Transition metal mediated exo selective Diels-Alder reactions: Preparation of 2-cobalt-substituted 1,3-dienes containing C2 symmetric 2,3-dibenzobicyclo[2.2.2]octanedione dioxime equatorial ligands and their use in thermal and Lewis acid catalyzed 4 + 2 cycloadditions

Article abstract of DOI:10.1021/jo951505o

The preparation of C₂ symmetric 2,3-dibenzobicyclo[2.2.2]octanedione dioxime is reported. This ligand is then used in the preparation of a (pyridine)(glyoxime)₂cobalt(III) chloride complex. The chloride is reduced to a cobaloxime anion which reacted with allenic electrophiles to produce (pyridine)(glyoxime)₂cobalt-1,3-dienyl complexes. Thermal and Lewis acid catalyzed Diels-Alder reactions of these dienyl complexes as well as the complexes with glyoxime = diphenylglyoxime and dimethylglyoxime are reported. In most cases these Diels-Alder reactions are anti (exo) selective, and in many cases diastereoselectivities are >20:1. Cycloadduct demetalation reactions are also reported which preserve cycloaddition stereochemistry and provide cobalt complexes which can be recycled into the starting dienyl complex.

Full text of DOI:10.1021/jo951505o

J . Org. Chem. 1996, 61, 133-141
133
Tr a n sition Meta l Med ia ted Exo Selective Diels-Ald er Rea ction s:
P r ep a r a tion of 2-Coba lt-Su bstitu ted 1,3-Dien es Con ta in in g C
2
Sym m etr ic 2,3-Diben zobicyclo[2.2.2]octa n ed ion e Dioxim e
Equ a tor ia l Liga n d s a n d Th eir Use in Th er m a l a n d Lew is Acid
Ca ta lyzed 4 + 2 Cycloa d d ition s
Marcus W. Wright and Mark E. Welker*,†
Department of Chemistry, Wake Forest University, P.O. Box 7486, Winston-Salem, North Carolina 27109
Received August 14, 1995X
The preparation of C
ligand is then used in the preparation of a (pyridine)(glyoxime)
chloride is reduced to a cobaloxime anion which reacted with allenic electrophiles to produce
pyridine)(glyoxime) cobalt-1,3-dienyl complexes. Thermal and Lewis acid catalyzed Diels-Alder
2
symmetric 2,3-dibenzobicyclo[2.2.2]octanedione dioxime is reported. This
2
cobalt(III) chloride complex. The
(
2
reactions of these dienyl complexes as well as the complexes with glyoxime ) diphenylglyoxime
and dimethylglyoxime are reported. In most cases these Diels-Alder reactions are anti (exo)
selective, and in many cases diastereoselectivities are >20:1. Cycloadduct demetalation reactions
are also reported which preserve cycloaddition stereochemistry and provide cobalt complexes which
can be recycled into the starting dienyl complex.
In tr od u ction
Recently, we have been preparing cobalt-substituted
1
,3-dienes (3) and examining the rates, regioselectivities,
and stereoselectivities of their reactions with dienophiles
in Diels-Alder reactions.1 Tada et al. have reported
alternative preparations of some cobaloxime dienes as
well as results of their cycloaddition reactions.2 Several
other groups have also recently reported that the alter-
nate strategy of transition-metal substitution in the
dienophiles can have a pronounced effect on cycloaddition
diastereoselectivities.3 We have found that for di- and
trisubstituted dienophiles (4) the diastereoselectivities of
these 4 + 2 cycloadditions range from about 5:1 anti:syn
(exo:endo selectivity) for L ) different pyridines and R )
Me to >20:1 for L ) DMAP and R ) Ph. The diastereo-
selectivities seen are unusual for acyclic dienes in that
products arising from exo transition states are the major
products. In contrast, monosubstituted dienophiles re-
acted with these complexes with low diastereoselectivities
Exp er im en ta l Section
Gen er a l Meth od s. For a description of instrumentation
and chromatographic adsorbents used, see ref 1b. Cobalt
chloride hexahydrate and diisobutylaluminum chloride were
purchased from Strem Chemicals and used as received.
Trimethylaluminum, diethylaluminum chloride, and diisobu-
tylaluminum hydride were purchased from Aldrich Chemicals
(1:1 to 1:5, anti:syn (exo:endo)) with the major products
always resulting from reaction through an endo transi-
tion state. In this paper, we report the synthesis of a
cobalt-substituted diene with large C symmetric equato-
2
rial ligands and the results of this ligand modification
as well as Lewis acid catalysis on the diastereoselectivi-
ties of subsequent Diels-Alder reactions.
1
b
and used as received. 4-Acetoxy-1,2-pentadiene (20), (3E)-
,3-pentadien-2-yl(pyridine)bis(dimethylglyoximato)cobalt-
III) (22a ),1b (3E)-1,3-pentadien-2-yl(pyridine)bis(diphenylgly-
1
(
1
b
oximato)cobalt(III) (22b), bicyclo[2.2.2]oct-5-ene-cis-2,3-diyl
4
carbonate (8), dibenzobicyclo[2.2.2]octane-cis-2,3-diyl carbon-
ate (15), and dibenzobicyclo[2.2.2]octane-cis-2,3-diol (16) were
prepared according to previously described methods.
5
5
Bicyclo[2.2.2]octa n e-cis-2,3-d iyl Ca r bon a te (9). Unsat-
†
urated carbonate 84 was hydrogenated by modification of a
Henry Dreyfus Teacher-Scholar Awardee (1994-99).
X
Abstract published in Advance ACS Abstracts, December 15, 1995.
6
literature procedure using Adam’s catalyst. Unsaturated
(
1) (a) Smalley, T. L.; Wright, M. W.; Garmon, S. A.; Welker, M. E.;
carbonate 8 (3.125 g, 18.8 mmol) was dissolved in THF (20
Rheingold, A. L. Organometallics 1993, 12, 998. (b) Wright, M. W.;
Smalley, T. L.; Welker, M. E.; Rheingold, A. L. J . Am. Chem. Soc. 1994,
mL). Adam’s catalyst (PtO
and the solution was degassed for 5 min with N
was shaken in a Parr hydrogenation apparatus at 47 psi of
(24 h). Filtration followed, and removal of solvent yielded
2
, 0.075 g, 0.331 mmol) was added,
1
16, 6777. (c) Stokes, H. L.; Richardson, B. M.; Wright, M. W.; Vaughn,
S. P.; Welker, M. E.; Liable-Sands, L.; Rheingold, A. L. Organometallics
995, in press.
2) (a) Tada, M.; Shimizu, T. Bull. Chem. Soc. J pn. 1992, 65, 1252.
b) Tada, M.; Mutoh, N.; Shimizu, T. J . Org. Chem. 1995, 60, 550.
3) (a) Sabat, M.; Reynolds, K. A.; Finn, M. G. Organometallics 1994,
3, 2084. (b) Gilbertson, S. R.; Zhao, X.; Dawson, D. P.; Marshall, K.
2
. The reaction
1
H
2
(
(
(
(4) Lambert, J . B.; Holcomb, A. G., J . Am. Chem. Soc. 1971, 93,
1
3952-3954.
L. J . Am. Chem. Soc. 1993, 115, 8517. (c) Anderson, B. A.; Wulff, W.
D.; Powers, T. S.; Tribbitt, S.; Rheingold, A. L. J . Am. Chem. Soc. 1992,
(5) Newman, M. S.; Addor, R. W. J . Am. Chem. Soc. 1955, 77, 3789-
3793.
1
14, 10784. (d) Barluenga, J .; Canteli, R.-M.; Florez, J .; Garcia-Granda,
(6) Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry, 5th
ed.; Wiley: New York, 1989; pp 64-7, 311-312, 320-321, 596.
S.; Gutierrez-Rodriguez, A. J . Am. Chem. Soc. 1994, 116, 6949.
