Asymmetric Catalytic Friedel-Crafts Reaction of Silyl Enol Ethers with Fluoral: A Possible Mechanism of the Mukaiyama-aldol Reactions

Article abstract of DOI:10.1021/ol990330s

(Matrix Presented) The catalytic asymmetric Friedel-Crafts reaction of silyl enol ethers with fluoral proceeds under Mukaiyama-aldol conditions to give silyl enol ether products. The sequential diastereoselective reactions of the resultant silyl enol ethe

Full text of DOI:10.1021/ol990330s

ORGANIC
LETTERS
1
999
Vol. 1, No. 12
013-2016
Asymmetric Catalytic Friedel−Crafts
Reaction of Silyl Enol Ethers with
Fluoral: A Possible Mechanism of the
Mukaiyama-Aldol Reactions
2
†
Akihiro Ishii, Jun Kojima, and Koichi Mikami*
Department of Chemical Technology, Tokyo Institute of Technology,
Ookayama, Meguro-ku, Tokyo 152-8552, Japan
kmikami@o.cc.titech.ac.jp
Received October 25, 1999
ABSTRACT
The catalytic asymmetric Friedel−Crafts reaction of silyl enol ethers with fluoral proceeds under Mukaiyama-aldol conditions to give silyl enol
ether products. The sequential diastereoselective reactions of the resultant silyl enol ethers with electrophiles provide highly enantiopure
functionalized organofluorine compounds of material and pharmaceutical interest.
The Mukaiyama-aldol reaction of silyl enol ethers (A) is one
of the most important carbon-carbon bond-forming reactions
in organic synthesis (Scheme 1). Therefore, its application
under Mukaiyama-aldol conditions to give allylic alcohols
(B) (step 1), in which case sequential reactions of the silyl
1
+
enol ether products (B) with electrophiles (E ) could yield
4
more functionalized aldols (C′) possessing adjacent stereo-
genic centers at both the R and â positions with high enantio-
and diastereoselectivity (step 2). We report herein the
asymmetric catalytic F-C reaction of silyl enol ethers, of
which the mechanism may be involved in the Mukaiyama-
Scheme 1
(1) Reviews: (a) Mukaiyama, T. Org. React. 1982, 28, 203. (b) Evans,
D. A.; Nelson, J. V.; Taber, T. R. Topics in Stereochemistry; Interscience:
New York, 1982; Vol. 13. (c) Heathcock, C. H. Asymmetric Synthesis;
Morrison, J. E., Ed.; Academic Press: New York, 1984; Vol. 3.
(2) (a) Nelson, S. G. Tetrahedron: Asymmetry 1998, 9, 357. (b) Gr o¨ ger,
H.; Vogl, E. M.; Shibasaki, M. Chem. Eur. J. 1998, 4, 1137. (c) Bach, T.
Angew. Chem., Int. Ed. Engl. 1994, 33, 417.
(3) Reviews: (a) Smith, M. B. Organic Synthesis; McGraw-Hill: New
York, 1994; pp 1313. (b) Heaney, H. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp
7
33. (c) Roberts, R. M.; Khalaf, A. A. In Friedel-Crafts Alkylation
Chemistry. A Century of DiscoVery; Dekker: New York, 1984. (d) Olah,
G. A. Friedel-Crafts Chemistry; Wiley-Interscience: New York, 1973.
(4) Chiral syn- or anti-R,â-dihydroxy thioesters as R-protected forms:
(a) Kobayashi, S.; Horibe, M. J. Am. Chem. Soc. 1994, 116, 9805. (b)
Mukaiyama, T.; Shiina, I.; Uchiro, H.; Kobayashi, S. Bull. Chem. Soc. Jpn.
to the asymmetric catalytic synthesis of aldols (C) has been
2
investigated in depth for the past decade. An asymmetric
3
catalytic Friedel-Crafts-type (F-C) reaction might proceed
1
994, 67, 1708. Chiral R-amino-â-hydroxy esters: (c) Ito, Y.; Sawamura,
†
On leave from Chemical Research Center, Central Glass Co. Ltd.,
M; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405. (d) Ito, Y.; Sawamura,
M; Shirakawa, E.; Hayashizaki, K.; Hayashi, T. Tetrahedron 1988, 44, 5253.
Kawagoe, Saitama 350-1151.
1
0.1021/ol990330s CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/11/1999

