Asymmetric methoxyselenenylations with camphor-based selenium electrophiles

Article abstract of DOI:10.1039/a806707d

The asymmetric methoxyselenenylation of olefins was achieved with a series of camphor-based selenenyl triflates, of which the readily available 2-oxo analog 2a proved the most effective.

Full text of DOI:10.1039/a806707d

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Asymmetric methoxyselenenylations with camphor-based selenium
electrophiles
Thomas G. Back* and Siqiao Nan
Department of Chemistry, University of Calgary, Calgary, Alberta, Canada, T2N 1N4
Received (in Corvallis, OR) 21st August 1998, Accepted 26th August 1998
Table 1a Methoxyselenenylation of trans-dec-5-ene
The asymmetric methoxyselenenylation of olefins was
achieved with a series of camphor-based selenenyl triflates,
of which the readily available 2-oxo analog 2a proved the
most effective.
Bu
OMe
R*Se
Bu
3
Electrophilic selenium compounds have proven of considerable
utility in a variety of organic transformations.1 Asymmetric
variations of such processes are made possible by employing
selenium reagents containing chiral auxiliary groups. For
example, the treatment of an olefin with a chiral selenium
electrophile in the presence of methanol results in an asym-
metric methoxyselenenylation, leading to the formation of a
β-alkylseleno methyl ether containing up to two new chiral
centers (Scheme 1). Such processes are known to proceed via
Entry
R*SeOTf
Isolated yield of 3 (%)
drb,c
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
88
94:6
d
65
63
66:34
82:18
85:15
51
e
e
2g
a All reactions were performed in dichloromethane at Ϫ78 ЊC.
b dr = diastereomeric ratio. c Measured by NMR integration. d Triflate
2b cyclized to the corresponding selenenamide. e No methoxyselenenyl-
ation occurred under these conditions.
OMe
R*Se
MeOH
+
R*SeX
R*Se
OMe
Scheme 1 R* = chiral auxiliary group; X = leaving group.
diastereoselectivity.5 Subsequently to our disclosure of the
preparation of the novel diselenides 1a–c and of their appli-
cation to asymmetric cyclizations,4,5 Tiecco and coworkers6
reported the use of 1a in methoxyselenenylations, via the
corresponding selenenyl sulfate. We now report the results of
our investigation of asymmetric methoxyselenenylations with
electrophiles derived from 1a–g.7
anti-addition,2 resulting in the formation of two diastereomeric
products, whose ratio is controlled by the chiral auxiliary group.
Enantioselective access to deselenized products is then made
possible by oxidative or reductive removal of the selenium
residue. Thus, several groups have devised chiral selenium
electrophiles for use in asymmetric methoxyselenenylations.3
Over the past few years, we have prepared a series of novel
diselenides 1a–g derived from camphor for use in our ongoing
studies of asymmetric selenium reactions.4,5 Diselenide 1a was
obtained in one step from the lithium enolate of camphor and
elemental selenium,4b and was in turn easily converted into di-
selenides 1b–g (Scheme 2).4c,5 We recently reported that the
An evaluation of the camphorselenenyl triflates 2a–g, derived
from 1a–g (Scheme 2), in the methoxyselenenylation of trans-
dec-5-ene at Ϫ78 ЊC in dichloromethane was first performed.
Triflates 2a, 2c, 2d and 2e behaved in the expected manner,
affording the corresponding adducts 3a, 3c, 3d and 3e, respect-
ively (Table 1). Under these conditions, triflate 2b underwent
cyclization to the corresponding selenenamide,8 while 2f and 2g
also failed to afford the corresponding adducts 3, presumably
because of strong coordination of the endo-oxygen func-
tions with the selenium moiety. Interestingly, triflate 2a, which
was derived from 1a, the most readily available of the above
diselenides, afforded the highest diastereoselectivity of the
corresponding adduct 3, compared to 2c, 2d and 2e. The
selenenyl chloride and bromide derived from 1a gave lower
chemical yields and diastereomeric ratios (dr’s), while the
corresponding selenenyl tetrafluoroborate and hexafluoro-
phosphate gave comparable dr’s to the triflate, but in some cases
lower yields. Substantially lower dr’s resulted when the reaction
was performed at higher temperatures.
H
Se
i
)
2
O
O
1a
ii
R*SeSeR*
1a–g
2 R*SeOTf
2a–g
H
H
OH
R* =
The results of the asymmetric methoxyselenenylations of a
series of other olefins under the above optimized conditions
are shown in Table 2. The products were isolated by chrom-
atography (generally the diastereomers were obtained unsepar-
ated) and characterized by IR, 1H- and 13C-NMR, and low and
high resolution mass spectroscopy. The dr’s were determined by
1H- or 77Se-NMR integration.
A typical procedure follows (Entry 1 in Table 2): Diselenide
1a (50 mg, 0.11 mmol) and 100 mg of 4 Å molecular sieves were
stirred in 3 mL of dry dichloromethane. A 1.0 M solution of
