Lanthanide-Catalyzed Hydroamination of Hindered Alkenes in Synthesis: Rapid Access to 10,11-Dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imines

Full text of DOI:10.1021/jo990626b

J . Org. Chem. 1999, 64, 6515-6517
6515
substrates are cyclized under essentially neutral condi-
tions with modest catalyst loading. Although the initial
studies of this reaction focused on monosubstituted
alkenes (because of the hindered nature of the catalysts),
this requirement has been relaxed through rational
modification of the catalyst structure.9 A particularly
interesting target for this technology is the tetracyclic
amine MK-801.10 The dibenzocycloalkyl motif is present
in a variety of biologically active agents,11 with MK-801
displaying potent anticonvulsant and neuroprotective
properties.12 The quaternary methyl group located R to
the amine suggests a simple hydroamination retrosyn-
thesis (eq 1). The 1,1-diaryl substitution of the alkene
presented a significant steric challenge to catalysis, but
the entropic advantage afforded by the close proximity
of the reactive partners was anticipated to offset this
difficulty.
La n th a n id e-Ca ta lyzed Hyd r oa m in a tion of
Hin d er ed Alk en es in Syn th esis: Ra p id
Access to 10,11-Dih yd r o-5H-d iben zo-
[a ,d ]cycloh ep ten -5,10-im in es
Gary A. Molander* and Eric D. Dowdy
Department of Chemistry and Biochemistry, University of
Colorado at Boulder, Boulder, Colorado 80309-0215
Received April 13, 1999
In tr od u ction
Lanthanide reagents mediate a wide range of powerful
organic transformations not possible utilizing more tra-
ditional methods.1 Unique catalytic reactivity is also
exhibited by the metallocene complexes of the lanthanide
and group 3 metals. Lacking valence d electrons used by
late transition metals for oxidative addition/reductive
elimination,2 the high reactivity of the metallocenes
arises from olefin insertion and σ-bond metathesis reac-
tions.3 Long investigated as olefin polymerization cata-
lysts,4 these complexes have recently been utilized for
small-molecule synthesis.5 By combining olefin insertion
reactions with a variety of intra- and intermolecular
trapping steps, cyclization/hydrogenolysis, cyclization/
hydrosilylation, and hydroamination reactions have been
accomplished.5 The catalytic complexes exhibit predict-
able chemoselectivity in polyfunctional substrates: protic
groups such as amines are metalated first with subse-
quent olefin insertion if a strategically located and
sterically accessible alkene is present.6 In polyolefinic
substrates lacking an amine, the catalysts will insert
alkenes with predictable preference for the less hindered
functional unit. The greatest strength of the method is
the potential of the complex to insert multiple alkenes
before the functionalization step. In this manner complex
polycyclic products can be generated from simple sub-
strates in a rapid fashion.7
Previously reported approaches to the synthesis of
MK-801 include a thermal, transannular addition of a
hydroxylamine to an exocyclic alkene to form the nitrogen
bridge.10a Although very efficient (96%), this reaction
requires vigorous heating (refluxing xylenes or decane)
and requires an additional step to remove the hydroxyl
group from the amine. Another known approach to this
ring system is the LDA-mediated addition of a secondary
amine to an exocyclic alkene.10c Although this reaction
proceeds at room temperature, the requirement that the
amine be secondary hampers the generality of this
process, allowing only the production of N-substituted
derivatives of MK-801. We anticipated that the lan-
thanide-catalyzed intramolecular hydroamination reac-
tion would avoid each of these problems because it is
known to proceed under mild conditions and to operate
efficiently on a wide variety of aminoolefin substrates.8
The organolanthanide-catalyzed intramolecular hy-
droamination reaction is a powerful entry into a variety
of heterocyclic systems.8 Easily prepared aminoalkene
Resu lts a n d Discu ssion
* To whom correspondence should be addressed at the Department
of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania
19104-6323.
(1) (a) Molander, G. A. Chem. Rev. 1992, 92, 29. (b) Molander, G.
