Efficient Lewis acid catalyzed intramolecular Cannizzaro reaction

Full text of DOI:10.1021/jo0010734

J . Org. Chem. 2000, 65, 8381-8383
8381
Ta ble 1. Ch r om iu m -Ca ta lyzed Ca n n izza r o Rea ction of
Ar yl Glyoxa lsa
Efficien t Lew is Acid Ca ta lyzed
In tr a m olecu la r Ca n n izza r o Rea ction
Albert E. Russell, Steven P. Miller, and
J ames P. Morken*
Department of Chemistry, Venable and Kenan Laboratories,
The University of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290
morken@unc.edu
Received J uly 17, 2000
We have recently initiated a program directed toward
the development of stereoselective metal-catalyzed in-
tramolecular hydride transfer reactions. The catalytic
aldol-Tishchenko reaction is one such process wherein
an organized transition state results in diastereoselective
product formation.1 For similar reasons, we expected that
an intramolecular Cannizzaro reaction (eq 1) might occur
a
All reactions were carried out with 10 mol % Cr(ClO4)3‚6H2O
with stereocontrol in the presence of an appropriate
Lewis acid catalyst. This transformation results in the
production of synthetically useful R-hydroxy esters di-
rectly from readily available glyoxals2 under neutral
conditions. Current precedent for an intramolecular
Lewis acid (as opposed to Bronsted base) catalyzed
Cannizzaro reaction is limited to reaction conditions
requiring high temperature (60 °C) and/or high catalyst
loading (20 mol % catalyst) and, in some cases, involves
competitive side reactions.2,3 Herein, we report that the
intramolecular Cannizzaro reaction may be brought
about at room temperature with as little as 1 mol % of
an appropriate Lewis acid catalyst. While initial studies
indicate that the reaction may be subject to asymmetric
catalysis, preliminary mechanistic experiments also in-
dicate that common C2-symmetric ligands are not ap-
propriate for this reaction and that design of new ligand
motifs may be required to realize high enantioselectivity
in this metal-catalyzed process.
at room temperature for 24 h in 2:1 2-propanol:dichloroethane
solvent. bPercent yield is of isolated material after silica gel
chromatography. All compounds were characterized by 1H NMR,
13C NMR, IR, and elemental analysis.
addition of 10% catalyst to an 2-propanol-dichloroethane
solution of the glyoxal substrate (most often employed
as the hydrate) followed by a 24 h reaction period. The
reactions were carried out on the benchtop with no
particular precautions to exclude moisture or oxygen from
the reaction vessel. Of the 20 metal complexes examined,
it was found that Cu(ClO4)2‚6H2O, Cu(OTf)2, and Cr-
(ClO4)3‚6H2O gave the highest levels of reactivity; reac-
tions with Fe(ClO4)3‚6H2O, Mg(ClO4)2‚6H2O, Al(ClO4)3‚
9H2O, Li(ClO4)‚3H2O, and Y(ClO4)3 provided no product.
To explore substrate scope with Cr(ClO4)3‚6H2O, the
series of reactions presented in Table 1 was examined.5
It was found that various aromatic glyoxals are converted
to R-hydroxy esters with isolated yields ranging from 40
to 84%. Notably, under the influence of the chromium-
(III) catalyst, alcohol functionality is tolerated in the
starting material (entry 5, Table 1).
As a preliminary test reaction, catalytic conversion of
phenyl glyoxal hydrate to isopropyl mandelate was
examined in the presence of a number of metal salts. In
these experiments, 2-propanol was used as a cosolvent
thereby necessitating that catalysts are tolerant of protic
reaction conditions.4 The experimental protocol involves
To initiate studies in asymmetric catalysis, an arrayed
catalyst evaluation approach was employed.6 This cata-
lyst discovery strategy revealed Cu(OTf)2-PhBox7 and
Ni(ClO4)2-BINAP8 as two metal-ligand combinations
able to effect the Cannizzaro reaction in an enantiose-
(1) (a) Mascarenhas, C. M.;, Duffey, M. O.; Liu, S.-Y.; Morken, J . P.
