Iron tricarbonyl stabilized pentadienyl cation as initiator for cascade polycyclizations: A diastereoselective entry into octahydrophenanthrenes

Article abstract of DOI:10.1021/jo048557a

A new example is provided of completely diastereoselective polycyclization, affording the octahydrophenanthrene framework. Generation of an iron tricarbonyl stabilized pentadienyl carbocation is the triggering event of the cascade reaction. The carbocation is generated by anchimerically assisted regiospecific protonation of a double bond adjacent to the iron tricarbonyl diene moiety. Tetrafluoroboric acid ether complex appears to be the optimum reagent, affording good yields, even under catalytic conditions.

Full text of DOI:10.1021/jo048557a

SCHEME 1. E vs Z Pendant Olefin Behavior
Iron Tricarbonyl Stabilized Pentadienyl
Cation as Initiator for Cascade
Polycyclizations: A Diastereoselective
Entry into Octahydrophenanthrenes
Anthony J. Pearson* and Victor P. Ghidu
Case Western Reserve University, Department of Chemistry,
Cleveland, Ohio 44106
anthony.pearson@case.edu
Received August 18, 2004
SCHEME 2. Synthesis of Polyene Substrates
Abstract: A new example is provided of completely dias-
tereoselective polycyclization, affording the octahydrophenan-
threne framework. Generation of an iron tricarbonyl stabi-
lized pentadienyl carbocation is the triggering event of the
cascade reaction. The carbocation is generated by anchi-
merically assisted regiospecific protonation of a double bond
adjacent to the iron tricarbonyl diene moiety. Tetrafluorobo-
ric acid ether complex appears to be the optimum reagent,
affording good yields, even under catalytic conditions.
Iron tricarbonyl diene complexes continue to evolve as
useful auxiliaries in synthetic organic chemistry.1
A
recent example of biomimetic double cyclization of poly-
olefinic substrates, using the iron tricarbonyl pentadienyl
cation as initiator, illustrates its versatility in generating
diastereoselectivity.2 This work has its roots in Johnson’s
seminal work on “Nonenzymic Biogenetic-like Olefinic
Cyclizations” and related works,3 the first to prove correct
the Stork-Eschenmoser postulate,4 which inspired nu-
merous research groups in developing new methods for
this type of tandem reaction, seeking to improve and
introduce new ways to achieve diastereoselectivity and
enantioselectivity. The high appeal of this reaction lies
in its ability to create a number of new C-C bonds and
introduce several stereocenters in one step.
Herein we present another protocol for this transfor-
mation, derived from our new method to generate car-
bocations that are stabilized by a neighboring diene-
Fe(CO)3 group.5 Several substrates were prepared, which
cyclized in very good yields, even under catalytic condi-
tions, and complete diastereoselectivity was observed.
Our focus was on pendant E-substituted olefins, since a
simple cyclization employing a pendant Z-substituted
olefin afforded only traces of the desired cyclization
product (Scheme 1). We believe that the Z-substituted
double bond in 1b places a high steric demand on the
cyclization reaction.
The substrates were prepared as described in Scheme
2, starting with commercially available cinnamyl and
hydrocinnamyl derivatives, following literature proce-
dures.6 Whereas 3-methoxy- (4b) or 2,3-dimethoxy-
(1) (a) Pearson, A. J. Iron Compounds in Organic Synthesis;
Academic Press: London, 1994. (b) Donaldson, W. A. Aldrichim. Acta
1997, 30 (1), 17-24. (c) Kno¨lker, H. J.; Braier, A.; Bro¨cher, D. J.;
Ca¨mmerer, S.; Fro¨hner, W.; Gonser, P.; Hermann, H.; Herzberg, D.;
Reddy, K. R.; Rohde, G. Pure Appl. Chem. 2001, 73 (7), 1075.
(2) Franck-Neumann, M.; Geoffroy, P.; Hanss, D. Tetrahedron Lett.
2002, 43, 2277-2280.
(6) (a) Albrecht, M.; Riether, C. Synthesis 1997, 8, 1997. (b) Bode,
J. W.; Doyle, M. P.; Protopopova, M. N.; Zhou, Q. L. J. Org. Chem.
1996, 61, 9146. (c) Browder, C. C.; Marmsater, F. P.; West, F. G. Org.
Lett. 2001, 3 (19), 3033. (d) Pearson, A. J.; Mesaros, E. F. Org. Lett.
2001, 3 (17), 2665. (e) Clive, D. L. J.; Hisaindee, S. J. Org. Chem. 2000,
65, 4923. (f) Back, T. G.; Nava-Salgado, V. O.; Payne, J. E. J. Org.
