Reactivity of acyclic (pentadienyl)iron(1+) cations with phosphonate stabilized nucleophiles: Application to the synthesis of oxygenated metabolites of carvone

Article abstract of DOI:10.1016/j.tet.2015.12.035

The addition of phosphonate stabilized carbon nucleophiles to acyclic (pentadienyl)iron(1+) cations proceeds predominantly at an internal carbon to afford (pentenediyl)iron complexes. Those complexes bearing an electron withdrawing group at the σ-bound carbon (i.e., 13/14) are stable and isolable, while complexes which do not contain an electron withdrawing group at the σ-bound carbon undergo CO insertion, reductive elimination and conjugation of the double bond to afford cyclohexenone products (21/22). Deprotonation of the phosphonate 13/14 or 21 and reaction with paraformaldehyde affords the olefinated products. This methodology was utilized to prepare oxygenated carvone metabolites (±)-25 and (±)-26.

Full text of DOI:10.1016/j.tet.2015.12.035

Accepted Manuscript
Reactivity of acyclic (pentadienyl)iron(1+) cations with phosphonate stabilized
nucleophiles: Application to the synthesis of oxygenated metabolites of carvone
Do W. Lee, Charles F. Manful, Jayapal Reddy Gone, Yuzhi Ma, William A. Donaldson
PII:
S0040-4020(15)30283-0
10.1016/j.tet.2015.12.035
TET 27361
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 August 2015
Revised Date: 7 December 2015
Accepted Date: 14 December 2015
Please cite this article as: Lee DW, Manful CF, Gone JR, Ma Y, Donaldson WA, Reactivity of acyclic
(pentadienyl)iron(1+) cations with phosphonate stabilized nucleophiles: Application to the synthesis of
oxygenated metabolites of carvone, Tetrahedron (2016), doi: 10.1016/j.tet.2015.12.035.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Reactivity of acyclic (pentadienyl)iron(1+)
cations with phosphonate stabilized
nucleophiles: Application to the synthesis of
oxygenated metabolites of carvone
Leave this area blank for abstract info.
Do W. Lee, Charles F. Manful, Jayapal Reddy Gone, Yuzhi Ma and William A. Donaldson*
Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881 USA

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Reactivity of acyclic (pentadienyl)iron(1+) cations with phosphonate stabilized
nucleophiles: Application to the synthesis of oxygenated metabolites of carvone
Do W. Lee, Charles F. Manful, Jayapal Reddy Gone, Yuzhi Ma and William A. Donaldson*
Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881 USA
Phone: 414-288-7374; email: william.donaldson@marquette.edu
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The addition of phosphonate stabilized carbon nucleophiles to acyclic (pentadienyl)iron(1+)
cations proceeds predominantly at an internal carbon to afford (pentenediyl)iron complexes.
Those complexes bearing an electron withdrawing group at the σ-bound carbon (i.e. 13/14) are
stable and isolable, while complexes which do not contain an electron withdrawing group at the
σ-bound carbon undergo CO insertion, reductive elimination and conjugation of the double bond
to afford cyclohexenone products (21/22). Deprotonation of the phosphonate 13/14 or 21 and
reaction with paraformaldehyde affords the olefinated products. This methodology was utilized
to prepare oxygenated carvone metabolites (±)-25 and (±)-26.
Available online
Keywords:
Dienyl-iron Cations
Nucleophilic Addition
Horner-Emmons Olefination
Cyclocarbonylation
Terpenes
2009 Elsevier Ltd. All rights reserved
.
1. Introduction
Nucleophilic addition to cationic polyenyl-metal complexes is
an exemplar of organometallic chemistry. Where these reactions
proceed in good yield and with high regioselectivity, they have
been utilized in organic synthesis.1 There are numerous
examples of the reaction of (cyclohexadienyl)- and
(cycloheptadienyl)Fe(1+) cations (1a-d, eqn. 1) with stabilized
carbon nucleophiles such as malonates,2a-j β-ketoesters,2k-m β-
diketones,2n-p 2-cyano acetates,2q-r and arylsulfonyl acetates.2s-t
We and others have examined the reactivity of acyclic
(pentadienyl)iron(1+) cations 5 with nucleophiles.5 While certain
nucleophiles attack at the pentadienyl terminus to generate E,Z-
diene complexes 6, other nucleophiles react via attack at an
internal pentadienyl carbon to generate 2-substituted (3-pentene-
1,5-diyl)Fe complexes 7. This latter reactivity is relatively
In spite of their potential as synthons for Horner-Emmons
olefination, there are few examples of the reaction of dienyl-iron
cations3 or other organometallic cations4 with phosphonate
stabilized carbon nucleophiles. Stephenson, et al., reported the
+
reaction of (cyclohexadienyl)Fe(CO)3 cations 3a/b with the
potassium salt of α-phosphoramide acetates proceeded with good
regioselectivity, but in only modest yields (eqn. 2).3
Furthermore, the products 4 were not further processed into the
corresponding alkenes via reduction of the ester and subsequent
elimination.
Scheme 1. Nucleophilic attack on acyclic pentadienyl-iron
cations 5.

2
Tetrahedron
ACCEPTED MANUSCRIPT
unique to acyclic (pentadienyl)Fe+ cations compared to their
Deprotection of the silyl ether of alkylated β-ketophosphonate
cyclic counterparts 1. Complexes 7a, in which the R1 substituent
attached to the iron-bonded sp3 carbon is not an electron-
withdrawing group, are not stable and these eventually
decompose to cyclohexenone products 8, via CO insertion
followed by reductive elimination and olefin isomerization.6,7 In
contrast, those complexes 7b which possess an electron-
withdrawing R1 substituent are stable, isolable species which are
14b, gave the alcohol 17 (Scheme 3), which upon Swern
oxidation afforded aldehyde 18; both 17 and 18 were obtained as
a mixture of diastereomers. Subsequent intramolecular Horner-
Emmons olefination of 18 gave the cyclohexenone 19 as a single
1
diastereomer. Notably, a signal at δ 6.20 ppm in the H NMR
spectrum corresponds to H3’ and signals at δ 198.4, 143.9, and
141.8 ppm in the 13C NMR spectrum correspond to the carbonyl
and olefinic carbons of the cyclohexenone fragment.
resistant to CO insertion.
Oxidatively induced-reductive
elimination of complexes 7b generate vinylcyclopropane-
carboxylates 10.8
We herein report on the reaction of acyclic (pentadienyl)iron
cations with phosphonate stabilized carbon nucleophiles,
culminating in an application to the synthesis of oxygenated
metabolites of carvone.
2. Results and Discussion9
Addition of the anion generated from trimethyl
phosphonoacetate or diethyl (2-oxopropyl)phosphonate to (1-
methoxypentadienyl)iron cation (11)10 proceeded at the C2
carbon to afford the 2-substituted (pentenediyl)iron complexes
13a or 13b (Scheme 2, Table 1). In a similar fashion, addition of
the anions generated from trimethyl phosphonoacetate or [6-(t-
butyldiphenylsilyl)oxy]-2-oxohexylphosphonic acid dimethyl
ester11 with cation (12)8k afforded the (pentenediyl)iron
complexes 14a or 14b. Complexes 13a, 13b, 14a, 14b were
obtained as inseparable mixtures of diastereomers at the indicated
(*) carbon, as determined by 1H NMR spectroscopy. Each
exhibited two doublet signals in the range δ 0.01-0.80 ppm which
were assigned to the hydrogen attached to the σ-bound carbon
(H1) of each diastereomer.8c,i,k That 13a, 14a, and 13b were
diastereomeric at the indicted carbon was further corroborated by
their conversion to a single enoate or enone (15a, 16a or 15b)
upon Horner-Emmons olefination with paraformaldehyde.