A.; Harris, C. R. Chem. Rev. 1996, 96, 307. (c) Molander, G. A. Acc.
Chem. Res. 1998, 31, 603.
(2) Hegedus, L. S. Transition Metals in the Synthesis of Complex
Organic Molecules; University Science Books: Mill Valley, CA, 1994.
(3) Schumann, H.; Meese-Marktscheffel, J . A.; Esser, L. Chem. Rev.
1995, 95, 865.
(4) (a) Marks T. J .; Ernst R. D. In Comprehensive Organometallic
Chemistry; Wilkinson G., Stone, F. G. A., Abel E. W., Eds.; Pergamon
Press: Oxford, 1982; Vol. 3, Chapter 21. (b) Watson P. L.; Parshall G.
W. Acc. Chem. Res. 1985, 18, 51. (c) Edelmann F. T. In Comprehensive
Organometallic Chemistry II; Abel E. W., Stone F. G. A., Wilkinson
G., Eds.; Pergamon Press: Oxford, 1995; Vol. 4, Chapter 2. (d)
Edelmann F. T. Top. Curr. Chem. 1996, 179, 247.
(5) (a) Molander, G. A. Chemtracts 1998, 11, 237. (b) Molander, G.
A.; Dowdy E. D. In Topics In Organometallic Chemistry; Kobayashi,
S., Ed.; Springer-Verlag: New York, 1999; Vol. 2, pp 120-154.
(6) Gagne´, M. R.; Stern, C. L.; Marks, T. J . J . Am. Chem. Soc. 1992,
114, 275.
(7) (a) Molander, G. A.; Dowdy, E. D.; Schumann, H. J . Org. Chem.
1998, 63, 3386. (b) Molander, G. A.; Nichols, P. J . J . Org. Chem. 1998,
63, 2292. (c) Molander, G. A.; Retsch, W. H. J . Org. Chem. 1998, 63,
5507.
The cyclization substrate 2 is structurally similar to
commercially available dibenzosuberone 3, requiring only
the installation of the alkene and primary amine func-
tional groups (Scheme 1). Wittig olefination of 3 proceeds
rapidly and in high yield to give alkene 4.13 The polar
(8) (a) Li, Y.; Marks, T. J . J . Am. Chem. Soc. 1996, 118, 9295. (b)
Li, Y.; Marks T. J . J . Am. Chem. Soc. 1998, 120, 1757.
(9) Molander, G. A.; Dowdy, E. D. J . Org. Chem. 1998, 63, 8983.
(10) (a) Christy, M. E.; Anderson, P. S.; Britcher, S. F.; Colton, C.
D.; Evans, B. E.; Remy, D. C.; Engelhardt, E. L. J . Org. Chem. 1979,
44, 3117. (b) Yasuda, M.; Wakisaka, T.; Kojima, R.; Tanabe, K.; Shima,
K. Bull. Chem. Soc. J pn. 1995, 68, 3169. (c) Evans, B. E.; Anderson,
P. S.; Christy, M. E.; Colton, C. D.; Remy, D. C.; Rittle, K. E.;
Engelhardt, E. L. J . Org. Chem. 1979, 44, 3127.
(11) (a) Piwinski, J . J .; Wong, J . K.; Green, M. J .; Ganguly, A. K.;
Billah, M. M.; West, R. E., J r.; Kreutner, W. J . Med. Chem. 1991, 34,
457. (b) J ung, M. E.; Miller, S. J . J . Am. Chem. Soc. 1981, 103, 1984.
(c) Nomoto, T.; Takayama, H. J . Chem. Soc., Chem. Commun. 1982,
1113. (d) Moore, A. Drugs Today (Barcelona) 1978, 14, 467.
(12) Rajev, S.; Sharp, F. R. In Highly Selective Neurotoxins: Basic
and Clinical Applications; Kostrzewa, R. M., Ed.; Humana Press:
Totowa, NJ , 1998; pp 355-384.
