Negishi, E.-I. Organometallics of Main Group Metals in Organic
Synthesis; New York John Wiley: New York, 1980; p 286. (b) Zweifel,
G.; Miller, J. A. Org. React. 1984, 34, 375.
a Yield of isolated pure compound based on 5. b Determined by 1H NMR
on the crude reaction mixture.
far superior to our previously reported procedure4a-d since
it uses a substoichiometric amount of triethylamine and an
1
(8) Kinetics of deprotonation can be followed by H NMR. The use of
a concentrated (1.5 M) toluene DIBALH solution enables the direct
observation of the reaction, without the need for a deuterated solVent.
(9) About 5% competitive hydroalumination product was detected when
the metalation was conducted at room temperature.
(7) Binger, P. Angew. Chem., Int. Ed. Engl. 1963, 2, 686.
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Org. Lett., Vol. 6, No. 14, 2004