Silicon-(thio)urea Lewis acid catalysis

Article abstract of DOI:10.1021/ja110685k

We present a new class of catalysts based on the combination of N,N′-diaryl(thio)ureas and weak silicon Lewis acids (e.g., SiCl ₄). Such silicon-(thio)urea catalysts effectively catalyze the stereospecific rearrangement of epoxides to quaternary carbaldehydes.

Full text of DOI:10.1021/ja110685k

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Siliconꢀ(Thio)urea Lewis Acid Catalysis
Radim Hrdina,§ Christian E. M€uller,§ Raffael C. Wende,§ Katharina M. Lippert,§ Mario Benassi,‡
Bernhard Spengler,‡ and Peter R. Schreiner*,§
§Institute of Organic Chemistry, Justus-Liebig University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany
‡Institute of Inorganic and Analytical Chemistry, Justus-Liebig University, Schubertstr. 60, 35392 Giessen, Germany
S Supporting Information
b
Scheme 1. In Situ Preparation of the Siliconꢀ(Thio)urea
ABSTRACT: We present a new class of catalysts based on
the combination of N,N0-diaryl(thio)ureas and weak silicon
Lewis acids (e.g., SiCl4). Such siliconꢀ(thio)urea catalysts
effectively catalyze the stereospecific rearrangement of ep-
oxides to quaternary carbaldehydes.
Catalyst (X = O, S)
oth (thio)urea1 and silicon-based catalysts have been suc-
B
cessful individually for a large variety of reactions. Herein we
show that the use of a catalyst that combines an N,N0-diaryl-
(thio)urea with a weak SiCl2R2 Lewis acid is a powerful new
approach. There are three strategies to activate silicon for
catalysis: incorporation into a strained cycle,2 connection to a
strongly electron-withdrawing group,3 and activation with Lewis
bases.4 Here we combine the first and second approach by in situ
formation of a strained silacycle2h from readily available
precursors: (thio)urea derivatives, halosilanes, and tertiary
amines (Scheme 1).
Scheme 2. Rearrangement of Epoxides to Aldehydes or Ke-
tones Catalyzed by Lewis Acids
We chose as our test reaction the rearrangement5 of trisub-
stituted epoxides to aldehydes, which is demanding in terms
of selectivity for the alkyl versus hydrogen shift, availability of
catalytic variants, and stereospecificity (Scheme 2). For instance,
Pd,6 Bi,7 Ir,8 In,9 V,10 Er,11 Fe,12 and Cu13 complexes promote
the hydrogen shift, while B,14 Al,15 and Cr16 favor alkyl migration.
The rearrangement of alkyl groups cis to an aryl moiety is
particularly challenging; indeed, such alkyl migrations occur
stereospecifically only for Cr complexes.16 The selectivities
are highly sensitive to the substitution pattern of the epoxide.
Quaternary carbaldehydes are versatile building blocks in
organic synthesis and are attractive targets for catalysis.
1-Phenyl-1,2-cyclohexene oxide (1a) was selected to deter-
mine the optimal conditions for the rearrangement. Various
chlorosilanes X were chosen to react with thiourea T1 to give the
Scheme 3. Screening of Silane Precursorsa
a NMR yields are given.
corresponding catalysts T1 X. The rearrangement proceeded
3
(Scheme 5). The precursor alkenes were prepared by a Wittig
reaction that produced mixtures of E and Z isomers; m-chloro-
peroxybenzoic acid (m-CPBA) oxidation furnished the corre-
sponding epoxides. The product distributions and conversions as
well as the E/Z ratios of the unreacted epoxide starting materials
for the rearrangement are summarized in Scheme 5 and the SI.
Typically, the alkyl shift trans to the aryl moiety was considerably
faster than that for the cis configuration, reaching completion
within 1 h (vs 18 h for cis).
well in polar aprotic solvents such as dichloromethane (DCM),
chloroform, and acetonitrile. In tetrahydrofuran (THF), toluene,
and EtOAc, no product formed. No combination of reagents
other than that given in Scheme 3 led to the rearrangement
product [for details, see the Supporting Information (SI)].
The yield of the rearrangement may depend on the electron-
withdrawing ability of the (thio)urea derivative or the propensity
for formation of the catalyst (TX AꢀUX A) by SiCl4 (A) in
3
3
combination with various N,N0-diaryl(thio)ureas (TXꢀUX)
(Scheme 4).
Catalyst T1 A proved to be the most reactive and was
applied in the rearrangement of various trisubstituted epoxides
Received: November 29, 2010
Published: April 28, 2011
3
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2011 American Chemical Society
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Scheme 4. Screening of N,N0-Diaryl(thio)urea Precursorsa
a NMR yields are given.
Scheme 5. Rearrangement of Epoxides to Quaternary Alde-
hydes Using SiliconꢀThiourea Catalyst T1 A
3
Figure 1. (AꢀF) 1H and 13C NMR spectra, respectively, of (A, D) T1
alone; (B, E) after addition of 1 equiv of DIPEA (the NH signals are
under the broadened signal at 7.8 ppm); and (C, F) after addition of
2 equiv of DIPEA and 1 equiv SiCl4 to give T1 A. (G) 29Si NMR
3
spectrum of T1 A.
3
We then turned our attention to the viability of our structural
proposal17 for the best catalyst T1 A (see Scheme 1) by utilizing
3
a combination of NMR and IR spectroscopy, mass spectrometry
(see the SI), and density functional theory (DFT) computations
(Figures 1 and 2). The changes in the 1H and 13C NMR chemical
shifts upon addition of 1 equiv of N,N-diisopropylethylamine
(DIPEA) to T1 (Figure 1A, B and D, E) suggest monodepro-
tonation of T1. Although the pKa value of T1 is not known, it is
likely to be just below or around that of protonated DIPEA
