Lewis base activation of Lewis acids catalytic enantioselective allylation and propargylation of aldehydes [2]

Full text of DOI:10.1021/ja016017e

J. Am. Chem. Soc. 2001, 123, 6199-6200
6199
fear of a competing background reaction because the catalytically
pertinent species always contains the chiral directing group.
Lewis Base Activation of Lewis Acids: Catalytic
Enantioselective Allylation and Propargylation of
Aldehydes
Scott E. Denmark* and Thomas Wynn
Roger Adams Laboratory, Department of Chemistry
UniVersity of Illinois, Urbana, Illinois 61801
ReceiVed April 13, 2001
ReVised Manuscript ReceiVed May 15, 2001
In the 22 years since the landmark report by Koga et al. of a
catalytic enantioselective Diels-Alder reaction,1 asymmetric
catalysis by chiral Lewis acids has become one of the most heavily
investigated fields of research.2 Because of the central importance
of carbon-carbon bond-forming reactions, a myriad of chiral
Lewis acid catalyst systems have been developed for many trans-
formations. Typically, these catalysts are generated by the combi-
nation of a strong Lewis acid with a chiral ligand either in situ
or in a separate preparation. In nearly all examples of main group,
early transition metal, and lanthanide-based Lewis acids, asym-
metric modulation with chiral ligands leads to deactivation of the
catalyst due to the basicity of the donor atoms of the ligand. An
important consequence of this behavior is the need for either inde-
pendent synthesis of the chiral Lewis acid or an excess of the
ligand to ensure suppression of competitive, achiral background
reaction from the nascent Lewis acid. Indeed, this deactivation
of the parent Lewis acid by the ligand has been used to attenuate
the activity of Lewis acid catalysts to increase selectivity.3 Espe-
cially because of ligand substitutions, careful design of a chiral
Lewis acid catalyst is needed if high selectivities are to be realized.
There are however, certain circumstances in which a Lewis
basic donor ligand can enhance the activity of a Lewis acidic
acceptor. This counter-intuitive situation is clearly anticipated,
according to a set of empirical bond-length and charge-density
variation rules formulated by Gutmann.4 Specifically, Gutmann’s
fourth rule states that upon coordination of a polyatomic donor
to a polyatomic acceptor there will be a net increase in electron
density on the donor atom and a net decrease of electron density
on the acceptor atom.5 Thus, upon coordination of a Lewis base,
the central atom of a Lewis acid becomes more electrophilic with
the excess charge residing on the peripheral ligands! Taken to its
logical limit, this transfer of electron density would result in an
ionization of one of the ligands from the Lewis acid. Once the
ligand is ionized, a full positive charge can be formally assigned
to the central atom.6
In recent years the development and application of chiral Lewis
base catalysis of aldol and allylation reactions have been inves-
tigated in these laboratories.9 Mechanistic evidence supports the
postulate that the chiral phosphoramide ionizes a chloride from
the trichlorosilyl fragment in the enolate or allyl unit. The
subsequent discovery that a catalytic amount of a chiral phos-
phoramide could activate silicon tetrachloride to open meso
epoxides, thus forming enantioenriched chlorohydrins, suggested
a more general application of the concept. We describe herein
the demonstration that a weak Lewis acid, SiCl4, can be activated
by a chiral Lewis base to catalyze the allylation and propargylation
of aldehydes, Scheme 1.10,11
Initial feasibility studies showed that the combination of SiCl4
and HMPA could promote the addition of allyltributylstannane
to benzaldehyde.12 Control reactions revealed that there was no
appreciable background reaction of these components in the
absence of a Lewis base. Moreover, we also demonstrated that
transmetalation from tin to silicon did not occur under the
conditions of the reaction.10
(3) (a) Palazzi, C.; Colombo, L.; Gennari, C. Tetrahedron Lett. 1986 27,
1735. (b) Kadota, I.; Gevorgyan, V.; Yamada, J.; Yamamoto, Y. Synlett 1991,
823. (c) Suzuki, I, Yamamoto, Y. J. Org. Chem. 1993, 58, 4783. (d) Kadota,
I.; Kobayashi, K.; Asao, N.; Yamamoto, Y. J. Chem. Soc., Chem. Commun.
1995, 1271. (e) Mikami, K.; Terada, M.; Korenaga, T.; Matsumoto, Y.;
Matsukawa, S. Acc. Chem. Res. 2000, 33, 391.
(4) (a) Gutmann, V. The Donor-Acceptor Approach to Molecular Interac-
tions; Plenum Press: New York, 1978. (b) Jensen, W. B. The Lewis Acid-
Base Concepts; Wiley-Interscience: New York, 1980; Chapter 4.
(5) “...although a donor-acceptor interaction will result in a net transfer
of electron density from a donor species to an acceptor species, it will, in the
case of polyatomic species, actually lead to a net increase or “pileup” of
electron density at the donor atom of the donor species and to a net decrease
or “spillover” of electron density at the acceptor atom of the acceptor species.”
ref 4b, pp 136-137.
