A catalytic asymmetric Wagner-Meerwein shift [2]

Full text of DOI:10.1021/ja010504c

7162
J. Am. Chem. Soc. 2001, 123, 7162-7163
Scheme 1. Catalytic Asymmetric Wagner-Meerwein Shift
A Catalytic Asymmetric Wagner-Meerwein Shift
Barry M. Trost* and Tatsuro Yasukata
Department of Chemistry, Stanford UniVersity
Stanford, California 94305-5080
ReceiVed February 26, 2001
The Wagner-Meerwein rearrangement,1 a carbon-to-carbon
1,2-migration, typically of an alkyl, vinyl, or aryl group to an
adjacent carbocationic center, as depicted in eq 1, requires
Scheme 2. Synthesis of Substratesa
differentiation of the prochiral faces of the sp2 migration terminus
in 2 to proceed asymmetrically. To the extent that migration of
R and departure of X in 1 are concerted to any degree instead of
proceeding through a free carbocation, then the reaction becomes
asymmetric if the starting material can be available enantiomeri-
cally pure. Synthetically, it would be valuable to impose chirality
upon the carbocation 2 using a catalyst that may differentiate the
prochiral faces of the sp2 carbon. Scheme 1 outlines a possibility
to effect such a process. A chiral catalyst can initiate ionization
by preferential complexation to one of the two prochiral faces of
the alkene 3 to generate preferentially 4 or 5 and subsequently 6
or ent-6. In this communication, we realize what we believe to
be the first catalytic asymmetric Wagner-Meerwein shift not
involving chiral substrates which has led to asymmetric syntheses
of cyclobutanones, cyclopentanones, γ-butyrolactones, and δ-
valerolactones.
a (a) n-C4H9Li, THF, ClCO2CH3, 56%. (b) i. RLi (for 9, 10 and 12) or
RMgCl (for 11), CuI (for 9 and 12) or CuBr•DMS (for 10 and 11), ether,
-70°; ii. DIBAL-H, ether, -70°. (c) ClCO2CH3, C5H5N, CH2Cl2, room
temperature. (d) CCl3OCO2CCl3, CF3CH2OH, C5H5N, CH2Cl2, room
temperature. (e) CH3OH, TsOH, room temperature.
Table 1. Catalytic Asymmetric Wagner-Meerwein Shift
entry substrate mol % TMG °C time (h) cycloalkanone % yield % ee
1
2
13a
13a
14a
15a
15a
16a
17a
28
0
2
rt
rt
60
0
0
rt
2
19
19
22
22
22
23
24
25
32
32
32
32
33
34
35
quant.b
quant.b
58
85
92
91
85
90
92
70
89
77
81
87
89
82
69
93
3
We chose to examine a ring expansion protocol1-4 for which
the substrates were easily accessed via cuprate additions, as shown
in Scheme 2 and Table 1.5,6 By this protocol, only the Z
geometrical isomers were obtained.7 The methyl substrate 13a7
was initially examined to test the feasibility of the reaction as
shown in eq 2. Exposing 13a to 2.5 mol % of the Pd(0) complex
3
2
5
4
20
50
50
50a
2
5
quant.b
quant.b
quant.b
62
5
8
6
0.67
7
rt 24
8
0
rt
rt
rt
8
2
2.5
5
91
9
30
2
quant.b
94
10
11
12
13
14
15
30
20
50
100
50
50
50
30
90
30
rt 24
60
60
60
52
15b
16b
31
3
6
4
90
57
73
a In this case, 50 mol % N,N-diisopropylethylamine was used instead
of TMG. b Quantitative yield.
18 and 7 mol % dppb led to smooth ring expansion product 198
in THF at room temperature. The low isolated yield of 36%
appears to derive from the volatility of the product. Using a chiral
ligand like BINAP9 or DIOP9 led to a very slow reaction and
only produced very low yields of product (2-11%) of very low
ee (5-16%). On the other hand, our standard chiral ligand 2010
promoted the reaction with even higher efficiency than dppb since
it gave a quantitative yield of 19 (by GC) after only 2 h at room
temperature. Gratifyingly, the ee was already a respectable 64%.
