EnantioselectiVe Dialkylzinc Addition to Aldehydes
the use of excess Ti(OiPr)4, can be also classified as a
neighboring acid-base catalytic system, type b.11,12 In brief,
these type b catalyses involve only the terminal acid and base
functions without conjugation inside the ligands.
In contrast, in the present study we explored a conjugate
Lewis acid-Lewis base catalysis with 4 (Figures 1c and 3).
The key to designing the catalysts is a conjugation between a
2-naphthol moiety and a 3-phosphoryl group (PdO) to doubly
activate electrophile and nucleophile.13,14 In particular, we
examined the enantioselective dialkylzinc addition to aldehydes
(5) using BINOL-Zn(II) catalysts bearing phosphine oxides
[P(dO)R2], phosphonates [P(dO)(OR)2], or phosphoramides
[P(dO)(NR2)2] at the 3,3′-positions (Figure 3).15-17
Results and Discussion
Evaluation of Conjugate Acid-Base Catalyst, 3,3′-Diphe-
nylphosphoryl-BINOL-Zn(II). First, 10 mol % of 3,3′-
diphenylphosphoryl-BINOL, (R)-7, was used to catalyze the
addition of diethylzinc (3 equiv) to aldehydes (5) in THF/toluene
(1:1) at room temperature.4-8 The results are summarized in
Table 1. In particular, aromatic aldehydes with electron-donating
or -withdrawing groups showed high enantioselectivities (up
to 95% ee) (entries 1-11). The reactions also proceeded
smoothly for heteroaromatic aldehydes and R,â-unsaturated
aldehydes (entries 12-14 and 21-25). For aliphatic aldehydes,
in which competitive reduction often occurs along with ethy-
lation, the corresponding secondary aliphatic alcohols were
obtained with high enantioselectivities (up to 94% ee) (entries
FIGURE 1. Double activation of aldehyde and organometal reagents
(M-R).
by a Lewis acid-Lewis base, and (c) double activation by a
conjugate Lewis acid-Lewis base (Figure 1). Usually, orga-
nomagnesium and organoaluminum reagents belong to type a.
Most of the reported enantioselective dialkylzinc additions to
aldehydes are type b in which the Lewis acid and the Lewis
base are attached each other.4,9 To the best of our knowledge,
there have been no reports on conjugate acid-base catalysis
such as type c in enantioselective dialkylzinc additions, which
involves an electron charge transfer at the ligand interior.4 Thus,
type c catalysis offers an advantage at enhancing catalytic
activity because the direct linkage between the acid and base
in type b may weaken or negate both activities.
In principle, catalysis with N,O-ligands such as Noyori’s
DAIB (1) is based on type b as a neighboring acid-base
catalytic system to activate aldehyde and dialkylzinc, respec-
tively (Figure 2).5 For O,O-ligands, 1,1′-bi-2-naphthol (BINOL)
derivatives are important because of their simple C2-symmetric
structures and synthetic utility. Particularly, Ti(IV)-BINOLate
complex (2) has been developed by using type b catalysis.8b,10
The 3,3′-di(o-alkoxyphenyl)-BINOL (3) described by Pu and
co-workers, which has overcome the problem associated with
(11) (a) Huang, W.-S.; Hu, Q.-S.; Pu, L. J. Org. Chem. 1998, 63, 1364-
1365. (b) Huang, W.-S.; Pu, L. Tetrahedron Lett. 2000, 41, 145-149. (c)
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Tetrahedron 2002, 58, 8189-8193.
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C.; Pu, L. Angew. Chem., Int. Ed. 2006, 45, 273-277.
(13) Resonance behaviors of conjugate aromatic compounds involving
C(sp2)sPdO/C(sp2)sOsH and C(sp2)dPsOs/C(sp2)dO‚‚‚H+ have been
studied. For an excellent textbook on organophosphorus chemistry see Quin,
L. D. A Guide to Organophosphorus Chemistry; Wiley: New York, 2000,
and the references therein.
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J. Org. Chem, Vol. 71, No. 17, 2006 6475