Asymmetric Dearomatization of the Furan Ring Promoted by Conjugate Organolithium Addition to (Menthyloxy)(3-furyl)carbene Complexes of Chromium

Article abstract of DOI:10.1002/chem.200305241

The sequential low-temperature addition reaction of an organolithium compound and methyl triflate to (menthyloxy)(3-furyl)carbene complexes of chromium and tungsten proceeded with excellent regioselectivity (1,4-addition) and diastereoselectivity (2,3-trans disposition of the nucleophile and electrophile groups) to afford new 2,3-disubstituted (2,3-dihydro-3-furyl)-carbene complexes. In addition, a high degree of diastereofacial selectivity was achieved by employing alkenyllithium compounds. After detachment of both the metal fragment and the chiral auxiliary group, trisubstituted 2,3-dihydrofuran derivatives containing a quaternary stereogenic center at the C3 position were obtained. The characterization, including X-ray crystallography, of a novel type of stable four-membered chelate (η ²-alkene)tetracarbonyl-carbene complex of chromium is also reported.

Full text of DOI:10.1002/chem.200305241

J. Barluenga et al.
5725
Chem. Eur. J. 2003, 9, 5725 5736
DOI: 10.1002/chem.200305241
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

FULL PAPER
Asymmetric Dearomatization of the Furan Ring Promoted by Conjugate
Organolithium Addition to (Menthyloxy)(3-furyl)carbene Complexes of
Chromium
Josÿ Barluenga,*[a] Sandip K. Nandy,[a] Y. R. Santosh Laxmi,[a] Josÿ RamÛn Suµrez,[a]
Isabel Merino,[a] Josefa FlÛrez,[a] Santiago GarcÌa-Granda,[b] and
Josÿ Montejo-Bernardo[b]
Abstract: The sequential low-tempera-
ture addition reaction of an organo-
lithium compound and methyl triflate
to (menthyloxy)(3-furyl)carbene com-
plexes of chromium and tungsten pro-
ceeded with excellent regioselectivity
(1,4-addition) and diastereoselectivity
(2,3-trans disposition of the nucleophile
and electrophile groups) to afford new
2,3-disubstituted (2,3-dihydro-3-furyl)-
carbene complexes. In addition, a high
degree of diastereofacial selectivity was
achieved by employing alkenyllithium
compounds. After detachment of both
the metal fragment and the chiral aux-
iliary group, trisubstituted 2,3-dihydro-
furan derivatives containing a quater-
nary stereogenic center at the C3 posi-
tion were obtained. The characteriza-
tion, including X-ray crystallography,
of a novel type of stable four-mem-
bered chelate (h2-alkene)tetracarbonyl-
carbene complex of chromium is also
reported.
Keywords: asymmetric synthesis ¥
carbene
complexes
¥
dearomatization ¥ dihydrofurans ¥
nucleophilic addition
Introduction
Birch reductive alkylation of chiral amides of 3-methyl-2-
furoic acid.[4] Furans have been widely used as dienes[5] and
less frequently as dienophiles[6] in [4+2] cycloaddition reac-
tions with alkenes, alkynes, or allenes[5] and with reactive
dienes,[6] respectively. These aromatic heterocycles also
behave as dienes in [4+3] cycloaddition reactions with in
situ generated 2-oxyallyl cations[7] or vinylcarbenoids,[8] as
dipolarophiles in [3+2] cycloadditions to nitrones[9] and ni-
trile oxides,[10] and as olefins in [2+2] photocycloadditions to
carbonyl compounds[11] and in rhodium(ii)-[12a] or copper(i)-
catalyzed[12b] [2+1] cycloadditions to metal-stabilized a-keto-
carbenoids. All these cycloaddition processes lead to differ-
ent bicyclic or tricyclic skeletons in which the conjugated p
system of the furan ring is broken up. Oxidation of the
furan ring without ring opening represents another way by
which this heteroaromatic nucleus has been modified with
concomitant dearomatization.[13] Product formation is a
function of both the substitution pattern on the ring and the
oxidation reagent employed. For example, 2,5-dialkoxy-2,5-
dihydrofurans are formed as a mixture of diastereoisomers
by bromination or chlorination of furans in hydroxylic sol-
vents[14] or by using electrochemical procedures,[15,16] while
butenolides are obtained from 2-(trimethylsilyl)furans under
the influence of peracetic acid.[17] Additionally, furan dearo-
matization has been achieved by preformation of the cation-
ic pentaammine(h2-furan)osmium(ii) complex followed by
successive reaction with an electrophile and then a moder-
The transformation of readily available aromatic compounds
into functionalized alicyclic derivatives is widely recognized
as a useful strategy for the construction of valuable synthetic
intermediates.[1] In the case of furans, the successful utiliza-
tion of these heterocycles in organic synthesis often relies
on the ability to dearomatize them with a high degree of
regio- and stereochemical control. There are a number of
different methods that, with unequal scope, allow the dearo-
matization of the furan ring.[2] Reduction of furans under
Birch-type conditions leads to 2,5-dihydrofurans.[3] High
levels of diastereoselectivity have been obtained in the
[a] Prof. Dr. J. Barluenga, Dr. S. K. Nandy, Dr. Y. R. S. Laxmi,
J. R. Suµrez, Dr. I. Merino, Dr. J. FlÛrez
Instituto Universitario de QuÌmica Organometµlica ™Enrique Moles∫
Unidad Asociada al CSIC, Universidad de Oviedo
Juliµn ClaverÌa 8, 33006 Oviedo (Spain)
Fax : (+34)98-510-3450
E-mail: barluenga@sauron.quimica.uniovi.es
[b] Dr. S. GarcÌa-Granda, J. Montejo-Bernardo
Departamento de QuÌmica FÌsica y AnalÌtica
X-ray analyses, Facultad de QuÌmica, Universidad de Oviedo
Juliµn ClaverÌa 8, 33006 Oviedo (Spain)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author: ORTEP plots of
the X-ray crystal structures of minor-4e and 12 are provided.
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DOI: 10.1002/chem.200305241
Chem. Eur. J. 2003, 9, 5725 5736

5725 5736
ate nucleophile present in the reaction medium. After de-
complexation of osmium, 2,2- or 2,3-disubstituted-2,3-dihy-
drofuran derivatives are formed with a high degree of dia-
stereoselectivity.[18] More recently the acid-catalyzed metha-
nol addition to dihapto-coordinated rhenium complexes of
furan[19] leading to dihapto-coordinated 2-methoxy-2,3-dihy-
drofuran complexes has been reported.[20]
Our research into dearomatization chemistry promoted
by nucleophilic addition to electron-deficient Fischer aryl-
carbene complexes followed by electrophilic trapping of the
intermediate anionic complex[21] has led us to apply this
methodology to aromatic heterocycles. We report here the
regio- and diastereoselective dearomatization of the furan
ring which has been achieved by a sequential nucleophile e-
lectrophile addition reaction to the pentacarbonylchromium
((ꢀ)-menthyloxy)(3-furyl)carbene complex and which pro-
ceeds with high asymmetric induction when alkenyllithium
compounds are employed as nucleophiles.
reaction of the appropriate tetramethylammonium complex
thus formed with pivaloyl chloride and (ꢀ)- or (ꢁ)-menthol
led to menthyloxycarbene complexes 1a,b, which after silica
gel column chromatography were isolated as a stable dark-
red thick oil (ꢀ)-1a and an orange solid (ꢀ)-1b.
Conjugate addition of alkyllithiums and phenyllithium:
When an alkyllithium or phenyllithium was added to a solu-
tion of carbene complex (ꢀ)-1a, (ꢁ)-1a, or (ꢀ)-1b in dieth-
yl ether a very fast reaction took place at ꢀ808C, and we
observed an immediate color change of the starting carbene
complex. The reaction was quenched with methyl triflate at
this low temperature and after purification by silica gel
column chromatography gave pentacarbonylcarbene com-
plex 2, tetracarbonylcarbene complex 3, or a mixture of
these two carbene complexes depending on the nature of
both the organolithium reagent and the starting carbene
complex 1 (Scheme 2 and Table 1).
In the case of chromium carbene complexes (ꢀ)-1a and
(ꢁ)-1a, the reaction with tert-butyllithium provided exclu-
sively the corresponding tetracarbonyl complexes 3a and (ꢁ)-
3a (Table 1, entries 1 and 2), while the experiments with cy-
clopentyllithium, neopentyllithium, butyllithium, and phe-
nyllithium furnished a mixture of the corresponding penta-
and tetracarbonyl complexes 2 and 3. These products were
isolated in practically equimolar ratios in the case of BuLi
and PhLi (Table 1, entries 6 9) and as mixtures in which the
tetracarbonyl derivative was favored ((CH2)4CHLi; Table 1,
entry 4) or was clearly the major component (tBuCH2Li;
Table 1, entry 5). In addition, we observed that except for
compounds 2e:3e (R=Ph), these mixtures evolved to the
corresponding tetracarbonyl complex on standing. In con-
trast, the reactions of tungsten carbene complex (ꢀ)-1b with
tBuLi and PhLi gave only pentacarbonyl complexes 2ab and
2eb, respectively (Table 1, entries 3 and 10). Compounds 2
and 3 were each generated as a mixture of two diaster-
eoisomers which have the same relative configuration at the
newly created stereogenic centers, as will be shown below.
The diastereoselectivity of the reaction seems to depend on
the substitution pattern of the organolithium reagent. The
highest value (84:16) was observed in the reaction with the
tertiary alkyllithium (tBuLi). The diastereoselectivity was
lower (79:21) with both the secondary derivative
((CH2)4CHLi) and the aryllithium (PhLi) and even lower
with the primary alkyllithiums (BuLi 70:30; tBuCH2Li
60:40).