Changing the solvent had little effect except for acetonitrile in
which the ee plummeted to 15%. A very slight increase to 67%
occurred in toluene which led to the latter being adopted as our
solvent of choice. Changing the ligand to the stilbene diamine
derived one 2111 significantly increased the ee to 85%. Other
ligands gave mainly lower ee’s. The final boost in ee came upon
the addition of base. While adding inorganic bases such as lithium
or cesium carbonate had little effect, tetramethylguanidine (TMG)
had a notable effect. Adding 1 equiv had an extremely deleterious
effect on both the conversion and the enantioselectivity. On the
(1) For an overview of Wagner-Meerwein rearrangements and related
reactions, see: Hanson, J. R. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Pattenden, G., Eds.; Pergamon Press: Oxford, 1991; Vol. 3,
Chapter 3.1, pp 705-720; Ricknorn, B., idem.; Chapter 3.2, pp 721-732,
and Chapter 3.3, pp 733-776; Covency, D.; Chapter 3.4, pp 777-802.
(2) For asymmetric synthesis of cyclobutanones based upon a pinacol
rearrangement of chiral scalemic cyclopranol substrates, see: Miyata, J.;
Nemoto, H.; Ihara, M. J. Org. Chem. 2000, 65, 504; Yoshida, M.; Ismail, M.
A.-H.; Nemoto, H.; Ihara, M. J. Chem. Soc., Perkin I 2000, 2629 and earlier
references therein.
(5) Substrate 7 available by acetylide addition to the hemiacetal of
cyclopropanone. Cf. Salau¨n, J.; Bennani, F.; Compain, J.-C.; Fadal, A.; Ollivier,
J. J. Org. Chem. 1980, 45, 4129; Wasserman, H. H.; Cochoy, R. E.; Baird,
M. S. J. Am. Chem. Soc. 1969, 91, 2375.
(3) For Pd(0)-catalyzed rearrangements of vinyloxaspirohexanes, see: Kim,
S.; Uh, K. H.; Lee, S.; Park, J. H. Tetrahedron Lett. 1991, 32, 3395.
(4) For leading references to various Pd-catalyzed ring expansion reactions,
see: Larock, R. C.; Reddy, C. K. Org. Lett. 2000, 2, 3325; Yoshida, M.;
Sugimoto, K.; Ihada, M. Tetrahedron Lett. 2000, 41, 5089; Nishimura, T.;
Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010; Nemoto, H.; Miyata, J.;
Yoshida, M.; Raku, N.; Fukumoto, K. J. Org. Chem. 1997, 62, 7850; Jeong,
I.-Y.; Nagao, Y. Synlett 1999, 576; Liebeskind, L. S.; Bombrun, A. J. Org.
Chem. 1994, 59, 177; Demuth, M.; Pandey, B.; Wietfield, B.; Said, H.; Viader,
J. HelV. Chim. Acta 1988, 71, 1392; Clark, G. R.; Thiensathit, S. Tetrahedron
Lett. 1985, 26, 2503; Boontanonda, P.; Grigg, R. Chem. Commun. 1977, 583.
(6) For cuprate additions, see: Kozlowski, J. A. In ComprehensiVe Dynamic
Synthesis; Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon:
Oxford, 1991; Vol. 4, Chapter 1.4.8.8, pp 185-187.
(7) New compounds have been characterized spectroscopically, and
elemental composition was performed by combustion analysis or high-
resolution mass spectrometry.
(8) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Bodganowicz, M. J. J. Am.
Chem. Soc. 1977, 99, 3088.
(9) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter 1.
(10) Trost, B. M. Acc. Chem. Res. 1996, 29, 355.
10.1021/ja010504c CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/28/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 29, 2001 7163
Scheme 3. Mechanistic Rationale
Comparison of the observed rotation to that of a known sample14
demonstrates the absolute configuration as S.
The success of the ring expansion of vinylcyclopropanols led
us to investigate the reactions of vinylcyclobutanols. The sub-
strates were made in analogous fashion, as shown in Scheme 2
for 15, 16 and 30, and eq 4 for 31. The preparation of 8 (n ) 2,
R ) CO2C2H5) involved the direct addition of ethyl 3-lithiopro-
piolate to cyclobutanone followed by THP protection. The slower
rates of reaction led to the use of the trifluoroethyl carbonates,
as shown in eq 5. The behavior of 30 paralleled the behavior of
other hand, adding 20 mol % TMG saw some deterioration in
rate but the ee increased to 92%. Decreasing the mol % to 10, 5,
2, and 1 saw a corresponding increase in rate (i.e. reaction times
decreased from 7 to 5, 3, and 2 h, respectively, for quantitative
conversion and yield) and a maintaining of the ee at 92%. While
we generally adopted 2 mol %, subsequent work showed that
the preferred amount varied with substrate.
