Rhodium-catalyzed hydrocarbonylation of a homoallylamine via n-h activation and application for synthesis of yohimbane alkaloids

Article abstract of DOI:10.1021/om500498u

We describe syntheses of n-yohimbane and alloyohimbane using Rh-catalyzed hydrocarbonylation, which provides a practical methodology to synthesize a δ-lactam from a secondary homoallyl amine. We have also observed an unexpected transformation where the am

Full text of DOI:10.1021/om500498u

Article
pubs.acs.org/Organometallics
Rhodium-Catalyzed Hydrocarbonylation of a Homoallylamine via
N−H Activation and Application for Synthesis of Yohimbane
Alkaloids
Wen-Hua Chiou,* Yu-Wei Wang, Chien-Lun Kao, Po-Chou Chen, and Chen-Chang Wu
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan, Republic of China
S
* Supporting Information
ABSTRACT: We describe syntheses of n-yohimbane and alloyohimbane
using Rh-catalyzed hydrocarbonylation, which provides a practical method-
ology to synthesize a δ-lactam from a secondary homoallyl amine. We have
also observed an unexpected transformation where the amine proton served
as a hydride to participate in hydrocarbonylation. The D-labeled experimental
results and preliminary DFT-calculations suggest that the transformation can
be rationalized by oxidative cleavage of the homoallyl amines to a metal
hydride complex.
INTRODUCTION
RESULTS AND DISCUSSION
Yohimbane alkaloids 1 (Figure 1), which are members of the
Rauwolfia alkaloid family, possess a characteristic pentacyclic
■
■
The transition metal-catalyzed cyclization reaction of alkenes
has played an important role in organic syntheses.1 Among
these catalytic cyclization reactions, Rh-catalyzed hydro-
carbonylation and hydroformylation of functionalized alkenes
provide powerful catalytic processes for the syntheses of
heterocycles as well as carbocycles.2 By means of reasonable
design, the reactions also allow the formation of some
complicated molecules in a cascade manner, which bring
about advantages of novelty, elegance, and efficiency.3 Since
Knifton has reported synthesis of a γ-lactam by Rh-catalyzed
cyclization of allyl amines, many valuable conditions have been
developed for this useful transformation.4 Krafft et al. have
reported amine-directed regioselective Rh-catalyzed hydro-
carboxylation of homoallylic amines in the presence of
hydrogen chloride and trimethylphosphite, to yield δ-lactam
derivatives in good yields.5 Alper et al. have presented that
employment of either a zwitterionic Rh complex or HRh-
(CO)(PPh3)3 in the presence of sodium borohydride and 2-
propanol could be used for conversion of allyl amines to γ-
lactams.6 Ojima et al. have described the extensive investigation
of the Rh-catalyzed hydrocarbonylation for syntheses of
azabicycles.7 These reported cyclization conditions are usually
involved with the presence of hydrogen sources, such as syn
gas, protic sources, and sodium borohydride.
During the course of our investigation on the syntheses of
yohimbane-typed alkaloids, we have observed that treatment of
a homoallylamine with Rh(I)/phosphite ligands under a neat
CO atmosphere could yield a δ-lactam, also. Here we report
our serendipitous findings and present a plausible mechanism
for the formation of lactams through hydrogen-free Rh-
catalyzed hydrocarbonylation. Preliminary studies including
isotope experiments and DFT calculations suggest that the
origin of the hydrogen for hydride addition could be best
explained by oxidative cleavage of the homoallylamine to a
metal hydride complex.
