Novel intramolecular cyclocarbonylations involving π-alkene-hydridoiron intermediates: From [η5-C5H5(CO)2Fe]-substituted (Z)-enals to α,β- butenolides and γ-butyrolactones

Article abstract of DOI:10.1002/(SICI)1521-3765(19990301)5:3<1038::AID-CHEM1038>3.0.CO;2-6

In order to broaden the application of [η⁵-C₅H₅(CO)₂Fe]-substituted enals, reaction cascades were developed for the construction of five-membered lactone skeletons, initiated by the regioselective reduction of t

Full text of DOI:10.1002/(SICI)1521-3765(19990301)5:3<1038::AID-CHEM1038>3.0.CO;2-6

FULL PAPER
Novel Intramolecular Cyclocarbonylations Involving p-Alkene-Hydridoiron
Intermediates: From [h5-C5H5(CO)2Fe]-Substituted (Z)-Enals
to a,b-Butenolides and g-Butyrolactones
Karola Rück-Braun,* Christian Möller[a]
Abstract: In order to broaden the application of [h5-C5H5(CO)2Fe]-substituted enals,
reaction cascades were developed for the construction of five-membered lactone
skeletons, initiated by the regioselective reduction of the aldehyde functionality with
sodium borohydride or K-Selectride. Depending on the iron compound and the
reagent employed, a,b-butenolides or g-lactones were obtained. The key steps in the
reaction cascade for the formation of a,b-butenolides involve carbonylation and
reductive elimination. Labeling experiments, which were carried out to provide
mechanistic details of the subsequent g-lactone formation, are in agreement with a
reduction step which involves a p-alkene hydridoiron intermediate. Proposed
reaction pathways are given.
Keywords: carbonylations ´ domino
reactions ´ enals ´ iron ´ lactones
complexes.[9] The sequential insertion of carbon monoxide
and alkynes into alkylmanganese pentacarbonyl complexes at
high pressure (2 ± 10 kbar) gives acyl-coordinated manganese
complexes, which, upon treatment with the diisobutylalumi-
niumhydride-butyllithium complex, furnish a,b-butenolides
by an intramolecular version of the Reppe reaction.[10]
We recently reported the synthesis of a,b-unsaturated g-
lactams from titanium tetrachloride-mediated transformations
of analogous (Z)-configured vinyl iron formyl complexes 2
with electron-rich primary amines.[11] These iron compounds
are readily available from the corresponding 3-halogeno (Z)-
alkenals[11, 12] 1 and the sodium ferrate complex [h5-C5H5-
(CO)2Fe]Na by an addition ± elimination process. In order to
promote the practical application of the iron compounds 2
and to gain further insight into the mechanism of g-lactam
formation,[11, 12] reactions with other nucleophiles were inves-
tigated. In this paper reaction cascades initiated by the attack of
hydride at the aldehyde group of 2 to give either a,b-butenolides
3 or the saturated g-lactones 4 (Scheme 1) are presented.
In the course of our investigations, differences in the
reactivity of the iron compounds as well as in the progress of
the reaction cascades, initiated by a series of hydride donors,
were observed. Labeling studies provided mechanistic details
and thereby a basis on which to establish a reasonable
working hypothesis regarding the reaction mechanism. Thus,
the reduction to the saturated g-lactones 4 can be traced back
to the formation of a p-alkene-hydridoiron intermediate after
ring closure to produce the butenolide framework during
reductive elimination.
Introduction
Well-defined carbonylation reactions have been developed
for use in organic synthesis in recent years.[1] Various concepts
and strategies rely on intramolecular cyclocarbonylations. For
instance, titanium-catalyzed[2] and iron-promoted syntheses[3]
of bicyclic ring systems from enynes have been recently
reported. During the last two decades, many efforts have been
directed towards the development of catalytical and stoichio-
metric palladium-mediated carbonylation methodologies.[1, 4]
Whereas the synthesis of lactones could be achieved starting
from hydroxyvinyl iodides,[5] triflates,[6] allyl alcohols, or
ortho-halogeno-substituted benzylalcohols, the construction
of lactams was accomplished, for example, from allylamines
or the appropriately substituted benzylamines as the starting
materials.[1, 6b] Higher temperatures and pressures of carbon
monoxide are usually required for these transformations. In
addition, stoichiometric multicomponent carbonylations have
also attracted considerable interest. For example, hydroxybu-
tenolides have been obtained from the cobalt-mediated
ꢀ
reaction of [(CO)4Co]Na, MeI, HC CR, H2O, and 2CO in
a sequential insertion cascade.[7, 8] More recently, other teams
have applied a related methodology to the synthesis of a,b-
butenolides by the use of organomanganese pentacarbonyl
[a] Priv. Doz. Dr. K. Rück-Braun, Dipl.-Chem. C. Möller
Institut für Organische Chemie der Universität
J.-J.-Becherweg 18 ± 20, 55099 Mainz (Germany)
Fax : (‡ 49)6131-39-4786
E-mail: rueck-braun.k@primusonline.de
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Chem. Eur. J. 1999, 5, No. 3

1038±1044
tions with hydride donors were examined. Fortunately, sodium
borohydride, the reducing reagent which was examined first,
was found to work well. The treatment of 2a and 2b with 1.1 ±
1.4 equivalents of NaBH4 in ethanol or ethanol/dichloro-
methane at room temperature afforded the a,b-butenolides
3a and 3b, exclusively, as indicated by IR and NMR
spectroscopy of the crude products obtained (Scheme 2).
Scheme 1. Synthesis of a,b-butenolides 3 and g-butyrolactones 4 from the
reactions of [h5-C5H5(CO)2Fe]-substituted enals 2 with reducing reagents.
Results and Discussion
The iron compounds 2 are available from the reaction of
ferrates and the corresponding b-halogeno vinyl aldehydes 1,
as described previously.[11, 12] The latter can be prepared, for
example, from the appropriate a-methylene ketones and
Vilsmeier± Haack reagents.[13] For instance, the compounds
2e and 2 f (Table 1) were synthesized in a two-step sequence
starting from thiochromanone and 4-tert-butyl-cyclohexa-
none: the corresponding ketones were treated with DMF/
PBr3 to give the desired b-bromo enals 1e and 1 f (see the
Experimental Section), which were then treated with the
sodium ferrate complex to yield the fairly air-stable iron
compounds 2e (66%) and 2 f (70%) after column chroma-
tography.
Scheme 2. Fp ˆ [h5-C5H5(CO)2Fe].
The characteristic nÄ(C ˆ O) band of these compounds is
observed at ꢁ1750 cm 1 in dichloromethane. In general, after
complete consumption of the starting materials (TLC mon-
itoring) the reaction mixtures were immediately hydrolyzed
by the addition of saturated aqueous NH4Cl solution. The
crude products were purified by flash chromatography on
Florisil to furnish 3a and 3b in 67% and 50% yield. This also
separated the ferrocene byproduct that stems from the iron
fragment. Iron oxide and hydroxide residues can be removed
by precipitation and filtration, as described in detail in the
Experimental Section.
During an attempt to utilize iron derivatives 2 in reaction
cascades leading to five-membered lactone skeletons, reac-
Table 1. Reactions of [h5-C5H5(CO)2Fe]-substituted (Z)-enals 2d-2 f with
NaBH4 (method A) and K-Selectride (method B).
In the case of compound 2c, the treatment with NaBH4 was
complete within 30 min and gave two new products. After
acidic workup and purification by chromatography, the main
product was found to be the saturated g-lactone 4c (nÄ ˆ
Reactant Method Time [h]
Yield [%][a]
Ratio[b]
[3:4]
3
4
1
2
3
4
5
6
7
8
2d
2d
2d
2e
2e
2 f
2 f
2 f
A
A
B
A
A
A
A
B
3
5.25
3
54 (3 ‡ 4)
63:37
0:100
0:100
45:55
0:100
55:45
55:45
0:100
±
±
4d: 57
4d: 27
4e: 28
4e: 38
trans-4 f: 31[c]
trans-4 f: 28[c]
cis-4 f: 36
1
1773 cm ), which was isolated in 74% yield along with the
4.5
3e: 23
±
3 f: 38
3 f: 34
±
minor product lactone 5 in 19% yield (Scheme 3).
