C O M M U N I C A T I O N S
an electrostatic interaction between the positively charged phos-
phorus and the enolate oxygen as a necessary stabilizing interaction
2
driving the C-C bond-forming step. However, any intermediate
exhibiting this type of electrostatic interaction will necessarily lead
to the cis-disubstituted phosphonium ketone (Scheme 4, E and F).
Our results, in which the trans intermediate salt has been isolated
from the MBH alkylation under kinetically controlled conditions,
suggest that this electrostatic interaction, while typically an
electronically favorable interaction, is not the overriding electronic
influence defining the stereochemical outcome of the cyclization.
These results obtained in the MBH alkylation also suggest that the
oxygen-phosphorus electrostatic interaction in the transition state,
long considered to be a key component in the traditional MBH
reaction, is not a requirement for successful MBH alkylation.
Extrapolation of these results to MBH reactions with aldehydes
may provide insight on successful and unsuccessful procedures in
particular those involving asymmetric induction.
Figure 1. Structural representation for phosphonium salt 3. Br is disordered
with a half water molecule; Br(2) and the water are removed for clarity.
Scheme 3
In summary, we have isolated for the first time a MBH
intermediate exhibiting unprecedented trans geometry of the
phosphonium salt and acyl group. The lack of the previously
accepted electrostatic stabilization of the zwitterionic intermediate
in this alkylation provides new insight into the MBH mechanism.
Further work on the mechanism of the MBH reaction and
application of these findings is in progress.
Scheme 4
Acknowledgment. The NSF and the MDS Research Foundation
graciously supported this work (M.E.K.). K.A.A. wishes to
acknowledge the NSF and the UF for funding of the purchase of
the X-ray equipment.
Supporting Information Available: Experimental procedures and
spectral data for the preparation of 1, 2, 5, and 6, and X-ray
crystallographic data for 3. This material is available free of charge
via the Internet at http://pubs.acs.org.
salt 3 was formed under kinetic or thermodynamic conditions, enone
1
3 3 3
was treated with 1 equiv of PMe in (CD ) COD (0.17 M) for 5
min. A lower concentration was used to ensure that the intermediate
remained in solution. Intermediate 3 that precipitated during the
reaction conducted at a higher concentration was identical to ketone
References
3
that was isolated from the solution. Analysis of intermediate 3
(
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1
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(
(
(
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(
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(
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The generally accepted explanation regarding the putative
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