Coupling of β-cyanocarbene-chromium complexes with 2-alkynylbenzoyl derivatives: A [5+5]-cycloaddition approach to phenanthridines

Article abstract of DOI:10.1055/s-2006-950286

The coupling of β-cyanocarbene complexes and 2-alkynylbenzoyl derivatives has been examined. The reaction afforded phenanthridine derivatives in a complex tandem process involving carbene-alkyne coupling, isobenzofuran formation, intramolecular Diels-Alder reaction using a nitrile dienophile, and deoxygenation. The chemistry could not be reproduced in non-chromium-based systems. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950286

PAPER
3661
Coupling of b-Cyanocarbene-Chromium Complexes with 2-Alkynylbenzoyl
Derivatives: A [5+5]-Cycloaddition Approach to Phenanthridines
b
-Cyanocarbene-
i
Chrom
n
ium
C
omple
a
Department of Chemistry and Biochemistry, New Mexico State University, MSC 3C, Las Cruces, NM 88003, USA
Fax +1(505)6462649; E-mail: jherndon@nmsu.edu
Received 9 June 2006
Dedictaed to Professor Martin F. Semmelhack on the occasion of his 65th birthday
R
Cr(CO)5
Abstract: The coupling of b-cyanocarbene complexes and 2-alky-
nylbenzoyl derivatives has been examined. The reaction afforded
MeO
+
phenanthridine derivatives in a complex tandem process involving
carbene–alkyne coupling, isobenzofuran formation, intramolecular
Diels–Alder reaction using a nitrile dienophile, and deoxygenation.
The chemistry could not be reproduced in non-chromium-based
systems.
COR
CN
B
A
OMe
OMe
R
R
Key words: carbene complexes, chromium, cycloadditions,
alkynes, nitriles, Diels–Alder reactions
O
O
N
N
R
This manuscript reports on the scope, limit, and mechanis-
tic considerations for the preparation of isoquinoline de-
rivatives through coupling of b-cyanocarbene complexes
and 2-alkynylbenzoyl systems.1 In the original design of
this reaction depicted in Scheme 1, coupling of the func-
tionalized alkyne A and the b-cyanocarbene complex B
will initially generate an isobenzofuran intermediate C,2
which could potentially undergo an intramolecular Diels–
Alder reaction with the nitrile dienophile, resulting in D.
Only limited studies where nitriles serve as dienophiles in
Diels–Alder reactions have appeared. Although Diels–
Alder reactions of nitriles with simple dienes are known,3
only one example of the Diels–Alder reaction between a
nitrile and a furan/isobenzofuran has been reported.4 The
reverse reaction has ample precedent, and is a key step in
the synthesis of furans from oxazoles and alkynes.5
Isobenzofurans can be generated through expulsion of ni-
triles from simpler analogues of D, which occurs upon
mild thermolysis.6
C
D
R
Scheme 1
(Equation 2) using Cr(CO)5 dianion.9 A similar route was
employed for the direct conversion of b-cyanoamides 4 to
b-cyano aminocarbene complexes 7 (Equation 3).10 These
latter routes were used for the preparation of o-cyano-
phenylcarbene complexes 6. Alkoxycarbene complexes
2a,c,d and 6a are unstable in comparison with analogous
complexes lacking a cyano group. These carbene com-
plexes are difficult to purify and rapidly acquire a green-
ish color in the air. Aminocarbene complexes 2e and
phosphine-substituted11 complex 2b were more stable
than alkoxy pentacarbonylcarbene analogues. Alkynyl-
benzoyl starting materials were prepared through well-
established methods.
Cr(CO)4L
Cr(CO)4L
R1
Cr(CO)4L
R1
1. n-BuLi
MeO
CN
MeO
We are not aware of any precedent for b-cyano Fischer
carbene complexes. Three methods were successfully de-
veloped for the synthesis of this class of compounds. The
simplest method involves the alkylation of simple carbene
complexes 1 (Equation 1, see Figure 1 for identity of R
groups) with bromo- or iodoacetonitrile.7 A problem with
this method is that alkylation of the simple methylcarbene
complexes 1a,b produces only the dialkylation product
2a. Only alkoxycarbene complexes could be prepared us-
ing this method. Aminocarbene complexes could not be
alkylated using this procedure, possibly due to a compet-
ing proton transfer process.8 An alternative method in-
MeO
2. XCH2CN
2a
2
1
CN
CN
Equation 1
Cr(CO)5
R1
O
R1
1. K2Cr(CO)5
MeO
Cl
2. Me4NBr
3. MeOTf
R2
NC
R2
2
3
NC
Equation 2
Cr(CO)5
O
volves synthesis from b-cyano acid chlorides
3
K2Cr(CO)5,
TMSCl
R1
R1
R2
Me2N
Me2N
SYNTHESIS 2006, No. 21, pp 3661–3669
x
x.
x
x
.
2
0
0
6
R2
2
4
NC
NC
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950286; Art ID: Z11806SS
© Georg Thieme Verlag Stuttgart · New York
Equation 3

3662
B. K. Ghorai et al.
PAPER
O
Cr(CO)4L
Bu
Cr(CO)4L
Cr(CO)4L
R1
Y
X
MeO
CH2-R1
MeO
CN
+
1
R2
NC
R4
NC
CHO
2a,b
2
NC
7a
5
a L = CO
b L = PBu3
Cr(CO)5
X
OMe CN
OMe CN
O
NC
Bu
Bu
6
R3
7
Cr(0)
complexes 1
compounds 2
a R1 = H, L = CO
a R1 = CH2CN, R2 = H, X = OMe, L = CO
b R1 = CH2CN, R2 = H, X = OMe, L = PBu3
c R1 = n-Pr, R2 = H, X = OMe, L = CO
d R1,R2 = -(CH2)4- (cis), X = OMe, L = CO
e R1,R2 = -(CH2)4- (cis), X = NMe2, L = CO
O
C
O
N
b R1 = H, L = PBu3
c R1 = Pr, L = CO
N
8a
9a
OMe CN
OMe
complexes 6
a X = OMe
(from 5, X = Cl)
b X = NMe2
compounds 7
CN
a R3 = H, R4 = n-Bu
b R3 = Me, R4 = n-Bu
c R3 = Ph, R4 = n-Bu
d R3, R4 = H
Bu
Bu
MeO
NC
N
N
e R3 = NMe2, R4 = Bu
f R3 = NMe2, R4 = TMS
12
11
10a
Scheme 2
Figure 1 Legend for correlation of substituent identifiers with sub-
stituent patterns.
action of Fischer carbene complexes.12 Formation of com-
pound 10a likely involves generation of isobenzofuran 8a
followed by intramolecular Diels–Alder reaction to afford
adduct 9a, which is deoxygenated to afford compound
10a.13 The origin of acetonitrile loss product 11 is unclear.
