Exploratory studies on reactions of cobaloxime π-cations with C-nucleophiles: Irreversible alkene decomplexation versus nucleophilic capture

Article abstract of DOI:10.1021/jo951319i

(β-Hydroxyalkyl)- and (β-acetoxyalkyl)cobaloximes can undergo facile acid-catalyzed β-heteroatom exchange with oxygen and nitrogen nucleophiles in an S_N1-like mechanism via cationic metal-alkene π-complex intermediates (cobaloxime π-cations). The reaction of cobaloxime π-cations with carbon nucleophiles has not been previously reported. The results reported in this paper demonstrate that cobaloxime π-cations are reasonably good electrophiles. They are sufficiently reactive to add to the electron-rich sp² centers in allyltrimethylsilane and pyrrole. A major side reaction for intermolecular reactions is irreversible alkene decomplexation. An intramolecular pyrrole cyclization (22 to 23, 83% yield) significantly raised the yield for nucleophilic addition compared to that of the analogous intermolecular couplings (12b tb 13b, 32% yield and 17 to 18, 29% yield). The results of these studies provide a foundation for the design and evaluation of modified cobalt ligands with the goal of suppressing alkene decomplexation and enhancing reaction of cobaloxime π-cations with C-nucleophiles.

Full text of DOI:10.1021/jo951319i

J . Org. Chem. 1996, 61, 831-837
831
Exp lor a tor y Stu d ies on Rea ction s of Coba loxim e π-Ca tion s w ith
C-Nu cleop h iles: Ir r ever sible Alk en e Decom p lexa tion ver su s
Nu cleop h ilic Ca p tu r e
J ennifer L. Gage and Bruce P. Branchaud*
Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253
Received J uly 20, 1995X
(â-Hydroxyalkyl)- and (â-acetoxyalkyl)cobaloximes can undergo facile acid-catalyzed â-heteroatom
exchange with oxygen and nitrogen nucleophiles in an SN1-like mechanism via cationic metal-
alkene π-complex intermediates (cobaloxime π-cations). The reaction of cobaloxime π-cations with
carbon nucleophiles has not been previously reported. The results reported in this paper
demonstrate that cobaloxime π-cations are reasonably good electrophiles. They are sufficiently
reactive to add to the electron-rich sp2 centers in allyltrimethylsilane and pyrrole. A major side
reaction for intermolecular reactions is irreversible alkene decomplexation. An intramolecular
pyrrole cyclization (22 to 23, 83% yield) significantly raised the yield for nucleophilic addition
compared to that of the analogous intermolecular couplings (12b to 13b, 32% yield and 17 to 18,
29% yield). The results of these studies provide a foundation for the design and evaluation of
modified cobalt ligands with the goal of suppressing alkene decomplexation and enhancing reaction
of cobaloxime π-cations with C-nucleophiles.
Sch em e 1
(â-Hydroxyalkyl)- and (â-acetoxyalkyl)cobaloximes are
known to undergo facile acid-catalyzed â-heteroatom
exchange with oxygen and nitrogen nucleophiles.1 Gold-
ing2 discovered that the solvolysis of homochiral (2-
acetoxypropyl)cobaloxime (2, Scheme 1) with benzyl alco-
hol to produce 4 proceeded with retention of configura-
tion, although no yield was given. Several studies by
Brown,3 Silverman and Dolphin,4 and others have inves-
tigated the mechanism of this reaction. Brown used low-
temperature 13C NMR to directly observe the cobaloxime
π-cation of ethene, formed by acid treatment of (2-hy-
droxyethyl)- and (2-alkoxyethyl)cobaloximes.3b At -30
°C there were two 13C resonances, 41 ppm apart, for the
ethene carbons. These results indicated that even a sym-
metrical alkene such as ethene forms an unsymmetrical
rapidly equilibrating cobaloxime π-cation (Scheme 2).
We became interested in the possibility of using (â-
hydroxyalkyl)cobaloximes for carbon-carbon bond for-
mation via cobaloxime π-cations as shown in Scheme 3.
In such a scheme, the cobalt-carbon bond would play
multiple roles in bond constructions, displaying ionic
reactivity in the cobaloxime π-cation step (7-9) and
radical reactivity in further synthetic transformations via
radical processes.5 The likelihood of success for the
sequence of reactions shown in Scheme 3 hinges on the
reactivity of cobaloxime π-cations as electrophiles. The
studies described in this paper were designed to deter-
mine whether cobaloxime π-cations are sufficiently elec-
trophilic to react with alkenes in C-C bond constructions.
possible cobaloxime π-cation and its properties and
reactions can be used as a key reference standard for
comparison with other cobaloxime π-cations. Reaction
of ethylene oxide (10a ) with NaCo(dmgH)2py provided
(â-hydroxyethyl)cobaloxime, a known compound,6 in 69%
isolated yield. Acetylation of (â-hydroxyethyl)cobaloxime
with Ac2O and pyridine in CH2Cl2 provided (2-acetoxy-
ethyl)cobaloxime (12a ) in 81% isolated yield. Reaction
of 12a with allyltrimethylsilane and BF3‚Et2O in CH2-
(5) For some representative examples or reactions of B12 and B12
-
like alkylcobalt complexes see: (a) Okabe, M.; Tada, M. Chem. Lett.
1980, 831. (b) Scheffold, R.; Rytz, G.; Walder, L. In Modern Synthetic
Methods; Scheffold, R., Ed.; J ohn Wiley & Sons: New York, 1983; Vol.
3, pp 355-440. (c) J ohnson, M. D. Acc. Chem. Res. 1983, 16, 343. (d)
Ladlow, M.; Pattenden, G. Tetrahedron Lett. 1984, 25, 4317. (e) Torii,
S.; Inokuchi, T.; Yukawa, T. J . Org. Chem. 1985, 50, 5875. (f) Baldwin,
J . E.; Li, C. S. J . Chem. Soc., Chem. Comm. 1987, 166. (g) Branchaud,
B. P.; Meier, M. S.; Choi, Y. Tetrahedron Lett. 1988, 29, 167. (h) Gupta,
B. D.; Roy, S. J . Chem. Soc., Perkin Trans. 2 1988, 1377. (i) Pattenden,
G. Chem. Soc. Rev. 1988, 17, 361. (j) Ghosez, A.; Go¨bel, T.; Giese, B.
Chem. Ber. 1988, 121, 1807. (k) Branchaud, B. P.; Meier, M. S. J . Org.
Chem. 1989, 54, 1320. (l) Branchaud, B. P.; Detlefsen, W. D. Tetra-
hedron Lett. 1991, 32, 6273. (m) Clark, A. J .; J ones, K. Tetrahedron
1992, 48, 6875. (n) Giese, B.; Carboni, B.; Go¨bel, T.; Muhn, R.;
Wetterich, F. Tetrahedron Lett. 1992, 33, 2673. (o) Giese, B.; Erdmann,
P.; Go¨bel, T.; Springer, R. Tetrahedron Lett. 1992, 33, 4545. (p) Martin,
O. R.; Xie, F.; Kakarla, R.; Benhamza, R. Synlett 1993, 165. (q) Auer,
L.; Weymuth, C.; Scheffold, R. Helv. Chim. Acta 1993, 76, 810. (r) Fry,
A. J .; Sirisoma, U. N. J . Org. Chem. 1993, 58, 4919. (s) Zhang, D. Z.;
Scheffold, R. Helv. Chim. Acta 1993, 76, 2602.