Figure 1. Structures of Yohimbane alkaloids.
indole ring framework in structure and exhibit a wide range of
crucial pharmacological activities.8 Various strategies have been
developed for the syntheses of yohimbane-type alkaloids, briefly
classified as follows: amino-Claisen rearrangement,9 aziridine-
allylsilane-mediated cyclization,10 conjugate addition/conden-
sation,11 desymmetrized ring cleavage of carbobicyclics,12
Diels−Alder cycloaddition,13 dipolar cycloaddition,14 Fry
reaction of pyridium salts,15 intramolecular Michael annula-
tion,16 nitrogen insertion,17 organotin-aided three-compound
coupling,18 photocyclization of enamides,19 radical-mediated
cyclization,20 sugar chiral auxiliary,21 and Wolff rearrange-
ment.22
We anticipate that yohimbane 1 can be obtained by
intramolecular condensation/reduction (i.e., Bischler−Napier-
alski reaction) of lactam 2, formed by Rh-catalyzed hydro-
carbonylation or carbonylation of amine 3. Alkenylamine 3 is
easily synthesized by coupling 3-indoleacetic acid and alkenyl-
amine 6 followed by reduction (Scheme 1).
Received: May 12, 2014
Published: August 7, 2014
© 2014 American Chemical Society
4240
dx.doi.org/10.1021/om500498u | Organometallics 2014, 33, 4240−4244

Organometallics
Article
Scheme 1. Retrosynthetic Analysis
Table 1. Hydrocarbonylation of Amine 3
a
b
b
entry
CO (atm)
H2 (atm)
2a, %
2b, %
1
2
3
40
60
80
40
20
0
61
56
53
28
24
25
Our synthesis commenced with the preparation of 2-
methylene-cyclohexaneacetate (5) (Scheme 2), readily available
a
Scheme 2. Synthesis of Amine 3
All reactions were run with 1.0 mmol of amine 3, Rh(acac)(CO)2 (1
b
mol %), and P(OPh)3 (2 mol %) in toluene at 65 °C. Isolated yield.
Since the formation of the Rh−H complex is essential for
triggering the subsequent corresponding reactions, it was
unanticipated that the reaction proceeded without employment
of hydrogen sources, compare to the reported methods such as
exposure of a Rh(I) salt in CO/H2 atmosphere at room
temperature24 and addition of hydrogen chloride5 or sodium
borohydride.6 Therefore, the results brought about the question
of how to form the Rh−H complex. In fact, the question did
not attract too much attention in early reports,25 but prompted
us to explore more mechanistic insights especially in pure CO
conditions. Therefore, we have performed isotope labeling
experiments in the hydrocarbonylation reactions (Table 2).
Table 2. Hydrocarbonylation of Amine 3 with Different
Additives
by Wittig olefination of commercially available 2-cyclo-
hexanoneacetate. Reaction of freshly distilled DMSO with
NaH at 70 °C for 1 h produced methylsulfinyl carbanion,
followed by addition of PPh3MeBr salt to yield a Wittig reagent
methylene triphenylphosphorane (PPh3CH2). Subsequent
addition of 2-cyclohexanoneacetate furnished alkene product 7
in 86% yield.23 Treatment of ester 5 in basic hydrolysis
conditions gave the corresponding acid, which was combined
with diphenylphosphorazidate (DPPA) and triethylamine in
the presence of tert-BuOH to afford BOC-protected amine 6 as
a Curtius rearrangement product in 75% yield over two steps.
Removal of the BOC protecting group was easily accomplished
by treating protected amine 6 with TFA in dichloromethane at
room temperature, yielding free amine 4 in 97% yield. Amine 4
was coupled with 3-indoleacetic acid using the EDC/HOBt
activation protocol to produce indoleacetamide 7 in 96% yield.
Subsequent reduction of indoleacetamide with LiAlH4
produced amine 3 in 88% yield, as the substrate in the Rh-
catalyzed hydrocarbonylation.