Scheme 3.
Intramolecular Horner-Emmons olefination to
generate cyclohexenone (pentenediyl)iron complex 19.
The regioselectivity for addition of the phosphonate stabilized
nucleophiles to cation 11 is similar to the addition of malonate,
arylsulfonyl acetates and alkenyl Grignards to this same
cation.8a,c,e,f,i In contrast, the regioselectivity for addition to 12 is
considerably greater than that for addition of alkenyl Grignards to
this cation.8k Additionally, the functionality introduced onto the
(pentenediyl) ligand by the present sequence of nucleophilic
addition/Horner-Emmons olefination would not be available
within an alkenyl Grignard reagent.
In contrast to the above results, reaction of (pentadienyl)iron
cation 20 with sodium trimethyl phosphonylacetate gave a
mixture of regioisomeric cyclohexenones 21a/22a, each of which
consisted of a mixture of diastereomers at the indicated (*)
carbon (Scheme 4, Table 2). The ratio of 21a:22a was
1
determined by integration of the H NMR signals for H3 of 21a
compared to the integration of the H3 signal for 22a. Olefination
of the mixture of 21a/22a with paraformaldehyde gave a mixture
of 23a/24a; a pure sample of 23a could be obtained by column
chromatography. In a similar fashion, reaction of 20 with sodium
diethyl (2-oxopropyl)phosphonate or with sodium diethyl
(phenylsulfonyl)-methanephosphonate gave
a
mixture of
Scheme 2. Addition of phosphonate stabilized nucleophiles to (1-
methoxycarbonylpentadienyl)iron(1+) cations, and subsequent
21b/22b or 21c respectively; each of which consisted of a
mixture of diastereomers. Olefination of the mixture of 21b/22b
with formaldehyde gave a mixture of 23b/24b, while olefination
of 21c gave the vinylsulfonate 23c. The structures of 21 and 23
were assigned as 5-substituted-2-methylcyclohexenones on the
basis of their NMR spectral data. In particular, the signals for H-
3 and the Me-2 appear at ca. δ 6.7-6.6 (m) and 1.75-1.80 (s) ppm
HWE olefination. Ar
=
2,5-dimethoxyphenyl; R”
=
(CH2)4OSiPh2t-Bu. Reagents: i) Na+ –CH[P(O)(OR’)2R]; ii) base,
paraformaldehyde.
Table 1. Addition of phosphonate stabilized nucleophiles to (1-
methoxycarbonylpentadienyl)iron(1+) cations, and subsequent
HWE olefination (E = CO2Me)
1
respectively in their H NMR spectra, while the signals for C1,
C2, C3 and Me-2 appear at ca. δ 199, 135, 144, and 15.9 ppm
R5
R
R’
Product
(yield)
Base
Product
(yield)
respectively in their 13C NMR spectra.
Formation of cyclohexenone product 21 is rationalized by
nucleophilic attack at an internal pentadienyl carbon of 20 to
afford the (pentenediyl)iron complex 9 (R1 = H, R5 = Me,
Scheme 1). Carbonyl insertion followed by reductive elimination
and subsequent conjugation of the double bond affords 21.
H
H
CO2Me
Me
13a (69%) NaH
13b (66%) NaH
14a (85%) n-BuLi
14b (98%)
15a (84%)
15b (50%)
16a (90%)
C(O)Me Et
Me
Ar C(O)R” Me
Ar CO2Me
Ar = 2,5-dimethoxyphenyl; R” = (CH2)4OSiPh2t-Bu

3
3. Conclusions
ACCEPTED MANUSCRIPT
In contrast to the addition of α-phosphoramide acetate anions
to (cyclohexadienyl)iron(1+) cations, the addition of phosphonate
stabilized carbon nucleophiles to acyclic (pentadienyl)iron(1+)
cations occurs primarily at an internal dienyl carbon to form
(pentenediyl)iron complexes. The fate of the (pentenediyl)iron
products depends on the presence or absence of an electron
withdrawing ester substituent at the σ-bound carbon. Horner
Wadsworth Emmons olefination of the phosphonate addition
products generates (2-alkenyl-3-pentene-1,5-yl)iron complexes or
5-alkenyl-2-methyl-2-cyclohexenones. The latter are suitable
precursors for the preparation of 10-hydroxycarvone and
carvonic acid.
4. Experimental
4.1. General Data.
All reactions involving moisture or air sensitive reagents were
carried out under an nitrogen atomosphere in oven-dried
glassware with anhydrous solvents. THF and ether were distilled
from sodium/benzophenone. Purifications by chromatography
were carried out using flash silica gel (32-63 µ). NMR spectra
were recorded on either a Varian Mercury+ 300 MHz or a Varian
UnityInova 400 MHz instrument. CDCl3, CD3OD, d6-acetone
were purchased from Cambridge Isotope Laboratories. 1H NMR
spectra were calibrated to 7.27 ppm for residual CHCl3, 3.31 ppm
for CD2HOD, or 2.05 ppm for d5-acetone. 13C NMR spectra were
calibrated from the central peak at 77.23 ppm for CDCl3, 49.15
ppm for CD3OD, or 29.92 ppm for d6-acetone. Coupling
constants are reported in Hz. Elemental analyses were obtained
from Midwest Microlabs, Ltd., Indianapolis, IN, and high-
resolution mass spectra were obtained from the University of
Nebraska Center for Mass Spectrometry and the COSMIC lab at
Old Dominion University.
Scheme 4. Addition of phosphonate stabilized nucleophiles to (1-
methylpentadienyl)Fe(CO)3+ cation.
Table 2. Addition of phosphonate stabilized nucleophiles to (1-
methylpentadienyl)iron(1+) cations, and subsequent HWE
olefinationa
R
OR’
OMe
OEt
Product
Product
(ratio,a yield)
(ratio,a yield)
CO2Me
COMe
SO2Ph
21a+22a
(10:1, 87%)
23a+24a
(10:1, 69%)
21b+22b
(6:1, 74%)
23b+24b
(6:1, 89%)
OEt
21c (47%)
23c (72%)
aRatio of constitutional isomeric products determined by 1H
NMR integration of the β-hydrogen signals.
4.2. Tricarbonyl(5-(methoxycarbonyl)-4-(1-
methoxycarbonyldimethylphosphonomethyl)-2-penten-1,5-
diyl)iron. (±)-13a.