Resu lts a n d Discu ssion
Initial studies focused on the cobaloxime π-cation of
ethene (shown in Scheme 2) since it is the simplest
X Abstract published in Advance ACS Abstracts, December 15, 1995.
(1) (a) Ecker, H.; Ugi. I. J . Organomet. Chem. 1976, 118, C55. (b)
Parfenov, E. A.; Yurkevich, A. M. Zh. Obshch. Khim. 1972, 42,
2350.
(2) Golding, B. T.; Sakrikar, S. J . Chem. Soc., Chem. Commun. 1972,
1183.
(3) (a) Brown, K. L.; Ramamurthy, S.; Marynick, D. S. J . Organomet.
Chem. 1985, 287, 377-94. (b) Brown, K. L.; Ramamurthy, S. Orga-
nometallics 1982, 1, 413-15.
(6) Schrauzer, G. N.; Windgassen, R. J . J . Am. Chem. Soc. 1967,
89, 143.
(4) Silverman, R. B.; Dolphin, D. J . Am. Chem. Soc. 1976, 98, 4626.
0022-3263/96/1961-0831$12.00/0 © 1996 American Chemical Society

832 J . Org. Chem., Vol. 61, No. 3, 1996
Gage and Branchaud
Sch em e 2
Sch em e 5
Sch em e 3
Reaction of 12b with allyltrimethylsilane and BF3‚Et2O
in CH2Cl2 failed to provide any of the carbon-coupled
product 11b, although 12b was completely consumed in
the reaction. Coupling of 12b with the more nucleophilic
pyrrole in methanol using PPTS as a catalyst was
successful, providing 13b, with complete regioselectivity
for C-C bond construction at the more substituted
carbon, in a modest 32% yield.
The most plausible interpretation of the results with
12a and 12b is that the cobaloxime π-cations have two
possible fates: trapping with C-nucleophile or irrevers-
ible alkene decomplexation.3 Since the alkene products
from reactions of 12a and 12b are too volatile to
conveniently isolate and quantitate, a larger substrate
with a less volatile alkene elimination product was
studied. In Scheme 5, (R-chloromethyl)napthalene (14)
was coupled with allylmagnesium bromide to provide
4-(1-naphthyl)-1-butene (15) in 87% yield.8 The alkene
moiety in 15 was epoxidized with m-chloroperoxybenzoic
acid (mCPBA) to provide 1,2-epoxy-4-(1-naphthyl)butane
in essentially quantitative yield. Reaction of the epoxide
with NH4I and LiClO4 in acetonitrile, again by the
method of Chini et al.,7 provided iodide 16 in 51% yield.
Reaction of 16 with NaCo(dmgH)2py in methanol pro-
vided a 53% yield of the â-hydroxy cobaloxime which was
reacted with Ac2O and pyridine in CH2Cl2 to provide 17
in 16% yield. The yield of 17 is low because it is unstable
and decomposes during chromatographic purification on
silica gel. Reaction of 17 with pyrrole in methanol using
PPTS as a catalyst led to the production of 18 in 29%
yield, with complete regioselectivity for C-C bond con-
struction at the more substituted carbon, and alkene 15
in 58% yield. These results demonstrate that alkene
decomplexation from the transient cobaloxime π-cation
is the major side reaction limiting the efficiency of
intermolecular coupling.
Sch em e 4
Cl2 provided 11a in 12% isolated yield; these are the best
conditions found for this reaction after exploring several
Lewis acid, solvent, and temperature parameters. Ex-
perimentation with other carbon nucleophiles led to the
discovery that pyrrole, a more electron-rich nucleophile,
reacted with 12a in methanol using pyridinium p-
toluenesulfonate (PPTS) as a catalyst to form 13a in 88%
yield (Scheme 4).
To test the effect of an alkyl substituent, (2-acetoxy-
butyl)cobaloxime (12b) was examined. Direct reaction
of NaCo(dmgH)2py with 10b proceeded in low yields.
Conversion of 10b to 1-iodobutan-2-ol was accomplished
in 98% yield using NH4I and LiClO4 in acetonitrile by
the method of Chini et al.7 Reaction of 1-iodobutan-2-ol
with NaCo(dmgH)2py provided (2-hydroxybutyl)cobaloxime
(63%) which was acetylated with Ac2O and pyridine in
CH2Cl2 to provide (2-acetoxybutyl)cobaloxime (12b) in
54% yield (33% overall yield for three steps from 10b).
Since intermolecular pyrrole couplings with alkyl-
substituted systems such as 12b (to form 13b in 32%
yield) and 17 (to form 18 in 29% yield) were feasible,
albeit in low yield, an analogous cyclization reaction was
expected to be much more favorable and high-yielding.
To examine this issue, a (â-hydroxyalkyl)cobaloxime with
an attached pyrrole moiety (22) was synthesized (Scheme
6). Selective 1,2-diol protection of 1,2,4-butanetriol (19)
using p-toluenesulfonic acid (pTsOH) in acetone9 pro-
ceeded in 86% yield to provide 1,2-O-isopropylidenebu-
tane-1,2,4-triol which was converted to tosylate 20 using
(7) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Tetrahedron 1992,
48, 3805.
(8) Lambert, J . B.; Fabricius, D. M.; Hoard, J . A. J . Org. Chem. 1979,
44, 1480.

Reactions of π-Cations with C-Nucleophiles
J . Org. Chem., Vol. 61, No. 3, 1996 833
Sch em e 6
Sch em e 8
Sch em e 7
p-toluenesulfonyl chloride (TsCl), triethylamine, and
4-(dimethylamino)pyridine (DMAP) in CH2Cl2 in es-
sentially quantitative yield. N-Alkylation of the potas-
sium salt of pyrrole anion [formed by reaction of pyrrole
with KOH in dimethyl sulfoxide (DMSO)]10 proceeded in
94% yield, and subsequent acid-catalyzed cleavage of the
acetonide group provided 21 in 86% yield (81% overall
for two steps from 20). Selective tosylation of the
primary alcohol moiety in 21 using TsCl, Et3N, and
DMAP in CH2Cl2 (essentially quantitative) followed by
reaction with NaCo(dmgH)2py in MeOH (55%) provided
(2-hydroxy-4-N-pyrrolylbutyl)cobaloxime (22) in 54% over-
all yield for two steps from 21. Mild acid catalysis using
PPTS in MeOH smoothly and efficiently converted 22
into cyclized product 23 in 83% yield.
transition state (29), as shown in Scheme 8. Exo cycliza-
tion, however, to form intermediate 30 would have to
proceed through a high-energy 5-membered ring transi-
tion state (28) which has much ring strain and numerous
eclipsing interactions on the incipient 5-membered ring.
Much of this strain is almost certainly the result of the
necessity of maintaining the planarity of the pyrrole ring
with the CH2 directly attached to the pyrrole nitrogen
since a more conformationally flexible cyclization to form
a cyclic ether (33 to 34, eq 1) is known to proceed with
exclusively exo regiochemistry via nucleophilic attack at
the more substituted carbon to provide 34 in 70% yield.1b
Interestingly, the intramolecular pyrrole reaction (22
to 23) provided exactly the opposite regiochemistry to the
analogous intermolecular pyrrole reactions (12b to 13b
and 17 to 18). The intermolecular reactions apparently
result from nucleophilic capture of the more stable isomer
of the hyperconjugated cobaloxime π-cation (25 in Scheme
7). Attack at the more substituted center can be ratio-
nalized as a charge effect in which the nucleophile is
attracted to the most positive center (the most substi-
tuted center in 25). For the intramolecular reaction, ring
strain, eclipsing interactions, and possibly some stereo-
electronic effects apparently become dominant. Hand-
held molecular models and simple molecular mechanics
modeling of possible intermediates 30 (either diastere-
omer) and 31 clearly show that endo cyclization to form
intermediate 31 and then product 23 can proceed through
a relatively strain-free and low-energy 6-membered ring
Con clu sion
The results reported in this paper demonstrate that
cobaloxime π-cations are reasonably good electrophiles
and are sufficiently reactive to add to electron-rich sp2
centers. It might be possible to exploit this interesting
and potentially useful reactivity for applications in
organic synthesis. Unfortunately, the cobaloxime π-cat-
ions derived from the simple dimethylglyoxime-based
cobaloximes used in the present study undergo facile and
apparently irreversible alkene decomplexation in com-
petition with the desired reaction with nucleophiles.
