Asymmetric methoxyselenenylations and cyclizations with 3-camphorseleno electrophiles containing oxime substituents at C-2. Formation of an unusual oxaselenazole from an oxime-substituted selenenyl bromide

Article abstract of DOI:10.1021/jo016061c

Di[(1R)-2-Oximo-endo-3-bornyl] diselenide (4) and its benzoate derivative 5 were prepared from the corresponding known 2-keto diselenide 1. Treatment of 4 and 5 with bromine, followed by silver triflate in methanol-dichloromethane, generated the corresponding selenenyl triflates 6b and 7b. The latter reagents reacted with a variety of mono-, di-, and trisubstituted alkenes to afford the corresponding 1,2-addition products (β-methoxy selenides) in a highly diastereoselective manner. The free oxime 6b was particularly effective in such methoxyselenenylations, giving diastereomeric ratios (d.r.s) ranging from 86:14 to > 98:2. Even cis-disubstituted alkenes, which typically give poor d.r.s in similar additions with other chiral selenium electrophiles, underwent highly stereoselective additions with this reagent. Reductive deselenizations of the adducts obtained from styrene and cis- and trans-stilbene provided the corresponding methyl ethers, whose absolute configurations were determined by comparison with authentic samples. As expected, the dominant enantiomers thus obtained from cis- and trans-stilbene, using either 6b or 7b, had opposite configurations. Moreover, each geometrical isomer of stilbene produced methyl ethers with the same configuration when treated with either the oxime 6b or the benzoate 7b. Coordination effects between the substituents at the 2-position of the camphor molecule and the positive selenium atoms in the intermediate seleniranium ions are believed to play an important role in determining the stereochemical outcome of methoxyselenenylations. Selenenyl triflate 6b and selenenyl chloride 7c were also investigated in the electrophilic cyclizations of several unsaturated alcohols and carboxylic acids. However, diastereoselectivities were typically much lower than in the methoxyselenenylations. When the selenenyl bromide 6a, derived from the addition of bromine to the corresponding diselenide 4, was allowed to stand in the absence of an alkene, it underwent intramolecular cyclization with the oxime hydroxyl group, followed by further bromination, to afford the unusual oxaselenazole 11, whose structure was determined by spectroscopic means as well as by X-ray crystallography.

Full text of DOI:10.1021/jo016061c

J . Org. Chem. 2002, 67, 499-509
499
Asym m etr ic Meth oxyselen en yla tion s a n d Cycliza tion s w ith
3-Ca m p h or selen o Electr op h iles Con ta in in g Oxim e Su bstitu en ts a t
C-2. F or m a tion of a n Un u su a l Oxa selen a zole fr om a n
Oxim e-Su bstitu ted Selen en yl Br om id e
Thomas G. Back,* Ziad Moussa, and Masood Parvez
Department of Chemistry, University of Calgary, Calgary, Alberta, Canada T2N 1N4
tgback@ucalgary.ca
Received August 27, 2001
Di[(1R)-2-Oximo-endo-3-bornyl] diselenide (4) and its benzoate derivative 5 were prepared from
the corresponding known 2-keto diselenide 1. Treatment of 4 and 5 with bromine, followed by silver
triflate in methanol-dichloromethane, generated the corresponding selenenyl triflates 6b and 7b.
The latter reagents reacted with a variety of mono-, di-, and trisubstituted alkenes to afford the
corresponding 1,2-addition products (â-methoxy selenides) in a highly diastereoselective manner.
The free oxime 6b was particularly effective in such methoxyselenenylations, giving diastereomeric
ratios (d.r.s) ranging from 86:14 to >98:2. Even cis-disubstituted alkenes, which typically give poor
d.r.s in similar additions with other chiral selenium electrophiles, underwent highly stereoselective
additions with this reagent. Reductive deselenizations of the adducts obtained from styrene and
cis- and trans-stilbene provided the corresponding methyl ethers, whose absolute configurations
were determined by comparison with authentic samples. As expected, the dominant enantiomers
thus obtained from cis- and trans-stilbene, using either 6b or 7b, had opposite configurations.
Moreover, each geometrical isomer of stilbene produced methyl ethers with the same configuration
when treated with either the oxime 6b or the benzoate 7b. Coordination effects between the
substituents at the 2-position of the camphor molecule and the positive selenium atoms in the
intermediate seleniranium ions are believed to play an important role in determining the
stereochemical outcome of methoxyselenenylations. Selenenyl triflate 6b and selenenyl chloride
7c were also investigated in the electrophilic cyclizations of several unsaturated alcohols and
carboxylic acids. However, diastereoselectivities were typically much lower than in the methoxy-
selenenylations. When the selenenyl bromide 6a , derived from the addition of bromine to the
corresponding diselenide 4, was allowed to stand in the absence of an alkene, it underwent
intramolecular cyclization with the oxime hydroxyl group, followed by further bromination, to afford
the unusual oxaselenazole 11, whose structure was determined by spectroscopic means as well as
by X-ray crystallography.
In tr od u ction
selenenyl chlorides and bromides (X ) Cl or Br) undergo
anti-addition to variously substituted alkenes in inert
solvents via bridged seleniranium ions, with predomi-
nantly Markovnikov regiochemistry in the case of un-
symmetrical alkenes. When the reaction is performed in
a nucleophilic solvent such as water or methanol, incor-
poration of the solvent into the product occurs in place
of the halide, again with anti stereochemistry. Finally,
when the alkene moiety is tethered to a nucleophilic
substituent, intramolecular attack of the latter upon the
intermediate seleniranium ion takes place, leading to the
corresponding cyclized product.2,3 These reactions are
illustrated in Scheme 1. The selenium residue can then
be removed reductively4 or oxidatively5 to afford satu-
rated or unsaturated final products, respectively.
Organoselenium reagents and reactions have become
well established in the repertoire of synthetic organic
chemists.1 The additions of electrophilic selenium species
of the general structure RSeX (X ) a halide or other
leaving group) to alkenes are of particular interest and
have been widely studied for several decades.2 Thus,
* To whom correspondence should be addressed. Phone:
(403) 220-6256. Fax: (403) 289-9488.
(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 reviews of electrophilic selenium reactions, see: (a) Beaulieu,
P. L.; De´ziel, R. In Organoselenium Chemistry - A Practical Approach;
Back, T. G., Ed.; Oxford University Press: Oxford, 1999; Chapter 3.
(b) Tiecco, M. In Topics in Current Chemistry: Organoselenium
Chemistry; Wirth, T., Ed.; Springer-Verlag: Berlin, 2000; Vol. 208, pp
7-54. (c) Back T. G. In Organoselenium Chemistry; Liotta, D., Ed.;
Wiley: New York, 1987; Chapter 1. (d) Back, T. G. In The Chemistry
of Organic Selenium and Tellurium Compounds; Patai, S., Ed.;
Wiley: Chichester, 1987; Vol. 2, Chapter 3. (e) Paulmier, C. Selenium
Reagents and Intermediates in Organic Synthesis; Pergamon Press:
Oxford, 1986; Chapters 7 and 8. (f) Schmid, G. H.; Garratt, D. G. In
The Chemistry of Double-Bonded Functional Groups. Supplement A,
Part 2; Patai, S., Ed.; Wiley: New York, 1977; Chapter 9.
(3) For reviews of cyclizations induced with electrophilic selenium
reagents, see: (a) Petragnani, N.; Stefani, H. A.; Valduga, C. J .
Tetrahedron 2001, 57, 1411. (b) Nicolaou, K. C.; Petasis, N. A. Selenium
in Natural Products Synthesis; CIS: Philadelphia, 1984; Chapter 7.
(c) Nicolaou, K. C.; Petasis, N. A.; Claremon, D. A. In Organoselenium
Chemistry; Liotta, D., Ed.; Wiley: New York, 1987; Chapter 2. Such
processes have been termed “cyclofunctionalizations”; see: (d) Clive,
D. L. J .; Chittattu, G.; Curtis, N. J .; Kiel, W. A.; Wong, C. K. J . Chem.
Soc., Chem. Commun. 1977, 725. (e) Clive, D. L. J .; Russell, C. G.;
Chittattu, G.; Singh, A. Tetrahedron 1980, 36, 1399.
10.1021/jo016061c CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/03/2002

500 J . Org. Chem., Vol. 67, No. 2, 2002
Back et al.
Sch em e 1
Sch em e 2
We recently investigated a series of 3-camphorseleno
derivatives in asymmetric methoxyselenenylations
(additions of selenenyl electrophiles R*SeX in the pres-
ence of methanol as the external nucleophile) of alkenes
and cyclizations of unsaturated alcohols and carboxylic
acids.9 These compounds are easily prepared from the
diselenide 1, which is in turn available in a one-pot step
from (1R)-(+)-camphor and elemental selenium (Scheme
2).10 The best results for methoxyselenenylations were
obtained with the 2-keto selenenyl triflate derivative
2a ,9b,9c whereas cyclizations of unsaturated alcohols or
carboxylic acids were most effectively carried out with
the selenenyl chloride 3, containing a spiro-oxazolidinone
moiety at C-2.9a,9c However, the stereoselectivity in both
series of reactions was variable, ranging from diastere-
omeric ratios (d.r.s) of >95:5 to <60:40. Subsequent to
our initial communication,9a Tiecco et al.11 reported
similar studies of the selenenyl sulfate analogue 2b at 0
°C, but generally obtained comparable or poorer diaste-
reoselectivity than that afforded by the triflate 2a at the
The above processes often result in the creation of new
stereocenters, and the task of developing enantioselective
variations is of particular current importance.6 In prin-
ciple, this can be achieved by employing chiral, optically
pure reagents R*SeX, where R* is a chiral auxiliary
group. The preparation of the initial adduct is thus
achieved diastereoselectively, followed by enantioselec-
tive formation of the final deselenized product. Several
types of chiral selenium electrophiles have been inves-
tigated for this purpose,7,8 but diastereoselectivity tends
to be highly dependent upon the conditions and substitu-
tion patterns of the alkene substrates, thereby limiting
the scope and general effectiveness of this method.
o
lower temperature of -78 C. We now report the exten-
(4) For a review of deselenizations of selenium compounds, see:
Back, T. G. In Organoselenium Chemistry - A Practical Approach;
Back, T. G., Ed.; Oxford University Press: Oxford, 1999; Chapter 9.
(5) Oxidative deselenization most commonly takes place by syn-
elimination of the corresponding selenoxide; for reviews, see: (a) Back,
T. G. In Organoselenium Chemistry - A Practical Approach; Back, T.
G., Ed.; Oxford University Press: Oxford, 1999; Chapter 2. (b)
Nishibayashi, Y.; Uemura, S. In Topics in Current Chemistry: Orga-
noselenium Chemistry; Wirth, T., Ed.; Springer-Verlag: Berlin, 2000;
Vol. 208, pp 201-233.
sion of our earlier work to the preparation of the novel
2-oxime-containing diselenides 4 and 5 and the investi-
gation of their corresponding selenenyl derivatives 6 and
7, respectively, in a series of asymmetric methoxysele-
nenylations and cyclizations. The selenenyl triflates 6b
and 7b proved to be remarkably effective in asymmetric
methoxyselenenylations, with the free oxime 6b being
particularly advantageous in additions to cis-alkenes.12
On the other hand, cyclizations attempted with reagents
6 or 7 were less successful, giving relatively poor stereo-
selectivities.