10.1021/jo990626b CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/04/1999

6516 J . Org. Chem., Vol. 64, No. 17, 1999
Notes
Sch em e 1a
Sch em e 2a
a
Key: (a) NBS, AIBN, CCl4; (b) 40% aqueous MeNH2, THF,
20% (two steps); (c) 6% [CpTMS2NdMe]2, C6D6, 50 °C, 2 h, 94%.
preparation was shortened by direct conversion of the
bromide used in Scheme 1 to an amine by treatment with
aqueous methylamine in THF. Careful flash chromatog-
raphy of the crude reaction mixture yielded 20% of pure
7 along with a similarly sized fraction of impure material.
Exposure of this compound to the cyclization conditions
provided N-methyl-MK-801 (8) in good yield. The facile
nature of this transformation is remarkable in light of
the highly hindered nature of both reactive partners.
a
Key: (a) Ph3PMeBr, KOt-Bu, 98%;(b) NBS, AIBN, CCl4; (c)
H2O, THF, 62% (two steps); (d) (PhO)2P(O)N3, DEAD, Ph3P, 75%;
(e) LiAlH4, 88%; (f) 1% [CpTMS2NdMe]2, C6D6, 40 °C, 2 h, 98%.
Con clu sion s
functionality was created by benzylic bromination medi-
ated by NBS with thermal initiation using AIBN.14 The
bromide prepared was quite labile, and could be isolated
in only modest purity and yield after chromatography.
NMR analysis of the crude material obtained by simply
filtering the succinimide from the mixture and concen-
trating the filtrate revealed the presence of the bromide
in good yield. An improved yield was realized by hydro-
lyzing the crude bromide directly, providing 5 in 62%
yield (two steps).15 The alcohol was converted to the
amine (2) via the azide by Mitsunobu inversion with
diphenylphosphoryl azide16 and subsequent LAH reduc-
tion. This sequence was superior to a Mitsunobu reaction
with phthalimide followed by deprotection owing to
higher yields and greater ease of purification.
Intramolecular hydroamination reactions of hindered
aminoolefins are catalyzed by sterically open lanthanide
metallocene catalysts. The ease of preparation and rela-
tively high air stability simplify the use of [CpTMS2NdMe]2
as a hydroamination catalyst.18 The cyclizations proceed
under mild conditions to give heterocyclic products in
high yield. Combined with a short substrate synthesis,
these reactions provide rapid entry to the nitrogen-
bridged dibenzocycloalkane series of pharmaceutically
active chemicals typified by MK-801. N-Substituted de-
rivatives are accessible by this method as well, thereby
increasing the versatility of the synthetic method.
Exp er im en ta l Section
The conversion of the tricyclic aminoalkene to MK-801
proved to be quite facile when exposed to an appropriate
Rea gen ts. CCl4 was distilled from CaH2. Et2O, THF, and
C6D6 were distilled from sodium benzophenone ketyl. NBS was
recrystallized from hot H2O immediately prior to use and dried
thoroughly in vacuo. [CpTMS2NdMe]2 was prepared by a litera-
ture procedure17 and handled in a nitrogen-filled glovebox. All
other reagents were used as received.
lanthanide catalyst. [CpTMS2NdMe]2 was chosen as the
17
precatalyst for this reaction as it possesses both good
reactivity toward hindered alkenes and ease of prepara-
tion. The reaction was carried out simply by combining
the substrate with [CpTMS2NdMe]2 in C6D6 under a nitro-
gen atmosphere. The solution was transferred to a sealed
NMR tube to allow in situ monitoring of the progress of
the reaction. As little as 1 mol % [CpTMS2NdMe]2 was
sufficient to transform the substrate rapidly under mild
heating. The product was isolated by filtering the crude
reaction mixture through Florisil to remove the catalyst.
The crude oil was purified by Kugelrohr distillation,
giving a 98% yield of material that was spectroscopically
identical to material described in the literature, and was
found to be analytically pure by combustion analysis.