Intramolecular cyclization instead of intermolecular cou-
pling significantly raises the yield for nucleophilic addi-
tion in competition with alkene decomplexation, but
focusing solely on cyclizations limits the potential scope
of the reaction and is only a partial solution to the
problem. It should be possible to alter the steric and
electronic properties of cobaloxime ligands or the ligands
(9) Hayashi, H.; Nakanishi, K.; Brandon, C.; Marmur, J . J . Am.
Chem. Soc. 1973, 95, 8749.
(10) Heaney, H.; Ley, S. V. J . Chem. Soc., Perkin. Trans. 1 1973,
499.

834 J . Org. Chem., Vol. 61, No. 3, 1996
Gage and Branchaud
evolved, and the mixture grew lighter in color. The reaction
mixture was kept at or below 0 °C for 3.5 h and then was
allowed to warm to rt slowly overnight. The mixture was
partially neutralized with 1.0 M HCl to pH 8, dried over Na2-
SO4 for 2 h, and then filtered with suction through a fritted
glass funnel. This crude reaction mixture was adsorbed onto
15 g of silica gel and was purified by gravity column chroma-
tography (0-100% EtOAc/hexanes and then 0-10% EtOH/
EtOAc). The orange product band was collected in a N2-filled
flask. Removal of solvents in vacuo provided 3.64 g of an
orange powder (69% yield). 1H NMR δ 1.69 (t, J ) 6, 2 H),
2.15 (s, 12 H), 3.03 (t, J ) 6, 2 H), 7.33 (t, J ) 6.3, 2 H), 7.74
(t, J ) 7.2, 1 H), 8.57 (d, J ) 5.4, 2 H), 18.19 (O-H-O bridge,
br s); 13C NMR δ 12.09, 65.38 , 125.28, 137.61, 149.74, 150.00;
IR (KBr, cm-1) 3409 (br, s), 2945 (m), 2910 (m), 1553 (s), 1441
(m), 1237 (s); MS (FAB) m/ z 414 (M + 1), 334 (M - py), 289
[Co(dmgH)2]; HRMS calcd for CoC15H25N5O5 (M + 1) 414.1187,
found 414.1190.
(2-Acetoxyeth yl)coba loxim e (12a ). A flame-dried reac-
tion vessel was charged with (â-hydroxyethyl)cobaloxime (1.03
g, 2.5 mmol), dry CH2Cl2 (∼40 mL), Ac2O (1.0 mL, 10.6 mmol,
distilled), and pyridine (1.0 mL, 12.4 mmol, distilled), and then
the solution was deoxygenated for 30 min followed by stirring
at rt for 24 h. Additional pyridine (0.6 mL, 7.4 mmol) was
then added, and the reaction was followed by TLC until all
starting material was consumed; the solvent was then removed
in vacuo. The crude product was purified by flash column
chromatography (0-100% EtOAc/hexanes) to provide 0.92 g
of 12a as an orange powder (81% yield): 1H NMR δ 1.54 (t, J
) 8.1, 2 H), 1.95 (s, 3 H), 2.14 (s, 12 H), 3.73 (t, J ) 8.1, 2 H),
7.32 (t, J ) 6.6, 2 H), 7.72 (t, J ) 7.5, 1 H), 8.55 (d, J ) 5.1, 2
H), 18.19 (br s); 13C NMR δ 12.00, 21.09, 22.63 (br), 66.70,
125.20, 137.60, 149.85, 149.79, 170.75; IR (KBr) cm-1 3430 (br,
w), 2924 (w), 1729 (s), 1560 (m), 1230 (s); MS (FAB) m/ z 456
(M + 1), 376 (M - py), 289; HRMS calcd for CoC17H27N5O6 (M
+ 1) 456.1293, found 456.1300.
1-Iod obu ta n -2-ol. This compound was synthesized accord-
ing to the method of Chini et al.7 LiClO4 (1.53 g, 14.4 mmol)
and NH4I (2.0 g, 13.8 mmol) were placed in a flask and purged
with N2. Acetonitrile (∼20 mL, distilled) and 1,2-epoxybutane
(0.82 mL, 9.5 mmol) were added via syringe. The mixture was
protected from light and stirred at rt for 3 h. Half of the
solvent was then removed in vacuo, and the residue was
diluted with water. This mixture was extracted with Et2O
(3×), and then the combined Et2O layers were washed with
water and saturated NaCl, dried over MgSO4, gravity filtered,
and concentrated in vacuo to provide 1.86 g of a pale yellow
oil (98%): 1H NMR δ 0.97 (t, J ) 7.5, 3 H), 1.59 (m, 2 H), 1.85
(br s, 1 H), 3.24 (dd, J ) 6.6, 10.2, 1 H), 3.42 (dd, J ) 10.2, 1
H), 3.45 (m, 1 H); 13C NMR δ 9.87, 15.91, 29.47, 72.19; IR (neat,
cm-1) 3372 (br s), 2963 (s), 2934 (s), 2876 (s); MS (EI) m/ z
200 (M), 183 (M - OH); HRMS calcd for C4H9IO 199.9700,
found 199.9708.
(2-Hyd r oxybu tyl)coba loxim e. CoCl2‚6H2O (2.85 g, 12
mmol), dimethylglyoxime (2.74 g, 23.6 mmol), 50% NaOH (1.74
g, 22 mmol), and pyridine (1.0 mL, 12.4 mmol) were added to
deoxygenated MeOH (65 mL), and the mixture was deoxygen-
ated for 10 min. The solution was then cooled over an ice bath,
NaBH4 (0.64 g, 16.9 mmol) was added in two aliquots, and
the mixture was stirred for 10 min (greenish-brown color). A
solution of 1-iodobutan-2-ol (2.5 g, 12.5 mmol) in deoxygenated
MeOH (10 mL) was transferred via cannula into the reaction.
After the mixture was stirred for 2 h over an ice bath, NaBH4
(0.2 g, 5.3 mmol) was added. After an additional hour, the
reaction mixture was adsorbed onto silica gel. A layer of sand,
silica gel (∼100 g), and the silica adsorbed with the product
were placed (listed bottom to top) in a 600 mL fritted glass
funnel. The column was eluted under aspirator vacuum with
CH2Cl2 and then EtOAc until the eluent ran almost colorless
to yield 3.32 g of an orange powder (63% yield). Gravity
chromatography (0-100% EtOAc/hexanes) provided a sample
suitable for spectral analysis. 1H NMR δ 0.80 (t, J ) 7.5, 3
H), 1.11 (t, J ) 9.6, 1 H), 1.32 (m, 2 H), 2.13 (s, 12 H), 2.19 (m,
overlapping with a peak at 2.13 ppm), 2.36 (impurity, s), 2.81
(m, 1 H), 7.34 (t, J ) 6.6, 2 H), 7.75 (t, J ) 7.2, 1 H), 8.55 (d,
J ) 4.8, 2 H); 13C NMR δ 10.55, 12.13, 30.66, 36.99 (br), 75.46,
in other coenzyme B12 model complexes to both suppress
the alkene decomplexation reaction and enhance the
reactivity with nucleophiles. One possible solution to
both problems would be to make the cobaloxime moiety
more electron deficient, thus the more electrophilic
cobalt-containing moiety should more strongly bond with
the alkene, enhancing its lifetime, and it should also
simultaneously make the complexed alkene more reactive
with nucleophiles. Ongoing and future studies will
address these fundamental issues and also explore the
development of new synthetic methodology and potential
synthetic applications.