(6) For recent reviews, see: (a) Wirth, T. Tetrahedron 1999, 55, 1.
(b) Wirth, T. Angew. Chem., Int. Ed. 2000, 39, 3741.
(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 some specific examples, see: (b) Fujita,
K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetrahedron 1997, 53, 2029.
(c) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetrahedron Lett.
1995, 36, 5219. (d) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1994,
923. (e) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1992, 1123. (f)
Tomoda, S.; Fujita, K.; Iwaoka, M. J . Chem. Soc., Chem. Commun.
1990, 129. (g) Tomoda, S.; Iwaoka, M. Chem. Lett. 1988, 1895. (h)
De´ziel, R.; Malenfant, E.; Thibault, C.; Fre´chette, S.; Gravel, M.
Tetrahedron Lett. 1997, 38, 4753. (i) De´ziel, R.; Goulet, S.; Grenier,
L.; Bordeleau, J .; Bernier, J . J . Org. Chem. 1993, 58, 3619. (j)
Fukuzawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H. J . Org. Chem.
1997, 62, 7711. (k) Fukuzawa, S.; Kasugahara, Y.; Uemura, S.
Tetrahedron Lett. 1994, 35, 9403. (l) Wirth, T.; Fragale, G.; Spichty,
M. J . Am. Chem. Soc. 1998, 120, 3376. (m) Wirth, T.; Ha¨uptli, S.;
Leuenberger, M. Tetrahedron: Asymmetry 1998, 9, 547. (n) Wirth, T.;
Fragale, G. Synthesis 1998, 162. (o) Wirth, T.; Fragale, G. Chem. Eur.
J . 1997, 3, 1894. (p) Wirth, T.; Angew. Chem., Int. Ed. Engl. 1995, 34,
1726. (q) Fragale, G.; Neuburger, M.; Wirth, T. J . Chem. Soc., Chem.
Commun. 1998, 1867. (r) Santi, C.; Fragale, G.; Wirth, T. Tetrahe-
dron: Asymmetry 1998, 9, 3625. (s) Wirth, T.; Kulicke, K. J .; Fragale,
G. J . Org. Chem. 1996, 61, 2686. (t) Tiecco, M.; Testaferri, L.; Santi,
C.; Tomassini, C.; Marini, F.; Bagnoli, L.; Temperini, A. Tetrahedron:
Asymmetry 2000, 11, 4645. (u) Tiecco, M.; Testaferri, L.; Bagnoli, L.;
Marini, F.; Temperini, A.; Tomassini, C.; Santi, C. Tetrahedron Lett.
2000, 41, 3241. (v) Uchiyama, M.; Satoh, S.; Ohta, A. Tetrahedron Lett.
2001, 42, 1559.
(8) For examples, see: refs 7b, 7h, 7n, 7p, 7q, and 7u and (a)
Nishibayashi, Y.; Srivastava, S. K.; Takada, H.; Fukuzawa, S.; Uemura,
S. J . Chem. Soc., Chem. Commun. 1995, 2321. (b) Takada, H.;
Nishibayashi, Y.; Uemura, S. J . Chem. Soc., Perkin Trans. 1 1999,
1511. (c) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. J . Chem. Soc.,
Chem. Commun. 1995, 1641. (d) De´ziel, R.; Malenfant, E. J . Org. Chem.
1995, 60, 4660. (e) De´ziel, R.; Malenfant, E.; Thibault, C. Tetrahedron
Lett. 1998, 39, 5493. (f) Uchiyama, M.; Oka, M.; Harai, S.; Ohta, A.
Tetrahedron Lett. 2001, 42, 1931.
(9) (a) Back, T. G.; Dyck, B. P. J . Chem. Soc., Chem. Commun. 1996,
2567. (b) Back, T. G.; Nan, S. J . Chem. Soc., Perkin Trans. 1 1998,
3123. (c) Back, T. G.; Dyck, B. P.; Nan, S. Tetrahedron 1999, 55, 3191.
(10) Back, T. G.; Dyck, B. P.; Parvez, M. J . Org. Chem. 1995, 60,
703.
(11) (a) Tiecco, M.; Testaferri, L.; Santi, C.; Marini, F.; Bagnoli, L.;
Temperini, A. Tetrahedron Lett. 1998, 39, 2809. (b) Tiecco, M.;
Testaferri, L.; Marini, F.; Santi, C.; Bagnoli, L.; Temperini, A.
Tetrahedron: Asymmetry 1999, 10, 747. For related hydroxyselene-
nylations, see: (c) Tiecco, M.; Testaferri, L.; Santi, C.; Marini, F.;
Bagnoli, L.; Temperini, A.; Tomassini, C. Eur. J . Org. Chem. 1998,
2275.
(12) Preliminary communication: Back, T. G.; Moussa, Z. Org. Lett.
2000, 2, 3007.

Asymmetric Methoxyselenenylations and Cyclizations
J . Org. Chem., Vol. 67, No. 2, 2002 501
Ta ble 1. Meth oxyselen en yla tion s of Alk en es w ith
6b a n d 7ba
Sch em e 3
Resu lts a n d Discu ssion
The preparation of diselenides 4 and 5 from 1 was
straightforward and is shown in Scheme 3. Bromination
of each diselenide produced selenenyl bromides 6a and
7a in situ, which were treated with silver triflate to
generate the corresponding selenenyl triflates 6b and 7b,
respectively. Alternatively, treatment of 5 with sulfuryl
chloride generated the selenenyl chloride 7c, whereas the
similar chlorination of 4, which contains a free hydroxyl
group, produced a complex mixture of products instead
of the corresponding selenenyl chloride. We assumed that
the free hydroxyl group of selenenyl derivatives (Z)-6a
and (Z)-6b would be capable of coordinating with the
positive selenium atom in the transition states leading
to the corresponding seleniranium ion intermediates
formed in electrophilic additions or cyclizations. Improve-
ments in the diastereoselectivity of similar processes
were previously noted when coordinating substituents
were present in other chiral auxiliary groups.13 The
corresponding benzoates 7 were included for comparison
with the free oximes 6. An X-ray crystal structure of
diselenide 5 (see Supporting Information) confirmed the
Z-configuration of the oxime moiety. We infer a similar
Z-geometry for its precursor 4 and for the corresponding
selenenyl derivatives 6 and 7. Moreover, the relatively
short interatomic distances of 2.95 and 2.97 Å between
the oxime oxygen and selenium atoms are noteworthy
in 5, suggesting that the oxime benzoate moiety might
also be capable of coordinating with the selenium atom
in seleniranium ions derived from reagents 7 and various
alkenes.14
a
All reactions were performed in dichloromethane/methanol at
-78 °C. d.r. ) diastereomeric ratio. c Measured by 77Se NMR
integration. d Products could not be separated from impurities that
precluded an unambiguous determination of yield and d.r. e Minor
distereomer was not detected; ratio is based on the estimated
minimum detection threshold. f Measured by 1H NMR integration.
b
greater than those at higher temperatures. In general,
the mixtures of unseparated diastereomers were isolated
and measurement of their d.r.s was attempted by 1H
NMR integration. In cases where this was precluded by
incomplete resolution of the proton signals of the respec-
tive diastereomers, 77Se NMR integration was used
instead.15
Table 1 shows that both the oxime 6b and its O-
benzoate derivative 7b are highly effective in methoxy-
selenenylations, with both compounds affording compa-
The methoxyselenenylation of a series of alkenes with
6b and 7b in dichloromethane-methanol is summarized
in Table 1. Attempted use of the selenenyl bromides 6a
and 7a , or the chloride 7c, gave inferior results. All
reactions were performed at -78 °C, where d.r.s were
(13) Specific examples are found in refs 7 and 8. For a theoretical
analysis, see: (a) Wang, X.; Houk, K. N.; Spichty, M.; Wirth, T. J . Am.
Chem. Soc. 1999, 121, 8567. (b) Spichty, M.; Fragale, G.; Wirth, T. J .
Am. Chem. Soc. 2000, 122, 10914.
(14) The 77Se NMR spectra of diselenides 4 and 5 are quite similar
to those of the original 2-keto derivative 1 (4: δ 377.3; 5: δ 375.3; and
1: δ 375.2 ppm relative to dimethyl selenide), indicating that any O-Se
coordination is very weak in the diselenides 4 and 5. However, it is
reasonable to expect that such coordination would be considerably
enhanced as the selenium atom assumes a positive charge during the
formation of seleniranium ions from the corresponding selenenyl
triflates. For an NMR study of intramolecular nonbonded O-Se
interactions, see: Komatsu, H.; Iwaoka, M.; Tomoda, S. J . Chem. Soc.,
Chem. Commun. 1999, 205.
(15) The chemical shifts of 77Se NMR signals cover a broad range
(>2000 ppm) and are highly sensitive to even minor structural changes.
Consequently, they tend to be well separated even in closely related
compounds such as diastereomers. For a review, see: Luthra, N. P.;
Odom, J . D. In The Chemistry of Organic Selenium and Tellurium
Compounds; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1986;
Vol. 1, Chapter 6.

502 J . Org. Chem., Vol. 67, No. 2, 2002
Back et al.
Sch em e 4
rable or superior d.r.s compared to that of the previously
investigated9b,c 2-keto derivative 2a . The reaction was
successful with monosubstituted, gem-, cis-, and trans-
disubstituted, and trisubstituted alkenes. The regio-
chemistry favors the Markovnikov isomers, where the
selenium residue is incorporated at the less substituted
position of the alkene. This is consistent with achiral
precedents,2 as well as those with other camphorseleno
species.9c,11a The results obtained with the free oxime 6b
in the case of cis-disubstituted substrates (entries 4, 7,
8, and 11) are particularly noteworthy, as asymmetric
methoxyselenenylations with other chiral selenium elec-
trophiles, including the benzoate 7b , typically give
significantly lower d.r.s with cis-alkenes than with their
trans isomers. It has been pointed out7a,g that the
mechanism for diastereoselection is different for cis- and
trans-alkenes. In the case of trans-alkenes (as well as
mono-, gem-di-, and trisubstituted ones), diastereoselec-
tivity is determined by the facial selectivity of the reagent
toward the alkene during the formation of the selenira-
nium ion. On the other hand, the overall stereochemistry
for additions to cis-alkenes is established in the second
step, where the two diastereomers are produced by
backside attack of the nucleophile at the two respective
carbon atoms of the seleniranium ion. This is illustrated
in Scheme 4, where the resulting absolute configurations
are shown for the deselenized products of methoxysele-
nenylations of cis- and trans-stilbene proceeding via
electrophilic addition to either face of the alkene, followed
by ring-opening by attack of methanol at either of the
respective carbon atoms of the intermediate seleniranium
ions. For reasons not yet clearly understood, the free
oxime reagent 6b appears to be particularly effective in
guiding the approach of the nucleophile preferentially
toward one of the carbon atoms of the seleniranium ion.