To a stirring suspension of sodium hydride (175 mg, 7.2 mmol)
in dry THF (120 mL) at 0 C under N2, was added trimethyl
o
10-Hydroxycarvone (25, Scheme 5) has been isolated from
Hyssopus cuspidatus, a plant used in Chinese folk medicine for
the treatment of fever and broncusus asthma.12a This terpene has
also been isolated as a minor carvone metabolite from cultured
cells of the Madagascar periwinkle, Catharanthus roseus,12b and
as an excreted metabolite of carvone in the urine of rabbits,13a and
human volunteers,13b,c while carvonic acid (26) has also been
phosphonoacetate (885 mg, 4.86 mmol). The reaction mixture
was stirred for 30 min, and then a solution/suspension of (±)-11
(2.00 g, 4.86 mmol) in dry THF (60 mL) was added. The
reaction mixture was stirred overnight, and then quenched with
water. The mixture was diluted with CH2Cl2 and the layers were
separated. The aqueous layer was extracted once with CH2Cl2
and the combined organic extracts were washed once with
saturated aqueous NaCl, and dried (MgSO4), and concentrated
under reduced pressure. The residue was purified by column
chromatography (SiO2, ethyl acetate) to afford the product (±)-
13a (372 mg, 69%) as a yellow oil; δH (400 MHz, CDC13) 4.69-
4.39 (2H, m, H-3 and H-4), 3.81-3.55 (14H, m, 4 x OCH3 and H-
2 and H-6), 2.67-2.39 (2H, m, H-5exo and H-5endo), 0.33 and
0.01 (1H total, 2 x d, J 8.7 Hz each, H-1). δC (partial, 100 MHz,
CDCl3) 210.2, 209.9, 209.7, 209.6, 203.5, 203.3, 179.7, 179.6,
167.3 (d, JCP 5.3 Hz), 166.7 (d, JCP 4.7 Hz), 97.9, 97.4, 62.7,
62.6, 60.8, 60.6, 37.4 (JCP 3.8 Hz), 37.0 (JCP 4.0 Hz), 13.3 (JCP
1.9 Hz), 12.1 (JCP 14.1 Hz). HRMS (FAB): MNa+–3CO, found
385.0110. C12H19O7PFeNa requires 385.0114.
isolated as
a
human metabolite of carvone.13b,c 10-
Hydroxycarvone has been prepared from carvone by
regioselective chlorination at C10 and subsequent solvolysis of
the halide.14,15 Saponification of 23a afforded carvonic acid 26.
Attempted reduction of 26 with borane gave a complex mixture
of products.
Alternatively, α-deprotonation of the
cyclohexenone 23a with LDA, followed by addition of DIBAL
gave 25 after workup. The spectral data obtained for 25 and 26
were consistent with their literature values.13b,14a
HO
HO2C
(±)-23a
Me
Me
O
O
4.3. Tricarbonyl(5-(methoxycarbonyl)-4-(1-diethylphosphono-2-
oxopropyl)-2-penten-1,5-diyl)iron. (±)-13b.
(±)-26
(52%)
(±)-25
(76%)
xs LDA/–78 oC;
then DIBAL
LiOH
THF/MeOH/H2O
The reaction of the anion generated from diethyl (2-oxopropyl)
phosphonate (240 mg, 1.21 mmol) and sodium hydride in dry
THF with cation 11 (500 mg, 1.21 mmol) was carried out in a
Scheme 5. Synthesis of oxygenated metabolites of carvone.

4
Tetrahedron
fashion similar to the preparation of 13a. The residue was
4.64 (1H total, 2 x d, J 12.8 Hz each, H-5), 4.57 and 4.30 (1H
ACCEPTED MANUSCRIPT
purified by column chromatography (SiO2, ethyl acetate) to
afford (±)-13b (365 mg, 66%) as a yellow oil; δH (400 MHz,
CDCl3) 4.79-4.50 (2H, m, H-3 and H-4), 4.29-4.05 (4H, m, –
OCH2CH3), 4.01-3.87 and 3.72-3.63 (2H total, H-2 and H-6),
3.76 and 3.74 (3H total, 2 x s, OCH3), 2.98-2.51 (2H, m, H-5exo
and H-5endo), 2.37 and 2.18 (3H total, 2 x s, COCH3), 1.48-1.31
(6H, m, –OCH2CH3), 0.44 and 0.01 (1H total, 2 x d, J 8.4 Hz
each, H-1). δC (partial, 100 MHz, CDCl3) 210.0 [209.7] (COMe),
203.3 [203.2], 201.9 [201.8], 201.21 [201.20] (Fe-CO), 179.6
[179.5] (-CO2CH3), 97.0 [96.8] (C-4), 64.2, 61.7, 61.5, 54.4, 51.3
[51.2] (-CO2CH3), 36.5, 36.1, 32.3, 29.8, 12.5, 11.9 [11.8] (C-1).
HRMS (FAB): MNa+, found 397.0476. C14H23O6PFeNa requires
397.0474.
total, 2 x t, J 7.2 Hz each, H-3), 3.92, 3.86, 3.79, 3.76, 3.74, 3.73,
3.72, 3.71, 3.67 and 3.65 (17 H total, 10 x s and m, OCH3 and
CH2OSi), 3.00 (0.5H, dd, JHH 11.7, JPH 22.0 Hz,
3
2
3
2
CH(COR)P(O)(OMe)2), 2.92 (0.5H, dd, JHH 11.8, JPH 21.3 Hz,
CH(COR)P(O)(OMe)2), 2.73-2.64 (1H, m), 2.40-2.30 (1H, m),
1.75-1.45 (4H, m), 1.022 and 1.018 (9H, 2 x s, SiC(CH3)3), 0.80
and 0.33 (1H total, 2 x d, J 8.4 Hz each, H-1); δP (162 MHz,
CDCl3) 21.0, 22.0. Due to the presence of two diastereomers, as
well as 31P coupling, interpretation of the 13C NMR spectrum was
not attempted.
4.6. Tricarbonyl(4-(1-methoxycarbonylethenyl)-5-
(methoxycarbonyl)-2-penten-1,5-diyl)iron. (±)-15a
To a solution of (±)-13a (40 mg, 0.088 mmol) in dry THF (3 mL)
at 0 oC was added NaH (2.6 mg). The mixture was stirred for 15
min, and then paraformaldehyde (2.6 mg, 0.11 mmol) was added
4.4. Tricarbonyl(5-(methoxycarbonyl)-4-(1-
methoxycarbonyldimethylphosphonomethyl)-1-(2,5-
dimethoxyphenyl)-2-penten-1,5-diyl)iron. (±)-14a
o
at 0 C. The reaction mixture was warmed to room temperature
The anion generated from trimethyl phosphonoacetate (0.40 g,
2.2 mmol) and NaH (58 mg, 2.4 mmol) in dry THF (10 mL) at 0
oC was added by cannula to a solution of (±)-12 (1.1 g, 2.0
mmol) in dry CH2Cl2 (50 mL) at –78 oC. After stirring for 1h at –
78 oC, the reaction mixture was slowly warmed to room
temperature, and then quenched with saturated aqueous NH4Cl.
Workup of the reaction mixture was similar to that for 13a. The
residue was purified by column chromatography (SiO2, gradient
ethyl acetate → ethyl acetate-methanol = 4:1) to afford (±)-14a
as a yellow solid (0.99 g, 85%). An analytically pure mixture of
diastereomers (ca. 2:1 ratio) was obtained by recrystallization
from CH2Cl2/hexanes; mp 150-151 oC; [Found: C, 47.37; H,
4.92. C23H30O12PFe requires C, 47.20; H, 5.17%]; δH (400 MHz,
CDCl3) major diastereomer 6.70-6.85 (3H, m, ArH), 5.27 (1H,
dd, J 7.2, 12.7 Hz, H-4), 4.66 (1H, d, J 12.8 Hz, H-5), 4.32 (1H,
t, J 7.2 Hz, H-3), 3.87, 3.72, 3.69, 3.67 (19H total, 4 x s & m,
over a 3 h period and then quenched with H2O. The mixture was
diluted with CH2Cl2 and the layers were separated. The aqueous
layer was extracted once with CH2Cl2 and the combined organic
extracts were washed once with saturated aqueous NaCl, and
dried (MgSO4), and concentrated under reduced pressure. The
residue was purified by column chromatography (SiO2, hexanes–
ethyl acetate = 17:3) to afford (±)-15a (25 mg, 84%) as a yellow
oil which solidified in the refrigerator. δH (400 MHz, CDCl3)
6.08 (1H, d, J 1.2 Hz, C=CH2), 5.36 (1H, d, J 1.6 Hz, C=CH2),
4.70 (1H, td, J 7.4, 12.0 Hz, H-4), 4.60 (1H, t, J 7.2 Hz, H-3),
4.11 (1H, br t, J 8.2 Hz, H-2), 3.72 (3H, s, OCH3), 3.69 (3H, s,
OCH3), 3.48 (1H, td, J 1.8, 7.6 Hz, H-5exo), 2.21 (1H, dd, J 2.0,
12.4 Hz, H-5endo), 0.34 (1H, d, J 8.8 Hz, H-1). δC (100 MHz,
CDCl3) 211.0, 210.4, 204.1, 180.1, 166.3, 142.7, 123.5, 97.8,
62.1, 53.9, 51.7, 51.3, 40.0, 11.0. HRMS (FAB): M2Na+–6CO,
found 555.0386. (C11H14O4Fe)2Na requires 555.0386.