Exp er im en ta l Section
Ma t er ia ls a n d Met h od s. All reactions were performed
under a N2 atmosphere and were stirred with a magnetic stir
bar. All chromatography was performed on silica gel unless
otherwise noted; gravity chromatography was performed with
Mallinckrodt silica gel (60-230 mesh), and flash chromatog-
raphy was performed with EM Science silica gel 60 (finer than
230 mesh). Commercial reagent grade solvents and chemicals
were used unless otherwise noted. CH2Cl2 was dried by
passage through a column of neutral or basic Al2O3 (Aldrich:
activated, Brockmann I, ∼150 mesh) into a nitrogen-filled flask
or storage vessel. TsCl was purified by washing an Et2O
solution with saturated NaHCO3 repeatedly, drying the or-
ganic layer over MgSO4, then suction filtering through Celite,
slightly concentrating the solution, and then crystallizing by
cooling over dry ice to obtain pure TsCl. In all reactions with
cobaloximes, solvents were deoxygenated by bubbling with N2
for 1 min/mL of solution unless otherwise noted. Since
alkylcobaloximes are somewhat air sensitive in solution,
chromatography fractions were concentrated in vacuo as soon
as possible with the water bath temperature not exceeding 40
°C during rotary evaporation. Decomposition points of co-
baloximes are not reported since the temperature range of
decomposition for metal-1,2-dioxime complexes varies with
conditions.11 1H and 13C NMR spectra were recorded at 300
and 75 MHz, respectively, in CDCl3; the residual CHCl3 was
defined as 7.26 and 77.00 ppm, respectively. Coupling con-
stants are reported in hertz. Due to anisotropic effects, more
than two 13C NMR signals associated with dimethylglyoxime
monoanion ligands of alkylcobaloximes are often observed,
thus providing more 13C signals than might be expected for
an apparently symmetric metal-ligand system. Alkylco-
baloximes have a broad 13C NMR resonance for the carbon
attached to cobalt due to quadrapolar relaxation of the carbon
by the cobalt.12 Attached proton tests (APT) were performed
at 75 MHz, but with a shorter data acquisition time than the
decoupled 13C; therefore the carbon attached to the cobalt was
not detected. Optically active (S)-1,2,4-butanetriol was used
in the synthesis of compound 23 because the possibility of an
exo cyclization on 22 (instead of the endo cyclization that
produced 23) would have provided some interesting stereo-
chemical results. Since the endo cyclization to produce 23
occurred, optical rotation data on 20, 21, 22, and other
intermediates in its synthesis were not collected because that
information was no longer relevant to this study.
(2-Hyd r oxyeth yl)coba loxim e.6 CoCl2‚6H2O (3.0 g, 12.6
mmol) was added to deoxygenated MeOH (20 mL), and the
solution was deoxygenated for an additional 5 min followed
by the addition of dimethylglyoxime (3.0 g, 25.8 mmol), 50%
NaOH (2.4 g, 30 mmol), and pyridine (1.10 mL, 13.6 mmol).
The brown solution was cooled to -5 °C, and then NaBH4 (1.6
g, 42.3 mmol) was added followed by stirring for 10 min
(greenish-black mixture). Ethylene oxide (0.75 mL, 15 mmol),
which had been condensed into a Schlenk tube at -78 °C, was
transferred via cannula into the reaction mixture. Gas was
(11) Schrauzer, G. N.; Windgassen R. J . J . Am. Chem. Soc. 1966,
88, 3738.
(12) Brown, K. L.; Satyanarayana, S. Inorg. Chem. 1992, 31, 1366
and references therein.

Reactions of π-Cations with C-Nucleophiles
J . Org. Chem., Vol. 61, No. 3, 1996 835
125.26, 137.58, 149.89, 150.10; IR (KBr, cm-1) 3494 (br, m),
2945 (m), 2896 (m), 1553 (s), 1230 (s); MS (FAB) m/ z 443 (M
+ 2), 442 (M + 1), 363 (M - py), 289; HRMS calcd for
CoC17H30N5O5 (M + 2) 443.1579, found 443.1580.
1229 (s); MS (FAB) m/ z 462 (M+), 383 (M - py), 289; HRMS
calcd for CoC19H27N6O4 462.1425, found 462.1440.
(2-(r-P yr r olyl)bu tyl)coba loxim e (13b). This compound
was produced from reaction of (2-acetoxybutyl)cobaloxime
(12b) with pyrrole according to the general procedure for
pyrrole coupling. Flash chromatography (0-100% EtOAc/
hexanes) yielded a yellow-orange powder: 1H NMR δ 0.71 (t,
J ) 7.2, 3 H), 1.36 (m, 2 H), 1.58 (impurity, br s), 1.96, 2.00 (s,
12 H), 2.17 (m, J ) 8.7, ∼2 H), 2.33 (t, J ) 8.7, 1 H), 5.70 (br
s, 1 H), 6.00 (d, J ) 2.7, 1 H), 6.52 (br s, 1 H), 7.30 (t, J ) 6.3,
2 H overlapped with CHCl3), 7.71 (t, J ) 7.5, 1 H), 8.22 (br s,
1 H), 8.53 (d, J ) 5.4, 2 H), 18.20 (s); 13C NMR (peak
assignments are based on an APT NMR experiment) δ 11.91
(CH3, dmgH CH3), 32.10 (CH2), 33.45 (absent on APT, br s),14
41.02 (CH), 102.50 (CH), 107.57 (CH), 114.91 (CH), 125.05
(CH), 137.32 (CH), 138.47 (quaternary C), 149.81 (CH), 149.93
(CH), 149.97 (CH), 150.03 (quaternary C); IR (KBr, cm-1) 3413
(br, m), 2960 (w), 2924 (w), 2361 (vw), 2296 (vw), 1684 (m),
1560 (s), 1232 (s); MS (FAB) m/ z 191 (M + 1); HRMS calcd
for CoC21H32N6O4 (M + 1) 491.1817, found 491.1831.
4-(1-Na p h th yl)-1-bu ten e (15). Caution: Stench. This
compound was synthesized by the procedure of Lambert et al.8
A commercial solution of allylmagnesium bromide in Et2O was
used, and 6.65 g of 15 was obtained as a pale yellow oil (87%
yield). Gravity chromatography (0-5% CH2Cl2/hexanes) yielded
a sample suitable for spectral analysis: 1H NMR δ 2.60 (q, J
) 7.8, 2 H), 3.24 (t, J ) 7.8, 2 H), 5.11 (d, J ) 10.2, 1 H), 5.18
(d, J ) 17.1, 1 H), 6.03 (m, J ) 6.6, 10.2, 17.1, 1 H), 7.38-7.60
(m, 4 H), 7.78 (d, J ) 8.1, 1 H), 7.92 (d, J ) 7.5, 1 H), 8.11 (d,
J ) 7.8, 1 H); 13C NMR δ 32.44, 34.78, 114.89, 123.70, 125.39,
125.45, 125.50, 125.73, 125.88, 125.90, 126.62, 128.76, 131.84,
133.87, 137.88, 138.21; IR (neat, cm-1) 3066 (m), 2936 (m),
1640 (w), 1597 (w), 1510 (w), 1396 (w), 796 (s); MS (EI) m/ z
182 (M), 141 (naph - CH2+); HRMS calcd for C14H14 182.1096,
found 182.1099.