Table 1. Asymmetric Friedel-Crafts Reactions of Silyl Enol Ethers with Fluoral Catalyzed by BINOL-Ti Complex
5
aldol reaction. Sequentially, diastereoselective reactions of
enol ether (2a) with fluoral (run 1). The F-C product (3a)
the F-C products with fluoral can thus produce highly
was easily separated from the usual aldol product (4a) by
simple flash chromatography. Notably, the enantiomeric
excess of the major product (Z)-3a was found to be excellent
(98% ee). In contrast, the reaction of trimethylsilyl enol
ether (2b) gave only the usual aldol-type product (4b) (run
2). The sterically bulky silyl and electron-withdrawing
trifluoromethyl substituents might be important for prevent-
ing inter- or intramolecular nucleophilic attack on the silyl
group in the zwitterion intermediate (D) where the aromatic
6
functionalized organofluorine compounds that are of mate-
7
8
rial and pharmaceutical interest.
1
0
The F-C reaction of silyl enol ethers was investigated
using a chiral binaphthol-derived titanium (BINOL-Ti)
9
i
2 2
complex (1) prepared from (R)-BINOL and Cl Ti(OPr ) in
the presence of MS 4 Å (Table 1). Importantly, the F-C
product (3a) rather than the usual aldol product (4a) was
obtained in the catalytic reaction of tert-butyldimethylsilyl
substituent stabilizes the benzylic carbenium ion (Scheme
(
5) The recent mechanistic works of this reaction: (a) Hollis, T. K.;
11
2
).
Bosnich, B. J. Am. Chem. Soc. 1995, 117, 4570. (b) Carreira, E. M.; Singer,
R. A. Tetrahedron Lett. 1994, 35, 4323. (c) Denmark, S. E.; Chen, C.-T.
Tetrahedron Lett. 1994, 35, 4327. (d) Denmark, S. E.; Henke, R. B. J. Am.
Chem. Soc. 1991, 113, 2177. (e) Mikami, K.; Matsukawa, S. J. Am. Chem.
Soc. 1993, 115, 7039. (f) Mikami, K.; Matsukawa, S. J. Am. Chem. Soc.
Scheme 2
1
994, 116, 4077. (g) Bernardi, A.; Capelli, A. M.; Gennari, C.; Goodman,
J. M.; Paterson, I. J. Org. Chem. 1990, 55, 3576. (h) Li, Y.; Paddon-Row,
M. N.; Houk, K. N. J. Org. Chem. 1990, 55, 481.
(
6) In particular, asymmetric catalysis of carbon-carbon bond-forming
reactions is the most attractive method. (a) Review: Iseki, K. Tetrahedron
998, 54, 13887. (b) Mikami, K.; Yajima, T.; Takasaki, T.; Matsukawa,
1
S.; Terada, M.; Uchimaru, T.; Maruta, M. Tetrahedron 1996, 52, 85. (c)
Mikami, K.; Yajima, T.; Terada, M.; Uchimaru, T. Tetrahedron Lett. 1993,
3
4, 7591. (d) Soloshonok, V. A.; Hayashi, T. Tetrahedron Lett. 1994, 35,
2
713 and references therein.
Indeed, the use of sterically more demanding triisoprop-
ylsilyl enol ether (2c) led to the preferential (90% isolated
(
7) Reviews: (a) Resnati, G.; Soloshonok, V. A., Eds. Tetrahedron 1996,
5
2, 1. (b) Olah, G. A.; Chambers, R. D.; Prakash, G. K. S. Synthetic Fluorine
Chemistry; Wiley: New York, 1992.
8) Reviews: (a) Soloshonok, V. A., Ed. Enantiocontrolled Synthesis of
(
(10) Chiral HPLC conditions, 4a: Daicel, CHIRALPAK OD-H, n-
hexane/i-PrOH 95:5, 0.8 mL/min, 254 nm, tR ) 10 min (3S), 12 min (3R).
anti-4d,f: Daicel, CHIRALPAK AS, n-hexane/i-PrOH 98:2, 0.8 mL/min,
254 nm, tR ) 11 min (2R,3S), 38 min (2S,3R) for anti-4d, tR ) 28 min
(2R,3S), 64 min (2S,3R) for anti-4f. anti-4e: Daicel, CHIRALPAK AS,
n-hexane/i-PrOH 95:5, 0.8 mL/min, 254 nm, tR ) 19 min (2R,3S), 37 min
(2S,3R).
Fluoro-organic Compounds; John Wiley & Sons: Chichester, 1999. (b)
Ojima, I., McCarthy, J. R., Welch, J. T., Eds. Biomedical Frontiers of
Fluorine Chemistry; American Chemical Society: Washington, D.C., 1996.
(
c) Resnati, G. Tetrahedron 1993, 49, 9385.
9) Mikami, K.; Motoyama, Y.; Terada, M. J. Am. Chem. Soc. 1994,
16, 2812.
(
1
2014
Org. Lett., Vol. 1, No. 12, 1999