Coupling of dicyanocarbene complex 2a with alkyne al-
dehyde 7a was examined initially (Scheme 2 and Table 1,
entry A). This coupling reaction afforded enol ether 12
(0–20% yield) and the phenanthridine derivatives 10a and
11. Enol ether 12 results from a known decomposition re-
Table 1 Coupling of b-Cyanocarbene Complexes with Alkynylbenzoyl Systems
O
X
X
X
OMe
R4
R1
R2
R4
R1
R2
R4
R1
R2
R4
Bu
+
+
+
+
2 or 6
+ 7
N
N
N
N
N
15
13
10
14
R3
R3
R3
R3
11
R2
H
Entrya Reactants
R1
R3
R4
X
10 (13)b
11
14
15
–
Ac
Bd
C
D
E
2a + 7a
2b + 7a
2c + 7a
2d + 7d
2e + 7d
2d + 7b
2c + 7e
6a + 7a
6b + 7a
6b + 7c
CH2CN
CH2CN
n-Pr
H
n-Bu
n-Bu
n-Bu
H
OMe
OMe
OMe
OMe
NMe2
OMe
OMe
OMe
NMe2
NMe2
40%
48%
–
36%
–
H
H
19%
–
–
H
H
–
–
–
–
–
–
–
–
53%
–
-(CH2)4-
H
21%
(42%)
39%
–
–
–
-(CH2)4-
H
H
–
–
F
-(CH2)4-
Me
NMe2
H
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
–
–
Ie
n-Pr
H
–
37%
–
J
–
–
–
–
–
–
–
20%
40%
59%
K
L
–
H
–
–
Ph
–
a Table entry letters correspond to substituent identifiers in adducts.
b The yield in parentheses is the yield for ketone 13
c Compound 12 was also formed in 0–20% yield.
d Adducts are denoted by substituent identifier a.
e See the negative result in Equation 4 for entries G and H.
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

PAPER
b-Cyanocarbene-Chromium Complexes
3663
This compound does not arise from loss of acetonitrile
from 10a since formation of this compound does not de-
pend on reaction time and since 10a is not converted to 11
under the reaction conditions. Use of the phosphine ana-
logue 2b led to only 10a and 11 (entry B), however the ra-
tio was different. The added stability of complex 2b
relative to 2a likely suppresses competing carbene com-
plex decomposition.
OMe
n-Bu
n-Pr
CH2CN
(CO)4
2c
Cr
O
+
7e
16i
NMe2
Coupling of various b-cyanocarbene complexes with 2-
alkynylbenzoyl derivatives has been examined (Table 1).
Moderately efficient formation of the net dehydrogena-
tion product 14c was observed using the monocyanocar-
bene complex 2c (entry C). The reaction was less efficient
for formation of tetracyclic compound 10d (entry D) how-
ever the reaction process was considerably more efficient
using the more stable aminocarbene complex 2e (entry E),
which afforded the ketone 13e after enamine hydrolysis.
The analogous reaction using ketone 2b was also more ef-
ficient (entry F), possibly due to the increased stability of
the isobenzofuran intermediate.14 Norbornene-carbene
complexes 2g,h (Equation 4) did not afford any identifi-
able products from coupling with alkyne 7a, possibly due
to the strain associated with this ring system. Alknylbenz-
amide 7e couples with carbene complex 2c (entry I and
Scheme 3) to afford the expected compound 14i, accom-
panied by a sizable amount of an uncyclized compound
tentatively identified as the E/Z mixture of dienylnitrile
amide 18. Formation of 18 can occur through allylic CH
activation from intermediate isobenzofuran 16i to afford
the dienylchromium species 17, which then affords the
product 18 after reductive elimination. Previous studies
have also suggested that isobenzofuran formation is more
difficult from amides versus ketones and aldehydes.15
Arylcarbene complex analogues 6a,b were also tested
(entries J–L). Similar trends were noted in the formation
of compound 15 in that higher yields were obtained using
an aminocarbene complex (entry L) or if an isobenzofu-
ran-stabilizing substituent (phenyl, entry K) is present.
OMe
OMe
n-Bu
n-Pr
n-Bu
n-Pr
CH2CN
(CO)4
CN
8i
O
Cr
H
O
NMe2
17
NMe2
OMe
OMe
n-Bu
n-Pr
n-Bu
n-Pr
CH2CN
18
N
14i
CONMe2
NMe2
Scheme 3
8a and 9a in Scheme 2) driven toward product formation
through reductive removal of the oxygen bridge by chro-
mium(0) byproducts, or (3) involvement of chromium-
complexed intermediates. In order to better evaluate the
feasibility of key Diels–Alder events, the thermodynamic
parameters of select reactions were evaluated using DFT
calculations (Scheme 4, all values are in kcal/mol). The
isobenzofuran-nitrile Diels–Alder reaction is slightly en-
dothermic in all examples depicted in Scheme 4, however
the entropic effects are less detrimental to the free energy
of the intramolecular reactions in intramolecular systems.
If the deoxygenation process (conversion of L to M) is in-
cluded in the overall thermodynamic cycle, the overall re-
action becomes exothermic. Use of a carbonyl ligand of
chromium hexacarbonyl as the hypothetical reducing
agent results in a very favorable reaction process for the
conversion of the Diels–Alder adduct to the isoquinoline.
The overall conversion of isobenzofuran intermediate J to
dihydrophenanthrene M is also now an energetically fea-
sible process.
N
H
H
X
CN
X
+
(CO)5Cr
Bu
Bu
2g,h
X
2, 10
g X = OMe
h X = NMe2
10g,h
7a
CHO
Experiments were designed that would determine the fea-
sibility of intramolecular isobenzofuran-nitrile Diels–Al-
der reactions (Scheme 5). Compound 19 was prepared16
and subjected to reaction with acid. These conditions are
expected to generate isobenzofuran intermediate 20.17
The Diels–Alder adduct 22 was not observed under these
reaction conditions. The only identifiable product from
this reaction was tentatively assigned as alkylideneph-
thalan 21. Alkylidenephthalans are often obtained from
isobenzofurans through a 1,5-hydrogen shift process.18
Equation 4
The key step for the novel annulation reactions in Table 1
is the Diels–Alder reaction between an isobenzofuran and
a nitrile, which is not expected to be favorable.5,6 The
unique success of the nitrile-isobenzofuran Diels–Alder
step in this reaction is likely due to either: (1) an unusually
favorable six-membered-ring-forming Diels–Alder reac-
tion, (2) equilibrium of isobenzofuran-nitriles and the re-
spective Diels–Alder adducts (e.g. the interconversion of
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

3664
B. K. Ghorai et al.
PAPER
Reflux in
dioxane for
12 h
Bu
∆H = +3.1
Cr(CO)5
C
N
+
+
O
O
∆G = +18.0
Me
OMe
N
CHO
1a
E
F
7a
G
OMe
O
N
O
OMe
Me
∆H = +0.8
∆G = +6.3
Bu
Me
Bu
O
O
O
O
Ph
24
O
H
N
N
C
O
H
I
N
O
N
Ph
23
x Cr(CO)3 ????
