α-Acetoxysulfones as 'chiral aldehyde' equivalents [8]

Full text of DOI:10.1021/ja000627h

6120
J. Am. Chem. Soc. 2000, 122, 6120-6121
Table 1. Typical Examples of the AAA Reaction to Form
R-Acetoxysulfonesa
r-Acetoxysulfones as “Chiral Aldehyde” Equivalents
time
Barry M. Trost, Matthew L. Crawley, and Chul Bom Lee
entry
1
R
R1 ligand (h)
yieldb
89%
er
(ee)d
C6H5
C6H5
H
ent-3
5
98:2
(96%)
Department of Chemistry, Stanford UniVersity
ent-2a
Stanford, California 94305-5080
2
3
4
5
6
7
CH3
H
H
3
3
3
3
3
24 85%c 2b
97.5:2.5 (95%)
92.5:7.5 (85%)
99:1
o-O2N-C6H4
n-C3H7
n-C6H13
(CH2)4
(CH2)4
2
4
6
93% 2c
94% 2d
73% 2e
ReceiVed February 22, 2000
ReVised Manuscript ReceiVed May 12, 2000
(98%)
H
97.5:2.5 (95%)
24 80%c 2f >99:<1 (>99%)
ent-3 24 85%
ent-2f
ent-3 10 85%
ent-2g
>99:<1 (>99%)
Stereocontrolled additions to double bonds represent an im-
portant method for asymmetric synthesis. The flexibility of the
functionality of an R,â-unsaturated aldehyde has led to the search
for effecting asymmetric additions to the double bond. Recently
practiced strategies involve converting aldehydes into acetals with
chiral diols.1,2 A more efficient strategy would employ a chiral
aldehyde derivative in which the chirality was created catalytically.
We were attracted to an R-acetoxysulfone, 2, since it places the
stereogenic center adjacent to the double bond. Further, the
aldehyde should be capable of being liberated under very mild
conditions in which it could be reacted further. The two questions
that must be addressed are (1) can such compounds be easily
accessed with high enantiopurity and (2) will such derivatives
exercise differential reactivity of the diastereotopic faces of the
adjacent double bond?
8
i-C3H7
H
>99:<1 (>99%)
9
TBDMSOCH2
H
H
3
1
1
92% 2h
92%
ent-2h
97:3
97:3
(94%)
(94%)
10 TBDMSOCH2
ent-3
11 C2H5O2C
CH3
3
12 85%c 2i
99:1
(98%)
a All reactions were run using 2 mol % 4, 6 mol % 3 (or ent-3), 20
mol % THAB with 1.0-1.5 equiv of sodium benzenesulfinate, 1.0 equiv
Gem-diacetate in 1:1 water/methylene chloride at 0.4-0.5 M at room
temperature unless noted otherwise. b Yields are for isolated pure
product. c Yield based upon reacted starting material. d Determined by
chiral HPLC using chiralcel OD and typically eluting with 9:1 heptane/
2-propanol.
Table 2. Diastereoselective Dihydroxylation Acetoxysulfonesa
Our strategy for the catalytic asymmetric synthesis of R-ac-
etoxysulfones, 2, derives from two observations: (1) the ability
of sulfinates to function as nucleophiles in the asymmetric allylic
alkylation (AAA) reaction3 and (2) the ability to desymmetrize
allylic gem diesters 1.4 The geminal esters 1 are readily accessed
by the acid-catalyzed (0.1-1.0 mol % of either sulfuric acid or
ferric chloride) addition of acetic anhydride and an aldehyde5 or
by the palladium-catalyzed redox addition of acetic acid to
propargyl acetates.6 Exposing a mixture of the geminal acetate 1
and sodium benzenesulfinate to a catalyst formed by mixing 2
mol % π-allylpalladium chloride dimer (4) and 6 mol % ligand
3 (or ent-3)7 in a two-phase aqueous methylene chloride mixture
employing tetrahexylammonium bromide (THAB) as a phase-
transfer catalyst led to smooth reaction at room temperature to
produce the acetoxysulfones. Further reactions of the R-acetoxy-
sulfones did not occur under the conditions of the reaction. The
results are summarized in Table 1.8
entry
R
R1
time (h) productb yieldc
drd
1
2
3
4
5
6
7
8
9
C6H5
C6H5
H
CH3
H
H
H
24
24
12
5
12
4
12
12
12
ent-5a
5b
5c
5d
5e
ent-5f
5g
ent-5g
6
77%
57%
83%
80%
84%
86%
82%
81%
94%
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
95:5
o-O2N-C6H4
n-C3H7
n-C6H13
i-C3H7
TBDPSOCH2
TBDPSOCH2
C2H5O2C
H
CH3
95:5
93:7
a All reactions were performed using 5% osmium tetroxide (4%
aqueous solution) and 3 equiv of NMO at 0.1-0.2 M of substrate in
methylene chloride at 0-5 °C. b All new compounds have been fully
characterized spectrally and elemental composition established by high-
resolution mass spectrometry and/or combustion analysis. c Isolated
yields of pure compounds. d Determined by H NMR spectroscopy.
