in a low yield. With the O-vinylpantolactone (3c), the same
catalytic and endo selective effects were observed (entries 5
and 6), but in this case the facial discrimination proved to
3 3
With Eu(fod) or Pr(fod) as the catalyst, facial discrimina-
tion remained the same but catalytic and endo selective
effects decreased until disappearance from latest to earliest
rare earth salts (entries 6-9). Yb(III) and Cu(II) triflate
activation caused dominant or exclusive decomposition of
the acyl imine 1 (entries 10 and 11). However, the selective
formation in low yield of the exo-â isomer in the former
case suggested a determining influence of the catalyst-Lewis
acidity on the mechanistic features of the reaction (entry 10).
This stereodivergence was fully demonstrated when the
reaction between 1 and 3c was performed in TMSOTf- or
13
be complete. Indeed, after 3 days in refluxing cyclohexane
in the presence of 5 mol % of Yb(fod) , 4c was obtained as
3
a mixture of two cis/trans isomers in a 9/1 ratio (entry 6).
Chromatography afforded the crystalline major isomer of 4c
in a 74% yield. Nearly the same result was obtained after a
simple crystallization of the crude product from Et
2
O. The
absolute configuration (4R,6S,2′S) of this adduct was estab-
14
lished by X-ray crystallography (Figure 1) and is consistent
SnCl
4). Interestingly, after conventional aqueous workup, di-
hydroxazine 4c was obtained in a high combined yield and
4
-mediated conditions at low temperature (entries 12-
1
16
showed a large predominancy for the “exo-â” isomer over
the “endo-â”. Moreover, in the second case, only both â
isomers were obtained in a 6/1 trans/cis ratio (entry 13). After
crystallization in Et O, the pure major adduct 4c-“exo-â” was
2
obtained in 62% yield. Finally, when the previous conditions
were reapplied to 1 and 3b, dihydroxazine 4b was readily
obtained with an unexpected “endo-â” selectivity (entry 15).
These last facts strongly suggest that the SnCl
4
-mediated
formation of adducts 4 follows a stepwise mechanism: an
17
acyclic stannic intermediate (zwitterionic or not, Figure 2)
Figure 2.
would undergo a subsequent ring closure with a cis/trans
preferency depending on the nature of the R* group (entries
1
3 and 15).
Comparing the effects of the various Lewis acids tested
led us to the following conclusions: (a) oxophilic Lewis acids
Yb(fod) , Eu(fod) , SnCl , TMSOTf) are efficient catalytic
or stoichiometric promoters of 4 formation, (b) a prevalent
azaphilicity of Cu(OTf) could explain its degradative effect
upon the N-acyl imine 1, and (c) the concerted character
of the heterocycloaddition seems strongly dependent on the
nature of the Lewis acid employed. Such a control on the
concertedsendo selectivesVs stepwise pathway had been
previously exemplified in dihydropyran syntheses.19
Figure 1. Crystal structure of the adduct 4c-endo-â obtained in
(
3
3
4
3
Yb(fod) -catalyzed conditions and related transition state.
2
1
8
with an endo-â approach of the dienophile in the expected
concerted transition state. The exo-R stereostructure could
be assigned to the minor isomer after identification of the
4
c-exo-â isomer obtained by isomerization of the 4c-endo-â
1
5
isomer.
From these results, different asymmetric pathways were
selectable in order to perform a straightforward synthesis of
(
13) Use of other solvents gave lower conversion and/or selectivity.
(
14) C22H23NO4, (M ) 780.83); crystal dimensions 0.36 × 0.33 × 0.33
(R)- (or S)-N-benzoyl-3-phenylpropanal (5).
mm, trigonal, space group P32, a ) 11.144 (2) Å, c ) 27.418(7) Å, V )
949(1) Å , Z ) 6, Dx ) 1.235 mg‚m , µ ) 0.85 cm , T ) 293 K.
3
-3
-1
2
Automatic CAD4 NONIUS diffractometer, Mo KR radiation (λ ) 0.7107
Å), scan method ω/2θ, 7156 data measured, 4953 independent reflections,
R(int) ) 0.008. After Lorenz and polarization corrections, the structure was
solved with SIR-97 which revealed the non-hydrogen atoms. After
anisotropic refinement, all the hydrogen atoms were found using Fourier
difference. The whole structure was refined with SHELXL97 by the full
least-squares techniques (use of F magnitude; x, y, z, âij for C, O, and N
atoms, x, y, z, in riding mode for H atoms; 488 variables and 4953
(15) This isomerization was performed in refluxing toluene with 5% of
Yb(fod)3 overnight.
(16) For entries 10-15 (Table 1), “exo/endo” isomers were so named
since a nonconcerted mechanism for their formation is expected (vide supra).
(17) The total lack of turnover (Table 1, entries 14 and 15) observed
with SnCl4 may suggest an irreversible evolution of the latter.
(18) It must be mentionned that the structure of 1 does not allow the
formation of a stable Cu(II)-chelated complex, in contrast to that of R-imino
esters. The enantioselective alkylation of N-tosyl-R-imino esters using a
Cu(I) chiral complex was recently reported: Ferraris, D.; Young, B.;
Dudding, T.; Leckta, T. J. Am. Chem. Soc. 1998, 120, 4548.
2
2
2
observations; calc w ) 1/(σ (Fo ) + (0.0983P) + 0.55P) where P )
2
2
(
(
Fo + 2Fc )/3 with the resulting R ) 0.064, Rw ) 0.14, and Sw ) 1.053
-3
residual ∆F < 0.20ꢀ Å ).
Org. Lett., Vol. 2, No. 5, 2000
587
Gizecki, Patricia