0
022-3263/96/1961-0133$12.00/0 © 1996 American Chemical Society

1
34 J . Org. Chem., Vol. 61, No. 1, 1996
Wright and Welker
a tan-colored solid. Sublimation at 110 °C/5 mmHg yielded
.092 g (18.38 mmol, 97.8%) of saturated carbonate (9): mp,
Diben zobicyclo[2.2.2]octan e-cis-2,3-diyl Car bon ate (15).
1
3
This compound was prepared as described previously, but H
1
NMR data was not previously reported:5 1H NMR (CDCl
this compound sublimes rather than melts; H NMR (CDCl
3
)
3
)
4
4
2
1
.68 (s, 2H), 2.02 (s, 2H), 1.91-1.65 (m, 4H), 1.55-1.40 (m,
7.41-7.34 (m, 4H), 7.30-7.20 (m, 4H), 4.89 (m, 2H), 4.60 (m,
2H) ppm.
1
3
H) ppm; C NMR (CDCl
7.07), CH (20.96, 17.61) ppm; IR (CDCl
780, 1373, 1359, 1168 cm ; EI LRMS 55 (33.2), 67 (56.3), 78
3
, DEPT C (155.27), CH (76.74,
2
3
) 2946, 2875, 1862,
Diben zobicyclo[2.2.2]octa n e-cis-2,3-d iol (16). This com-
-
1
1
pound was prepared as described previously, but H NMR data
was not previously reported:5 1H NMR (CDCl
4H), 7.25-7.14 (m, 4H), 4.40 (m, 2H), 4.03 (m, 2H), 2.37 (s,
2H, OH) ppm.
) 7.41-7.26 (m,
(
100), 123 (0.94), 124 (1.3), 168 (M, 7.3), 169 (M + 1, 1.4), 170
3
(M + 2, 0.13). Anal. Calcd for C : C, 64.27; H, 7.19.
9
H
12
O
3
Found: C, 64.02; H, 7.29.
Bicyclo[2.2.2]octa n e-cis-2,3-d iol (10). A modification of
a literature procedure was used to synthesize diol 10.4
Saturated carbonate 9 (3.773 g, 22.43 mmol) was added to 25%
NaOH (35 mL) and refluxed (4 h). Cooling to 25 °C and adding
Diben zobicyclo[2.2.2]octa n e-2,3-d ion e (17). Oxidation
10
of diol 16 to known dione 17 was accomplished by an
activated Swern oxidation.11 A procedure analogous to that
reported for 11 above was used with CH
(2.30 mL, 32.34 mmol), trifluoroacetic anhydride (4.13 mL,
29.24 mmol), diol 16 (2.424 g, 10.17 mmol), and Et N (9.41
2 2
Cl (133 mL), DMSO
1
.2 M HCl (50 mL) neutralized the solution. The aqueous
solution was extracted with Et
O (6 × 50 mL). The combined
organic layers were washed with water (2 × 50 mL). The ether
solution was dried with Na SO , and the solvent was removed
by rotary evaporation. The crude solid was sublimed at 115
C/5 mmHg to yield a white solid (10) (2.614 g, 18.38 mmol,
2
3
mL, 67.45 mmol) to yield 17 as a yellow solid (1.955 g, 8.35
2
4
mmol, 82.1%) that was determined to be identical to previously
1
12
reported data by H NMR comparison.
°
2,3-Diben zobicyclo[2.2.2]octan edion e Dioxim e (18r an d
1
12
8
2.0%): mp, this compound sublimes rather than melts; H
NMR (CDCl ) 3.75 (s, 2H), 2.90 (s, 2H), 1.90-1.76 (m, 2H),
.73-1.65 (m, 2H), 1.63-1.52 (m, 2H), 1.51-1.40 (m, 2H)
18â). Oximation following the previously reported procedure
3
yielded a 1:1 mixture of dioxime isomers. Starting with dione
17 (3.08 g, 13.15 mmol), we obtained after chromatography
on silica (3:1 CH Cl /EtOAc) â-dioxime (18â, 1.204 g, 4.56
1
1
1
1
1
3
.34-1.25 (m, 2H) ppm; C NMR (CDCl
8.28 ppm; IR (CDCl ) 3627, 3513, 2940, 2870, 1472, 1460,
399, 1010 cm . Anal. Calcd for C : C, 67.57; H, 9.92.
3
) 68.43, 31.13, 23.03,
2
2
3
mmol, 34.7%, R ) 0.76). Elution with EtOAc yielded R-di-
f
-
1
8
H
14
O
2
oxime (18R, 1.180 g, 4.47 mmol, 34.0%, R ) 0.36, 3:1 CH Cl /
f
2
2
1
2
Found: C, 67.54; H, 9.91.
EtOAc). The following modification of the reported procedure
Bicyclo[2.2.2]octa n e-2,3-d ion e (11). Oxidation of 2,3-diol
produced much more R-dioxime (18R). Dione 17 (3.394 g, 14.49
mmol) was dissolved in MeOH (200 mL) followed by hydroxy-
lamine hydrochloride (6.044 g, 87.0 mmol) and K CO (6.077
1
0 was accomplished by modification of a literature procedure.7
DMSO (1.59 mL, 22.36 mmol) was added to freshly distilled
CH Cl (100 mL) under N , and the mixture was cooled to -60
C. Trifluoroacetic anhydride (2.85 mL, 20.19 mmol) was
added dropwise, and the mixture was stirred for 10 min. Diol
0 (1.00 g, 7.03 mmol) was dissolved in 2:1 CH Cl /DMSO (70
2
3
2
2
2
g, 43.5 mmol). The solution was heated for 3-5 min with a
°
heat gun. TLC on silica (3:1 CH Cl /EtOAc) revealed that all
2
2
the dione was consumed, and a spot at R ) 0.36 corresponding
f
1
2
2
to R-dioxime was very intense with the â-dioxime spot, R )
f
mL) and added dropwise over 10 min. The solution was
colorless and homogeneous after 30 min of stirring. The
0.76, being very faint. Filtering the hot solution through Celite
and removal of solvent yielded a white solid contaminated with
some K CO . Triturating the solid with 3 × 40 mL THF and
reaction mixture was stirred for an additional 1 h, and Et
6.50 mL, 46.6 mmol) was added dropwise. The solution
turned yellow immediately and was stirred for 90 min at -60
C and then warmed to about 5 °C. The mixture was then
3
N
2
3
(
removal of solvent yielded a white powdery solid. The solid
was vacuum dried and chromatographed on silica (3:1 CH2-
°
Cl /EtOAc) yielding â-dioxime (18â) followed by R-dioxime
2
poured into 2 M HCl (260 mL) and stirred for 5 min (Caution:
use a well-ventilated hood). The biphasic solution was shaken
well, and the organic layer was separated. The aqueous layer
(18R). 18â (1.055 g, 27.5 mmol, 27.5%, R ) 0.76, 3:1
f
1
CH Cl /EtOAc): mp 193 °C dec; H NMR (THF-d ) 11.39 (s,
2
2
8
1H), 11.13 (s, 1H), 7.55-7.30 (m, 4H), 7.25-7.00 (m, 4H), 6.01
was extracted with 6 × 20 mL of CH
organic layers were washed with 5 × 45 mL of water and then
dried with MgSO The solvent was removed by rotary
evaporation in the hood to yield a yellow foul-smelling paste.
The paste was dissolved in CH Cl (10 mL) and cooled to 0
C. Pentane was added until the solution was very pale yellow
2
Cl
2
.
The combined
(s, 1H), 5.06 (s, 1H) ppm; LR FABMS calcd for C H O N
2
1
6
12
2
+
264, found in 3-NBA + Li matrix 271.3 (M + Li) , 277.3 (M -
+
4
.
