a maximum at the 4-tert-butyl-substituted metal-ligand
complex, 1d (entry 4). The 4-NMe2 substituent (1f) gave no
product, possibly due to amine poisoning of the Lewis acid
(entry 6), and for 3,5-dimethyl substituents (1g), steric
encumbrance reduces reactivity and selectivity. In the best
case (1d), the product was obtained in 97% yield after 8 h
at -50 °C.
Table 2. Comparison of Activity and Enantioselectivity for eq
1 as a Function of Protic Additive
entrya
additive
convn (%)b
% eec
74
1
2
36
0
t-BuOH
3
H2O
0
We tested the above additives because we thought they
would catalyze the rate of product and/or counterion
substitution at the metal. Since the effect is counterion
dependent, these data point to the break-up of contact ion
4
5
6
7
8
9
10
HOCMe(CF3)2
HOC(CF3)3
HOCH(CF3)2
3-CF3-C6H4OHd
3-CF3-C6H4OHe
3-CF3-C6H4OH
C6F5OH
80
77
78
45
61
74
77
76
80
80
75
77
77
77
-
pairs between P2Pt2+ and OTf- or SbF6 as a turnover-
defining event in catalysis. Although the additive plays a
minor role with less coordinating, kinetically more labile
-
a 2 mol % of catalyst,10 methylenecyclohexane (0.5 mmol), ethyl
glyoxylate (1.5 mmol), and additive (1.0 mmol, if present) in 1.5 mL of
CH2Cl2. b Conversion for a 5 h run, measured by GC and corrected for
response factors. c % ee measured by chiral phase GC (Cyclodex-â). d 0.05
mmol. e 0.5 mmol.
anions such as SbF6 , associative exchange catalysis of the
stronger binding triflate could substantially increase the rate
of accessing B.
-
accelerate [Cu((S,S)-t-Bu-box)](X2) (X ) OTf-, SbF6 )
Lewis acid-catalyzed Mukaiyama Michael-type reactions by
decomposing a turnover-inhibiting catalyst-product com-
plex.2a,16 The additive appears to selectively affect catalyst
turnover and not the stereodefining step.
With a convenient reaction protocol in hand, we optimized
enantioselectivity by varying the P-Ph portion of the [((S)-
MeOBiphep)Pt](OTf)2 catalyst. As shown in Table 3, the
Another possible role for the acidic additives is reducing
the coordinating power of the counterion though hydrogen
bonding. This could stabilize the solvent-separated ion pair
(B) and play a thermodynamic role in accelerating catalysis.
The higher propensity of triflate to H-bond18 would magnify
the effect and lead to a larger activation compared to the
Table 3. Comparison of Activity and Enantioselectivity for eq
1 as a Function of Chiral Ligand
-
already weakly bound SbF6 anion.
entrya
complex
convn (%)b
% eec
Regarding electronic variations on the MeOBiphep cata-
lyst, one could use either the kinetic or thermodynamic
argument to predict that the more electrophilic the metal,
the stronger and hence more inhibiting, contact ion pair
formation will be. The electronic effects on reaction rate are
consistent with this notion (4-CF3 < 4-H < 4-t-Bu, Table
3). In either case, these acidic phenol additives mechanisti-
cally differ from those reported by Evans in Cu(II)-catalyzed
Mukaiyama Michael reactions.2a,3,19
Related to the above scenario is the increased reproduc-
ibility of reactions run with acidic phenol additives. Water
is a competitive inhibitor of catalysis; however, the acidic
phenols can reverse its effects. For example, adding 2 equiv
of H2O (relative to catalyst) to the reaction in eq 1 lowers
the conversion from 36 to 27% (72% ee), but the reactivity
and selectivity return to the expected levels (72% conversion,
76% ee, cf. entry 6, Table 1) with 3-CF3-C6H3OH (1 mmol).
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
77
52
63
79
78
0
77
69
68
85
83
1g
48
56
a 2 mol % of catalyst,10 methylenecyclohexane (0.5 mmol), ethyl
glyoxylate (1.5 mmol), and C6F5OH (1.0 mmol) in 1.5 mL of CH2Cl2, -50
°C. b Conversion for a 5 h run, measured by GC and corrected for response
factors. c % ee measured by chiral phase GC (Cyclodex-â).
diphosphine basicity does indeed influence the enantio-
selectivity17 and activity. Interestingly, electron-withdrawing
groups (1b,c) slowed the reaction and lowered the % ee,
while electron-donating groups were beneficial to both, with
(16) (a) Evans, D. A.; Rovis, T.; Kozlowski, M. C.; Downey, C. W.;
Tedrow, J. S. J. Am. Chem. Soc. 2000, 122, 9134-9142. (b) Evans, D. A.;
Willis, M. C.; Johnson, J. N. Org. Lett. 1999, 1, 865-868. (c) Evans, D.
A.; Rovis, T.; Kozlowski, M. C.; Tedrow, J. S. J. Am. Chem. Soc. 1999,
121, 1994-1995.
(17) For recent examples of electronic effects in asymmetric catalysis,
see: (a) Murakami, M.; Minamida, R.; Itami, K.; Sawamura, M.; Ito, Y.
Chem. Commun. 2000, 2293-2294. (b) RajanBabu, T. V.; Redetich, B.;
You, K. K.; Ayers, T. A.; Casalnuovo, A. L.; Calabrese, J. C. J. Org. Chem.
1999, 64, 3429-3447. (c) Schnyder, A.; Togni, A.; Wiesli, U. Organome-
tallics 1997, 16, 255-260.
(18) For an example of catalyst immobilization to a silica support by
H-bonding of the triflate counterion to acidic surface sites, see: de Rege,
F. M.; Morita, D. K.; Ott, K. C.; Tumas, W.; Broene, R. D. Chem. Commun.
2000, 1797-1798.
(19) For examples where C6F6OH additives either chemically modify
the catalyst or the (complex) counterion, see: (a) Sun, Y.; Metz, M. V.;
Stern, C. L.; Marks, T. J. Organometallics 2000, 19, 1625-1627. (b) Ishii,
A.; Soloshonok, V. A.; Mikami, K. J. Org. Chem. 2000, 65, 1597-1599.
(c) Sato, H.; Tojima, H.; Ikimi, K. J. Mol. Catal. A: Chem. 1999, 144,
285-293.
Org. Lett., Vol. 3, No. 8, 2001
1235