1
5
yield) formation of the F-C product (3c) in excellent yields
and enantioselectivity (run 3). Furthermore, the F-C product
was also obtained in the reaction with glyoxylate esters.
However, only the usual aldol product was detected in the
reaction with benzaldehyde. The reaction of silyl enol ethers
reactions such as the carbonyl-ene reaction; the (R)-BINOL-
Ti catalyst produces an (R)-alcohol product.
The sequential diastereoselective reactions of the silyl enol
ether products were then examined with electrophiles
(Scheme 4). However, the epoxidation reactions of the
1
2
(2d,e,f) bearing a methyl substituent at the R position also
gave F-C products (3d,e,f) with similarly high enantio-
10
selectivity (runs 4-6). Under Mukaiyama-aldol conditions
catalyzed by the BINOL-Ti complex (Scheme 3), aliphatic
Scheme 4
Scheme 3
2
ketone-derived silyl enol ethers (R ) R′CH ) yield the ene-
tetrasubstituted silyl enol ethers (3) involve two conflicting
type homoallylic alcohol products (E).5 In sharp contrast,
the aromatic ketone-derived silyl enol ethers (R ) Ar) now
yielded the allylic (F) rather than homoallylic alcohol
products.
e
(1,3)
(1,2)
16,17
allylic (A) strains (A
vs A ) (Figure 2).
(Z)-Allylic
The stereochemical assignment of the F-C products
(
3a,d,e,f) deserves special comment. On the basis of the
1
chemical shifts of two types of allylic protons in the H NMR
spectra, the major isomers of the F-C products (3) were
determined to be Z (Figure 1).13 The major isomer of the
1
Figure 1. Chemical shifts in H NMR spectra.
F-C product (3c) was also determined to be Z on the basis
of similarities in their movement on TLC and the chemical
1
shift of hydroxyl proton in the H NMR spectra. The absolute
configuration of (Z)-3e was determined to be R by Mosher’s
method.14 Thus, the sense of asymmetric induction was the
same as that observed in BINOL-Ti-catalyzed asymmetric
Figure 2. Transition state of epoxidation by m-CPBA.
alcohols are generally reported to be epoxidized with high
(
11) The F-C products were not obtained in the reaction of aliphatic
(1,3)
syn (threo) selectivity due to the strong A
strain (Figure
ketone-derived silyl enol ethers without aromatic substituents such as 1-tert-
butyldimethylsilyloxy-1-cyclohexene and 2-tert-butyldimethylsilyloxy-1-
heptene.
2a). In cotrast, anti (erythro) selectivity is reported in the
(1,2)
large A
strain (Figure 2b). The oxidation reaction of the
(
12) Heathcock, C. H.; Buse, C. T.; Kleschick, W. A.; Pirrung M. C.;
Sohn, J. E.; Lampe, J. J. Org. Chem. 1980, 45, 1066. See ref 1b.
13) Both vinylic proton and allylic proton of the major isomer are
F-C product by m-CPBA proceeded, however, highly
diastereoselectively and yielded the syn-diastereomer in its
(
1
observed at upper field than the minor one in H NMR spectra (CDCl3) of
a (vinylic proton, 5.08 ppm (major), 5.15 ppm (minor); allylic proton,
18
unprotected form.
3
4
.46 ppm (major), 4.98 ppm (minor)): Rummens, F. H. A.; de Haan, J. W.
Org. Magn. Res. 1970, 2, 351.
14) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. The
chemical shift of vinylic methyl proton in H NMR spectra (CDCl3) of
(15) (a) Corey, E. J.; Barnes-Seeman, D.; Lee, T. W.; Goodman, S. N.
Tetrahedron Lett. 1997, 37, 6513. (b) Mikami, K.; Terada, M.; Nakai, T.
J. Am. Chem. Soc. 1990, 112, 3949; 1989, 111, 1940.
(
1
MTPA ester of (Z)-3e: 1.79 ppm (S), 1.55 ppm (R); δS - δR ) positive.
(16) Hoffmann, R. W. Chem. ReV. 1989, 89, 1841.
Org. Lett., Vol. 1, No. 12, 1999
2015

