The crystallographic structure of a Lewis acid-assisted chiral Bronsted acid as an enantioselective protonation reagent for silyl enol ethers

Article abstract of DOI:10.1021/ja021000x

It is difficult to control the enantioselectivity in the protonation of silyl enol ethers with simple chiral Bronsted acids, mainly due to bond flexibility between the proton and its chiral counterion, the orientational flexibility of the proton, and the fact that the proton sources available are limited to acidic compounds such as chiral carboxylic acids. To overcome these difficulties, we have developed a Lewis acid-assisted chiral Bronsted acid (LBA) system. The coordination of Lewis acids with Bronsted acids restricts the orientation of protons and increases their acidity. Optically active binaphthol (BINOL) derivative·SnCl₄ complexes are very effective as enantioselective protonation reagents for silyl enol ethers. However, their exact structures have not yet been determined. We describe here optically active 1,2-diarylethane-1,2-diol derivative·SnCl₄ as a new type of LBA for the enantioselective protonation as well as its crystallographic structure. A variety of optically active 1,2-diarylethane-1,2-diols could be readily prepared by asymmetric syn-dihydroxylation. This is a great advantage over BINOL for the flexible design of a new LBA. The most significant finding is that we were able to specify the conformational direction of the H-O bond of LBA, which has some asymmetric inductivity, by X-ray diffraction analysis. The stereochemical course in the enantioselective protonation of silyl enol ethers using LBA would be controlled by a linear OH/π interaction with an initial step. The absolute stereopreference in enantioselective reactions using BINOL·SnCl₄ can also be explained in terms of this uniformly mechanistic interpretation. Copyright

Full text of DOI:10.1021/ja021000x

Published on Web 12/07/2002
The Crystallographic Structure of a Lewis Acid-Assisted Chiral Brønsted Acid
as an Enantioselective Protonation Reagent for Silyl Enol Ethers
Kazuaki Ishihara, Daisuke Nakashima,† Yukihiro Hiraiwa,† and Hisashi Yamamoto*,†
Graduate School of Engineering, Nagoya UniVersity, SORST, Japan Science and Technology Corporation (JST),
Furo-cho, Chikusa, Nagoya 464-8603, Japan
Received July 22, 2002; E-mail: yamamoto@uchicago.edu
Scheme 1. Preparation of (R,R′)-1,2-Diarylethane-1,2-diol
It is difficult to control the enantioselectivity in the protonation
of silyl enol ethers with chiral Brønsted acids, mainly due to bond
flexibility between the proton and its chiral counterion, the
orientational flexibility of the proton, and the fact that the proton
sources available are limited to acidic compounds such as carboxylic
acids. To overcome these difficulties, we have developed a Lewis
acid-assisted chiral Brønsted acid (LBA) system.1,2 The coordination
of Lewis acids with Brønsted acids restricts the orientation of
protons and increases their acidity. Optically active binaphthol
(BINOL) derivative‚SnCl4 complexes are very effective as enan-
tioselective protonation reagents for silyl enol ethers.1 However,
their exact structures have not yet been determined.3 We describe
here optically active 1,2-diarylethane-1,2-diol derivative‚SnCl4 as
a new type of LBA for the enantioselective protonation as well as
its crystallographic structure.
Derivativesa
a 1 (Ar ) Ph), >99% ee; 2 (Ar ) 3,4,5-F3C6H2), ee was not determined;
3 (Ar ) C6F5), 82% ee f 94% ee after recrystallization; 4 (Ar ) 3,5-
(CF3)2C6H3), >99% ee; 5 (Ar ) Ph, R ) Me), >99% ee; 6 (Ar ) 3,5-
(CF3)2C6H3, R ) Bn), >99% ee; 7 (Ar ) 3,5-(CF3)2C6H3, R ) o-FC6H4CH2),
>99% ee; 8 (Ar ) 3,5-(CF3)2C6H3, R ) Me), >99% ee.
Table 1. Enantioselective Protonation of 9 with (R,R)-LBAsa
As shown in Scheme 1, (R,R)-2-4 were prepared in high
chemical and optical yields by Sharpless syn-dihydroxylation of
the corresponding (E)-1,2-diarylethenes, which were in turn ob-
tained by McMurry or Wittig reactions.4 The selective mono-
etherification5 of 2-4 effectively increased their solubility in organic
solvents.
The enantioselective protonation of 9 was examined using (R,R)-
1-4 (1.1 equiv) and SnCl4 (1.1 equiv) (Table 1). The reaction
proceeded in CH2Cl2 at -78 °C and gave (S)-10 with 96% ee (entry
4). The same enantioselectivity was observed using (R,R)-6 (entry
5). (R,R)-4 was almost insoluble under the above conditions, while
(R,R)-6 dissolved in CH2Cl2 and toluene even at -78 °C. The
enantioselectivity was somewhat diminished in toluene (entry 6).