Org. Lett. 1999, 1, 1427-1429. (b) Lu, L.; Chang, H. Y.; Fang, J . M. J .
Org. Chem. 1999, 64, 843-853. (c) Mahrwald, R.; Costisella, B.
Synthesis 1996, 1087-1089.
(2) Fuson, R. C.; Emerson, W. S.; Gray, H. W. J . Am. Chem. Soc.
1939, 61, 480.
(3) (a) Maruyama, K.; Murakami, Y.; Yoda, K.; Mashino, T.; Nishi-
naga, A. J . Chem. Soc., Chem. Commun. 1992, 1617-1618. (b) J in,
S.-J .; Arora, P. K.; Sayre, L. M. J . Org. Chem. 1990, 55, 3011-3018.
(c) Okuyama, T.; Kimura, K.; Fueno, T. Bull. Chem. Soc. J pn. 1982,
55, 2285-2286.
(4) There are few reports of chiral Lewis acid catalysts that are
effective in protic solvents. For two recent reports, see: (a) Otto, S.;
Boccaletti, G.; Engberts, B. F. N. J . Am. Chem. Soc. 1998, 120, 4238.
(b) Kobayashi, S.; Nagayama, S.; Busujima, T.; Chem. Lett. 1999, 71.
(5) Metal perchlorates pose an explosion hazard. See: Prudent
Practices for Handling Hazardous Chemicals in Laboratories; National
Academy Press: Washington, D.C., 1981; p 65.
(6) Taylor, S. J .; Morken, J . P. J . Am. Chem. Soc., 1999, 121, 12202.
For recent reviews of high-throughput screening see: (a) Bein, T.
Angew. Chem., Int. Ed. 1999, 38, 323. (b) Shimizu, K. D.; Snapper, M.
L.; Hoveyda, A. H. Chem. Eur. J . 1998, 4, 1885. (c) Francis, M. B.;
J amison, T. F.; J acobsen, E. N. Curr. Op. Chem. Biol. 1998, 2, 422.
(7) 2,2′-Isopropylidenebis(4-phenyl-2-oxazoline). For reviews of Cu-
bisoxazoline complexes in the asymmetric activation of carbonyls,
see: J ohnson, J . S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325.
J ørgensen, K. A.; J ohannsen, M.; Yao, S.; Audrain, H.; Thorhauge, J .
Acc. Chem. Res. 1999, 32, 605.
10.1021/jo0010734 CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/05/2000

8382 J . Org. Chem., Vol. 65, No. 24, 2000
Notes
Ta ble 2. Cu (II)-P h Box Ca ta lyzed Asym m etr ic
Ca n n izza r o Rea ction a
Sch em e 2
ylglyoxal to the catalytic reaction conditions resulted in
1
the corresponding Cannizzaro reaction products. Both H
a
All reactions were carried out at room temperature for 24 h
and 2H NMR spectroscopic analysis show that <5%
deuterium is incorporated in the naphthyl-derived prod-
uct and <5% hydrogen is incorporated at the carbinol
position of the mandelate product. Since no crossover
occurs in the hydride transfer step, it is reasonable to
speculate that the Lewis acid-catalyzed Cannizzaro reac-
tion proceeds by an intramolecular 1,2 hydride shift. This
experiment also indicates that the current reaction does
not proceed through an enediol intermediate similar to
that invoked for the Lobry de Bruyn-Alberda van Eken-
stein reaction,12 as the enediol is known to participate
in proton exchange with solvent and would therefore
result in nonstoichiometric deuterium incorporation in
the crossover experiment described above.13
in 2:1 2-propanol:dichloroethane solvent. bPercent yield is of
isolated material after silica gel chromatography. All compounds
were characterized by 1H NMR, 13C NMR, IR and elemental
analysis. Determined by chiral GLC analysis. Absolute configu-
ration determined by comparison to authentic material.