Although this is a simple transformation, the high purity
of the product is evidence of the remarkable selectivity
of the catalyst. Neither intermolecular oligomerization
nor olefin polymerization reactions were observed at all,
and the amination was completely selective for the
hindered end of the alkene. This selectivity is likely aided
by the close proximity of the reactive functional groups
of 2.
5-Met h ylen e-10,11-d ih yd r o-5H -d ib en zo[a ,d ]cycloh ep -
ten e (4). A flame-dried flask was charged with 2.72 g (23 mmol)
of KOt-Bu suspended in 35 mL of dry Et2O under Ar. Next,
methyltriphenylphosphonium bromide (8.22 g, 23 mmol) was
added in one lot, and the yellow mixture was stirred at ambient
temperature for 30 min. The mixture was cooled to 0 °C, and 3
(4.16 g, 20 mmol) was added in small portions. After being
warmed to room temperature, the mixture was stirred for 1 h
before being diluted with 100 mL of pentane. A small amount
of water was added to quench the excess reagent, and the mix-
ture was filtered through a plug of silica gel. The silica was
rinsed with additional pentane, and the filtrate was concentrated
by rotary evaporation. The residue was purified by Kugelrohr
distillation to yield 4.05 g (19.6 mmol, 98%) of the title compound
as a colorless oil that crystallized on standing: mp 66-67 °C;
1
ot 85 °C, 0.01 mmHg; H NMR (500 MHz, CDCl3) δ 7.36-7.34
(m, 2H), 7.22-7.15 (m, 4H), 7.13-7.11 (m, 2H), 5.42 (s, 2H), 3.15
(s, 4H); 13C NMR (125 MHz, CDCl3) δ 151.8, 141.1, 138.3, 128.9,
128.1, 127.6, 126.2, 117.5, 33.2; IR (CHCl3) 3061.2, 3015.8,
1616.0 cm-1; HRMS calcd for C16H14+ 206.1096, found 206.1113;
N-Substituted derivatives were also rapidly accessed
by this protocol (Scheme 2). In this case substrate
(15) Meyers, A. I.; Higashiyama, K. J . Org. Chem. 1987, 52, 4592.
(16) Simon, C.; Hosztafi, S.; Makleit, S. Tetrahedron Lett. 1993, 34,
6475.
(17) Molander, G. A.; Dowdy, E. D.; Noll B. C. Organometallics 1998,
17, 3754.
(18) Keitsch, M. Unpublished results.
(13) Fitjer, L.; Quabech, U. Synth. Commun. 1985, 15, 855.
(14) Dubey, S. K.; Kumar, S. J . Org. Chem. 1986, 51, 3407.

Notes
J . Org. Chem., Vol. 64, No. 17, 1999 6517
LRMS (EI+) m/z 206 (100), 205 (83), 178 (18), 128 (12), 91 (21).
Anal. Calcd for C16H14: C, 93.16; H, 6.84. Found: C, 92.89; H,
7.19.