In contrast, in the presence of commercially available (R,R)-
hydrobenzoin (1) and SnCl4, protonation did not proceed completely
at -78 °C, and the ee value was relatively low (entry 1). (R,R)-2
and 3 exhibited good reactivity, but the ee values were low (entries
2 and 3).
Monoalkyl ethers (R,R)-6-8 were examined for the enantio-
selective protonation of various silyl enol ethers in the presence of
SnCl4. The results are summarized in Table 2. The corresponding
ketones and carboxylic acids were isolated in quantitative yield.
High enantioselectivities were observed for the protonation of
trimethylsilyl enol ethers derived from aromatic ketones and ketene
bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids.6 Al-
though dichloromethane was used for the protonation of silyl enol
ethers, toluene was a better solvent for highly reactive ketene bis-
(trimethylsilyl)acetals, because the protonation proceeded more
quickly in a polar solvent. The scope of substrates that are suitable
for enantioselective protonation was extended by using the new
chiral LBA complexes in place of (R)-BINOL derivatives‚SnCl4.
For example, the enantioselectivities in the protonation of silyl enol
ether derived from 11 and ketene disilylacetal derived from 17 were
chiral Brønsted
acidb
ee (%)
entry
solvent
[config.]c
1d
1
toluene-CH2Cl2
(1:1 (v/v))
CH2Cl2
CH2Cl2
CH2Cl2
66 [S]
2
3
4
5
6
2e
3f
4
6
6
51 [S]
35 [R]
96 [S]
96 [S]
91 [S]
CH2Cl2
toluene
a A 0.2 M solution of 9 (0.1 mmol) was added dropwise to a solution of
chiral Brønsted acid (0.11 mmol) and SnCl4 (0.11 mmol) over a 5 min
period at -78 °C. b Unless otherwise noted, >99% ee of chiral Bronsted
acids was used. c The ee value of 10. d The reaction was carried out at -78
°C for 1.5 h, but some 9 remained. e The ee value of 2 ([R]26.6 ) -54.0
D
(c 0.36, CHCl3)) was unknown. f 94% ee of 3 was used.
increased from 37 to 83% ee (entry 1) and from 37 to 76% ee
(entry 7), respectively. Nonsteroidal antiinflammatory drugs7 such
as naproxen (12)7 and ibuprofen (13) were obtained with 86 and
90% ee, respectively (entries 2 and 3). The absolute stereopreference
for ketene bis(trimethylsilyl) acetals was similar to that for 9.
To understand the absolute stereopreference in the protonation,
the crystallization of LBA was attempted. In most cases, however,
SnCl4-free Brønsted acids were preferentially crystallized in the
presence of SnCl4, because Brønsted acid‚SnCl4 was less likely to
undergo crystallization than was Brønsted acid, and the complex-
ation was reversible.3 Fortunately, a colorless crystal of (R,R)-5‚
SnCl4 was obtained from a 1:1 molar mixture of (R,R)-5 and SnCl4
in dichloromethane at 0 °C. This result can be explained in terms
of the relatively tight complexation between SnCl4 and (R,R)-5,
which is less acidic than (R,R)-6-8 and (R)-BINOL derivatives.
Single-crystal X-ray diffraction analysis of this LBA revealed the
structure shown in Figure 1. Although the activated proton (Hact)
in (R,R)-5‚SnCl4 could not be located exactly, the high electron
density was certainly distributed in the pseudoequatorial direction.
Interestingly, the apical Sn1-Cl3 bond is ca. 0.05 Å longer than
† Current address: Department of Chemistry, University of Chicago, 5735 South
Ellis Avenue, Chicago, IL 60637.
9
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J. AM. CHEM. SOC. 2003, 125, 24-25
10.1021/ja021000x CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Enantioselective Protonation of Silyl Enol Ethers or
Ketene Disilyl Acetals with (R,R)-LBAs
Figure 2. Proposed tranition-state assemblies.