c
Sch em e 1
On the basis of our observations, we propose the
reaction mechanism described in Scheme 2. Initial reac-
tion of the arylglyoxal with 2-propanol provides hemi-
acetal 4. Subsequent coordination of 4 to the catalyst
followed by intramolecular hydride transfer, presumably
by a three-center transition state, might then provide the
observed reaction product. In support of this conjecture
is that 1H NMR (CDCl3) analysis of the arylglyoxal
hydrate in the presence of 5 equiv of 2-propanol shows
only the presence of hemiacetal 4; resonances for the
aldehyde and hydrate could not be detected. Under this
paradigm, enantioselective transformation would result
from a dynamic resolution whereby the chiral transition-
metal complex selectively binds and catalyzes the rear-
rangement of one enantiomer of an equilibrating mixture
of the stereoisomers of 4.14 This mechanistic scheme
highlights the challenge in design of an effective catalyst
for enantioselective transformation. The enantiomer of
4 that is expected to bind a C2 symmetric catalyst in a
lective fashion. In the presence of 10 mol % of a 1:1
complex of Cu(OTf)2 and (S,S)-Ph-box (see Table 2),
phenyl glyoxal hydrate is converted to R-isopropyl man-
delate in 28% ee and 57% yield. Notably, similar levels
of enantioselectivity and yield can be obtained with 5 mol
% and 1 mol % catalyst loading. When nonaromatic
substituted bis(oxazoline) ligands were employed in place
of PhBox, significantly diminished yields were obtained.
For instance, when 10 mol % t-Bu-box was used as the
ligand the Cannizzaro adduct could not be detected by
1H NMR analysis of the crude mixture. Such unusual
reactivity discrepancies, upon substitution of aromatic
oxazoline-derived ligands for their alkyl-substituted coun-
terparts, have been noted in the recent literature by
Evans9 and J ørgensen.10
To provide a mechanistic foundation for rational
catalyst modification, the crossover experiment in Scheme
1 was carried out. Subjection of a 1:1 mixture of deute-
rium-labeled phenyl glyoxal11 and nonlabeled 2-naphth-
(12) For a review of this reaction, see: Speck, J . C. Adv. Carbohydr.
Chem. 1958, 13, 63-103.
(8) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J . Am. Chem. Soc. 1980, 102, 7932.
(9) Evans, D. A.; Burgey, C. S.; Paras, N. A.; Vojkovsky, T.; Tregay,
S. W. J . Am. Chem. Soc. 1998, 120, 5824. For mechanistic investiga-
tions, see: Evans, D. A.; J ohnson, J . S.; Burgey, C. S.; Campos, K. R.
Tetrahedron Lett. 1999, 40, 2879.
(10) J ohannsen, M.; J ørgensen, K. A. J . Org. Chem. 1995, 60, 5757.
(11) Hall, S. S.; Doweyko, A. M.; J ordan, F. J . Am. Chem. Soc. 1978,
100, 5934.
(13) In contrast, Mg(NO3)2-catalyzed rearrangement of analogous
R-ketohemimercaptals in basic D2O results in significant deuterium
incoporation. See: Hall, S. S.; Poet, A. Tetrahedron Lett. 1970, 33,
2867-2868.
(14) At present, we cannot rule out enantioselective addition of
2-propanol to metal-coordinated arylglyoxal as
a mechanism for
enantioselective transformation. Steric interactions that would govern
this addition process should be similar to those proposed for binding
of the chiral metal complex to hemiacetal 4.

Notes
J . Org. Chem., Vol. 65, No. 24, 2000 8383
“matched” fashion (iPrO directed away from steric bulk,
see 5) will experience a more substantial steric penalty
upon hydride transfer and pyramidalization of the newly
forming stereocenter (aryl directed toward steric bulk of
ligand, see 6) than does the “mismatched” enantiomer
of hemiacetal 4. We suspect that these counteracting
steric interactions, generated by the C2 symmetric envi-
ronment about the ligand, lead to low selectivity and that
design of new ligand motifs may be required to realize a
highly selective transformation.
Ack n ow led gm en t. The authors are grateful to the
National Science Foundation (CAREER Award) and to
Amoco Chemicals for research funding. J .P.M. acknowl-
edges receipt of a Packard Foundation Fellowship and
a DuPont Young Professor Grant.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for all compounds and experimental details are available
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0010734