20
2.7
20
0.8
In contrast, the NaBH4-mediated reactions of the iron
compounds listed in Table 1 (method A) gave mixtures of the
corresponding a,b-butenolides 3 and g-lactones 4, which were
isolated upon hydrolysis of the reaction mixtures immediately
after complete consumption of the starting materials (see
Scheme 1 and Table 1, entries 1, 4 and 6).
[a] Isolated yield. [b] 1H NMR spectroscopy of the crude reaction mixture.
[c] Ratio trans:cis ˆ 86:14 for 4 f.
However, if the reaction time for the iron compounds 2d
and 2e was prolonged, then only the saturated g-lactones 4d
and 4e were obtained. Compound 4e was isolated in
significantly lower yield (Table 1, entries 2 and 5). For the g-
lactones 4c (Scheme 3) and 4e the cis-configuration was
assigned, in accordance with the coupling constants (J ꢁ
8.3 Hz) in the 1H NMR spectra.[14] In contrast, for the
aliphatic g-lactone 4 f (Table 1, entries 6 and 7), obtained
from 2 f and NaBH4, the predominant formation of the trans-
Abstract in German: Fünfringlactone können aus b-Cyclo-
pentadienyl(dicarbonyl)eisen-substituierten (Z)-Enalen über
intramolekulare Reaktionskaskaden unter Carbonylierung
durch den Einsatz von Reduktionsmitteln, wie Natriumbor-
hydrid oder K-Selectride, hergestellt werden. In Abhängig-
keit vom Reduktionsmittel und der Reaktivität der eingesetz-
ten eisenorganischen Verbindung sind a,b-Butenolide oder
gesättigte g-Lactone isolierbar. Die Ergebnisse mit deuterier-
ten Reagenzien beweisen, daû die Bildung der gesättig-
ten g-Lactone durch Reduktion der Doppelbindung nach
Carbonylierung und reduktiver Eliminierung über den
intermediär gebildeten p-Olefinhydridoeisenkomplex bewirkt
wird.
1
isomer (ratio trans:cis ˆ 86:14) was ascertained by H NMR
spectroscopy.[15]
Evidently, the outcome of the reaction cascade depends on
the reactivity of the b-cyclopentadienyl(dicarbonyl)iron-sub-
stituted (Z)-enals 2 and the reaction time. Variation of the
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K. Rück-Braun, C. Möller
FULL PAPER
Labeling experiments were
undertaken to clarify the for-
mation of the saturated g-lac-
tones. The treatment of the iron
compound 2c with NaBD4 in
ethanol gave the g-lactone 6 in
ꢁ70% yield and, according to
1H NMR spectroscopy, exclu-
sively deuterated at C5 of the
Scheme 3. Labeling experiments with 2c.
lactone skeleton (Scheme 3). In
amount of NaBH4 from 1.0 to 2.0 equivalents did not result in
any change. Thus, the reactivity of the iron compounds 2 and
consequently of the corresponding intermediates involved in
the reaction cascades (Scheme 4) is strongly influenced by the
addition, the side product 7 was isolated in 17% yield, with
deuterium incorporated in position 5 (see the Experimental
Section). This proves that NaBH4 does not bring about the
reduction of the a,b-unsaturated lactone moiety in the course
of the reaction cascade.
In an alternative procedure, compound 2c was treated with
NaBD4 in [D1]ethanol to furnish 8 in 57% yield, along with
the deuterated side product 9 (37%). In product 8 the
1
incorporation of deuterium was detected by H NMR spec-
troscopy at positions 3, 4, and 5 (100% deuteration) on the
lactone moiety. These results led us to envision the working
hypothesis shown in Scheme 4.
The formation of the a,b-butenolides can be rationalized by
the reaction cascades shown, starting with the attack of the
hydride at the aldehyde group to give the boron alkoxide A.
The latter would then undergo an intramolecular carbon-
ylation reaction by nucleophilic attack at one of the CO
ligands (pathway A) to give the ferrilactone intermediate B,
as previously discussed for the formation of a,b-unsaturated
g-lactams.[12] In analogy, a vinyl migration step followed by
intramolecular nucleophilic attack of the alkoxide at the acyl
iron intermediate C (pathway B) also has to be consid-
ered.[11, 12] However, after reductive elimination the stabiliza-
tion of the remaining iron moiety with vacant coordination
sites by h2-coordination to the double bond of the a,b-
butenolide framework seems to be reasonable. Proton trans-
fer from the solvent to an electron-rich or even charged iron
intermediate (structure B) during the carbonylation or the
reductive elimination step would furnish a p-alkene hydri-
doiron species D, as outlined in Scheme 4. This intermediate
would be responsible for the subsequent reduction step that
yields the a-iron-substituted lactone compound E or its iron
enolate F by conjugate addition to the a,b-unsaturated
lactone moiety. Thus, the transfer of a proton from the
solvent to either intermediate E or F yields the saturated
lactone. The reactions performed with deuterated reagents
underline this hypothesis. Evidently, the formation of the
byproducts 5, 7, and 9 takes place by an alternative pathway, as
depicted in Scheme 5. An attack by the hydride function
(structure G) or by the negatively charged iron center
(structure H) on the methylene group next to the ring oxygen
in an internal SN2 process would result in the opening of the
chromanone ring with the phenol residue functioning as a
leaving group. Pathway B would give an allyliron intermedi-
ate I prior to protonation to yield 5. The deuterium
incorporation determined for 7 and 9 also supports these
assumptions.
Scheme 4. Proposed mechanism for the formation of g-lactone that
involves a p-alkene-hydridoiron intermediate.
electronic properties of the substituents at the alkene unit. In
the case of the chromanone derivative 2c, activation of the
aryl-substituted a,b-unsaturated moiety by the alkoxy sub-
stituent in the ortho-position at the aryl residue has to be
considered. So far, only the five-membered iron compound 2g
(R1, R2 ˆ (CH2)3, Scheme 1) did not form a lactone frame-
work upon reduction of the aldehyde group with NaBH4 to
the boron alkoxide, possibly for steric reasons.[12]
Additional reducing reagents were examined for certain
iron complexes; LiAlH4 proved to be less efficient compared
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Intramolecular Cyclocarbonylations
1038±1044
mediated process described above, K-Selectride gives rise to a
sequential transformation[16] that leads to a ferrilactone
intermediate (Scheme 4, pathway A, structure B). The IR
data are in agreement with the bands expected for such
electron-rich or even anionic intermediates, with the charac-
teristic n(CO) absorptions shifted to lower frequencies
compared with the reported neutral, stable complexes of
related structures.[4, 17, 18] These intermediates decompose only
upon the addition of water, evidently by a well-defined
reaction sequence, to afford the g-lactone derivatives 4. In
contrast to the NaBH4 reaction, here the addition of water is
necessary for the reaction cascade to proceed after the
carbonylation step. However, the latter should indeed pro-
ceed according to pathway A, Scheme 4, as supported by the
IR data. When the reaction of 2c with K-Selectride was
hydrolyzed with D2O the incorporation of deuterium at
positions 3 and 4 was observed for 10 (see Scheme 3 and the
Experimental Section).