Chem. 2001, 66, 4361. (g) Tokumasu, M.; Ando, H.; Hiraga, Y.; Kojima,
S.; Ohkata, K. J. Chem. Soc., Perkin Trans. 1 1999, 489. (h) Taber, D.
F.; Rahimizadeh, M.; You, K. K. J. Org. Chem. 1995, 60, 529. (i) Bell,
P. T.; Dasgupta, B.; Donaldson, W. A. J. Organomet. Chem. 1997, 538,
75.
(3) (a) Johnson, W. S. Acc. Chem. Res. 1968, 1, 1. (b) van Tamelen,
E. E. Acc. Chem. Res. 1968, 1, 111. (c) Johnson, W. S.; Lindell, S. D.;
Steele, J. J. Am. Chem. Soc. 1987, 109, 5852.
(4) (a) Stork, G.; Burgstahler, A. W. J. Am. Chem. Soc. 1955, 77,
5068. (b) Eschenmoser, A.; Ruzicka, L.; Jeger, O.; Arigoni, D. Helv.
Chim. Acta 1957, 38, 1890.
(5) Pearson, A. J.; Ghidu, V. P. Org. Lett. 2002, 4 (23), 4069.
10.1021/jo048557a CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/06/2004
J. Org. Chem. 2004, 69, 8975-8978
8975

SCHEME 3. Double Cyclization Mechanism
CHART 1. Cyclization Products and Their
Demetalated Counterpartsa
substituted (4c) esters were readily reduced by LiAlH4
to afford the corresponding saturated alcohols (5b,c) in
high yields, the 4-methoxy-substituted cinnamic ester
(4d) yielded only 20% of the corresponding alcohol (5d)
along with a complex mixture of inseparable compounds,
presumably due to the electron rich nature of the
substrate. An alternate hydrogenation/esterification/
reduction route had to be employed in this case. Horner-
Emmons olefination of aldehydes 6a-d provided the
disubstituted olefins 7a-d in very good yields and with
complete E selectivity.
We began our exploration of cationic polycyclization
with substrate 17b, which was considered to bear the
most reactive terminator (p-OMe-substituted phenyl ring
with respect to the cyclization position). We initially used
our previously reported cyclization method, HCOOH
neat, 50 °C.5 Disappointingly, only 35% yield of cycliza-
tion product 18b could be isolated from a very complex
product mixture (Scheme 3). This is not surprising
because formic acid will not only protonate the double
bond adjacent to the iron tricarbonyl diene moiety, an
event that triggers the cyclization reaction, but is suf-
ficiently nucleophilic to compete with the pendant olefin
for the same cation. In the case of the polycyclization
reaction, an extra cationic intermediate 17b′′ appears on
the reaction pathway, increasing the possibility of side
reactions (Scheme 3).
a Reagents and conditions: (a) 25% molar HBF4‚OEt2, 0 °C,
CH2Cl2, 4 h. (b) Stoichiometric HBF4‚OEt2, 0 °C, CH2Cl2, 4 h. (c)
10-30 equiv of Me3NO, acetone, room temperature, overnight. (d)
Saturated CuCl2 in ethanol. An asterisk indicates numbers based
on reacted starting material.
Simple pendant olefin substrates follow a “cyclization-
nucleophile insertion” pathway, affording formyloxy de-
rivatives,5 thus benefitting from the double role of the
formic acid. At the same time, simple pendant aromatic
substrates, or combined olefin/aromatic terminators, only
require the acid to perform the protonation step. Since
the proton is being regenerated in the termination step,
a catalytic amount of acid should be sufficient to promote
the reaction. Therefore we decided to replace formic acid
with an acid that has a less nucleophilic conjugate base.
Tetrafluoroboric acid ether complex proved to be the best
reagent, affording very clean cyclizations in dry dichlo-
romethane at 0 °C. Both stoichiometric and catalytic
amounts (ca. 25% molar) of acid were employed. Along
with the expected cyclization product 18b, obtained in
53% yield, its regioisomer 18b′ was also isolated in 30%
yield (Chart 1). The remaining substrates followed a
similar path. Substrate 17a afforded the expected cy-
clization product 18a, albeit in low yield under catalytic
conditions, due to the reduced nucleophilicity of the
unactivated phenyl ring. However, most of the unreacted
starting material was recovered. While extending the
reaction time was considered a logical way to improve
the yield, demetalation of the starting material over
longer reaction time was somewhat of a drawback and
prevented the overall increase of the yield. Under stoi-
chiometric conditions complex 18a was obtained in 50%
yield, along with ca. 45% demetalated product 19a, which
suggests a near quantitative cyclization reaction. Sub-
strates 17c and 17d, designed to cyclize unambiguously
to a single product, also performed very well, with 17c
affording a superior yield, while 17d was somewhat
lower, due to the less favorable position of the methoxy
activating substituent (Chart 1).