We also wished to determine the absolute configura-
tions of the new stereocenters formed in representative
products in Table 1 after reductive deselenization. We
chose the adducts obtained from styrene and cis- and
trans-stilbene for this purpose, since the corresponding
deselenized products are relatively nonvolatile and easy
to isolate, and authentic samples of known absolute
Sch em e 5
configuration are available for comparison. Thus, the
adduct obtained from selenenyl triflate 6b and styrene
was subjected to deselenization with triphenyltin hy-
dride16 and the product 8 was compared to an authentic
sample of (R)-8 obtained from the treatment of com-
mercially available (R)-1-phenylethanol with sodium
hydride and iodomethane (Scheme 5). GC analysis of the
deselenized product 8 with a chiral Cyclodex B column
indicated that the enantiomeric ratio (e.r.) was 98:2 in
favor of the (R)-enantiomer. This ratio confirms the
similarly high d.r. of the initial adduct (94:6), as mea-
sured by NMR integration (Table 1, entry 5). Further-
more, it is consistent with the formation of the selenira-
nium ion stereoisomer 9 (Scheme 5), where coordination
(16) 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.

Asymmetric Methoxyselenenylations and Cyclizations
J . Org. Chem., Vol. 67, No. 2, 2002 503
Ta ble 2. Cycliza tion s w ith 6b a n d 7ca
Sch em e 6
of the oxime hydroxyl group with the selenium atom
occurs and the bulky styrene phenyl substituent occupies
the least congested quadrant around the styrene double
bond.
a
All reactions were performed in dichloromethane/methanol at
-78 °C. d.r. ) diastereomeric ratio. c Measured by 77Se NMR
b
integration. Measured by 1H NMR integration. e The products
d
Similarly, deselenization of the adducts obtained from
trans- and cis-stilbene and each of the selenenyl triflates
6b and 7b (Table 1, entries 3 and 4) afforded R-meth-
oxybibenzyl (10) with the e.r.s indicated in Scheme 6. A
scalemic mixture of (R)- and (S)-10 was independently
obtained in the ratio of 37:63 by a literature method17,18
and was compared with the four deselenized products in
Scheme 6 by GC analysis on a chiral column. Thus, it
was determined that the product obtained from either
the free oxime 6b or the benzoate 7b and trans-stilbene
contained (R)-10 as the major enantiomer. As expected,
the reaction of cis-stilbene with either 6b or 7b favored
the opposite (S)-configuration. In each case, the e.r.s of
the deselenized products (Scheme 6) showed close cor-
relation with the d.r.s of the corresponding methoxyse-
lenenylation products (Table 1).
We also investigated the cyclizations of several unsat-
urated alcohols with selenenyl reagents 6 and 7. Al-
though similar cyclization reactions had been previously
carried out most effectively with the selenenyl chloride
3 (as opposed to the corresponding triflate) in the 2-spiro-
oxazolidinone series of chiral auxiliaries,9a,9c we were
unable to generate the corresponding selenenyl chloride
cleanly by chlorination of the diselenide 4 (vide supra),
containing the free oxime hydroxyl group. Instead, the
triflate 6b was generated in the usual manner and
employed in a variety of cyclizations, the results of which
are shown in Table 2. On the other hand, the selenenyl
chloride 7c was easily formed from diselenide 5 (oxime
benzoate substituent) and cyclizations performed with 7c
could not be separated from impurities that precluded an unam-
biguous determination of yield and d.r.
are also shown in Table 2. The selenenyl bromides 6a
and 7a were less successful at effecting cyclizations and
gave either no cyclized products or poor yields, while the
selenenyl triflate 7b gave complex mixtures that were
difficult to separate. The cyclizations performed with 6b
and 7c proceeded by 5-exo- and 6-exo-tet closures of the
corresponding seleniranium ions, as established by NMR
analysis. This is consistent both with Baldwin’s Rules19
and related precedents.9c,20 In contrast to the highly
diastereoselective methoxyselenenylations with 6b and
7b listed in Table 1, and to the earlier cyclization results
obtained with spiro-oxazolidinone 3,9a,9c the present cy-
clizations with 6b and 7c proved to be disappointing,
affording generally low d.r.s. Similar cyclizations of
4-pentenoic acid with 6b or 7c also provided the corre-
sponding lactones with poor diastereoselectivity (Table
2). The unexpected difference between the remarkably
high d.r.s observed in the methoxyselenenylations shown
in Table 1 and the low ones measured in the related
cyclizations in Table 2 indicates that subtle factors that
are not yet fully understood play a determining role in
these processes.
An unexpected product was formed when the selenenyl
bromide 6a was prepared in situ in the usual way from
equimolar amounts of diselenide 4 and bromine in the
absence of both silver triflate and an unsaturated sub-
strate. The resulting bright red product could be isolated
via careful and rapid flash chromatography and was
stable for several weeks in the refrigerator at -5 °C.
Spectroscopic and elemental analyses suggested the
unusual structure 11, which was confirmed by X-ray
crystallography.21 Very few cyclic structures containing
the N-O-Se moiety have been reported to date, but
include some oxaselenaazapentalenes22 and, very re-
cently, an oxaselenazolidine.23
(17) 1,2-Diphenylethanol was partially resolved by the method of:
Gerrard, W.; Kenyon, J . J . Chem. Soc. 1928, 2564. The product was
then treated with sodium hydride and methyl iodide to afford the
corresponding authentic scalemic methyl ether 10, obtained in an
enantiomeric ratio of 63:37, as measured by chiral GC analysis.
(18) It has been previously established that the (S)-enantiomer of
1,2-diphenylethanol is dextrorotatory; see: Berti, G.; Bottari, F.;
Ferrarini, P, L.; Macchia, B.; J . Org. Chem. 1965, 30, 4091. Since the
scalemic mixture of authentic 1,2-diphenylethanol that we obtained
was also dextrorotatory, the major enantiomer in this mixture must
also have the (S)-configuration; therefore, we assume that so does the
major isomer in the corresponding authentic scalemic mixture of
methyl ethers 10. The major (S)-enantiomer in the scalemic mixture
of 10 had the shorter retention time, and a baseline separation of the
two enantiomers was possible with a chiral Cyclodex B GC column.
(19) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734.
(20) In some other cyclizations of seleniranium ions, different exo
vs endo product distributions were observed under kinetic and
thermodynamic conditions; see ref 9c and Gruttadauria, M.; Meo, P.
L.; Noto, R. Tetrahedron 2001, 57, 1819.

504 J . Org. Chem., Vol. 67, No. 2, 2002
Back et al.
Sch em e 7
F igu r e 1. ORTEP diagram of 11
of the C-3 proton from δ 4.65 to 5.34 (d, J ) 3.8 Hz) was
consistent with the expected formation of the correspond-
ing selenenyl bromide 7a . No further change was ob-
served even after 6 h, or when an excess of bromine was
added. Thus, the further conversion of 7a to the corre-
sponding selenium tribromide apparently does not take
place under these conditions. This in turn suggests that
path b is less likely than path a in Scheme 7, assuming
that the selenium tribromide 15 is formed with similar
difficulty from diselenide 4 via the further bromination
of selenenyl bromide 6a . When an equimolar amount of
bromine was added to the free oxime 4, its signals
disappeared immediately and a new signal was observed
at δ 5.25 (dd, J ) 4.1, 1.0 Hz) and similarly attributed to
the C-3 proton of the selenenyl bromide 6a . After several
hours at room temperature, NMR analysis of the mixture
revealed that new signals from 11 had appeared at the
expense of the peak at δ 5.25 from 6a , along with
unidentified minor products that were presumably formed
from selenol 14. Unfortunately, intermediates 12 and 13
could not be identified when the reaction was monitored
either at room temperature or at -40 °C. Treatment of
4 with 3 or more molar equiv of bromine at room
temperature resulted in the clean formation of 11. These
results are consistent with path a in Scheme 7, in which
rapid conversion of the diselenide 4 to the selenenyl
bromide 6a is followed by the slower transformation of
6a to heterocycle 11.
The X-ray structure of 11 is shown in Figure 1 as an
ORTEP diagram. The relatively short bond lengths of
1.790 and 1.313 Å confirm the double-bond character of
the C-Se and C-N bonds, respectively. The O and Se
atoms are clearly joined by a covalent bond with a bond
length of 1.981 Å. The molecules occur as pairs in the
unit cell, where the respective O-Se-Br moieties are
associated and aligned head-to-tail (see Supporting
Information). The O-Se-Br bond angle of 175.94° indi-
cates a nearly linear geometry.
The facile cyclization of the electrophilic selenenyl
bromide moiety of 6a with the adjacent oxime function
to afford 12 (and ultimately 11, as shown in Scheme 7)
suggests that more reactive electrophilic selenium ana-
logues of 6a should undergo similar cyclizations even
more readily. Thus, it is possible that methoxyselenyla-
tions and other electrophilic reactions carried out with
the selenenyl triflate 6b proceed via initial cyclization
to 12, which then functions as the true electrophilic
reagent in subsequent interactions with alkenes. This in
turn could account for the differences in diastereoselec-
tivity observed between selenenyl triflate 6b, containing
A possible explanation for the formation of 11 is that
cyclization of 6a gradually takes place to produce 12,
which then undergoes bromination by the original sele-
nenyl bromide (or by bromine if it is present in excess),
followed by deprotonation of 13 (Scheme 7, path a). The
byproduct selenol 14 regenerates the original diselenide
4 upon exposure to air or is recycled to the selenenyl
bromide in the presence of excess bromine, thereby
permitting the formation of additional 11. Thus, as
expected, the yield of 11 improved from 52 to 76% when
3 mol of bromine per mole of diselenide was employed
instead of only 1 mol. Alternatively, we considered that
the selenenyl tribromide 15 may be formed when the
diselenide 4 is treated with excess bromine (Scheme 7,
path b), followed by displacement of bromide ion from
the selenium atom by the oxime hydroxyl group and
elimination of HBr to afford 11. When product 11 was
reduced by sodium borohydride, followed by aerial oxida-
tion, it regenerated diselenide 4, along with unseparated
byproducts tentatively identified as the C-3 epimers
of 4.
In an attempt to obtain additional insight into the
formation of 11, we studied the bromination of dis-
elenides 4 and 5 by 1H NMR spectroscopy. When the
oxime benzoate 5 in CDCl3 was treated with an equimo-
lar amount of bromine in carbon tetrachloride, it cleanly
produced a single new product, in which a downfield shift
(21) For
a review of structural organoselenium and tellurium
chemistry, see: Hargittai, I.; Roszondai, B. In The Chemistry of Organic
Selenium and Tellurium Compounds; Patai, S., Rappoport, Z., Eds.;
Wiley: Chichester, 1986; Vol. 1, Chapter 3.
(22) (a) Allen, C.; Boeyens, J . C. A.; Briggs, A. G.; Denner, L.;
Markwell, A. J .; Reid, D. H.; Rose, B. G. J . Chem. Soc., Chem. Commun.
1987, 967. (b) Dingwall, J . G.; Dunn, A. R.; Reid, D. H.; Wade, K. O.