With alkenylamine 3 in hand, reaction of amine 3 was carried
out in the cyclized conditions, i.e., Rh(acac)(CO)2-P(OPh)3 (2
mol %) catalyst at 65 °C under 80 atm of CO and H2 (1:1) in
toluene, to produce two separable lactam diastereomers, the
major one, 2a, in 61% and the minor one, 2b, in 28% isolated
yield, respectively (entry 1, Table 1). Reaction under CO (60
atm) and H2 (20 atm) also produced the cyclized lactam
product 2a in 56% yield and product 2b in 24% yield, which
means reduction of the hydrogen partial pressure did not have a
significant effect on product distribution (entry 2). However, to
our surprise, the reaction could proceed smoothly in pure CO
conditions (80 atm), to yield product 2a in 53% yield and
product 2b in 25% yield (entry 3). The reaction with pure CO
proceeded relatively slowly with respect to that with H2 but was
not complete within 48 h.
a
b
b
entry
CO (atm)
additive
2a, %
2b, %
c
1
2
3
4
60
60
60
60
D2
40
17
36
25
14
14
19
14
d
CD3OD
d2-dione
d2-dione
e
f
a
All reactions were run with 1.0 mmol of amine 9, Rh(acac)(CO)2 (1
mol %), and P(OPh)3 (2 mol %) in toluene at 65 °C. Isolated yield.
D2 20 atm. 5% v/v CD3OD in toluene. 2,2-Dideuteriocyclohexane-
b
c
d
e
f
1,3-dione, 25 mol %. 50 mol %.
Reaction of amine 3 was carried out in CO (60 atm) and D2
(20 atm) to yield the deuterated products 2a in 40% yield and
2b in 14% yield (entry 1, Table 2). On the basis of 13C NMR
studies, the ratio of deuterated product lactam D-2b to
hydrogenated product lactam H-2b in lactam 2b was about
2.8:1, while the ratio was 2.5:1 in lactam 2a (Figure 2).26
Reaction with CD3OD additive as deuterium source reduced
the yield, providing H-incorporated lactam 2a in only 17% yield
and 2b in only 14% yield (entry 2). Employment of 2,2-
dideuteriocyclohexane-1,3-dione27 as additive (25 mol %, entry
3) did not afford any D-incorporated product either, but rather
H-incorporated product 2a in 36% yield and 2b in 19% yield.
More 2,2-dideuteriocyclohexane-1,3-dione (50 mol %, entry 4)
could not provide any D-labeled product, but gave a lower yield
(H-incorporated lactam 2a in 25% yield and 2b in 14% yield).
The presence of H-incorporated product in the reaction
under D2 indicates two different pathways are involved in
hydrocarbonylation: one with the Rh−H complex and the
4241
dx.doi.org/10.1021/om500498u | Organometallics 2014, 33, 4240−4244

Organometallics
Article
complete so that the Rh−H and the Rh−D complexes are both
present in the system.
To verify the hypotheses,30 we try to locate the
corresponding TSs by DFT calculations at the level of
LanL2DZ, using N-methyl-3-butenamine as the aminoalkene
substrate for minimizing calculation cost. Thus, two sets of
transition-state geometries (TSA and TSB) have been
obtained; one describes the processes in the pure CO conditions
(TSA) and the other describes those in the presence of a CO/D2
atmosphere (TSB). These geometries represent the transition-
state structures in the processes including oxidative cleavage of
the N−H bond (TSOC), hydride addition to the olefin (TSHD),
alkyl migration to a CO ligand (TSMIG), reductive elimination
to the lactam product (TSRE), and H−D exchange of the Rh−
H complex to the Rh−D complex (TSD2), described as follows.
In the pure CO conditions (Scheme 3), treatment of
Rh(acac)(CO)2 with P(OPh)3 under pure CO conditions gives
Scheme 3. Proposed Mechanism for Rh-Catalyzed
Hydrocarbonylation of N-Methyl-3-butenamine in a Pure
CO Atmosphere
Figure 2. Expanded 13C spectra of 2b obtained from (a) CO/D2
(Table 2, entry 1) and (b) CO/H2 (Table 1, entry 2).