Given the success of the rearrangement, Table 1 (entries 1-8)
summarizes the results of the ring expansion to form chiral
cyclobutanones according to eq 3. In going from methyl to
13b with respect to the effect of TMG. As the amount of TMG
was increased from 2 to 100 mol %, the ee increased from 77 to
89% but at the expense of conversion from Q down to 52% (see
Table, entries 9-12). In all the remaining cases (entries 13-15)
the reactions were performed using 50 mol % TMG at 60° as a
compromise between rate and ee. The absolute configuration of
32 was established by correlation to a compound of known
configuration as shown in eq 6.15
n-butyl, a significant slowing of the reaction occurred. Thus, even
at 60° (entry 3), the reaction was still incomplete after 5 h. A
significant improvement occurred by switching to the better
leaving group trifluoroethyloxycarboxylate. Even at 0° (entry 4),
the reaction went to completion to form cyclobutanone 227 in 5
h. Increasing the amount of TMG to 50 mol % saw an increased
reaction time of 8 h, but the ee increased to 90% (entry 5). The
phenethyl substrate 16a required only 40 min at room temperature
to give a quantitative yield of 23 of 92% ee (entry 6). The phenyl
substrate 17a posed the most difficulty as revealed in entry 7.
On the other hand, the alkyne substrate 28 proved interesting.
The substrate was readily available from alkynoate 26 (eq 4).
The observations to date support the notion that the enantio-
discriminating step is the initial ionization as depicted in Scheme
3.16 The effect of base on ee supports this interpretation. Addition
of base should increase the rate of the 1,2-shift relative to
interconversion of the two diastereomeric complexes 36 and 37
by π-σ-π mechanisms. If the enantiodiscriminating step were
the bond migration, the equilibration would have to be fast
compared to the 1,2-shift. Thus, base should have decreased not
increased the ee if the 1,2-shift was enantiodetermining. Additional
support for this interpretation derives from the effect of the
addition of tetra-n-butylammonium chloride or TBAT. These
additives are known16 to enhance π-π interconversion and,
therefore, should increase ee if the 1,2-shift is enantiodetermining.
However, in both cases, the opposite effect is seensthat is, the
ee decreases upon their addition. Scheme 3 reveals that, using
the cartoons to represent the π-allylpalladium intermediates
previously developed,16 structures 36 and 37 are the two possible
diastereomeric complexes. Due to the unfavorable steric interac-
tions present in 37 but not 36, ionization to diastereomer 36 should
be preferred and the S product formedsas observed. Thus, the
chiral complexes developed previously for asymmetric additions
of nucleophiles to π-allylpalladium complexes are excellent in
controlling enantioselectivity in a Wagner-Meerwein shifts
validating the premise that preferential complexation of enan-
tiotopic faces of a carbocation can induce asymmetry. Further-
more, the versatility of the access to the requisite substrates and
the functionality of the obtained products should make this
approach an attractive asymmetric synthetic strategy.
Pd-catalyzed addition of 3-butyn-1-ol to alkynoate11 26 produced
directly the Z-alkenoate 277 exclusively. Silylation, DIBAL-H
reduction, and esterification completed the sequence to the
substrate 28.7 The catalytic asymmetric rearrangement occurred
facilely at 0° to give the desired ring expansion product chemo-
and enantioselectively (entry 8).
The absolute configuration of 19 was established by the
Baeyer-Villiger reaction13 to form γ-butyrolactone 29 with high
chemoselectivity (eq 3). The ee of the product is identical to that
of the starting material indicating a 100% chirality transfer (ct).
Acknowledgment. We thank the National Science Foundation and
the National Institute of Health, General Medical Sciences, for their
generous support of our programs. We are also indebted to Shionogi and
Co., Ltd. for sponsoring the visit of T.Y. Mass spectra were provided by
the Mass Spectrometry Regional Center of the University of California-
San Francisco, supported by the NIH Division of Research Resources.
(11) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992,
114, 9327.
(12) Trost, B. M.; Sorum, M.; Chan, C.; Harms, A. E.; Ru¨hter, G. J. Am.
Chem. Soc. 1997, 119, 698.
(13) Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95, 5321.
(14) Okazaki, T.; Ohsuka, A.; Kotake, M. Nippon Kagaku Kaishi 1973,
359; Felix, D.; Melera, A.; Seibl, J.; Kovats, E. HelV. Chim. Acta 1963, 46,
1513.
(15) Sato, T.; Maeno, H.; Noro, T.; Fujisawa, T. Chem. Lett. 1988, 1739.
(16) Cf. Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 4545.
Supporting Information Available: Experimental procedures for
13a-b, 14a, 15a-b, 16a-b, 17a, 19, 22-25, 28-35 (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA010504C