J . Chem. Soc., Perkin Trans. 1 1972, 1360. (c) Llaguno, E.; Paul, I. C.
J . Chem. Soc., Perkin Trans. 2 1972, 2001.
(23) Kano, N.; Nakanishi, N.; Daicho, Y.; Kawashima, T. Chem. Lett.
2001, 610.

Asymmetric Methoxyselenenylations and Cyclizations
J . Org. Chem., Vol. 67, No. 2, 2002 505
in 5 mL of dry dichloromethane at -40 °C under argon. After
15 min, a 0.70 M solution of silver triflate (0.53 mmol) in
methanol was added, which resulted in an immediate dis-
charge of the orange selenenyl bromide color and produced a
light brown heterogeneous mixture. After another 15 min, the
mixture was cooled to -78 °C, and trans-5-decene (0.18 mL,
0.94 mmol) was added; stirring was continued for 1 h. The
reaction was quenched with aqueous NaHCO3 solution and
concentrated in vacuo. The residue was chromatographed
(elution with 10% ethyl acetate-hexanes) to afford 111 mg
(73% based on 4) of the addition product as a pale yellow oil:
IR (neat) 3375, 1649, 1376, 1091, 938 cm-1; 1H NMR (200 MHz)
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), 1.45-1.20 (m, 10 H), 0.98 (s, 6 H),
0.96-0.85 (m, 6 H), 0.81 (s, 3 H); 13C NMR (50 MHz) major
diastereomer: δ 168.2, 85.4, 58.1, 52.5, 50.2, 48.4, 47.6, 39.6,
31.8, 31.7, 31.3, 30.5, 28.3, 24.1, 22.9, 22.7, 19.1, 18.9, 14.1,
11.8; 77Se NMR major diastereomer: δ 292.7, minor diastere-
omer: δ 394.0, integrating in the ratio of 92:8; MS (m/z, %)
417 (3, M+), 399 (8), 228 (10), 148 (54), 106 (67), 69 (100), 41
(80); HRMS calcd for C21H39NO2Se 417.2146, found 417.2124.
Methoxyselenenylations with 7b were performed by the
same procedure, using diselenide 5 instead of 4. The other
reactions listed in Table 1 were performed similarly, and the
properties of the resulting products are as follows.
Meth oxyselen en yla tion of tr a n s-5-Decen e w ith 7b
(Ta ble 1, En tr y 1): IR (neat) 1746, 1649 cm-1; 1H NMR (200
MHz) major diastereomer: δ 8.37-8.28 (m, 2 H), 7.62-7.39
(m, 3 H), 4.64 (d, J ) 4.2 Hz, 1 H), 3.37 (s, 3 H), 3.27-3.16 (m,
1 H), 3.09-2.98 (m, 1 H), 2.44-2.25 (m, 1 H), 2.06-1.97 (m, 1
H), 1.89-1.20 (m, 15 H), 1.18 (s, 3 H), 1.09 (s, 3 H), 0.97-0.86
(m, 9 H); 13C NMR (50 MHz) major diastereomer: δ 176.2,
164.0, 132.8, 130.2, 129.4, 128.1, 85.8, 58.4, 53.8, 48.3, 44.9,
39.7, 32.1, 31.5, 31.2, 30.6, 28.6, 23.5, 22.9, 22.8, 22.6, 20.0,
19.1, 14.1, 13.9, 11.8; 77Se NMR major diastereomer: δ 251.8,
minor diastereomer: δ 279.7, integrating in the ratio of 94:6;
MS (m/z, %) 521 (<1), 69 (100); HRMS calcd for C28H43NO3Se
521.2408, found 521.2423.
a free oxime substituent, and its benzoate 7b. Unfortu-
nately, attempts to isolate 12 have not yet been suc-
cessful.
In conclusion, it was demonstrated that the presence
of an oxime or oxime benzoate substituent at C-2 of the
camphor moiety of the corresponding selenenyl triflates
6b and 7b dramatically improves the diastereoselectivity
of methoxyselenenylations, relative to the 2-keto ana-
logue 2a . The efficacy of the free oxime 6b in the
methoxyselenenylations of cis-alkenes is particularly
noteworthy as these substrates tend to provide low d.r.s
with other chiral selenium electrophiles. This may be the
result of cyclization of selenenyl triflate 6b to 12 prior to
electrophilic addition to the alkene. The isolation of the
oxaselenazole 11 from the selenenyl bromide 6a supports
this hypothesis. It was also found that neither 6b, 7b,
nor 7c serves as an effective reagent for the asymmetric
cyclizations of unsaturated alcohols and carboxylic acids,
for which the previously reported spiro-oxazolidinone 3
is recommended.
Exp er im en ta l Section
1H and 13C NMR spectra were recorded in deuteriochloro-
form and are reported relative to residual chloroform or TMS
as the internal standard. 77Se NMR spectra are reported
relative to dimethyl selenide (δ 0.0 ppm). Mass spectra were
obtained by EI at 70 eV. Chromatography refers to flash
chromatography on silica gel (230-400 mesh), unless other-
wise noted.
Di[(1R)-2-oxim o-en d o-3-b or n yl] Diselen id e (4). Dis-
elenide 110 (5.00 g, 10.9 mmol) and hydroxylamine hydrochlo-
ride (6.00 g, 86.3 mmol) were refluxed in 200 mL of pyridine
for 16 h. The mixture was poured into 400 mL of ether, washed
five times with 5% HCl, water, and NaCl solution, dried (Na2-
SO4), and concentrated in vacuo. The product was chromato-
graphed (20% ethyl acetate-hexanes) to afford 5.20 g (98%)
of a mixture of geometrical isomers of the diselenide 4 in the
ratio of 83:17 (NMR integration). Further chromatography (7%
ethyl acetate-hexanes) afforded (3.90 g, 73%) of the Z,Z isomer
Meth oxyselen en yla tion of 1-Decen e w ith 6b (Ta ble 1,
En tr y 2): IR (neat) 3281, 1644 cm-1 1H NMR (200 MHz)
;
major diastereomer: δ 8.18 (br s, 1 H), 3.93 (d, J ) 4.6 Hz, 1
H), 3.53 (m, 3 H), 3.38 (s, 3 H), 2.01 (m, 1 H), 1.89-1.43 (m, 8
H), 1.39-1.21 (m, 10 H), 0.99 (s, 3 H), 0.97 (s, 3 H), 0.90 (crude
t, 3 H), 0.83 (s, 3 H); 13C NMR (50 MHz) major diastereomer:
δ 168.3, 77.6, 58.7, 52.5, 50.6, 48.4, 41.9, 39.1, 32.4, 31.9, 29.7,
29.6, 29.5, 29.3, 27.6, 24.2, 22.6, 19.1, 19.0, 14.1, 11.8; 77Se
NMR major diastereomer: δ 275.3, minor diastereomer: δ
184.6, integrating in the ratio of 94:6 (two minor impurities,
<5%) were also detected at δ 367.6 and 193.5;24 MS (m/z, %)
417 (1, M+), 148 (68), 106 (94), 83 (81), 69 (100); HRMS calcd
for C21H39NO2Se 417.2146, found 417.2159.
Met h oxyselen en yla t ion of tr a n s-St ilb en e w it h 6b
(Ta ble 1, En tr y 3): IR (neat) 3281, 1601 cm-1; 1H NMR (200
MHz) δ 9.00 (br s, 1 H), 7.53-7.14 (m, 10 H), 4.73 (s, 2 H),
3.09 (s, 3 H), 2.78 (d, J ) 3.8 Hz, 1 H), 1.65-1.3 (m, 5 H), 0.96
(s, 3 H), 0.81 (s, 3 H), 0.47 (s, 3 H); 13C NMR (50 MHz) δ 168.0,
141.2, 140.1, 128.5, 128.3, 128.1, 127.7, 126.7, 87.9, 56.9, 52.4,
50.1, 49.9, 48.1, 40.9, 31.8, 23.6, 18.8, 18.7, 11.8; 77Se NMR δ
347.2; MS (m/z, %) 457 (<1, M+), 179 (73), 121 (100); HRMS
calcd for C25H31NO2Se 457.1520, found 457.1537. The minor
diastereomer was not detected, and the ratio in Table 1 is
based on the estimated minimum detection threshold.
Met h oxyselen en yla t ion of tr a n s-St ilb en e w it h 7b
(Ta ble 1, En tr y 3): IR (neat) 1744, 1647 cm-1; 1H NMR (200
MHz) major diastereomer: δ 8.35-8.27 (m, 2 H), 7.74-7.51
(m, 3 H), 7.31-7.12 (m, 10 H), 4.61 (d, J ) 8.6 Hz, 1 H), 4.08
1
4 as a yellow solid foam: IR (film) 3237, 1667 cm-1; H NMR
(200 MHz) δ 8.90 (br s, 2 H), 4.59 (dd, J ) 4.4, 1.6 Hz, 2 H),
2.25 (m, 2 H), 2.04-1.44 (m, 8 H), 1.01 (s, 12 H), 0.86 (s, 6 H);
13C NMR (50 MHz) δ 167.2, 52.9, 49.7 48.0, 43.7, 32.0, 23.8,
19.4, 19.2, 11.8; 77Se NMR δ 377.3; MS (m/z, %) 492 (<1, M+),
474 (6), 228 (19), 41 (100); HRMS calcd for C20H32N2O2Se2
492.0794, found 492.0812.
Di[(1R)-2-O-ben zoyl Oxim o-en d o-3-bor n yl] Diselen id e
(5). Benzoyl chloride (4.37 mL, 37.7 mmol), DMAP (229 mg,
1.87 mmol), and the 83:17 mixture of geometrical isomers of
diselenide 4 (4.62 g, 9.42 mmol) were stirred for 9 h at room
temperature in 200 mL of pyridine. The mixture was poured
into 400 mL of ether, washed five times with 5% HCl, water,
and NaCl, dried (Na2SO4), and concentrated in vacuo. The
residue was chromatographed (elution with 10% ethyl acetate-
hexanes) to afford 5.80 g (88%) of 5 as a similar 83:17 mixture
of geometrical isomers. Recrystallization from chloroform-
hexanes afforded yellow crystals of the pure Z,Z diselenide:
mp 165-167 °C; IR (film) 1747, 1647 cm-1; 1H NMR (200 MHz)
δ 8.26-8.19 (m, 4 H), 7.65-7.55 (m, 2 H), 7.50-7.40 (m, 4 H),
4.65 (d, J ) 4.3 Hz, 2 H), 2.24-2.13 (m, 2 H), 2.14-2.01 (m, 2
H), 1.89-1.58 (m, 6 H), 1.18 (s, 6 H), 1.05 (s, 6 H), 0.90 (s, 6
H); 13C NMR (50 MHz) δ 175.0, 163.7, 133.2, 130.0, 128.9,
128.4, 54.4, 49.5, 48.3, 43.7, 31.5, 23.8, 19.6, 19.2, 11.7; 77Se
NMR δ 375.3; MS (m/z, %) 456 (11), 229 (80), 93 (100). Anal.