C6D6 to rinse the vial. The mixture was then removed from the
glovebox and heated to 40 °C, and the progress of the reaction
was monitored by GC sampling of small aliquots. After 2 h the
starting material was completely consumed. The solution was
filtered through Florisil with Et2O to remove the catalyst, and
the filtrate was concentrated in vacuo. The residue was purified
by Kugelrohr distillation to yield 0.056 g (0.253 mmol, 98%) of
the title compound as a colorless oil: ot 100 °C, 0.01 mmHg; 1H
NMR (500 MHz, CDCl3) δ 7.28-7.24 (m, 2H), 7.10-7.03 (m, 5H),
6.93-6.91 (m, 1H), 4.69 (d, J ) 5.6 Hz, 1H), 3.44 (dd, J ) 16.7,
5.8 Hz, 1H), 2.72 (d, J ) 16.8 Hz, 1H), 2.53 (br s, 1H), 1.91 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 152.1, 144.7, 144.4, 132.3,
130.2, 128.1, 126.9, 126.6, 125.7, 121.6, 121.4, 118.6, 64.1, 58.4,
34.4, 20.2; IR (neat) 3210.2, 3016.1, 1600.5 cm-1; HRMS calcd
for C16H14N+ (M - H)+ 220.1126, found 220.1142; LRMS (EI+)
m/z 221 (100), 220 (93), 206 (33), 178 (74). Anal. Calcd for
5-Meth ylen e-10-h yd r oxy-10,11-d ih yd r o-5H-d iben zo[a ,d ]-
cycloh ep ten e (5). A solution of 4 (0.155 g, 0.75 mmol), NBS
(0.186 g, 1.04 mmol), and AIBN (0.005 g) in 20 mL of CCl4 was
heated to reflux for 2 h. At that time GC analysis of an aliquot
indicated the complete consumption of 4. The mixture was
cooled, filtered, and concentrated. The residue was dissolved in
4 mL of 25% H2O in THF and stirred at room temperature for
48 h. The solution was then poured onto CH2Cl2 and washed
with saturated aqueous NaCl. The organic layer was dried over
Na2SO4, filtered, and concentrated. The crude oil was purified
by flash chromatography on SiO2 followed by Kugelrohr distil-
lation to yield the title compound as a colorless oil (0.104 g, 0.47
mmol, 62%) that crystallized very slowly upon standing: ot 115
°C, 0.01 mmHg; Rf 0.35 (25% EtOAc/hexanes); 1H NMR (500
MHz, CDCl3) δ 7.49-7.47 (m, 1H), 7.39-7.37 (m, 1H), 7.32-
7.24 (m, 2H), 7.23-7.18 (m, 4H), 5.52 (d, J ) 1.6 Hz, 1H), 5.36
(d, J ) 1.6 Hz, 1H), 5.10 (td, J ) 8.3, 2.8 Hz, 1H), 3.45 (dd, J )
14.5, 2.8 Hz, 1H), 3.20 (dd, J ) 14.5, 7.9 Hz, 1H), 1.88 (d, J )
8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 151.0, 142.7, 139.6,
138.7, 133.4, 130.1, 129.4, 128.5, 128.2, 127.8, 127.7, 127.5, 126.9,
117.8, 70.7, 40.6; IR (neat) 3349.7, 3062.5, 1616.3 cm-1; HRMS
calcd for C16H14O+ 222.1045, found 222.1037; LRMS (EI+) m/z
222 (35), 204 (36), 178 (100). Anal. Calcd for C16H14O: C, 86.45;
H, 6.35. Found: C, 86.78; H, 6.51.
C
16H15N: C, 86.84; H, 6.83; N, 6.33. Found: C, 86.61; H, 7.05;
N, 6.23.
10-Meth ylam in o-5-m eth ylen e-10,11-dih ydr o-5H-diben zo-
[a ,d ]cycloh ep ten e (7). A solution of 4 (1.031 g, 5.0 mmol), NBS
(1.068 g, 6.0 mmol), and AIBN (0.005 g) in 20 mL of CCl4 was
heated to reflux for 2 h. At that time GC analysis of an aliquot
indicated the complete consumption of 4. The mixture was
cooled, filtered, and concentrated. The residue was dissolved in
4 mL of THF; 2 mL of 40% aqueous MeNH2 was added, and the
mixture was stirred at room temperature for 48 h. The reaction
mixture was diluted with Et2O and extracted (2×) with 10% HCl.