∆H = +0.5
∆G = +5.2
H
O
25
Scheme 6
C
N
J
K
∆H = –1.5
In consideration of the result depicted in Scheme 6, calcu-
lations using chromium complexed vinylisobenzofuran
intermediates were examined (Scheme 7). Both the (h5-
furan)Cr(CO) complex N and the (h6-arene)Cr(CO)3
complex O were subjected to DFT energy minimization
using the 6-31G* basis set. The arene complex O is more
stable than the furan complex N, despite the fact that this
imparts a carbonyl ylide structure to the furan ring system.
Cycloaddition of acetonitrile to the furan complex N,
leading to arene complexed adduct P is slightly exother-
mic. Initial formation of furan-complexed isobenzofurans
followed by cycloaddition to form arene-complexed ad-
ducts could be exothermic and exergonic in an intramo-
lecular reaction.
Cr(CO)6
∆G = –8.0
∆H = –2.0
O
N
∆G = –13.2
N
M
L
+ Cr(CO)6
+ CO2 + Cr(CO)5
Scheme 4
O
OH CH(OMe)2
H+
CN
CN
20
19
∆H = –9.9
∆G = –9.4
O
O
Cr(CO)3
Cr(CO)3
O
O
N
N
O
∆H = –0.6
∆G = +13.4
∆H = +9.3
∆G = +22.8
CN
22
MeCN
MeCN
21
Scheme 5
Based on observations of related reaction processes,2b
there is some degree of stabilization imparted to the
isobenzofuran intermediate (see Scheme 6). In reference
2b it was noted that the three-component coupling of alky-
nylbenzaldehyde 7a, carbene complex 1a, and N-phenyl-
maleimide (24) actually produced an adduct 25 in
moderate yield (52%) under the conditions noted in
Scheme 6. Based on previous descriptions of isobenzo-
furans,14 the free isobenzofuran intermediate 23 should
not have a lifetime of more than a few seconds at 100 °C,
and thus the reaction in Scheme 6 should not have yielded
any Diels–Alder adducts. The successful use of these con-
ditions suggest that isobenzofuran intermediates generat-
ed through chromium carbene–alkyne coupling reactions
have substantially greater lifetimes than typical isobenzo-
furans, possibly due to stabilization by complexation to
chromium.
N
O
P
Me
Cr(CO)3
Scheme 7
Based on the studies in Schemes 6 and 7, the success of
this nitrile-isobenzofuran Diels–Alder reaction could be
attributed to either of two scenarios: (1) presence of a suit-
able reductant that can drive the unfavorable isobenzofu-
ran/Diels–Alder adduct equilibrium toward cycloadduct
formation through a deoxygenation–aromatization pro-
cess, or (2) initial formation of furan-complexed isoben-
zofuran intermediate which undergoes
energetically favorable Diels–Alder reaction to afford the
arene-complexed Diels–Alder adduct.
a
more
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

PAPER
b-Cyanocarbene-Chromium Complexes
IR (neat): 2235, 2008, 1883 cm–1.
3665
In summary, nitrile-isobenzofuran Diels–Alder reactions,
a previously undocumented reaction process, can be use-
1H NMR (CDCl3): d = 4.70 (s, 3 H), 4.45 (m, 1 H), 2.45–2.78 (m, 4
ful for phenanthridine synthesis.19 Although the reaction H), 1.60–1.78 (m, 6 H), 1.25–1.55 (m, 12 H), 0.97 (br t, J = 6.8 Hz,
9 H).
produces the final phenanthridines in mediocre yield, the
13C NMR (CDCl3): d = 338.6 (d), 222.2, 221.9, 116.8, 64.6, 58.3,
27.8 (d), 25.4, 24.3 (d), 18.8, 13.6.
complex structure arises through the coupling of simple
and readily available components in a single reaction pro-
cess proceeding through several distinct mechanistic
events. All of our efforts to understand the reaction com-
putationally have led us to the conclusion that this reac-
tion should have never worked at all. Considerable efforts
to optimize the efficiency of this process have to date pro-
duced only mediocre yields, however given the thermody-
namic unfavorability of the key step, the difficulty in
optimization of this reaction is understandable.
Carbene Complex 2c
General Procedure 1 was followed using carbene complex 1c (0.52
g, 1.78 mmol), n-BuLi (1.1 mL of a 1.6 M hexane solution, 1.76
mmol) and iodoacetonitrile (0.45 g, 2.67 mmol). Purification using
flash chromatography (silica gel, hexane–EtOAc, 9:1) gave 2c
(0.507 g, 87%).
IR (neat): 2240, 2063, 1919 cm–1.
1H NMR (CDCl3): d = 4.85 (s, 3 H), 4.22 (m, 1 H), 2.39 (t, J = 6.5
Hz, 1 H), 1.2–1.8 (m, 5 H), 0.95 (t, J = 6.5 Hz, 3 H).
1H and 13C NMR spectra were recorded on a Varian 200 MHz or a
400 MHz spectrometer. Chemical shifts are reported in parts per
million (d) downfield from the reference tetramethylsilane. Cou-
pling constants (J) are reported in Hertz (Hz). A PerkinElmer
1720X spectrometer was used to record the IR spectra and band po-
sitions are reported in reciprocal centimeters (cm–1). Only key diag-
nostic bands are reported, C–H stretching frequencies in the region
2800–3100 cm–1 are not reported. Mass spectra (EI) were obtained
at the University of California at Riverside or at the University of
Nebraska. Flash column chromatography was performed using
thick walled glass columns and ‘flash grade’ silica gel. TLC was
done using precoated 0.25 mm silica gel plates purchased from
Sorbtech. The relative proportion of solvents in mixed chromatog-
raphy solvents refers to the v/v ratio. All commercially available re-
agents were purchased in reagent grade and used without
purification. Et2O, THF and dioxane were distilled from sodium
benzophenone ketyl. All reactions were performed in an inert atmo-
sphere created by a slight positive pressure (ca. 0.1 psi) of N2.
Carbene Complexes 2d and 6a;20 General Procedure 2
1. Dipotassium Pentacarbonylchromate: Graphite (64 equiv) was
heated at 150–160 °C while being stirred under argon for 2 h. The
graphite was cooled to r.t. and potassium (8 equiv) was added as
tiny pieces under a positive flow of argon. The mixture was heated
to 160 °C with stirring for 1 h. THF was added to the bronze colored
material and cooled to –78 °C. Cr(CO)6 (3.5 equiv) was then added
under a positive flow of argon. The mixture was stirred for 30 min
at –78 °C and placed in an ice-bath until a thick slurry of product
was formed. This mixture was directly used in the next step.
