Catalytic asymmetric rearrangement of α,α-disubstituted α-siloxy aldehydes to optically active acyloins using axially chiral organoaluminum Lewis acids

Article abstract of DOI:10.1021/ja063051q

A catalytic asymmetric rearrangement of α,α-dialkyl-α-siloxy aldehydes has been developed based on the design of a stereochemically defined, axially chiral organoaluminum Lewis acid 3. For instance, treatment of (S,S)-4 (1.1 equiv) with Me₃Al in toluene at room temperature for 30 min generated (S,S)-3 (5 mol %), and subsequent reaction with α-siloxy aldehyde 1a (R = CH₂Ph) at -20 °C for 12 h resulted in the smooth rearrangement to afford the corresponding α-siloxy ketone 2a (R = CH₂Ph) in 96% isolated yield with 87% ee (S). The scope of this unprecedented stereoselective rearrangement has been investigated with representative substrates, in which impressive kinetic resolution of racemic, α,α-disubstituted α-siloxy aldehydes has also been achieved. These results clearly demonstrate the utility of the present approach for the catalytic enantioselective synthesis of various acyloins and tertiary α-hydroxy aldehydes not readily accessible by the previously known asymmetric methodologies. Copyright

Full text of DOI:10.1021/ja063051q

Published on Web 02/10/2007
Catalytic Asymmetric Rearrangement of r,r-Disubstituted r-Siloxy Aldehydes
to Optically Active Acyloins Using Axially Chiral Organoaluminum Lewis
Acids
Takashi Ooi,† Kohsuke Ohmatsu, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received May 2, 2006; E-mail: maruoka@kuchem.kyoto-u.ac.jp
Table 1. Catalytic Asymmetric Rearrangement of
R,R-Dialkyl-R-siloxy Aldehydes 1 with (S,S)-3a
The skeletal rearrangements involving 1,2-carbon-to-carbon
migration are fundamental yet powerful methods for the structural
reorganization of organic molecules through the consecutive or
concurrent cleavage and formation of carbon-carbon bonds,1 often
making it feasible to construct otherwise inaccessible molecular
frameworks. However, precise control of the stereochemical
outcome together with the migratory aptitude is not a trivial task
mainly because of the proneness to generate an intermediary
carbocation under the conventional conditions. Thus, research for
the elaboration of stereoselective variants had long been circum-
vented. The delivery of effective Lewis acids to this field resulted
in an important progress, enabling the stereospecific reaction using
chiral substrates, which generally establishes complete chirality
transfer with either stoichiometric or catalytic amount of an
appropriate promoter.2 Nevertheless, such endeavors are still very
limited, and in turn, examples of success in the enantioselectiVe
1,2-rearrangement of achiral substrates by the use of chiral activator,
especially in a catalytic quantity, have been extremely rare despite
its conceptual and practical significance.3 In conjunction with our
recent studies on the organoaluminum-promoted selective rear-
rangement of aminocarbonyl compounds,4 we here report our own
approach toward this subject, that is, the development of skeletal
rearrangement of R,R-dialkyl-R-siloxy aldehydes 1, which can be
efficiently catalyzed by newly designed chiral organoaluminum
Lewis acid 3 with high enantioselectivity, thereby offering a facile
access to various optically active acyloins (Scheme 1).5
entry
R1
R2
% yieldb
% eec
product
3
1
2
3
4
5
6
7
8
9
PhCH2 (1a)
PhCH2 (1a)
PhCH2 (1a)
PhCH2 (1a)
p-MeO-C6H4CH2 (1b)
p-F-C6H4CH2 (1c)
p-Cl-C6H4CH2 (1d)
2-NaphCH2 (1e)
Me3
Et3
t-BuMe2
Et3
Et3
Et3
96
99
99
96
98
97
94
95
81
84
94
97
77
87
80
87
85
90
86
85
83
80
74
74
2a
2a
2a
2a
2b
2c
2d
2e
2f
Et3
Et3
trans-PhCHdCHCH2 (1f) Et3
10
11
12
(CH3)2CdCHCH2 (1g)
(CH3)2CHCH2 (1h)
c-Hex (1i)
Et3
Et3
Et3
2g
2h
2i
a The reaction was carried out with either 10 mol % (entries 1-3) or 5
mol % (entries 4-12) of (S,S)-3 in toluene at -20 °C for 12 h. b Isolated
yield. c Enantiopurity was determined by HPLC analysis. The absolute
configuration of 2a was determined to be S by comparison of the optical
rotation with a literature value after desilylation.4
Scheme 1
On the basis of our preliminary studies on the search for suitable
chiral Lewis acid catalysts with R,R-dibenzyl-R-trimethylsiloxy
aldehyde (1a, R2 ) Me) as a representative substrate,6 we designed
a new axially chiral organoaluminum Lewis acid 3 that possesses
the chiral environment created by the 2-[3,5-bis(trifluoromethyl)-
phenyl]-substituted naphthyl moiety being extended over the
coordination site of the aluminum, possibly enabling rigorous
stereocontrol.