The acidic extracts were washed with Et2O before being made
basic with NaOH. The aqueous layer was then extracted (2×)
with CH2Cl2. After drying with Na2SO4, concentration of the
solution afforded the crude material as a yellow oil. Purification
by flash chromatography on SiO2 using 25% EtOAc and 5% Et3N
in hexanes yielded two fractions: 0.233 g (0.99 mmol, 20%) of
analytically pure material and an additional 0.25 g of 90% pure
material. The pure fraction was further purified by Kugelrohr
distillation to yield the title compound as a pale yellow oil: ot
120 °C, 0.05 mmHg; 1H NMR (500 MHz, CDCl3) δ 7.43-7.41
(m, 1H), 7.38-7.30 (m, 2H), 7.30-7.24 (m, 1H), 7.23-7.21 (m,
3H), 7.20-7.18 (m, 1H), 5.49 (d, J ) 1.6 Hz, 1H), 5.45 (d, J )
1.6 Hz, 1H), 4.11 (dd, J ) 8.1, 2.8 Hz, 1H), 3.40 (dd, J ) 15.9,
2.8 Hz, 1H), 3.24 (dd, J ) 15.9, 8.1 Hz, 1H), 2.49 (s, 3H), 1.40
(br s, 1H); 13C NMR (125 MHz, CDCl3) δ 151.6, 140.3, 140.2,
139.9, 135.0, 130.3, 128.2, 128.1, 127.8, 127.7, 127.7, 127.0, 126.4,
117.6, 60.7, 38.6, 34.3; IR (neat) 3333.7, 3060.8, 3021.1, 1614.1
cm-1; HRMS calcd for C17H17N+ 235.1361, found 235.1375;
LRMS (EI+) m/z 235 (100), 220 (44), 204 (98), 178 (48). Anal.
Calcd for C17H17N: C, 86.77; H, 7.28; N, 5.95. Found: C, 86.47;
H, 7.45; N, 6.07.
10-Azid o-5-m eth ylen e-10,11-d ih yd r o-5H-d iben zo[a ,d ]cy-
cloh ep ten e (6). Triphenylphosphine (0.263 g, 1.0 mmol) was
dissolved in dry THF, and the solution was treated with diethyl
azodicarboxylate (0.175 g, 1.0 mmol) in THF. Next, diphen-
ylphosphoryl azide (0.276 g, 1.0 mmol) was added dropwise
followed by a THF solution of 5 (0.186 g, 0.84 mmol). After 1 h
the mixture was concentrated in vacuo and purified by flash
chromatography to yield the title compound (0.155 g, 0.63 mmol,
75%) as a white solid: mp 62-64 °C; Rf 0.45 (5% EtOAc/
hexanes); 1H NMR (500 MHz, CDCl3) δ 7.43-7.41 (m, 1H), 7.37-
7.35 (m, 1H), 7.33-7.26 (m, 3H), 7.25-7.20 (m, 3H), 5.54 (d, J
) 1.6 Hz, 1H), 5.39 (d, J ) 1.6 Hz, 1H), 4.90 (dd, J ) 8.3, 2.8
Hz, 1H), 3.47 (dd, J ) 14.7, 3.0 Hz, 1H), 3.25 (dd, J ) 14.7, 8.3
Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 150.4, 142.1, 139.8, 134.8,
133.4, 129.6, 129.3, 129.0, 128.4, 128.3, 127.9, 127.6, 127.2, 118.4,
62.4, 38.2; IR (CHCl3) 3024.4, 2099.7, 1617.9 cm-1; HRMS calcd
+
for C16H13N3 247.1109, found 247.1113; LRMS (EI+) m/z 247
(1), 218 (100), 205 (35). Anal. Calcd for C16H13N3: C, 77.71; H,
5.30; N, 16.99. Found: C, 77.21; H, 5.59; N, 16.52.