To establish stereochemistry we relied on NMR analy-
sis. This proved to be a difficult endeavor for the
cyclization products 18a-d, due to extensive overlapping
of diagnostic resonances. Two mild methods of demeta-
8976 J. Org. Chem., Vol. 69, No. 25, 2004

lation7 were employed to afford the tricyclic demetalated
products 19a-d, for which extensive 1D and 2D (COSY)
analysis revealed the expected all-trans cyclization prod-
ucts, consistent with the Stork-Eschenmoser hypoth-
esis.4
By employing correlation spectroscopy (COSY) the
angular hydrogen resonances were easily assigned. Analy-
sis of coupling constants reveals that hydrogen atoms H1,
H4a, and H10a are all axial, consistent with a trans ring
junction and equatorial position for the demetalated
diene moiety (1D and 2D spectra included in Supporting
Information).
In conclusion, we have described new examples of a
catalytic, completely diastereoselective double cyclization
reaction of polyolefinic substrates, using an iron tricar-
bonyl-stabilized pentadienyl cation as the initiator. With
the advent of new methods for the preparation of enan-
tiopure iron tricarbonyl diene complexes8 such as 16,
enantiospecific cyclizations should be easily available.
2.68 (dd, J ) 9.4, 7.1 Hz, 2H), 2.37-2.27 (2H), 2.17-2.03 (4H),
1.94 (t, J ) 9.1 Hz, 1H), 1.50-1.30 (4H); 13C NMR (50 MHz,
CDCl3) δ (ppm) Z isomer (major) 212.5, 142.2, 130.9, 130.7, 130.2,
130.1, 128.5, 128.3, 125.8, 85.4, 82.3, 57.0, 56.9, 36.1, 34.5, 32.2,
28.0, 19.3, and E isomer (minor) 131.8, 131.7, 130.1, 128.4, 125.8,
84.8, 81.1, 62.3, 56.8, 32.8. IR (film, cm-1) 3027, 2923, 2855, 2037,
1966. HRMS (EI) M+ - 2CO calcd for C20H24OFe 336.1177, found
336.1172.
(()-Tricarbonyl[(2S)-2-5-η-(2E,4E,10E)-13-(3-methoxyphen-
yl)trideca-2,4,6,10-tetraene]iron, inseparable mixture of
6Z and 6E isomers (17b): yellow oil, 69% yield. TLC Rf 0.4
(EtOAc:hexanes ) 1:24). 1H NMR (200 MHz, CDCl3) δ (ppm)
7.20 (dd, J ) 8.8, 7.5 Hz, 1H), 6.81-6.70 (3H), 5.50-5.25 (4H),
5.14 (ddd, J ) 8.8, 5.1, 0.6 Hz, 1H), 5.03 (ddd, J ) 8.2, 5.4, 0.7
Hz, 1H), 3.80 (s, 3H), 2.65 (dd, J ) 10.0, 7.2 Hz, 2H), 2.38-2.23
(2H), 2.22-2.00 (4H), 1.93 (t, J ) 8.72 Hz, 1H), 1.45-1.35 (4H);
13C NMR (50 MHz, CDCl3) δ (ppm) Z isomer (major) 212.4, 159.5,
143.8, 130.8, 130.6, 130.1, 130.0, 129.1, 120.9, 114.2, 111.0, 85.3,
82.2, 56.8, 56.7, 55.1, 36.1, 34.3, 32.1, 27.9, 19.2, and E isomer
(minor) 131.7, 84.7, 81.0, 62.2, 56.7, 36.0, 34.2, 29.5. IR (film,
cm-1) 2039, 1967. HRMS (FAB) M+ calcd for C23H26O4Fe
422.1180, found 422.1166.
(()-Tricarbonyl[(2S)-2-5-η-(2E,4E,10E)-13-(2,3-dimethoxy-
phenyl)trideca-2,4,6,10-tetraene]iron, inseparable mix-
ture of 6Z and 6E isomers (17c): yellow oil, 83% yield. TLC
Experimental Section
1
Rf 0.35 (EtOAc:hexanes ) 1:10). H NMR (200 MHz, CDCl3) δ
Complexes 1a and 2a are already reported.5 Complex 2b was
not fully characterized due to extremely low yields that could
not be improved.