2. Tetramethylammonium Salt of the Chromium Carbene Complex:
To the solution of dipotassium pentacarbonylchromate in THF at
–78 °C obtained from step 1, the acid chloride (1 equiv) in THF was
added dropwise. The resulting mixture was stirred at –78 °C for 15
min, at 0 °C for 1.5 h, and at r.t. for 1 h. The solvent was removed
under reduced pressure. Cold H2O was added to the residue and fil-
tered through Celite. To the filtrate was added a sat. aq solution of
Me4NBr, leading to immediate precipitation of the ammonium salt.
The precipitate was removed by extracting the aqueous layer with
CH2Cl2. The organic layer was then dried (Na2SO4) and the solvent
removed on a rotary evaporator to give a pale yellow solid.
Carbene Complexes 2a–c; General Procedure 1
To a solution of carbene complex 1a–c (1 mmol) in Et2O (20 mL)
was added n-BuLi (1 mmol) at –78 °C. After 0.5 h, this solution was
added to a solution of haloacetonitrile (10 mmol) in THF (20 mL)
at 0 °C by means of canula. The mixture was stirred for 2 h at 0 °C.
The solvent was removed in a rotary evaporator. Flash column chro-
matography of the crude product over silica gel gave the product
2a–c. Complexes 2a–c were quite unstable and were used within a
few hours after purification.
3. Alkylation of Tetramethylammonium Acylate Salt: To a solution
of the ammonium salt (1 equiv) in CH2Cl2 obtained in step 2, was
added methyl triflate (1.2 equiv) at 0 °C. The mixture was then
stirred at 0 °C for 0.5 h and at r.t. for 1 h. The mixture was filtered
through Celite, washed with sat. aq NaHCO3 solution, H2O, brine,
and dried (Na2SO4). The solvent was removed on a rotary evapora-
tor to yield the carbene complex. Purification was done by flash col-
umn chromatography using hexane–EtOAc (4:1) as the eluting
solvent. Both of these complexes were highly unstable and used
within a few hours after purification.
Carbene Complex 2a
General Procedure 1 was followed using carbene complex 1a
(0.400 g, 1.6 mmol), n-BuLi (2.9 mL of a 1.4 M hexane solution,
4.0 mmol) and bromoacetonitrile (0.28 mL, 4.0 mmol). Purification
using flash chromatography (silica gel, hexane–EtOAc, 3:1) gave
carbene complex 2a (0.400 g, 46%) contaminated with 5–10% of
bromoacetonitrile.
IR (neat): 2259, 2066, 1919, 1454 cm–1.
1H NMR (CDCl3): d = 4.90 (s, 3 H), 4.50 (quintet, J = 6.6 Hz, 1 H),
2.65 (dd, J = 17.4, 6.6 Hz, 2 H), 2.58 (dd, J = 17.4, 6.6 Hz, 2 H).
Carbene Complex 2d
General Procedure 2 was followed using dipotassium pentacarbon-
ylchromate [prepared from graphite (2.34 g, 195 mmol), potassium
metal (0.95 g, 24.3 mmol), and Cr(CO)6 (2.42 g, 11.0 mmol)], cis-
2-cyanocyclohexanecarbonyl chloride (0.55 g, 3.2 mmol),21 and
methyl triflate (0.63 g, 3.84 mmol). The crude product was purified
by flash chromatography to give 2d as a dark yellow solid (0.670 g,
61%).
13C NMR (CDCl3): d = 353.9, 222.6, 215.8, 116.5, 69.0, 59.3, 19.3.
IR (neat): 2264, 2063, 1919 cm–1.
Carbene Complex 2b
1H NMR (CDCl3): d = 4.90 (s, 3 H), 3.96 (m, 1 H), 3.08 (m, 1 H),
General Procedure 1 was followed using carbene complex 1b (0.30
g, 0.92 mmol),11 n-BuLi (0.44 mL of a 1.6 M hexane solution, 0.70
mmol) and bromoacetonitrile (0.85 g, 0.71 mmol). Purification us-
ing flash chromatography (silica gel, hexane–EtOAc, 4:1) gave 2b
(0.14 g, 88%) and starting material 1b (0.16 g).
1.58–2.20 (m, 6 H), 1.25–2.20 (m, 6 H), 1.25–1.58 (m, 2 H).
13C NMR (CDCl3): d = 358.3, 215.6, 214.2, 130.8, 69.6, 68.2, 30.6,
29.6, 25.6, 24.8, 22.0.
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

3666
B. K. Ghorai et al.
PAPER
Carbene Complex 6a
Coupling of Carbene Complex 2a with 2-hex-1-ynylbenzalde-
hyde (7a) (Table 1, Entry A)
General Procedure 2 was followed using dipotassium pentacarbon-
ylchromate [prepared from graphite (2.34 g, 195 mmol), potassium
metal (0.95 g, 24.3 mmol) and Cr(CO)6 (2.42 g, 11.0 mmol)], acid
chloride 5a (0.53 g, 3.2 mmol), and methyl triflate (0.63 g, 3.84
mmol). The crude product was purified by passage through a short
silica gel column to give 6a (0.378 g, 35%) and was immediately
used in the next step as it was unstable.
General Procedure 4 was followed using carbene complex 2a (100
mg, 0.30 mmol) and 2-hex-1-ynylbenzaldehyde (7a;24 60 mg, 0.32
mmol). The crude product was purified using flash chromatography
on silica gel with hexane–EtOAc (1:1) as eluent to yield products
10a (36 mg, 40%), 11 (29 mg, 36%), and a compound tentatively
identified as enol ether 12 (5 mg, 13%, yield varies widely between
experimental runs).
IR (KBr): 2068, 1930 cm–1.
1H NMR (CDCl3): d (poorly resolved) = 7.52–7.80 (m, 2 H), 7.30–
7.50 (m, 2 H), 4.95 (s, 3 H).
10a
IR (neat): 2239, 1615, 1551 cm–1.
1H NMR (CDCl3): d = 8.99 (s, 1 H), 8.09 (d, J = 8.4 Hz, 1 H), 7.94
(d, J = 8.4 Hz, 1 H), 7.67 (t, J = 7.5 Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1
H), 3.84 (s, 3 H), 3.45 (m, 1 H), 3.00–3.30 (m, 2 H), 2.65–3.00 (m,
2 H), 2.18–2.5 (m, 2 H), 1.10–1.50 (m, 4 H), 0.80 (t, J = 7 Hz, 3 H).
13C NMR (CDCl3): d = 156.8, 148.4, 144.6, 133.0, 130.5, 128.8,
128.3, 126.7, 124.5, 118.4, 118.1, 58.1, 36.6, 31.0, 30.4, 28.2, 22.5,
18.8, 13.7.
Carbene Complexes 2e and 6b; General Procedure 3
To the solution of dipotassium pentacarbonylchromate (prepared
using general procedure 2, step 1) in THF at –78 °C, the amide (1
equiv) in THF was added dropwise. The resultant mixture was
stirred at –78 °C for 0.5 h, warmed to 0 °C for 1 h, and cooled to
–78 °C. Chlorotrimethylsilane (3 equiv) was then added. After 0.5
h, the mixture was warmed to r.t. Neutral Al2O3 (2.5 g/1 mmol of
amide) was added to absorb the product, and the solvent was re-
moved under reduced pressure. The resulting dry powder was puri-
fied by flash chromatography on a silica gel column using hexane–
CH2Cl2 (1:1) as eluent.