other with the Rh−D complex. Apparently, since the amino
proton has appeared as the only proton source to give the Rh−
H complex, the results suggest that the Rh−H complex should
be subjected to an H−D exchange process to the Rh−D
complex, probably through D2 addition followed by H−D
elimination. In addition, although deuterium sources such as
CD3OD and 2,2-dideuteriocyclohexane-1,3-dione (entries 2, 3,
and 4, Table 2) are added in the system, there is only the H-
incorporated product. The absence of D-incorporated product
in reactions with deuterium additives excludes the possibility of
proton movement from the amine through other molecules,
finally to the metal. Therefore, based on these results, a Rh-
mediated oxidative cleavage of N−H is required for the
formation of the Rh−H complex, especially in the absence of a
hydrogen atmosphere.28
Since Krafft has reported X-ray crystallographic investigations
that disclose that a homoallylamine behaves as an N-ligand for
complexation with Rh to give a rhodium amino-olefin
complex,29 and a subsequent acyl intermediate can adopt a
trans configuration of the nitrogen with trimethylphosphite,5
these results inspired us to consider that Rh(I) undergoes
complexation with the homoallylamine and the phosphite
ligand in a pure CO atmosphere to yield a trans complex and
then transforms to an acyl-metal intermediate. Thus, taking into
account the results observed above, we propose the catalytic
cycle in the absence of a hydrogen atmosphere commences with
complexation of the metal with the homoallylamine substrate
and a ligand to a complex, which undergoes oxidative cleavage
to give the Rh−H complex. Once the Rh−H complex appears,
subsequent reactions including hydride addition, alkyl migra-
tion, and reductive elimination follow to furnish a lactam as the
final product and regenerate the metal species for the next
catalytic cycle. The Rh−H complex, derived from oxidative
cleavage of the N−H bond, is also indispensable to explain the
formation of the H-incorporated product in the presence of a
CO/D2 atmosphere. The formation of the mixture of the H- and
D-incorporated products implies the H−D exchange is not
catalyst complex A. Complexation with N-methyl-3-butenamine
affords rhodium amino-olefin complex IA, which undergoes
oxidative cleavage to yield the key Rh−H complex IIA. Hydride
addition follows to give rhodazacycle IIIA and then association
with one CO molecule to form complex IVA. Next, alkyl
migration of Rh complex IVA generates acyl intermediate VA,
followed by reductive elimination to yield lactam P as the final
product, and regenerates the catalyst complex A to complete
the whole catalytic cycle.
In the presence of a CO/D2 atmosphere (Scheme 4), the
Rh(I) salt is activated with the phosphite ligand to yield 3-
deuterio-2,4-pentadione and the active catalyst Rh−D complex
B, and then complexation with N-methyl-3-butenamine gives
rhodium amino-olefin complex IB. Rh complex IB can undergo
hydride addition to give alkylrhodium complex IIB, which is
then subject to oxidative cleavage of the N−H bond to yield
Rh−H complex IIIB. Formed by losing one CO molecule from
metal complex IIIB, complex III′B can undergo H−D exchange
with D2, to give Rh−D complex IIIB and a H−D molecule.31
Subsequent association with one CO molecule produces
dicarbonyl complex IIIB again, which continues the following
alkyl migration and reductive elimination to give the lactam
product and the metal species VB. Coordination with one CO
4242
dx.doi.org/10.1021/om500498u | Organometallics 2014, 33, 4240−4244

Organometallics
Article
not been reported yet. We have also proposed the mechanism
in which the corresponding transition states have been
supported by DFT calculations. Subsequent full calculations
on this mechanism and extension of the methodology toward
other natural products of interest are currently under way.
Scheme 4. Proposed Mechanism for Rh-Catalyzed
Hydrocarbonylation of N-Methyl-3-butenamine in a CO/D2
Atmosphere
EXPERIMENTAL SECTION
■
General Materials and Methods. All reagents, solvents, and
chemicals were purchased from commercial sources and used as soon
as possible. All solvents were dried by using appropriate drying agents
and distilled under argon before use. The reaction flasks were dried in
a 110 °C oven, allowed to cool to room temperature in a desiccator,
and assembled under an argon atmosphere. All reactions were carried
out under argon except hydrocarbonylation. TLC analyses were
carried out and visualized with 10% PMA solution or UV light.