The relative configulation of the diol product 5 was
determined to be syn by X-ray analysis of a single crystal
stereoselective to give the anti-diastereomer but in a similar
stereoselective manner to that shown in m-CPBA oxidation
(Scheme 4).
19
20,21
(Figure 3). The sterically highly demanding trifluoromethyl
In summary, we have reported the Friedel-Crafts-type
reaction of silyl enol ethers as a possible mechanism in the
Mukaiyama-aldol reaction. In addition, the sequential dia-
stereoselective reactions of the resultant silyl enol ether
products with electrophiles were shown to give highly
functionalized trifluoro aldols with high enantio- and dia-
stereoselectivity.
Supporting Information Available: Experimental details
and spectral data for (Z)-3a,c-f, syn-5 and anti-4e. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL990330S
Figure 3. ORTEP drawing of syn-5.
(19) The single-crystal growth was carried out in a 1:1 n-hexane/
dichloromethane mixed solvent at room temperature. X-ray crystallographic
analysis was performed with a Rigaku AFC7R diffractometer (graphite
monochromator, Mo KR radiation, λ ) 0.71069 Å). The structure was solved
by direct method (SIR92), expanded using Fourier techniques (DIRDIF94),
and full-matrix least-squares refinement (SHELXL-93). Crystal data for
C12H13F3O3, colorless, crystal dimensions 0.30 × 0.20 × 0.10 mm,
substituent is located outside because of the larger A(1,3) strain
with either the sterically demanding silyl or aromatic groups
depending on the geometry. Likewise, the protodesilylation
reaction of the F-C product ((Z)-3e) was also highly
monoclinic, space group P21 (no. 4), a ) 10.345(2), b ) 10.538(3), c )
3
1
1.747(2) Å, â ) 90.97(1)°, V ) 1280.3(4) Å , · ) 4, Fcalcd ) 1.360 g
-
3
-1
cm , µ (Mo KR) ) 1.24 cm , T ) 233 K, 3112 reflections were
independent and unique, and 1754 with I > 2σ(I) (2θmax ) 55.0°) were
used for the solution of the structure. The non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were included but not refined. R ) 0.042,
Rw ) 0.156. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the Cambridge
Crystallographic Data Center as supplementary publication no. CCDC-
133938. Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB@ 1EZ, UK (fax: (+44) 1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk). We are grateful to Dr. Masahiro
Terada for his useful discussion and technical support on the X-ray analysis.
(20) The anti-diastereomer selectivity of R-methyl-â-hydroxy ketone (4e)
was determined to be 96% by HPLC analysis (Daicel, CHIRALPAK AS,
n-hexane/i-PrOH 95:5, 0.8 mL/min, 254 nm, tR ) 16 min (syn), 37 min
(anti)).
(
17) (a) Schwesinger, R.; Willaredt, J. In Houben-Weyl E21; Helmchen,
G., Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart,
996; Vol. 8. (b) Sharpless proposed the formation of hydrogen bond
1
between hydroxy groups and m-CPBA: Sharpless, K. B.; Verhoeven, T.
R. Aldrichimca Acta 1979, 12, 63. (c) Berti, G. In Topics of Stereochemistry;
Allinger, N. L., Eliel, E. L., Eds.; Wiley: New York, L 1973; Vol. 7, pp
41, 147. (d) Vedejs, E.; Dent, W. H. J. Am. Chem. Soc. 1989, 111, 6861.
e) Hauser, F. M.; Mal, D. J. Am. Chem. Soc. 1984, 106, 1862. (f) Mihelich,
E. D. Tetrahedron Lett. 1979, 20, 4729. (g) Rossiter, B. E.; Verhoeven, T.
R.; Sharpless, K. B. Tetrahedron Lett. 1979, 20, 4733. (h) Chautemps, P.;
Pierre, J.-L. Tetrahedron 1976, 32, 549. (i) Chamberlain, P.; Roberts, M.
L.; Whitham, G. H. J. Chem. Soc. B 1970, 1374.
1
(
(
18) The diastereomeric excess of R,â-dihydroxy ketone (5) was
1 19
determined to be >95% by H and F NMR analysis. The relative
configuration was estimated to be syn on the basis of the chemical shifts of
R-methyl carbons in C NMR spectra (CDCl3) of 5 (syn 23.4 ppm, anti
5.1 ppm): Heathcock, C. H.; Pirrung M. C.; Sohn, J. E. J. Org. Chem.
979, 44, 4294.
(21) The relative configuration was determined to be anti on the basis
1
3
13
of the chemical shifts of R-methyl carbon in C NMR spectra (CDCl3) of
2
1
4d (syn 11.9 ppm, anti 16.3 ppm), 4e (anti 16.5 ppm), respectively. See ref
18.
2016
Org. Lett., Vol. 1, No. 12, 1999