(ppm) 6.98 (dd, J ) 8.5, 7.3 Hz, 1H), 6.77 (d, J ) 8.0 Hz, 2H),
5.60-5.25 (4H), 5.13 (dd, J ) 8.6, 4.9 Hz, 1H), 5.02 (ddd, J )
8.1, 4.7, 0.8 Hz, 1H), 3.86 (s, 1H), 3.82 (s,1H), 2.68 (dd, J ) 10.0,
5.7 Hz, 2H), 2.34-2.22 (2H), 2.17-2.00 (4H), 1.94 (t, J ) 8.9
Hz, 1H), 1.50-1.30 (4H); 13C NMR (50 MHz, CDCl3) δ (ppm) Z
isomer (major) 212.4, 152.7, 147.1, 136.0, 130.8, 130.7, 130.5,
129.7, 123.6, 121.9, 110.0, 85.3, 82.1, 60.6, 56.9, 56.8, 55.6, 33.7,
32.1, 30.0, 27.9, 19.2. HRMS (FAB) M+ - 3CO calcd for C20H28O2-
Fe 368.1439, found 368.1399.
Representative Experimental Procedure for the Prepa-
ration of Polyene Substrates 1b, 17a-d. Phosphonium salt
15c (0.49 g, 0.85 mmol, 1 equiv) was concentrated from dichlo-
romethane and dried overnight in vacuo. Under Ar atmosphere,
10 mL of dry THF was added via syringe. n-BuLi (2.5 M in
hexanes, 0.68 mL, 2 equiv9) was added dropwise at -78 °C. The
mixture was stirred for 30 min at -78 °C. A solution of 0.36 g
(1.8 equiv) of iron tricarbonyl sorbaldehyde complex 16 in 5 mL
of dry THF was transferred by cannula into the reaction flask.
Stirring was continued for 30 min at -78 °C, the cold bath was
removed, and the reaction flask was allowed to warm to room
temperature. Reaction progress was monitored by TLC. The
reaction was quenched by addition of saturated NH4Cl solution
(5 mL). The organic phase was diluted with diethyl ether,
washed with saturated NaHCO3 solution, water, and brine, and
dried (MgSO4). Removal of the solvent under reduced pressure
and flash chromatography separation afforded 319.5 mg (83%)
of complex 17c as a yellow oil.
(()-Tricarbonyl[(2S)-2-5-η-(2E,4E,10E)-13-(4-methoxyphen-
yl)trideca-2,4,6,10-tetraene]iron, inseparable mixture of
6Z and 6E isomers (17d): yellow oil, 51% yield. TLC Rf 0.36
(EtOAc:hexanes ) 1:25). 1H NMR (200 MHz, CDCl3) δ (ppm)
7.10 (unresolved AA′ quartet, 2H), 6.82 (unresolved AA′ quartet,
2H), 5.50-5.25 (4H), 5.14 (dd, J ) 8.8, 4.8 Hz, 1H), 5.03 (ddd, J
) 7.8, 5.3, 0.5 Hz, 1H), 3.79 (s, 3H), 2.61 (dd, J ) 9.8, 7.3 Hz,
2H), 2.35-2.00 (6H), 1.93 (t, J ) 9.3 Hz, 1H), 1.45-1.30 (4H);
13C NMR (50 MHz, CDCl3) δ (ppm) Z isomer (major) 212.5, 157.7,
134.3, 130.9, 130.8, 130.3, 130.0, 129.4, 113.7, 85.4, 82.3, 57.0,
56.9, 55.3, 35.2, 34.8, 32.2, 28.0, 19.3. HRMS (FAB) M+ calcd
for C23H26O4Fe 422.1180, found 422.1095.
Representative Experimental Procedure for the Cy-
clization Reactions. To 45.5 mg (0.1 mmol) of complex 17c in
1 mL of CH2Cl2, under Ar at 0 °C, was added 1 drop of HBF4‚
OEt2 (85% in diethyl ether, ca. 0.25 equiv). After 4 h at 0 °C, no
further conversion by TLC could be observed. The reaction was
quenched by addition of water (2 mL). The organic phase was
diluted with diethyl ether, then washed with satd aq NaHCO3
solution, water, and brine. Evaporation of solvents under
reduced pressure and recrystallization with dichloromethane/
pentane afforded 39 mg (85% yield) of complex 18c.
1H NMR spectra are reported for the Z/E mixtures; as the Z
isomer is the major one, it is assumed that the resolved signals
belong to it. Whenever possible, two sets of 13C NMR are
reported; major signals are again assumed to belong to the major
Z isomer.