MS: m/z (%) = 307 (M+ + 1, 13), 306 (M+, 55), 291 (M+ – CH3, 10),
266 (45), 210 (100), 180 (21), 167 (24).
HRMS: m/z calcd for C20H22N2O: 306.17322; found: 306.17373.
11
Carbene Complex 2e
IR (neat): 2957, 2871, 1616, 1495 cm–1.
General Procedure 3 was followed using dipotassium pentacarbon-
ylchromate [prepared from graphite (1.78 g, 148 mmol), potassium
metal (0.72 g, 18.5 mmol) and Cr(CO)6 (2.42 g, 8.4 mmol)], cis-
N,N-dimethyl-2-cyanocyclohexanecarboxamide (0.82 g, 4.55
mmol),22 and chlorotrimethylsilane (1.50 g, 14.0 mmol). The crude
product was purified by flash chromatography to give 2e (0.650 g,
40%).
IR (neat): 2053, 1903 cm–1.
1H NMR (CDCl3): d = 3.98 (s, 3 H), 3.93 (br s, 1 ), 3.55 (s, 3 H),
3.29 (br s, 1 H), 1.3–2.3 (m, 8 H).
1H NMR (CDCl3): d = 9.10 (br s, 1 H), 8.69 (d, J = 8.4 Hz, 1 H),
8.12 (d, J = 9.0 Hz, 1 H), 8.04 (d, J = 7.7 Hz, 1 H), 7.84 (t, J = 7.3
Hz, 1 H), 7.71 (t, J = 7.3 Hz, 1 H), 7.44 (d, J = 9.0 Hz, 1 H), 4.01 (s,
3 H), 3.35 (t, J = 8.0 Hz, 2 H), 1.75–1.98 (m, 2 H), 1.50–1.75 (m, 2
H), 1.09 (t, J = 7.5 Hz, 3 H).
13C NMR (CDCl3): d = 157.1, 150.8, 139.8, 133.2, 130.3, 129.2,
128.8, 127.3, 127.0, 126.6, 113.3, 56.4, 30.8, 28.2, 23.2, 13.9.
MS: m/z (%) = 267 (M+ + 2, 6), 266 (M+ + 1, 26), 265 (M+, 54), 222
(100), 206 (5), 191 (7), 179 (29), 152 (7).
13C NMR (CDCl3): d = 280.0, 217.2, 213.8, 131.1, 62.0, 56.1, 46.7,
HRMS: m/z calcd for C18H19NO: 265.146664; found: 265.145879.
31.7, 31.3, 28.2, 26.2, 22.3.
1225
IR (neat): 2248 (m), 1652 (s) cm–1.
Carbene Complex 6b
General Procedure 3 was followed using dipotassium pentacarbon-
ylchromate [prepared from graphite (2.34 g, 195 mmol), potassium
metal (0.95 g, 24.3 mmol) and Cr(CO)6 (2.42 g, 11.0 mmol)], amide
5b23 (1.04 g, 6.0 mmol) and chlorotrimethylsilane (1.95 g, 18.0
mmol). The crude product was purified by flash chromatography to
give 6b (1.35 g, 64%).
IR (neat): 2057, 1918 cm–1.
1H NMR (CDCl3): d = 7.55–7.78 (m, 2 H), 7.34 (d, J = 8 Hz, 1 H),
6.95 (d, J = 8 Hz, 1 H), 4.13 (s, 3 H), 3.19 (s, 3 H).
1H NMR (CDCl3): d = 6.40 (br s, 1 H), 3.73 (s, 3 H), 3.28 (s, 2 H),
3.14 (s, 2 H).
Coupling of Carbene Complex 2b with 2-Hex-1-ynylbenzalde-
hyde (7a) (Entry B)
General Procedure 4 was followed using carbene complex 2b
(0.165 g, 0.33 mmol) and 2-hex-1-ynylbenzaldehyde (7a;24 0.056
g, 0.30 mmol). The crude product was purified using flash chroma-
tography on silica gel with hexane–EtOAc (1:1) as eluent to yield
products 10a (0.044 g, 48%) and 11 (0.015 g, 19%).
13C NMR (CDCl3): d = 272.3, 216.1, 213.8, 154.7, 134.0, 133.0,
126.7, 121.4, 100.6, 51.4, 46.4.
Coupling of Carbene Complex 2c with 2-Hex-1-ynylbenzalde-
hyde (7a) (Entry C)
Coupling of b-Cyanocarbene Complexes 2 or 6 with o-Alkynyl-
benzoyl Derivatives 7; General Procedure 4
General Procedure 4 was followed using carbene complex 2c (0.150
g, 0.45 mmol) and 2-hex-1-ynylbenzaldehyde (7a;24 0.075 g, 0.40
mmol). In this experiment Ph3P (0.118 g, 0.45 mmol) was added
and toluene was used as the solvent (in place of dioxane). The crude
product was purified using flash chromatography on silica gel using
hexane–EtOAc (4:1) as eluent to yield product 14c (0.065 g, 53%).
To a refluxing solution of o-alkynylbenzoyl derivative 7 (1 equiv)
in dioxane (10 mL) under argon was added dropwise a 0.05 M so-
lution of carbene complex 2 or 6 (1.1 equiv) in dioxane over a 2 h
period. After the addition was complete, the mixture was allowed to
reflux for a period of 16–24 h. The mixture was cooled to r.t. and
concentrated on a rotary evaporator. EtOAc (25 mL) was added and
the residue was filtered through Celite. The solvent was removed on
a rotary evaporator and the crude products were purified by flash
column chromatography.
IR (neat): 2958, 2871, 1591, 1446 cm–1.
1H NMR (CDCl3): d = 9.15 (s, 1 H), 8.71 (d, J = 8 Hz, 1 H), 8.04 (d,
J = 8.0 Hz, 1 H), 7.96 (s, 1 H), 7.83 (t, J = 7.7 Hz, 1 H), 7.68 (t,
J = 7.7 Hz, 1 H), 3.85 (s, 3 H), 3.43 (t, J = 8.0 Hz, 2 H), 2.87 (t,
J = 7.7 Hz, 2 H), 1.70–1.93 (m, 4 H), 1.52–1.70 (m, 2 H), 1.05 (t,
J = 7.3 Hz, 3 H), 1.03 (t, J = 7.3 Hz, 3 H).
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

PAPER
b-Cyanocarbene-Chromium Complexes
3667
13C NMR (CDCl3): d = 156.8, 152.4, 142.8, 137.3, 133.3, 132.4,
130.3, 129.5, 129.3, 127.3, 126.5, 126.0, 122.4, 61.6, 32.4, 31.8,
28.7, 23.2 (2 C), 14.2, 13.9.