Purifications were performed by flash chromatography on commer-
cially available silica gel. All NMR spectra, including H, 13C, DEPT,
1
gHSQC, gCOSY, and gHMBC, were recorded on a 600 or 400 MHz
NMR spectrometer.
Hydrocarbonylation. Rh(acac)(CO)2 (2.7 mg, 10.0 μmol, 1 mol
%) and P(OPh)3 (6.0 μL, 20 μmol, 2 mol %) were dissolved in
toluene (2 mL) under argon. The catalyst solution was degassed by a
freeze−thaw procedure at least three times. Substrate amine 9 (1.0
mmol, 1.00 equiv) was placed in a 50 mL bottle. The catalyst solution
was transferred to the reaction flask containing the substrate by a pipet,
followed by addition of additives. The total volume was adjusted to 20
mL with toluene. The reaction flask was placed in a 300 mL stainless
steel autoclave and then was pressurized up to the desired pressure
with CO followed by H2 or D2. The reaction mixture was stirred at 65
°C for 16−20 h. Upon completion of the reaction, the gas was
carefully released in a good ventilated hood, and the reaction mixture
was concentrated under reduced pressure to give a crude residue. The
crude product was purified by flash chromatography on silica gel using
EtOAc/n-Hex as the eluant to give the product.
2a: yellow solid; mp 161−162 °C; Rf = 0.24; EtOAc/n-Hex = 1:2.
1H NMR (600 MHz, 25 °C, CDCl3, δ): 1.31−1.37 (m, 4H, H-16,
H17, H-18, and H-19), 1.40−1.48 (m, 4H, H-16, H17, H-18, and H-
19), 1.85−1.90 (m, 1H, H-15), 1.94−1.99 (m, 1H, H-20), 2.37 (dd, J
= 6.0, 18.0 Hz, 1H, H-14), 2.42 (dd, J = 7.2, 18.0 Hz, 1H, H-14),
3.03−3.07 (m, 2H, H-6 × 2), 3.11 (dd, J = 6.6, 12.6 Hz, 1H, H-21),
3.17 (dd, J = 6.0, 12.6 Hz, 1H, H-21), 3.61 (ddd, J = 6.6, 6.6, 15.0 Hz,
1H, H-5), 3.74 (ddd, J = 4.8, 4.8, 15.0 Hz, 1H, H-5), 6.97 (s, 1H, H-2),
7.11 (t, J = 7.8 Hz, 1H, H-10), 7.17 (t, J = 7.8 Hz, 1H, H-11), 7.36 (d,
J = 7.8 Hz, 1H, H-12), 7.68 (d, J = 7.8 Hz, 1H, H-9), 9.17 (brs, 1H, H-
1). 13C NMR (150 MHz, 25 °C, CDCl3, δ): 22.4 (t, C-6), 22.8 (t, 2C,
C-17 and C-18), 26.2 (t, C-19), 28.1 (t, C-16), 32.2 (d, C-15), 32.6 (d,
C-20), 35.0 (t, C-14), 48.1 (t, C-5), 50.9 (t, C-21), 111.2 (d, C-12),
112.3 (s, C-7), 118.4 (d, C-9), 118.8 (d, C-10), 121.4 (d, C-11), 122.2
(d, C-2), 127.3 (s, C-8), 136.3 (s, C-13), 169.3 (s, C-3). EI-HRMS
(m/z): [M]+ calcd for C19H24N2O+, 296.1889; found, 296.1885 (Δ =
1.4 ppm).
molecule reproduces the original metal species B. It is worthy
to note not only Rh−H complex IIIB but also Rh−H complex
B can undergo the “hydride washed out” process, i.e., H−D
exchange, yielding Rh−D complex B. The models provide an
explanation for the origin of hydride of the Rh-catalyzed
carbonylation in the pure CO atmosphere, as well as the
appearance of both H- and D-incorporated lactam products in
the presence of D2 gas.