Scheme 5. Proposed mechanism for the formation of byproduct 5.
with NaBH4. For instance, in the range of 08C to room
temperature the reaction of 2c with LiAlH4 (0.5 equiv) in
THF for 18 hours gave unsatisfactorily results: the g-lactone
4c was isolated in 7% yield. The formation of 5 was detected
Conclusions
So far, a considerable amount of progress has been achieved
in the development of reaction cascades that lead to five-
membered lactone skeletons starting from iron-substituted
enals 2 and the appropriate hydride donors. Efforts will be
continued to improve the yields and the selectivity of a,b-
butenolide versus g-lactone formation reaction. Furthermore,
additional reducing reagents will be examined to clarify the
reaction pathway and the factors which influence the carbon-
ylation step, the reductive elimination sequence, and the
formation of p-alkene-hydridoiron intermediates during the
course of the reaction cascades. Our current interest is
directed towards the development of reaction cascades
initialized by the addition of C-nucleophiles to furnish
5-substituted a,b-butenolides.
1
by H NMR spectroscopy of the crude product. Attempts to
employ diisobutylaluminiumhydride (DIBALH) in THF at
788C as the reagent for lactone formation were completely
unsuccessful. Although the reduction of the aldehyde moiety
of 2c was nearly quantitative (IR monitoring), additional
reaction steps were not observed.
The application of K-Selectride as the reagent was also
investigated; these reactions were studied in THFat 308C to
room temperature (method B in Table 1, Scheme 1). Only the
iron compound 2b gave the corresponding a,b-butenolide 3b
1
(19%), as ascertained by the H NMR spectra of the crude
reaction product. As can be seen in Table 1, for all other
examples only the saturated g-lactones were detected by TLC
or 1H NMR spectroscopy after hydrolysis and were isolated in
yields of 27 ± 65%. The reaction of 2 f and K-Selectride only
gave cis-4 f, in contrast to the results of the NaBH4-mediated
domino process (Table 1, entries 6, 7, and 8). The latter was
isolated in 36% yield after flash chromatography. Upon
treatment of compound 2c with K-Selectride, the formation
of the ring-opened byproduct 5 (see Scheme 3) was detected
only in isolated cases, possibly depending upon the hydrolysis
procedure employed.
Experimental Section
All reactions were carried out under an atmosphere of argon in oven-dried
glassware by standard needle/syringe techniques. THF was dried and
distilled from potassium/benzophenone under argon and degassed (ultra-
sound) before use. Solvents for chromatography were of technical quality
and were purified as follows: petroleum ether (40 ± 608C) was distilled
from P2O5, ethyl acetate from K2CO3, and diethyl ether from KOH/
Cu(i)Cl. K-Selectride (1m in THF) was purchased from Aldrich, sodium
amalgam (2%) from Lancaster, and [{Cp(CO)2Fe}2] from Fluka. Buffer
solutions were used as indicated (pH 6: 7.86 g citric acid monohydrate ‡
22.28 g Na2HPO4 ´ 2H2O in 1.0 L of water; pH 7: 3.99 g citric acid
monohydrate ‡ 28.84 g Na2HPO4 ´ 2H2O in 1.0 L of water). All reactions
were monitored by analytical thin-layer chromatography (TLC, silica gel,
Much attention was devoted to the improvement of the
hydrolysis procedure and thus the yield. However, signifi-
cantly lower yields were observed under a variety of acidic
and alkaline conditions. It is possible that undesirable side
reactions can occur during hydrolysis because of the presence
of the borane. In all the examples presented in Table 1
(method B) the turnover was monitored by IR spectroscopy.
Thus, the disappearance of the characteristic n(CO) stretching
frequencies of the starting materials and the appearance of
Merck 60
F254 plates) and visualized by UV light, basic potassium
permanganate, or acidic phosphomolybdic acid/cerium(iv)sulfate. The
products were purified by column chromatography on Baker silica gel
(0.06 ± 0.2 mm) and by flash chromatography on Merck silica gel 60 (230 ±
400 mesh) or Florisil (140 ± 200 mesh, supplied by Fluka), unless otherwise
stated. Melting points were measured on a Büchi apparatus and are
uncorrected. IR spectra were recorded on a Perkin ± ElmerFT IR-
Spectrometer 1760X. NaCl cells were used for IR monitoring. 1H and
13C NMR spectra were recorded on a Bruker AC200, or a Bruker AM400
in CDCl3, unless otherwise stated. For some signal assignments, standard
techniques such as homo- and heteronuclear decoupling experiments,
1
two new absorptions at nÄ ˆ 1970 ± 1960 cm and 1820 ±
1
1
1810 cm , as well as a shoulder at ꢁ1850 ± 1830 cm was
observed, in addition to a new absorption at nÄ ˆ 1690 ±
1
1670 cm . Evidently, unlike the domino process which
furnishes a,b-unsaturated g-lactams[11, 12] and the NaBH4-
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K. Rück-Braun, C. Möller
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2D COSY or heterocorrelation were employed. Mass spectra were
obtained on a Varian MATCH7a or a Finnigan MAT95. The elemental
analyses were performed by the Microanalytical Division of the Institute of
Organic Chemistry, Johannes Gutenberg-Universität, Mainz (Germany).
bed above gave 1.47 g (70%) of 2 f as a dark yellow, amorphous solid. M.p.
1518C; Rf ˆ 0.47 (petroleum ether/ethyl acetate 2:1); 1H NMR (200 MHz,
C6D6): d ˆ 10.07 (s, 1H, CHO), 3.91 (s, 5H, C5H5), 3.06 ± 2.93 (m, 1H),
2.66 ± 2.59 (m, 2H), 2.33 ± 2.19 (m, 1H), 1.64 ± 1.56 (m, 1H), 1.26 ± 1.05 (m,
2H), 0.94 (s, 9H); 1H NMR (200 MHz, [D6]DMSO): d ˆ 9.71 (s, 1H, CHO),
5.15 (s, 5H, C5H5), 3.00 ± 2.91 (m, J ˆ 7.9 Hz, 1H), 2.66 ± 2.57 (m, 1H),
2.42 ± 2.33 (m, J ˆ 3.9, 7.3 Hz, 1H,), 1.81 ± 1.59 (m, J ˆ 7.4 Hz, 2H), 1.23 ±
1.12 (m, J ˆ 3.4 Hz, 1H), 0.92 ± 0.89 (m, 1H, overlayed by the adjacent
singlet), 0.82 (s, 9H); 13C NMR (13C{1H} DEPT 135 NMR, 50.3 MHz): d ˆ
216.3 (s), 215.8 (s), 196.9 (d), 146.1 (s), 87.2 (d), 51.9 (t), 43.5 (d), 32.0 (s),
29.0 (t), 27.4 (t), 27.0 (q); IR (KBr): nÄ ˆ 3115, 2958, 2934, 2865, 2838, 1997,
1951, 1756, 1716, 1683, 1634, 1544, 1364 cm 1; IR (CH2Cl2): ˆ 2018, 1965,
1635 cm 1; MS (FAB): m/z (%) ˆ 342.9 (18), 313.9 (18), 286.8 (43), 285.8
(100); C18H22FeO3 (342.2): calcd C 63.00, H 6.42; found C 63.01, H 6.37.