Coupling of Carbene Complex 2d with 1-(2-Hex-1-ynylphe-
nyl)ethanone (7b) (Entry F)
General Procedure 4 was followed using carbene complex 2d (0.10
g, 0.29 mmol) and 1-(2-hex-1-ynylphenyl)ethanone (7b;27 0.052 g,
0.26 mmol). The crude product was purified using flash chromatog-
raphy over silica gel with hexane–EtOAc (1:1) as eluent to yield
product 10f (0.035 g, 40%).
MS: m/z (%) = 309 (M+ + 2, 3), 308 (M+ + 1, 20), 307 (M+, 59), 292
(M+ – CH3, 4), 264 (100), 234 (16), 222 (9), 204 (9), 192 (13), 165
(5).
HRMS: m/z calcd for C21H25NO: 307.193615; found: 307.194478.
IR (neat): 2930, 1627 cm–1.
Coupling of Carbene Complex 2c with 2-Ethynylbenzaldehyde
(7d) (Entry D)
General Procedure 4 was followed using carbene complex 2c (0.345
g, 1.0 mmol) and 2-ethynylbenzaldehyde (7d;26 0.117 g, 0.90
mmol). The crude product was purified using flash chromatography
on silica gel with hexane–EtOAc (4:1) as eluent to yield product
10d (0.050 g, 21%).
1H NMR (CDCl3): d = 8.07 (d, J = 8.0 Hz, 2 H), 7.40–7.60 (m, 2 H),
3.75 (s, 3 H), 3.20 (m, 1 H), 2.93 (s, 3 H), 2.55–2.92 (m, 3 H), 1.10–
1.60 (m, 12 H), 0.77 (t, J = 7.0 Hz, 3 H).
13C NMR (CDCl3): d = 159.4, 154.3, 149.6, 133.1, 128.6, 128.1,
126.3, 125.9, 125.2, 125.1, 116.5, 57.6, 41.8, 36.4, 31.0, 28.2, 26.3,
25.8, 24.8, 22.8, 22.7, 22.3, 13.8.
MS: m/z (%) = 337 (M+ + 2, 2), 336 (M+ + 1, 26), 335 (M+, 100),
320 (M+ – CH3, 31), 306 (M+ – C2H5, 9), 292 (35), 280 (22), 262
(10), 224 (10), 145 (15).
IR (neat): 2933, 1634 cm–1.
1H NMR (CDCl3): d = 8.97 (s, 1 H), 8.01 (d, J = 8.0 Hz, 1 H), 7.92
(d, J = 8.0 Hz, 1 H), 7.68 (t, J = 7.5 Hz, 1 H), 7.53 (t, J = 7.5 Hz, 1
H), 6.08 (s, 1 H), 3.57 (s, 3 H), 3.45 (br s, 1 H, line width at half
height = 15 Hz), 2.84 (m, 1 H, line width at half height = 12 Hz),
2.28 (m, 1 H), 1.35–1.90 (m, 7 H).
HRMS: m/z calcd for C23H29NO: 335.224.915; found: 335.225687.
Coupling of Carbene Complex 2c with Alkynylbenzamide 7e
(Entry I)
The cis stereochemistry was assigned based on the relatively narrow
line widths for the ring junction protons at d = 3.45 and 2.84. In the
trans-isomer, these protons would be axial and would couple to two
other axial protons, and should feature much wider and discernable
patterns.
13C NMR (CDCl3): d = 164.8, 146.1, 131.8, 130.3, 128.4, 127.3,
126.4, 124.5, 122.0, 89.1, 55.3, 41.8, 39.4, 26.4, 25.2, 24.1, 23.9.
General Procedure 4 was followed using carbene complex 1c (0.485
g, 1.32 mmol) and alkynylbenzamide 7e28 (0.245 g, 1.00 mmol).
The crude product was purified using hexane–EtOAc (4:1) as the
eluent to yield the highly fluorescent product 14i (0.135 g, 37%).
Two additional nonfluorescent compounds were also isolated (total
0.160 g, 43%) and assigned as isomers of 18; a small amount of the
slowest-running compound was isomerically pure.
MS: m/z (%) = 266 (M+ + 1, 18), 265 (M+, 99), 264 (27), 263 (M+ –
H2, 100), 248 (40), 236 (27), 234 (27), 222 (35), 210 (99), 192 (36),
180 (16), 166 (29).
14i
IR (neat): 1579 (m) cm–1.
1H NMR (CDCl3): d = 8.57 (d, J = 8.8 Hz, 1 H), 8.21 (dd, J = 8.8,
1.8 Hz, 1 H), 7.68 (td, J = 8.8, 1.8 Hz, 1 H), 7.63 (s, 1 H), 7.55 (td,
J = 8.8, 1.8 Hz, 1 H), 3.80 (s, 3 H), 3.34 (t, J = 7.8 Hz, 2 H), 3.10 (s,
6 H), 2.78 (t, J = 7.6 Hz, 2 H), 1.77 (m, 4 H), 1.57 (m, 2 H), 1.03 (t,
J = 7.4 Hz, 3 H), 1.01 (t, J = 7.2 Hz, 3 H).
HRMS: m/z calcd for C18H19NO: 265.146664; found: 265.145504.
Coupling of Carbene Complex 2e with 2-Ethynylbenzaldehyde
(7d) (Entry E)
General Procedure 4 was followed using carbene complex 2e (0.355
g, 1.0 mmol) and 2-ethynylbenzaldehyde (7d;26 0.116 g, 0.89
mmol). In this experiment Ph3P (0.262 g, 1.0 mmol) and toluene
was used as the solvent (in place of dioxane). The crude product was
purified using flash chromatography on silica gel with hexane–
EtOAc (1:1) as eluent to yield product 13e (0.095 g, 42%).
13C NMR (CDCl3): d = 159.7, 154.7, 141.8, 136.8, 135.8, 131.4,
128.9, 127.3, 127.1, 126.4, 125.5, 121.8, 120.7, 61.5, 42.5, 32.4,
31.7, 28.9, 23.6, 23.3, 14.3, 13.9.
MS: m/z (%) = 350 (M+, 100), 335 (38), 321 (24).
HRMS: m/z calcd for C23H30N2O: 350.23581; found: 350. 23678.
IR (neat): 2933, 1713, 1623 cm–1.
18
1H NMR (CDCl3): d = 9.16 (s, 1 H), 7.10 (d, J = 7.7 Hz, 1 H), 7.70–
7.85 (m, 2 H), 7.61 (m, 1 H), 4.02 (d, J = 21.8 Hz, 1 H), 3.76 (d,
J = 21.8 Hz, 1 H), 3.49 (ddd, J = 10.7, 5.0, 3.8 Hz, 1 H), 3.06 (br s,
1 H, line width at half height = 10 Hz), 2.44 (m, 1 H), 2.07 (m, 1 H),
1.79 (m, 1 H), 1.40–1.70 (m, 4 H), 1.25 (m, 1 H).