The tandem organolithium methyl triflate addition reac-
tion to tungsten carbene complex (ꢀ)-1b did not improve
the results obtained with the corresponding chromium com-
plex (ꢀ)-1a. As pointed out, the experiments carried out
with (ꢀ)-1b and tBuLi or PhLi led to the corresponding
pentacarbonylcarbene complex 2ab or 2eb with lower
chemical yields but similar diastereomeric ratios (Table 1,
entries 3 and 10 versus entries 1 and 8, respectively). The
structures of products 2 and 3 were established on the basis
of their spectroscopic data and in the case of tetracarbonyl-
carbene complexes 3, a single-crystal X-ray diffraction of
the minor isomer of 3a (minor-3a)[23] revealed that the
vacant coordination site at the chromium atom is capped by
Results and Discussion
3-Furylcarbene complexes 1 were synthesized from 3-bro-
mofuran by sequential treatment with butyllithium, the cor-
responding hexacarbonylmetal (chromium or tungsten), and
tetramethylammonium bromide (Scheme 1).[22] Subsequent
Scheme 1. Preparation of 3-furylcarbene complexes 1. i) BuLi, THF,
ꢀ808C; ii) M(CO)6, 08C!RT; iii) Me4NBr, H2O, 0 8C!RT; iv) tBuCOCl,
CH2Cl2, DMF, ꢀ458C; v)R*OH, ꢀ458C!RT.
Abstract in Spanish: La reacciÛn a baja temperatura de com-
plejos (mentiloxi)(3-furil)carbeno de cromo o wolframio con
un compuesto organolÌtico y posteriormente con triflato de
metilo ocurriÛ con excelente regioselectividad (adiciÛn nu-
cleÛfila 1,4) y diastereoselectividad (disposiciÛn relativa 2,3-
trans de los sutituyentes procedentes del nucleÛfilo y electrÛfi-
lo) dando lugar a nuevos complejos (2,3-dihidro-3-furil)car-
beno 2,3-disustituÌdos. Ademµs, en esta reacciÛn se observÛ
un alto grado de diastereoselectividad facial cuando se utilizÛ
como nucleÛfilo un alquenillitio. La eliminaciÛn del fragmen-
to metµlico (oxidaciÛn al aire) y del auxiliar quiral (reduc-
ciÛn con LiAlH4) condujo a 2,3-dihidrofuranos trisustituidos
que contienen un centro estereogÿnico cuaternario en la posi-
ciÛn C3. Asimismo, se describe un nuevo tipo de complejos
quelato de cuatro eslabones (h2-alqueno)tetracarbonilcarbeno
estables cuya caracterizaciÛn incluye un anµlisis de difracciÛn
de rayos X.
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
Table 1. Furan dearomatized products 2, 3, 4, and 5 prepared from 3-furylcarbene complexes 1 and organolithium compounds by sequential conjugate
addition, oxidation, and reduction.
1
R
2:3
Ratio[a]
Yield [%][b]
dr[c]
4
Yield [%][d]
dr[e]
5[f]
Yield [%][g]
ee [%]
1
2
3
4
5
6
7
8
9
(ꢀ)-1a
(ꢁ)-1a
(ꢀ)-1b
(ꢀ)-1a
(ꢀ)-1a
(ꢀ)-1a
(ꢁ)-1a
(ꢀ)-1a
(ꢁ)-1a
(ꢀ)-1b
tBu
tBu
3a[h]
66
62
53
65
71
66
60
62
64
37
84:16
84:16
4a
78
80
39
85
82
80
85
83
80
84:16
5a
(ꢁ)-5a
90
82
78[i]
(ꢁ)-3a[h]
(ꢁ)-4a
4a[k]
4b
4c
4d
84:16
[l]
tBu
2ab[j]
2b:3b
2c:3c
2d:3d
86:14
(CH2)4CH[m]
35:65[n]
10:90[q]
50:50[n]
50:50[n]
47:53[t]
47:53
79:21
60:40
70:30
70:30
79:21
78:22
5b
5c
5d
92
85
84
92
83
82
[o]
[p]
[p]
tBuCH2
Bu
Bu
Ph
Ph
56:44[r]
70:30
70:30
78:22
78:22
76:24
30[s]
57[s]
(ꢁ)-2d:(ꢁ)-3d
(ꢁ)-4d
(ꢁ)-5d
2e:3e
4e
5e
(ꢁ)-2e:(ꢁ)-3e,
2eb[j]
(ꢁ)-4e
(ꢁ)-5e
10
Ph
[a] Ratio of the corresponding pentacarbonyl:tetracarbonyl (2:3) complexes determined by 1H NMR spectroscopy. [b] Isolated yield after column chro-
matography based on the corresponding carbene complex 1. [c] Diastereomeric ratio was determined by 1H NMR spectroscopy; integration of signals
corresponding to the tetracarbonyl complex. [d] Isolated yield after column chromatography based on the corresponding carbene complex 3/2 or mixture
of carbene complexes 2:3. [e] Diastereomeric ratio determined from the 1H NMR spectrum. [f] Single diastereoisomer. [g] Isolated yield after column
chromatography based on compound 4. [h] Only the tetracarbonyl complex was observed in this experiment. [i] Enantiomeric excess determined by
1H NMR analysis of the corresponding Mosher ester 6 in comparison with racemic mixture (ꢁ)-6. [j] Only the pentacarbonyl complex was observed in
this experiment. [k] Oxidation of tungsten carbene complex 2ab was carried out with C5H5N+ꢀOꢀ in THF at room temperature. [l] Poor resolution in
1
the H NMR spectrum: two diastereoisomers in an approximate ratio of 86:14. [m] Cyclopentyl. [n] After overnight in the refrigerator the pentacarbonyl
1
complex completely converted to the tetracarbonyl complex. [o] Poor resolution in the H NMR spectrum. [p] Not determined. [q] These two complexes
were separated by silica gel column chromatography. [r] Determined by 13C NMR spectroscopy (inverse gated decoupling experiment). [s] Enantiomeric
excess determined by HPLC analysis on a chiral support (Chiralcel OD-H column) in comparison with the corresponding racemic mixture. [t] Pentacar-
bonyl complex 2e did not convert to tetracarbonyl complex 3e after several days in the refrigerator.
nation of the alkene moiety to
chromium is readily observed
in the 1H NMR spectra of 3
(complexed double bond) in
comparison with those of 2 (un-
complexed
double
bond)
(Table 2). While the resonance
of vinyl proton H3 of com-
plexes 3 is shifted to higher
field relative to that of the cor-
responding complex 2, the
signal of vinyl proton H2 of 3 is
shifted downfield. The crystal
chosen for the above X-ray
structure determination was
grown by cooling (ꢀ58C) a sol-
ution of a mixture of 3a and
minor-3a (approximately 84:16
ratio) in dry pentane. After
crystallization, the solid product
Scheme 2. Conjugate addition of organolithium compounds to 3-furylcarbene complexes 1. Only the major dia-
stereoisomer of compounds 2, 3, 4, and 6 and the major enantiomer of products 5 are shown. i) R-Li, Et2O,
ꢀ808C; ii) MeOTf, ꢀ808C!RT; iii) air, hn, hexane, RT; iv) LiAlH4, THF, 08C!RT; v) MeOH/H2O, NaCl.
the carbon carbon double bond to form a four-membered
ring olefin-chelated complex with an almost perpendicular
arrangement of the Cr=C and C=C bonds (Figure 1).[24,25]
Presumably owing to the enol ether nature of the double
bond in addition to geometrical constraints, the alkene
ligand is not bonded symmetrically to Cr. The bond length
of Cr to the more electron-rich carbon atom C3
(2.374(3) ä) is significantly shorter than that of Cr to C2
(2.663(3) ä). These distances are slightly or much longer, re-
spectively, than the CrꢀC(olefin) bond lengths reported for
cis-(h2-olefin)(tetracarbonyl)(carbene)chromium complexes
was separated from the solution by decantation. 1H NMR
spectra of the crystals and the residue obtained after solvent
removal from the solution indicated that the crystals were
enriched in the minor isomer (3a:minor-3a 1:1.9), whereas
the solution was enriched in the major one (3a:minor-3a,
2.1:1). Based on these observations and according to follow-
ing results we assume that the crystal selected for the X-ray
analysis belongs to the minor isomer of 3a. In addition, this
analysis unequivocally determined the relative and absolute
configuration of the newly formed stereogenic centers and
revealed a trans disposition of the tBu and Me groups.
Due to the strong electron-withdrawing ability of the
pentacarbonylmetal fragment, the furan ring directly
bonded to the carbene carbon of complexes 1 becomes elec-
tron deficient enough to undergo regioselective nucleophilic
attack with an organolithium (RꢀLi) at C2 to generate the
c]
(2.238 2.414 ä, mean 2.312 ä)[25a but are in agreement
with those found in a related (h1-phosphine)(h2-electron-rich
alkene)(tricarbonyl)(carbene)chromium complex with a bi-
cyclic chelate structure (h2-(EtOꢀC=CH)Cr: CrꢀCH
2.384(4) ä, CrꢀC 2.619(4) ä).[26] The unsymmetrical coordi-
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Chem. Eur. J. 2003, 9, 5725 5736

Furan Dearomatization
5725 5736
Table 2. 1H NMR Chemical shifts of H2, H3, and H5 hydrogens corresponding to carbene complexes 2 and
3.[a]
dency of complexes 2 (M=Cr)
to eliminate a CO ligand corre-
lates with the steric bulk of the
R
group
(tBu>tBuCH2 >
(CH2)4CH>Ph>Bu; Table 1).
In the case of compound 2e
(R=Ph), the planar geometry
of the Ph group may allow it to
adopt a more favorable confor-
mation which could account for
the lower bias to give product
3e. Decarbonylation of penta-
Compound
R
dH2 [ppm]
dH3 [ppm]
dH5 [ppm]
2b
3b
2d
3d
2e
3e
(CH2)4CH[b]
6.43
7.26
6.32
7.26
6.54
7.52
5.58
4.36
5.74
4.42
6.19
4.70
4.18
3.77
4.16
3.96
5.05
5.13
(CH2)4CH[b]
Bu
Bu
Ph
Ph
carbonylcarbene complexes
2
(M=W) was not observed
under the reaction conditions.
