New chiral auxiliaries for highly stereoselective asymmetric methoxyselenenylations

Article abstract of DOI:10.1021/ol000187z

Replacement of the 2-keto group of readily available di(endo-3-camphoryl) diselenide with oxime or O-benzoyloxime substituents, followed by conversion into the corresponding selenenyl triflates, produced highly effective chiral selenium electrophiles for

Full text of DOI:10.1021/ol000187z

ORGANIC
LETTERS
2
000
Vol. 2, No. 19
007-3009
New Chiral Auxiliaries for Highly
Stereoselective Asymmetric
Methoxyselenenylations
3
Thomas G. Back* and Ziad Moussa
Department of Chemistry, UniVersity of Calgary, Calgary, Alberta, Canada T2N 1N4
tgback@ucalgary.ca
Received July 13, 2000
ABSTRACT
Replacement of the 2-keto group of readily available di(endo-3-camphoryl) diselenide with oxime or O-benzoyloxime substituents, followed by
conversion into the corresponding selenenyl triflates, produced highly effective chiral selenium electrophiles for the asymmetric oxyselenenylation
of alkenes in the presence of methanol.
Organoselenium chemistry has many proven applications in
1
modern organic synthesis. The development of asymmetric
Scheme 1
variations of selenium-mediated transformations has the
potential to further increase their usefulness, and several
strategies have been designed for this purpose in the past
2
few years. Among such reactions, the 1,2-additions of
selenium electrophiles to alkenes in the presence of nucleo-
3
philes have attracted particularly keen interest. These
processes typically proceed with Markovnikov regiochem-
istry and via anti addition of the selenium moiety and the
nucleophile because of the intermediacy of bridged seleni-
ranium ions (Scheme 1). Cyclizations occur when the
nucleophile is tethered to the alkene (Scheme 1). Further-
(
1) (a) Organoselenium Chemistry - A Practical Approach; Back, T.
G., Ed.; Oxford University Press: Oxford, 1999. (b) Topics in Current
Chemistry: Organoselenium Chemistry; Wirth, T., Ed.; Springer-Verlag:
Berlin, 2000; Vol. 208.
(
2) For a recent review, see: Wirth, T. Tetrahedron 1999, 55, 1-28.
(3) For reviews of electrophilic selenium reactions, see: (a) Beaulieu,
P. L.; D e´ ziel, R. In ref 1, Chapter 3. (b) Back T. G. In Organoselenium
Chemistry; Liotta, D., Ed.; Wiley: New York, 1987; Chapter 1. (c) Back,
T. G. In The Chemistry of Organic Selenium and Tellurium Compounds;
Patai, S., Ed.; Wiley: Chichester, 1987; Vol. 2, Chapter 3. (d) Paulmier,
C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon
Press: Oxford, 1986; Chapters 7 and 8. (e) Schmid, G. H.; Garratt, D. G.
In The Chemistry of Double-bonded Functional Groups. Supplement A, Part
more, asymmetric variations of these reactions require the
control of facial selectivity, which can, in principle, be
achieved by attaching a chiral auxiliary group to the selenium
atom of the electrophilic reagent. This leads to the diaste-
2
; Patai S., Ed.; Wiley: New York, 1977; Chapter 9.
1
0.1021/ol000187z CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/19/2000