(6) (a) This is conceptually distinct from Bronsted acid activation of Lewis
acids (Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561) or
Lewis acid activation of Lewis acids (Ishimaru, K.; Monda, K.; Yamamoto,
Y.; Akiba, K. Tetrahedron 1998, 54, 727). (b) For an example of a highly
reactive Lewis acid in which a basic, peripheral ligand is cationic see: Hayashi,
Y.; Rohde, J. J.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 5502.
(7) The ligand-ionization effect has been postulated in several reactions of
Lewis base activation of Lewis acids. (a) Chojnowski, J.; Cypryk, M.; Mich-
alski, J.; Wozniak, L. J. Organomet. Chem. 1985, 288, 275. (b) Corriu, R. J.
P.; Dabosi, G.; Martineau, M. J. Organomet. Chem. 1980, 186, 25. (c) Bassin-
dale, A. R.; Lau, J. C.-Y.; Taylor, P. G. J. Organomet. Chem. 1995, 499, 137.
(8) Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1059.
(9) (a) Denmark, S. E.; Stavenger R. A. Acc. Chem. Res. 2000, 33, 432.
(b) Denmark, S. E.; Fu, J. J.Am. Chem. Soc. 2000, 122, 12021. (c) Denmark,
S. E, Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 6161.
(d) Denmark, S. E.; Su, X.; Nishigaichi, Y. J. Am. Chem. Soc. 1998, 120,
12990. (e) Denmark, S. E.; Barsanti, P. A.; Wong, K. T.; Stavenger, R. A. J.
Org. Chem. 1998, 63, 2428.
(10) For recent reviews of allylmetal additions see: (a) Denmark, S. E.,
Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000; Chapter 10. (b) Chemler, S. R.; Roush, W. R. In Modern
Carbonyl Chemistry; Otera, J.; Ed.; Wiley-VCH: Weinheim, 2000; Chapter
11. (c) StereoselectiVe Synthesis, Methods of Organic Chemistry (Houben-
Weyl); Edition E21; Helmchen, G., Hoffmann, R. W., Mulzer, J., Schaumann,
E., Eds.; Thieme: Stuttgart, 1996; Vol. 3; pp 1357-1602. (d) Yamamoto,
Y.; Asao, N. Chem. ReV. 1993, 93, 2207
(11) For a review of Lewis acid-catalyzed, allylmetal additions see:
Yanagisawa, A. In ComprehensiVe Asymmetric Catalysis, Vol. II; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds. Springer-Verlag: Heidelberg, 1999;
Chapter 27.
(12) Allyltrimethylsilane proved to be unreactive. Burfeindt, J.; Patz, M.;
Mu¨ller, M.; Mayr, H. J. Am. Chem. Soc., 1998, 120, 3629.
The generation of a cationic species results in a significant
increase in the Lewis acidity of the central atom; thus, the Lewis
base has actiVated the Lewis acid.7 The concept of Lewis base
activation leads to intriguing possibilities for ligand-accelerated
catalysis because the Lewis acid is most active when coordinated
to the Lewis base.8 Thus, by use of a chiral Lewis base, a highly
active and chirally modified Lewis acid is generated. In this
scenario a weak, achiral Lewis acid can be used in bulk without
(1) Hashimoto, S.-I.; Komeshima, N.; Koga, K. J. Chem. Soc., Chem.
Commun. 1979, 437.
(2) (a) Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic
Synthesis; CRC Press: Boca Raton, FL, 1996. (b) Lewis Acids in Organic
Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim, 2001.
10.1021/ja016017e CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/30/2001

6200 J. Am. Chem. Soc., Vol. 123, No. 25, 2001
Communications to the Editor
Table 2. Allylation of Aldehydes with 5ca
Scheme 1
entry
R1
product yield, %b ee, %c
1
2
3
4
5
6
7
8
C6H5 (1a)
3a
3b
3c
3d
3e
3f
91
90
91
75
92
94
92
65
94
83
65
11d
22
94
93
62
4-NO2C6H4 (1b)
(E)-C6H5CHdCH (1c)
(E)-C6H5CHdC(CH3) (1d)
C6H5C≡C (1e)
1-naphthyl (1f)
2-naphthyl (1g)
2-furyl (1h)
3g
3h
a All reactions employed 1.1 equiv SiCl4, 1.2 equiv of 2, 0.05 equiv
5c, at 0.5 M in CH2Cl2 at -78 °C for 6 h. b Yields of chromatographi-
cally homogeneous material. c Determined by CSP-SFC. d Configura-
tion not determined.
selectivities, substitution in the cinnamyl series (1c vs 1d) led to
a dramatic decrease in selectivity. The absolute configuration of
all products was shown to be R by correlation (see Supporting
Information).
Table 1. Allylation of Benzaldehyde Promoted by
Phosphoramidesa
entry
promoter
tether length
yield, %b
ee, %c
Finally, we have briefly explored the scope of the nucleophile.