Presumably, in these complexes
[a] Spectra were recorded in CDCl3. [b] Cyclopentyl.
the steric crowdedness is smaller due to the greater size of
the tungsten atom (atomic radii: Cr 1.35 ä, W 1.37 ä)[29a]
and the consequently longer metal carbene carbon
bond.[29b,c] Additionally, dissociation of
a
WꢀCO bond
(DG° =28.0 kcalmolꢀ1) is more difficult than dissociation of
a CrꢀCO bond (DG° =24.0 kcalmolꢀ1).[30]
The presence of a bulky alkoxy group bonded to the car-
bene carbon seems to be necessary to efficiently direct nu-
cleophile attack to the heteroaromatic ring. Thus, when
analogous reactions were carried out with (methoxy)(3-fur-
yl)carbene complex 7 we observed either lower chemical
yield of the conjugate addition product 8a (reaction with a
tertiary alkyllithium: RLi=tBuLi)[31] or a mixture of two
products 8b and 9b (reaction with a primary alkyllithium:
RLi=BuLi); the major product 9b arises from an initial ad-
dition of the organolithium to the carbene carbon
(Scheme 3). Carbene-complex 9b is particularly unstable. It
must be purified and stored rigorously under N2 to avoid a
very fast oxidative transformation to the corresponding car-
boxylic ester 10b. Formation of 9b could involve 1,2-nucleo-
philic addition of BuLi to carbene complex 7 to give tetra-
hedral intermediate B, which subsequently would undergo
migratory insertion of carbon monoxide followed by O-
methylation of lithium acylchromate intermediate C.[32] The
relative configuration of products 8 was elucidated from a
NOESY experiment carried out with carboxylic ester 11a[33]
generated by air light oxidation of carbene complex 8a.
Figure 1. X-ray crystal structure of tetracarbonyl complex minor-3a
(ORTEP, thermal ellipsoids with 30% probability). Selected bond lengths
[ä], bond angles [8], and torsion angle [8]: C2 C3 1.336(4), Cr C2
2.663(3), Cr C3 2.374(3), Cr C11 1.982(2), Cr C23 1.895(3), Cr C25
1.818(3), C11 C4 1.526(4), C11 O2 1.316(3); C11-Cr-C3 63.74(10), C23-
Cr-C3 98.07(12), C25-Cr-C3 163.10(11), C2-C3-Cr 87.0(2), C4-C11-Cr
106.62(16), C11-C4-C3 98.6(2); C11-Cr-C3-C2 114.8(2).
Removal of the metal fragment and chiral auxiliary group:
The metal moiety of complexes 2 and 3 was eliminated by
oxidation of the metal carbene functional group which led
to the corresponding carboxylic ester 4 (Scheme 2 and
Table 1). In the case of the chromium derivatives, the oxida-
tion was carried out by simply exposing a hexane solution of
either the appropriate tetracarbonylcarbene complex 3 or a
mixture of the corresponding penta- and tetracarbonylcar-
bene complexes 2 and 3 to the air in the presence of light.
Oxidation of tungsten carbene complex 2ab, which was a
much slower reaction, was best performed with pyridine N-
oxide in THF as solvent. Compounds 4 were each isolated
as a mixture of two diastereoisomers in a ratio analogous to
that observed at the level of the starting carbene complex 2
and 3 (Table 1, entries 1 9). The two diastereoisomers of
anionic enolate-type intermediate A (Scheme 2) which sub-
sequently reacts with MeOTf in a regio- and diastereoselec-
tive electrophilic attack at C3 from the face opposite to the
R group at C2.[27] The initially formed pentacarbonylcarbene
complexes 2 of chromium undergo a spontaneous dissocia-
tion of a CO ligand to give tetracarbonylcarbene complexes
3 in which the alkene unit is attached to the metal. The driv-
ing force for this CO dissociation could be relaxation of the
steric strain induced by the bulky carbene ligand, which has
the larger groups at C2 and C3 placed on the same side of
the ring and in addition contains a quaternary carbon center
at the a position to the carbene carbon.[28] Indeed, the ten-
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
Scheme 4. Reduction of compounds 4e and minor-4e. i) LiAlH4, THF,
08C!RT; ii) MeOH/H2O, NaCl.
Scheme 3. Organolithium additions to methoxycarbene complex 7. i) R-
Li, Et2O, ꢀ808C; ii) MeOTf, ꢀ808C!RT.
carboxylic ester 4e (R=Ph) were easily separated by silica
gel column chromatography. An X-ray crystallographic
study of a single crystal of the minor isomer (minor-4e) con-
firmed its structure and the absolute configuration previous-
ly assigned to the newly formed stereogenic carbons.[34]
The chiral auxiliary group was successfully removed by
lithium aluminum hydride reduction of esters 4 (the mixture
of diastereoisomers summarized in Table 1 was used as start-
ing material). After hydrolysis the corresponding primary al-
cohol 5 was isolated as a single diastereoisomer (Scheme 2
and Table 1). The structure and relative stereochemistry of
products 5 was confirmed by one- and two-dimensional
NMR experiments carried out with alcohols 5b and 5e.[33]
The enantiomeric purity of trisubstituted dihydrofurans 5
was checked in the case of compounds 5d (R=Bu, 30% ee)
and 5e (R=Ph, 57% ee) by HPLC analysis on a chiral sup-
port and in the case of compound 5a (R=tBu, 78% ee),
which could not be resolved in the chiral HPLC columns
used, by 1H NMR analyses of Mosher esters 6 and (ꢁ)-6
prepared by reaction of 5a with (R)-a-methoxy-a-trifluoro-
methylphenylacetyl chloride [(R)-MTPA-Cl] according to
Mosher×s protocol (Scheme 2).[35]
Parallel reductions of the previously separated diaster-
eoisomeric esters 4e and minor-4e afforded enantiomerical-
ly pure alcohols (+)-5e and (ꢀ)-5e, respectively, as shown
in Scheme 4. The ee values of products (+)-5e and (ꢀ)-5e
were similarly determined by chiral-phase HPLC analysis.
Scheme 5. Reactions with (E)-2-phenylethenyllithium. i) reagent, Et2O,
ꢀ808C; ii) MeOTf, ꢀ808C!RT; iii) air, hn, hexane, RT; iv) LiAlH4,
THF, 08C!RT; v) MeOH/H2O, NaCl.
(E)-5 f and (Z)-5 f with high and very high enantiomeric
purity, respectively. The same sequence of reactions was car-
ried out starting with racemic carbene complex (ꢁ)-1a. The
enantiomeric ratio of products (E)-5 f and (Z)-5 f was like-
wise determined by chiral-phase HPLC analysis. The struc-
ture and relative configuration of diastereomeric alcohols
(E)-5 f and (Z)-5 f were ascertained on the basis of the
NMR data.[33] The absolute configuration assigned to these
compounds has been assumed by analogy.
In contrast, the reaction of the carbene complex (ꢀ)-1a
with (Z)-2-phenylethenyllithium[37] followed by quenching
with methyl triflate afforded exclusively the Z diaster-
eoisomer isolated as a 65:35 mixture of penta- and tetracar-
bonylcarbene complexes (Z)-2 f and (Z)-3 f, which after oxi-
Reactions with alkenyllithium compounds: The sequential
reaction of chromium carbene complex (ꢀ)-1a with (E)-2-
phenylethenyllithium[36] and methyl triflate under reaction
conditions analogous to those mentioned above yielded a
complex mixture of at least four major compounds that was
directly submitted to air light oxidation (Scheme 5). After
purification a 1:1 mixture of carboxylic esters (E)-4 f (with
the expected trans exocyclic C=C double bond) and (Z)-4 f
(with the unexpected cis exocyclic C=C double bond) was
obtained. These E/Z diastereoisomers, each one of which
1
had a single set of signals in the H and 13C NMR spectra,
were separated by column chromatography. Independent
LiAlH4 reduction of (E)-4 f and (Z)-4 f furnished alcohols
5730
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Furan Dearomatization
5725 5736
dative cleavage of the metal moiety provided carboxylic
ester (Z)-4 f as a single diastereoisomer (Scheme 6). Reduc-
tion of (Z)-4 f, as previously described, furnished alcohol
D/D’ to Z anionic derivative F could take place through the
benzylic cyclopropylmethyl anion intermediate E. However,
so far, we do not have any evidence to support this hypothe-
sis.
Conclusion
This tandem organolithium addition methyl triflate alkyla-
tion represents an efficient new strategy to successfully dear-
omatize the furan ring of Fischer (menthyloxy)(3-furyl)car-
bene complexes with complete regio- and stereocontrol.
This methodology provides tetracarbonyl- and/or pentacar-
bonylcarbene complexes in which two carbon-based sub-
stituents have been added across the heteroarene 2-posi-
tioned C=C double bond. Furthermore, the reactions with
alkenyllithium derivatives proceed with very high asymmet-
ric induction. After successive elimination of the metal unit
(air light oxidation) and chiral auxiliary group (LiAlH4 re-
duction), this methodology allows access to functionalized
2,3,3-trisubstituted 2,3-dihydrofurans as enantiomerically
pure compounds.[41]
Chromium carbene complexes are effective starting ma-
terials for this synthetic procedure. Lower chemical yields
and a more sluggish oxidation process was observed in the
experiments with the corresponding tungsten derivative.
Presumably as a result of steric hindrance, the initially
formed pentacarbonylcarbene complexes of chromium un-
derwent a spontaneous intramolecular displacement of a cis-
CO ligand by the electron-rich C=C double bond to give
(h2-alkene)tetracarbonylcarbene complexes containing an
unprecedented chelated four-membered ring structure that
was unambiguously characterized by X-ray analysis, and
which revealed that the olefin function is bonded unsymmet-
rically to the metal. The unpredicted isomerization of an E
carbon carbon double bond to the corresponding Z isomer
observed in this work may also be explained on the basis of
unfavorable steric interactions.