(()-Tricarbonyl[(2S)-2-5-η-(2E,4E,10Z)-2,4,6,10-dodecatet-
raene]iron, inseparable mixture of 6Z and 6E isomers
(1b): yellow oil, 51% yield (82% borsm). TLC Rf 0.6 (hexanes).
1H NMR (200 MHz, CDCl3) δ (ppm) 5.53-5.32 (4H), 5.14 (dd, J
) 9.0, 4.8 Hz, 1H), 5.03 (dd, J ) 8.2, 5.1 Hz, 1H), 2.23-2.03
(4H), 1.94 (t, J ) 9.1 Hz, 1H), 1.61 (d, J ) 5.2 Hz, 3H), 1.45-
1.32 (4H); 13C NMR (50 MHz, CDCl3) δ (ppm) Z isomer (major)
212.4, 130.9, 130.7, 129.6, 124.5, 85.3, 82.2, 56.9, 56.7, 27.8, 26.5,
19.2, 12.8, and E isomer (minor) 131.8, 131.7, 130.8, 129.5, 124.3,
84.7, 81.0, 62.2, 56.7. IR (film, cm-1) 2045, 1966. HRMS (FAB)
M+ calcd for C15H18O3Fe 302.0605, found 302.0612.
(()-Tricarbonyl((2S)-2-5-η-5-((1R,4aR,10aR)-1,2,3,4,4a,9,-
10,10a-octahydrophenanthren-1-yl)-(2E,4E)-pentadiene)-
iron (18a): yellow solid, mp 173 °C, 35% yield (83% yield borsm).
TLC Rf 0.38 (hexanes). 1H NMR (200 MHz, CDCl3) δ (ppm) 7.35-
7.30 (1H), 7.20-7.06 (3H), 5.03 (unresolved AB quartet, 2H),
1.43 (d, J ) 6.2 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ (ppm)
140.1, 136.7, 128.9, 126.1, 125.8, 125.6, 84.3, 83.9, 70.3, 57.6,
48.3, 46.8, 43.2, 37.0, 31.4, 30.1, 26.9, 26.7, 19.2. IR (KBr pellet,
cm-1) 2946, 2925, 2911, 2865, 2853, 2837, 2035, 1968. HRMS
(EI) M+ calcd for C22H24O3Fe 392.1075, found 392.1115.
(()-Tricarbonyl((2S)-2-5-η-5-((1R,4aR,10aR)-7-methoxy-
1,2,3,4,4a,9,10,10a-octahydro-phenanthren-1-yl)-(2E,4E)-
pentadiene)iron (18b): yellow solid, mp 170 °C, 53% yield. TLC
(()-Tricarbonyl[(2S)-2-5-η-(2E,4E,10E)-13-phenyltrideca-
2,4,6,10-tetraene]iron, inseparable mixture of 6Z and 6E
1
isomers (17a): yellow oil, 80% yield. TLC Rf 0.4 (hexanes). H
NMR (200 MHz, CDCl3) δ (ppm) 7.35-7.15 (5H), 5.51-5.29 (4H),
5.15 (dd, J ) 8.6, 5.1 Hz, 1H), 5.04 (dd, J ) 7.7, 5.0 Hz, 1H),
(7) (a) Pearson, A. J.; Dorange, I. B. J. Org. Chem. 2001, 66, 3140.
(b) Thomson, D. J. J. Organomet. Chem. 1976, 108, 381.
(8) (a) Kno¨lker, H. J. Chem. Rev. 2000, 100, 2941. (b) Tsai, M. S.;
Rao, U. N.; Hsueh, P. Y.; Yeh, M. C. P. Organometallics 2001, 20, 289.
(9) Careful NMR analysis of the phosphonium salts revealed 0.5 to
1.0 equiv of water present, thus requiring excess of base.
1
Rf 0.28 (EtOAc:hexanes ) 1:25). H NMR (200 MHz, CDCl3) δ
(ppm) 7.21 (d, J ) 8.5 Hz, 1H), 6.71 (dd, J ) 8.6, 2.7 Hz, 1H),
6.60 (d, J ) 2.6 Hz, 1H), 5.02 (unresolved AB quartet, 2H), 3.77
(s, 3H), 2.85-2.73 (2H), 2.48-2.20 (3H), 1.99-1.85 (2H), 1.62-
J. Org. Chem, Vol. 69, No. 25, 2004 8977

1.49 (3H), 1.41 (d, J ) 6.2 Hz, 3H), 1.36-1.27 (2H), 1.19-0.93
(3H); 13C NMR (50 MHz, CDCl3) δ (ppm) 157.4, 137.9, 132.4,
127.0, 113.4, 111.8, 84.2, 83.8, 70.3, 57.5, 55.2, 48.1, 46.9, 42.6,
37.0, 31.5, 30.3, 26.9, 26.5, 19.1. IR (KBr pellet, cm-1) 2039, 1967,
1953. HRMS (FAB) M+ calcd for C23H26O4Fe 422.1180, found
422.1168.