3
2
OCH3 and H-2), 2.71 (1H, dd, JHH 11.3, JPH 20.6 Hz,
CH(CO2Me)P(O)(OMe)2), 0.77 (1H, d, J 8.5 Hz, H-1); minor
diastereomer: 6.85-6.70 (3H, m, ArH), 5.33 (1H, dd, J 7.2, 12.7
Hz, H-4), 4.61 (1H, d, J 12.8 Hz, H-5), 4.52 (1H, t, J 7.2 Hz, H-
3), 3.76, 3.74, 3.69, 3.67, 3.64, 3.59 (19H, 6 x s & m, OCH3 and
H-2), 2.69 (1H, dd, 3JHH 11.3, 2JPH 20.6 Hz,
CH(CO2Me)P(O)(OMe)2), 0.44 (1H, d, J 8.5 Hz, H-1); δC (100
MHz, CDCl3) major diastereomer: 210.2, 209.4, 203.7, 179.8,
167.4 (JCP 5.2 Hz), 153.6, 151.3, 128.3, 113.4, 111.5, 109.4, 93.5,
70.2, 55.9, 55.8, 54.7, 54.0, 53.4, 53.3, 52.8, 52.5, 51.4, 37.0 (JCP
7.5 Hz), 12.8 (JCP 8.5 Hz); minor diastereomer: 210.0, 209.4,
203.8, 179.7, 166.8 (JCP 4.9 Hz), 153.6, 151.3, 128.3, 113.4,
111.5, 109.4, 93.0, 56.2, 55.9, 54.8, 54.5, 53.6, 53.5, 52.7, 51.4,
37.5 (JCP 4.2 Hz), 11.6 (JCP 13.9 Hz); δP (CDCl3, 162 MHz) 21.4
(major), 21.6 (minor).
4.7. Tricarbonyl(4-(1-methenyl-2-oxypropyl)-5-
(methoxycarbonyl)-2-penten-1,5-diyl)iron. (±)-15b
The Horner-Emmons olefination of (±)-13b (360 mg, 0.789
mmol) with sodium hydride (1.13 mmol) in dry THF (30 mL),
followed by the addition of paraformaldehyde (24 mg, 0.80
mmol) was carried out in a fashion similar to the preparation of
15a. Purification of the residue by column chromatography
(SiO2, hexanes-ethyl acetate = 17:3) gave (±)-15b (131 mg, 50%)
as a yellow oil. δH (400 MHz, CDCl3) 5.91 (1H, d, J 1.8 Hz,
C=CHZ), 5.51 (1H, d, J 1.8 Hz, C=CHE), 4.69 (1H, t, J 7.0 Hz, H-
3), 4.61 (1H, td, J 7.5, 11.6 Hz, H-4), 4.15 (1H, t, J 9.0 Hz, H-2),
3.72 (3H, s, OCH3), 3.45 (1H, d, J 8.4 Hz, H-5exo), 2.25 (3H, s,
COCH3), 2.18 (1H, d, J 11.2 Hz, H-5endo), 0.36 (1H, d, J 8.8 Hz,
H-1); δC (100 MHz, CDCl3) 210.8, 210.1, 204.0, 180.4, 142.9,
124.0, 97.8, 62.4, 54.1, 52.0, 51.6, 40.3, 11.5. HRMS (FAB):
M2Na+, found 523.0483. (C11H14O3Fe)2Na requires 523.0477.
4.5. Tricarbonyl[4-(6-t-butyldiphenylsilyloxy-1-
(dimethylphosphonyl)-2-oxohexyl)-5-methoxycarbonyl-1-(2,5-
dimethoxyphenyl)-2-penten-1,5-diyl]iron. (±)-14b
4.8. Tricarbonyl(5-(methoxycarbonyl)- 4-(1-
methoxycarbonylethenyl)-1-(2,5-dimethoxyphenyl)-2-penten-1,5-
diyl)iron (±)-16a
A solution of the anion prepared from [6-(t-butyldiphenyl-
silyl)oxy]-2-oxohexylphosphonic acid dimethyl ester (0.46 g, 1.0
mmol) and NaH (48 mg, 1.2 mmol) in dry THF (30 mL) at 0 oC,
was subsequently cooled to –78 oC and a solution of (±)-12 (0.82
g, 1.5 mmol) in dry CH2Cl2 (50 mL) was added with stirring.
Workup of the reaction mixture was similar to that for 14a. The
residue was purified by column chromatography (SiO2, hexanes-
ethyl acetate = 4:1 → 2:1 gradient) to afford an equimolar
mixture of diastereomers (±)-14b (0.85 g, 98%) as a yellow solid;
mp 44-46 oC; [Found: C, 58.37; H, 5.99. C42H54O12PSiFe requires
C, 58.27; H, 6.29%]; δH (400 MHz, CDCl3) 7.68-7.62 (4H, m,
SiPh2), 7.43-7.33 (6H, m, SiPh2), 6.88-6.79 (3H, m, ArH), 5.35
and 5.15 (1H total, 2 x dd, J 7.2, 12.8 Hz each, H-4), 4.70 and
To a solution of (±)-14a (0.40 g, 0.68 mmol) in dry THF (20
mL) at –78 oC was added a solution of n-butyl lithium in hexanes
(0.47 mL, 1.6 M, 0.75 mmol). The mixture was stirred for 1 h,
and then paraformaldehyde (41 mg, 1.36 mmol) was added. The
reaction mixture was warmed to room temperature over a 3 h
period and then quenched with saturated aqueous NH4Cl. The
mixture was extracted several times with ether and the combined
organic extracts were dried (Na2SO4), and concentrated under
reduced pressure.
The residue was purified by column
chromatography (SiO2, hexanes–ethyl acetate = 4:1) to afford

5
o
(±)-16a (0.30 g, 90%) as a yellow solid. mp 163-166 C (dec).
645.0801. Due to the presence of two diastereomers, as well as
ACCEPTED MANUSCRIPT
[Found: C, 54.37; H, 4.66. C22H22O9Fe requires C, 54.34; H,
4.56%]; δH (400 MHz, CDCl3) 6.87 (1H, d, J 2.4 Hz, ArH), 6.86-
6.77 (2H, m, ArH), 6.11 (1H, d, J 2.0 Hz, C=CHZ), 5.45 (1H, d, J
2.0 Hz, C=CHE), 5.41 (1H, dd, J 7.2, 12.4 Hz, H-4), 4.52 (1H, t, J
7.2 Hz, H-3), 4.42 (1H, d, J 12.4 Hz, H-5), 4.23 (1H, br t, J 8.4
Hz, H-2), 3.89, 3.76, 3.75 and 3.72 (12H total, 4 x s, OCH3), 0.85
(1H, d, J 8.8 Hz, H-1); δC (100 MHz, CDCl3) 210.3, 209.9, 204.3,
180.4, 166.5, 153.7, 151.4, 142.6, 128.7, 124.3, 113.2, 111.6,
109.4, 93.4, 69.8, 56.1, 56.0, 55.9, 51.9, 51.6, 40.5, 10.6.