4-Bromo-2H-1-benzothiopyran-3-carbaldehyde (1e): To a solution of
DMF (12.7 mL, 165 mmol) in chloroform (70 mL) was added PBr3
(12.5 mL, 132 mmol) dropwise at 08C, as described in the literature,[11, 12]
the mixture was stirred for 90 min. A solution of thiochroman-4-one
(5.41 g, 32.9 mmol) in chloroform (50 mL) was added and the reaction
mixture was heated to reflux for 45 min (TLC monitoring), cooled to 08C,
and then hydrolyzed by careful addition of saturated aqueous NaHCO3
(200 mL), solid NaHCO3, and water (300 mL). The aqueous layer was
separated and extracted repeatedly with chloroform. The combined
organic phases were washed with brine (100 mL) and dried (MgSO4),
and the solvent evaporated. Column chromatography on silica gel
(petroleum ether/ether 5:1) gave 6.19 g (74%) of 1e, as a yellow oil, which
solidified on cooling; Rf ˆ 0.64 (petroleum ether/ether 2:1); m.p. 60 ± 618C;
1H NMR (200 MHz): d ˆ 10.18 (s, 1H, CHO), 7.96 ± 7.91 (m, 1H, arom CH),
7.33 ± 7.23 (m, 3H, arom CH), 3.66 (s, 2H); 13C NMR (100.6 MHz): d ˆ
191.3, 139.2, 137.6, 132.9, 131.4, 131.2, 129.1, 127.6, 126.1, 24.5; IR (KBr): nÄ ˆ
2987, 2911, 2865, 1662, 1629, 1582, 1544, 1455, 1431, 1417, 1298, 1265, 1232,
1209, 1159, 1135, 1071, 1042, 938, 887, 866, 776, 724, 706, 620 cm 1; MS (EI,
70 eV): m/z (%) ˆ 256 (51), 227 (49), 175 (89), 147 (100), 102 (40), 77 (14),
75 (15), 69 (26), 45 (21); C10H7BrOS (255.1): calcd C 47.08, H 2.77; found C
47.17, H 2.70.
4,5-Dihydronaphtho[1,2-c]furan-3(1H)-one (3a):
Method A and general workup procedure: A stirred solution of 2a[11, 12]
(510 mg, 1.53 mmol) in ethanol/dichloromethane (30 mL, 2:1) was cooled
to 08C, and neat NaBH4 (65 mg, 1.72 mmol) was added. After 150 min
(TLC monitoring), saturated aqueous NH4Cl solution (60 mL) was added,
and the mixture was then concentrated in vacuo to 20% of the original
solvent volume. The mixture was diluted with dichloromethane (100 mL)
and 2n HCl (100 mL). The separated aqueous layer was extracted with
CH2Cl2 (100 mL). The combined organic phases were washed with 2n HCl
(100 mL), brine (100 mL), dried (MgSO4), and concentrated in vacuo. The
crude product was purified by flash chromatography (Florisil, petroleum
ether/ethyl acetate 8:1) to afford 3a (189 mg, 67%) as a beige amorphous
solid. Rf ˆ 0.68 (petroleum ether/ethyl acetate 2:1); m.p. 103 ± 1058C;
1H NMR (400 MHz): d ˆ 7.33 (t, J ˆ 7.5 Hz, 1H, arom CH), 7.26 ± 7.22 (m,
2H, arom CH), 7.10 (d, J ˆ 7.3 Hz, 1H, arom CH), 5.10 (s, 2H, CH2O), 2.98
(t, J ˆ 8.2 Hz, 2H), 2.56 (t, J ˆ 8.2 Hz, 2H); 13C NMR (100.6 MHz): d ˆ
173.3, 156.0, 137.3, 130.9, 128.5, 127.9, 126.9, 124.7, 123.4, 68.7, 27.7, 18.1; IR
(CH2Cl2): nÄ ˆ 1751 cm 1; C12H10O2 (186.2): calcd C 77.40, H 5.41; found C
76.90, H 5.36.
2-Bromo-5-tert-butyl-1-cyclohexen-1-carbaldehyde (1 f): To a solution of
DMF (20.0 mL, 258 mmol) in chloroform (120 mL) PBr3 (18.6 mL,
196 mmol) was added dropwise at 08C. The mixture was stirred for
60 min, then a solution of 4-tert-butylcyclohexanone (10.0 g, 64.8 mmol) in
chloroform (100 mL) was added. The mixture was heated to reflux for
45 min (TLC monitoring), cooled to 08C, and then hydrolyzed by careful
addition of saturated aqueous NaHCO3 (250 mL), solid NaHCO3, and
water (600 mL). The aqueous layer was separated and extracted repeatedly
with CH2Cl2. The combined organic phases were washed with brine, dried
(MgSO4), and the solvent evaporated. Column chromatography on silica
gel (petroleum ether/ether 20:1) gave 13.3 g (83%) of 1 f as a pale yellow
liquid; Rf ˆ 0.69 (petroleum ether/ether 4:1); 1H NMR (400 MHz): d ˆ 9.98
(s, 1H, CHO), 2.77 ± 2.71 (m, 2H), 2.53 ± 2.46 (m, 1H), 1.88 ± 1.75 (m, 2H),
1.39 ± 1.21 (m, 2H), 0.85 (s, 9H); 13C NMR (100.6 MHz): d ˆ 193.7 (CHO),
143.2 (C2), 135.3 (C1), 43.0 (C5), 40.0 (C3), 32.2 (C(CH3)3), 27.1 (C(CH3)3),
26.7 (C6), 25.7 (C4); IR (film): nÄ ˆ 2962, 2901, 2867, 1620, 1471, 1422, 1396,
1384, 1367, 1230, 1211, 1009 cm 1; C11H17BrO (245.2): calcd C 53.89, H 6.99;
found C 53.99, H 7.01.
3,4,5,6-Tetrahydro-1H-benzo[3,4]cyclohepta[1,2-c]furan-1-one (3b): To a
solution of 2b[11, 12] (0.60 g, 1.72 mmol) in ethanol/dichloromethane (45 mL,
2:1) was added NaBH4 (78 mg, 2.1 mmol) at 08C and the reaction mixture
was stirred for 75 min (TLC monitoring). Then a solution of saturated
aqueous NH4Cl (30 mL) was added, and the mixture was subsequently
concentrated in vacuo to 20% of the original solvent volume. After dilution
with CH2Cl2 (80 mL), the combined organic phases were washed with
saturated aqueous NaHCO3 solution (80 mL) and brine (80 mL), dried
(MgSO4), and concentrated in vacuo. The crude product was analyzed by
1H NMR spectroscopy and then purified by flash chromatography on
Florisil with petroleum ether/ethyl acetate (20:1 to 5:1) to furnish 3b
(174 mg, 50%) as a pale yellow oil, which solidified on standing ( 228C).
M.p. 828C, pale yellow crystals; Rf ˆ 0.36 (petroleum ether/ethyl acetate
2:1); 1H NMR (400 MHz): d ˆ 8.20 (dd, J ˆ 1.5, 7.6 Hz, 1H, H10), 7.28 (dt,
J ˆ 1.5, 7.6 Hz, 1H, H9), 7.22 (dt, J ˆ 1.5, 7.6 Hz, 1H, H8), 7.13 (dd, J ˆ 1.2,
7.6 Hz, 1H, H7), 4.73 (s, 2H, OCH2), 2.80 (m, 2H, H6a/b), 2.68 (t, J ˆ
7.0 Hz, 2H, H4a/b), 2.06 (m, 2H, H5a/b); 13C NMR (100.6 MHz): d ˆ 173.4
(s), 161.4 (s, C3a), 142.6 (s, C6a), 128.9 and 128.8 (d, C10 and C10a), 128.4
(d, C8), 126.3 (d, C9), 123.8 (s, C10b), 71.5 (t, C3), 34.8 (t, C6), 29.8 (t, C4),
26.1 (t, C5); IR (CH2Cl2): ˆ 1753 cm 1; IR (KBr): nÄ ˆ 3456 (broad), 3064,
3026, 2957, 2943, 2917, 2896, 2862, 1735, 1697, 1639, 1599, 1493, 1456, 1446,
1418, 1390, 1351, 1300, 1279, 1219, 1167, 1162 cm 1; C13H12O2 (200.2) ´
0.5H2O: calcd C 74.62, H 6.26; found C 74.32, H 5.96.