5.93 (2H), 5.57-5.51 (1H), 5.33 (dd, J ) 13.8, 9.0 Hz, 1H), 3.70
(s, 3H), 2.72-2.68 (2H), 2.35 (dd, J ) 12.6, 3.0 Hz, 1H), 2.24 (t,
J ) 11.4 Hz, 1H), 1.94 (dm, J ) 12.6 Hz, 1H), 1.84 (dquint, J )
13.2, 3.0 Hz, 1H), 1.78 (qd, J ) 10.4, 3.6 Hz, 1H), 1.68 (d, J )
7.8 Hz, 3H), 1.44 (qt, J ) 13.2, 3.6 Hz, 1H), 1.03 (qd, J ) 10.8,
3.0 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ (ppm) 157.4, 138.5,
136.4, 132.8, 131.8, 130.3, 127.1, 126.6, 113.6, 111.7, 55.2, 47.5,
(()-Tricarbonyl((2S)-2-5-η-5-((1R,4aR,10aR)-5-methoxy-
1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)-(2E,4E)-
pentadiene)iron (18b′): yellow oil, 30% yield. TLC Rf 0.50
(EtOAc:hexanes ) 1:25). 1H NMR (200 MHz, CDCl3) δ (ppm)
7.07 (t, J ) 8.0 Hz, 1H), 6.74-6.64 (2H), 5.08-4.94 (2H), 3.78
(s, 3H), 1.42 (d, J ) 6.1 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
(ppm) 158.8, 139.8, 128.9, 126.1, 121.5, 108.1, 84.2, 84.1, 70.3,
57.4, 55.0, 49.8, 48.7, 42.7, 37.8, 31.8, 31.7, 27.3, 25.9, 19.2.
(()-Tricarbonyl((2S)-2-5-η-5-((1R,4aR,10aR)-7,8-
dimethoxy-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-
yl)-(2E,4E)-pentadiene)iron (18c): yellow solid, 85% yield.
TLC Rf 0.26 (EtOAc:hexanes ) 1:10). 1H NMR (600 MHz, CDCl3)
δ (ppm) 7.02 (d, J ) 9.0 Hz, 1H), 6.76 (d, J ) 8.4 Hz, 1H), 5.03
(unresolved AB quartet, 2H), 3.84 (s, 3H), 3.79 (s, 3H), 3.03 (dd,
J ) 17.4, 4.2 Hz, 1H), 2.55 (ddd, J ) 18.0, 12.6, 6.0 Hz, 1H),
2.41-2.38 (2H), 2.28 (t, J ) 9.0 Hz, 1H), 1.96-1.89 (2H), 1.48
(qt, J ) 13.2, 3.6 Hz, 1H), 1.42 (d, J ) 6.0 Hz, 3H), 1.33-1.23
(2H), 1.19-1.11 (2H), 1.01-0.95 (2H), 0.81 (t, J ) 9.0 Hz, 1H);
13C NMR (50 MHz, CDCl3) δ (ppm) 150.2, 146.1, 133.6, 131.2,
121.2, 109.8, 84.2, 83.8, 70.3, 59.8, 57.5, 55.7, 48.1, 46.3, 42.6,
36.9, 31.5, 26.5, 26.4, 24.0, 19.2. HRMS (EI) M+ - CO calcd for
44.9, 42.7, 33.7, 31.1, 30.3, 27.8, 26.0, 18.1. IR (KBr pellet, cm-1
)
2926, 2855. HRMS (FAB) M+ calcd for C20H26O 282.1984, found
282.1975.