31P coupling, interpretation of the 13C NMR spectrum was not
attempted.
4.11. Tricarbonyl(5-(methoxycarbonyl)- 4-(6-oxo-1-
cyclohexenyl)-1-(2,5-dimethoxyphenyl)-2-penten-1,5-diyl)iron.
(±)-19
To a suspension of NaH (8 mg, 0.3 mmol) in dry THF (10
mL) at 0 C under N2 was added dropwise a solution of (±)-18
o
(0.10 g, 0.16 mmol) in dry THF (10 mL). The reaction mixture
was stirred for 5 h, warmed to room temperature, and then heated
at reflux for 4 h. After cooling to room temperature, the reaction
mixture was quenched with saturated NH4Cl (20 mL) and the
resulting mixture was extracted several times with CH2Cl2. The
combined extracts were concentrated under reduced pressure, and
the residue purified by column chromatography (SiO2, hexanes–
ethyl acetate = 1:1) to afford (±)-19 (40 mg, 50%) as a bright
4.9. Tricarbonyl[4-(1-(dimethylphosphonyl)-6-hydroxy-2-
oxohexyl)-5-methoxycarbonyl-1-(2,5-dimethoxyphenyl)-2-penten-
1,5-diyl]iron. (±)-17
To a solution of (±)-14b (1.00 g, 1.15 mmol) in dry THF (50
mL) under N2, was added a solution of TBAF in THF (2.3 mL,
1M, 2.3 mmol). The reaction mixture was stirred at room
temperature for 18 h, concentrated under reduced pressure, and
the residue purified by column chromatography (SiO2, ethyl
acetate → ethyl acetate-methanol = 4:1) to afford an equimolar
mixture of diastereomers (±)-17 as a yellow solid (0.58 g, 80%).
o
yellow solid. mp 160-162 C; δH (400 MHz, CDCl3) 6.85-6.75
(3H, m, ArH), 6.49 (1H, br s, H-3’), 5.29 (1H, dd, J 7.0, 12.2 Hz,
H-4), 4.63 (1H, t, J 7.6 Hz, H-3), 4.36 (1H, d, J 12.8 Hz, H-5),
4.20 (1H, br t, J 8.4 Hz, H-2), 3.90, 3.74, 3.73 (9H, 3 x s, OCH3),
2.36-2.25 (4H, m), 1.89-1.84 (2H, m), 0.86 (1H, d, J 8.8 Hz, H-
1); δC (100 MHz, CDCl3) 210.6, 210.1, 204.4, 198.4, 180.6,
153.7, 151.4, 143.9, 141.8, 129.1, 113.0, 111.6, 109.3, 93.1, 69.4,
58.3, 56.0, 55.9, 51.6, 39.3, 38.9, 25.9, 22.7, 9.7. HRMS (ESI):
MNa+, found 519.0712. C24H24O8FeNa requires 519.0718.
o
mp 45-47 C; δH (400 MHz, CDCl3) 6.88-6.77 (3H, m, ArH),
5.33 and 5.20 (1H total, 2 x dd, J 7.2, 12.8 Hz each, H-4), 4.68
and 4.64 (1H total, 2 x d, J 12.8 Hz each, H-5), 4.32 and 4.13
(1H total, t, J 7.1 Hz each, H-3), 3.96-3.92 (1H, m), 3.91, 3.90,
3.76, 3.74, 3.73, 3.72, 3.69, 3.68, 3.66 (15H, 9 x s, OCH3), 3.60-
3
2
3.56 (2H, m), 3.03 (0.5H, dd, JHH 11.7, JPH 22.0 Hz,
4.12. Carvonic acid methyl ester (±)-23a
3
2
CH(COR)P(O)(OMe)2), 2.92 (0.5H, dd, JHH 11.7, JPH 21.1 Hz,
CH(COR)P(O)(OMe)2), 2.86-2.56 (1H, m), 2.40-2.30 (1H, m),
2.20 (1H, br s), 1.75-1.45 (4H, m), 0.74 and 0.33 (1H total, 2 x d,
J 8.4 Hz each, H-1); δC (100 MHz, CDCl3) 210.0 [209.9], 209.4
[209.1], 204.1 (d, JPC 4.7), 203.7 [203.5], 203.1 (d, JPC 3.7),
179.9 [179.7], 153.6, 151.2, 128.2, 113.2, 111.5, 109.2 [109.1],
92.7 [92.6], 70.0, 61.9, 60.9, 60.6, 59.7, 56.0, 55.81, 55.77, 55.7,
55.4, 55.2, 53.3, 53.2, 53.1, 52.9, 51.4, 51.3, 45.3, 42.9, 36.9,
36.5, 31.6 [31.5], 19.5 [19.4], 12.4, 11.7 [11.6]; δP (162 MHz,
CDCl3) 21.9, 21.0. HRMS (ESI): MNa+, found 647.0958.
C26H33O12PFeNa requires 647.0957.
To a solution of the anion generated from trimethyl
phosphonoacetate (0.533 g, 2.73 mmol) and NaH (262.3 mg,
5.460 mmol) in dry THF (50 mL) at 0 oC, was added solid cation
20 (1.0 g, 2.7 mmol) in one portion. The reaction mixture
warmed to room temperature and stirred for 2 h, during this time
a yellow-brown turbidity began to appear. The reaction mixture
was diluted CH2Cl2 (50 mL), saturated solution of methanolic
NaHCO3 (80 mL) was added, and the mixture stirred overnight.
Water (30 mL) was added, and the mixture extracted several
times with CH2Cl2. The combined extracts were dried (MgSO4)
and concentrated. The residue was purified by flash column
chromatography (SiO2, ethyl acetate–hexanes = 50% → 70%
gradient) to afford a mixture of diastereomeric cyclohexenones
21a/22a as a light yellow oil (458 mg, 87%). Due to the complex
4.10. Aldehyde (±)-18
To a solution of oxalyl chloride (0.13 g, 1.0 mmol) in dry CH2Cl2
o
(10 mL) at –78 C under N2 was added dropwise a solution of
1
DMSO (0.14 mL, 2.0 mmol) in dry CH2Cl2 (10 mL). The
reaction mixture was stirred for 2 min, and then a solution of (±)-
17 (0.30 g, 0.48 mmol) in dry CH2Cl2 (10 mL) was added
dropwise over a period of 5 min. After stirring for 15 min,
triethylamine (0.5 g, 5.0 mmol) was added and the reaction
mixture was stirred for 5 min. The reaction mixture was warmed
to room temperature over a period of 1 h, and quenched with
water (50 mL). The mixture was extracted several times with
CH2Cl2, and the combined extracts were concentrated under
reduced pressure. The residue purified by column
chromatography (SiO2, ethyl acetate–methanol = 10:1) to afford
an equimolar mixture of diastereomers (±)-18 (0.30 g, quant.) as
a yellow solid. mp 40-42 oC; δH (400 MHz, CDCl3) 9.76 and 9.70
(1H total, 2 x t, J 1.0 Hz each, CHO), 6.90-6.70 (m, 3H, ArH),
5.35 and 5.22 (1H total, 2 x dd, J 7.2, 12.8 Hz each, H-4), 4.71
and 4.65 (1H total, 2 x d, J 12.8 Hz each, H-5), 4.54 and 4.32
(1H total, 2 x t, J 7.2 Hz each, H-3), 3.92, 3.91, 3.80, 3.78, 3.77,
3.75, 3.74, 3.715, 3.71, 3.70, 3.68, 3.67 (16H, 12 x s and m,
nature of the H and 13C NMR spectra, this mixture was not
further characterized.