To complete the syntheses of alloyohimbane and yohimbane,
lactam 2a was subjected to the Bischler−Napieralski reaction
conditions, i.e., refluxing with POCl3 in benzene followed by
addition of NaBH4, resulting solely in the formation of yellow
solid 1a in 75% yield (Scheme 5). The product could be
Scheme 5. Synthesis of Alloyohimbane and Yohimbane
recrystallized in methanol to give a single crystal for X-ray
crystallography, which was determined as alloyohimbane
(CCDC 902980). Thus, the major product lactam 2a was
assigned unambiguously as a cis conjunction. Similarly,
treatment of lactam 2b with the identical reaction conditions
afforded n-yohimbane 1b in 70% isolated yield, which displayed
identical 13C NMR data to that reported in the literature.32
2b: yellow solid; mp 208−210 °C; Rf = 0.24; EtOAc/n-Hex = 1:2.
1H NMR (600 MHz, 25 °C, CDCl3, δ): 0.88−0.95 (m, 2H, H-16 and
H-19), 1.18−1.29 (m, 2H, H-17 × 2*), 1.33−1.40 (m, 2H, H-15 and
H-20), 1.62−1.66 (m, 1H, H-19), 1.70−1.76 (m, 3H, H-16 and H-18
× 2*), 2.01 (dd, J = 11.4, 17.4 Hz, 1H, H-14), 2.47 (dd, J = 3.6, 17.4
Hz, 1H, H-14), 2.89 (t, J = 11.4 Hz, 1H, H-21), 2.98−3.07 (m, 2H, H-
6 × 2), 3.11 (dd, J = 4.8, 11.4 Hz, 1H, H-21), 3.60−3.70 (m, 2H, H-5
× 2), 7.03 (s, 1H, H-2), 7.12 (t, J = 7.8 Hz, 1H, H-10), 7.18 (t, J = 7.8
Hz, 1H, H-11), 7.36 (d, J = 7.8 Hz, 1H, H-12), 7.66 (d, J = 7.8 Hz, 1H,
H-9), 8.28 (brs, 1H, H-1). 13C NMR (150 MHz, 25 °C, CDCl3, δ):
22.9 (t, C-6), 25.6 (t, 2C, C-17 and C-18), 29.7 (t, C-19), 32.6 (t, C-
16), 37.0 (d, C-15), 38.3 (d, C-20), 39.4 (t, C-14), 47.9 (t, C-5), 54.4
(t, C-21), 111.1 (d, C-12), 113.2 (s, C-7), 118.7 (d, C-9), 119.2 (d, C-
10), 121.89 (d, C-2), 121.91 (d, C-11), 127.5 (s, C-8), 136.3 (s, C-13),
169.7 (s, C-3). EI-HRMS (m/z): [M]+ calcd for C19H24N2O+,
296.1889; found, 296.1885 (Δ = 1.4 ppm).
CONCLUSION
■
We describe the syntheses of alloyohimbane and n-yohimbane
featuring a Rh-catalyzed hydrocarbonylation strategy. This
reaction proceeds under either a CO/H2 or pure CO
atmosphere. The results with deuterium additives under pure
CO gas show the essential Rh−H complex does not result from
the proton transfer of the NH through molecules to the metal
in hydrocarbonylation of a homoallylamine, but suggest an
intramolecular direct amino proton transfer from the nitrogen
atom to the rhodium atom. This process can be viewed as an
Rh-mediated oxidative cleavage of the N−H bond, which has
Computational Details. All DFT calculations were performed at
the level of LanL2DZ, using the Gaussian 09 package. All transition-
4243
dx.doi.org/10.1021/om500498u | Organometallics 2014, 33, 4240−4244

Organometallics
Article
state geometries were confirmed by vibration analyses at the same
level. Thermal corrections were calculated at 1 atm and 298.15 K in
the gas phase.
(16) Stork, G.; Livingston, D. A. Chem. Lett. 1987, 105−108.
(17) Aube, J.; Ghosh, S.; Tanol, M. J. Am. Chem. Soc. 1994, 116,
9009−9018.