reoselective formation of initial 1,2-adducts, with enanti-
oselective formation of final products after deselenization
of the former.
based diselenides, 3a and 4a, containing oxime and O-
benzoyloxime substituents at C-2 instead of the original keto
group and their conversion into the corresponding triflates
3d and 4d, respectively. These modifications, especially in
the case of 3d, have resulted in a dramatic improvement in
the diastereomeric ratios obtained in the methoxyseleneny-
lation of a series of variously substituted olefins.
We recently showed that diselenide 1a can be conveniently
prepared in one pot from camphor, via its enolate, and
4
elemental selenium. Moreover, 1a can be easily converted
into electrophiles, such as the corresponding selenenyl halides
4
(1b,c X ) Cl, Br) and triflate (1d; X ) OTf) (Scheme 2),
Thus, the readily available diselenide 1a was converted
into the novel oxime 3a with hydroxylamine hydrochloride
in refluxing pyridine. Acylation of 3a with benzoyl chloride
in pyridine at room temperature in the presence of catalytic
DMAP afforded 4a. The geometry of the oxime moiety of
Scheme 2
4
a was determined to be Z by X-ray crystallography and is
similarly inferred to be Z in 3a. Diselenides 3a and 4a were
converted into the corresponding selenenyl bromides 3c and
4
c, respectively, with bromine in dichloromethane and then
into the corresponding selenenyl triflates 3d and 4d with
methanolic silver triflate. Methoxyselenenylation of a series
of alkenes was performed with the resulting selenenyl triflates
8
at -78 °C. The results are given in Table 1. The products
Table 1. aMethoxyselenenylations of Alkenes with 3d and 4d
which can in turn be employed in diastereoselective 1,2-
5
additions and cyclizations. The keto group of the camphor
moiety of 1a also provides the opportunity for further
structural modifications of the auxiliary to improve the facial
selectivity of such reactions. Thus, while the selenenyl triflate
1d proved to be the most stereoselective of several camp-
horseleno reagents studied for asymmetric oxyselenenyla-
5
a,b
tions (where the nucleophile is an alcohol or water), the
corresponding spiro-oxazolidinone 2b was more effective in
cyclizations.5 Subsequently, the selenenyl sulfate 1e was
a,c
6
independently studied but afforded generally lower diaste-
reoselectivity than the triflate 1d.
The principal drawback to the use of our and other
5
6,7
existing chiral selenium electrophiles for oxyselenenylations
and related processes is that the stereoselectivity is highly
variable and dependent upon the substitution pattern of the
substrate and the conditions of the reaction. Thus, there is a
need for new reagents capable of delivering more consistent
results. We now report the preparation of two new camphor-
(
10.
4) Back, T. G.; Dyck, B. P.; Parvez, M. J. Org. Chem. 1995, 60, 703-
7
(
5) For asymmetric electrophilic reactions of 1b-1d and 2b-2d, see:
(
(
(
a) Back, T. G.; Dyck, B. P.; Nan, S. Tetrahedron 1999, 55, 3191-3208.
b) Back, T. G.; Nan, S. J. Chem. Soc., Perkin Trans. 1 1998, 3123-3124.
c) Back, T. G.; Dyck, B. P. J. Chem. Soc., Chem. Commun. 1996, 2567-
2
568.
(
6) (a) Tiecco, M.; Testaferri, L.; Santi, C.; Marini, F.; Bagnoli, L.;
were isolated by flash chromatography as unseparated
mixtures of diastereomers, and the diastereomeric ratios (dr)
were measured by integration of either their H or Se NMR
Temperini, A. Tetrahedron Lett. 1998, 39, 2809. (b) Tiecco, M.; Testaferri,
L.; Marini, F.; Santi, C.; Bagnoli, L.; Temperini, A. Tetrahedron Asymmetry.
999, 10, 747-757.
1
77
1
3008
Org. Lett., Vol. 2, No. 19, 2000