IR (neat): 2246 (m), 1640 (s) cm–1.
1H NMR (CDCl3): d = 7.40–7.15 (m, 4 H), 6.42 (s, 1 H), 3.44 (s, 3
H), 3.21 (s, 2 H), 3.03 (s, 3 H), 2.81 (s, 3 H), 2.30–2.15 (m, 4 H),
1.55–1.20 (m, 6 H), 0.91 (t, J = 7.0 Hz, 3 H), 0.82 (t, J = 7.8 Hz, 3
H).
13C NMR (CDCl3): d = 170.6, 154.6, 137.5, 136.7, 133.4, 130.7,
129.1, 128.5, 127.5, 126.1, 118.7, 111.6, 56.3, 38.5, 34.6, 32.9,
30.1, 29.5, 22.8, 21.6, 16.6, 14.1, 13.7.
The cis stereochemistry was assigned based on the appearance of
the ring junction protons at d = 3.49 (ddd, J = 10.7, 5.0, 3.8 Hz), and
d = 3.06 (br s, line width at half height = 10 Hz). In the trans isomer,
these protons would be axial and would couple to two other axial
protons, and should feature much wider and discernable patterns.
The pattern at d = 3.49 is consistent with an axial proton coupled to
one other axial proton and two equatorial protons, as expected in the
cis isomer. The pattern at d = 3.06 is consistent with contribution
from multiple small couplings, as expected for an equatorial proton.
13C NMR (CDCl3): d = 209.4, 152.6, 151.4, 134.7, 131.0, 128.5,
127.1, 126.8, 121.8, 120.4, 48.1, 45.8, 38.7, 31.8, 26.0, 24.4, 22.0.
MS: m/z (%) = 252 (M+ + 1, 23), 251 (M+, 100), 234 (5), 222 (38),
208 (15), 196 (97), 180 (49), 167 (41), 152 (15), 115 (19).
Coupling of Carbene Complex 6a with 2-Hex-1-ynylbenzalde-
hyde (7a) (Entry J)
General Procedure 4 was followed using carbene complex 6a
(0.385 g, 1.10 mmol) and 2-hex-1-ynylbenzaldehyde (7a;24 0.186 g,
1.0 mmol). The crude product was purified using flash chromatog-
raphy on silica gel with hexane–EtOAc (9:1) as eluent to yield prod-
uct 15j (0.130 g, 40%).
IR (neat): 1615 (m), 1590 (m), 1519 (m), 146 (m) cm–1.
1H NMR (CDCl3): d = 9.61 (overlapping s and d, J = 8.0 Hz), 8.84
(d, J = 8.5 Hz, 1 H), 8.21 (t, J = 7.7 Hz, 2 H), 8.00 (t, J = 7.4 Hz, 1
HRMS: m/z calcd for C17H17NO: 251.131014; found: 251.130288.
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

3668
B. K. Ghorai et al.
PAPER
H), 7.82 (m, 3 H), 4.00 (s, 3 H), 3.51 (t, J = 8.1, 2 H), 1.88 (m, 2 H),
1.62 (sextet, J = 7.3 Hz, 2 H), 1.03 (t, J = 7.3 Hz, 3 H).
13C NMR (CDCl3): d = 154.7, 150.1, 133.7, 130.5, 129.3, 127.8,
127.6, 127.3, 126.8, 126.1, 125.3, 121.9, 61.8, 31.7, 28.7, 23.0,
13.7.
Acknowledgment
This research was supported by the NIH Score Program and the Pe-
troleum Research Fund, Administered by the American Chemical
Society.
MS: m/z = 315 (M+, 70), 272 (M+ – C3H7, 100), 229 (29), 185 (19),
316 (21).
References
HRMS: m/z calcd for C22H21NO: 315.16232; found: 315.16012.
(1) For a preliminary account of this work, see: Ghorai, B. K.;
Jiang, D.; Herndon, J. W. Org. Lett. 2003, 5, 4261.
(2) (a) For the latest examples of this reaction, see: Li, R.;
Zhang, L.; Camacho-Davila, A.; Herndon, J. W.
Tetrahedron Lett. 2005, 46, 5117. (b) For the first example,
see: Jiang, D.; Herndon, J. W. Org. Lett. 2000, 2, 1267.
(3) Most examples involve electron-deficient nitriles; recent
examples include: (a) Volle, J. N.; Schlosser, M. Eur. J.
Org. Chem. 2002, 1490. (b) Junge, H.; Oehme, G.
Tetrahedron 1998, 54, 11027.
(4) Diels–Alder adducts have only been characterized by
combustion analysis and IR spectra, and other structural
alternatives were not considered: Tagmazyan, K. T.;
Mkrtchyan, R. S.; Babayan, A. T. J. Org. Chem. USSR 1974,
10, 1657.
Coupling of Carbene Complex 6b with 2-Hex-1-ynylbenzalde-
hyde (7a) (Entry K)
General Procedure 4 was followed using carbene complex 6b
(0.385 g, 1.10 mmol) and 2-hex-1-ynylbenzaldehyde (7a;24 0.186 g,
1.0 mmol). The crude product was purified using flash chromatog-
raphy on silica gel with hexane–EtOAc (9:1) as eluent to yield prod-
uct 15k (0.130 g, 40%).
IR (neat): 2915, 1940, 1615, 1379 cm–1.
1H NMR (CDCl3): d = 9.44 (m, 1 H), 9.38 (s, 1 H), 8.79 (d, J = 8.4
Hz, 1 H), 8.03–8.20 (m, 2 H), 7.60–7.84 (m, 4 H), 3.53 (t, J = 7.8
Hz, 2 H), 3.19 (s, 6 H), 1.55–1.75 (m, 2 H), 1.25–1.50 (m, 2 H), 0.91
(t, J = 7.0 Hz, 3 H).
13C NMR (CDCl3): d = 151.0, 147.9, 141.2, 135.1, 133.6, 132.5,
132.3, 129.4, 128.6, 127.7, 127.1, 126.4, 126.3, 125.9, 125.7, 124.3,
122.6, 44.3 (2 C), 32.1 (2 C), 23.1, 13.9.
(5) Hassner, A.; Fischer, B. Heterocycles 1993, 35, 1441.
(6) Whitney, S. E.; Winters, M.; Rickborn, B. J. Org. Chem.
1990, 55, 929.
(7) For a related process using a-bromoesters, see: Casey, C. P.;
Anderson, R. L. J. Organomet. Chem. 1974, 73, C28.
(8) Aminocarbene complexes are about 10 pKa units less acidic
than the corresponding alkoxycarbene complexes:
Bernasconi, C. F.; Leyes, A. E.; Ragains, M. L.; Shi, Y.;
Wang, H.; Wulff, W. D. J. Am. Chem. Soc. 1998, 120, 8632.
(9) (a) Semmelhack, M. F.; Lee, G. R. Organometallics 1987, 6,
1839. (b) Reed, A. D.; Hegedus, L. S. Organometallics
1997, 16, 2313.