H + 2Li) . 18R (2.684 g, 10.15 mmol, 70.1%, R ) 0.36, 3:1
f
CH Cl /EtOAc) was determined to be identical to previously
2
2
1
12
2
2
reported data by H NMR comparison.
°
Ch lor o(p yr id in e)bis(9,10-eth a n oa n th r a cen e-11,12-d i-
on e d ioxa m a to)coba lt(III) (19). Modification of a literature
procedure was used to synthesize 19.12 Clean dioxime 18R
(0.500 g, 1.89 mmol) and CoCl (H O) (0.225 g, 0.956 mmol)
and almost all of the dione was precipitated. The yellow solid
was collected by suction filtration and washed with 3 × 10
mL of pentane. The yellow solid was vacuum dried to yield
2
2
6
1
1 (0.818 g, 5.92 mmol, 84.2%) that was determined to be
were dissolved in 95% EtOH (200 mL) and heated to about 70
°C. Pyridine (0.153 mL, 1.89 mmol) was added, and heating
was stopped, but vigorous stirring open to air was continued.
After cooling to 25 °C, air was bubbled through the solution
for 45 min. After stirring for an additional 3 h, the reaction
mixture was cooled to 0 °C, and water (50 mL) was added.
The tan-colored precipitate was collected by vacuum filtration
and washed with water (3 × 10 mL). Vacuum drying yielded
the chloride complex 19 (1.03 g, 1.47 mmol, 78.2%) that was
1
8
identical to previously reported data by H NMR comparison.
,3-â-Bicyclo[2.2.2]octa n ed ion e Dioxim e (12). Hydroxy-
lamine hydrochloride (0.476 g, 6.85 mmol) and KOH (4.49 g,
2
6
7.94 mmol) were dissolved in water:EtOH (1:2, 15 mL). Dione
1
1 (0.383 g, 2.77 mmol) was added, and the solution was
9
a
refluxed. After 2 days, the reaction mixture was cooled and
4
O. After drying with MgSO ,
extracted with 5 × 20 mL of Et
2
the solvent was removed by rotary evaporation to yield a white
1
1
solid 12 (0.390 g, 2.55 mmol, 91.9%): mp 189 °C; H NMR
determined to be identical to previously reported data by H
NMR comparison.12
(
(
(
6
1
C
3
D
6
O) 11.05 (s, 1H), 10.20 (s, 1H), 3.50 (m, 2H), 1.84-1.35
m, 8H) ppm; EI LRMS 53 (44), 67 (71), 82 (100), 93 (89), 108
36), 120 (52), 133 (77), 150 (40, M - H O); CI LRMS 53 (67),
2
7 (80), 77 (82), 81 (100), 91 (84), 105 (31), 122 (44), 133 (51),
(3E)- a n d (3Z)-1,3-P en t a d ien -2-yl(p yr id in e)b is(9,10-
eth an oan th r acen e-11,12-dion e dioxam ato)cobalt(III) (21E
a n d 21Z). Synthesis of the AG diene 21 was accomplished
+
+
13
51 (33, M - OH); LR FABMS calcd for C
8
H
12
O
2
N
2
(168),
via alkylation of the chloride complex 19. A representative
+
+
found in 3-NBA + Li matrix 169.2 (M + H) , 175.2 (M + Li)
synthesis follows: Chloride complex 19 (0.675g, 0.964 mmol)
was added to 95% EtOH (300 mL). While being rapidly stirred
and degassed, the solution was cooled to -20 °C. When the
+
and in 3-NBA + Na matrix 191.2 (M + Na) , 213.2 (M - H +
+
2
Na) . Anal. Calcd for C
8
H
12
N
2
O
2
: C, 57.13; H, 7.19; N, 16.66.
Found: C, 57.79; H, 7.05; N, 16.91.
(
10) Scharf, H. D.; Kuesters, W. Chem. Ber. 1972, 105, 564.
(
7) Amon, C. M.; Banwell, M. G.; Gravatt, G. L. J . Org. Chem. 1987,
2, 4851-4855.
8) Rrebke, R.; Krieger, H.; Esser, H.; Sch u¨ fer, H. K.; Alder, V. K.
Chem. Ber. 1955, 88, 23-35.
9) (a) Becker, P. N.; Bergman, R. G. Organometallics 1983, 2, 787.
b) Bonner, M. P.; Thornton, E. R. J . Am. Chem. Soc. 1991, 113, 1299.
(11) The representative procedure presented in ref 7 was used except
HCl was omitted during the aqueous workup.
(12) Stephenson, N. A.; Morales, L.; Warburton, P. R.; Chmielewski,
P. J .; Busch, D. H. J . Coord. Chem. 1991, 23, 91-111.
(13) (a) Schrauzer, G. N.; Deutsch, E. J . Am. Chem. Soc. 1969, 91,
3341. (b) Schrauzer, G. N.; Kohnle, J . Chem. Ber. 1964, 97, 3056.
5
(
(
(

Preparation of 2-Cobalt-Substituted 1,3-Dienes
solution had reached -15 to -20 °C, NaBH (0.182 g, 4.82
J . Org. Chem., Vol. 61, No. 1, 1996 135
dissolved in degassed CH Cl (310 mL) and cooled to 0 °C in
4
2
2
mmol) was added and an instant color change from brown to
dark purple occurred. The solution was allowed to stir for 2
a Hanovia 450 W photolysis reactor equipped with a vycor
filter. The solution was photolyzed for 5 h. The solvent was
removed by rotary evaporation to yield a green powder. The
powder was triturated with 1.7:1 pentane/ether (5 × 4 mL).
The solvent was removed by rotary evaporation to yield a
yellow oil. Kugelr o¨ hr distillation at 110 °C/1 mmHg yielded
pure anti diastereomer 28 (0.0295 g, 0.178 mmol, 49.1%) that
was determined to be identical to previously reported material
which was enriched in this diastereomer1b by H NMR
comparison as well as the diastereomer from previously
1
b
h at -20 °C. 4-Acetoxy-1,2-pentadiene (20) (0.134 g, 1.060
mmol) was added via syringe. The reaction mixture was
allowed to warm to 25 °C slowly and stirred for 8 h. The
volume of the bright orange solution was reduced by two-thirds
via rotary evaporation (bath at 30 °C) and poured into H
800 mL) containing pyridine (1 mL). The orange solid
obtained was isolated via vacuum filtration and washed with
O (3 × 20 mL). The orange solid was vacuum dried to yield
1 (1.430 g, 1.954 mmol, 68%). The yield of the diene complex
2
O
(
1
H
2
1
4
reported data on thermal reactions of E and Z piperylenes:
2
1
H NMR (CDCl
.83 (m, 2H), 3.32 (ddd, J ) 9.6, 8.4, 5.5 Hz, 1H), 2.77 (dd, J
9.6, 5.5 Hz, 1H), 2.64-2.34 (m, 3H), 1.25 (d, J ) 6.8 Hz,
H) ppm; 13C NMR (CDCl
) 173.90, 173.14, 132.67, 125.22,
6.04, 38.91, 29.74, 22.04, 19.89 ppm. The residual green
3
) of pure anti isomer not previously reported
ranges from about 70 to 80%. The ratio of trans:cis isomers,
however, varies considerably from batch to batch (>20:1 to 1:1).