Whereas, the use of (Z)-2-butenyltributylstannane yielded a
disappointing 2/1 mixture of anti/syn homoallylic alcohols,
allenyltributylstannane 7 showed very promising results (Scheme
2). Under the standard reaction conditions, 7 afforded homopro-
pargyl alcohols in excellent yields and enantioselectivities with
several aldehydes. In no case was the isomeric allenyl alcohol
detected. These reactions were generally slower than the allyl
additions due to the lower reactivity of allenylstannanes compared
to that of allylstannanes.16 As in the allylation process, only 1,2-
addition was observed with cinnamaldehyde.
1
2
3
4
5
6
4ad
4b
5a
5b
5c
-
-
3
4
5
6
85
83
81
86
89
84
79
53
84
81
93
69
5d
a All reactions employed 2.0 equiv of SiCl4, 1.2 equiv of 2, 0.05
equiv of promoter, at 0.5 M CH2Cl2 at -78 °C for 6 h. b Yield of
chromatographically homogeneous material. c Determined by CSP-
SFC. d 0.10 equiv of 4b was used.
We next turned our attention to the potential for asymmetric
induction. From the wide range of chiral phosphoramides at our
disposal13 several structural motifs were examined, and we were
delighted to discover that a binaphthyl-based phosphoramide 4a
(the most selective catalyst for epoxide opening9e) could indeed
produce the homoallylic alcohol 3a with high yield and enantio-
selectivity with just 5 mol % of catalyst (Table 1, entry 1).
Previous mechanistic studies revealed a second-order dependence
on the phosphoramide in the allyl addition and aldol reactions,
which led us to investigate alkyl-linked bis-phosphoramides as
promoters.9b,14 To determine the existence and optimal arrange-
ment for cooperativity, several binaphthyl bis-phosphoramides
with differing tether lengths were synthesized (Scheme 1,
5a-d), and the results of their behavior as catalysts are collected
in Table 1. Although all four bis-phosphoramides are effective
catalysts for the allylation, 5c (bearing a five-methylene linker)
gave the highest enantioselectivity. The variation in selectivity
among the dimers and their behavior compared to those of the
control monomer 4b strongly support the hypothesis of a “two-
phosphoramide pathway”.9b,14
Further optimization of the allylation with 5c focused on the
effects of solvent, halosilane source, and loading. Simple replace-
ment of one chlorine led to dramatic differences in reactivity in
the order HSiCl3 > SiCl4 . MeSiCl3 ≈ PhSiCl3. Even though
HSiCl3 was nearly as effective, silicon tetrachloride was selected
as the optimal silicon source. A survey of the SiCl4 loading
revealed only a modest dependence of enantioselectivity on
stoichiometry, but more importantly that the reaction proceed to
only 50% completion with 0.5 equiv. This suggested that the
product alkoxytrichlorosilane was not capable of participating as
a Lewis acid precursor.
Scheme 2
In summary we have demonstrated a new concept for the gen-
eration of a chirally modified and activated Lewis acid by Lewis
base-promoted ionization of a weak Lewis acid. This method of
catalyst generation precludes the need for independent preparation
of the ligated Lewis acid and allows for the use of stoichiometric
amounts of the precursor which enhances reaction rate. This chiral
phosphoramide‚SiCl4 system successfully catalyzed the addition
of allyl- and allenylstannes to aldehydes with high yields and
good to excellent stereoinduction. Application of this catalyst
system to other carbon-carbon bond-forming reactions and
development of new base-activated Lewis acids are in progress.
Acknowledgment. We are grateful to the National Science Foundation
for generous financial support (NSF CHE 9803124). Dr. S. K. Ghosh is
thanked for the preparation and characterization of 5c.
Supporting Information Available: Full characterization of all
catalysts and products along with representative procedures for the
addition reactions (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
JA016017E
With an optimized procedure in hand, we next examined the
scope of the reaction with various aldehydes (Table 2). A variety
of unsaturated aldehydes were found to react under these condi-
tions, but the enantioselectivities were highly dependent on the
aldehyde structure.15 Aromatic aldehydes gave the best results
followed by olefinic and then propargylic aldehydes. No obvious
trend in electronic or steric contributions is readily apparent. For
example, the effect of substitution next to the aldehyde was
inconsistent: 1- and 2-naphthaldehyde both gave similarly high
(13) Denmark, S. E.; Su, X.; Nishigaichi, Y.; Coe, D. M.; Wong, K.-T.;
Winter, S. B. D.; Choi, J. Y. J. Org. Chem. 1999, 64, 1958.
(14) Denmark, S. E.; Pham, S. M. HelV. Chim. Acta 2000, 83, 1846.
(15) Aliphatic aldehydes did not yield homoallylic products when subjected
to the standard conditions. NMR studies identified the rapid generation of
chloroalkoxytrichlorosilanes (aldehyde adducts) which did not react with 3.
(16) For other examples of catalytic enantioselective propargylation, see:
(a) Keck, G. E.; Krishnamurthy, D.; Chen, X. Tetrahedron Lett. 1994, 35,
8323. (b) Yu, C.-M.; Yoon, S.-K.; Choi, H.-S.; Baek, K. J. Chem. Soc., Chem.
Commun. 1997, 763. (c) Yu, C.-M.; Yoon, S.-K.; Baek, K.; Lee, J.-Y. Angew.
Chem., Int. Ed. 1998, 37, 2392.