signals. The products were further characterized by IR and
C NMR spectroscopy, as well as by low- and high-
resolution mass spectrometry.
Finally, the adduct obtained in entry 4 with 3d was treated
1
3
with triphenyltin hydride and AIBN to obtain the corre-
12
sponding deselenized product 5 (Scheme 3). A comparison
Table 1 shows that the electrophilic addition can be
performed with monosubstituted, gem-, cis-, or trans-
disubstituted, or trisubstituted alkenes. In general, selenenyl
triflate 3d afforded superior or comparable yields and
diastereoselectivities than did the benzoylated analogue 4d.
The differences between the dr’s achieved with the two
reagents are especially striking in entries 3 and 6, where cis-
disubstituted alkenes were substrates. This is especially
relevant because cis-disubstituted alkenes often afford par-
ticularly poor stereoselectivity in asymmetric oxyseleneny-
Scheme 3
9
lations. Moreover, it has been demonstrated that the
stereoselectivities of these processes are often improved when
a substituent capable of coordination with the selenium atom
2,7a,10
is present in the chiral auxiliary.
Thus, the superior
performance of the free oxime 3d may be the result of
coordination of the oxime hydroxyl group with the selenium
center during the addition to the alkene.11
(7) For a review of asymmetric oxyselenenylations, see: (a) Fujita, K.
In ReViews on Heteroatom Chemistry; Oae, S., Ed.; MYU, Tokyo, 1997;
Vol. 16, pp 101-117. For examples of other chiral auxiliaries used in
oxyselenenylations, see: (b) D e´ ziel, R.; Malenfant, E.; Thibault, C.;
Fr e´ chette, S.; Gravel, M. Tetrahedron Lett. 1997, 38, 4753-4756. (c) D e´ ziel,
R.; Goulet, S.; Grenier, L.; Bordeleau, J.; Bernier, J. J. Org. Chem. 1993,
5
8, 3619-3621. (d) Fukuzawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H.
J. Org. Chem. 1997, 62, 7711-7716. (e) Fujita, K.; Murata, K.; Iwaoka,
M.; Tomoda, S. Tetrahedron 1997, 53, 2029-2048. (f) Fujita, K.; Murata,
K.; Iwaoka, M.; Tomoda, S. Tetrahedron Lett. 1995, 36, 5219-5222. (g)
Tomoda, S.; Fujita, K.; Iwaoka, M. J. Chem. Soc., Chem. Commun. 1990,
of 5 with an authentic sample of the (R)-enantiomer13 by
GC on a chiral column (Cyclodex B) revealed that the
enantiomeric ratio of the deselenized product was 98:2 in
favor of the (R)-enantiomer. This confirmed the high dr
shown in entry 4 of Table 1 and was consistent with the
intermediacy of the seleniranium ion stereoisomer 6 (Scheme
29-130. (h) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1992, 1123-
1
998, 1867-1868. (l) Wirth, T.; Fragale, G. Chem. Eur. J. 1997, 3, 1894-
1
902. (m) Wirth, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 1726-1728.
3
), which allows the placement of the bulky styrene phenyl
(
3
n) Wirth, T.; Fragale, G.; Spichty, M. J. Am. Chem. Soc. 1998, 120, 3376-
group into the least congested quadrant around the alkene
double bond in the preceding transition state.
381. (o) Wirth, T.; H a¨ uptli, S.; Leuenberger, M. Tetrahedron: Asymmetry
1
998, 9, 547-550.
(
8) Typical procedure (Table 1, entry 1): Diselenide 3a (0.18 mmol)
In summary, the new chiral selenenyl triflate 3d, and to a
lesser extent the related 4d, can be used in highly diaste-
reoselective methoxyselenenylations. The success of 3d with
cis-alkenes is particularly noteworthy. Further experiments
to improve the diastereoselectivity of these and related
processes and to gain additional insight into the mechanism
are in progress.
in dry CH2Cl2 was treated with Br2 (0.18 mmol) at -40 °C, followed by
the addition of AgOTf (0.53 mmol) in methanol. The mixture was cooled
to -78 °C, trans-5-decene (0. 94 mmol) was added, and the reaction was
quenched with an aqueous NaHCO3 solution after 1 h. The product was
isolated as a pale yellow oil by flash chromatography over silica gel (elution
with 10% ethyl acetate-hexanes) to afford 111 mg (73%, based on 3a):
-
1 1
IR (neat) 3375, 1649, 1376, 1091, 938 cm ; H NMR (200 MHz, CDCl3)
major diastereomer, δ 3.78 (d, J ) 4.3 Hz, 1 H), 3.57-3.46 (m, 1 H), 3.40
(
s, 3 H), 3.38-3.32 (m, 1 H), 2.08-2.00 (m, 1 H), 1.91-1.52 (m, 6 H),
13
1
.45-1.20 (m, 10 H), 0.98 (s, 6 H), 0.96-0.85 (m, 6 H), 0.81 (s, 3 H); C
NMR (50 MHz, CDCl3) δ 168.2, 127.6, 85.4, 58.1, 52.5, 50.2, 48.4, 47.6,
Acknowledgment. We thank the Natural Sciences and
Engineering Research Council of Canada (NSERC) for
financial support.
3
9.6, 31.8, 31.7, 31.3, 30.5, 28.3, 24.1, 22.9, 22.7, 19.1, 18.9, 14.1, 11.8;
7
7
Se NMR (CDCl3) major diastereomer, δ 292.7 (relative to Me2Se ) 0
ppm); minor diastereomer, δ 394.0; mass spectrum, m/z (relative intensity)
+
4
17 (3, M ), 399 (8), 228 (10), 148 (54), 106 (67), 69 (100), 41 (80). Exact
mass calcd for C21H39NO2Se: 417.2146. Found: 417.2124.
9) It has been pointed out (see refs 7a and 7i) that the stereochemistry
OL000187Z
(
of oxyselenenylations of symmetrically cis-disubstituted alkenes is fixed
in the second step, where ring opening of the seleniranium intermediate
occurs, rather than in the initial addition of the electrophile to the alkene.
This is in contrast to unsymmetrical or trans-disubstituted alkenes, where
the stereochemistry is set in the first step and may account for the poorer
diastereoselectivities generally observed with cis-alkenes. The reason for
the particular effectiveness of 3d with cis-alkenes is not known.
oxygen would involve a more strained four- instead of five-membered ring.
(b) The 77Se NMR spectra of diselenides 3a and 4a are very similar to that
of 1a (δ 377.3, 375.3, and 375.2 ppm relative to dimethyl selenide,
respectively), suggesting that coordination effects are not significant in the
parent diselenides 3a and 4a. However, the X-ray structure of 4a reveals
relatively short interatomic distances of 2.95 and 2.97 Å between the oxime
O and Se atoms of the two camphorseleno moieties. Thus, O-Se
coordination should be possible in species where the selenium atom assumes
a more strongly positive character.
(10) For a theoretical analysis of some asymmetric oxyselenenylations
where an Se-coordinating substituent is present in the chiral auxiliary, see:
Wang, X.; Houk, K. N.; Spichty, M.; Wirth, T. J. Am. Chem. Soc. 1999,
1
21, 8567-8576.
(12) Clive, D. L. J.; Chittattu, G. J.; Farina, V.; Kiel, W. A.; Menchen,
S. M.; Russell, C. G.; Singh, A.; Wong, C. K.; Curtis, N. J. J. Am. Chem.
Soc. 1980, 102, 4438-4447.
(13) Authentic (R)-5 was obtained from (R)-1-phenylethanol by treatment
with NaH and iodomethane.
(
11) (a) Coordination via the oxime nitrogen is less likely because it
would require isomerization to the more crowded E-oxime in order to render
the nitrogen atom’s nonbonding electrons accessible to the selenium atom.
Moreover, coordination through nitrogen instead of through the oxime
Org. Lett., Vol. 2, No. 19, 2000
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