Calcd for C34H40N2O4Se2: C, 58.45; H, 5.77; N, 4.01. Found:
C, 58.23; H, 5.84; N, 4.00. X-ray crystallographic data for 5 is
shown in Supporting Information.
(24) While it is not possible to determine with certainty which, if
any, of the three minor 77Se NMR peaks stem from the minor
diastereomer of the methoxyselenenylation reaction and which are
from trace impurities, the ratio of 94:6 is based on the integration of
the signal from the major diastereomer at δ 275.3 and the strongest
of the three weaker signals at δ 184.6. Thus, this ratio is the minimum
possible value for the diastereomeric ratio.
Met h oxyselen en yla t ion of tr a n s-5-Decen e w it h 6b
(Typ ica l P r oced u r e, Ta ble 1, En tr y 1). A 1.0 M solution of
bromine (0.18 mmol) in tetrachloromethane was added drop-
wise to a stirred solution of diselenide 4 (89 mg, 0.18 mmol)

506 J . Org. Chem., Vol. 67, No. 2, 2002
Back et al.
(d, J ) 8.6 Hz, 1 H), 3.12 (d, J ) 3.6 Hz, 1 H), 3.09 (s, 3 H),
2.08-1.86 (m, 1 H), 1.77-1.20 (m, 4 H), 1.05 (s, 3 H), 0.93 (s,
3 H), 0.55 (s, 3 H), minor diastereomer: δ 8.26-8.19 (m, 2 H),
4.54 (d, J ) 7.2 Hz, 1 H), 4.18 (d, J ) 7.2 Hz, 1 H), 0.62 (s, 3
H); 13C NMR (50 MHz) major diastereomer: δ 176.7, 164.0,
140.3, 139.3, 133.0, 130.1, 129.6, 129.2, 128.3, 128.2, 128.0,
127.8, 127.4, 127.1, 87.5, 57.1, 53.8, 50.1, 48.7, 48.2, 41.4, 31.4,
23.7, 19.6, 18.8, 11.6; 77Se NMR major diastereomer: δ 355.8.
Signals from the minor diastereomer could not be clearly
discerned in either the 13C or 77Se NMR spectra. The average
integration of three separate sets of 1H NMR signals gave the
ratio of 90:10. Attempted EI mass spectrometry resulted in
extensive fragmentation. The product was subjected to dese-
lenization (vide infra), and the deselenized product was
characterized further.
Meth oxyselen en ylation of Cyclopen ten e with 6b (Table
1
1, En tr y 7): IR (neat) 3308, 1652 cm-1; H NMR (200 MHz)
major diastereomer: δ 7.86 (br s, 1 H), 4.04 (dd, J ) 4.4, 1.4
Hz, 1 H), 3.81-3.73 (m, 1 H), 3.69-3.58 (m, 1 H), 3.32 (s, 3
H), 2.19 (m, 1 H), 2.09-1.47 (m, 10 H), 1.01 (s, 3 H), 0.98 (s,
3 H), 0.86 (s, 3 H); 13C NMR (50 MHz) major diastereomer: δ
167.7, 90.0, 56.7, 52.4, 50.1, 48.3, 43.0, 39.0, 31.9, 31.6, 30.9,
24.0, 23.0, 19.2, 18.9, 11.8, minor diastereomer: δ 167.6, 88.7,
49.8, 48.2, 43.1, 38.9, 32.5, 31.7, 31.1, 29.6, 23.9, 22.9, 19.3;
77Se NMR major diastereomer: δ 293.3, minor diastereomer:
δ 297.9, integrating in the ratio of 87:13; MS (m/z, %) 345 (1,
M+), 313 (2), 148 (39), 106 (100); HRMS calcd for C16H27NO2-
Se 345.1207, found 345.1218.
Meth oxyselen en ylation of Cyclopen ten e with 7b (Table
1
1, En tr y 7): IR (neat) 1744, 1647 cm-1; H NMR (200 MHz)
Meth oxyselen en yla tion of cis-Stilben e w ith 6b (Ta ble
major diastereomer: δ 8.33-8.17 (m, 2 H), 7.64-7.41 (m, 3
H), 4.44 (dd, J ) 4.4, 1.5 Hz, 1 H), 3.86-3.78 (m, 1 H), 3.23 (s,
superimposed on m at δ 3.28-3.18, total 4 H), 2.37-1.45 (m,
11 H), 1.19 (s, 3 H), 1.09 (s,3 H), 0.95 (s, 3 H), minor
diastereomer: δ 4.32 (dd, J ) 4.3, 1.7 Hz, 1 H), 3.31 (s, 3 H),
1.06 (s, 3 H); integration of signals at δ 4.44 and 4.32 gave a
ratio of 75:25; 13C NMR (50 MHz) major diastereomer: δ 176.2,
163.9, 132.9, 130.0, 129.4, 128.2, 89.3, 56.7, 53.8, 48.6, 48.5,
42.3, 39.8, 31.4 (two signals), 30.3, 23.6, 22.8, 19.8, 19.1, 11.7,
minor diastereomer: δ 176.9, 164.1, 129.6, 89.7, 56.8, 53.9,
49.5, 43.4, 40.4, 31.5, 30.8, 24.0, 22.6, 19.5; MS (m/z, %) 449
(<1, M+), 328 (3), 227 (11), 148 (45), 132 (40), 97 (100); HRMS
calcd for C23H31NO3Se - PhCO2 328.1180, found 328.1189.
Meth oxyselen en yla tion of Cycloh exen e w ith 6b (Ta ble
1
1, En tr y 4): IR (neat) 3415, 1636 cm-1; H NMR (200 MHz)
major diastereomer: δ 7.24-7.07 (m, 10 H), 4.73 (d, J ) 9.2
Hz, 1 H), 4.58 (d, J ) 9.2 Hz, 1 H), 3.34 (d, J ) 5.0 Hz, 1 H),
3.28 (s, 3 H), 1.79-1.51 (m, 5 H), 0.93 (s, 3 H), 0.87 (s, 3 H),
0.51 (s, 3 H), minor diastereomer: δ 4.76 (d, J ) 9.0 Hz, 1 H),
4.57 (d, J ) 9.0 Hz, 1 H), 3.26 (s, 3 H); 13C NMR (50 MHz)
major diastereomer: δ 168.4, 139.8, 130.0, 129.6, 127.9 (2
signals), 127.6, 127.2, 126.9, 88.2, 57.0, 52.5, 52.1, 50.0, 48.1,
38.9, 32.1, 24.1, 18.9, 18.6, 11.7; 77Se NMR major diastere-
omer: δ 366.6, minor diastereomer: δ 454.9, integrating in
the ratio of 90:10; MS (m/z, %) 457 (<1, M+), 439 (1), 409 (2),
121 (100). The product was subjected to deselenization (vide
infra), and the deselenized product was characterized further.
Meth oxyselen en yla tion of cis-Stilben e w ith 7b (Ta ble
1
1, En tr y 8): IR (neat) 3342, 1661 cm-1; H NMR (200 MHz)
1
1, En tr y 4): IR (neat) 1744, 1649 cm-1; H NMR (200 MHz)
major diastereomer: δ 4.24 (dd, J ) 4.3, 1.7 Hz, 1 H), 3.40 (s,
3 H), 3.34-3.13 (m, 2 H), 2.26-2.09 (m, 2 H), 2.08-1.99 (m, 1
H), 1.93-1.16 (m, 10 H), 0.99 (s, 3 H), 0.96 (s, 3 H), 0.82 (s, 3
H), minor diastereomer: δ 4.18 (dd, J ) 4.1, 1.5 Hz, 1 H), 3.39
(s, 3 H), 1.05 (s, 3 H), 0.92 (s, 3 H); integration of peaks at δ
4.24 and 4.18 gave a ratio of 88:12; 13C NMR (50 MHz) major
diastereomer: δ 168.6, 85.15, 56.7, 52.4, 50.3, 48.3, 44.7, 39.7,
32.0, 31.6, 30.6, 26.1, 24.1, 23.6, 19.1, 19.0, 11.7; 77Se NMR
major diastereomer δ 303.9; MS (m/z, %) 359 (1, M+), 341 (4),
major diastereomer: δ 8.41-8.33 (m, 2 H), 7.78-7.46 (m, 3
H), 7.23-6.96 (m, 9 H), 6.93-6.78 (m, 1 H), 4.52 (d, J ) 9.4
Hz, 1 H), 4.34 (d, J ) 9.4 Hz, 1 H), 3.75 (d, J ) 3.9 Hz, 1 H),
3.23 (s, 3 H), 2.05-1.82 (m, 1 H), 1.80-1.47 (m, 4 H), 1.11 (s,
3 H), 0.92 (s, 3 H), 0.62 (s, 3 H), minor diastereomer: δ 8.32-
8.26 (m, 2 H), 4.26 (d, J ) 8.7 Hz, 1 H), 3.85 (d, J ) 3.9 Hz, 1
H), 0.97 (s, 3 H); integration of the signals at δ 3.75 and 3.85
gave the ratio of 77:23; 13C NMR (50 MHz) major diastere-
omer: δ 177.7, 164.4, 139.3, 139.0, 132.9, 132.8, 130.2, 129.1,
128.5, 128.2, 127.9, 127.2, 88.5, 56.9, 54.1, 51.9, 49.4, 48.2, 41.0,
31.7, 23.9, 19.3, 18.7, 11.7, minor diastereomer: δ 176.8, 164.0,
138.9, 133.1, 129.0, 127.8, 127.7, 88.7, 57.2, 53.9, 51.5, 48.6,
48.4, 40.2, 23.6, 19.8. Attempted EI mass spectrometry re-
sulted in extensive fragmentation. The product was subjected
to deselenization (vide infra), and the deselenized product was
characterized further.
81 (100); HRMS calcd for
359.1371.
C17H29NO2Se 359.1364, found
Meth oxyselen en yla tion of Cycloh exen e w ith 7b (Ta ble
1
1, En tr y 8): IR (neat) 1745, 1647 cm-1; H NMR (200 MHz)
major diastereomer: δ 8.38-8.29 (m, 2 H), 7.67-7.40 (m, 3
H), 4.63 (dd, J ) 4.3, 1.2 Hz, 1 H), 3.34 (s, 3 H), 3.30-3.13 (m,
1 H), 2.88-2.76 (m, 1 H), 2.33-1.98 (m, 4 H), 1.90-1.24 (m, 9
H), 1.18 (s, 3 H), 1.08 (s, 3 H), 0.94 (s, 3 H), minor diastere-
omer: δ 8.21-8.12 (m, 2 H), 7.63-7.51 (m, 3 H), 4.48 (dd, J )
4.6, 1.7 Hz, 1 H), 3.36 (s, 3 H), 1.03 (s, 3 H), 0.94 (s, 3 H);
integration of signals at δ 4.63 and 4.48 gave a ratio of 62:38;
13C NMR (50 MHz) major diastereomer: δ 176.7, 164.1, 132.8,
130.1, 129.5, 128.2, 85.4, 56.4, 48.7, 48.4, 43.1, 39.9, 31.5 (two
signals), 31.4, 30.5, 25.9, 24.1, 23.6, 19.9, 19.0, 11.7, minor
diastereomer: δ 178.6, 164.3, 85.8, 56.5, 54.1, 31.4, 30.7, 25.6,
23.4, 19.4, 19.1; MS (m/z, %) 105 (99), 81 (100), 77 (95); HRMS
calcd for C24H33NO3Se 463.1626, found 463.1621.