(2-Acetoxybu tyl)coba loxim e (12b). (2-Hydroxybutyl)-
cobaloxime (1.35 g, 3.1 mmol) was acetylated according to the
procedure for 12a above, except that 6.25 equiv of Ac2O and
24 equiv of pyridine were used. The reaction time was 40.5 h
at which time the starting material was still present (as
1
determined by H NMR). The silica gel used for chromatog-
raphy was first deactivated by swirling the silica with 5%
pyridine/MeOH (enough to make a homogeneous slurry) and
then removing the volatiles in vacuo until the silica was a
powder. Gravity chromatography (0-95.5% EtOAc/hexanes
containing 0.5% pyridine) yielded 0.52 g of a bright yellow-
orange powder (43% isolated yield, 54% calculated yield as
determined by 1H NMR and based on recovered starting
material): 1H NMR; δ 0.76 (t, J ) 7.5, 3 H), 1.38-1.67 (m, 4
H), 2.01 (s, 3 H), 2.12, 2.15 (singlets, 12 H total), 3.86 (m, 1
H), 7.30 (t, J ) 6.9, 2 H), 7.71 (t, J ) 7.5, 1 H), 8.58 (d, J )
5.7, 2 H) 18.19 (br s); 13C NMR δ 9.87, 11.95, 21.45, 28.37,
28.40, 77.37, 125.06, 137.45, 149.51, 149.80, 149.87, 170.78;
IR (KBr, cm-1) 3431 (br, w), 2966 (m), 2917 (m), 1729 (s), 1560
(s), 1244 (s); MS (FAB) m/ z 484 (M + 1), 404 (M - py), 289;
HRMS calcd for CoC19H31N5O6 (M + 1) 484.1606, found
484.1630.
Allyltr im eth ylsila n e Cou p lin g Con d ition s. (2-Acetoxy-
alkyl)cobaloxime was added to a reaction flask, and the flask
was purged with N2. Dry CH2Cl2 (to make the solution 0.02
M in cobaloxime) was transferred via cannula, allyltrimeth-
ylsilane (22 equiv) was added via syringe, and the mixture
was deoxygenated. BF3‚Et2O (1.2 equiv, Aldrich Sure Seal)
was added via syringe. The reaction mixture immediately
changed from orange to dark orange in color. The mixture
was stirred ∼14 h at rt, the solvents were removed in vacuo,
and the residue was flash chromatographed (0-100% EtOAc/
hexanes). Reactions were carried out with 0.09-0.25 mmol
of cobaloxime.
4-P en ten ylcoba loxim e (11a ). This compound was pro-
duced from the reaction of (2-acetoxybutyl)cobaloxime and
allyltrimethylsilane according to the general procedure above
and was isolated as an orange solid in 12% yield: 1H NMR δ
1.00 (m, 2 H), 1.60 (t, J ) 8, 2 H), 1.96 (q, J ) 7.5, 2 H), 2.11
(s, 12 H), 4.83 (dd, J ) 10.5, 18, 2 H), 5.72 (m, J ) 6.6, 9.9,
17.1, 1 H), 7.29 (t, J ) 6.6, 2 H), 7.69 (t, J ) 7.8, 1 H), 8.58 (d,
J ) 5.1, 2 H), 18.22 (s); 13C NMR δ 11.97, 11.99, 29.67, 30.00,
34.66, 113.60, 125.11, 137.34, 139.03, 149.10, 149.86, 150.03;
IR (KBr, cm-1) 3431 (broad, w), 2917 (s), 2854 (m), 1560 (s),
1237 (s); MS (FAB) m/ z 438 (M + 1), 358 (M - py), 289; HRMS
calcd for CoC18H29N5O4 (M + 1) 438.1551, found 438.1542.
P yr r ole Cou p lin g Con d ition s. MeOH (volume adjusted
so that cobaloxime is ∼7.6 mM) was deoxygenated. The
cobaloxime (1 equiv), pyrrole (125 equiv), and PPTS (2 equiv)
were added, and the solution was deoxygenated an additional
5 min. The solution was stirred while protected from ambient
light for 18 h. The reaction mixture was then transferred,
concentrated in vacuo, taken up in CH2Cl2, and poured through
a fritted glass funnel containing a thin layer of sand, silica
gel (2.5 g), and another thin layer of sand (listed bottom to
top) using additional CH2Cl2 as needed for quantitative
transfer. The silica gel was eluted under aspirator vacuum
with EtOAc (30 mL), and the solution was concentrated in
vacuo to give a product mixture. Product yield was quanti-
tated by 1H NMR using Ph3CH as an internal standard.
Reactions were carried out with 0.07-0.4 mmol of cobaloxime.
Reported yields are an average of three reactions.
1,2-Ep oxy-4-(1-n a p h th yl)bu ta n e. mCPBA (8.52 g, 80-
85% purity, ∼39.5 mmol) was added to a solution of 4-(1-
naphthyl)-1-butene (15) (4.51 g, 24.7 mmol) in CH2Cl2 (∼300
mL) and stirred. White precipitate was present during the
reaction. After 6.5 h, the reaction was complete as determined
by TLC. The reaction mixture was then concentrated in vacuo,
taken up in Et2O, washed with saturated NaHCO3, water, and
saturated NaCl, dried over MgSO4, suction filtered through
Celite, and concentrated in vacuo to give a pale yellow powder
which contained mCPBA. It was then taken up in CH2Cl2 and
stirred vigorously with saturated Na2S2O3 for 45 min. The
layers were then separated, and the organic layer was washed
with saturated Na2S2O3 and saturated NaHCO3. The drying
steps were repeated, and the product was concentrated in
vacuo to give 4.87 g of an orange oil (99% yield). Flash
chromatography (0-40% EtOAc/hexanes) gave a sample suit-
able for spectral analysis: 1H NMR δ 1.89-2.01 (m, 1 H),
2.03-2.15 (m, 1 H), 2.54 (dd, J ) 2.7, 4.8, 1 H), 2.80 (t, J )
4.5, 1 H), 3.02-3.08 (m, 1 H), 3.18-3.40 (m, 2 H), 7.38-7.47
(m, 2 H), 7.49-7.58 (m, 2 H), 7.77 (d, J ) 7.8, 1 H), 7.89 (d, J
) 8.7, 1 H), 8.08 (d, J ) 8.1, 1 H); 13C NMR δ 29.21, 33.50,
47.11, 51.86, 123.53, 125.47, 125.85, 125.95, 126.83, 128.78,
131.70, 133.88, 137.27; IR (neat, cm-1) 3046 (m), 2926 (m),
2989 (m), 1600 (m), 1510 (m); MS (EI) m/ z 198 (M), 141
(naph - CH2+); HRMS calcd for C14H14O 198.1045, found
198.1044.