10-Am in o-5-m et h ylen e-10,11-d ih yd r o-5H-d ib en zo[a ,d ]-
cycloh ep ten e (2). Lithium aluminum hydride (0.118 g, 3.1
mmol) was suspended in 20 mL of dry Et2O before the azide
(0.380 g, 1.54 mmol) dissolved in 20 mL of Et2O was added
dropwise. The mixture boiled spontaneously during this addition,
and was stirred for an additional 30 min. TLC analysis of an
aliquot indicated the reaction was complete. The mixture was
cooled to 0 °C and quenched by the dropwise addition of 10%
aqueous NaOH until H2 evolution ceased. The mixture was next
filtered through Celite, and the filtrate was concentrated by
distillation at atmospheric pressure. The residue was purified
by Kugelrohr distillation at reduced pressure to yield the title
compound (0.287 g, 1.30 mmol, 84%) as a colorless oil: ot 105
°C, 0.01 mmHg; 1H NMR (500 MHz, CDCl3) δ 7.38-7.26 (m,
4H), 7.23-7.16 (m, 4H), 5.46 (d, J ) 1.6 Hz, 1H), 5.37 (d, J )
1.6 Hz, 1H), 4.44 (dd, J ) 8.0, 3.0 Hz, 1H), 3.46 (dd, J ) 14.7,
N,5-Dim eth yl-10,11-dih ydr o-5H-diben zo[a ,d]cycloh epten -
5,10-im in e (8). The reaction was carried out in the same
manner as for the preparation of 1 using 50 mg (0.212 mmol) of
7 and 6 mg (6.5 mol %) of [CpTMS2NdMe]2. The reaction was
found to be complete after 2 h at 40 °C by NMR and GC analysis
of a small aliquot. Analogous workup and purification yielded
the title compound (47 mg, 0.200 mmol, 94%) as a colorless oil:
ot 115 °C, 0.05 mmHg; 1H NMR (500 MHz, CDCl3) δ 7.28-7.26
(m, 1H), 7.24-7.22 (m, 1H), 7.11-7.05 (m, 4H), 7.05-7.01 (m,
1H), 6.90-6.88 (m, 1H), 4.35 (d, J ) 5.5 Hz, 1H), 3.34 (dd, J )
17.3, 5.5 Hz, 1H), 2.51 (d, J ) 17.3 Hz, 1H), 2.36 (s, 3H), 1.82 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 151.1, 142.7, 140.9, 132.3,
129.6, 126.9, 126.8, 126.6, 126.2, 123.5, 121.6, 118.9, 65.8, 62.9,
32.4, 28.5, 17.4; IR (neat) 3022.5, 1613.4 cm-1; HRMS calcd for
3.0 Hz, 1H), 3.02 (dd, J ) 14.7, 8.0 Hz, 1H), 1.45 (br s, 2H); 13
C
C
17H16N+ (M - H)+ 234.1283, found 234.1266; LRMS (EI+) m/z
NMR (125 MHz, CDCl3) δ 151.5, 142.2, 142.0, 139.0, 134.7, 130.4,
128.5, 128.2, 128.1, 127.7, 127.6, 127.0, 126.6, 117.8, 52.4, 41.3;
IR (neat) 3367.3, 3295.6, 3022.1, 1614.2 cm-1; HRMS calcd for
235 (100), 220 (13), 204 (12), 178 (29). Anal. Calcd for C17H17N:
C, 86.77; H, 7.28; N, 5.95. Found: C, 86.56; H, 7.44; N, 5.95.
C
16H15N+ 221.1204, found 221.1201; LRMS (EI+) m/z 221 (63),
Ack n ow led gm en t. We gratefully acknowledge the
National Institutes of Health (Grant GM48580) and
NATO for their generous support of this research.
E.D.D. thanks Smith Kline-Beecham for their support
in the form of a graduate fellowship administered by
the Organic Division of the American Chemical Society.
204 (100), 203 (92), 178 (85). Anal. Calcd for C16H15N: C, 86.84;
H, 6.83; N, 6.33. Found: C, 86.84; H, 7.21; N, 6.20.
5-Met h yl-10,11-d ih yd r o-5H -d ib en zo[a ,d ]cycloh ep t en -
5,10-im in e (MK-801) (1). In
a nitrogen-filled glovebox
[CpTMS2NdMe]2 (0.001 g, 0.9 mol %) was weighed into a vial and
dissolved in 0.5 mL of C6D6. Next, 0.057 g (0.258 mmol) of 5
was added, and the light blue solution was transferred into a
tube equipped with a Teflon-valved top using another 0.5 mL of
J O990626B