(18) Yamaguchi, R.; Hamasaki, T.; Sasaki, T.; Ohta, T.; Utimoto, K.;
Kozima, S.; Takaya, H. J. Org. Chem. 1993, 58, 1136−1143.
(19) Naito, T.; Miyata, O.; Tada, Y.; Nishiguchi, Y.; Kiguchi, T.;
Ninomiya, I. Chem. Pharm. Bull. 1986, 34, 4144−4149.
(20) Kaoudi, T.; Miranda, L. D.; Zard, S. Z. Org. Lett. 2001, 3, 3125−
3127.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
All experimental procedures, characterization data, and H and
13C NMR spectra for compounds 3−7, the crystallographic
data of 1a, and calculated transition-state geometry figures. A
text file of all Cartesian coordinates of computed transition
states in .xyz format for convenient visualization. This material
is available free of charge via the Internet at http://pubs.acs.org.
(21) Isobe, M.; Fukami, N.; Goto, T. Chem. Lett. 1985, 1, 71−74.
(22) Kametani, T.; Suzuki, T.; Unno, K. Tetrahedron 1981, 37,
3819−3923.
(23) Medarde, M.; Caballero, E.; Tome,
́
F.; García, A.; Montero, M.
, R.; Feliciano, A. S. Eur. J. Med. Chem. 1993, 28, 887−892.
J.; Carron
́
(24) Leeuwen, P. W. N. M. v.; Claver, C. In Rh-Catalyzed
Hydroformylation; Leeuwen, P. W. N. M. v., Claver, C., Eds.; Kluwer
Academic Publishers: Dordrecht, 2002.
AUTHOR INFORMATION
Corresponding Author
*E-mail (W.-H. Chiou): wchiou@dragon.nchu.edu.tw. Fax:
+886-4 22862547. Tel: +886-4-22840411-420.
Notes
■
(25) Sanches-Delgado et al. proposed a mechansitic study for the
́
cyclization of N-alkylallylamines under syn gas. See: Sanchez-Delgado,
R. A.; Rosa, R. G. d.; Ocando-Mavarez, E. J. Mol. Catal. 1996, 108,
125−129.
(26) The C-15 signal in H-2a shows a singlet at δ 32.2, while that in
D-2a shows a triplet at δ 31.8. For H-2b, the peak of C-15 is located at
δ 37.0, and that in D-2b is at δ 36.5. The related integral values can be
obtained by the inverse gate decoupling technique.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The research was supported by the Ministry of Science and
Technology, Taiwan (NSC101-2113-M-005-009-MY3), R.O.C.
The authors are grateful to the National Center for High-
Performance Computing for computation facilities.
(27) For the preparation of deuterium-labeled dione, see: Baldwin, J.
E.; Kaplan, M. S. J. Am. Chem. Soc. 1971, 93, 3969−3977. NMR
analysis showed 63% deuterium incorporation at the C-2 position.
(28) To our best understanding, the oxidation of N−H by Rh has not
been reported in the literature, although there are many examples of
Pd-mediated N−H cleavage.
REFERENCES
■
(1) (a) Ojima, I. In Catalytic Asmmetric Synthesis, 2nd ed.; Ojima, I.,
Ed.; Wiley-VCH: New York, 2000. (b) In Transition Metals for Organic
Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH Verlag GmbH & Co.
KGaA: Weinheim, 2004. (c) In Handbook of Cyclization Reactions; Ma,
S., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2010.
(2) (a) Eilbracht, P.; Barfacker, L.; Buss, C.; Hollmann, C.; Kitsos-
Rzychon, B. E.; Kranemann, C. L.; Rische, T.; Roggenbuck, R.;
Schmidt, A. Chem. Rev. 1999, 99, 3329−3365. (b) Ojima, I.; Tsai, C.-
Y.; Tzamarioudaki, M.; Bonafoux, D. In Organic Reactions, 1st ed.;
Overman, L. E., Ed.; John Wiley & Sons: New York, 2000; Vol. 56, pp
1−354. (c) Breit, B.; Seiche, W. Synthesis 2001, 1−36. (d) Chiou, W.-
H.; Lee, S.-Y.; Ojima, I. Can. J. Chem. 2005, 83, 681−692.
