Arylation of Aldehydes and Ketones Using AlArEt2(THF)
catalysts for the asymmetric aryl transfer to aldehydes. Fu and
co-workers4 reported the first diphenylzinc addition to 4-chlo-
robenzaldehyde by using a chiral azaferrocene as a catalyst, and
subsequently, chiral catalysts have been developed by Pu5 and
Bolm6 for direct diphenylzinc additions to aldehydes affording
phenyl addition products in high enantioselectivities. To improve
the atomic-efficiency of phenyl transfer and to compensate for
the competitive noncatalytic pathway, mixed zinc reagents of
Ph2Zn/Et2Zn7 as a phenyl source were developed for the
enantioselective phenyl additions to aldehydes. Bolm and co-
workers8 later developed systems for the enantioselective
synthesis of diarylmethanols through the use of arylboronic acids
or arylboranes in combination with Et2Zn in situ to generate
various arylzinc compounds for the asymmetric addition reac-
tions. The studies extended the reaction scope from the phenyl
addition to aryl addition reactions, and this strategy has been
further demonstrated by Dagmen,9 Chan,10 Zhao,11 Braga,12 and
Jin.13 The enantioselective aryl transfer to aldehydes has also
been reported employing a zinc reagent prepared in situ from
ZnCl2 and phenylmagnesium bromide by Soai et al.14 or
aryllithium by Walsh and a co-worker.15 Recently, Knochel16
and Pu17 reported that arylzinc compounds generated in situ
from a reaction of aryliodide with dialkylzinc reacted with
aldehydes to give the desired secondary alcohols in high yields
and enantioselectivities.
excellent enantioselectivities. Yus and co-workers20 have de-
veloped catalytic systems for asymmetric aryl additions to
ketones employing in situ generated arylzinc reagents by heating
ZnEt2 and ArB(OH)2 or Ph3B compounds. Recently Ishihara
and co-workers21 also reported mixed zinc reagents of Ph2Zn/
Et2Zn as a phenyl source for enantioselective phenyl additions
to ketones employing an in situ prepared chiral phosphoramides-
Zn(II) complex.
In contrast, organoaluminum reagents are more reactive than
the zinc or boron reagents and have been applied to a variety
of asymmetric addition reactions.22 Recently, we have demon-
strated that AlAr3(THF) compounds are effective reagents in
asymmetric aryl additions to aldehydes.23 The addition reactions
catalyzed by the titanium catalyst of 10 mol% commercially
available (R)-H8-BINOL are complete in only 10 min at 0 °C,
and afford a wide variety of secondary alcohols including
diarylmethanols in excellent enantioselectivities of >90% ee.
Furthermore, the AlAr3(THF) compounds have been proven to
be highly efficient aryl transfer reagents for ketones, affording
tertiary alcohols in excellent stereocontrol.24 Subsequently, the
asymmetric 1,2 or 1,4 additions of arylaluminum reagents to
cyclic enones using in situ prepared AlPhMe2 were demonstrated
by Zezschwitz25 et al. and by Hoveyda26 et al. A copper-
catalyzed asymmetric conjugate addition of AlArEt2 reagents
to enones was also reported by Alexakis and co-workers.27
To further explore and to improve the atomic-efficiency of
arylaluminum reagents for asymmetric catalytic aryl additions
to organic carbonyls, we herein report the catalytic asymmetric
AlArEt2(THF) addition to aldehydes employing a titanium(IV)
complex of (R)-H8-BINOL or to ketones using a titanium
catalyst of (S)-BINOL. The AlArEt2(THF) compounds are
superior and atomic-efficient reagents for additions to organic
carbonyls, affording secondary and tertiary alcohols in excellent
enantioselectivities of up to 98% ee.
In sharp contrast to aldehydes, there are few examples of
catalytic enantioselective aryl additions to ketones due to the
attenuated reactivities of ketones. An early example was reported
by Fu and a co-worker,18 who employed a catalytic system of
ZnPh2 and 15 mol% (+)-DAIB (3-exo-(dimethylamino)-
isoborneol) to afford tertiary alcohols with enantioselectivities
of up to 91% ee. Walsh and co-workers19 demonstrated that
titanium complexes of trans-1,2-bis(hydroxycamphorsulfonyl-
amino)cyclohexane were excellent catalysts for asymmetric
ZnPh2 additions to ketones or R,ꢀ-unsaturated ketones with
Results and Discussion
Syntheses and 1H NMR Studies of the Aluminum
Reagents. A series of AlArEt2(THF) (Ar ) Ph (1a), 4-MeC6H4
(1b), 4-MeOC6H4 (1c), 4-Me3SiC6H4 (1d), 2-naphthyl (1e))
(Scheme 1) were prepared easily from the reaction of
AlEt2Br(THF) with 1 equiv of ArMgBr in THF. Compounds 1
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