Rotary evaporation at 20-30 °C usually yields >20:1 E:Z diene
complex 21. The complex can be chromatographed on silica
5
)
3
4
3
(
3:1 CH
on silica with CH
isomerization: mp 215 °C dec; H NMR (CDCl
2
Cl
2
/EtOAc, 1% pyridine, R
f
) 0.65); however, loading
powder (0.210 g, 0.319 mmol, 88%) was believed to be
2
Cl followed by removal of solvent caused
2
-
+ 15
(29): 1H NMR (CDCl
1
(AG)
2
CoCl
2
(PyrH)
3
) 7.83 (d, J ) 5.0
3
) 7.88 (t, J )
.4 Hz, 2H), 7.42 (dd, J ) 5.8, 3.3 Hz, 4H), 7.26-7.19 (m, 5H),
Hz, 2H), 7.48-7.30 (m, 4H), 7.29-7.18 (m, 5H), 7.17-7.02 (m,
4
7
6
1
1
1
1
1
1
3
4
5
H), 7.00-7.88 (m, 4H), 6.77 (apparent t, J ) 5.0 Hz, 2H),
.12 (dd, J ) 5.8, 3.3 Hz, 4H), 7.01-6.92 (m, 4H), 6.76 (t, J )
.6 Hz, 2H), E diene [5.82 (m, 1H), 5.52 (s, 4H), 4.46 (dq, J )
5.0, 6.6 Hz, 1H), 4.04 (s, 1H), 3.86 (s, 1H), 1.06 (dd, J ) 6.6,
.7 Hz, 3H)], Z diene [5.67 (m, 1H), 5.53 (s, 4H), 4.75 (dq, J )
1.0, 6.9 Hz, 1H), 4.29 (s, 1H), 3.75 (s, 1H), 0.65 (dd, J ) 6.8,
.66 (s, 4H). This compound which was insoluble in the
pentane/ether trituration step above was converted to the
chloride complex 19 as described below.
Regen er ation of (P yr idin e)bis(9,10-eth an oan th r acen e-
1
1,12-d ion e d ioxim a to)coba lt(III) Ch lor id e (19). The
green salt 29 (0.152 g, 0.238 mmol) was suspended in methanol
10 mL). Pyridine (18.7 µL, 0.231 mmol) was added, and the
.8 Hz, 3H)] ppm; 13C NMR (CDCl
) E diene 151.70, 148.93,
40.12, 139.48, 137.91, 137.05, 127.14, 126.71, 124.88, 124.72,
24.58, 120.58, 113.05, 45.92, 17.92 ppm; IR (CDCl ) 3692,
606, 3074, 3025, 2912, 1702, 1604, 1494, 1460, 1249, 1229
3
(
3
solution was heated to about 60 °C and then allowed to stir
for 8 h. The solution was then cooled to 0 °C, and after 20
min, water (20 mL) was added. The resulting brown solid was
-
1
cm . Anal. Calcd for C42
.57. Found: C, 68.85; H, 4.70; N, 9.47.
a n ti-4,4,7,7,8,9-Hexa h yd r o-4-m eth yl-1,3-d ioxoisoben -
zofu r a n -5-yl)(p yr id in e)bis(9′,10′-eth a n oa n th r a cen e-11′,-
2′-d ion e d ioxim a to)coba lt(III) (24c). A 2:1 and 16:1 (E:
Z) mixture of diene 21 (1.40 g, 1.913 mmol) was added to
degassed CHCl (100 mL). Maleic anhydride (0.750 g, 7.653
34 4 5
H O N Co: C, 68.94; H, 4.68; N,
9
2
filtered to yield pyr(DBG) CoCl (19) (0.118 g, 0.169 mmol, 70%)
(
which was identical to 19 reported above as determined by
1
H NMR comparison.
1
cis- a n d tr a n s-1-(1-Oxoeth yl)-2-m eth yl-3-cycloh exen e
(
30 a n d 31). A 1.4:1 ratio of an unknown diasteromeric
mixture of 26c and 27c (0.330 g, 0.451 mmol) was dissolved
in degassed CH Cl (310 mL) and cooled to 0 °C in a Hanovia
50 W photolysis reactor equipped with a vycor filter. The
3
mmol) was added to the heterogeneous solution. After stirring
for 8 h, the homogeneous solution volume was reduced to about
2
2
4
2
0 mL by rotary evaporation. The orange solution was
chromatographed on silica (CH Cl /1% pyridine). Elution of
a single orange band (3:1 CH Cl /EtOAc containing 1% pyri-
dine, R ) 0.81) yielded one diastereomer (24c) as determined
solution was photolyzed for 6 h. The solvent was removed by
rotary evaporation to yield a green residue. The residue was
triturated with 1:1 pentane/ether (8 × 2 mL). The solvent was
removed by rotary evaporation to yield a 1.4:1 mixture of 30:
2
2
2
2
f
1
1
by H NMR: mp 200 °C dec; H NMR (CDCl
3
) 7.98 (d, J ) 5.0
3
1 as a light yellow oil. Chromatography on silica with 1:1
Hz, 2H), 7.44-7.32 (m, 4H), 7.30-7.22 (m, 5H), 7.16-7.09 (m,
ether/pentane failed to remove the yellow color. Kugelr o¨ hr
distillation at 90 °C/30 mmHg yielded a 1.4:1 mixture of
diastereomers 30:31 (0.054 g, 0.435 mmol, 86.6%) that was
4
5
1
H), 7.04-6.80 (m, 4H), 6.88 (t, J ) 6.4 Hz, 2H), 5.53 (s, 2H),
.51 (s, 2H), 5.05 (dd, J ) 4.1, 1.6 Hz, 1H), 2.35-2.16 (m, 2H),
.96 (m, 1H), 1.70-1.50 (m, 2H), 0.62 (d, J ) 7.1 Hz, 3H) ppm;
1
determined to be identical to authentic samples by H NMR
3
IR (CDCl ) 3693, 3605, 3074, 2964, 1776, 1729, 1606, 1249,
1
8
1
6
-
1
spectroscopic comparison.
2 2
(pyrH) [(AG) CoCl
2
The residual green powder
] was collected and vacuum dried to yield
9 (0.267 g, 0.363 mmol, 80.5%) which was determined to be
229 cm ; HRMS calcd for C46
H
37
O
7
N
5
Co 830.2024, found
+
-
+
30.1993 (M + H) . Anal. Calcd for C46
36 7 5
H O N Co: C, 66.59;
H, 4.37. Found: C, 64.67; H, 4.59.
cis- a n d tr a n s-1-(1-Oxoeth yl)-2-m eth yl-3-cycloh exen -
-yl)(p yr id in e )b is(9′,10′-e t h a n oa n t h r a ce n e -11′,12′-d i-
on e d ioxim a to)coba lt(III) (26c a n d 27c). A 2:1 and 16:1
E:Z) mixture of diene 21 (0.340 g, 0.465 mmol) was added to
degassed CHCl (75 mL) and cooled to -20 °C. Methyl vinyl
identical to the material reported in the other photolysis above
by spectroscopic comparison.
Kin etics of Z:E Isom er iza tion for th e AG Dien yl
Com p lex 21. These kinetics experiments were carried out
(
4
(
3
in CDCl with a 10-fold excess of dienophile, and rate constants
3
were determined from the first-order decay of proton signals
ketone (0.773 g, 9.29 mmol) was added, and the solution was
allowed to stand at -20 °C for 15 days. The solution was then
cooled to -78 °C, and pentane was added (50 mL). The orange
precipitate was collected by vacuum filtration and washed with
pentane (3 × 10 mL). Vacuum drying yielded a 2:1 mixture
1
monitored by H NMR. The appearance of cycloadduct 24c
was monitored by integrating the signal from the methyl
protons at various times and correcting the observed value if
necessary for any changes due to variations in instrument
tuning using the integration of the signal from the methyl
protons of the internal standard tert-butyl alcohol. More
spectra were acquired early in the reaction (a spectrum every
600 s for six spectra and every 720 s for five spectra), and fewer
at later time (a spectrum every 900 s for five spectra and then
every 1200 s for three spectra). Monitoring of the methyl
signal’s appearance was carried out for almost 1 half-life.