1-Iod o-4-(1-n a p h th yl)bu ta n -2-ol (16). This compound
was synthesized from 1,2-epoxy-4-(1-naphthyl)butane accord-
ing to the methodology of Chini et al.7 as described above for
the preparation of 1-iodobutan-2-ol. The reaction time was
12 h; 1.89 g of the iodide was obtained. Gravity chromatog-
raphy (0-100% Et2O/hexanes) and then recrystallization from
Et2O/hexanes/CH2Cl2 gave 1.05 g of pale yellow 0.25 in. needles
(51% yield): mp 102.5-105.5 °C; 1H NMR δ 2.01 (dd, J ) 7.5,
15, 2 H), 2.15 (d, J ) 5.4, 1 H), 3.09-3.20 (m, 1 H), 3.25-3.41
(overlapped m, 3 H), 3.64 (br d, J ) 3.9, 1 H), 7.35-7.44 (m,
2 H), 7.47-7.57 (m, 2 H), 7.74 (d, J ) 7.8, 1 H), 7.88 (d, J )
7.5, 1 H), 8.08 (d, J ) 8.1, 1 H); 13C NMR δ 16.42, 29.05, 37.47,
70.52, 123.65, 125.54, 125.93, 126.11, 126.89, 128.83, 131.70,
133.93, 137.43; IR (KBr, cm-1) 3398 (br, s), 3354 (br, s), 2947
(2-(r-P yr r olyl)eth yl)coba loxim e (13a ). This compound
was produced from reaction of (2-acetoxyethyl)cobaloxime
(12a ) with pyrrole according to the general procedure for
pyrrole coupling. Flash chromatography (0-100% EtOAc/
hexanes) yielded an orange powder: 1H NMR δ 1.78 (t, J ) 9,
2 H), 2.09 (s), 2.19 (t, 14 H together), 5.83 (s, 1 H), 6.04 (m, 1
H), 6.57 (m, 1 H), 7.32 (t, J ) 6.9, 2 H), 7.72 (t, J ) 7.2, 1 H),
8.62 (d, J ) 5.7, 2 H), 18.25 (br s); 13C NMR δ 11.96, 27.95,
104.26, 108.00, 115.54, 125.17, 132.84, 137.46, 149.18, 149.54,
149.83, 150.00; IR (KBr, cm-1) 3275 (m), 2910 (m), 1553 (s),

836 J . Org. Chem., Vol. 61, No. 3, 1996
Gage and Branchaud
(m), 2915 (w); MS (EI) m/ z 326 (M), 141 (naph - CH2+); HRMS
calcd for C14H15IO 326.0169, found 326.0166.
4.16 (m, 1 H); 13C NMR δ 25.45, 26.66, 35.75, 59.66, 69.24,
74.31, 108.67; IR (neat, cm-1) 3427 (br, s), 2991 (s), 2936 (s),
2882 (s), 1382 (s), 1225 (s), 1061 (s).
(2-H yd r oxy-4-(1-n a p h t h yl)b u t yl)cob a loxim e. CoCl2‚
6H2O (2.18 g, 9.2 mmol), dimethylglyoxime (2.14 g, 18.4 mmol),
50% NaOH (1.46 g, 18.3 mmol), and pyridine (0.75 mL, 9.3
mmol) were added to deoxygenated MeOH (35 mL). The
mixture was deoxygenated an additional 10 min and then
cooled over an ice bath. Two aliquots of NaBH4 (0.69 g total,
18.2 mmol) were added over a 30 min period, and the mixture
was stirred. Iodide 16 (2.15 g, 6.6 mmol) was then added as
a deoxygenated solution in MeOH and THF (15 and 10 mL,
respectively), and the reaction mixture was allowed to warm
to rt and stirred for 2 h. NaBH4 (0.15 g, 4 mmol) was added,
and the reaction mixture was stirred for 4 h. NaBH4 (0.15 g,
4 mmol) was again added, and the reaction mixture was stirred
for an additional hour. The crude reaction mixture was
adsorbed directly onto silica gel. Gravity chromatography was
performed with deoxygenated solvents (0-100% EtOAc/hex-
anes). The orange product band was collected in a N2-filled
flask and concentrated in vacuo to give 1.97 g of an orange
foam (53% yield). Repeated gravity chromatography gave a
sample suitable for spectral analysis: 1H NMR δ 1.17 (t, J )
9.6, 1 H), 1.73 (m, 1 H), 1.89 (m, 2 H), 2.03/2.04 (two s, 12 H),
2.20 (d, J ) 9.3, 1 H), 2.84 (m, 2 H), 3.15 (m, 2 H), 7.31-7.36
(m, 4 H), 7.43-7.50 (m, 2 H), 7.67 (m, 2 H), 7.80 (d, J ) 7.5,
1 H), 8.08 (d, J ) 8.1, 1 H), 8.53 (d, J ) 5.1, 2 H), 18.20 (very
broad); 13C NMR δ 11.97, 29.00, 37.00, 38.45, 72.54, 124.25,
125.22, 125.38, 125.55, 126.05, 128.41, 132.04, 133.75, 137.57,
138.91, 149.71, 149.81, 150.08, 150.13; IR (KBr, cm-1) 3475
(br, m), 1957 (w), 2916 (w), 1559 (s), 1446 (s), 1241 (s); MS
(FAB) m/ z 568 (weak M + 1), 289.
1,2-O-Isop r op ylid en eb u t a n e-1,2,4-t r iol 4-p -Tolu en e-
su lfon a te (20). This compound was previously prepared by
Tanis et al.13 TsCl (9.78 g, 51.3 mmol) was added to a flame-
dried reaction flask. Dry CH2Cl2 (∼250 mL) was transferred
via cannula into the flask, Et3N (13 mL, 93.3 mmol, stored
over molecular sieves) was added via syringe, and the white
gas given off was purged from the flask with N2. DMAP (∼10
mg, 0.08 mmol) was added. The reaction mixture was cooled
over an ice bath, and 1,2-O-isopropylidenebutane-1,2,4-triol
(7.1 g, 48.6 mmol) was added as a solution in dry CH2Cl2 via
cannula. The mixture was stirred for 3.5 h at 0-5 °C and
then allowed to warm to rt after which it was stirred an
additional 6 h, and the reaction was determined to be complete
by TLC. The reaction mixture was then transferred and
concentrated in vacuo. The residue was taken up in EtOAc
(250 mL), washed with saturated NaHCO3 and saturated
NaCl, dried over MgSO4, suction filtered through Celite, and
concentrated in vacuo to give 14.49 g of an orange oil (99%
yield). Gravity chromatography (0-100% Et2O/hexanes) gave
a sample suitable for spectral analysis: isolated as a yellow
oil; 1H NMR δ 1.29 (s, 3 H), 1.34 (s, 3 H), 1.56 (impurity), 1.89
(m, 2 H), 2.45 (s, 3 H), 3.51 (t, J ) 7.5, 1 H), 4.02 (dd, J ) 6,
8.1, 1 H), 4.10-4.18 (m, 3 H), 7.36 (d, J ) 8.1, 2 H), 7.80 (d, J
) 8.4, 2 H); 13C NMR δ 21.32, 25.31, 26.62, 32.96, 67.24, 68.83,
72.10, 108.73, 127.64, 129.66, 133.50, 144.61; IR (neat, cm-1
)
2995 (m), 2940 (m), 2884 (m), 1607 (m), 1370 (s), 1188 (s); MS
(EI) m/ z 301 (M + 1), 243 (M - acetone), 155, 139; HRMS
calcd for C14H21SO5 (M + 1) 301.1110, found 301.1120.