1
In all cases, except for that of o-nitrocinnamaldehyde (entry
3), the ee was g94%. In the case of trisubstituted alkenes as
substrates (entries 2, 6, 7, and 11), the reactions were slower and
did not go to completion within 24 h. The presence of a strong-
electron-withdrawing group on the double bond (entry 11) did
not adversely affect the reaction. In all cases, only one regioiso-
meric product was observed. Simply changing the chirality of
the ligand inverts the chirality of the product (entries 6 and 7, 9
and 10). The absolute configuration is based upon the mnemonic7
and the fact that the sulfinate nucleophile follows the mnemonic
in other asymmetric alkylations involving different types of
enantiodiscrimination.3 The acetoxysulfones are quite stable and
easily handled and chromatographed without special precautions.
Most are white crystalline solids.
Having this new class of novel enantiomerically enriched acetal
derivatives, their ability to provide for discrimination of diaste-
reotopic faces of the adjacent double bond was probed. The value
of diols and the lack of reports of asymmetric dihydroxylation of
R,â-unsaturated aldehydes9 led us to explore the dihydroxylation
catalyzed simply by osmium tetroxide. Simply stirring a meth-
ylene chloride solution of the acetoxysulfone with 5 mol %
osmium tetroxide (used as an aqueous solution), with NMO as
(1) Fujiwara, J.; Fukutani, Y.; Hasegawa, M.; Maruoka, K.; Yamamoto,
H. J. Am. Chem. Soc. 1984, 106, 5004; Fukatani, Y.; Maruoka, K.; Yamamoto,
H. Tetrahedron Lett. 1984, 25, 5911; Ghribi, A.; Alexakis, A.; Normant, J. F.
Tetrahedron Lett. 1984, 25, 3083; Mori, A.; Arai, I.; Yamamoto, H.
Tetrahedron 1986, 42, 6447; Mash, E. A.; Hemperly, S. B.; Nelson, K. A.;
Heidt, P. C.; Van Deusen, S. J. Org. Chem. 1990, 55, 2045; Mash, E. A.;
Arterburn, J. B. J. Org. Chem. 1991, 56, 885.
(2) For reviews, see: Rossiter, B. E.; Swingle, N. M. Chem. ReV. 1992,
92; Alexakis, A.; Mangeney, P. Tetrahedron: Asymmetry 1990, 1, 477;
Whitesell, J. K. Chem. ReV. 1989, 89, 1581.
(3) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J. Am. Chem. Soc. 1995,
117, 9662.
(4) Trost, B. M.; Lee, C. B.; Weiss, J. M. J. Am. Chem. Soc. 1995, 117,
7247.
(5) For some recent references, see: Pinnick, H. W.; Kochhar, K. S.; Bal,
B. S.; Rajadhyaksha, S. N.; Deshpande, R. P. J. Org. Chem. 1983, 48, 1765;
Fry, A. J.; Rho, A. K.; Sherman, L. R.; Sherwin, C. S. J. Org. Chem. 1991,
56, 3283; Deka, N.; Kalita, D. J.; Borah, R.; Sarma, J. C. J. Org. Chem. 1997,
62, 1563; Sydnes, L. K.; Soderberg, B. C. Tetrahedron 1997, 53, 12679.
Chandra, K. L.; Saravanan, P.; Singh, V. K. Synlett 2000, 359.