Meth oxyselen en yla tion of Styr en e w ith 6b (Ta ble 1,
En tr y 5): IR (neat) 3293, 1668 cm-1 1H NMR (200 MHz)
;
major diastereomer: δ 7.41-7.28 (m, 5 H), 4.46 (dd, J ) 8.4,
4.6 Hz, 1 H), 3.81 (d, 4.3 Hz, 1 H), 3.27 (s, 3 H), 3.21 (dd, J )
12.1, 8.4 Hz, 1 H), 3.01 (dd, J ) 12.3, 4.8 Hz, 1 H), 2.00-1.92
(m, 1 H), 1.9-1.47 (m, 5 H), 0.98 (s, 3 H), 0.95 (s, 3 H), 0.75 (s,
3 H); 13C NMR (50 MHz) major diastereomer: δ 168.0, 141.5,
128.4, 127.8, 126.5, 84.5, 56.9, 52.4, 50.0, 48.3, 39.5, 32.8, 31.9,
23.9, 19.1, 18.9, 11.8; 77Se NMR major diastereomer: δ 212.1,
minor diastereomer: δ 206.3, integrating in the ratio of 94:6;
MS (m/z, %) 381 (<1, M+), 363 (1, M+ - H2O), 121 (100); HRMS
calcd for C19H27NO2Se 381.1207, found 381.1203.
Meth oxyselen en yla tion of R-Meth ylstyr en e w ith 7b
(Ta ble 1, En tr y 6): IR (neat) 1744, 1647 cm-1; 1H NMR (200
MHz) major diastereomer: δ 8.38-8.23 (m, 2 H), 7.69-7.42
(m, 3 H), 7.39-7.18 (m, 5 H), 3.54 (d, J ) 3.6 Hz, 1 H), 3.10 (s,
3 H), 3.00 (d, J ) 12.3 Hz, 1 H), 2.80 (d, J ) 12.5 Hz, 1 H),
2.16-1.98 (m, 1 H), 1.9-1.7 (m, 3 H), 1.66 (s, 3 H), 1.63-1.45
(m, 1 H), 1.11 (s, 3 H), 0.98 (s, 3 H), 0.71 (s, 3 H), minor
diastereomer: δ 4.05 (d, J ) 4.1 Hz, 1 H), 3.08 (s, 3 H), 2.92
(d, J ) 7.0 Hz, 1 H), 1.14 (s, 3 H), 1.02 (s, 3 H), 0.81 (s, 3 H);
integration of the signals at δ 3.54 and 4.05 provided the ratio
of 82:18; 13C NMR (50 MHz) major diastereomer: δ 176.6,
164.0, 143.3, 133.0, 130.0, 128.2, 128.1, 127.4, 127.3, 126.4,
79.5, 53.9, 53.8, 51.0, 48.3, 39.6, 38.5, 31.4, 23.5, 22.3, 19.7,
19.0, 11.7, minor diastereomer: δ 143.7, 126.2, 79.2, 50.8, 48.6,
40.2, 38.8, 22.8; MS (m/z, %) 377 (1), 135 (76), 105 (100); HRMS
calcd for C27H33NO3Se 499.1626, found 499.1645.
Meth oxyselen en ylation of 1-Meth yl-1-cycloh exen e with
1
6b (Ta ble 1, En tr y 9): IR (neat) 3326, 1639 cm-1; H NMR
(200 MHz) δ 8.08 (br s, 1 H), 3.94 (dd, J ) 4.1, 1.5 Hz, 1 H),
3.38 (dd, J ) 8.6, 3.9 Hz, 1 H), 3.24 (s, 3 H), 2.22-2.08 (m, 1
H), 2.06-1.98 (m, 1 H), 1.95-1.20 (m, 11 H), 1.32 (s, 3 H),
0.99 (s, 6 H), 0.85 (s, 3 H); 13C NMR (50 MHz) δ 167.9, 77.2,
52.5, 50.2, 48.8, 48.4, 48.2, 39.6, 34.7, 31.8, 30.6, 24.7, 24.1,
22.3, 21.1, 19.3, 19.0, 11.7; 77Se NMR δ 258.7; MS (m/z, %)
373 (<1, M+) 355 (1), 95 (93), 41 (100); HRMS calcd for C18H31
-
NO2Se 373.1520, found 373.1512. The minor diastereomer was
not detected, and the ratio in Table 1 is based on the estimated
minimum detection threshold.
Meth oxyselen en ylation of 1-Meth yl-1-cycloh exen e with
1
7b (Ta ble 1, En tr y 9): IR (neat) 1746, 1649 cm-1; H NMR
(200 MHz) δ 8.40-8.25 (m, 2 H), 7.67-7.37 (m, 3 H), 4.52 (d,
J ) 4.3 Hz, 1 H), 3.14 (s, 3 H), 3.02 (dd, J ) 9.1, 3.8 Hz, 1 H),
2.35-2.19 (m, 1 H), 2.18-1.15 (m, 12 H), 1.29 (s, 3 H), 1.16 (s,
3 H), 1.07 (s, 3 H), 0.91 (s, 3 H); 13C NMR (50 MHz) δ 176.5,
164.1, 132.8, 130.1, 129.5, 128.2, 77.7, 53.8, 48.4 (two signals),

Asymmetric Methoxyselenenylations and Cyclizations
48.3, 48.2, 40.7, 34.5, 31.4, 30.4, 25.1, 23.8, 22.2, 20.2, 20.0,
J . Org. Chem., Vol. 67, No. 2, 2002 507
(13.5 mg) were added, and heating was continued for 1 h. The
reaction mixture was then concentrated in vacuo, and the
residue was purified by chromatography (elution with 5% ethyl
acetate-hexanes) to afford 38 mg (38%) of 8 containing traces
of tin-containing impurities. This was subjected to GC analysis
using a chiral 30 m × 0.32 mm Cyclodex B column, which
provided a nearly baseline separation of the two enantiomers
of 8, obtained in the ratio of 98:2. This mixture was compared
to authentic (R)-8 prepared by the treatment of authentic,
commercial (R)-1-phenylethanol with sodium hydride and
methyl iodide in THF solvent for 3 h. The resulting authentic
(R)-8 was identical by chiral GC to the major diastereomer of
8 obtained in the above deselenization. The identity of the
product was confirmed by NMR and GC-MS analysis.
Deselen iza tion of Ad d u cts fr om cis- a n d tr a n s-Stil-
ben e a n d 6b or 7b. The mixtures of diastereomers obtained
from the methoxyselenenylation of cis- and trans-stilbene with
6b and 7b (Scheme 6 and Table 1, entries 3 and 4) were
deselenized as in the preceding procedure. The resulting
products 10 were compared with an authentic mixture of (R)-
and (S)-10, obtained in the ratio of 37:63 by a literature
method.17,18 GC analysis on a chiral Cyclodex B column thus
permitted identification of the major and minor enantiomers
of 10 obtained by deselenization, as well as their ratio. The
identity of each enantiomer in the deselenized product mix-
tures was further confirmed by adding the deselenized product
to a racemic mixture of authentic 10 and observing whether
the peak with the shorter or longer retention time (corre-
sponding to S- and R-enantiomers, respectively) was enhanced.
The results are summarized in Scheme 6. The identity of the
deselenized products was further confirmed by IR, NMR, MS,
and HRMS analysis.
19.0, 11.7; 77Se NMR δ 274.8; MS (m/z, %) 355 (5, M+
-
PhCOOH), 127 (80), 105 (99), 95 (100); HRMS calcd for C25H35
-
NO3Se - PhCOOH 355.1414, found 355.1445. The minor
diastereomer was not detected, and the ratio in Table 1 is
based on the estimated minimum detection threshold.
Meth oxyselen en ylation of 1-P h en yl-1-cycloh exen e with
1
6b (Ta ble 1, En tr y 10): IR (neat) 3405, 1639 cm-1; H NMR
(200 MHz) major diastereomer: δ 8.15 (br s, 1 H), 7.53-7.2
(m, 5 H), 3.73 (br s, 1 H), 2.97 (s, 3 H), 2.62-2.53 (m, 1 H),
2.51-2.3 (m, 1 H), 2.16-1.98 (m, 2 H), 1.73-1.18 (m, 11 H),
0.85 (s, 3 H), 0.76 (s, 3 H), 0.43 (s, 3 H); 13C NMR (50 MHz,)
major diastereomer: δ 168.8, 143.9, 127.7, 127.0, 81.0, 52.7,
52.2, 50.4, 50.1, 47.9, 41.5, 31.9, 29.7, 25.7, 23.8, 22.6, 20.9,
18.7, 18.6, 11.7; 77Se NMR major diastereomer: δ 298.7, minor
diastereomer: δ 390.5, integrating in the ratio of 90:10; MS
(m/z, %) 435 (1, M+), 417 (6), 91 (100); HRMS calcd for C23H33
-
NO2Se 435.1677, found 435.1696.
Meth oxyselen en ylation of 1-P h en yl-1-cycloh exen e with
7b (Ta ble 1, En tr y 10): IR (neat) 1746, 1648 cm-1; 1H NMR
(200 MHz) major diastereomer: δ 8.42-8.32 (m, 2 H), 7.74-
7.53 (m, 3 H), 7.50-7.35 (m, 2 H), 7.22-7.09 (m, 3 H), 3.04
(m, 1 H), 3.00 (s, 3 H), 2.71-2.46 (m, 2 H), 2.42-2.34 (m, 1
H), 2.18-1.89 (m, 4 H), 1.79-1.33 (m, 7 H), 1.03 (s, 3 H), 0.96
(s, 3 H), 0.46 (s, 3 H); 13C NMR (50 MHz) major diastereomer:
δ 175.9, 163.8, 143.7, 133.0, 130.2, 129.4, 128.1, 127.8, 127.4,
127.3, 80.8, 53.6, 50.5, 48.9, 47.8, 47.7, 39.3, 31.3, 30.2, 25.3,
23.4, 22.3, 20.9, 20.0, 18.8, 11.6; 77Se NMR major diastere-
omer: δ 295.9, minor diastereomer: δ 287.8, integrating in
the ratio of 95:5; other minor signals in the 77Se NMR spectrum
were observed at 387.9 and 19.2 ppm and were attributed to
impurities present in amounts of ca. 7 and <1%, respectively;25
MS (m/z, %) 539 (<1, M+), 417 (3, M+ - PhCOOH), 105 (100);
HRMS calcd for C30H37NO3Se - PhCOOH 417.1571, found
417.1565.