(pKa = 11.4); diphenylurea has a pKa of 13.4,18 so it is reasonable
to assume that the thiourea congener with the four added CF3
groups is considerably more acidic. Hence, there should be a
Figure 2. B3LYP/6-31þG(d,p)-optimized structure of T1 A. NBO
3
charges (in e) and selected bond lengths (in Å) and angles (in deg)
are shown.
protonation/deprotonation equilibrium between T1 and the
base, as also evidenced by the disappearance (in part under the
CH signal at 7.8 ppm) of the NꢀH resonances. The CdS carbon
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Scheme 6. Stereospecificity of the Rearrangement and Ab-
solute Configurations of the Productsa
a Isolated yields are given.
Figure 3. Change in ee over time in the rearrangement of (S,R)-1d to
Scheme 7. Chemoselectivity: Alkyl versus Hydrogen Shift
(R)-2d catalyzed by T1 A.
3
Scheme 8. Simplified Mechanistic Proposal for the Epoxide
Rearrangements Catalyzed by T1 X [Ar = 3,5-Bis(trifluoro-
3
methyl)benzene]
signal appeared upfield (by 10.6 ppm), in agreement with
stronger shielding of the delocalized anion. The IR spectra of
the same solutions (Figure S3 in the SI) support this analysis: the
single NꢀH signal for T1 at 3375.2 cmꢀ1 split into two and lost
intensity significantly. Upon addition of 1 equiv of SiCl4 (along
with another 1 equiv of DIPEA) to this mixture, T1 A formed
3
(Figure 1C, F), and the CdS carbon signal moved downfield by
15.1 ppm. The NꢀH signal no longer exchanged and appeared at
9.6 ppm. Similar changes were observed in the 29Si spectra
(Figure 1G; also see the SI). We also identified a 4J coupling of
the thiourea ortho protons with Si, indicating that they must be in
close proximity (Figure S17). The IR difference spectra (Figure
S23) of a 1:2 mixture of T1 and DIPEA with and without A
also showed the disappearance of the T1 NꢀH absorption
(3400 cmꢀ1) and the appearance of the ammonium salt NꢀH
rearranged in good yields to the corresponding aldehydes 2b
and 2d, respectively, within 1 h with only marginal losses of
enantiopurity. The absolute configurations of the products were
determined by comparison with published data.19
The enantioenriched Z derivatives (S,R)-1b and (S,R)-1d
(from Shi epoxidation)20 underwent partial hydrogen shifts,
leading to ketones as byproducts: 3% ketone 3b (74% ee) and
5% ketone 3d (76% ee) formed. We screened the chemoselec-
tivities (Scheme 7) with T1 X and found that T1 A was the
bands at 2661 cmꢀ1
.
1
Additionally, we identified small signals in the H and 13C
3
3
NMR spectra (Figure 1C, F) indicative of a small concentration
most selective, affording 85% aldehyde 2b (76% ee) and only 3%
ketone 3b (74% ee). For comparison, the rearrangement of
(S,R)-1b catalyzed by 25 mol % Et2AlCl21 in toluene gave 47%
aldehyde (R)-2b stereospecifically, with the same stereochemis-
of another species, probably a dimer of T1 A. Our high-resolu-
3
tion (nanospray negative-ion mode) mass spectrometric experi-
ments (Figures S18ꢀS22) underline this observation. While it
is unlikely that a spirocycle with Si in the center is involved,17 we
were unable to draw definitive conclusions about the exact nature
of this minor component.
try as with T1 X. This implies that these catalyst systems are
3
mechanistically similar.
Surprisingly, the enantiopurity of the rearranging (S,R)-1b
B3LYP/6-31þG(d,p) computations (Figure 2; also see the SI)
and (S,R)-1d increased over time with all T1 X (as shown for
3
identified T1 A as a minimum with a planar four-membered
T1 A in Figure 3). The product ee also increased until it reached
3
3
central ring. The natural bond orbital (NBO) charges indicated
that this structure may be regarded as an internal salt of a
resonance-stabilized thiourea dianion with a Si dication. The
large positive charge on Si in the complex suggests high tunability
of the catalyst through substitution.
Next, the stereospecificity of the rearrangement was studied
utilizing the E and Z isomers of 1b and 1d (Scheme 6). When
that of the starting material. The increase in the enantiomeric
purity of the starting material was not due to autocatalysis by the
product, as demonstrated by a negative control experiment
utilizing racemic 1b with 5 mol% T1 A [(R)-2b (10%, 76%
3
ee)]. We preliminarily rationalize these findings in terms of a
mechanism similar to a kinetic resolution of nonracemic starting
materials.22 The increase in ee during the reaction may be due to
diastereomeric transition structures formed in the simplest case
5 mol% T1 A was used, the enantioenriched (E)-epoxides
3
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We have shown that Lewis acid catalysis can be combined with
(thio)urea catalysis, as exemplified by the novel catalyst T1 A
3
that enables the stereospecific rearrangement of trisubstituted
epoxides to quaternary aromatic carbaldehydes. A natural exten-
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’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
spectroscopic data for new compounds. This material is available
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Corresponding Author
prs@org.chemie.uni-giessen.de
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’ ACKNOWLEDGMENT
This work was supported by the Alexander-von-Humboldt
Foundation (fellowship to R.H.). M.B. and B.S. acknowledge
financial support by the Hessian Ministry of Science and Arts
(HMWK) through LOEWE Focus “AmbiProbe“.
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