Scheme 6. Reaction with (Z)-2-phenylethenyllithium. i) reagent, Et2O,
ꢀ808C; ii) MeOTf, ꢀ808C!RT; iii) air, hn, hexane, RT; iv) LiAlH4,
THF, 08C!RT; v) MeOH/H2O, NaCl; vi) reagent, Et3N, DMAP, CH2Cl2,
08C!RT.
(Z)-5 f practically as a single enantiomer. In order to ascer-
tain the absolute configuration of the stereogenic centers
formed in these alkenyllithium addition reactions, primary
alcohol (Z)-5 f was transformed into the camphanate deriva-
tive 12 by reaction with (1S)-(ꢀ)-camphanoyl chloride. A
single-crystal X-ray analysis of 12 confirmed the relative and
absolute configuration as outlined in Schemes 5 and 6.[38]
The unexpected trans!cis C=C double bond isomerization
found in the experiments with (E)-2-phenylethenyllithium
but not in the reactions with the corresponding Z isomer
could be promoted by a release of the steric congestion,
which will be higher in intermediate D/D’ than in intermedi-
ate F as a result of the Ph group orientation towards either
the ™wall∫ of CO moieties (D) or the bulky alkoxy group
(D’) (Scheme 7).[39,40] Conversion of E anionic intermediate
Experimental Section
General: All reactions involving organometallic species were carried out
under an atmosphere of dry N2 using oven-dried glassware and syringes.
All common reagents and solvents were obtained from commercial sup-
pliers and used without further purification unless otherwise indicated.
THF and Et2O were distilled from sodium/benzophenone under N2 im-
mediately prior to use, MeOH and DMF from CaH2, and CH2Cl2 from
phosphorus pentoxide (P4O10). The solvents used in column chromatogra-
phy (hexane and AcOEt) were used as received. TLC was performed on
aluminum-backed plates coated with silica gel 60 with F254 indicator
(Scharlau). Flash column chromatography was carried out on silica
gel 60, 230 240 mesh. 1H NMR (200, 300, 400 MHz) and 13C NMR (75.5,
100 MHz) spectra were measured at room temperature on a Bruker AC-
200, AC-300, and AMX-400 instruments, respectively, with tetramethylsi-
lane (d=0.0, 1H NMR) or CDCl3 (d=77.00, 13C NMR) as internal stan-
dard. Carbon multiplicities were assigned by DEPT techniques. Low-res-
olution electron impact (EI, 70 eV) or FAB+ mass spectra (LRMS)
were obtained on an HP 5987A instrument, and the intensities are re-
ported as a percentage relative to the base peak after the corresponding
m/z value. High-resolution mass spectra (HRMS) were determined on a
Finnigan MAT 95 spectrometer. Optical rotations were measured at
Scheme 7. Proposed mechanism for the C=C bond isomerization.
5731
Chem. Eur. J. 2003, 9, 5725 5736
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
room temperature with a Perkin Elmer 241 polarimeter using a Na
lamp; sample concentrations are reported in g per 100 mL of solvent.
Enantiomer compositions were determined by HPLC analysis with a
chiral column in comparison with the corresponding racemic mixtures,
and were carried out on a Waters LC-1 instrument with a UV/Vis photo-
diode array detector at a flow rate of 1.0 mLminꢀ1 and employing a Chir-
alcel OD-H column for 5d (hexane/EtOH 1000:1), 5e, (+)-5e, (ꢀ)-5e
(hexane/EtOH 2000:1), (E)-5 f (hexane/EtOH 1500:1); and a Chiralcel
OJcolumn for ( Z)-5 f (hexane/EtOH 750:1).
by column chromatography (silica gel, hexane) to give compounds 2 and
3. Yields and ratios are listed in Table 1 and Schemes 5 and 6.
cis-[1-[h2-(2S,3S)-2-tert-Butyl-3-methyl-2,3-dihydro-3-furyl]-1-
[(1R,2S,5R)-menthyloxy]methylidene]tetracarbonylchromium (3a): Data
on the 84:16 mixture of diastereoisomers: red oil; Rf =0.30 (hexane);
1H NMR (300 MHz, CDCl3): d=0.89 (s, 9H), 0.93 (d, J=7.0 Hz, 3H),
0.97 (d, J=6.5 Hz, 3H), 0.98 (d, J=7.0 Hz, 3H), 0.98 1.10 (m, 1H), 1.50
(s, 3H), 1.12 1.26 (m, 2H), 1.52 1.71 (m, 1H), 1.72 1.80 (m, 3H), 2.00
2.10 (m, 1H), 2.27 2.31 (m, 1H), 3.83 (s, 1H), 4.33 (d, J=2.2 Hz, 1H),
4.90 (td, J=10.7, 4.8 Hz, 1H), 7.42 ppm (d, J=2.2 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3): d=15.6, 18.8, 21.2, 22.1, 22.8, 25.5, 27.2, 31.3, 33.4,
33.9, 40.6, 47.8, 65.2, 68.1, 90.1, 101.4, 146.0, 220.4, 221.2, 228.8, 233.7,
352.1 ppm; LRMS (70 eV, EI): m/z (%): 470 (2) [M +], 219 (24), 138
(40), 95 (68), 83 (59), 57 (100); HRMS (70 eV, EI): m/z: calcd for
C24H34CrO6 [M +]: 470.1736; found: 470.1761. Resolvable resonances of
minor isomer: 1H NMR (300 MHz, CDCl3): d=0.77 (d, J=6.5 Hz, 3H),
3.88 (s, 1H), 4.26 (d, J=2.2 Hz, 1H), 4.96 5.11 (m, 1H), 7.39 ppm (d, J=
2.2 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=15.3, 20.7, 31.6, 41.3, 47.3,
91.6, 101.7 ppm.
Materials: Commercially available solutions of BuLi (1m in hexane),
tBuLi (1.5m in pentane), and LiAlH4 (1m in THF) were used as received.
Phenyllithium,[42] neopentyllithium,[43] cyclopentyllithium,[44] (Z)-b-bro-
mostyrene,[37] and pentacarbonyl-[1-(3-furyl)-1-methoxymethylidene]-
chromium (7)[45] were prepared according to literature procedures. (Z)-
or (E)-2-Phenylethenyllithium were preformed by addition at ꢀ808C of
2 equiv tBuLi to (Z)- or (E)-b-bromostyrene dissolved in Et2O and the
mixture was stirred for 2 h at ꢀ808C and then for 30 min at room tem-
perature.
General procedure for the preparation of 3-furylcarbene complexes 1:
BuLi (1.6m in hexane, 15.9 mL, 25 mmol) was added dropwise to a solu-
tion of 3-bromofuran (2.30 mL, 25.5 mmol) in dry THF (33 mL) cooled
to ꢀ808C. The mixture was stirred for 1 h at this temperature. The result-
ing solution was transferred by using a cannula to a suspension of the
corresponding M(CO)6 (24 mmol) in THF (75 mL) at 08C. The mixture
was stirred for 20 min at 08C and then for 2 h at room temperature. The
solvents were removed by using a rotary evaporator. The residue ob-
tained was dissolved in deoxygenated H2O (60 mL) and cooled in an ice
bath. Me4NBr (4.16 g, 27 mmol) was then added and the mixture was stir-
red for 20 min. The aqueous layer was extracted with CH2Cl2 (100 mL).
The organic layer was dried over Na2SO4 and concentrated under re-
duced pressure to give pentacarbonyl-[1-(3-furyl)-1-[(tetramethylammo-
nio)oxy]methylidene]chromium as a red solid (6.01 g, 67%) or pentacar-
bonyl-[1-(3-furyl)-1-[(tetramethylammonio)oxy]methylidene]tungsten as
a yellow solid (7.16 g, 59%). Pivaloyl chloride (3.07 mL, 25 mmol) and
DMF (2 drops) were added to a solution of the corresponding ammoni-
um salt (16 mmol) in dry CH2Cl2 (100 mL) at ꢀ458C. After the mixture
had been stirred at ꢀ458C for 1 h, a solution of the appropriate alcohol
(+)- or (ꢁ)-menthol (3.90 g, 25 mmol) in dry CH2Cl2 (20 mL) was added
dropwise at ꢀ458C. The resulting mixture was stirred overnight allowing
it to warm slowly to room temperature without removing the cold bath.
The reaction was quenched with silica gel, the solvents were removed
under reduced pressure, and the residue was purified by column chroma-
tography (silica gel, hexane) to give the corresponding carbene complex
1. Yields are listed in Scheme 1.
[1-[(2S,3S)-2-tert-Butyl-3-methyl-2,3-dihydro-3-furyl]-1-[(1R,2S,5R)-men-
thyloxy]methylidene]pentacarbonyltungsten (2ab): Data on the 86:14
mixture of diastereoisomers: orange oil; 1H NMR (300 MHz, CDCl3):
d=0.83 (d, J=6.9 Hz, 3H), 0.89 1.03 (m, 9H), 1.06 (s, 9H), 1.07 1.54 (m
with s at 1.28, 5H), 1.65 2.46 (m, 4H), 3.96 (s, 1H), 5.30 5.37 (m, 1H),
5.41 (d, J=3.1 Hz, 1H), 6.70 ppm (d, J=3.1 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3): d=16.1, 21.3, 21.7, 22.0, 23.2, 25.3, 27.4, 27.8 (3C),
31.7, 34.0, 40.8, 43.4, 48.5, 73.5, 98.5, 104.6, 115.6, 198.3 (4C), 202.3,
347.9 ppm.