Analyses were carried out by graphic means; a linear plot on
1
of diastereomers (26c:27c) as determined by 200 MHz H NMR
(
0.350 g, 0.437 mmol, 94%). Running the reaction at 25 °C
for 8 h yielded a 1:1 mixture (99% yield) and 0 °C for 3 days
yielded 1.4:1 ratio of 26c:27c (93% yield): mp 190 °C dec;
1
spectroscopic data for 26c and 27c. H NMR (CDCl
3
) 8.60-
7
7
2
1
.94 (m, 2H), 7.42-7.30 (m, 4H), 7.29-7.19 (m, 5H), 7.17-
.05 (m, 4H), 7.02-6.91 (m, 4H), 6.82 (apparent t, J ) 5.3 Hz,
H), 2.31-2.00 (m, 1H), 1.79-1.52 (m, 2H), 1.25-1.14 (m, 1H),
.13-1.00 (m, 1H), 0.99-0.84 (m, 1H), major isomer 26c [5.49
(
s, 4H), 4.60 (d, J ) 6.2 Hz, 1H), 1.85 (s, 3H), 0.02 (d, J ) 6.8
Hz, 3H)], minor isomer 27c [5.52 (s, 4H), 4.51 (s, 1H), 1.80 (s,
(14) (a) Brocksom, T. J .; Constantino, M. G. J . Org. Chem. 1982,
47, 3450. (b) Brocksom, T. J .; Constantino, M. G. An. Acad. Bras. Cienc.
1982, 54, 655.
3
3
H), 0.34 (d, J ) 6.8 Hz, 3H)] ppm; IR (CDCl
3
) 3196, 3074,
-
1
(15) Nakahara, A. Bull. Chem. Soc. J pn. 1955, 28, 207.
(16) (a) Guner, O. F.; Ottenbrite, R. M.; Shillady, D. D.; Alston, P.
V. J . Org. Chem. 1988, 53, 5348. (b) Bonnesen, P. V.; Puckett, C. L.;
Honeychuck, R. V.; Hersh, W. H. J . Am. Chem. Soc. 1989, 111, 6070.
c) Smith, D. A.; Sakan, K.; Houk, K. N. Tetrahedron Lett. 1986, 27,
4877.
046, 3026, 2959, 1700, 1605, 1460, 1449, 1228, 1070 cm
.
+
HRMS calcd for (M + H ) C46
02.2436.
a n ti-4,4,7,7,8,9-H exa h yd r o-4-m et h yl-1,3-d ioxoisob en -
zofu r a n (28). Cycloadduct 24c (0.300 g, 0.362 mmol) was
41 5 5
H O N Co 802.2440, found
8

1
36 J . Org. Chem., Vol. 61, No. 1, 1996
Wright and Welker
semilogarithmic paper of methyl peak integrals against time
yielded the half-time t1/2, and the rate constant was obtained
from the equation kobs ) 0.693/t1/2. A 2:1 (E:Z) mixture of AG
diene 21 (0.016 g, 0.0218 mmol) was dissolved in 0.7 mL of
(dmg) to diphenylglyoxime (dpg) as the equatorial ligand
for our dienyl complexes had improved anti (exo) selec-
tivities of subsequent Diels-Alder reactions. If we stayed
with the glyoxime ligand set, we thought bicyclic gly-
oximes offered the best chance to present steric bulk to
incoming dienophiles. Bicyclic glyoximes derived from
readily available bicyclo[2.2.1]heptanes were known, but
3
CDCl . Maleic anhydride (0.0214 g, 0.218 mmol) was added
and thoroughly mixed. Nineteen FIDs were taken at 26 °C.
All of the trans diene 21 was consumed by the time the first
spectrum was collected and transformed (T ) 3 min). The rate
constant for growth of the anti anhydride 24c was determined
2
since these ligands are not C symmetric, they produce
-
5
-5 -1
to be 4.4 × 10 ( 1.3 × 10
NMR Titr a tion Exp er im en ts w ith th e DMG Dien e 22a ,
MA, a n d AlMe
. In a dry 5 mm NMR tube, DMG diene 22a 1b
0.010 g, 0.0229 mmol) was added under N , and 0.6 mL of
dry, degassed CDCl was added via syringe. After equilibra-
s
and t1/2 ) 4.4 h.
mixtures of geometrical isomers when two of them are
17
coordinated to a transition-metal center. Therefore, we
3
decided to prepare glyoximes derived from bicyclo[2.2.2]-
octane precursors since they offered the advantage of
(
2
3
tion of the NMR probe and sample to -45 °C, a precooled
2
being C symmetric. We first attempted to prepare the
simplest glyoxime of this framework, 2,3-bicyclo[2.2.2]-
solution of maleic anhydride was added (0.229 M, 0.1 mL,
0
.0229 mmol). To determine the temperature where cycload-
octanedione dioxime. Dione 11 had been prepared previ-
dition occurs thermally, the probe was warmed in 10 °C
increments and held for 20 min. Cycloaddition occurred at
8
ously from commercially available but expensive bicyclo-
[2.2.2]octene. We chose a somewhat lengthier strategy
-
30 °C with an estimated half-life of 2 h. Both anti and syn
diastereomers were seen. AlMe reactions were carried out
by successive additions of 2.0 M AlMe in hexanes (0.012 mL,
.0115 mmol equals 1 equiv) at -45 °C where no thermal
utilizing readily available 1,3-cyclohexadiene (6) and
3
vinylene carbonate (7).4 Diels-Alder reaction of 6 and
,5
3
0
7
was followed by hydrogenation of the resulting unsat-
uncatalyzed cycloaddition is taking place. Lewis acid additions
started with 0.5 equiv and ended with 4 equiv in 0.5 equiv
increments. Spectra were taken after each addition and then
again after 15 min to observe any change. Changes in the
pyridine resonances were monitored as well as the alkene H's
on the diene.
P r ep a r a tive Lew is Acid Ca ta lyzed Rea ction s. The
following is a representative procedure for the Lewis acid
catalyzed reactions of cobalt dienes 22a , 22b, and 22c with
MVK or MA. A small vial with a stir bar was flame dried
urated bicyclic carbonate 8 to yield the saturated bicyclic
carbonate 9.6 Hydrolysis of the carbonate was easily
accomplished with 5% NaOH4 to produce the diol 10
which was oxidized via an activated Swern oxidation to
the known dione 11.8 Many attempts were made to
convert dione 11 to the R-dioxime. Standard procedures
7
using NH
2
OH-HCl and KOH yielded only â-dioxime
9a
(12). Procedures previously reported to oximate steri-
1
8
cally hindered ketones were also used without success.
2
and cooled under a stream of N . Diene 22a (100 mg, 0.230
mmol) was introduced into the vial and purged with nitrogen
for 2-3 min. The vial was then capped by crimping on a septa-
Refluxing 11 with NH
2
2
OH-HCl and NaOAc in H O/
EtOH9b also produced 12. The â isomer is a poor ligand
containing top, and dry CH
by cooling to -45 °C. Precooled AlMe
2
Cl
2
(3.2 mL) was added followed
(2.0 M in hexanes, 0.230
mL, 0.460 mmol) was added slowly via a dry syringe and
allowed to stir 10 min. Next, precooled BCl (1.0 M in CH
Cl , 58 µL, 0.058 mmol), or other Lewis acids as described in
for the type of chemistry we wanted to do so we had to
look for other C symmetric glyoximes which could be
2
prepared as the R isomer.