Meth oxyselen en ylation of Cycloh epten e with 6b (Table
1, En tr y 11): IR (neat) 3302, 1657 cm-1; 1H NMR (200 MHz)
major diastereomer: δ 7.88 (br s, 1 H), 4.19 (dd, J ) 4.3, 1.5
Hz, 1 H), 3.63-3.42 (m, 2 H), 3.36 (s, 3 H), 2.19-1.23 (m, 15
H), 1.00 (s, 3H), 0.98 (s, 3H), 0.85 (s, 3H), minor diastere-
omer: δ 4.06 (dd, J ) 4.1, 1.4 Hz, 1 H), 3.35 (s, 3 H), 1.04 (s,
3 H), 0.91 (s, 3 H); 13C NMR (50 MHz) major diastereomer: δ
168.0, 87.9, 56.7, 52.4, 50.2, 48.3, 46.9, 39.7, 32.0, 31.1, 30.3,
28.7, 26.8, 24.0, 22.0, 19.1, 19.0, 11.7, minor diastereomer: δ
170.7, 88.3, 54.5, 53.4, 50.0, 47.9, 41.0, 33.3, 21.5, 11.1; 77Se
NMR major diastereomer: δ 328.9, minor diastereomer: δ
301.0, integrating in the ratio of 86:14; MS (m/z, %) 373 (3,
M+), 148 (78), 106 (100); HRMS calcd for C18H31NO2Se
373.1520, found 373.1538.
Meth oxyselen en ylation of Cycloh epten e with 7b (Table
1, En tr y 11): IR (neat) 1745, 1650 cm-1; 1H NMR (200 MHz)
major diastereomer: δ 8.39-8.07 (m, 2 H), 7.69-7.38 (m, 3
H), 4.48 (dd, J ) 4.5, 1.4 Hz, 1 H), 3.60-3.37 (m, 1 H), 3.28 (s,
3 H), 3.22-3.06 (m, 1 H), 2.40-1.30 (m, 15 H), 1.18 (s, 3 H),
1.08 (s, 3 H), 0.95 (s, 3 H), minor diastereomer: δ 3.33 (s, 3
H), 1.27 (s, 3 H), 1.05 (s, 3 H); integration of signals at δ 3.28
and 3.33 gave a ratio of 73:27; 13C NMR (50 MHz) major
diastereomer: δ 176.6, 164.1, 132.9, 130.1, 130.0, 128.3, 87.4,
56.4, 53.9, 48.7, 48.5, 45.6, 40.1, 31.5, 30.9, 29.8, 28.6, 26.5,
23.7, 21.9, 19.9, 19.1, 11.8, minor diastereomer: δ 177.6, 129.7,
129.5, 87.8, 56.7, 54.0, 49.5, 46.7, 40.4, 31.6, 30.8, 30.2, 29.7,
26.1, 23.9, 22.3, 19.6; MS (m/z, %) 477 (<1, M+), 356 (2), 146
(29), 127 (61), 95 (100); HRMS calcd for C25H35NO3Se - PhCO2
356.1493, found 356.1512.
Cycliza tion of 4-P en ten -1-ol w ith 6b (Typ ica l P r oce-
d u r e, Ta ble 2, En tr y 1). A 1.0 M solution of bromine (0.20
mmol) in tetrachloromethane was added dropwise to a stirred
solution of diselenide 4 (100 mg, 0.20 mmol) in 5 mL of dry
dichloromethane at -40 °C under argon. After 15 min, a 0.70
M methanol solution of silver triflate (0.63 mmol) was added
to the reaction mixture. After another 15 min, the mixture
was cooled to -78 °C, and 4-penten-1-ol (0.083 mL, 0.80 mmol)
was added; stirring was continued for 1 h. The mixture was
then concentrated in vacuo, triturated with
a minimum
amount of chloroform, and filtered through a plug of silica gel.
Reconcentration of the filtrate and chromatography (elution
with 10% ethyl acetate-hexanes) afforded 73.4 mg (55%) of
the cyclization product as a colorless oil: IR (neat) 3297, 1456
cm-1; H NMR (200 MHz), coinciding signals from both dia-
1
stereomers: δ 4.22-4.03 (m, 1 H), 3.98 (d, J ) 5.0 Hz, 1 H),
3.92-3.69 (m, 2 H), 3.10-2.74 (m, 2 H), 2.12-2.01 (m, 1 H),
1.98-1.50 (m, 8 H), 0.99 (s, 3 H), 0.97 (s, 3 H), 0.82 (s, 3 H);
13C NMR (50 MHz) major diastereomer: δ 167.9, 79.3, 68.2,
52.4, 50.0, 48.3, 39.5, 31.9, 31.7, 30.5, 25.9, 23.9, 19.1, 18.9,
11.8, minor diastereomer: δ 167.9, 78.9, 68.2, 49.8, 39.2, 31.6,
26.0; 77Se NMR major diastereomer: δ 192.6, minor diastere-
omer: δ 187.3, integrating in the ratio of 60:40; MS (m/z, %)
314 (1, M+ - OH), 313 (1, M+ - H2O), 41 (100); HRMS calcd
for C15H25NO2Se - OH 314.1023, found 314.1027.
Cycliza tion of 4-P en ten -1-ol w ith 7c (Typ ica l P r oce-
d u r e, Ta ble 2, En tr y 1). Sulfuryl chloride (6.4 µL, 0.08 mmol)
was added to an ice-cooled solution of diselenide 5 (44.0 mg,
0.063 mmol) in 1.5 mL of dry dichloromethane. The resulting
orange solution was stirred at 0 °C for 15 min and then cooled
to -78 °C, at which time 25.5 µL of 4-penten-1-ol (0.25 mmol)
was added and stirring was continued for 45 min. The mixture
was then warmed to room temperature and concentrated in
vacuo. The crude product was taken up in a minimum amount
of chlorofrom and filtered through a plug of silica gel. The
filtrate was reconcentrated under reduced pressure and chro-
matographed (elution with 15% ethyl acetate-hexanes) to
afford 34.7 mg (63% based on 5) of the corresponding cyclic
Deselen iza tion of th e Ad d u ct fr om Styr en e a n d 6b. A
mixture of triphenyltin hydride (517 mg, 1.47 mmol) and AIBN
(26.9 mg) was added to a solution of the methoxyselenenylation
product obtained from styrene with 6b (Table 1, entry 5) (277
mg, 0.73 mmol) in 5 mL of refluxing toluene. After 2 h,
additional triphenyltin hydride (260 mg, 0.74 mmol) and AIBN
1
ether as a colorless oil; IR (neat) 1743, 1649 cm-1; H NMR
(200 MHz) major diastereomer: δ 8.31-8.19 (m, 2 H), 7.65-
7.39 (m, 3 H), 4.32 (dd, J ) 4.4, 1.4 Hz, 1 H), 4.13-3.94 (m, 1
H), 3.91-3.64 (m, 2 H), 2.81-2.63 (m, 2 H), 2.25-1.48 (m, 9
H), 1.17 (s, 3 H), 1.07 (s, 3 H), 0.92 (s, 3 H), minor diastere-
(25) We tentatively assign the peak at δ 287.8 to the minor
diastereomer because of its similar chemical shift to that of the major
diastereomer at δ 295.9. The other signals that were detected at δ 387.9
and 19.2 are therefore assigned to minor impurities.

508 J . Org. Chem., Vol. 67, No. 2, 2002
Back et al.
omer: δ 4.40 (dd, J ) 4.4, 1.4 Hz, 1 H); integration of signals
at δ 4.32 and 4.40 gave a ratio of 67:33; 13C NMR (50 MHz)
major diastereomer: δ 176.5, 164.1, 132.9, 130.0, 129.5, 128.2,
78.8, 68.2, 54.0, 49.0, 48.5, 40.2, 31.6, 31.5, 30.1, 25.9, 23.7,
19.6, 19.1, 11.7, minor diastereomer: δ 176.3, 164.0, 129.4,
78.9, 68.3, 48.7, 39.6, 31.7, 31.6, 29.7, 25.9, 23.6, 19.7; MS (m/
0.87 (s, 3 H), integration of signals at δ 1.03 and 0.99 gave a
ratio of 66:34; 13C NMR (50 MHz) major diastereomer: δ 176.5,
164.9, 154.4, 133.4, 131.6, 130.1, 128.8, 128.5, 123.7, 120.2,
115.7, 61.9, 54.0, 48.6, 48.4, 40.1, 39.5, 31.5, 32.0, 23.6, 19.6,
19.1, 11.6, minor diastereomer: δ 176.5, 154.5, 131.5, 130.2,
128.3, 61.7, 48.5, 48.2, 40.4, 39.7; MS (m/z, %) 362 (1), 361
(<1), 131 (100); HRMS calcd for C26H29NO3Se - PhCOOH
361.0945, found 361.0966.
z, %) 313 (1, M+ - PhCOOH), 77 (100); HRMS calcd for C22H29
NO3Se - PhCOOH 313.0945, found 313.0933.
-
The other reactions listed in Table 2 were performed
similarly to the above two procedures, and the properties of
the resulting products are as follows.
Cycliza tion of 4-P en ten oic Acid w ith 6b (Ta ble 2,
En tr y 5): IR (neat) 3417, 1772, 1640, cm-1 1H NMR (200
;
MHz) both diastereomers: δ 4.92-4.65 (m, 1 H), 3.99-3.86
(m, 1 H), 3.30-3.11 (m, 1 H), 3.09-2.90 (m, 1 H), 2.71-2.32
(m, 4 H), 2.13-1.90 (m, 1 H), 1.82-1.66 (m, 3 H), 1.62-1.49
(m, 1 H), 0.99 (s, 3 H), 0.97 (s, 3 H), 0.83 (s, 3 H); 13C NMR (50
MHz) major diastereomer: δ 176.8, 167.9, 79.8, 52.4, 49.8,
48.5, 40.3, 31.9, 29.8, 28.8, 27.6, 23.9, 19.0, 18.9, 11.7, minor
diastereomer: δ 176.6, 167.7, 80.5, 50.0, 40.1, 28.8, 28.0; 77Se
NMR major diastereomer: δ 175.8, minor diastereomer: δ
190.2, integrating in the ratio of 58:42; MS (m/z, %) 345 (1,
M+), 327 (3, M+ - H2O), 41 (100); HRMS calcd for C15H23NO3-
Se 345.0843, found 345.0866.
Cycliza tion of 4-P en ten oic Acid w ith 7c (Ta ble 2, en tr y
5): IR (neat) 1774, 1744, 1649 cm-1; 1H NMR (200 MHz) both
diastereomers: δ 8.20 (d, J ) 7.9 Hz, 2 H), 7.65-7.41 (m, 3
H), 4.79-4.59 (m, 1 H), 4.36 (d, J ) 4.1 Hz, 1 H), 2.96-2.72
(m, 2 H), 2.62-2.45 (m, 2 H), 2.41-2.22 (m, 1 H), 2.14-2.07
(m, 1 H), 2.04-1.59 (m, 5 H), 1.18 (s, 3 H), 1.06 (s, 3 H), 0.94
(s, 3 H); 13C NMR (50 MHz) major diastereomer: δ 176.2,
176.0, 164.0, 133.1, 129.9, 129.3, 128.4, 79.5, 54.0, 48.6, 40.6
(two signals), 31.5, 28.9, 28.6, 27.7, 23.6, 19.6, 19.1, 11.7, minor
diastereomer: δ 79.7, 54.0, 48.7, 40.6, 27.7; 77Se NMR major
diastereomer: δ 188.7, minor diastereomer: δ 192.6, integrat-
ing in the ratio of 56:44; MS, (m/z, %) 327 (11, M+ - PhCOOH),
105 (100), 77 (86); HRMS calcd for C22H27NO4Se - PhCOOH
327.0738, found 327.0731.