bromine (0.11 mL, 0.11 mmol) in tetrachloromethane was
added dropwise at Ϫ78 ЊC under nitrogen, with stirring. After
15 min, a 0.70 M methanol solution of silver triflate (0.45 mL,
0.30 mmol) was added, followed after another 15 min by trans-
O
NHAc
a
b
H
H
H
O
OR
H
H
OR
N
O
d R = H
e R = OAc
f R = H
g R = OAc
H
c
Scheme 2 Reagents and conditions: i, LDA, Se, then O2; ii, Br2, AgOTf.
selenenyl chlorides derived from 1a–c can be employed in
asymmetric selenium-mediated cyclizations of unsaturated
alcohols and carboxylic acids, with 1c affording the highest
J. Chem. Soc., Perkin Trans. 1, 1998, 3123–3124
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Table 2a Methoxyselenenylations of olefins with 2a
Isolated
OMe
Ph
OMe
i
R*Se
Ph
(R)-4
Entry
Substrate
Product
yield (%)
drb,c
(S)
Scheme 3 Reagents and conditions: i, Ph3SnH, AIBN, toluene, ∆.
MeO
Bu
Bu
1
2
3
4
88
94:6
Bu
Bu
Bu
SeR*
Bu
The above results indicate that this protocol provides moder-
ate to high diastereoselectivity with a diverse range of olefins,
including aryl, alkyl, mono-, di- and trisubstituted substrates.
In contrast to the asymmetric cyclizations reported earlier,5
trans-olefins afford substantially higher dr’s than their cis
isomers (cf. entry 1 vs. 2 and entry 3 vs. 4 in Table 2). The choice
of C-2 substituent in the camphor moiety is crucial and its
requirements are, surprisingly, different from those of the
related asymmetric cyclizations. The stereoselectivity is
enhanced by low temperatures and non-nucleophilic counter-
ions, and dr’s obtained with the above protocol are comparable
to or higher than those obtained with the corresponding
selenenyl sulfate.6
Bu
Bu
88
75:25
84:16
69:31
MeO
MeO
SeR*
Ph
65d
66
Ph
Ph
Ph
Ph
SeR*
Ph
Ph
Ph
MeO
Ph
SeR*
SeR*
OMe
OMe
5
6
Ph
77
88
74:26
83:17
SeR*
Ph
Ph
OMe
7
8
71
69
81:19
87:13
O
SeR*
O
Acknowledgements
SeR*
OMe
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for financial support.
MeO
9
10
11
71
90
73
75:25
84:16
86:14
SeR*
OMe
References
1 (a) C. Paulmier, Selenium Reagents and Intermediates in Organic
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SeR*
Ph
Ph
OMe
SeR*
a All reactions were performed in dichloromethane at Ϫ78 ЊC. b dr =
diastereomeric ratio. c Measured by 1H- or 77Se-NMR integration.
d The product contained a small amount of diselenide 1a after chrom-
atography. The yield is based on NMR integration of the isolated
product mixture.
dec-5-ene (0.10 mL, 0.53 mmol). Stirring was continued for 1 h
at Ϫ78 ЊC. The reaction was quenched with aqueous NaHCO3,
diluted with 10 mL of dichloromethane, washed with water and
brine, dried, filtered, and concentrated in vacuo. The residue
was chromatographed (elution with 5% ethyl acetate–hexanes)
to afford 78 mg (88%) of the addition product as a pale yellow
oil: IR (film) 1738 (C᎐O) cmϪ1; 1H NMR (major diastereomer):
᎐
δ 3.78 (d, J 4.7 Hz, 1 H), 3.42 (s, 3 H), 3.49–3.32 (m, 2 H), 2.21–
2.19 (m, 1 H), 1.86–1.25 (m, 16 H), 1.02 (s, 3 H), 0.93 (s, 3 H),
0.92 (s, 3 H), 0.92–0.89 (m, 6 H); (minor diastereomer): δ 3.99
(d, J 4.8 Hz, 1 H), 3.39 (s, 3 H); 13C NMR (major diastereomer):
δ 218.5, 85.4, 58.4, 58.2, 48.9, 47.0, 46.6, 46.0, 31.7, 31.4, 30.9,
30.6, 28.5, 23.7, 23.1, 22.8, 19.8, 14.3 (two signals), 14.2, 10.0;
(minor diastereomer): δ 85.8, 57.9, 30.7 (two signals), 23.5, 19.8;
m/z (rel. int.) 402 (21%, Mϩ), 370 (19), 230 (50), 151 (65), 101
(100), 69 (99) (Calc. for C21H38O2Se: 402.2040. Found:
402.2059).
4 (a) T. G. Back, B. P. Dyck and M. Parvez, J. Chem. Soc., Chem.
Commun., 1994, 515; (b) T. G. Back, B. P. Dyck and M. Parvez,
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of Calgary, 1996.
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6 M. Tiecco, L. Testaferri, C. Santi, F. Marini, L. Bagnoli and
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7 These results were reported in part at the 80th annual conference of
the Canadian Society for Chemistry, Windsor, Ontario, June, 1997
and are based on the M.Sc. Thesis of S. Nan, University of Calgary,
1998.
The absolute configuration of the major product in entry 5
was determined to be (S) by reductive deselenization9 to the
(R)-methyl ether 4 (Scheme 3), the major enantiomer of which
was identical to the product of O-methylation of authentic
(R)-1-phenylethanol, as determined by GC analysis with a
Cyclodex B column. The enantiomeric ratio of the deselenized
product was 72:28, in excellent accord with the dr of its pre-
cursor (74:26).
8 T. G. Back and B. P. Dyck, J. Am. Chem. Soc., 1997, 119, 2079.
9 D. L. J. Clive, G. J. Chittattu, V. Farina, W. A. Kiel, S. M. Menchen,
C. G. Russell, A. Singh, C. K. Wong and N. J. Curtis, J. Am. Chem.
Soc., 1980, 102, 4438.
Communication 8/06707D
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J. Chem. Soc., Perkin Trans. 1, 1998, 3123–3124