4-[Cyclopentadienyl(dicarbonyl)iron]-2H-1-benzothiopyran-3-carbalde-
hyde (2e): To the aldehyde 1e (2.00 g, 7.84 mmol) dissolved in THF
(70 mL), a solution of [Cp(CO)2Fe]Na, prepared from [{Cp(CO)2Fe}2]
(1.53 g, 4.31 mmol) and sodium amalgam (12.6 g, 11.0 mmol) in THF
(60 mL),[11, 12] was added by means of a cannula at 788C over a period of
30 min. The reaction mixture was stirred for 15 min at 788C and then
warmed to room temperature over a period of 1 h (IR monitoring). The
solution was concentrated in vacuo (bath temperature 58C) and the residue
purified by column chromatography on silica gel with i) petroleum ether/
ether (2:1) to separate [{Cp(CO)2Fe}2], ii) ether/acetone (1:1) to yield
1.81 g (66%) of 2e as a green-brown foam, sufficiently pure for further
transformations, but too unstable to be stored for a prolonged time at low
temperature. Rf ˆ 0.33 (petroleum ether/ethyl acetate 2:1); 1H NMR
(200 MHz, [D6]DMSO): d ˆ 10.02 (s, 1H, CHO), 7.85 (dd, J ˆ 1.0, 7.8 Hz,
1H, arom CH), 7.33 ± 7.20 (m, 2H, arom CH), 7.12 (dt, J ˆ 7.3 Hz, 1H, arom
CH), 5.47 (s, 5H, C5H5), 3.34 (s, 2H, CH2S); 1H NMR (200 MHz, C6D6):
d ˆ 10.26 (brs, 1H, CHO), 7.55 ± 6.89 (m, 4H, arom CH), 4.12 (s, 5H, C5H5),
1.62 (s, 2H, CH2S); 13C NMR (50.3 MHz, [D5]pyridine, selected data): d ˆ
Method B: A solution of 2b (1.24 g, 3.56 mmol) in THF (60 mL) was
treated with K-Selectride (3.9 mL, 1m solution in THF) at 308C. The
mixture was stirred for 40 min (TLC monitoring), buffer (pH 6, 150 mL)
added, and the reaction mixture then diluted with ether (100 mL). The
aqueous layer was washed twice with ether (50 mL). The organic phases
were combined and washed with brine (100 mL), dried (MgSO4), and
concentrated in vacuo. The crude product was purified by flash chroma-
tography on Florisil with petroleum ether/ethyl acetate (20:1 to 12:1) to
yield 3b (137 mg, 19%).
194.7, 179.5, 148.8, 146.5, 136.6, 128.0, 127.8, 125.2, 87.7, 25.9; IR
1
(CH2Cl2): ˆ 2028, 1978, 1638 cm 1; IR (THF): nÄ ˆ 2023, 1973, 1645 cm
;
MS (FAB): m/z (%) ˆ 353.7 (11), 352.7 (43), 324.7 (32), 323.7 (48), 296.7
(53), 295.7 (100).
2-[Cyclopentadienyl(dicarbonyl)iron]-5-tert-butyl-1-cyclohexen-1-carbal-
dehyde (2 f): The iron complex was synthesized according to the procedure
described for 2e starting from 1 f (1.50 g, 6.12 mmol) dissolved in THF
(60 mL) and [Cp(CO)2Fe]Na, prepared from [{Cp(CO)2Fe}2] (1.20 g,
3.39 mmol) and sodium amalgam (10.0 g, 8.7 mmol) in THF (50 mL).
Column chromatography performed under the same conditions as descri-
3-Phenyl-tetrahydro-2-furanone (4d):
Method A: To the iron complex 2d[11, 12] (0.50 g, 1.62 mmol) dissolved in
ethanol (30 mL) was added NaBH4 (92 mg, 2.43 mmol) at 08C. The
solution was stirred for 3 h (TLC monitoring). Then a saturated aqueous
NH4Cl solution (50 mL) was added, and the reaction mixture concentrated
1042
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Chem. Eur. J. 1999, 5, No. 3

Intramolecular Cyclocarbonylations
1038±1044
in vacuo, as described for 3a. The residue was diluted with ether (50 mL),
and the separated aqueous layer was extracted repeatedly with ether (5 Â
30 mL). The combined organic phases were dried (MgSO4) and concen-
trated in vacuo. Purification by flash chromatography (Florisil, petroleum
ether/ethyl acetate 18:1 to 8:1) afforded a mixture of 3d and 4d (63:37;
140 mg, 54%), as indicated by 1H NMR spectroscopy. Selected data for 2,5-
(dd, J ˆ 10.7, 8.3 Hz, 1H), 2.84 ± 2.70 (m, 1H), 2.48 ± 2.34 (m, 1H), 2.12 ±
1.97 (m, 1H), 1.87 ± 1.74 (m, 1H), 1.69 ± 1.56 (m, 1H), 1.48 ± 1.26 (m, 2H),
1.19 ± 0.99 (m, 1H), 0.98 ± 0.80 (m, 1H overlayed by the adjacent singlet),
0.80 (s, 9H); 13C NMR (50.3 MHz): d ˆ 180.0, 69.9, 42.3, 39.0, 35.1, 32.4,
27.3, 24.6, 24.5, 23.9; IR (CH2Cl2): nÄ ˆ 1768 cm 1; MS (EI): m/z (%) ˆ 196
(7), 140 (53), 95 (23), 86 (7), 80 (9), 67 (7), 57 (100); C12H20O2 (196.3): calcd
C 73.43, H 10.27; found C 73.30, H 10.28.
Dihydro-3-phenyl-2-furanone (3d): 1H NMR (200 MHz): 7.84 (t, J ˆ
1
3.9 Hz, 2H), 7.63 (s, 1H), 4.91 (s, 2H); IR (CH2Cl2): ˆ 1760 cm
.
5-tert-Butyl-4,5,6,7-tetrahydro-1(3H)isobenzofuranone (3 f): Rf ˆ 0.35 (pe-
troleum ether/ether 2:1); 1H NMR (400 MHz): d ˆ 4.65 (d, J ˆ 17.4 Hz, 1H,
CH2O), 4.58 (d, J ˆ 17.5 Hz, 1H, CH2O), 2.35 ± 2.27 (m, 2H, H4eq and H7eq),
2.04 ± 1.96 (m, 3H, H6eq, H4ax and H7ax), 1.41 ± 1.34 (m, 1H, H5), 1.19 ± 1.09
(m, 1H, H6), 0.87 (s, 9H); 13C NMR (100.6 MHz): d ˆ 174.0 (C1), 161.9
(C3a), 126.2 (C7a), 71.8 (C3), 43.9 (C5), 32.2 (C(CH3)3), 27.1 (C(CH3)3),
25.2 (C4), 23.3 (C6), 20.9 (C7); IR (CH2Cl2): nÄ ˆ 1749 cm 1; IR (film): nÄ ˆ
3441, 2961, 2869, 1756, 1685, 1471, 1440, 1396, 1367, 1348, 1258, 1227, 1160,
1110, 1088, 1035 cm 1; MS (EI, 70 eV): m/z (%) ˆ 194 (19), 138 (82), 93
(14), 69 (10), 57 (100), 41 (23); C12H18O2 (194.3) ´ 0.25H2O: calcd C 72.51, H
9.38; found C 72.41, H 9.36.
Following the procedure given above, the iron compound 2d (1.13 g,
3.67 mmol) dissolved in ethanol/dichloromethane (66 mL, 2:1) was treated
with NaBH4 (153 mg, 4.04 mmol). The reaction mixture was worked up
after 5 h to afford 4d (338 mg, 57%), exclusively, as a pale yellow liquid;
Rf ˆ 0.36 (petroleum ether/ethyl acetate 2:1); 1H NMR (200 MHz): d ˆ
7.33 ± 7.26 (m, 5H), 4.51 ± 4.27 (m, 2H), 3.80 (t, J ˆ 9.5 Hz, 1H), 2.79 ± 2.62
(m, 1H), 2.53 ± 2.33 (m, 1H); 13C NMR (50.3 MHz): d ˆ 177.6, 136.8, 128.9,
128.0, 127.6, 66.6, 45.5, 31.6; IR (CH2Cl2): nÄ ˆ 1773 cm 1; MS (EI, 70 eV):
m/z (%) ˆ 162 (34), 117 (100), 104 (14), 103 (20), 91 (34), 77 (14); C10H10O2
(162.2): calcd C 74.06, H 6.21; found C 74.14, H 6.20.
