dition of CH2I2 to the reaction mixture prior to imine 2 led
to a switch from cyclopropylamine 4 to the homoallylic
amine 5, in 58% yield and 5:1 diastereoselectivity, favoring
the anti-isomer 5a (Scheme 2).7 The yield was slightly
analysis of lactams 20a and 20b, formed by hydrolysis and
cyclization of phosphinoylamines 11a and 11b, respectively,
and later confirmed by an X-ray analysis of 20a (Scheme
3). 1H coupling constants were characteristic for 1,2-diaxial
Scheme 2
Scheme 3
increased by lowering the temperature, but the effect on
diastereoselectivity was minimal.8 No reversal of stereose-
lectivity occurred upon addition of BF3‚OEt2, in contrast to
the allylation of aldehydes with allylzirconium reagents.9
The reaction scope is illustrated in Table 1.10 Some
functional groups on the alkyne segment, such as silyl ethers
(entry 3), did not interfere with the reaction; however, the
use of silyl esters or internal alkynes resulted in both lower
yield and reduced diastereoselectivity (entries 4 and 2).
Electron-donating and -withdrawing groups on the aldimine
were tolerated and had no effect on product ratios (entries 5
and 6). N-Tosylimines such as 16 were also suitable
substrates but provided decreased diastereoselectivity (entry
7). However, while the formation of N-diphenylphosphi-
noylimines from enolizable aldehydes is elusive,6 the cor-
responding alkyl sulfonylimines are readily formed.11 Treat-
ment of hydrocinnamyl tosylimine 18 with the vinyl
zirconocene derived from alkyne 8 provided the homoally-
lated product 19a in excellent diastereoselectivity (entry 8).
The assignment of the relative stereochemistry of these
addition products was first based on the coupling constant
and gauche relationships in the major and minor addition
products and were in good agreement with literature val-
ues.12,13
We are rationalizing the formation of homoallylic products
by the homologation mechanism shown in Figure 1. First,
(4) For recent reviews, see: (a) Liard, A.; Kaftanov, J.; Chechik, H.;
Farhat, S.; Morlender-Vais, N.; Averbuj, C.; Marek, I. J. Organomet. Chem.
2001, 624, 26. (b) Fletcher, A. J.; Christie, S. D. R. J. Chem. Soc., Perkin
Trans. 1 2001, 1. (c) Erker, G. Acc. Chem. Res. 2001, 34, 309. (d) Marek,
I. Chem. ReV. 2000, 100, 2887-2900. (e) Takahashi, T.; Kotora, M.; Hara,
R.; Xi, Z. Bull. Chem. Soc. Jpn. 1999, 72, 2591. (e) Wipf, P.; Tsuchimoto,
T.; Takahashi, H. Pure Appl. Chem. 1999, 71, 415.
(5) (a) Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853. (b) Schwartz,
J.; Labinger, J. A. Angew. Chem., Int. Ed. Engl. 1976, 15, 333.
(6) Wipf, P.; Kendall, C.; Stephenson, C. R. J. J. Am. Chem. Soc. 2001,
123, 5122.
(7) In the absence of CH2I2, no homoallylic amine product was observed.
CH2Cl2 alone is not sufficient to induce the reaction, in contrast to
observations made in ref 6.
(8) In refluxing CH2Cl2, the diastereomeric ratio is 83:17, at room
temperature the ratio is 85:15, and at 0 °C the ratio is 86:14.
(9) Yamamoto, Y.; Saito, Y.; Maruyama, K. J. Organomet. Chem. 1985,
292, 311.
(10) Typical Procedure. A suspension of 195 mg (0.756 mmol) of Cp2-
ZrHCl in 2 mL of CH2Cl2 was treated at room temperature with 95.0 µL
(0.827 mmol) of 1-hexyne. After 2 min, the yellow solution was cooled to
-78 °C, treated with 375 µL (0.750 mmol) of Me2Zn (2.0 M solution in
toluene), warmed to room temperature over a period of 5 min, treated with
100 µL (1.24 mmol) of CH2I2, stirred for 2 min, and treated with a solution
of 76.0 mg (0.249 mmol) of imine 2 in 1 mL of CH2Cl2. The reaction
mixture was stirred at room temperature for 12 h, quenched with saturated
NH4Cl, diluted with EtOAc and saturated NaHCO3, filtered through Celite,
washed with H2O and brine, dried (MgSO4), filtered through a pad of
Florisil, and concentrated in vacuo. The residue was chromatographed on
deactivated SiO2 (1:9, hexanes/EtOAc containing 1% Et3N) to yield 71 mg
(71%) of 5a and 5b as an 85:15 (separable) mixture of diastereomers.
(11) Chemla, F.; Hebbe, V.; Normant, J.-F. Synthesis 2000, 75.
Figure 1. Proposed mechanism.
hydrozirconation of 1-hexyne followed by transmetalation
with Me2Zn affords vinylzinc intermediate 21.14,15 Rapid
reaction of 21 with CH2I2 is expected to give, after [1,2]-
shift,16 allylic zinc 22, which adds to aldimine 2 to form the
(12) (a) Bhagwatheeswaran, H.; Gaur, S. P.; Jain, P. C. Synthesis 1976,
615. (b) Ramage, R.; Hapton, D.; Parrott, M. J.; Kenner, G. W.; Moore, G.
A. J. Chem. Soc., Perkin Trans. 1 1984, 1357. (c) Desai, M. C.; Thadeio,
P. F.; Lefkowitz, S. L. Tetrahedron Lett. 1993, 34, 5831.
(13) On the basis of the assignments of 11a and 11b, all other major
products were identified as anti on the basis of the characteristic upfield
shift in the 1H NMR spectra for the substituted vinyl proton, relative to the
corresponding proton of the syn isomer. The assignment of 7a is still
tentative.
(14) In the absence of Me2Zn, no imine addition products are formed.
(15) Et2Zn can be used in place of Me2Zn; however, although the
selectivity for the formation of 5a increased to ca. 10:1, the yield dropped
to 47%.
(16) For precedence for this type of rearrangement, see: (a) Charette,
A. B.; Marcoux, J.-F. J. Am. Chem. Soc. 1996, 118, 4539. (b) McWilliams,
J. C.; Armstrong, J. D.; Zheng, N.; Bhupathy, M.; Volante, R. P.; Reider,
P. J. J. Am. Chem. Soc. 1996, 118, 11970. (c) Sidduri, A.; Rozema, M. J.;
Knochel, P. J. Org. Chem. 1993, 58, 2694. (d) Shibli, A.; Varghese, J. P.;
Knochel, P.; Marek, I. Synlett 2001, 818.
2774
Org. Lett., Vol. 3, No. 17, 2001