Pentacarbonyl-[1-[(2S,3S)-3-methyl-2-phenyl-2,3-dihydro-3-furyl]-1-
[(1R,2S,5R)-menthyloxy]methylidene]tungsten (2eb): Data on the 76:24
mixture of diastereoisomers: orange oil; 1H NMR (300 MHz, CDCl3):
d=0.69 (d, J=7.0 Hz, 3H), 0.81 (d, J=7.1 Hz, 3H), 0.83 1.25 (m, 6H),
1.27 1.48 (m, 2H), 1.51 (s, 3H), 1.55 1.79 (m, 4H), 4.62 (td, J=10.9,
4.0 Hz, 1H), 5.15 (s, 1H), 6.15 (d, J=2.6 Hz, 1H), 7.21 7.40 ppm (m,
5H); 13C NMR (75.5 MHz, CDCl3): d=29.9, 30.3, 30.6, 33.5, 33.6, 39.2,
41.2, 76.3, 92.0, 95.6, 110.6, 111.7, 126.4 (2C), 127.7 (2C), 128.6, 139.0,
145.8, 197.6 (4C), 201.8, 337.3 ppm. Resolvable resonances of minor
isomer: 1H NMR (300 MHz, CDCl3): d=0.61 (d, J=7.1 Hz, 3H), 1.82 (s,
3H), 4.85 (td, J=10.8, 4.0 Hz, 1H), 5.29 (s, 1H), 5.59 (d, J=2.6 Hz, 1H),
6.51 ppm (d, J=2.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=30.6,
47.7, 93.7, 96.2, 128.4, 146.1 ppm.
cis-Tetracarbonyl-[1-[h2-(2S,3S)-2-cyclopentyl-3-methyl-2,3-dihydro-3-
furyl]-1-[(1R,2S,5R)-menthyloxy]methylidene]chromium (3b): Data on a
65:35 mixture of 3b and 2b, respectively, each one as a likely 79:21 mix-
ture of diastereoisomers: red oil; 1H NMR (300 MHz, CDCl3): d=0.84
1.10 (m, 13H), 1.17 1.29 (m, 3H), 1.43 1.79 (m, 11H), 1.96 (m, 2H),
2.18 2.41 (m, 1H), 3.77 (d, J=10.8 Hz, 1H), 4.36 (d, J=2.0 Hz, 1H), 4.97
(td, J=10.7, 4.5 Hz, 1H), 7.26 ppm (d, J=2.0 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3): d=18.4, 17.9, 21.4, 22.6, 23.4, 24.5, 25.9, 26.3, 28.8,
31.9, 32.1, 34.4, 41.0, 41.6, 47.9, 66.3, 66.8, 90.2, 98.2, 147.6, 220.2, 220.9,
229.7, 234.5, 351.4 ppm. Resolvable signals of the corresponding penta-
carbonyl complex 2b: 1H NMR (300 MHz, CDCl3): d=4.18 (d, J=
5.4 Hz, 1H), 5.48 (d, J=2.9 Hz, 1H), 6.43 ppm (d, J=2.9 Hz, 1H). Re-
solvable signal of minor diastereoisomer of 2b: 1H NMR (300 MHz,
CDCl3): d=5.48 ppm (apparent d, 1H).
Pentacarbonyl-[1-(3-furyl)-1-[(1R,2S,5R)-menthyloxy]methylidene]chro-
1
mium [(ꢀ)-1a]: Red oil; Rf =0.37 (hexane); H NMR (300 MHz, CDCl3):
d=0.91 (d, J=7.0 Hz, 3H), 1.01 (d, J=6.5 Hz, 3H), 1.02 (d, J=6.1 Hz,
3H), 0.97 1.18 (m, 2H), 1.25 1.43 (m, 2H), 1.61 1.97 (m, 4H), 2.21 2.25
(m, 1H), 5.18 (m, 1H), 6.68 (s, 1H), 7.44 (s, 1H), 8.23 ppm (s, 1H);
13C NMR (75.5 MHz, CDCl3): d=17.5, 21.9, 22.0, 24.4, 26.8, 31.0, 34.0,
42.7, 48.7, 91.9, 107.1, 142.4, 143.3, 149.6, 216.9 (4C), 222.9, 323.6 ppm;
IR (neat): n˜ =2960, 2872, 2058, 1930, 1552, 1510 cmꢀ1; LRMS (70 eV, EI):
m/z (%): 426 (16) [M +], 398 (42), 315 (26), 314 (100), 286 (48); HRMS
(70 eV, EI): m/z: calcd for C20H23CrO7 [M ++H]: 427.0849; found:
427.0830.
cis-Tetracarbonyl-[1-[h2-(2S,3S)-3-methyl-2-neopentyl-2,3-dihydro-3-
furyl]-1-[(1R,2S,5R)-menthyloxy]methylidene]chromium (3c): Data on
the 56:44 mixture of diastereoisomers: red oil; Rf =0.29 (hexane);
1H NMR (300 MHz, CDCl3): d=0.84 (d, J=10.8 Hz, 6H), 0.90 (s, 18H),
0.93 1.17 (m, 12H), 1.18 1.35 (m, 8H), 1.68 1.84 (m, 16H), 1.90 2.19 (m,
4H), 4.06 4.11 (m, 2H), 4.41 4.43 (m, 2H), 4.92 5.03 (m, 2H), 7.30 ppm
(brs, 1H); 13C NMR (75.5 MHz, CDCl3): d=15.0, 15.9, 16.3, 20.7, 22.1,
22.9, 23.4, 25.4, 25.8 (3C), 29.4, 29.8, 30.0, 31.4, 31.5, 33.9, 41.6, 42.0, 42.5,
46.6, 47.4, 64.5, 64.7, 66.6, 67.1, 80.1, 90.2, 90.4, 91.5, 91.6, 219.8, 220.6,
229.2, 233.9, 234.1, 350.8, 352.7 ppm; LRMS (70 eV, EI): m/z (%): 484 (3)
[M +], 233 (72), 206 (56), 153 (100), 83 (66); HRMS (70 eV, EI): m/z:
calcd for C25H36CrO6 [M +]: 484.1938; found: 484.1917.
Pentacarbonyl-[1-(3-furyl)-1-[(1R,2S,5R)-menthyloxy]methylidene]tungs-
ten [(ꢀ)-1b]: Orange solid; 1H NMR (200 MHz, CDCl3): d=0.89 (d, J=
6.8 Hz, 3H), 0.91 1.15 (m, 6H), 1.19 1.41 (m, 3H), 1.60 2.00 (m, 5H),
2.15 2.31 (m, 1H), 5.07 (td, J=10.0, 4.4 Hz, 1H), 7.21 (dd, J=1.9, 0.8 Hz,
1H), 7.45 (dd, J=1.9, 1.3 Hz, 1H), 8.27 ppm (m, 1H); 13C NMR
(75.5 MHz, CDCl3): d=17.7, 21.8, 24.5, 27.0, 31.1, 34.1, 42.5, 48.5, 94.0,
107.8, 143.5, 144.3, 152.3, 197.7 (4C), 201.9, 296.1 ppm.
General procedure for the preparation of carbene complexes 2 and 3: A
solution of the corresponding organolithium compound (1.80 mmol) was
added dropwise to a solution of the appropriate 3-furylcarbene complex
1 (1.50 mmol) in Et2O (20 mL) at ꢀ808C. The mixture was stirred at this
temperature for 20 min. The initial red color turned dark red. Methyl tri-
flate (1.95 mmol) was then added at ꢀ808C and the stirring was contin-
ued for 30 min at this temperature and 1 h at room temperature. The sol-
vent was removed under reduced pressure and the residue was purified
cis-[1-[h2-(2S,3S)-2-Butyl-3-methyl-2,3-dihydro-3-furyl]-1-[(1R,2S,5R)-
menthyloxy]methylidene]tetracarbonylchromium (3d): Data on the 70:30
mixture of diastereoisomers: red oil; Rf =0.56 (hexane/AcOEt 9:1);
5732
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Furan Dearomatization
5725 5736
1H NMR (300 MHz, CDCl3): d=0.85 1.03 (m, 16H), 1.40 (s, 3H), 1.21
1.66 (m, 6H), 1.55 2.05 (m, 3H), 2.15 2.48 (m, 2H), 3.96 (m, 1H), 4.42
(d, J=2.0 Hz, 1H), 4.91 4.98 (m, 1H), 7.26 ppm (brs, 1H); 13C NMR
(75.5 MHz, CDCl3): d=13.8, 15.8, 16.6, 20.9, 22.3, 22.5, 22.9, 25.8, 26.7,
29.4, 31.5, 33.9, 41.4, 47.4, 65.2, 66.1, 89.9, 92.9, 147.4, 219.8, 220.6, 229.8,
234.08, 351.0 ppm; LRMS (70 eV, EI): m/z (%): 470 (4) [M +], 414 (3),
219 (60), 192 (57), 83 (100), 52 (91). Resolvable resonances of minor
isomer: 1H NMR (300 MHz, CDCl3): d=4.39 ppm (d, J=2.0, Hz, 1H);
13C NMR (75.5 MHz, CDCl3): d=13.7, 15.0, 16.5, 20.8, 22.1, 22.4, 22.5,
25.5, 28.6, 29.2, 31.4, 33.9, 41.2, 46.9, 65.0, 66.5, 91.5, 93.4, 146.7, 219.7,
220.6, 229.3, 233.9, 352.8 ppm. Resolvable signals of the corresponding
pentacarbonyl complex 2d: 1H NMR (300 MHz, CDCl3): d=4.08 4.17
(m, 1H), 5.20 5.26 (m, 1H), 5.74 (d, J=2.9 Hz, 1H), 6.31 6.32 ppm (m,
1H). Resolvable resonance of minor diastereoisomer: 1H NMR
(300 MHz, CDCl3): d=5.71 ppm (d, J=2.8 Hz, 1H).