(()-(1R,4aR,10aR)-5-Methoxy-1-((1E,3E)-penta-1,3-dienyl)-
1,2,3,4,4a,9,10,10a-octahydrophenanthrene (19b′): pale yel-
1
low oil, 79% yield. TLC Rf 0.42 (pentane). H NMR (600 MHz,
CDCl3) δ (ppm) 7.06 (t, J ) 7.8 Hz, 1H), 6.69 (d, J ) 7.8 Hz,
1H), 6.67 (d, J ) 8.4 Hz, 1H), 6.08-5.98 (2H), 5.64-5.56 (1H),
5.43 (dd, J ) 15.0, 9.6 Hz, 1H), 3.79 (s, 3H), 2.92 (d, J ) 12.6
Hz, 1H), 2.77 (td, J ) 14.7, 4.8 Hz, 1H), 2.66 (dq, J ) 16.2, 2.2
Hz, 1H), 2.49 (t, J ) 10.5 Hz, 1H), 1.98 (qd, J ) 10.4, 4.2 Hz,
1H), 1.89 (dquint, J ) 12.6, 2.4 Hz, 1H), 1.86-1.77 (2H), 1.75
(d, J ) 6.6 Hz, 3H), 1.60 (qt, J ) 13.2, 4.2 Hz, 1H), 1.09 (qd, J
) 12.6, 4.2 Hz, 1H), 0.97 (qd, J ) 12.0, 3.0 Hz, 1H); 13C NMR
(50 MHz, CDCl3) δ (ppm) 158.9, 140.2, 136.7, 131.8, 130.0, 129.1,
127.0, 126.1, 121.7, 108.1, 55.0, 48.0, 47.8, 43.0, 34.6, 31.9, 31.5,
26.9, 26.5, 18.1. IR (film, cm-1) 2923, 2855. HRMS (FAB) M+
calcd for C20H26O 282.1984, found 282.1984.
(()-(1R,4aR,10aR)-7,8-Dimethoxy-1-((1E,3E)-penta-1,3-
dienyl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene (19c):
off-white solid, mp 124 °C, 90% yield. TLC Rf 0.36 (EtOAc:
hexanes ) 1:10). 1H NMR (600 MHz, CDCl3) δ (ppm) 7.01 (d, J
) 8.4 Hz, 1H), 6.75 (d, J ) 8.4 Hz, 1H), 6.08-5.99 (2H), 5.64-
5.57 (1H), 5.40 (dd, J ) 13.2, 9.0 Hz, 1H), 3.84 (s, 3H), 3.78 (s,
3H), 2.93 (ddd, J ) 17.4, 5.4, 1.8 Hz, 1H), 2.58 (ddd, J ) 18.0,
12.0, 6.0 Hz, 1H), 2.41 (m, 1H), 2.29 (td, J ) 11.4, 3.0 Hz, 1H),
2.05 (ddt, J ) 12.6, 6.0, 2.4 Hz, 1H), 1.90 (dquint, J ) 13.2, 3.0
Hz, 1H), 1.83 (qd, J ) 10.4, 3.6 Hz, 1H), 1.75-1.71 (4H), 1.50
(qt, J ) 13.2, 4.2 Hz, 1H), 1.26-1.14 (3H), 1.05 (qd, J ) 10.8,
2.4 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ (ppm) 150.2, 146.2,
136.3, 134.0, 131.7, 131.6, 130.2, 127.1, 120.9, 109.7, 59.8, 55.7,
47.4, 44.3, 42.7, 33.6, 31.1, 27.2, 25.9, 23.9, 18.0. IR (KBr pellet,
cm-1) 3013, 3002, 2924, 2855, 2833. HRMS (FAB) M+ calcd for
C21H28O2 312.2089, found 312.2093.
C
23H28O4Fe 424.1337, found 424.1323.
(()-Tricarbonyl((2S)-2-5-η-5-((1R,4aR,10aR)-6-methoxy-
1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)-(2E,4E)-
pentadiene)iron (18d): yellow solid, mp 169 °C, 58% yield (88%
yield based on reacted starting material). TLC Rf 0.24 (EtOAc:
hexanes ) 1:25). 1H NMR (200 MHz, CDCl3) δ (ppm) 7.00 (d, J
) 8.4 Hz, 1H), 6.86 (d, J ) 2.4 Hz, 1H), 6.69 (dd, J ) 8.3, 2.6
Hz, 1H), 5.03 (unresolved AB quartet, 2H), 3.79 (s, 3H), 1.42 (d,
J ) 6.2 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ (ppm) 157.8, 141.4,
129.7, 128.9, 111.6, 111.3, 84.3, 83.9, 70.3, 57.6, 55.3, 48.3, 46.8,
43.4, 37.0, 31.4, 29.3, 27.1, 26.7, 19.2. IR (KBr pellet, cm-1) 2944,
2915, 2851, 2835, 2035, 1956. HRMS (FAB) M+ calcd for
C
23H26O4Fe 422.1180, found 422.1128.
Representative Experimental Procedure for the De-
metalation Reactions. Trimethylamine N-oxide (50 mg, 10
equiv) was added to 30 mg (1 equiv) of complex 18c in 2 mL of
1:1 acetone and ethanol. While the reaction was stirred at room
temperature for 24 h, ca. 15 equiv of Me3NO was added after
checking the reaction progress by TLC. The reaction mixture
was filtered through a Celite plug and evaporated. Recrystalli-
zation from dichloromethane/pentane afforded 18.7 mg (90%) of
compound 19c. Preparative TLC was also used for purification
of the demetalated products, both liquids and solids.