Method B: A stirred solution of 2d (635 mg, 2.06 mmol) dissolved in THF
(40 mL) was cooled to 08C and K-Selectride (2.1 mL, 1m, THF) was added.
The mixture was stirred for 3 h (IR monitoring) until TLC indicated
complete turnover. The mixture was diluted with saturated aqueous NH4Cl
solution (80 mL) and concentrated in vacuo. The mixture was partitioned
between CH2Cl2 (100 mL) and 2n HCl (50 mL). The aqueous layer was
separated, diluted with water (200 mL), and extracted with CH2Cl2 (4 Â
50 mL). The combined organic phases were washed with saturated aqueous
NaHCO3 solution (50 mL) and brine (50 mL), dried (MgSO4), and
concentrated in vacuo. Flash chromatography on Florisil with petroleum
ether/ethyl acetate (25:1 to 10:1) gave 4d (89 mg, 27%).
cis-4 f: Method B: To a solution of 2 f (1.42 g, 4.15 mmol) in THF (70 mL)
was added K-Selectride (4.5 mL, 1m, THF) at 08C. The reaction mixture
was stirred for 50 min (TLC monitoring) before a buffer solution (pH 6,
150 mL) was added. The reaction mixture was diluted with ether (100 mL)
and worked up as described above for compound 4d. After evaporation of
the solvent, the reminder was dissolved in ether (20 mL) and stored at room
temperature for 18 h. The fluffy precipitate (iron oxide and iron hydroxide)
was removed by filtration over a plug of Celite with ether. The filtrate was
concentrated and the crude product purified by flash chromatography on
Florisil with petroleum ether/ether (12:1 to 6:1 to 3:1) to yield cis-4 f
(290 mg, 36%), exclusively, as colorless crystals (petroleum ether/ether).
M.p. 94 ± 958C; Rf ˆ 0.38 (petroleum ether/ether 1:1); 1H NMR (200 MHz):
d ˆ 4.20 (dd, J ˆ 8.8, 4.4 Hz, 1H), 3.92 (d, J ˆ 8.8 Hz, 1H), 2.63 ± 2.60 (m,
1H), 2.47 ± 2.39 (m, 1H), 2.29 ± 2.20 (m, 1H), 1.88 ± 1.79 (m, 1H), 1.70 ± 1.46
(m, 2H), 0.93 ± 0.80 (m, 3H, overlayed by the adjacent singlet), 0.80 (s, 9H);
13C NMR (100.6 MHz): d ˆ 178.4, 72.1, 45.7, 39.4, 36.6, 32.2, 29.2, 27.3, 23.8,
23.6; IR (KBr): nÄ ˆ 3000, 2956, 2942, 2900, 2881, 2866, 2856, 1762, 1474,
1438, 1382, 1364, 1289, 1236, 1214, 1171, 1151 cm 1; C12H20O2 (196.3): calcd
C 73.43, H 10.27; found C 73.49, H 10.25.
1,3a,4,9b-Tetrahydro-3H-[1]benzothiopyrano[3,4-c]furan-1-one (4e):
A
solution of 2e (2.10 g, 5.96 mmol) in ethanol (120 mL) was treated with
NaBH4 (338 mg, 8.94 mmol) at 08C. The reaction mixture stirred for
255 min (TLC monitoring), diluted with saturated aqueous NH4Cl solution
(30 mL), and then worked up as described for compound 3a. The crude,
solid product obtained was separated by flash chromatography (Florisil,
petroleum ether/ethyl acetate 15:1 to 7:1) to afford firstly 3e (281 mg,
23%) and secondly 4e (340 mg, 28%), as pale yellow amorphous solids.
Under the same conditions as described above, a solution of 2e (1.61 g,
4.57 mmol) in ethanol (100 mL) was treated with NaBH4 (260 mg,
6.87 mmol) for 20 h to yield 4e (354 mg, 38%), exclusively.
Reaction of 2c with NaBH4 in ethanol (Method A): To a solution of 2c (1 g,
3 mmol) in ethanol (40 mL) was added NaBH4 (135 mg, 2.6 mmol) at 08C,
and the reaction mixture was stirred for 1 h at room temperature (TLC
monitoring). Then saturated aqueous NH4Cl solution (50 mL) was added,
and the solution was concentrated as described for 3a. The mixture was
diluted with CH2Cl2 (80 mL) and water (80 mL). The separated aqueous
layer was extracted with CH2Cl2 (2 Â 80 mL). The combined organic phases
were washed with water (80 mL) and brine (80 mL) and dried (MgSO4),
and the solvent evaporated. The crude, solid product was purified by flash
chromatography on Florisil with petroleum ether/ethyl acetate (9:1 to 5:1)
to give firstly 4c (420 mg, 74%) and secondly 5 (107 mg, 19%).
4e: Rf ˆ 0.66 (petroleum ether/ethyl acetate 1:2); m.p. 104 ± 1058C;
1H NMR (200 MHz): d ˆ 7.48 (t, J ˆ 3.5 Hz, 1H), 7.23 ± 7.14 (m, 3H), 4.53
(dd, J ˆ 9.8, 6.4 Hz, 1H), 4.32 (dd, J ˆ 9.3, 2.4 Hz, 1H), 3.82 (d, J ˆ 8.3 Hz,
1H), 3.23 ± 3.12 (m, 1H), 2.92 ± 2.81 (m, 2H); 13C NMR (50.3 MHz): d ˆ
175.8, 133.0, 132.0, 127.9, 127.8, 127.7, 125.8, 71.4, 43.3, 36.0, 29.5; IR
(CH2Cl2): nÄ ˆ 1777 cm 1; MS (FD): m/z (%) ˆ 206.0 (100); C11H10O2S
(206.3): calcd C 64.05, H 4.89; found C 64.15, H 4.94.
1,4-Dihydro-3H-[1]benzothiopyrano[3,4-c]furan-1-one (3e): Rf ˆ 0.71 (pe-
troleum ether/ethyl acetate 1:2); m.p. 139 ± 1408C; 1H NMR (200 MHz):
d ˆ 8.21 (q, 1H), 7.31 ± 7.16 (m, 3H), 4.87 (s, 2H), 3.76 (s, 2H); 13C NMR
(50.3 MHz): d ˆ 170.5, 152.5, 130.9, 129.4, 126.7, 126.3, 125.9, 125.3, 124.3,
69.7, 24.0; IR (CH2Cl2): nÄ ˆ 1760 cm 1; MS (FD): m/z (%) ˆ 204 (100);
C11H8O2S (204.3): calcd C 64.69, H 3.95; found C 64.62, H 3.92.
Reaction of 2c with K-Selectride/H2O (Method B): To a solution of 2c
(0.50 g, 1.49 mmol) in THF (30 mL) was added K-Selectride (1.5 mL, 1m,
THF) at 08C. The reaction mixture was stirred for 90 min (TLC
monitoring), diluted with saturated aqueous NH4Cl solution (20 mL), and
then worked up as described for 4d, except that ether was used for
extraction instead of CH2Cl2. Flash chromatography on Florisil with
petroleum ether/ethyl acetate (18:1 to 8:1) gave 4c (184 mg, 65%).
