Published on Web 05/23/2003
Mechanisms of Allene Stereoinversion by Imidozirconium Complexes
Forrest E. Michael, Andrew P. Duncan, Zachary K. Sweeney, and Robert G. Bergman*
Department of Chemistry and Center for New Directions in Organic Synthesis, UniVersity of California at Berkeley,
Berkeley, California 94720
Received February 24, 2003; E-mail: bergman@cchem.berkeley.edu
New routes to enantiopure allenes are important because of their
documented utility in organic synthesis.1-3 We recently reported
an efficient kinetic resolution of 1,3-disubstituted allenes using
enantiopure ethylenebis(tetrahydroindenyl) (ebthi) imidozirconium
compounds.4 In the course of that investigation, a remarkable
selective inversion of allene configuration was observed (Figure
1). Treatment of (S,S)-1 with either (R)- or (S)-1,2-cyclononadiene
resulted in formation of the same diastereomer of [2 + 2] cyclo-
adduct 2. In both cases, 1,2-cyclononadiene of predominantly (S)
configuration was isolated upon treatment of 2 with allene (C3H4).
To rationalize these observations, a stepwise [2 + 2] cycloaddition
pathway was proposed, proceeding via an unidentified intermediate
in which the original allene stereochemistry was lost.
4. Heating a solution of 6 in C6H6 at 95 °C for 1.5 d resulted in the
disappearance of the CD signal, indicating that under forcing
conditions, racemization of the metallacycle could occur. The allene
recovered from the sample after heating was also found to be
racemic.
Figure 3. Unexpected retention of diphenylallene stereochemistry.
The diphenylallene observations stimulated an investigation of
the reactions of 3 with a wider range of enantioenriched dialkyl-
allenes. This ultimately resulted in the finding that optically active
dialkylmetallacycles are, in fact, formed but racemize much faster
than their diaryl analogues (Figure 2). For example, a solution of
metallacycle 5, formed from 3 and (S)-1,3-diisopropylallene, was
initially CD active; however, the metallacycle underwent complete
racemization within 24 h at room temperature, and cleavage of
the metallacycle with carbodiimide yielded racemic allene.5 The
most economical conclusion from this observation is that 4,5-
nonadiene also leads initially to optically active metallacycle 4,
but that racemization occurs even more rapidly under the reaction
conditions.
The slow racemization rate of diphenylallene-derived metalla-
cycle 6 prompted an examination of the cycloaddition reaction using
both partners in enantioenriched form. This should allow both the
initial selectivity of the cycloaddition and the subsequent isomer-
ization processes to be directly observed. Accordingly, treatment
of (R,R)-1 with (R)-diphenylallene resulted in complete conversion
to a single metallacycle isomer, 7 (the “matched” isomer). The same
compound was also formed when an excess of rac-diphenylallene
was allowed to react with (R,R)-1. The relative configuration of 7
is the same as that of cyclononadiene adduct 2 and was assigned
by NOESY spectroscopy. Cleavage of 7 with carbodiimide regener-
ated (R)-diphenylallene with no detectable loss of enantioenrich-
ment. Complex 7 was stable at lower temperatures; however,
heating a solution of 7 for 24 h at 105 °C afforded a 3:1 equilibrium
mixture of (E) and (Z) olefin isomers 7 and 8 (Figure 4, top).
Reaction of (S)-diphenylallene with (R,R)-1 produced a new
metallacycle diastereomer, which was assigned as 9 (the “mis-
matched” isomer) by NOESY spectroscopy. Metallacycle 9 exists
in rapid equilibrium with (R,R)-1 at room temperature (Keq ) 1),
indicating that it is much less stable than matched diastereomer 7.
Compound 9 has the same double bond geometry as 7 but the
opposite configuration at the R-carbon of the metallacycle. Appar-
ently, interaction of the incoming allene with the imido substituent
causes more steric repulsion than interaction with the ebthi ligand
in the [2 + 2] cycloaddition transition state. Metallacycle 9 isomer-
izes much more readily than 7, progressing through mixtures of
Figure 1. Stereoinversion of allenes by an enantiopure imido complex.
We have now examined the reaction of a wider range of 1,3-
disubstituted allenes with both chiral and achiral imidozirconium
complexes. Our experiments have provided more extensive infor-
mation about these transformations, requiring new proposals for
both the mechanism of the cycloaddition reaction and the subse-
quent behavior of the metallacycle products.
To determine whether the cycloaddition proceeds through an
intermediate in which the chirality of the allene fragment is
destroyed, we interchanged the enantiopurity of the reaction partners
and carried out the reaction between enantioenriched allenes and
achiral imidozirconocene complex 3. In initial experiments with
4,5-nonadiene, circular dichroism (CD) spectroscopy revealed that
the resultant azazirconacyclobutane 4 was optically inactive within
30 min (Figure 2). The recovered 4,5-nonadiene was also racemic,
in accordance with the original stepwise cycloaddition mechanism.
Figure 2. Reaction of dialkylallenes with imidozirconocene complex.
When this reaction was extended to 1,3-diphenylallene, different
behavior was observed. In this case, treatment of enantiopure (R)-
1,3-diphenylallene (>95% ee) with achiral imidozirconocene
compound 3 afforded the expected metallacycle 6 (Figure 3). Treat-
ment of 6 with diisopropylcarbodiimide regenerated diphenylallene
with no detectable loss of enantiopurity (>95% ee (R)). Further-
more, CD spectroscopy on metallacycle 6 confirmed that it was
optically active, in contrast to dialkylallene-derived metallacycle
9
7184
J. AM. CHEM. SOC. 2003, 125, 7184-7185
10.1021/ja0348389 CCC: $25.00 © 2003 American Chemical Society