3.98 (d, J=8.8 Hz, 1H), 4.65 (td, J=10.8, 4.3 Hz, 1H), 4.90 (d, J=2.9 Hz,
1H), 6.42 ppm (d, J=2.9 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=
16.2, 21.4, 22.5, 23.4, 25.3, 25.7, 26.2, 29.6, 30.5, 31.8, 34.6, 41.0, 41.7, 47.3,
56.0, 75.5, 95.8, 108.2, 147.0, 174.2 ppm; LRMS (70 eV, EI): m/z (%): 334
(2) [M +], 197 (100), 151 (46), 116 (45), 83 (69), 69 (41); HRMS (70 eV,
EI): m/z: calcd for C21H34O3 [M +]: 334.2508; found: 334.2500. Resolvable
1
resonances of minor isomer: H NMR (300 MHz, CDCl3): d=4.00 (d, J=
8.8 Hz, 1H), 4.87 ppm (d, J=2.9 Hz, 1H); 13C NMR (75.5 MHz, CDCl3):
d=16.3, 29.2, 30.8, 41.6, 108.0 ppm.
(1R,2S,5R)-Menthyl
(2S,3S)-3-methyl-2-neopentyl-2,3-dihydrofuran-3-
carboxylate (4c): Data on the 60:40 mixture of diastereoisomers: color-
less oil; 1H NMR (300 MHz, CDCl3): d=0.73 (d, J=6.8 Hz, 3H), 0.88
1.10 (m, 7H), 0.91 (s, 8H), 1.38 (s, 3H), 1.43 1.69 (m, 9H), 1.85 2.01 (m,
2H), 4.15 4.19 (m, 1H), 4.59 4.68 (m, 1H), 4.92 (d, J=2.9 Hz, 1H),
6.38 6.41 ppm (m, 1H); 13C NMR (75.5 MHz, CDCl3): d=15.8, 20.8,
21.9, 22.9, 23.9, 25.7, 29.7 (3C), 30.1, 31.3, 34.1, 40.7, 43.5, 46.7, 56.3, 74.9,
88.3, 106.6, 146.9, 173.6 ppm; LRMS (70 eV, EI): m/z (%): 336 (2) [M +],
153 (100), 97 (42), 57 (20); HRMS (70 eV, EI): m/z: calcd for C21H36O3
[M +]: 336.2668; found: 336.2664. Resolvable resonances of minor
isomer: 1H NMR (300 MHz, CDCl3): d=1.31 (s, 3H), 4.89 ppm (d, J=
2.9 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=15.9, 20.8, 23.0, 25.9, 29.9,
31.3, 40.7, 43.8, 46.8, 56.4, 88.4, 106.7, 147.1, 173.6 ppm.
Pentacarbonyl-[1-[(2S,3S)-3-methyl-2-phenyl-2,3-dihydro-3-furyl]-1-
[(1R,2S,5R)-menthyloxy]methylidene]chromium and cis-tetracarbonyl-
[1-[h2-(2S,3S)-3-methyl-2-phenyl-2,3-dihydro-3-furyl]-1-[(1R,2S,5R)-men-
thyloxy]methylidene]chromium (2e:3e 47:53): Data on a 78:22 mixture
1
of diastereoisomers: red oil; H NMR (300 MHz, CDCl3): d=0.62 (d, J=
6.8 Hz, 6H), 0.66 (d, J=11.7 Hz, 6H), 0.70 1.30 (m, 36H), 1.49 1.73 (m
with 3s at 1.28, 1.30, and 1.49, 30H), 1.75 1.91 (m with s at 1.90, 6H),
4.59 4.71 (m, 2H), 4.70 (d, J=2.3 Hz, 2H), 4.78 4.92 (m, 2H), 5.05 (s;
1H of 2e), 5.12 (s; 1H of 3e), 5.17 (s; 1H of 3e), 5.27 (s; 1H of 2e), 5.61
(d, J=2.9 Hz, 2H), 6.20 (d, J=3.1 Hz; 2H of 3e), 6.54 (d, J=2.8 Hz,
2H), 7.18 7.24 (m, 20H), 7.52 ppm (d, J=2.8 Hz; 1H of 3e); 13C NMR
(75.5 MHz, CDCl3): d=18.3, 18.4, 18.8, 19.1, 23.3, 24.0, 24.2, 24.3, 24.4,
24.5, 24.6, 25.1, 25.3, 25.6, 28.1, 28.2, 32.8, 33.1, 33.5, 36.0, 36.1, 41.8, 42.6,
49.2, 50.3, 68.3, 70.8, 79.0, 79.4, 79.8, 92.0, 94.7, 95.1, 95.2, 96.5, 97.0,
112.6, 113.0, 128.0, 128.4, 130.0, 130.4, 130.6, 130.7, 130.9, 131.1, 131.2,
136.5, 142.6, 147.9, 148.2, 149.2, 219.1, 219.2, 222.7, 224.8, 225.0, 230.8,
236.5, 350.7, 363.1 ppm. Resolvable resonances of minor diastereoisom-
ers: 1H NMR (300 MHz, CDCl3): d=5.18 (s; 1H of 3e), 5.27 (s; 1H of
2e), 5.60 ppm (d, J=2.9 Hz; 1H of 2e).
(1R,2S,5R)-Menthyl (2S,3S)-2-butyl-3-methyl-2,3-dihydrofuran-3-carbox-
ylate (4d): Data on the 70:30 mixture of diastereoisomers: colorless oil;
1H NMR (300 MHz, CDCl3): d=0.73 (d, J=6.8 Hz, 3H), 0.84 0.99 (m,
9H), 1.38 (s, 3H), 1.30 1.58 (m, 1H), 1.64 1.89 (m, 2H), 1.91 2.03 (m,
2H), 4.09 4.14 (m, 1H), 4.61 (td, J=11.0, 4.3 Hz, 1H), 4.97 (d, J=
2.9 Hz, 1H), 6.36 ppm (d, J=2.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3):
d=14.2, 16.1, 21.1, 22.3, 22.9, 23.2, 25.3, 26.1, 29.0, 30.9, 31.7, 34.5, 41.1,
47.1, 56.3, 75.2, 90.9, 107.2, 146.2, 173.2, 173.8 ppm; LRMS (70 eV, EI):
m/z (%): 322 (1) [M +], 139 (100), 95 (12), 83 (13), 55 (13). Resolvable
resonances of minor isomer: 13C NMR (75.5 MHz, CDCl3): d=16.3, 31.2,
32.9, 47.2, 56.0, 75.3, 91.2, 146.6 ppm.
(1R,2S,5R)-Menthyl
(2S,3S)-3-methyl-2-phenyl-2,3-dihydrofuran-3-car-
boxylate (4e): White solid; Rf =0.48 (hexane/AcOEt 9:1); 1H NMR
(300 MHz, CDCl3): d=0.60 (d, J=6.8 Hz, 3H), 0.70 (d, J=6.6 Hz, 3H),
0.81 (d, J=6.8 Hz, 3H), 0.80 0.94 (m, 3H), 1.10 1.21 (m, 2H), 1.52 1.66
(m, 4H), 1.59 (s, 3H), 4.27 (td, J=10.8, 4.3 Hz, 1H), 5.14 (d, J=2.8 Hz,
1H), 5.18 (s, 1H), 6.60 (d, J=2,8 Hz, 1H), 7.34 7.24 ppm (m, 5H);
13C NMR (75.5 MHz, CDCl3): d=16.3, 21.4, 22.2, 23.3, 26.2, 26.9, 31.4,
34.4, 39.6, 47.1, 59.2, 74.9, 92.4, 107.4, 127.1 (2C), 128.6 (2C), 128.7,
138.4, 147.0, 172.8 ppm.
Pentacarbonyl-[1-[(2S,3S)-3-methyl-2-[(Z)-2-phenylethenyl]-2,3-dihydro-
3-furyl]-1-[(1R,2S,5R)-menthyloxy]methylidene]chromium [(Z)-2 f) and
cis-tetracarbonyl-[1-[h2-(2S,3S)-3-methyl-2-[(Z)-2-phenylethenyl]-2,3-di-
hydro-3-furyl]-1-[(1R,2S,5R)-menthyloxy]methylidene]chromium [(Z)-
3 f)]: A 65:35 mixture, respectively: red oil. Data for (Z)-2 f: 13C NMR
(75.5 MHz, CDCl3): d=16.8, 22.5, 26.0, 26.7, 28.7, 31.4, 34.5, 42.7, 48.6,
66.0, 67.7, 86.2, 95.0, 110.6, 126.8, 127.6 (2C), 123.1 (2C), 134.0, 136.2,
145.5, 217.0 (4C), 221.3, 361.6 ppm. Data for (Z)-3 f: 13C NMR
(75.5 MHz, CDCl3): d=16.3, 16.5, 21.4, 22.3, 23.4, 26.3, 32.0, 41.9, 47.7,
88.0, 90.6, 129.0, 133.3, 135.7, 146.7, 220.5, 223.2, 229.5, 234.5, 350.4 ppm.
(1R,2S,5R)-Menthyl (2R,3R)-3-methyl-2-phenyl-2,3-dihydrofuran-3-car-
boxylate (minor-4e): White solid; Rf =0.49 (hexane/AcOEt 9:1);
1H NMR (300 MHz, CDCl3): d=0.54 (d, J=6.8 Hz, 3H), 0.73 (d, J=
6.6 Hz, 3H), 0.77 (d, J=7.1 Hz, 3H), 0.78 0.89 (m, 3H), 1.05 1.35 (m,
3H), 1.22 1.61 (m, 3H), 1.62 (s, 3H), 4.27 (td, J=10.8, 4.3 Hz, 1H), 5.07
(d, J=2.8 Hz, 1H), 5.28 (s, 1H), 6.62 (d, J=2,8 Hz, 1H), 7.26 7.35 ppm
(m, 5H); 13C NMR (75.5 MHz, CDCl3): d=16.4, 21.3, 22.3, 23.5, 26.2,
27.6, 31.5, 34.5, 39.5, 46.9, 58.8, 75.2, 92.2, 107.4, 126.6 (2C), 128.4 (2C),
128.5, 138.4, 147.0, 172.9 ppm. Suitable single crystals for X-ray structure
analysis were obtained by cooling (in a freezer) a solution of minor-4e in
dry pentane.