(6) Trost, B. M.; Brieden, W.; Baringhaus, K. H. Angew. Chem., Int. Ed.
Engl. 1992, 31, 1335.
(7) Trost, B. M.; Van Vranken, D. L. Bingel, C. J. Am. Chem. Soc. 1992,
114, 9327. For a review, see: Trost, B. M. Acc. Chem. Res. 1996, 29, 355.
(8) All new compounds have been fully characterized spectroscopically
and elemental composition established by high-resolution mass spectrometry
and/or combustion analysis.
(9) Sharpless, K. B.; Kolb, H. C.; Van Nieuwenhze, M. S. Chem. ReV.
1994, 94, 2482; Sharpless, K. B.; Li, G.; Chang, H. T. Angew. Chem., Int.
Ed. Engl. 1996, 29, 355.
10.1021/ja000627h CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/10/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 25, 2000 6121
the stoichiometric reoxidant, at 0-5 °C produced the correspond-
ing diols as shown in eqs 2 and 3 and Table 2. Running the
is best in accord with the Stork-Houk-Ja¨ger “inside alkoxy”
model11a as in 9 which places the bulky electronegative phenyl-
sulfonyl moiety anti as well as the Vedejs model.11b
One of the advantages of the acetoxysulfone is the ease of its
unmasking under conditions suitable for the subsequent reactions
of the aldehyde, thereby avoiding the need to work with sensitive
aldehydes. For example, treatment of the acetonides 7a or 7b
with excess phenylmagnesium bromide led to alcohols 10a,b (eq
6), directly, with excellent dr (>98:2).
reaction at room temperature saw a significant drop in dr. For
example, in the case of entry 7, the dr at room temperature was
5:1 instead of 19:1 at 0-5 °C. In the case of entry 9, the initial
product, 5h, was not stable and underwent acetyl migration with
liberation of the free aldehyde 6 under the reaction conditions
(eq 4). The stereochemistry of ent-5a (Table 2, entry 1) was
The acetoxysulfones serve as a novel class of chiral aldehyde
equivalents that are acid-stable but base-labile. The two func-
tionalities impart good diastereoselectivity in an electrophilic
addition to the double bond. Thus, the availability of the
acetoxysulfones in high enantiopurity translates to an asymmetric
addition to one of the two enantiotopic faces of an R,â-unsaturated
aldehyde. The utility of this strategy is exemplified by diol ent-
5f obtained enantiomerically pure here compared with a 70% ee
in the asymmetric dihydroxylation of methyl E-4-methyl-2-
pentenoate to produce an intermediate toward lactacystin â-lac-
tone.12 The differences between the two functionalities suggests
many other ways that the stereochemistry of the acetoxysulfone
may translate into asymmetric bond-forming reactions involving
their allylic nature. These studies will be reported in due course.
established by conversion to its acetonide 7 followed by DIBAL-H
reduction, which led directly to the known primary alcohol 8 (eq
5) whose spectral data and sign of rotation establish the relative
Acknowledgment. We thank the National Science Foundation and
the National Institutes of Health, General Medical Sciences, for their
generous support of our programs. Mass spectra were provided by the
Mass Spectrometry Regional Center of the University of Californina-
San Francisco, supported by the NIH Division of Research Resources.
Supporting Information Available: Characterization data for 2a-
2i, 5a-5g, 6, 7a, 7b, 8a, 8b (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org. See any current masthead
page for ordering information and Web access instructions.
JA000627H
(11) (a) Haller, J.; Strassner, T.; Houk, K. N. J. Am. Chem. Soc. 1997,
119, 8031; (b) Vedejs, E.; McClure, C. K. J. Am. Chem. Soc. 1986, 108,
1094; (c) Also see: Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1994,
40, 2247.
(12) Soucy, F.; Grenier, L.; Behnke, M. L.; Destree, A. T.; McCormack,
T. A.; Adams, J.; Plamondon, L. J. Am. Chem. Soc. 1999, 121, 9967.
and absolute stereochemistry.10 The stereochemistries for the
remaining examples are assigned by analogy. This stereochemistry
(10) Zhou, W. S.; Yang, Z. C. Tetrahedron Lett. 1993, 34, 7075; Kazmaier,
U.; Schneider, C. Synthesis 1998, 1314.