(3) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int.
Ed. 2006, 45, 7134−7186.
(4) Knifton, J. F. J. Organomet. Chem. 1980, 188, 223−236.
(5) Krafft, M. E.; Wilson, L. J.; Onan, K. D. Tetrahedron Lett. 1988,
29, 6421−6424.
(6) Zhou, J. Q.; Alper, H. J. Org. Chem. 1992, 57, 3328−3331.
(7) Zhang, Z.; Ojima, I. J. Organomet. Chem. 1993, 454, 281−289.
(8) Baxter, E. W.; Marino, P. S. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Springer-Verlag: New York, 1992;
Vol. 8, p 197.
(29) Krafft, M. E.; Wilson, L. J.; Onan, K. D. Organometallics 1988, 7,
2528−2534.
(30) Although N-deuterium amine 3, i.e., N−D, should be a direct
substrate to study the mechanism, attempts to prepare deuterated
amine 3 were unsuccessful. The NH peak was intact after treatment of
amine 3 with CD3OD for one month. Addition of a trace amount of
CD3CO2D in CD3OD deteriorated amine 3. Use of excess strong
bases followed by addition of CD3OD or D2O resulted in a mixture of
indole protonated/deuterated product. Thus, the indole moiety may
not be appropriate for the investigation, and replacement with another
substituent is necessary.
(31) A Rh(V) species should be involved in the H−D exchange
process. For a Rh(V) species, see: Duckett, S. B.; Haddleton, D. M.;
Jackson, S. A.; Perutz, R. N.; Poliakoff, M.; Upmacis, R. K.
Organometallics 1988, 7, 1526−1532.
(32) Wenkert, E.; Chang, C.-J.; Chawla, H. P. S.; Cochran, D. W.;
Hagaman, E. W.; King, J. C.; Orito, K. J. Am. Chem. Soc. 1976, 98,
3645−3655.
(9) Baxter, E. W.; Labaree, D.; Ammon, H. L.; Mariano, P. S. J. Am.
Chem. Soc. 1990, 112, 7682−7692.
(10) Bergmeier, S. C.; Seth, P. P. J. Org. Chem. 1999, 64, 3237−3243.
(11) (a) Hua, D. H.; Bharathi, S. N.; Panangadan, J. A. K.; Tsujimoto,
A. J. Org. Chem. 1991, 56, 6998−7007. (b) Chen, H.-W.; Hsu, R.-T.;
Chang, M.-Y.; Chang, N.-C. Org. Lett. 2006, 8, 3033−3035.
(12) (a) Miyafuji, A.; Ito, K.; Katsuki, T. Heterocycles 2000, 52, 261−
272. (b) Tanaka, M.; Toyofuku, E.; Demizu, Y.; Yoshida, O.;
Nakazawa, K.; Sakai, K.; Suemune, H. Tetrahedron 2004, 60, 2271−
2281.
(13) (a) Martin, S. F.; Williamson, S. A.; Gist, R. P.; Smith, K. M. J.
Org. Chem. 1983, 48, 5170−5180. (b) Meyers, A. I.; Highsmith, T. K.;
Buonora, P. T. J. Org. Chem. 1991, 56, 2960−2964. (c) Sparks, S. M.;
Shea, K. J. Tetrahedron Lett. 2000, 41, 6721−6724.
(14) Padwa, A.; Beall, L. S.; Heidelbaugh, T. M.; Liu, B.; Sheehan, S.
M. J. Org. Chem. 2000, 65, 2684−2695.
(15) Lounasmaa, M.; Jokela, R. Tetrahedron 1990, 46, 615−622.
4244
dx.doi.org/10.1021/om500498u | Organometallics 2014, 33, 4240−4244