(2-Acetoxy-4-(1-n a p h th yl)bu tyl)coba loxim e (17). (2-
Hydroxy-4-(1-naphthyl)butyl)cobaloxime (1.04 g, 1.8 mmol)
was acetylated as previously described for compound 12b with
10 equiv of Ac2O and 11 equiv of pyridine in dry CH2Cl2. The
reaction was complete after 41.5 h as determined by TLC.
Gravity chromatography with deoxygenated solvents (0-80%
EtOAc/hexanes) gave 0.18 g of an orange solid (16% yield).
Repeated gravity chromatography on neutral Al2O3 (Aldrich:
activated, Brockmann I, ∼150 mesh) gave a sample suitable
for spectral analysis: 1H NMR δ 1.28 (EtOAc), 1.54-1.89 (m,
4 H), 1.989 (EtOAc), 2.04 (s, 3 H), 2.11 (s, 12 H), 2.37
(impurity), 2.98 (t, J ) 8.1, 2 H), 4.16 (m, 1 H), 7.30-7.51 (m,
6 H), 7.68 (m, 2 H), 7.81 (d, J ) 7.8, 1 H), 8.05 (d, J ) 8.4, 1
H), 8.57 (d, J ) 5.1, 2 H), 18.24 (s); 13C NMR δ 12.04/12.11,
21.58, 29.35, 36.55, 76.30, 124.07, 125.17-126.35 (6 peaks),
128.54, 131.93, 133.83, 137.53, 138.41, 149.76-150.05 (4
peaks), 170.92; IR (KBr, cm-1) 3438 (br, w), 3052 (w), 2928
(w), 1726 (m), 1560 (m), 1235 (s), 1089 (m); MS (FAB) m/ z
609 (weak M + 1), 530 (M - py), 289.
4-N-P yr r olyl-1,2-O-isopr opyliden ebu tan e-1,2-diol. This
compound was peviously prepared by Tanis et al.13 A flame-
dried reaction flask was charged with powdered KOH (12.33
g, 220 mmol) and dry DMSO (∼150 mL) and cooled in an ice
bath. Pyrrole (15 mL, 216 mmol, distilled) was added, and
the ice bath was removed after 5 min. The mixture was stirred
for an additional 45 min. Tosylate 20 (42.4 g, 141 mmol) was
added as a solution in DMSO dropwise via cannula over a 45
min period. The color gradually changed from light green to
brown. After the addition of 20 was complete, no tosylate
remained (as determined by TLC). The reaction mixture was
cooled in an ice bath, and water (100 mL) was added slowly.
The mixture was poured into a separatory funnel, more water
(150 mL) and Et2O (300 mL) were added, and the layers were
separated. The organic layer was washed with saturated
NaCl, dried over MgSO4, suction filtered through a small pad
of silica over Celite, and concentrated in vacuo to yield 25.99
g of a yellow oil (94% yield). Gravity chromatography (0-50%
Et2O/hexanes) gave a sample suitable for spectral analysis;
isolated as a yellow oil; 1H NMR δ 1.35 (s, 3 H), 1.43 (s, 3 H),
1.98 (q, J ) 6.6, 2 H), 3.47 (t, J ) 7, 1 H), 3.96 (dd, J ) 3.3, 6,
1 H), 4.02 (overlapping m, 3 H), 6.14 (t, J ) 2, 2 H), 6.66 (t, J
) 2, 2 H); 13C NMR δ 25.40, 26.82, 35.49, 45.95 65.76, 72.92,
108.01, 108.71, 120.28; IR (neat, cm-1) 2991 (s), 2936 (s), 2875
(m), 2371 (w), 2336 (w), 1505 (s), 1389 (s), 1218 (s); MS (EI)
m/ z 195 (M), 137, 120, 81, 80 (pyrrole - CH2+); HRMS calcd
for C11H17NO2 195.1260, found 195.1260.
4-N-P yr r olylbu ta n e-1,2-d iol (21). This compound was
previously prepared by Tanis et al.13 Deprotection was ac-
complished by the method of Hayashi et al.9 4-N-Pyrrolyl-
1,2-O-isopropylidenebutane-1,2-diol (5.26 g, 26.9 mmol) was
dissolved in MeOH (270 mL) and deoxygenated for 2 h. HCl
(0.1 M, 84 mL) was added, and the solution was further
deoxygenated for 45 min. The reaction mixture was protected
from light and stirred for 25 h; a white floating solid appeared.
MeOH (60 mL) and water (20 mL) were added, and it was
determined by TLC that no starting material was present.
Volatiles were removed in vacuo. The residue was taken up
in EtOAc (450 mL), washed with saturated NaHCO3 and
saturated NaCl, dried over MgSO4, suction filtered through
Celite, and concentrated in vacuo to a brown oil. The aqueous
layers were then re-extracted with EtOAc, and the organic
(4-(1-Na p h t h yl)-2-(r-p yr r olyl)b u t yl)cob a loxim e (18).
This compound was produced from reaction of 17 with pyrrole
according to the general procedure for pyrrole coupling except
that the reaction time was 15 h. The yields of 15 and 18 were
quantitated by 1H NMR using Ph3CH as an internal standard.
Reported yields are an average of three reactions. Gravity
chromatography (0-100% EtOAc/hexanes) gave an orange
solid: 1H NMR δ 1.26 (EtOAc), 1.48 (d, impurity), 1.75-1.82
(m, 4 H), 1.93/1.97 (two s, 12 H), 2.33-2.44 (â-CH, impurity,
m, 2 H), 2.88 (m, 2 H), 5.84 (s, 1 H), 6.06 (d, J ) 2.4, 1 H),
6.58 (s, 1 H), 7.20-7.33 (m, 4 H), 7.41 (m, 2 H), 7.65 (m, 2 H),
7.78, (m, 2 H), 7.41 (br s, 1 H), 8.54 (d, J ) 5.4), 18.20 (s); 13
C
NMR δ 11.87, 14.17 (impurity), 20.93 (impurity), 29.66 (im-
purity), 30.87, 34.00 (br), 39.64, 40.40, 60.29 (impurity), 102.99,
107.84, 115.21, 124.05, 125.05, 125.21, 125.51, 125.62, 126.14,
128.51, 131.95, 133.87, 137.34, 138.07, 139.21, 149.93, 150.11,
150.06; IR (KBr, cm-1) 3423 (br, w), 2931 (m), 1569 (m), 1241
(s); HRMS (FAB) calcd for CoC31H38N6O4 (M + 1) 617.2286,
found 617.2298.
1,2-O-Isop r op ylid en ebu ta n e-1,2,4-tr iol. This compound
was prepared according to the procedure of Hayashi et al.
using 19.46 g of 1,2,4-butanetriol (183.4 mmol).9 A 22.99 g
sample of 1,2-O-isopropylidenebutane-1,2,4-triol was obtained
as a pure, colorless oil without purification (86% yield): 1H
NMR δ 1.25 (s, 3 H), 1.30 (s, 3 H), 1.70 (m, 2 H), 2.99 (s, 1 H),
3.44 (t, J ) 7.5), 3.64 (m, 2 H), 3.97 (dd, J ) 6.3, 8.1, 1 H),
(13) Tanis, S. P.; Raggon, J . W. J . Org. Chem. 1987, 52, 819.