The mixture of diastereomeric
phosphonate esters (210 mg, 0.721 mmol) was added to a
suspension of sodium hydride (43 mg, 1.1 mmol) in dry THF (20
mL) at 0 ºC. The mixture was stirred at 0 ºC for 30 min.
Paraformaldehyde (43.4 mg, 1.48 mmol) was added slowly at a
rate such that the temperature remained below 30 ºC, and the
mixture was stirred for 1 h. The mixture was diluted with H2O
and extracted several times with CH2Cl2. The combined extracts
were dried (MgSO4) and concentrated. The residue was purified
by flash chromatography (SiO2, ether–hexanes = 0% → 75%
gradient) to afford a mixture of (±)-23a and (±)-24a (10:1 ratio
1
by H NMR integration) as a pale oil (136 mg, 97%). Careful
column chromatography gave a pure sample of 23a. νmax
(CH2Cl2) 3470, 2924, 2853, 1717, 1675 1457, 1375 cm−1; δH (400
MHz, CDCl3) 6.76-6.72 (1H, m, H-3), 6.27 (1H, s, C=CH2), 5.58
(1H, s, C=CH2), 3.74 (3H, s, OCH3), 3.29-3.20 (1H, m), 2.62
(1H, ddd, J 2.4, 4.0, 16.2 Hz, H-6), 2.62-2.53 (1H, m), 2.44 (1H,
dd, J 12.8, 16.0 Hz, H-6), 2.35-2.25 (1H, m), 1.79 (3H, s, 2-Me);
δC (100 MHz, CDCl3) 199.2, 167.0, 144.4, 142.4, 135.7, 124.8,
52.2, 43.1, 37.0, 31.9, 15.9. HRMS (ESI): MNa+, found
411.1786. C11H14O3)2Na requires 411.1778.
3
2
OCH3 and H-2), 2.99 (0.5H, dd, JH3H 11.6, JPH 22.0 Hz,
2
CH(COR)P(O)(OMe)2), 2.90 (0.5H, dd, JHH 11.6, JPH 21.2 Hz,
CH(COR)P(O)(OMe)2), 2.82 (0.5H, t, J 7.0 Hz), 2.77 (0.5H, t, J
7.2 Hz), 2.52-2.34 (3H, m), 1.95-1.75 (2H, m), 0.77 and 0.32
(1H total, 2 x d, J 8.4 Hz, H-1); δP (162 MHz, CDCl3) 21.7, 20.8.
HRMS (ESI): MNa+, found 645.0811. C26H31O12PFeNa requires

6
Tetrahedron
o
4.13. Diethyl (1-(4-methyl-3-oxocyclohex-4-en-1-yl)-2-
mg, 0.13 mmol). The mixture was stirred at 0 C for 30 min,
paraformaldehyde (14 mg, 0.47 mmol) was added slowly at such
a rate that the temperature remained below 30 oC and the reaction
mixture stirred for 1 h at room temperature. The reaction mixture
was diluted H2O (10 mL) and the mixture extracted several times
with CH2Cl2. The combined extracts were dried (MgSO4) and
concentrated. The residue was purified by flash column
chromatography (SiO2, ethyl acetate-hexane = 0-45% gradient) to
afford (±)-23c (25 mg, 72%) as a pale oil. δH (300 MHz, CDCl3)
7.85 (2H, d, J 7.7 Hz, ArH), 7.65 (1H, t, J 8.3 Hz, ArH), 7.55
(2H, t, J 7.7 Hz, ArH), 6.66 (1H, d, J 5.8 Hz, H-3), 6.53 (1H, s,
C=CH2), 5.89 (1H, s, C=CH2), 3.08-2.95 (1H, m), 2.67-2.55 (1H,
m), 2.43-2.23 (3H, s & m), 1.74 (3H, s, Me-2); δC (75 MHz,
CDCl3) 197.8, 153.1, 143.8, 138.9, 135.8, 134.1, 129.7, 128.3,
124.5, 43.6, 35.6, 33.0, 15.9. HRMS (ESI): MNa+, found
299.0712. C15H16O3SNa requires 299.0709.
ACCEPTED MANUSCRIPT
oxopropyl)phosphonate (±)-21b and diethyl (1-(2-methyl-3-
oxocyclohex-4-en-1-yl)-2-oxopropyl)phosphonate (±)-22b
To an ice cold stirring suspension of NaH (25 mg, 0.62 mmol)
in freshly distilled THF (10 mL) was added dropwise diethyl 2-
oxopropylphosphonate (79 mg, 0.41 mmol) in drops. The
o
resultant mixture was stirred at 0 C for 45 min. The solid cation
20 (150 mg, 0.409 mmol) was added slowly. The reaction
mixture was stirred at room temperature for 2 h. The reaction
mixture was diluted with CH2Cl2 (10 mL) and saturated
NaHCO3/MeOH (10 mL). The reaction was stirred for 24 h. The
reaction was quenched with water (10 mL). The organic portions
were extracted several times with CH2Cl2, washed with brine,
dried (Na2SO4) and concentrated. Purification of the residue by
flash column chromatography (SiO2, ethyl acetate-hexane = 0-
60% gradient) afforded an inseparable mixture of regioisomeric
1
4.16. 10-Hydroxycarvone (±)-25
cyclohexenones (±)-21b and (±)-22b (~ 7:1 ratio by H NMR
integration) as a colorless oil (89.7 mg, 74%). H NMR (CDCl3,
1
To a stirring solution of LDA in heptanes (0.91 mL, 2.0 M,
1.8 mmol) in THF (5 mL) at –78 ºC was added dropwise a
solution of 23a (91 mg, 0.61 mmol) in THF (1 mL). The reaction
mixture was stirred at this temperature for 30 min after which a
solution of DIBAL–H in hexanes (2.8 mL, 1.0 M, 2.8 mmol) was
slowly added. The reaction mixture was stirred at –78 ºC for 3 h,
after which the mixture was warmed to room temperature and
stirred for 1 h. The reaction was quenched with water, extracted
several times with CH2Cl2, and the combined extracts were
washed with brine and concentrated. The residue was purified by
flash column chromatography (SiO2, acetone–hexanes = 0% →
35% gradient) to afford (±)-25 (56 mg, 76%) as a yellow oil. δH
(300 MHz, CD3OD) 6.92-6.85 (1H, m, H-3), 5.14 (1H, s,
C=CH2), 4.96 (1H, s, C=CH2), 4.08 (2H, s, CH2OH), 2.88-2.76
(1H, m), 2.62-2.35 (4H, m), 1.76 (3H, br s, Me-2); δH (75 MHz,
CDCl3) 199.7, 150.4, 144.6, 135.8, 110.6, 65.1, 43.5, 38.5, 31.8,
15.9. The NMR spectral data for this product was consistent
with the literature values.14a
major isomer, 300 MHz) δ 6.75-6.62 (1H, m, H-3), 4.18-4.07
(4H, m, P(O)(OCH2CH3)2), 3.22 and 3.15 (1H total, 2 x dd, J 8.7,
9.3 Hz each, CH(COMe)P(O)(OEt)2), 2.89-2.66 (2H, m), 2.43-
2.21 (3H, m), 2.33 and 2.29 (3H total, 2 x s, C(O)Me), 1.75 (3H,
s, Me-2), 1.32 (6H total, t, J 7.2 Hz, OCH2CH3); ESI-HRMS m/z
325.1175 (calcd. for C14H23O5PNa (M+Na) m/z 325.1175). Due
to the presence of two diastereomers, as well as 31P coupling,
interpretation of the 13C NMR spectrum was not attempted.