The requisite ligand 4 can be synthesized from (S)-BINOL in a
seven-step sequence.7 Interestingly, the molecular structure of 4
visualized by the single-crystal X-ray diffraction analysis adopted
homochiral (S,S) configuration (Scheme 1, cylinder model),7,8 and
refluxing a solution of 4 in toluene for 24 h showed no conforma-
tional interconversion between (S,S) and (S,R) isomers. Thus,
treatment of (S,S)-4 (1.1 equiv) with Me3Al in toluene at room
temperature for 30 min generated in situ the stereochemically
defined methylaluminum catalyst (S,S)-3 (10 mol %),9 and subse-
quent reaction with 1a (R2 ) Me) at -20 °C for 12 h resulted in
clean formation of the desired R-siloxy ketone 2a (R2 ) Me) in
96% yield with 77% ee (entry 1 in Table 1). This promising result
prompted us to evaluate the effect of the trialkylsilyl group on the
stereoselectivity, and R-triethylsiloxy linkage in 1a was found to
be optimal, leading to the quantitative production of the rearranged
2a (R2 ) Et) with 87% ee under similar conditions (entry 2).
Notably, the catalyst loading can be reduced to 5 mol % without
significant loss of reactivity and selectivity (entry 4).
With the optimized conditions in hand, we conducted the
experiments to probe the scope of this new catalytic asymmetric
1,2-rearrangement, and the selected examples are included in Table
1.10 Generally, the reaction proceeded smoothly at -20 °C under
the influence of 5 mol % of (S,S)-3. A series of R-siloxy aldehydes
bearing R-benzylic substituents of different electronic properties
were tolerated (entries 5-8). The substrates having allylic R-sub-
† Current address: Department of Applied Chemistry, Graduate School of
Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan.
9
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J. AM. CHEM. SOC. 2007, 129, 2410-2411
10.1021/ja063051q CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Kinetic Resolution of Differently R,R-Disubstituted
R-Siloxy Aldehydes 5a
lective 1,2-rearrangement of R-alkoxycarbonyl compounds and
provides a unique tool for the synthesis of various acyloins and
tertiary R-hydroxy aldehydes of high enantiomeric purities. Further
intensive studies on the application of this approach are currently
underway in our laboratory.
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Scientific Research on Priority Areas “Advanced
Molecular Transformation of Carbon Resources” from the Ministry
of Education, Culture, Sports, Science and Technology, Japan. K.O.
is grateful to the Japan Society for the Promotion of Science for
Young Scientists for a Research Fellowship.