MS: m/z (%) = 330 (M+ + 2, 4), 329 (M+ + 1, 26), 328 (M+, 86), 313
(M+ – CH3, 8), 286 (22), 285 (100), 271 (85), 269 (53), 254 (10),
241 (16), 215 (6), 142 (13).
HRMS: m/z calcd for C23H24N2: 328.193949; found: 328.193884.
Coupling of Carbene Complex 6b with (2-Hex-1-ynylphe-
nyl)phenylmethanone (7c)29 (Entry L)
General Procedure 4 was followed using carbene complex 6b
(0.088 g, 0.25 mmol) and (2-hex-1-ynylphenyl)phenylmethanone
(2c; 0.055 g, 0.21 mmol). The crude product was purified using
flash chromatography on silica gel with hexane–EtOAc (3:1) as elu-
ent to yield product 15l (0.051 g, 60%).
(10) Schwindt, M. A.; Lejon, T.; Hegedus, L. S. Organometallics
1990, 9, 2814.
(11) Xu, Y. C.; Wulff, W. D. J. Org. Chem. 1987, 52, 3263.
(12) (a) McDonald, F. E.; Schultz, C. C.; Chatterjee, A. K.
Organometallics 1995, 14, 3628. (b) Aumann, R.;
Hinterding, P. Chem. Ber. 1990, 123, 2047. (c) Soderberg,
B. C.; Turbeville, M. J. Organometallics 1991, 10, 3951.
(13) Metal carbonyls perform similar reductions: Mitchell, R. H.;
Ward, T. R. Tetrahedron 2001, 57, 3689.
IR (neat): 2957, 1940, 1574, 1377 cm–1.
1H NMR (CDCl3): d = 9.50 (m, 1 H), 8.82 (d, J = 8.0 Hz, 1 H), 8.29
(d, J = 8.0 Hz, 1 H), 8.16 (m, 1 H), 8.02 (d, J = 8.0 Hz, 1 H), 7.50–
7.85 (m, 8 H), 3.56 (t, J = 7.5 Hz, 2 H), 3.23 (s, 6 H), 1.55–1.80 (m,
2 H), 1.25–1.50 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3 H).
(14) For a review of isobenzofurans, see: Friedrichsen, W. Adv.
13C NMR (CDCl3): d = 157.9, 148.0, 140.2, 140.0, 134.8, 133.9,
132.6, 132.4, 130.4 (2 C), 128.6, 128.5, 128.2 (3 C), 127.0, 126.7,
126.0, 125.9, 125.8, 125.7, 124.3, 122.1, 44.4 (2 C), 32.4, 32.2,
23.2, 13.9.
Heterocycl. Chem. 1999, 73, 1.
(15) Ghorai, B. K.; Herndon, J. W. Organometallics 2003, 22,
3951.
(16) This compound was prepared from o-tolunitrile in a three-
step sequence involving: (1) deprotonation with LDA
followed by allylation with allyl bromide, (2) oxidation of
the alkene to the aldehyde using OsO4/NaIO4, and (3)
reaction of the aldehyde with 2-(dimethoxymethyl)phen-
yllithium.
MS: m/z = 406 (M+ + 2, 3), 405 (M+ + 1, 24), 404 (M+, 80), 389
(M+ – CH3, 7), 361 (94), 347 (100), 331 (18), 316 (9), 172 (21).
HRMS: m/z calcd for C29H28N2: 404.225249; found: 404.226090.
Computational Details
(17) Berkowitz, D. B.; Choi, S.; Maeng, J. H. J. Org. Chem. 2000,
65, 847.
All compounds were built using the Gausview program. These
structures were then subjected to geometry optimization followed
by frequency calculation using the Gaussian03 program.30 All cal-
culations were performed at the B3LYP level using the 6-31G* ba-
sis set. A frequency calculation (also at the B3LYP level using the
6-31G* basis set) was performed on the geometry-optimized struc-
tures. All reaction energies refer to interconversion of energy mini-
mum conformations.
(18) Meegalla, S. K.; Rodrigo, R. Synthesis 1989, 942.
(19) For a review of phenanthridine synthesis, see:
Balasubramanian, M.; Keay, J. G. In Comprehensive
Heterocyclic Chemistry II, Vol. 5; McKillop, A. E.;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Elsevier: Oxford, 1996, 245–300.
(20) This is a variant of a literature procedure in reference 9b.
This procedure is very reliable if one is careful to cut the
potassium into small pieces and if the tetramethyl-
ammonium acylate salt is prepared prior to the alkylation
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York

PAPER
step. Otherwise we noted wide variances in the yields
b-Cyanocarbene-Chromium Complexes
3669
literature procedure: Herndon, J. W.; Zhang, Y.; Wang, K. J.
Organomet. Chem. 2001, 634, 1.
between different experimental runs.
(21) Prepared from cis-1,2-cyclohexanedicarboxylic anhydride
via amide formation (treatment with aqueous ammonia),
followed by amide dehydration (Ac2O), followed by acid
chloride formation (oxalyl chloride).
(22) Prepared from reaction of the acid chloride (ref. 21) with
aqueous dimethylamine.
(28) This compound was prepared from Sonogashira coupling of
hex-1-yne and N,N-dimethyl-2-iodobenzamide according to
a literature procedure. See reference 15.
(29) This compound was prepared from Sonogashira coupling of
hex-1-yne and 2-iodobenzophenone according to a literature
procedure: Tovar, J. D.; Swager, T. M. J. Org. Chem. 1999,
64, 6499.
(30) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.;
Cammi, R.; Menucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.;
(23) Armarego, W. L. F.; Sharma, S. C. J. Chem. Soc. C 1970,
1600.
(24) This compound was prepared from Sonogashira coupling of
hex-1-yne and 2-bromobenzaldehyde according to a
literature procedure: Sakamoto, T.; Kondo, Y.; Miura, N.;
Hayashi, K.; Yamanaka, H. Heterocycles 1986, 24, 2311.
(25) This compound is known; however, the spectral data are
inaccessible: (Laboratorios Made S.A., Spain) Span. Patent
74-423501; Chem. Abstr. 1976, 86, 189240.
(26) This compound was prepared from Sonogashira coupling of
trimethylsilylacetylene and 2-bromobenzaldehyde followed
by desilylation according to a literature procedure: Acheson,
R. M.; Lee, G. C. M. J. Chem. Soc., Perkin Trans. 1 1987,
2321.
Raghavachari, K.; Foresman, J. B.; Cioslowki, J.; Ortiz, J.
V.; Stefanov, B. B.; Liu, A.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith,
T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, M.; Callacombe, M.; Gill, P. M. W.; Johnson, B.
G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian03 Program;
Gaussian Inc.: Pittsburgh PA, 1998.
(27) This compound was prepared from Sonogashira coupling of
hex-1-yne and 2-bromoacetophenone according to a
Synthesis 2006, No. 21, 3661–3669 © Thieme Stuttgart · New York