Reactions of π-Cations with C-Nucleophiles
J . Org. Chem., Vol. 61, No. 3, 1996 837
layers were combined and worked up in the same manner to
give a total of 3.6 g of a brown oil (86% yield). Flash
chromatography (0-100% EtOAc/hexanes then 0-10% EtOH/
EtOAc) gave a sample suitable for spectral analysis: isolated
as a yellow oil; 1H NMR δ 1.83 (m, 2 H), 2.77 (br s, 1 H), 3.01
(br s, 1 H), 3.40 (dd, J ) 8, 11.1, 1 H), 3.54 (d, J ) 9.6, 2 H),
4.05 (t, J ) 6.9, 2 H), 6.15 (d, J ) 2, 2 H), 6.68 (d, J ) 2, 2 H);
13C NMR δ 34.34, 45.60, 66.47, 69.06, 108.01, 120.48; IR (neat,
cm-1) 3386 (br, s), 2936 (m), 2882 (m), 2371 (w), 2343 (w), 2248
(w), 1505 (s), 1293 (s), 1096 (s); MS (EI) m/ z 155 (M), 81
(pyrrole - CH2+); HRMS calcd for C8H13NO2 155.0946, found
155.0951.
raphy (0-100% EtOAc/hexanes) on deactivated silica gel (5%
pyridine/MeOH as described above) yielded an orange powder
suitable for spectral analysis: 1H NMR δ 1.03 (t, J ) 9.6, 1
H), 1.73 (m, 2 H), 2.07, 2.08 (two s, 13 H), 2.54 (m, 1 H), 2.83-
3.99 (two m, 2 H), 6.03 (s, 2 H), 6.58 (s, 2 H), 7.31 (t, J ) 6.6,
2 H), 7.72 (t, J ) 7.5, 1 H), 8.51 (d, J ) 5.4, 2 H), 18.01 (br s);
13C NMR δ 12.04, 12.09, 35.88 (br), 38.95, 45.96, 69.59, 107.35,
120.67, 125.23, 137.62, 149.69, 149.81, 150.20, 150.37; IR (KBr,
cm-1) 3470 (br, m), 2954 (w), 2926 (m), 1572 (s), 1454 (s), 1237
(s), 1097 (s); MS (FAB) m/ z 507 (M + 1); HRMS calcd for
CoC21H32N6O5 (M + 1) 507.1766, found 507.1749.
Coba loxim e 23. Cobaloxime 22 (0.84 g, 1.7 mmol) was
dissolved in MeOH (∼40 mL), and the solution was deoxygen-
ated for 35 min. PPTS (0.509 g, 2 mmol) was added, and the
reaction mixture was stirred for 20 h while protected from
ambient light. The product precipitated out of solution as a
bright yellow solid which was separated from the solution by
centrifugation at 10 °C (in centrifuge tubes topped off with
argon) followed by a MeOH rinse (MeOH deoxygenated with
argon). The tubes containing the yellow solid were purged
with N2 overnight. The yellow-orange powder was then
transferred, and the residual volatiles were removed in vacuo,
providing 0.67 g of a yellow powder (83% yield): 1H NMR δ
1.51 (m, 1 H), 1.75 (m, 1 H), 2.12 (s, 14 H), 2.40 (less than 1
H, imp), 2.95 (m, 1 H), 3.81 (m, 2 H), 5.71 (s, 1 H), 6.04 (s, 1
H), 6.40 (s, 1 H), 7.31 (t, J ) 6.6, 2 H), 7.71 (t, J ) 7.5, 1 H),
8.60 (d, J ) 5.1, 2 H), 18.01 (br s); 13C NMR (peak assignments
are based on an APT NMR experiment) δ 12.02 (CH3), 12.06
(CH3), 32.48 (CH2), 32.54 (CH2), 38.55 (not detected in APT
experiment),14 46.08 (CH2), 102.89 (CH), 107.70 (CH), 117.52
(CH), 125.11 (CH), 130.85 (quaternary C), 137.40 (CH), 149.72
(quaternary C), 149.96 (quaternary C), 150.02 (CH); IR (KBr,
cm-1) 3440 (br, m), 2922 (w), 2875 (w), 2363 (w), 2336 (w), 1559
(s), 1449 (s), 1238 (s), 1090 (s); MS (FAB); 290 [Co(dmgH)2];
HRMS calcd for CoC21H30N6O4 (M + 1) 489.1660, found
489.1647.
4-N-P yr r olylbu tan e-1,2-diol 1-p-Tolu en esu lfon ate. This
compound was previously prepared by Tanis et al.13 The
tosylate was synthesized from compound 21 (1.04 g, 6.7 mmol)
according to the procedure for the preparation of compound
20. Reaction time at 0-5 °C was 1.5 h before the reaction
was allowed to reach rt. The reaction mixture was then
transferred and concentrated in vacuo. The slushy yellow-
white mixture was taken up in EtOAc, washed with saturated
NaHCO3 and saturated NaCl, dried over MgSO4, suction
filtered through Celite, and concentrated in vacuo to give 2.03
g of an orange-brown oil (99% yield). Gravity chromatogra-
phy (0-100% EtOAc/hexanes) gave a sample suitable for
spectral analysis: isolated as a colorless oil which gave white
crystals when a chloroform solution of the oil was concentrated
1
in vacuo; mp 79.2-83 °C; H NMR δ 1.82 (m, 2 H), 2.30 (d, J
) 3.6, 1 H), 2.46 (s, 3 H), 2.76 (m, 1 H), 3.85 (dd, J ) 6.9, 10.2,
1 H), 3.93 (dd, J ) 3.0, 10.2, 1 H), 4.03 (t, J ) 6.9, 2 H), 6.12
(t, J ) 2, 2 H), 6.62 (d, J ) 2, 2 H), 7.25 (d, J ) 8.1, 2 H), 7.78
(d, J ) 8.7, 2 H); 13C NMR δ 21.47, 34.11, 45.13, 66.33, 73.55,
108.08, 120.40, 127.75, 129.85, 132.23, 145.05; IR (KBr, cm-1
)
3570 (sharp, m), 3106 (w), 2957 (w), 1355 (s), 1184 (s), 959 (s);
MS (EI) m/ z 310 (M + 1); HRMS calcd for C15H19NSO4
309.1035, found 309.1028.
(4-N-P yr r olyl-2-h yd r oxybu tyl)coba loxim e (22). CoCl2‚
6H2O (5.81 g, 24.4 mmol), dimethylglyoxime (5.65 g, 48.7
mmol), 50% NaOH (3.9 g, 48.8 mmol), and pyridine (2.0 mL,
24.7 mmol, distilled) were added to deoxygenated MeOH (84
mL), and the solution was deoxygenated for 7 more min. The
reaction mixture was cooled in an ice bath, NaBH4 (1.5 g, 40
mmol) was added in two aliquots, and the dark brown mixture
was stirred for 20 min. 4-N-Pyrrolylbutane-1,2-diol 1-p-
toluenesulfonate (4.37 g, 14.1 mmol) as a deoxygenated solu-
tion in MeOH was added via cannula. After 7 h at rt, the
solution was dark orange-red. The crude reaction mixture
was then filtered through a pad of silica gel, and the column
was eluted with EtOAc until the eluent ran light yellow.
The orange solution was concentrated in vacuo, then adsorbed
onto silica, placed on a fritted glass funnel, and eluted with
EtOAc; the orange solution was concentrated in vacuo to give
3.95 g of an orange powder (55% yield). Gravity chromatog-
Ack n ow led gm en t. J ames Navratil assisted in the
preparation of several synthetic intermediates shown
in Scheme 6. This research was supported by NSF CHE
8806805, NSF CHE 9423782, and a fellowship from the
U.S. Department of Education GAANN Program (J .G.).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of all compounds (43 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O951319I
(14) See Materials and Methods in Experimental Section.