from 14 with (R,R)-8‚SnCl4 can be understood in terms of two
proposed transition-state assemblies, TS-1 and TS-2, shown in
Figure 2. The ketene disilyl acetal should approach (R,R)-8‚SnCl4
from the re-face via the favored TS-1 due to the π-π electronic
attractive interaction between a Ph group of the substrate and a
3,5-(CF3)2C6H3 group closer to the Hact, while the approach from
the si-face via TS-2 would not be favorable due to steric repulsion
between Me3SiO groups and an SnCl4 or CF3 group.6 This model
can be adopted for all cases shown in Tables 1 and 2.10
The most significant finding is that we were able to specify the
conformational direction of the H-O bond of LBA, which has some
asymmetric inductivity, by X-ray diffraction analysis. The stereo-
chemical course in the enantioselective protonation would be
controlled by a linear OH/π interaction with an initial step. The
absolute stereopreference in enantioselective reactions using BINOL‚
SnCl4 can also be explained in terms of this uniformly mechanistic
interpretation.1,2
a The ee values were determined by HPLC or GC analysis of ketones or
methyl esters derived from carboxylic acids (cat. HfCl4‚(THF)2 in MeOH).8
b The ee values are indicated when (R)-BINOL derivatives‚SnCl4 were used
in toluene. c The ee value after recrystallization from a CH2Cl2-hexane
bilayer system.
Acknowledgment. This work was supported in part by a grant
from the Asahi Glass Foundation.
Supporting Information Available: Experimental procedures,
spectral data for all new compounds (PDF), and crystallographic data
(CIF). This material is available free of charge via the Internet at http://
pubs.acs.org.
References
Figure 1. ORTEP drawing of (R,R)-5‚SnCl4 (the O1-Hact bond distance
shown here is not certain, but its direction could be determined). Selected
distances (Å): O1-Hact ) 0.72(3), Sn1-Cl3 ) 2.40185(5), Sn1-Cl4 )
2.3522(6), intermolecular Hact‚‚‚C13 ) 2.402. Torsion angles (deg):
Cl3-Sn1-O1-Hact ) -64, Cl1-Sn1-O1-Hact ) 30. Bond angles
(deg): Sn1-O1-Hact ) 119(2), C2-O1-Hact ) -64(2), intermolecular
O1-Hact‚‚‚Cl3 ) 171.11.
(1) (a) Ishihara, K.; Kaneeda, M.; Yamamoto, H. J. Am. Chem. Soc. 1994,
116, 11179. (b) Ishihara, K.; Nakamura, S.; Kaneeda, M.; Yamamoto, H.
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the apical Sn1-Cl4 bond due to the intermolecular hydrogen
bonding interaction between Hact and Cl3. The protonation of 9
using crystalline (R,R)-5‚SnCl4 in dichloromethane at -78 °C gave
(S)-10 with 58% ee (cf. entry 1 in Table 1: (S)-10 with 66% ee).
This result supports the idea that the X-ray structure for (R,R)-5‚
SnCl4 is a real species of the protonation reagent.
The driving force in the enantioselective protonation is the OH/π
interaction between its π-bond orbital (HOMO) and the activated
proton (LUMO). It has been known that a linear O-H‚‚‚π bonding
interaction has the most preferable direction along with a hydrogen
bonding interaction.9 Therefore, the prochiral face of silyl enol ether
would approach the activated proton of LBA perpendicular to its
H-O bond.
(3) Only SnCl4-free BINOL derivatives crystallized from a 1:1 mixture of
BINOL derivatives and SnCl4.
(4) Donnoli, M. I.; Scafato, P.; Superchi, S.; Rosini, C. Chirality 2001, 13,
258.
(5) Greene, A. E.; Drian, C. L.; Crabbe, P. J. Am. Chem. Soc. 1980, 102,
7583.
(6) Low ee values were observed for the protonation of aliphatic silyl enol
ethers with chiral LBA (e.g. (R)-2-methylcyclohexanone, 23% ee).
(7) Harrington, P. J.; Lodewijk, E. Org. Process Res. DeV. 1997, 1, 72.
(8) Ishihara, K.; Ohara, S.; Yamamoto, H. Science 2000, 290, 1140.
(9) (a) Josien, M.-L.; Sourisseau, G. In Hydrogen Bonding; Hadzi, D.,
Thompson, H. W., Eds.; Pergamon Press: Elmsford, NY, 1959; pp 129-
137. (b) Pimentel, G. C. The Hydrogen Bond; Freeman: W. H. New York,
1960; p 194. (c) Ueji, S.; Nakatsu, K.; Yoshioka, H.; Kinoshita, K.
Tetrahedron Lett. 1982, 23, 1173.
The direction of the H-O bond in (R,R)-8 can be fixed by
chelation with SnCl4. On the basis of the X-ray diffraction analysis
of LBA and a linear OH/π interaction, the absolute stereopreference
in the enantioselective protonation of ketene disilylacetal derived
(10) The opposite absolute stereopreference observed in entry 3, Table 1 is
probably due to some unexpected interactions between o-F and Hact, Sn-
(IV), or Si(IV).
JA021000X
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