4.14. 2-Methyl-5-(1-methylene-2-oxopropyl)-2-cyclohexenone
(±)-23b and 6-Methyl-5-(1-methylene-2-oxopropyl)-2-
cyclohexenone (±)-24b
The Horner-Wadsworth-Emmons olefination of 21b/22b (74 mg,
0.25 mmol) with paraformaldehyde (14 mg, 0.47 mmol) was
carried out in a fashion similar to the preparation of 23a/24a. The
residue was purified by flash column chromatography (SiO2,
ethyl acetate-hexane: 0-60% gradient) to afford an inseparable
1
mixture of regioisomers (±)-23b and (±)-24b (~5:1 by H NMR
integration) as a pale oil (39 mg, 89%). 23b: δH (300 MHz,
CDCl3) 6.75-6.69 (1H, m, H-3), 6.14 (1H, C=CH2), 6.01 (1H, s,
C=CH2), 3.42-3.28 (1H, H-5), 2.58-2.42 (2H, m, H-6 & H-6’),
2.41-2.30 (4H, m & s, MeCO & H-4), 2.26-2.12 (1H, m, H-4’),
1.78 (3H, s, Me-2); δC (75 MHz, CDCl3) 199.5, 199.3, 150.7,
144.6, 135.6, 125.2, 43.1, 35.4, 32.1, 26.6, 15.9. 24b: δH (300
MHz, CDCl3, partial) 6.93-6.84 (m), 6.20 (s), 6.05-5.98 (m), 6.87
(s), 3.13-2.99 (m), 2.72-2.60 (m). HRMS (ESI): MNa+, found
201.0886. C11H14O2Na requires 201.0887.
4.17. Carvonic acid (±)-26
To
a
solution of (±)-23a (69 mg, 0.46 mmol) in
THF/methanol/H2O (2:2:1, 4 mL) was added in small portions
lithium hydroxide (116 mg, 2.77 mmol). The mixture was stirred
at room temperature for 1 h and then the mixture was acidified
with dilute aqueous HCl and the resulting mixture was extracted
several times with ethyl acetate. The combined extracts were
washed with brine, dried (NaSO4) and concentrated. The residue
was purified by flash chromatography (SiO2, acetone–hexanes =
0% → 50 % gradient) to afford carvonic acid (±)-26 (43 mg,
52%) as a yellowish oil. δH (300 MHz, CDCl3) 6.80-6.72 (1H, m,
H-2), 6.44 (1H, s, C=CH2), 5.72 (1H, s, C=CH2), 3.32-3.20 (1H,
m, H-5), 2.66 (1H, dd, J 2.8, 11.8 Hz, H-6), 2.62-2.57 (1H, m),
2.48 (1H, dd, J 9.6, 12.3 Hz, H-6’), 2.40-2.29 (1H, m), 1.80 (3H,
s, Me-2); δC (CDCl3, 75 MHz) 199.2, 144.4, 141.8, 135.8, 127.2,
43.1, 36.8, 31.8, 15.9, signal for COOH not observed. The NMR
spectral data for this product was consistent with the literature
values.13b
4.15. 2-Methyl-5-(1-phenylsulfonylethenyl)-2-cyclohexenone (±)-
23c
To an ice cold stirring suspension of NaH (25 mg, 0.62 mmol) in
freshly distilled THF (10 mL) was added dropwise diethyl
(phenylsulfonyl)methylphosphonate (116 mg, 0.409 mmol). The
o
resultant mixture was stirred at 0 C for 45 min. The solid cation
20 (150 mg, 0.409 mmol) was added slowly. The reaction
mixture was stirred at room temperature for 2 h. The reaction
mixture was diluted with CH2Cl2 (10 mL) and saturated
NaHCO3/MeOH (10 mL). The reaction was stirred for 24 h. The
reaction was quenched with water (10 mL). The organic portions
were extracted several times with CH2Cl2, washed with brine,
dried (Na2SO4) and concentrated. Purification of the residue by
flash column chromatography (SiO2, ethyl acetate-hexane = 0-
80% gradient) afforded 21c as a pale oil (76 mg, 47%). HRMS
(ESI): MNa+, found 423.1002. C18H25O6SPNa requires 423.1002.
This compound was used in the olefination reaction without
further characterization. To an ice-cold stirring suspension of
NaH (6 mg, 0.2 mmol) in dry THF (3 mL) was added 21c (50
Acknowledgments
This work was supported by the National Science Foundation
(CHE-0848870) and NSF instrumentation grant (CHE-0521323).
High-resolution mass spectra were obtained at the Old Dominion
University COSMIC facility.

7
Soc. 2006, 128, 5984-5985. (d) Chaudhury, S.; Li, S.; Bennett,
References and notes
ACCEPTED MANUSCRIPT
D. W.; Siddiquee, T.; Haworth, D. T.; Donaldson, W. A.
Organometallics 2007, 26, 5295-5303. (e) Manful, C. F.;
Donaldson, W. A. Eur. J. Org. Chem. 2014, 6787-6795.
1. (a) Harrington, P. J. Transition Metals in Total Synthesis, John
Wiley & Sons: New York, 1990. (b) Pearson, A. J. Science 1984,
223, 895-901; Birch, A. J.; Kelly, L. F.; Weerasuria, D. V. J. Org.
Chem. 1988, 53, 278-281; (c) Roe, C.; Stephenson, G. R. Org.
Lett. 2008, 10, 189-192; Bauer, I.; Knolker, H. J. In Chemistry of
Organoiron Compounds; Marek, I.; Rappoport, Z., Ed.; John
Wiley & Sons Ltd: Chichester, UK, 2014; pp 155–232;
7. For other organoiron routes to cyclohexenones see: (a) Aumann,
R. J. Am. Chem. Soc. 1974, 96, 2361-2362. (b) Schulze, M. M.;
Gockel, U. J. Organomet. Chem. 1996, 525, 155-158. (c) Taber,
D. F.; Kanai, K.; Jiang, Q.; Bui, G. J. Am. Chem. Soc. 2000, 122,
6807-6808. (d) Taber, D. F.; Bui, G.; Chen, B. J. Org. Chem.
2001, 66, 3423-3426. (e) Taber, D. F.; Joshi, P. V.; Kanai, K. J.
2. (a) Birch, A. J.; Kelly, L. F.; Thompson, D. J. J. Chem. Soc.,
Perkin Trans. 1 1981, 1006-1012. (b) Pearson, A. J.; Kole, S. L.;
Ray, T. J. Am. Chem. Soc. 1984, 106, 6060-6074. (c) Paquette, L.
A.; Daniels, R. G.; Gleiter, R. Organometallics 1984, 3, 560-567.
(d) Pearson, A. J.; Burello, M. P. Organometallics 1992, 11, 448-
456. (e) Millot, N.; Guillou, C.; Thal, C. Tetrahedron 1997, 53,
12553-12564. (f) Knoelker, H.-J.; Baum, E.; Heininger, M.
Tetrahedron Lett. 1997, 38, 8021-8024. (g) Ong, C. W.; Wang, J.
