OH/H2O to 1-en-3,4-diols 6 and then transformed into the
corresponding 1,3-dioxolanes 7 (Scheme 3). Syn/anti assign-
starting 3 (E/Z ) 35:65) and trapping by the aldehyde occurs
before any enrichment takes place by 1,3-metallotropic shift.
A rationale for our observation is possible considering
transition states (TS) A-D, where the more stable (Z)-4 is
assumed to react with its re face (Figure 2). Zimmermann-
type chairlike TSs C and D are generally considered to
account for the syn selectivity of Z-crotyl species.21 By
extending the same reasoning to (Z)-4, syn adducts should
always prevail because of the lack in D of 1,3 diaxial
destabilizing interactions. In our opinion boat (A) and twist-
boat (B) shaped TSs are more stable than C and D since
they preserve the attractive indium-oxygen interaction
present in (Z)-4. In TS A leading to anti-5, the saturated
aldehyde offers the si face in order to accommodate the R
chain in the less encumbered position. In TS B the unsatur-
ated aldehyde offers the re face, so enjoying π-π stabilizing
interaction between the acetyl group and the unsaturated
substituent. Aromatic aldehydes and cinnamaldehyde exhibit
the best stereopreference thanks to a more effective π-π
interaction.
Scheme 3
ments were attributed on the basis of the following observa-
tions: (i) The chemical shift of the homoallylic proton (H-
4) in syn-6 is always 0.1-0.3 ppm upfield from that of anti-
6, as previously reported in the literature.12 (ii) The difference
of chemical shifts of the two methyl groups in position 2 is
always greater in cis-7 (0.12-0.14 ppm), coming from anti-
6, than in trans-7 (0.01-0.04 ppm). (iii) Invariably, GC
retention times of trans dioxolanes 7 are shorter than those
of cis-7 (30-m column packed with HP-5 cross-linked 5%
Me Ph Silicone; temperature ramping from 50 to 250 °C, at
10 °C/min).
In regards to simple diastereoselectivity, we observed that
stereopreference in the addition to prochiral aldehydes mainly
depends on the nature of the aldehyde. While conjugated
aldehydes preferentially lead to syn adducts (entries 1-6,
14-16), saturated aldehydes favor the formation of anti
adducts (entries 7-13). The γ-oxygenated allyl indium
species most contiguous to 4, namely, methoxylated (Z)-
2d,6 was reported to react with benzaldehyde, cinnamalde-
hyde and octanal, always favoring syn adducts, with the syn/
anti ratios 87:13, 56:44, and 82:18, respectively. These results
indicate that the γ-acetoxy group exerts different effects with
respect to the γ-methoxy group.
Our standard protocol involves the preliminary formation
of 4 before the addition of the aldehyde; during the time
interval t1 1,3-metallotropic shift of indium is supposed to
take place, in our opinion favoring (Z)-4, thermodynamically
stabilized by an indium-oxygen interaction, as occurs in 2d.6
Increasing t1 (entry 4) does not improve diastereoselectivity,
and better results are obtained by lowering the reaction
temperature (entries 2, 4, 9, and 16).
On the other hand, if a classical Barbier procedure is
adopted, that means t1 ) 0 h, diastereoselectivity is quite
lower (entries 5 and 10). In these cases it is possible to
assume that the E/Z isomeric mixture of 4 reflects that of
Figure 2. Possible TSs for the addition of (Z)-4 to aldehydes.
In conclusion, summarizing the advantages of this route
to 1-en-3,4-diols, we observed that (i) starting material 3 is
easily accessible in multigram scale in a single reaction; (ii)
reaction of 3 with indium in THF is fast, almost complete
without using any excess of indium; and (iii) the addition to
aldehydes is complete in a few hours at room temperature
or lower, with a selectivity that mainly depends on the nature
of the aldehyde, namely, conjugated or saturated.
(20) Neuenschwander, M.; Bigler, P.; Christen, K.; Iseli, R.; Kyburz,
R.; Mu¨hle, H. HelV. Chim. Acta 1978, 61, 2047.
Studies on further applications of 3 are in process.
(21) (a) Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149. (b) Isaac,
M. B.; Paquette, L. A. J. Org. Chem. 1997, 62, 5333. (c) Li, C. J.
Tetrahedron 1996, 52, 5643. (d) Cintas, P. SynLett. 1995, 1087.
(22) Typical Procedure. To a suspension of indium powder (0.115 g, 1
mmol) in THF (1 mL) was added 1-acetoxy-3-bromo-1-propene 3 (0.175
mL, 1.5 mmol) at 0 °C. The heterogeneous mixture was stirred for 30 min
at 0 °C, the ice bath was removed, and stirring was continued for 3.5 h at
room temperature. The aldehyde was added (1 mmol) at 0 °C, and the
reaction mixture was stirred for 4 h at 0 °C.
(23) Auge´, J.; Lubin-Germain, N.; Thiaw-Woaye, A. Tetrahedron Lett.
1999, 40, 9245. For other indium-catalyzed Barbier reactions in the presence
of zinc or aluminum, see: (a) Steurer, S.; Podlech, J. AdV. Synth. Catal.
2001, 343, 251. (b) Araki, S.; Jin, S. J.; Idou, Y.; Butsugan, Y. Bull. Chem.
Soc. Jpn. 1992, 65, 1736.
Acknowledgment. This work was supported by MURST-
Rome (National Project “Stereoselezione in Sintesi Organica.
Metodologie e Applicazioni”) and University of Bologna
(funds for selected topics).
Supporting Information Available: 1H and 13C NMR
spectra of 5-7. This material is available free of charge via
OL016315G
Org. Lett., Vol. 3, No. 19, 2001
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