Cycliza tion of 5-Hexen -1-ol w ith 6b (Ta ble 2, En tr y 2):
IR (neat) 3297 cm-1; 1H NMR (200 MHz) major diastereomer:
8.90 (broad s, 1 H), 4.05-3.86 (m, 2 H), 3.57-3.25 (m, 2 H),
3.01-2.74 (m, 2 H), 2.10-1.98 (m, 1 H), 1.87-1.23 (m, 10 H),
0.98 (s, 3 H), 0.95 (s, 3 H), 0.81 (s, 3 H), minor diastereomer:
δ 8.98 (broad s, 1 H); 13C NMR (50 MHz) major diastereomer:
δ 167.7, 77.9, 68.6, 52.4, 49.8, 48.3, 39.2, 31.9, 31.3, 31.2, 25.8,
23.9, 23.4, 19.2, 19.0, 11.8, minor diastereomer: δ 167.9, 78.3,
50.0, 39.6, 32.0, 23.9, 19.1; 77Se NMR major diastereomer: δ
190.6, minor diastereomer: δ 196.6, integrating in the ratio
of 57:43; MS (m/z, %) 345 (4, M+), 148 (87), 106 (100), 99 (86),
67 (97), 43 (98); HRMS calcd for C16H27NO2Se 345.1207, found
345.1216.
Cycliza tion of 5-Hexen -1-ol w ith 7c (Ta ble 2, En tr y
1
2): IR (neat) 1749 cm-1; H NMR (200 MHz) major diastere-
omer: δ 8.30-8.20 (m, 2 H), 7.65-7.41 (m, 3 H), 4.37 (dd, J )
4.6, 1.5 Hz, 1 H), 4.02-3.87 (m, 1 H), 3.50-3.27 (m, 2 H), 2.81-
2.50 (m, 2 H), 2.23-2.00 (m, 2 H), 1.90-1.23 (m, 9 H), 1.17 (s,
3 H), 1.07 (s, 3 H), 0.92 (s, 3 H), minor diastereomer: δ 4.30
(dd, J ) 4.6, 1.5 Hz, 1 H); integration of signals at δ 4.37 and
4.30 gave a ratio of 60:40; 13C NMR (50 MHz) major diaste-
reomer: δ 176.3, 164.1, 132.9, 130.0, 129.4, 128.2, 78.0, 68.5,
53.9, 48.7, 48.5, 39.8, 31.9, 31.5, 30.2, 25.7, 23.6, 23.3, 19.7,
19.1, 11.7, minor diastereomer: δ 176.7, 164.1, 130.0, 129.5,
77.9, 49.1, 40.2, 31.8, 30.7, 23.8, 19.6; MS (m/z, %) 328 (2, M+
- PhCOO), 105 (80), 77 (100); HRMS calcd for C23H31NO3Se
- PhCOO 328.1180, found 328.1196.
In tr a m olecu la r Cycliza tion of Selen en yl Br om id e 6a .
Diselenide 4 (40 mg, 0.081 mmol) was dissolved in 2.0 mL of
dichloromethane. A 1 M tetrachloromethane solution of bro-
mine (0.24 mmol) was added dropwise at -40 °C under argon
with stirring. The red solution was cooled to -78 °C, and
stirring was continued for 30 min. The reaction mixture was
allowed to warm to -40 °C over 30 min, filtered through Celite,
and concentrated in vacuo. Rapid chromatography (elution
with 10% ethyl acetate-hexanes) afforded 40 mg (76%) of the
cyclized product 11 as a red oil, which solidified upon standing.
Recrystallization from ethanol or chloroform-hexanes afforded
Cycliza tion of (E)-4-Hexen -1-ol w ith 7c (Ta ble 2, En tr y
1
3): IR (neat) 1741 cm-1; H NMR (200 MHz) major diastere-
omer: δ 8.28-8.14 (m, 2 H), 7.62-7.38 (m, 3 H), 5.48-5.36
(m, 1 H), 4.35 (dd, J ) 4.3, 1.2 Hz, 1 H), 4.00-3.58 (m, 2 H),
3.49-3.30 (m, 1 H), 2.28-1.50 (m, 9 H), 1.32 (t, J ) 6.3 Hz, 3
H), 1.16 (s, 3 H), 1.05 (s, 3 H), 0.91 (s, 3 H), minor diastere-
omer: δ 4.45 (dd, J ) 4.3, 1.2 Hz, 1 H), 3.25-3.08 (m, 1 H),
2.71-2.50 (m, 1 H); 13C NMR (50 MHz), integration of signals
at δ 4.35 and 4.45 gave a ratio of 71:29, major diastereomer:
δ 176.0, 163.9, 133.1, 129.9, 129.2, 128.3, 79.2, 67.9, 53.7, 49.2,
48.6, 43.5, 39.7, 32.4, 31.3, 27.8, 23.7, 20.9, 19.8, 19.0, 11.7,
minor diastereomer: δ 176.8, 132.9, 130.0, 129.4, 128.2, 83.5,
68.3, 53.9, 48.7, 48.4, 39.8, 31.4, 28.9, 26.1, 23.6, 18.3, 17.9;
MS (m/z, %) 328 (3, M+ - PhCOO), 99 (81), 77 (100); HRMS
calcd for C23H31NO3Se - PhCOO 328.1180, found 328.1190.
Cycliza tion of 2-Allylp h en ol w ith 6b (Ta ble 2, En tr y
red crystals: mp 92-96 °C; IR (neat) 1445, 1376, 1031 cm-1
;
1H NMR (200 MHz): δ 3.96 (d, J ) 4.8 Hz, 1 H), 2.40-2.09
(m, 2 H), 1.55 (s, 3 H), 1.53-1.20 (m, 2 H), 1.10 (s, 3 H), 0.82
(s, 3 H); 13C NMR δ 205.3, 176.3, 62.3, 60.2, 54.4, 31.9, 25.2,
20.1, 18.8, 10.8;77Se NMR δ 1422.5; λmax (acetonitrile) 234 nm
(ꢀ 24,400), 313 nm (ꢀ 3,240), 368 nm (ꢀ 1260); MS (m/z, %) 244
(M+ - Br), 228 (9), 144 (100), 117 (95), 91 (87); HRMS calcd
for C10H14BrNOSe - Br 244.0241, found 244.0227. Anal. Calcd
for C10H14BrNOSe: C, 37.18; H, 4.37; N, 4.34; Br, 24.73.
Found: C, 38.44; H, 4.40; N, 4.13; Br, 26.37.26 X-ray crystal-
lographic data for 11 is shown in Figure 1 and Supporting
Information.
1
4): IR (neat) 3350 cm-1; H NMR (200 MHz) major diastere-
omer: δ 9.17 (broad s, 1 H), 7.22-7.04 (m, 2 H), 6.84 (t, J )
7.3 Hz, 1 H), 6.76 (d, J ) 8.0 Hz, 1 H), 5.18-4.94 (m, 1 H),
3.99 (d, J ) 4.3 Hz, 1 H), 3.47-3.22 (m, 2 H), 3.21-2.95 (m, 2
H), 2.17-2.08 (m, 1 H), 1.90-1.25 (m, 4 H), 1.01 (s, 3 H), 0.97
(s, 3 H), 0.85 (s, 3 H), minor diastereomer: δ 9.22 (broad s, 1
H), 4.11 (d, J ) 4.3 Hz, 1 H), 2.03-1.94 (m, 1 H), 1.02 (s, 3 H),
0.93 (s, 3 H), 0.91 (s, 3 H); 13C NMR (50 MHz) major
diastereomer: δ 167.8, 159.2, 127.9, 126.4, 124.9, 120.4, 109.4,
83.1, 52.4, 50.1, 48.4, 39.8, 35.7, 31.9, 30.4, 24.0, 19.1, 19.0,
11.8, minor diastereomer: δ 159.2, 127.9, 126.5, 109.3, 82.7,
49.7, 48.4, 39.4, 36.0, 30.3, 23.8, 19.1; 77Se NMR major
diastereomer: δ 194.0, minor diastereomer: δ 183.8, integrat-
ing in the ratio of 53:47; MS (m/z, %) 379 (1, M+), 131 (100);
HRMS calcd for C19H25NO2Se 379.1051, found 379.1061.
Cycliza tion of 2-Allylp h en ol w ith 7c (Ta ble 2, En tr y
When the reaction was repeated with equimolar amounts
of bromine and diselenide 4, the yield of 11 was 52% and
diselenide 4 was recovered in 15% yield.
Red u ction of 11. Sodium borohydride (87 mg, 2.3 mmol)
was added in portions to an ice-cooled solution of 11 (77 mg,
0.24 mmol) in 3.2 mL of ethanol. The red color was discharged
immediately to give a colorless heterogeneous mixture. Once
the addition was complete, the ice bath was removed and the
reaction was stirred at room temperature for 1 h. The reaction
was quenched with aqueous NH4Cl and left exposed to air.
the mixture was then extracted with several portions of ether
and dichloromethane, dried (Na2SO4), and concentrated in
vacuo. The crude product was chromatographed on silica gel
1
4): IR (neat) 1716 cm-1; H NMR (200 MHz) major diastere-
omer: δ 8.38-8.22 (m, 2 H), 7.66-7.39 (m, 3 H), 7.21-7.03
(m, 2 H), 6.95-6.76 (m, 2 H), 4.58-4.36 (m, 2 H), 3.49-2.79
(m, 4 H), 2.20-1.46 (m, 5 H), 1.14 (s, 3 H), 1.03 (s, 3 H), 0.88
(s, 3 H), minor diastereomer: δ 1.11 (s, 3 H), 0.99 (s, 3 H),
(26) Gradual decomposition of the analytical sample precluded us
from obtaining an elemental analysis in closer agreement with the
calculated values.

Asymmetric Methoxyselenenylations and Cyclizations
J . Org. Chem., Vol. 67, No. 2, 2002 509
(elution with 20% ethyl acetate-hexanes) to afford 44.7 mg
(76%) of a yellow foam that contained diselenide 4 as a major
constituent (TLC, 1H NMR, and 13C NMR). Other constituents
were tentatively identified as 3-epimers of 4.
analysis of 11 was provided by Canadian Microanalyti-
cal Service, Ltd.
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C, and 77Se
NMR spectra of 4, 5, and 11 and of the products shown in
Tables 1 and 2, as well as X-ray data for compounds 5 and 11
This material is available free of charge via the Internet at
http://pubs.acs.org.
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada (NSERC)
for financial support. We thank Dr. R. Yamdagni, Ms.
Q. Wu, and Ms. D. Fox for assistance in obtaining NMR
and mass spectra and elemental analyses. The Br
J O016061C