ligand exchange to a mixed cluster 2 (R ) i-Bu; Scheme 2).
The newly positioned isobutyl group could exert the desired
influence on the observed regioselectivity favoring, at least
initially, 3 (R ) i-Bu). It was eventually discovered that by
Scheme 1. Carboalumination with Catalyst 1
equilibrating only 5% Cp
2 2
ZrCl , 10% of inexpensive IBAO,
and Me Al, all in toluene at room temperature for only 15
3
min, a reagent was formed that effects highly selective
carboalumination. After the usual removal of solvent under
vacuum and redissolution in THF, introduction of an
electrophilic coupling partner affords the desired E-alkenyl
product. Scheme 3 shows a few representative examples, all
ligands on zirconium are replaced by the racemic ethylene
2
bridged bis-indenyl analogue, (ebi)ZrCl (i.e., the Brintzinger
4
catalyst, 1). Together with catalytic quantities of MAO, a
very selective CA takes place in toluene at rt (Scheme 1).
While straightforward procedurally, catalyst 1 is quite
Scheme 3. Representative Examples for CA with IBAO
2 2
expensive relative to the cost of Cp ZrCl . From an academic
perspective, given the requirement that both Al and Zr be
5
present within the catalytically active species, there might
be a simpler alternative that relies on changes at aluminum
rather than at the ligand(s) on zirconium. In this Letter we
disclose our latest efforts in this area leading to simplified
and economically attractive new procedures for gaining
essentially total control of regiochemistry in Negishi car-
boalumination reactions.
Fundamental mechanistic studies on carboalumination by
5
Negishi and Takahashi suggest that an Al p-orbital-alkyne-π
interaction directs a bimetallic aggregate 2 to the sterically
and stereochemically favored terminal position (Scheme 2).
Scheme 2. Potential Interaction of Catalyst with Allkyne
of which reflect >99% control of regiochemistry in the
carboalumination step. In the specific case of neutraceutical
7
coenzyme Q10, one immediate application of this new
3
technology, the 48-carbon side chain precursor 5 was
8
prepared from solanesol (4, Scheme 4), a waste product from
Scheme 4. Preparation of the CoQ10 Side Chain Precursor
Thus, a bulkier residue R on aluminum in 2 should enhance
regioselectivity. This would necessitate a “mixed” alane (i.e.,
2, R * Me) which, on the other hand, could also sterically
retard rates of carboalumination to an intolerable degree, as
already seen with variations of ligands on zirconium (e.g.,
3
2 2
Cp* ZrCl ).
To generate such a mixed alane in situ, advantage could
be taken of the rapid exchange of ligands on aluminum at
room temperature. Given the nontransferable nature of
tobacco plants. Treatment of 5 under these modified car-
boalumination conditions, which required 0.25 equiv of
5
isobutyl groups on Al (e.g., as in DIBAL), MAO’s isobutyl
6
analogue, isobutylaluminoxane (IBAO), might undergo
(6) Negishi, E. Organometallics in Organic Synthesis; Wiley, New York,
1
980; Vol. 1.
(
3) Lipshutz, B. H.; Butler, T.; Lower, A. J. Am. Chem. Soc. 2006, 128,
5396.
4) Wild, W. P.; Zsolnai, L.; Huttner, G.; Brintzinger, H. H. J.
(7) Littaru, G. P. The Fourth Conference of the International Coenzyme
1
Q10 Association; IOS Press: Amsterdam, The Netherlands, 2006. Littarru,
G. P. Energy and Defense. Facts and PerspectiVes on CoQ10 in Biology
and Medicine; Casa Editrice Scientifica Internazionale, 1994; p 1.
(8) (a) Rowland, R. L.; Latimer, P. H.; Giles, J. A. J. Am. Chem. Soc.
1956, 78, 4680. (b) Sheen, S. J.; Davis, D. L.; DeJong, D. W.; Chaolin, S.
F. J. Agric. Food Chem. 1978, 26, 259.
(
Organomet. Chem. 1982, 232, 233. Wild, F. W. R. P.; Wasiucionek, M.;
Huttner, G.; Brintzinger, H. H. J. Organomet. Chem. 1982, 288, 63.
(5) Negishi, E.; Kondakov, D. Y.; Choueiry, D.; Kasai, K.; Takahashi,
T. J. Am. Chem. Soc. 1996, 118, 9577.
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Org. Lett., Vol. 9, No. 19, 2007