5-tert-Butyl-perhydro-isobenzofuranone (4 f): A solution of the iron
compound 2 f (1.45 g, 4.24 mmol) in ethanol/dichloromethane (75 mL,
2:1) was treated with NaBH4 (176 mg, 4.65 mmol) for 160 min (TLC
monitoring). Then saturated aqueous NH4Cl solution (75 mL) was added,
and the reaction mixture was worked up according to the general
procedure given for compound 3a, except that the combined CH2Cl2
phases were washed with water (3 Â 50 mL), dried (MgSO4), and concen-
trated in vacuo. The residue was dissolved in petroleum ether/ether (30 mL,
1:1) and stored overnight at room temperature. The fluffy precipitate (iron
oxide and hydroxide) was removed by filtration over a plug of Celite with
ether. The filtrate was concentrated and the crude product was separated
by flash chromatography (Florisil, petroleum ether/ether 10:1 to 2:1) to
afford firstly 4 f (260 mg, 31%; mixture of trans- and cis-isomers, ratio:
86:14), as a orange-yellow foam, and secondly 3 f (316 mg, 38%) as a red-
orange oil.
1,3a,4,9b-Tetrahydro-3H-furo[3,4-c][1]benzopyran-1-one (4 c): beige
amorphous solid; m.p. 92 ± 938C; Rf ˆ 0.35 (petroleum ether/ethyl acetate
2:1); 1H NMR (400 MHz): d ˆ 7.51 (d, J ˆ 7.3 Hz, 1H), 7.18 (t, J ˆ 7.5 Hz,
1H), 6.99 (t, J ˆ 7.5 Hz, 1H), 6.87 (d, J ˆ 7.9 Hz, 1H), 4.48 (dd, J ˆ 9.2,
6.8 Hz, 1H), 4.24 (dd, J ˆ 11.4, 4.1 Hz, 1H), 4.18 (dd, J ˆ 9.5, 3.9 Hz, 1H),
3.78 (dd, J ˆ 11.5, 8.8 Hz, 1H), 3.73 (d, J ˆ 8.2 Hz, 1H), 3.06 (m,
1H);13C NMR (13C{1H} DEPT 135 NMR, 100.6 MHz): d ˆ 175.5 (s),
154.3 (s), 130.4 (d), 128.8 (d), 121.9 (d), 117.1 (d), 115.9 (s), 67.5 (t), 64.2
(t), 38.5 (d), 33.6 (d); IR (CH2Cl2): nÄ ˆ 1773 cm 1; IR (KBr): nÄ ˆ 3519, 2991,
2973, 2907, 2869, 1781, 1772, 1612, 1584, 1496, 1470, 1456, 1389, 1365, 1333,
1
1307, 1290, 1270, 1245, 1238, 1224, 1205, 1187, 1164, 1157, 1133, 1116 cm
;
MS (EI, 70 eV): m/z (%) ˆ 190 (48); C11H10O3 (190.2) ´ 2H2O: calcd C
58.40, H 6.24; found C 58.39, H 5.87.
trans-4 f: Rf ˆ 0.54 (petroleum ether/ether 2:1); 1H NMR {400 MHz, trans-
1,3-Dihydro-4-methyl-5-(2'-hydroxyphenyl)-1-furanone (5): Beige, amor-
phous solid, m.p. 98 ± 1008C; Rf ˆ 0.18 (petroleum ether/ethyl acetate 2:1);
isomer [ratio: 86:14]}: d ˆ 4.29 ± 4.20 (dd, J ˆ 8.3, 8.4 Hz, 1H), 4.14 ± 4.05
Chem. Eur. J. 1999, 5, No. 3
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0947-6539/99/0503-1043 $ 17.50+.50/0
1043

K. Rück-Braun, C. Möller
FULL PAPER
1H NMR (400 MHz): d ˆ 7.56 (brs, 1H), 7.26 (t, J ˆ 7.3 Hz, 1H), 7.12 (d, J ˆ
7.6 Hz, 1H), 6.98 (d, J ˆ 8.2 Hz, 1H), 6.95 (t, J ˆ 7.7 Hz, 1H), 4.88 (s, 2H),
2.17 (s, 3H); 13C NMR (100.6 MHz): d ˆ 175.8, 160.7, 154.6, 130.6, 130.5,
125.8, 120.6, 118.9, 117.1, 74.4, 13; IR (CH2Cl2): nÄ ˆ 1721 cm 1; MS (EI): m/z
(%) ˆ 191.1 (8), 190.1 (100), 161.1 (17), 147.0 (11), 145.1 (17), 133.1 (45),
131.0 (24), 115.0 (17), 105.0 (17), 105.0 (28); C11H10O3 (190.2): calcd C 69.48,
H 5.30; found C 69.44, H 5.35.
J ˆ 7.8 Hz, 1H), 6.87 (d, J ˆ 8.3 Hz, 1H), 4.49 (d, J ˆ 9.8 Hz, 1H), 4.21 (t,
J ˆ 9.7 Hz, 1H), 3.79 (d, J ˆ 9.8 Hz, 2H); 13C NMR (50.3 MHz): d ˆ 175.6,
154.3, 130.3, 128.8, 121.8, 117.1, 115.9, 67.5, 64.1, (38.4, 38.2, 38.0), (33.2, 33.0,
32.8); MS (FD): m/z ˆ 191.7 (100).
Acknowledgements
Reaction of 2c with NaBD4 in ethanol: As outlined above, the iron
compound 2c (1 g, 3 mmol) dissolved in ethanol (40 mL) was treated with
NaBD4 (139 mg, 3.3 mmol) at room temperature for 30 min (TLC
monitoring). Then saturated aqueous NH4Cl solution (50 mL) was added,
and the reaction mixture was worked up. The crude solid product was
purified by flash chromatography on Florisil with i) petroleum ether/ethyl
acetate (8:1 to 4:1) to yield firstly 6 (400 mg, 70%), ii) ethyl acetate as
eluent to yield secondly 7 (95 mg, 17%).
Compound 6: Pale yellow, amorphous solid; 1H NMR (400 MHz, deutera-
tion rate 100% at position 3): d ˆ 7.51 (dd, J ˆ 7.6, 0.9 Hz, 1H), 7.18 (dt, J ˆ
8.5, 1.5 Hz, 1H), 6.99 (dt, J ˆ 7.6, 1.2 Hz, 1H), 6.87 (dd, J ˆ 7.6, 0.9 Hz, 1H),
4.46 (d, J ˆ 6.8 Hz), 4.23 (dd, J ˆ 11.5, 4.1 Hz, 1H), 4.16 (d, J ˆ 3.5 Hz), 3.78
(dd, J ˆ 11.5, 8.8 Hz, 1H), 3.73 (d, J ˆ 8.2 Hz, 1H), 3.06 (m, 1H); 13C NMR
(100.6 MHz): d ˆ 175.8, 154.3, 130.4, 128.8, 121.9, 117.2, 116.0, (67.8, 67.6,
67.3), 64.3, 38.9, 33.6; IR (CH2Cl2): nÄ ˆ 1780 cm 1; MS (FD): m/z (%) ˆ
191.7 (19), 190.7 (100).
Compound 7: Pale yellow, amorphous solid; 1H NMR (400 MHz, deutera-
tion rate 50% at position 5): d ˆ 7.55 (brs, 1H), 7.27 (t, J ˆ 7.6 Hz, 1H), 7.13
(d, J ˆ 7.3 Hz, 1H), 6.99 (d, J ˆ 7.9 Hz, 1H), 6.95 (t, J ˆ 7.3 Hz, 1H), 4.89 (s),
4.88 (s), 2.18 (s, 3H); 13C NMR (100.6 MHz): d ˆ 175.8, (160.6, 160.5), 154.7,
130.6, 130.5, (125.94, 125.90), 120.7, 119.0, 117.1, [74.5, (74.4, 74.2, 73.9)]
13.9; IR (CH2Cl2): nÄ ˆ 3292 broad, 1764, 1723 cm 1; MS (EI, 70 eV): m/z
(%) ˆ 190.1 (100), 161.1 (30), 147.1 (30), 133.1 (80), 115.0 (24), 105.0 (50),
91.0 (19), 77.0 (47).