(()-(1R,4aR,10aR)-1-((1E,3E)-Penta-1,3-dienyl)-1,2,3,4,-
4a,9,10,10a-octahydrophenanthrene (19a): pale yellow oil,
78% yield. TLC Rf 0.50 (hexanes). 1H NMR (600 MHz, CDCl3) δ
(ppm) 7.31 (d, J ) 7.8 Hz, 1H), 7.14 (tm, J ) 7.2 Hz, 1H), 7.11
(tm, J ) 7.5 Hz, 1H), 7.07 (d, J ) 7.2 Hz, 1H), 6.09-6.01 (2H),
5.65-5.59 (1H), 5.43-5.39 (1H), 2.80 (dd, J ) 8.4, 3.6 Hz, 2H),
2.48-2.46 (1H), 2.38 (td, J ) 12.0, 3.0 Hz, 1H), 2.05-2.01 (1H),
1.93 (dquint, J ) 13.8, 3.0 Hz, 1H), 1.90-1.84 (1H), 1.77-1.74
(1H), 1.53 (qt, J ) 13.2, 4.2 Hz, 1H), 1.34-1.19 (3H), 1.14 (qd,
J ) 10.8, 2.4 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ (ppm) 140.5,
137.2, 136.3, 131.8, 130.3, 129.0, 127.2, 125.6, 125.5, 47.6, 44.7,
43.2, 33.7, 30.9, 30.0, 27.7, 26.1, 18.1. IR (film, cm-1) 3014, 2919,
2854. HRMS (EI) M+ calcd for C19H24 252.1878, found 252.1875.
(()-(1R,4aR,10aR)-7-Methoxy-1-((1E,3E)-penta-1,3-dienyl)-
1,2,3,4,4a,9,10,10a-octahydrophenanthrene (19b): off-white
solid, mp 64 °C, 30% yield. TLC Rf 0.34 (EtOAc:hexanes ) 1:25).
1H NMR (600 MHz, CDCl3) δ (ppm) 7.14 (d, J ) 8.4 Hz, 1H),
6.64 (dd, J ) 9.0, 3.0 Hz, 1H), 6.53 (d, J ) 3.0 Hz, 1H), 6.01-
(()-(1R,4aR,10aR)-6-Methoxy-1-((1E,3E)-penta-1,3-dienyl)-
1,2,3,4,4a,9,10,10a-octahydrophenanthrene (19d): off-white
solid, mp 93 °C, 82% yield. TLC Rf 0.36 (EtOAc:hexanes ) 1:25).
1H NMR (600 MHz, CDCl3) δ (ppm) 6.98 (d, J ) 8.4 Hz, 1H),
6.86 (d, J ) 1.8 Hz, 1H), 6.68 (dd, J ) 7.8, 1.8 Hz, 1H), 6.07-
5.99 (2H), 5.64-5.58 (m, 1H), 5.40 (dd, J ) 13.8, 9.0 Hz, 1H),
3.78 (s, 3H), 2.74-2.71 (2H), 2.43-2.40 (m, 1H), 2.34 (t, J )
12.0 Hz, 1H), 2.01 (dm, J ) 12.6 Hz, 1H), 1.92 (dquint, J ) 13.2,
3.6 Hz, 1H), 1.85 (qd, J ) 10.2, 3.0 Hz, 1H), 1.74 (d, J ) 6.6 Hz,
3H), 1.52 (qt, J ) 13.2, 3.6 Hz, 1H), 1.30-1.19 (3H), 1.11 (qd, J
) 11.0, 2.4 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ (ppm) 157.7,
141.8, 136.3, 131.8, 130.3, 129.7, 129.4, 127.1, 111.4, 111.1, 55.3,
46.6, 44.7, 43.4, 33.7, 31.0, 29.2, 27.9, 26.1, 18.1. IR (KBr pellet,
cm-1) 3015, 2917, 2853. HRMS (FAB) M+ calcd for C20H26
282.1984, found 282.1979.
O
Acknowledgment. This work was supported by a
grant from the National Science Foundation, and the
Chemistry Department of Case Western Reserve Uni-
versity.
Supporting Information Available: 1H and 13C NMR
spectra for compounds 1b, 17a-d, 18a-d, and 19a-d, as well
as COSY spectra for compound 19c. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO048557A
8978 J. Org. Chem., Vol. 69, No. 25, 2004