3
3
2
-
2
the text were then added slowly. A stock solution of the
dienophile was prepared in another flame-dried vial as fol-
lows: MA (25 mg/mL) in dry CH
2 2
Cl and MVK (16 mg/mL or
2
1 µL/mL) in dry CH Cl . The stock dienophile solution was
2
2
cooled to -45 °C, and the MVK solution (1.0 mL, 0.253 mmol)
was added slowly. The reaction mixture was left at -50 °C
for 2.7 days. A 50% aqueous solution of 2-propanol was cooled
to -10 to -20 °C. Slowly, the 50% aqueous solution (1 mL)
was added and stirred for 20 min at 0 °C. With vigorous
stirring, MgSO
mixture was filtered, and the MgSO
mL) CH Cl . The solvent was removed by rotary evaporation,
4
was slowly added at 0 °C. The reaction
4
was washed with (3 × 8
2
2
1
and the residue was vacuum dried. Crude H NMRs were
taken at this point to establish anti:syn ratios and compare to
1
b
previously reported data. Purification of cycloadducts was
accomplished by chromatography on silica (dmg complexes
require EtOAc as the elutent, dpg complexes require CH
2
Cl
2
,
The preparation of 2,3-dibenzobicyclo[2.2.2]octanedione
and AG complexes require 3:1 CH Cl :EtOAc containing 1%
2
2
dioxime (18) had been reported previously by Busch et
al. so we picked this C symmetric dioxime as our next
2
1
2
pyridine). The reaction of the dmg complex 22a with MVK
described above yielded a 1.6:1 mixture of 27a :26a (80.2%
yield). Reactions using 2.0 equiv of DIBALH required an
aqueous workup. The reactions were first quenched with 50%
aqueous 2-propanol (1.0 mL) and warmed to 25 °C. Saturated
target. The Busch group referred to this ligand as
anthraglyox, and we will simply abbreviate it as AG. The
dione 17 required for the preparation of AG had been
reported previously by Scharf and Kuesters.1 Their
route required the preparation of tetrachloroethylene
carbonate as well as dichlorovinylene carbonate, both of
which are strong lachrymators. We chose instead to do
0
aqueous NH
0 min. The biphasic solution was poured into a separatory
funnel and shaken well. The aqueous layer was washed with
CH Cl
(3 × 5.0 mL). The combined organic layers were dried
with MgSO , and solvent was removed by rotary evaporation.
4
Cl (1.5 mL) was added and stirred vigorously for
1
2
2
4
The residue was then vacuum dried and purified as mentioned
above.
(17) (a) Nakamura, A. Pure Appl. Chem. 1978, 50, 37. (b) Nakamura,
A.; Konishi, A.; Tatsuno, Y.; Otsuka, S. J . Am. Chem. Soc. 1978, 100,
3
443. (c) Nakamura, A.; Konishi, A.; Tsujitani, R.; Kudo, M.; Otsuka,
Resu lts a n d Discu ssion
S. J . Am. Chem. Soc. 1978, 100, 3449. (d) Ma, M. S.; Angelici, R. J .
Inorg. Chem. 1980, 19, 363.
(
18) (a) Bari, S. S.; Bose, A. K.; Chaudhary, A. G.; Manhas, M. S.;
2
C Sym m et r ic Glyoxim e P r ep a r a t ion . We knew
from our previous studies that switching from dimethyl-
Raju, V. S.; Robb, E. W. J . Chem. Ed. 1992, 69, 938-939. (b) Puciov a´ ,
M.; Toma, S. Collect. Czech. Chem. Commun. 1992, 57, 1507-1512.
1
b

Preparation of 2-Cobalt-Substituted 1,3-Dienes
J . Org. Chem., Vol. 61, No. 1, 1996 137
a Diels-Alder reaction between commerically available
5
vinylene carbonate 14 and anthracene (13) followed by
5
7
carbonate hydrolysis and activated Swern oxidation to
produce dione 17.
Synthesis of AG dienyl complex 21 was accomplished
via reduction of the chloride complex 19 in EtOH with
1
3
1b
NaBH
4
followed by the addition of allenic acetate 20.
Oximation of 17, following the reported procedure,12
yielded a 1:1 mixture of R- and â-dioxime isomers (18R
The ratio of trans:cis (21E:21Z) can vary considerably
from batch to batch (>20:1 to 1:1), depending on the
workup procedure used (due to facile thermal isomeriza-
tion of 21). Working with 21 at 20-30 °C results in the
isolation of 21E cleanly. The overall yield for production
of 21 via six steps is about 30%. Additional observations
about this E:Z isomerization and its possible effects on
the outcome of 4 + 2 cycloadditions are presented below.
and 18â). Heating 17 with NH
only 3-5 min with a heat gun rather than refluxing for
0 h12 yielded a 4:1 mixture of 18R:18â. The R and â
2
OH-HCl and K
2 3
CO for
3
isomers were easily separated by chromatography, and
the R isomer produced in abundance at short reaction
times proved to be identical to that reported by Busch et
1
2
2 3
al. It was determined by TLC that heat and K CO in
MeOH had no effect on isomerization. p-Toluenesulfonic
acid (PTSA) or hydroxylamine hydrochloride in MeOH
did cause isomerization of pure â-dioxime (18â) or R-di-
oxime (18R) to about a 1:1 mixture of R:â.
Th er m a l 4 + 2 Cycloa d d it ion s a n d Su b seq u en t
Dem eta la tion Rea ction s. Previously, we had shown
that anti (exo) selectivity of thermal Diels-Alder reac-
tions of cobalt-substituted dienes with maleic anhydride
improved as the size of the equatorial ligands increased
(
Table 1, entries 1-4).1b We had been able to get
selectivity for the anti (exo) diastereomer 24 up to 8.4:1
using commercially available glyoximes, but we hoped
that the bulky AG glyoxime complex 21 would be
significantly better than this. We were gratified to see
that 21 condensed with maleic anhydride to produce
exclusively the anti product 24c. The relative stereo-
chemistry of this cycloadduct was proven by the demeta-
lation reaction described below. We also found that we
could condense 16:1 and 2:1 (E:Z) mixtures of 21 with
MA and obtain the same diastereomeric ratio in the
product 24c.
P r ep a r a tion of Coba lt Ch lor id e a n d Coba lt Dien e
Com p lexes. Using clean R-dioxime (18R), cobalt chlo-
ride complex 19 was synthesized using a modification of
Busch’s procedure in significantly higher yield than
previously reported.12 The â-dioxime isomers (12 and
1
8â) failed to produce a cobalt chloride complex in this
We next turned to methyl vinyl ketone as a dienophile.
This small dienophile had reacted with our dmg diene
reaction.

1
38 J . Org. Chem., Vol. 61, No. 1, 1996
Wright and Welker
Ta ble 1. Th er m a l Rea ction s of Coba lt Dien e Com p lexes
w ith Ma leic An h yd r id e
selective addition of MA to diene 21 and also yielded the
pyridinium salt of the cobalt dichloride 29 which was
easily converted back into chloride 19, the complex we
used to prepare 21. The MVK cycloadducts 26c and 27c
were cleaved in the same manner to yield 30 (which was
determined to be identical to previously reported data
by 13C NMR spectroscopic comparison) and 31 in addi-
tion to 29. This cleavage reaction also established the
exo selective nature of the cycloaddition between 21 and
methyl vinyl ketone.
16
.
ratio
entry glyoxime
conditions
(anti:syn) yield, % no.
1
2
3
4
5
DMG
DPG
DPG
DPG
AG
THF, reflux
THF, reflux
CHCl3, 25 °C
CHCl3, -22 °C
CHCl3, 25 °C
2.3:1
6.0:1
4.9:1
8.4:1
>20:1
78
87
76
98
98
24a
24b
24b
24b
24c
Ta ble 2. Th er m a l Rea ction s of Coba lt Dien e Com p lexes
w ith Meth yl Vin yl Keton e
We next wanted to investigate the effect (if possible)
of Lewis acid catalysis on the stereochemical outcome of
these cycloadditions; however, some additional comments
on the E:Z isomerization of 21 are in order. We knew
that with MA only one diastereomer (24c) was formed
from any E:Z mixture of dienes (21). One explanation
for this could be that E diene 21 reacted via a completely
exo transition state much faster than Z diene 21. The Z
diene then isomerized to produce more E diene which is
removed by rapid exo selective cycloaddition much faster
than Z diene cycloadds with MA. As long as the E diene
reacted in a completely stereoselective fashion much
faster than the Z diene, we would observe only one
product. Another possible explanation for the stereo-
chemical outcome of this reaction is that the E diene
reacted via only an exo transition state and the Z diene
reacted via only an endo transition state. The E:Z
ratio
entry glyoxime
conditions
(anti:syn) yield, % no.