time
(h)
% yield
% eec,d
(config)
recovery
% eec,e
(config)
entry
5
of 6b
of 5 (%)b
s
1
2
3
4
5
6
5a
5a
5b
5c
5d
5e
12
15
11
12
3
49 (6a)
55 (6a)
49 (6b)
51 (6c)
57 (6d)
55 (6e)
86 (S)
79 (S)
86
85
63
51
45
51
49
43
44
84 (R)
92 (R)
85
83
90
39.5
22.7
44.2
22.8
15.6
17.5
Supporting Information Available: Representative experimental
procedures and spectroscopic characterization of new compounds
(PDF); the crystallographic data for (S,S)-4 (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
0.5
77
88
a The reaction was conducted with 5 mol % of (S,S)-3 in toluene at
-20 °C for the given reaction time. b Isolated yield. The ratio of 6 to the
product through the migration of R2 was >20:1. c Determined by HPLC
analysis. d The absolute configuration was determined by comparison of
the optical rotation with a reported value after desilylation.16 e For
assignment of the absolute configuration, see Scheme 2.
References
(1) For reviews, see: ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, Chapter 3,
pp 705-1014.
Scheme 2
(2) Pinacol-type rearrangement: (a) Suzuki, K.; Katayama, E.; Tsuchihashi,
G. Tetrahedron Lett. 1983, 24, 4997. (b) Suzuki, K.; Tomooka, K.;
Shimazaki, M.; Tsuchihashi, G. Tetrahedron Lett. 1985, 26, 4781 and
references therein. Epoxy ether rearrangement: (c) Maruoka, K.; Hase-
gawa, M.; Yamamoto, H.; Suzuki, K.; Shimazaki, M.; Tsuchihashi, G. J.
Am. Chem. Soc. 1986, 108, 3827. (d) Suzuki, K.; Miyazawa, M.;
Tsuchihashi, G. Tetrahedron Lett. 1987, 30, 3515. (e) Maruoka, K.; Ooi,
T.; Nagahara, S.; Yamamoto, H. Tetrahedron 1991, 47, 6983. (f) Suda,
K.; Kikkawa, T.; Nakajima, S.-i.; Takanami, T. J. Am. Chem. Soc. 2004,
126, 9554.
stituents also underwent highly enantioselective rearrangement,
featuring the advantage of this method to construct enantiomerically
enriched acyloins not readily accessible by the previously known
methodologies (entries 9 and 10).5 It should be emphasized that
extremely facile migration of a simple alkyl group was realized
with good enantioselectivity (entries 11 and 12).
(3) (a) Brunner, H.; Sto¨hr, F. Eur. J. Org. Chem. 2000, 2777. (b) Trost, B.
M.; Yasukata, T. J. Am. Chem. Soc. 2001, 123, 7162. (c) See also: Trost,
B. M.; Xie, J. J. Am. Chem. Soc. 2006, 128, 6044.
(4) Ooi, T.; Saito, A.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 3220.
(5) For asymmetric synthesis of R-hydroxy ketones, see oxidation by chiral
phase-transfer catalysis: (a) Masui, M.; Ando, A.; Shioiri, T. Tetrahedron
Lett. 1988, 29, 2835. Oxidation with chiral oxaziridines: (b) Davis, F.
A.; Sheppard, A. C.; Chen, B.-C.; Haque, M. S. J. Am. Chem. Soc. 1990,
112, 6679. Dihydroxylation of enol ethers: (c) Hashiyama, T.; Morikawa,
K.; Sharpless, K. B. J. Org. Chem. 1992, 57, 5067. Benzoin condensa-
tion: (d) Enders, D.; Kallfass, U. Angew. Chem., Int. Ed. 2002, 41, 1743.
Nitroso aldol synthesis: (e) Momiyama, N.; Yamamoto, H. J. Am. Chem.
Soc. 2003, 125, 6038. (f) Co´rdova, A.; Sunde´n, H.; Bøgevig, A.;
Johansson, M.; Himo, F. Chem.sEur. J. 2004, 10, 3673. (g) Hayashi,
Y.; Yamaguchi, J.; Sumiya, T.; Hibino, K.; Shoji, M. J. Org. Chem. 2004,
69, 5966. (h) Wang, W.; Wang, J.; Li, H.; Liao, L. Tetrahedron Lett.
2004, 45, 7235. (i) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc.