Financial support of this work by the Deutsche Forschungsgemeinschaft
and by the Kalkhof-Rose-Stiftung is gratefully acknowledged. We thank H.
Kolshorn and P. Amrhein for support of the NMR experiments.
[1] a) L. S. Hegedus, Organische Synthese mit Übergangsmetallen, VCH,
Weinheim, 1995, and references therein.
[2] N. Kablaoui, F. A. Hicks, S. L. Buchwald, J. Am. Chem. Soc. 1996, 118,
5818 ± 5819.
[3] A. J. Pearson, R. A. Dubbert, Organometallics 1994, 13, 1656 ± 1661.
[4] D. J. Thomson, in Comprehensive Organic Synthesis Vol. 3 (Eds.:
B. M. Trost, I. Flemming), Pergamon, Oxford, 1991, 1015 ± 1043, and
references therein.
[5] W.-Y. Yu, H. Alper, J. Org. Chem. 1997, 62, 5684 ± 5687, and references
therein.
[6] G. T. Crisp, A. G. Meyer, J. Org. Chem. 1992, 57, 6972 ± 6975; b) G. T.
Crisp, A. G. Meyer, Tetrahedron 1995, 51, 5585 ± 5596, and references
therein.
[7] H. Alper, J. K. Currie, H. Des Abbayes, J. Chem. Soc. Chem.
Commun. 1978, 311.
[8] M. Miura, K. Okura, A. Hattori, M. Nomura, J. Chem. Soc. Perkin
Trans. I 1989, 73 ± 76.
[9] B. L. Booth, R. G. Hargreaves, J. Chem. Soc. (A) 1970, 308 ± 314; P.
DeShong, D. R. Sidler, G. A. Slough, Tetrahedron Lett. 1987, 28,
2233 ± 2236; c) P. DeShong, D. R. Sidler, P. J. Rybczynski, G. A.
Slough, A. L. Rheingold, J. Am. Chem. Soc. 1988, 110, 2575 ± 2585.
[10] For iron- and tungsten-mediated sequential cyclocarbonylations, see:
a) U. Radhakrishnan, M. Periasamy, Organometallics 1997, 16, 1800 ±
1802; b) C.-C. Chen, J.-S. Fan, S.-J. Shieh, G.-H. Lee, S.-M. Peng, S.-L.
Wang, R.-S. Liu, J. Am. Chem. Soc. 1996, 118, 9279 ± 9287; c) S.-J.
Shieh, J.-S. Fan, M. Chandrasekharam, F.-L. Liao, S.-L. Wang, R.-
Shung Liu, Organometallics 1997, 16, 3987 ± 3992.
Reaction of 2c with NaBD4 in [D1]ethanol: To a solution of 2c (0.98 g,
2.9 mmol) in [D1]ethanol (CH3CH2OD, 40 mL) was added NaBD4 (135 mg,
3.2 mmol) at room temperature. The mixture was stirred for 1 h (TLC
monitoring), then a saturated aqueous NH4Cl solution (50 mL) was added,
and the reaction mixture was worked up as described above. Flash
chromatography on Florisil with petroleum ether/ethyl acetate (8:1 to 4:1)
gave firstly 8 (320 mg, 57%) and secondly 9 (210 mg, 37%).
Compound 8: Pale yellow, amorphous solid; 1H NMR (400 MHz, deutera-
tion rate 100% at positions 9b, 3a, and 3-Ha/3-Hb): d ˆ 7.52 (d, J ˆ 7.3 Hz,
1H), 7.18 (t, J ˆ 7.6 Hz, 1H), 6.99 (t, J ˆ 7.3 Hz, 1H), 6.87 (d, J ˆ 7.9 Hz,
1H), 4.47 (s, 0.5H), 4.24 (d, J ˆ 11.4 Hz, 1H), 4.17 (s, 0.5H), 3.80 (d, J ˆ
11.4 Hz, 1H); 13C NMR (100.6 MHz): d ˆ 171.3, 150.0, 126.0, 124.5, 117.6,
112.8, 111.5, (63.1, 62.9, 62.6), 59.8 (m, 33.8), (m, 28.8); MS (EI): m/z (%) ˆ
194.1 (16), 193.2 (56), 148.1 (51), 132.1 (100), 120.1 (18), 104.1 (11.5), 78.0
(22).
Compound 9: Pale yellow, amorphous solid: 1H NMR (400 MHz, deutera-
tion rate 100% at 4-CH3 and 95% at position 5-Ha/5-Hb): d ˆ 7.56 (brs,
1H), 7.28 ± 7.26 (m, 1H), 7.13 ± 7.11 (m, 1H), 7.00 ± 6.93 (m, 2H), 4.87 {brs,
CD(D/H)}, 2.16 (s, 2H); 13C NMR (100.6 MHz): d ˆ 171.6, 156.2, 150.4,
126.3, 126.2, 121.7, 116.4, 114.7, 112.8, (69.7, 69.5, 69.3), (9.5, 9.3, 9.1); MS
(FD): m/z (%) ˆ 194.1 (15), 193.1 (100), 192.1 (15), 163.1 (23.4), 149.0 (19),
135.1 (68.4), 117.1 (15), 107.0 (41), 93.0 (11), 78.0 (17).
[11] K. Rück-Braun, Angew. Chem. 1997, 109, 526 ± 528; Angew. Chem. Int.
Ed. Engl. 1997, 36, 509 ± 511.
Â
[12] K. Rück-Braun, T. Martin, M. Mikulas, Chem. Eur. J., 1999, 5, 1028 ±
1037.
[13] C. M. Marson, Tetrahedron 1992, 48, 3659 ± 3726, and references
therein.
[14] G. Pattenden, L. Roberts, Tetrahedron Lett. 1996, 37, 4191 ± 4194.
[15] I. Jardine, R. J. Strife, J. Kozlowski, J. Med. Chem. 1982, 25, 1077.
[16] a) L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137 ± 332; Angew.
Chem. Int. Ed. Engl. 1993, 32, 131; b) L. F. Tietze, Chem. Ind.
(London) 1995, 453 ± 457.
[17] a) R. C. Kerber, in Comprehensive Organometallic Chemistry II,
Vol. 7 (Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson), Pergamon,
New York, 1995, 101 ± 229; b) S. V. Ley, L. R. Cox, G. Meek, Chem.
Rev. 1996, 96, 423.
[18] a) R. B. King, M. B. Bisnette, Inorg. Chem. 1966, 5, 293; b) L. S.
Hegedus, O. P. Anderson, D. Zetterberg, G. Allen, K. Siirala-Hansen,
D. J. Olsen, A. B. Packard, Inorg. Chem. 1977, 16, 1887; c) W. P.
Fehlhammer, P. Hirschmann, A. Mayr, J. Organomet. Chem. 1982,
224, 153; d) S. Javaheri, W. P. Giering, Organometallics 1984, 3, 1927.
Reaction of 2c with K-Selectride/D2O: As outlined above, a solution of the
iron compound 2c (0.50 g, 1.49 mmol) in THF (30 mL) was treated with
K-Selectride (1.5 mL) at 08C. The mixture was stirred for 75 min, then D2O
(10 mL) was added, and the reaction mixture was worked up as described
above, except that ether was used for extraction. The crude solid product
was purified by flash chromatography on Florisil with petroleum ether/
ethyl acetate (18:1 to 10:1) to yield 10 (114 mg, 40%) as a pale-yellow,
amorphous solid. 1H NMR (200 MHz, deuteration rate 100% at posi-
tions 9b and 3a): d ˆ 7.52 (d, J ˆ 7.8 Hz, 1H), 7.19 (t, J ˆ 7.8 Hz, 1H), 7.03 (t,
Received: July 07, 1998 [F1245]
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