1
The H NMR spectrum had poor resolution.
General procedure for the preparation of esters 4: Either the correspond-
ing tetracarbonylcarbene complex 3 or a mixture of both penta- and tet-
racarbonylcarbene complexes
2 and 3 (1.0 mmol) was dissolved in
hexane (150 mL) and the resulting solution was exposed to air and sun-
light (in its absence a 100-W tungsten lamp was used) until the initial red
color of the starting carbene complex disappeared. The resulting colorless
solution was filtered through a plug of Celite. Evaporation of the solvent
and column chromatography (silica gel, hexane/ethyl acetate 97:3) afford-
ed pure compounds 4. Yields and ratios of isomers are given in Table 1
and Schemes 5 and 6.
(1R,2S,5R)-Menthyl (2S,3S)-3-methyl-2-[(E)-2-phenylethenyl]-2,3-dihy-
drofuran-3-carboxylate [(E)-4 f]: Colorless oil; 1H NMR (300 MHz,
CDCl3): d=0.57 (d, J=6.6 Hz, 3H), 0.66 (d, J=6.9 Hz, 3H), 0.84 (d, J=
7.1 Hz, 3H), 0.61 0.98 (m, 5H), 1.28 1.49 (m, 3H), 1.55 (s, 3H), 1.50
1.72 (m, 2H), 1.74 1.86 (m, 1H), 4.59 (td, J=11.0, 4.3 Hz, 1H), 4.77 (d,
J=8.0 Hz, 1H), 6.63 (d, J=15.9 Hz, 1H), 7.21 7.28 ppm (m, 5H);
13C NMR (75.5 MHz, CDCl3): d=16.2, 21.2, 22.0, 23.3, 25.4, 26.3, 31.5,
34.4, 41.3, 47.1, 57.8, 75.2, 91.1, 107.3, 124.4, 127.1 (2C), 128.3, 128.8
(2C), 133.7, 136.4, 146.3, 173.1 ppm.
(1R,2S,5R)-Menthyl (2S,3S)-2-tert-butyl-3-methyl-2,3-dihydrofuran-3-car-
boxylate (4a): Data on the 84:16 mixture of diastereoisomers: colorless
oil; Rf =0.55 (hexane/AcOEt 9:1); 1H NMR (200 MHz, CDCl3): d=0.71
(d, J=6.9 Hz, 3H), 0.90 (d, J=7.0 Hz, 3H), 0.91 (d, J=7.4 Hz, 3H),
0.95 0.98 (m, 2H), 1.05 (s, 3H), 1.16 1.45 (m, 3H), 1.46 (s, 3H), 1.63
1.71 (m, 2H), 1.89 1.97 (m, 1H), 2.10 2.16 (m, 1H), 3.87 (s, 1H), 4.61
(td, J=10.8, 4.4 Hz, 1H), 4.87 (d, J=2.8 Hz, 1H), 6.48 ppm (d, J=
2,8 Hz, 1H); 13C NMR (50 MHz, CDCl3): d=15.7, 21.0, 22.0, 22.8, 25.5,
26.4 (3C), 27.0, 31.3, 34.1, 34.2, 40.4, 47.2, 54.3, 75.4, 99.2, 109.0, 145.7,
174.4 ppm; LRMS (70 eV, EI): m/z (%): 322 (5) [M +], 169 (14), 139
(100), 83 (90), 57 (95).
(1R,2S,5R)-Menthyl (2S,3S)-3-methyl-2-[(Z)-2-phenylethenyl]-2,3-dihy-
drofuran-3-carboxylate [(Z)-4 f]: Colorless oil; Rf =0.37 (hexane/AcOEt
9:1); 1H NMR (300 MHz, CDCl3): d=0.79 (d, J=6.8 Hz, 3H), 0.86 1.02
(m, 9H), 1.43 1.45 (m, 2H), 1.47 (s, 3H), 1.68 (m, 2H), 2.03 (m, 2H),
4.69 (td, J=10.8, 4.3 Hz, 1H), 5.10 (d, J=10.3 Hz, 1H), 5.13 (d, J=
2,9 Hz, 1H), 5.75 (dd, J=11.1, 10.5 Hz, 1H), 6.37 (d, J=2.6 Hz, 1H),
6.71 (d, J=11.7 Hz, 1H), 7.28 7.39 ppm (m, 5H); 13C NMR (75.5 MHz,
CDCl3): d=15.7, 20.8, 21.9, 22.9, 25.2, 25.9, 31.2, 34.0, 40.4, 46.8, 57.0,
(1R,2S,5R)-Menthyl (2S,3S)-2-cyclopentyl-3-methyl-2,3-dihydrofuran-3-
carboxylate (4b): Data on the 79:21 mixture of diastereoisomers: color-
less oil; 1H NMR (300 MHz, CDCl3): d=0.72 (d, J=7.1 Hz, 3H), 0.79
1.09 (m, 9H), 1.25 1.58 (m, 8H), 1.59 2.03 (m, 9H), 2.21 2.27 (m, 1H),
5733
Chem. Eur. J. 2003, 9, 5725 5736
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
75.2, 84.9, 106.7, 126.5, 127.3, 128.1 (2C), 128.8 (2C), 133.6, 138.9, 145.2,
172.9 ppm.
(300 MHz, CDCl3): d=1.63 (s, 3H), 1.71 (brs, 1H), 3.33 3.48 (m, 2H),
4.64 (d, J=8.0 Hz, 1H), 4.85 (d, J=2.9 Hz, 1H), 6.53 (dd, J=15.9,
8.0 Hz, 1H), 6.54 (d, J=2.3 Hz, 1H), 6.70 (d, J=15.9 Hz, 1H), 7.25
7.45 ppm (m, 5H); 13C NMR (75.5 MHz, CDCl3): d=22.7, 51.5, 66.8,
91.8, 107.1, 124.8, 127.1 (2C), 128.4, 129.0 (2C), 134.3, 136.6, 147.0 ppm;
LRMS (70 eV, EI): m/z (%): 216 (23) [M +], 187 (33), 157 (64), 133
(100), 115 (71), 91 (93), 83 (43); HRMS (70 eV, EI): m/z: calcd for
C14H16O2 [M +]: 216.1152; found: 216.1152.
Formation of 4a by oxidation of tungsten carbene complex 2ab: Pyridine
N-oxide (0.40 g, 4.167 mmol) was added to a solution of carbene complex
2ab (0.30 g, 0.476 mmol) in THF (30 mL) and the mixture was stirred at
room temperature for 8 d. THF was then removed under reduced pres-
sure, and the residue was taken up in hexane and filtered through Celite.
Solvent removal under vacuum gave the crude product which was puri-
fied by column chromatography (silica gel deactivated with 10% Et3N in
hexane and using a mixture of hexane/AcOEt 95:5 as eluant) to yield 4a
(0.06 g, 0.181 mmol, 39%) as a colorless oil.
(2S,3R)-[3-Methyl-2-[(Z)-2-phenylethenyl]-2,3-dihydro-3-furyl]methanol
[(Z)-5 f]: Colorless oil; [a]2D0 =ꢀ32.1 (c=0.70 in CH2Cl2); 1H NMR
(300 MHz, CDCl3): d=1.07 (s, 3H), 1.70 (brs, 1H), 3.41 3.58 (m, 2H),
4.77 (d, J=2.9 Hz, 1H), 4.99 (d, J=10.3 Hz, 1H), 6.08 (dd, J=11.7,
10.3 Hz, 1H), 6.48 (d, J=2.6 Hz, 1H), 6.88 (d, J=11.7 Hz, 1H), 7.26
7.35 ppm (m, 5H); 13C NMR (75.5 MHz, CDCl3): d=23.0, 51.3, 66.8,
85.6, 107.0, 126.6, 127.8, 128.6 (2C), 129.0 (2C), 135.8, 136.4, 146.8 ppm;
LRMS (70 eV, EI): m/z (%): 216 (38) [M +], 187 (50), 169 (53), 157 (98),
129 (100), 115 (92), 91(93), 83 (79); HRMS (70 eV, EI): m/z: calcd for
C14H16O2 [M +]: 216.1152; found: 216.1150.
General procedure for the preparation of alcohols 5: The corresponding
carboxylic ester 4 (0.6 mmol) was dissolved in THF (6 mL) and LiAlH4
(1m in THF, 0.66 mmol, 0.66 mL) was added dropwise at 08C. After
30 min the ice bath was removed and the stirring was continued for 6 h at
room temperature. The resulting mixture was successively quenched at
08C with MeOH (dropwise until the vigorous gas evolution stopped) and
a saturated aqueous NaCl solution (5 mL). The aqueous layer was ex-
tracted with AcOEt. The combined organic layers were dried over
Na2SO4, filtered and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, hexane/ethyl acetate 9:1) to give
compounds 5. Yields are listed in Table 1 and Schemes 5 and 6.