1
2
3
4
5
6
DMG
DPG
DPG
AG
AG
AG
THF, reflux
THF, reflux
CHCl3, 25 °C
CHCl3, 25 °C
CHCl3, 0 °C
CHCl3, -20 °C
1:5.0
1.0:1
1.0:1
1.0:1
1.4:1
2.0:1
95
90
82
70
93
94
26a
26b
26b
26c
26c
26c
(
Table 2, entry 1) with a modest syn (endo) preference,
and the best we had been able to do for anti (exo)
selectivity with a commercially available glyoxime (dpg)
(
Table 2, entries 2 and 3) was 1:1 (26b:27b). The dpg
dienyl complex 22b proved unreactive toward MVK in
CHCl at -20 °C. We had high hopes for 21 in this
reaction, but they proved unwarranted. This dienyl
complex (21) did prove to be more reactive than the dpg
complex, but anti (exo) selectivity improved only slightly
to 2.0:1 (Table 2, entry 6). Once again, the relative
stereochemistry of the major cycloadduct 26c was proven
by demetalation as described below.
3
isomerization of diene complex (21) and subsequent
1
cycloaddition with MA were observed at 25 °C by
H
NMR spectroscopy. By monitoring the Diels-Alder
reaction of E:Z mixtures of 21 with maleic anhydride
under pseudo-first-order conditions in CDCl , we ob-
3
served complete disappearance of the E diene between
mixing and acquisition of the first free induction decay
Demetalation of complexes 24c and 26c was ac-
complished with concomitant cobalt recovery using pro-
cedures we have described previously.1b Initially we tried
AlMe -mediated cobalt-carbon bond cleavage, but these
3
(FID). We then observed first-order disappearance of the
Lewis acid conditions, which had worked for dmg and
dpg cycloadducts, were extremely slow (>24 h) and
resulted in isomerization and decomposition of the or-
ganic products. Photochemical cobalt-carbon bond ho-
molysis proved to be much more successful. The recov-
ered anhydride 28 from adduct 24c corresponded to the
anti diastereomer only. We had prepared 28 in diaste-
Z diene and first-order appearance of only the anti
-
5
-1
cycloadduct 24c with a rate constant of 4.4 × 10
.3 × 10 and t1/2 ) 4.4 h. Given our earlier observations
that pyr(dmg) Co-substituted Z dienes react with maleic
anhydride (under conditions where Z:E isomerization is
s
(
-5
1
2
1
c
not occurring) with half-lives on the order of 5 days, it
would appear that the latter possible explanation for our
observed results is highly unlikely and the rate constant
reomerically enriched form with the syn isomer
previously.1
b,14
This cleavage reaction established the exo

Preparation of 2-Cobalt-Substituted 1,3-Dienes
J . Org. Chem., Vol. 61, No. 1, 1996 139
Ta ble 3. 1H NMR Reson a n ces of AlMe3-21 Com p lexes
32 indicating that 21 reacts much quicker with AlMe
than 32.
3
resonance
chemical shift (ppm)
species
1
ortho H on pyridine
8.69 (app d)
21
32
33
34
21
32
33
34
21
32
8
7
7
.30 (app d)
.81 (app d)
.64 (app d)
vinyls
OH
4.49 (s), 4.39 (s)
4
4
5
.33 (s), 4.20 (s)
.33 (s), 4.25 (s)
.35 (d)
18.21 (s)
8.53 (s)
1
reported here is the rate constant for Z:E isomerization
of diene complex 21.
In summary, cycloaddition of AG diene 21 (regardless
of the E:Z ratio) with MA increased the anti (exo)
selectivity of the thermal Diels-Alder reaction to >20:
1
, confirming our earlier postulate that larger equatorial
ligands do aid with exo dienophile approach. However,
the thermal cycloaddition of 21 with MVK was disap-
pointing, 2:1 anti (exo) selectivity. The pursuit of even
larger equatorial ligands was possible, but we thought
that the effective size of the complexes and the dieno-
philes might be increased more easily through the careful
use of Lewis acids.
Lew is Acid Ca ta lyzed 4 + 2 Cycloa d d ition s of
Coba lt Dien yl Com p lexes. From our observation, the
main obstacle to the use of Lewis acids to promote Diels-
Alder reactions of these cobalt dienyl complexes (regard-
less of equatorial ligand) was that cobalt-carbon bonds
in cycloadducts as well as dienyl complexes are cleaved
by a variety of mild Lewis acids at -10 to 0 °C.1 Any
Lewis acid selected would have to be capable of catalyzing
3
With the addition of 1.5 equiv of AlMe , two species
were seen again. One species was the monocomplex
diene 32, and the new species was presumed to be the
3
bis-complexed diene 33. At 2.0 equiv of AlMe , only bis-
complexed diene 33 was seen (i.e. no oxime OH reso-
nances were present). Up to this point there was no
consumption of MA, indicating that Lewis acid reaction
with the diene is much faster than dienophile activation.
4
+ 2 cycloadditions at temperatures significantly lower
than -10 °C without effecting concomitant cobalt-carbon
bond cleavage.
We first established by NMR tube reactions that dmg
diene 22a was unreactive toward MA in CDCl
3
at -45
3
With 2.5 equiv of AlMe , another set of peaks appeared,
°
C and that it reacted very slowly with 1 equiv of MA at
corresponding to the single cycloadduct 34 (cycloaddition
approximately 50% complete). Holding the temperature
at -45 °C for 15 min revealed no further increase in the
amount of 34 present. This implied that all the Lewis
acid added over 2 equiv activated MA for cycloaddition
but probably remained complexed to the cycloadduct
rather than dissociating and activating more MA. This
observation is consistent with reports that Lewis acid
promoted Diels-Alder reactions involving R,â-unsatur-
-
30 °C with a half-life of about 2 h. With this informa-
tion in hand, we first proceeded to answer the question
of how the equatorial ligands’ Lewis base sites participate
in the complexation of Lewis acids. In an NMR tube
containing 1 equiv of MA and 22a in CDCl
3
at -45 °C,
we introduced 0.5 equiv of AlMe and observed two cobalt
3
1
species as determined by the H NMR o-pyridine protons,
OH, and vinyl resonances (Table 3). Control spectra were
carried out to confirm that signal changes were not due
1
9
ated esters many times are not catalytic in Lewis acid.
As the amount of AlMe was increased to 3 equiv, all MA
3
to AlMe
were the original diene 22a and what is postulated to be
the diene with a AlMe in place of one of the bridging
ligand OH protons 32. At 1 equiv of AlMe , we see only
one species corresponding to the monocomplexed diene
3
-pyridine adducts. The two species present
was consumed and only the single cycloadduct 34 was
observed.
2
3
(19) Keay, B. A.; Rauk, A.; Woo, W.; Rogers, C.; Hunt, I. R. J . Am.
Chem. Soc. 1995, 117, 1049.

1
40 J . Org. Chem., Vol. 61, No. 1, 1996
Wright and Welker
Ta ble 4. AlMe3-22a P r om oted Cycloa d d ition s
only anti diastereomer (24a ). Entry 4, Table 4, confirmed
our NMR observation that we would expect the first 2
equiv of Lewis acid to react with the diene with no Lewis
acid catalysis. If this occurred, the Diels-Alder reaction
would simply occur after aqueous quenching and warm-
ing, and we would expect the same diastereoselectivity
that was observed in the absence of Lewis acid. By just
3
adding 4 equiv of AlMe , we have accelerated the reaction
at -50 °C and induced a totally anti (exo) selective
addition of MA with the dmg diene. Unfortunately, this
observation means that attempts at using a chiral
aluminum Lewis acid to induce an enantioselective and
exo selective Diels-Alder reaction may be stoichiometric
in Lewis acid for this dienophile.