N.; Chien, T.-L. Organometallics 1998, 17, 1442-1445. (h) Anson,
C. E.; Hudson, R. D. A.; Osborne, S. A.; Smyth, D. G.;
Org. Chem. 2004, 69, 2268-2271. (f) Taber, D. F.; Sheth, R. B. J.
Org. Chem. 2008, 73, 8030-8032.
8. (a) Yun, Y.K.; W. A. Donaldson, W. A. J. Am. Chem. Soc., 1997,
119, 4084-5. (b) Godula, K.; Donaldson, W. A. Tetrahedron Lett.
2001, 42, 153-154. (c) Yun, Y. K.; Godula, K.; Cao, Y.;
Donaldson, W. A. J. Org. Chem. 2003, 68, 901-910. (d) Lukesh, J.
M.; Donaldson, W. A. Chem. Comm. 2005, 110-112. (e) Wallock,
N. J.; Donaldson, W. A. Org. Lett. 2005, 7, 2047-2049. (f)
Wallock, N. J.; Bennett, D. W.; Siddiquee, T. A.; Haworth, D. T.
Donaldson, W. A. Synthesis, 2006, 3639-3646. (g) Pandey, R. K.;
Lindeman S.; Donaldson, W. A. Eur. J. Org. Chem. 2007, 3829-
3831. (h) Siddiquee, T. A.; Lukesh, J. M.; S. Lindeman, S.;
Donaldson, W. A. J. Org. Chem., 2007, 72, 9802-9803. (i)
Pandey, R. K.; Wang, L.; Wallock, N. J.; Lindeman, S.;
Donaldson, W. A. J. Org. Chem. 2008, 73, 7236-7245. (j) Gone, J.
R.; Wallock, N. J.; Lindeman, S.; Donaldson, W. A. Tetrahedron
Lett. 2009, 50, 1023-1025. (k) Lee, D. W.; Pandey, R. K.;
Lindeman, S.; Donaldson, W. A. Org. Biomol. Chem. 2011, 9,
7742-7747.
9. All compounds are racemic mixtures of enantiomers. Only one
enantiomer has been pictured for clarity.
10. Tao, C.; Donaldson, W. A. J. Org. Chem. 1993, 58, 2134-2143.
11. Toshima, H.; Aramaki, H.; Ichihara, A. Tetrahedron Lett. 1999,
40, 3587-3590.
12. (a) Furukawa, M.; Makino, M.; Ohkoshi, E.; Uchiyama, T.;
Fujimoto, Y. Phytochem. 2011, 72, 2244-2252. (b) Hamada, H.;
Yasumune, H.; Fuchikami, Y.; Hirata, T.; Sattler, I.; Williams, H.
J.; Scott, A. I. Phytochem. 1997, 44, 615-621.
13. (a) Ishida, T.; Toyota, M.; Asakawa, Y.; Xenobiotica 1989, 19,
843-855. (b) Engel, W. J. Agri. Food Chem. 2001, 49, 4069-4075.
(c) Engel, W. J. Agri. Food Chem. 2002, 50, 1686.
Stephenson, G. R. Tetrahedron Lett. 1998, 39, 7603-7606. (i)
Chou, S.-S. P.; Liu, S.-H. J. Organomet. Chem. 1998, 555, 227-
236. (j) Graden, H.; Hallberg, J.; Kann, N.; Olsson, T. J. Comb.
Chem. 2004, 6, 783-788. (k) Pearson, A. J.; Richards, I. C.;
Gardner, D. V. J. Org. Chem. 1984, 49, 3887-3891. (l) Pearson, A.
J.; Kole, S. L.; Yoon, J. Organometallics 1986, 5, 2075-2081. (m)
Mincione, E.; Bovicelli, P.; Cerrini, S.; Lambda, D. Heterocycles
1985, 23, 1607-1610. (n) Birch, A. J.; Chamberlain, K. B.;
Thompson, D. J. J. Chem. Soc., Perkin Trans. 1 1973, 1900-1903.
(o) Birch, A. J.; Bogsanyi, D.; Kelly, L. F. J. Organomet. Chem.
1981, 214, C39-C42. (p) Yeh, M. C. P.; Tsao, W. C.; Wang, Y. J.;
Pai, H. F. Organometallics 2007, 26, 4271-4277. (q) Stephenson,
G. R.; Finch, H.; Owen, D. A.; Swanson, S. Tetrahedron 1993, 49,
5649-5662. (r) Sandoe, E. J.; Stephenson, G. R.; Swanson, S.
Tetrahedron Lett. 1996, 37, 6283-6286. (s) Pearson, A. J.; Roden,
B. A. J. Chem. Soc., Perkin Trans. 1 1990, 723-725. (t)
Stephenson, G. R.; Voyle, M.; Williams, S. Tetrahedron Lett.
1990, 31, 3979-3982.
3. Stephenson, G. R.; Milne, K. Aust. J. Chem. 1994, 47, 1605-1612.
Paoltai, I. M.; Stephenson, G. R.; Kane-Maguire, L. A. P. J.
Organometal. Chem. 1987, 319, C5-C10.
4.
For an intramolecular addition of phosphonate-stabilized
nucleophiles on cationic Ru-arenes see: Pigge, F. C.; Coniglio, J.
J.; Dalvi, R. J. Am. Chem. Soc. 2006, 128, 3498-3499. For
intermolecular substitution of haloarene-iron cations see:
Artamkina, G. A.; Pazonov, P. K.; Beletskaya, I. P. Tetrahedron
Lett. 2001, 42, 4385-4387.
14. (a) Xuan, M.; Paterson, I.; Dalby, S. M. Org. Lett. 2012, 14, 5492-
5495. (b) Weinges, K.; Schwarz, G. Liebigs Ann. Chem. 1993,
811-814.
15. Parenthetically, (±)-carvone has been prepared from racemic
tricarbonyl(2-methoxy-1-methylcyclohexadiene)iron in 3 steps,
14% overall yield: G. R. Stephenson, J. Chem. Soc., Perkin Trans.
1 1982, 2449-2456.
5. For reviews see: (a) Gree, R. Synthesis 1989, 341-355. (b) Gree,
R.; Lellouche, J. P. In Advances in Metal-Organic Chemistry,
Liebeskind, L. S., Ed.; JAI Press Inc.: Greenwich, CT, 1995; Vol.
4, pp 129-273. (c) Iwata, C.; Takemonto, Y. Chem. Commun.
1996, 2497-2504. (d) Donaldson, W. A. Aldrichimica Acta 1997,
30, 17-24. (e) Cox, L. R.; Ley, S. V. Chem. Soc., Rev. 1998, 27,
301-314. (f) Donaldson, W. A. Curr. Org. Chem. 2000, 4, 837-
868. (c) Donaldson, W. A.; Chaudhury, S. Eur. J. Org. Chem.
2009, 3831-3843. (d) Knoelker, H.-J. In Organometallics in
Synthesis, Third Manual, Schlosser, M. Ed.; John Wiley & Sons:
New Jersey, 2013; pp 545-776.
Supplementary Material
The supplementary data associated with this article include 1H
and 13C NMR spectra of compounds 13a, 13b, 14a, 14b, 15a,
15b, 16a, 17, 18, 19, 23a, 21b/22b, 23b/24b, 23c, 25, and 26,
and can be found in the online version at
6. (a) McDaniel, K. F.; Kracker, L. R., II Tetrahedron Lett. 1990, 31,
2373-2376. (b) Donaldson, W. A.; Shang, L.; Tao, C.; Yun, Y. K.;
Ramaswamy, M.; Young, V. G., Jr. J. Organomet. Chem. 1997,
539, 87-98. (c) Chaudhury, S.; Donaldson, W. A. J. Am. Chem.