2005, 127, 1080. Cross silyl benzoin reaction: (j) Linghu, X.; Potnick, J.
R.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126, 3070.
To further expand the scope of the present system, we investi-
gated the rearrangement of racemic, differently R,R-disubstituted
R-siloxy aldehydes 5, which uncovered the impressive level of
kinetic resolution (Table 2),11 making it feasible not only to broaden
the applicability but also to prepare optically active tertiary
R-hydroxy aldehydes.12 When 5a was treated with 5 mol % of
(S,S)-3 in toluene at -20 °C for 12 h, R-hydroxy ketone 6a was
obtained almost exclusively in 49% yield with 86% ee (S), and 5a
was recovered in 51% yield with 84% ee (entry 1, selectivity
factor: s ) 39.5).13 Performing the reaction for 15 h under otherwise
similar conditions enabled the isolation of 5a in 45% yield with
92% ee (entry 2). The absolute configuration of the recovered 5a
was determined to be R by conversion to the diol 7 (Scheme 2), a
known compound whose asymmetric synthesis was dependent upon
enzymatic resolution.14 This assignment confirms the highly ste-
reospecific rearrangement of (S)-5a to (S)-6a.15 Other examples
listed in Table 2 showed the migratory aptitude and stereoselectivity
corresponding to the combination of the two different R-substituents
in 5. These results demonstrate potential synthetic utility of our
approach and also suggest that the origin of the asymmetric
induction lies on the ability of 3 to discriminate the R-stereogenic
center of the substrates.
(6) For the results, see the Supporting Information.
(7) For detail, see the Supporting Information.
(8) 4 was obtained as two separable diastereomers in a (S,S)/(S,R) ratio of
8:1.
(9) For the generation of a similar cyclic methylaluminum complex from Me3-
Al and 2-hydroxy-2′-(trifluoromethanesulfonylamino)biphenyl, see: Ooi,
T.; Ichikawa, H.; Maruoka, K. Angew. Chem., Int. Ed. 2001, 40, 3610.
The mode of aggregation of 3 in solution is unclear at present.
(10) Unfortunately, the present system is not effective for symmetrically R,R-
diaryl-substituted R-siloxy aldehydes.
(11) For a recent review on nonenzymatic kinetic resolution, see: Vedejs, E.;
Jure, M. Angew. Chem., Int. Ed. 2005, 44, 3974.
(12) Tertiary R-hydroxy aldehydes are versatile chiral building blocks in natural
product syntheses. See, for example: (a) Cossy, J.; Bauer, D.; Bellosta,
V. Tetrahedron 2002, 58, 5909. (b) Kowashi, S.; Ogamino, T.; Kamei,
J.; Ishikawa, Y.; Nishiyama, S. Tetrahedron Lett. 2004, 45, 4393.
(13) The s values in this communication were calculated based on conversion
and ee of 5 assuming first-order dependence on 5. For discussion on the
validity of calculated s values, see: Keith, J. M.; Larrow, J. F.; Jacobsen,
E. N. AdV. Synth. Catal. 2001, 343, 5.
In summary, we have invented an asymmetric rearrangement of
R,R-dialkyl-R-siloxy aldehydes to R-siloxy ketones efficiently
catalyzed by the newly designed, axially chiral organoaluminum
Lewis acid under mild conditions, and a kinetic resolution of
racemic, differently R,R-disubstituted substrates has also been
achieved. This is the first example of catalytic, highly enantiose-
(14) (a) Hof, R. P.; Kellog, R. M. Tetrahedron: Asymmetry 1994, 5, 565. (b)
Hof, R. P.; Kellog, R. M. J. Chem. Soc., Perkin Trans. 1 1996, 2051.
(15) Attempted treatment of 5a with (S,S)-3 (10 mol %) in toluene at -20 °C
for 48 h furnished 6a quantitatiuvely with 8% ee (S).
(16) Giordani, A.; Carera, A.; Pinciroli, V.; Cozzi, P. Tetrahedron: Asymmetry
1997, 8, 253.
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