AlMe3
24 anti:syn
Since R,â-unsaturated ketones are known to partici-
pate in catalytic Lewis acid mediated Diels-Alder reac-
tions,19 we decided to investigate Lewis acid catalyzed
reactions of cobalt dienes (22a -c) with MVK. We could
anticipate that the first 2 equiv of Lewis acid would
complex the diene and then any excess would promote
entry
(equiv)
conditions
(% yield)
1
2
3
4
5
6
0.0
3.0
4.0
2.0
3.0
4.0
25 °C, 8 h
1:1 (81.3)
9.4:1 (66)
>20:1 (78.9)
1:1 (95.3)
9.0:1 (74.1%
>20:1 (72.6)
-50 °C, 19 h
-50 °C, 19 h
-78 °C, 22 h
-78 °C, 26.5 h
-78 °C, 26.5 h
the Diels-Alder reaction. Using 2.25 equiv of AlMe
cobalt dmg diene (22a ) we saw no product, which
indicated that AlMe was not strong enough to promote
the Diels-Alder reaction (Table 4), and the use of 2.25
equiv of a stonger Lewis acid such as BCl caused
3
with
The preparative scale reactions of MA and 22a with
AlMe produced largely expected results as determined
3
3
by NMR experiments (Table 4). One surprise was that
the diastereoselectivities, while good when 3 equiv of
Lewis acid was used, were not as high as those seen in
the NMR tube experiments. Complete anti (exo) selectiv-
ity required the addition of more Lewis acid. If the
3
significant complex decomposition even at -50 °C. We
thought that since the first 2 equiv of Lewis acid bind
irreversibly to the diene complex, we could then use the
first 2 equiv to both increase the steric bulk of the diene
and protect the diene from stronger Lewis acids that
3
cycloaddition is slow at 3 equiv of AlMe on the prepara-
tive scale or there are slight inaccuracies in Lewis acid
molarity, there could still be unreacted diene (22a ) and
MA present upon quenching and warm up. A purely
thermal Diels-Alder reaction (entry 1, Table 4) between
the remaining diene and MA would then decrease the
anti (exo) selectivity seen in the cycloadduct (entry 2,
would otherwise decompose it (i.e. BCl
2.0 equiv of AlMe followed by 0.25 equiv of a stronger
Lewis acid, AlEt Cl. Cycloaddition occurred but only 20%
after 2.7 days. Using 0.25 equiv of BCl following 2.0
equiv of AlMe did promote the desired catalytic reaction
3
). We tried using
3
2
3
3
Table 4). At 4 equiv of AlMe
we saw that there was complete exo addition to produce
3
(entries 3 and 6, Table 4),
at -50 °C with a 1.6:1 syn:anti (endo:exo) selectivity
(entry 3, Table 5). This reaction was significantly more
Ta ble 5. Lew is Acid Ca ta lyzed Diels-Ald er Rea ction s of 21 or 22 w ith MVK
entry
Lewis acid(s)
2.25 equiv of AlMe3
2.0 equiv of AlMe3, 0.25 equiv of AlEt2Cl
2.0 equiv of AlMe3, 0.25 equiv of BCl3
conditions
syn:anti (% yield)
DMG (22a)
1
2
3
-50 °C, 11 h
-50 °C, 11 h
-50 °C, 2.7 h
a
b
1.6:1 (80.2%)
DPG (22b)
4
5
6
7
8
0.0 equiv
2.25 equiv of AlMe3
2.0 equiv of AlMe3, 0.25 equiv of AlEt2Cl
2.0 equiv of DIBALH, 0.25 equiv of Et2Cl
2.0 equiv of DlBALH, 0.25 equiv of DlBALCl
-22 °C, 14 d
-50 °C, 12 h
-50 °C, 12 h
-50 °C, 1.5 d
-50 °C, 1.5 d
a
a
1:1.3 (81.7)
1:1.3 (83.4)
1:1.6 (90.1)
AG (21)
2.0 equiv of AlMe3, 0.25 equiv of BCl3
2.0 equiv of DlBALH, 0.25 equiv of BCl3
2.0 equiv of DiBALH, 0.25 equiv of DlBAlCl
9
0
1
-50 °C
-50 °C
-50 °C
a
c
c
1
1
a
Unreacted diene. b 10% complete after 11 h and 20% after 2.7 days. c 10% comlete after 5 d with a 1:1 ratio of diastereomers.

Preparation of 2-Cobalt-Substituted 1,3-Dienes
J . Org. Chem., Vol. 61, No. 1, 1996 141
exo selective than the purely thermal cycloaddition result
Ta ble 6. Best Selectivities An ti:Syn (Exo:En d o) Obta in ed
for a Va r iety of Dien op h iles
(5:1 endo:exo). This result indicated that we should try
using larger ligand sets on the first 2 equiv of Lewis acid
to see if this produced even more exo addition.
Increasing the size of the equatorial ligand using Lewis
acids was next pursued with the larger equatorial ligand
dienyl complexes 22b and 21. We knew that dpg diene
(
22b) failed to cyclize with 20 equiv of MVK in the
absence of Lewis acids at -22 °C (entry 4, Table 5). Once
again, using AlMe alone with a dienyl complex, this time
2b, failed to promote any cycloaddition (entry 5, Table
). Using 2 equiv of AlMe and 0.25 equiv of AlEt Cl
3
2
5
3
2
promoted cycloaddition, but the selectivity (1.3:1 anti:
syn (exo: endo), entry 6, Table 5 was only slightly better
than the thermal result at 25 °C (1:1). Adding a larger
Lewis acid (2.0 equiv of DIBALH) followed by 0.25 equiv
2
of AlEt Cl (entry 7, Table 5) had virtually no additional
effect. Using an even larger commercially available
Lewis acid combination (2.0 equiv of DIBALH followed
by 0.25 equiv of DIBAlCl), we saw a slight increase in
exo selectivity (entry 8, Table 5). Unfortunately, the very
sterically hindered AG dienyl complex 21 proved to be
essentially unreactive toward MVK under these low-
temperature Lewis acid catalyzed conditions (entries
have developed cobalt-carbon bond cleaving reactions
which allow recovery of the organic cycloadduct with
stereochemistry intact as well as a cobalt complex that
is easily converted back into our starting cobalt dienes
2
1 and 22.
9
-11, Table 5).
Ack n ow led gm en t. We thank the National Science
Foundation (CHE-9321454), the donors of the Petroleum
Research Fund administered by the American Chemical
Society, the Exxon Education Foundation, and the
Camille and Henry Dreyfus Foundation (Henry Dreyfus
Teacher-Scholar Award to M.E.W., 1994-99) for their
support. Low-resolution mass spectra were obtained on
an instrument purchased with the partial support of
NSF (CHE-9007366). The Nebraska Center for Mass
Spectrometry (NSF DIR9017262) performed high-
resolution mass spectral analyses. M.W.W. acknowl-
edges Sigma Xi for a student grant-in-aid.
Con clu sion s
Table 6 summarizes our results to date for thermal and
Lewis acid catalyzed Diels-Alder reactions of cobalt-
substituted dienes with tri-, di-, and monosubstituted
dienophiles. We have been able to achieve >20:1 anti
(
exo) selectivity for the tri- or disubstituted dienophiles.
The monosubstituted dienophile, MVK, has proven to be
the toughest case for us, and our best anti (exo) selective
Diels-Alder reaction for this dienophile produces the anti
(
exo) diastereomer in 2:1 excess over the syn (endo)
diastereomer. In all cases following cycloaddition, we
J O951505O