(2S,3R)-[2-tert-Butyl-3-methyl-2,3-dihydro-3-furyl]methyl
(S)-3,3,3-tri-
fluoro-2-methoxy-2-phenylpropionate (6): (R)-a-Methoxy-a-(trifluorome-
thyl)phenylacetyl chloride (R-MTPA-Cl, 106 mg, 0.42 mmol), Et3N
(0.072 mL, 0.52 mmol), and 4-dimethylaminopyridine (DMAP, 122 mg,
1 mmol) were added to a solution of 5a (60.0 mg, 0.35 mmol) in CH2Cl2
(3 mL). The mixture was stirred for 12 h at room temperature. Water was
then added (5 mL) and the reaction mixture was extracted with Et2O
(3î10 mL). The organic layer was dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude compound was purified
by column chromatography (silica gel, hexane/AcOEt 9:1) to give com-
pound 6 (133.2 mg, 93%) as a 86:14 mixture of diastereoisomers. Color-
less oil; 1H NMR (300 MHz, CDCl3): d=1.01 (s, 9H), 1.25 (s, 3H), 3.59
(s, 3H), 3.75 (s, 1H), 4.21 (d, J=11.5 Hz, 1H), 4.38 (d, J=10.5 Hz, 1H),
4.79 (d, J=2.6 Hz, 1H), 6.38 (d, J=2.6 Hz, 1H), 7.38 7.45 (m, 3H), 7.56
7.51 ppm (m, 2H); 13C NMR (75.5 MHz, CDCl3): d=24.3, 27.7 (3C),
31.9, 48.8, 55.9, 70.4, 98.2, 109.7, 121.9, 125.7, 127.7 (2C), 128.8 (2C),
130.0, 132.6, 146.1, 167.1 ppm; LRMS (70 eV, EI): m/z (%): 386 (5)
[M+], 189 (54), 140 (11), 139 (100), 105 (15), 95 (35); HRMS (70 eV, EI):
m/z: calcd for C20H25F3O4 [M +]: 386.1705; found: 386.1696. Resolvable
resonances of minor isomer: 1H NMR (300 MHz, CDCl3): d=1.06
(s, 9H), 3.60 (s, 3H), 4.74 ppm (d, J=2.8 Hz, 1H).
(2S,3R)-(2-tert-Butyl-3-methyl-2,3-dihydro-3-furyl)methanol (5a): Color-
less oil; Rf =0.14 (hexane/AcOEt 9:1); [a]2D0 =+29.4 (c=0.27 in CH2Cl2);
1H NMR (200 MHz, CDCl3): d=1.10 (s, 9H), 1.27 (s, 3H), 1.46 1.51 (m,
1H), 3.46 3.53 (m, 1H), 3.64 3.73 (m, 1H), 3.77 (s, 1H), 4.81 (d, J=
2.8 Hz, 1H), 6.49 ppm (d, J=2.8 Hz, 1H); 13C NMR (75.5 MHz, CDCl3):
d=24.5, 27.9 (3C), 34.4, 50.8, 66.3, 98.5, 109.6, 146.3 ppm; LRMS (70 eV,
EI): m/z (%): 170 (5) [M +], 140 (8), 139 (82), 95 (14), 83 (100); HRMS
(70 eV, EI): m/z: calcd for C10H18O2 [M +]: 170.1307; found: 170.1307.
(2S,3R)-(2-Cyclopentyl-3-methyl-2,3-dihydro-3-furyl)methanol (5b): Col-
orless oil; Rf =0.13 (hexane/AcOEt 9:1); [a]2D0 =+22.2 (c=0.30 in
CH2Cl2); 1H NMR (400 MHz, CDCl3): d=1.13 (s, 3H), 1.16 1.26 (m,
1H), 1.33 1.54 (m, 1H), 1.56 1.72 (m, 5H), 1.76 1.83 (m, 1H), 1.90 1.96
(m, 1H), 2.41 (m, 1H), 3.30 (d, J=11.0 Hz, 1H), 3.61 (m, 1H), 3.80 (d,
J=10.4 Hz, 1H), 4.73 (d, J=2.9 Hz, 1H), 6.46 ppm (d, J=2.9 Hz, 1H);
13C NMR (75.5 MHz, CDCl3): d=23.4, 25.1, 26.0, 29.4, 32.2, 39.8, 49.6,
66.6, 95.9, 107.9, 146.9 ppm; LRMS (70 eV, EI): m/z (%): 182 (19) [M +],
151 (80), 83 (100), 69 (56); HRMS (70 eV, EI): m/z: calcd for C11H18O2
[M +]: 182.1307; found: 182.1310.
The reactions of carbine-complex 7 with tBuLi, BuLi, or (E)-2-phenyle-
thenyllithium and MeOTf to give compounds 8a, 8b and 9b, and 13, re-
spectively, were carried out according to the general procedure described
for the preparation of carbene complexes 2 and 3. Yields are reported in
Scheme 3 and ref. [39].
(2S,3R)-(3-Methyl-2-neopentyl-2,3-dihydro-3-furyl)methanol (5c): Color-
less oil; Rf =0.17 (hexane/AcOEt 9:1); 1H NMR (300 MHz, CDCl3): d=
0.97 (s, 9H), 1.03 (s, 3H), 1.46 (d, J=14.8 Hz, 1H), 1.57 (brs, 1H), 1.84
(dd, J=14.6, 10.5 Hz, 1H), 3.23 (d, J=11.1 Hz, 1H), 3.43 3.49 (m, 1H),
4.07 (d, J=10.5 Hz, 1H), 4.76 (d, J=2.8 Hz, 1H), 6.51 ppm (d, J=2.8 Hz,
1H); 13C NMR (75.5 MHz, CDCl3): d=22.0, 30.2 (3C), 30.5, 41.6, 50.0,
66.3, 88.1, 106.6, 147.5 ppm; LRMS (70 eV, EI): m/z (%): 185 (35) [M +
+H], 153 (100), 97 (89), 85 (29); HRMS (70 eV, EI): m/z: calcd for
C11H20O2 [M +]: 184.1463; found: 184.1461.
(2S*,3S*)-[1-(2-tert-Butyl-3-methyl-2,3-dihydro-3-furyl)-1-(methoxy)me-
thylidene]pentacarbonylchromium (8a): Red oil; Rf =0.50 (hexane/
AcOEt 9:1); 1H NMR (300 MHz, CDCl3): d=0.95 (s, 9H), 1.28 (s, 3H),
3.90 (s, 1H), 4.91 (s, 3H), 5.59 (d, J=2.9 Hz, 1H), 6.61 ppm (d, J=
2.9 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=26.8, 27.6 (3C), 34.7, 67.2,
73.4, 103.2, 113.1, 147.3, 216.5 (4C), 223.2, 374.5 ppm.
(2S,3R)-(2-Butyl-3-methyl-2,3-dihydro-3-furyl)methanol (5d): Colorless
oil; Rf =0.16 (hexane/AcOEt 9:1); 1H NMR (200 MHz, CDCl3): d=0.94
(t, J=7.4 Hz, 3H), 1.26 1.49 (m, 4H), 1.10 (s, 3H), 1.52 186 (m, 3H),
3.32 (dd, J=11.0, 2.8 Hz, 1H), 3.51 (dd, J=11.0, 8.5 Hz, 1H), 4.00 (dd,
J=10.2, 2.6 Hz, 1H), 6.50 ppm (d, J=2.6 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3): d=14.3, 22.8, 23.0, 28.5, 29.8, 49.3, 66.2, 91.1, 107.3, 146.8 ppm;
LRMS (70 eV, EI): m/z (%): 171 (100) [M ++H], 153 (15), 139 (20), 65
(20); HRMS (70 eV, EI): m/z: calcd for C10H18O2 [M +]: 170.1307; found:
170.1301.
(2S*,3S*)-[1-(2-Butyl-3-methyl-2,3-dihydro-3-furyl)-1-(methoxy)methyli-
dene]pentacarbonylchromium (8b): Red oil; Rf =0.48 (hexane/AcOEt
9:1); 1H NMR (300 MHz, CDCl3): d=0.87 (brsignal, 3H), 1.05 1.56 (m,
9H), 4.17 (d, J=10.0 Hz, 1H), 4.89 (s, 3H), 5.75 (d, J=2.9 Hz, 1H),
6.37 ppm (d, J=2.9 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=13.5,
22.4, 27.4, 28.7, 30.6, 67.3, 75.6, 91.6, 110.7, 145.5, 216.3 (4C), 223.1,
371.7 ppm; LRMS (70 eV, EI): m/z (%): 374 (4) [M +], 358 (28), 262
(26), 241 (64), 223 (48), 167 (100); HRMS (70 eV, EI): m/z: calcd for
C16H19CrO7 [M ++H]: 375.0536; found: 375.0534.
(2S,3R)-(3-Methyl-2-phenyl-2,3-dihydro-3-furyl)methanol [(+)-5e]: Col-
orless oil; Rf =0.13 (hexane/AcOEt 9:1); [a]2D0 =+103.0 (c=0.36 in
CH2Cl2); 1H NMR (400 MHz, CDCl3): d=0.83 (dd, J=8.6, 4.8 Hz, 1H),
1.34 (s, 3H), 3.05 (dd, J=11.5, 8.5 Hz, 1H), 3.16 (dd, J=11.5, 4.8 Hz,
1H), 4.87 (d, J=2.8 Hz, 1H), 5.14 (s, 1H), 6.59 (d, J=2.8 Hz, 1H), 7.25
7.42 ppm (m, 5H); 13C NMR (75.5 MHz, CDCl3): d=23.5, 51.7, 66.8,
91.6, 108.0, 126.3 (2C), 128.4, 128.8 (2C), 137.5, 146.5 ppm; LRMS
(70 eV, EI): m/z (%): 190 (23) [M +], 159 (100), 144 (41), 131 (75), 91
(62); HRMS (70 eV, EI): m/z: calcd for C12H14O2 [M +]: 190.0991; found:
190.0993.
Pentacarbonyl-[2-(3-furyl)-1,2-dimethoxyhexylidene]chromium (9b): Red
1
oil; Rf =0.53 (hexane/AcOEt 9:1); H NMR (300 MHz, CDCl3): d=0.89
1.10 (m, 3H), 1.21 1.39 (m, 2H), 1.41 1.54 (m, 2H), 1.92 (td, J=14.0,
4.0 Hz, 1H), 2.13 (td, J=14.0, 5.1 Hz, 1H), 3.31 (s, 3H), 4.80 (s, 3H),
6.25 (s, 1H), 7.31 (s, 1H), 7.34 ppm (s, 1H); 13C NMR (75.5 MHz,
CDCl3): d=13.7, 23.2, 24.1, 34.6, 49.8, 67.6, 92.0, 109.4, 125.1, 141.1,
143.1, 216.9 (4C), 224.9, 365.8 ppm.
Methyl 2-(3-furyl)-2-methoxyhexanoate (10b): Colorless oil; Rf =0.32
(hexane/AcOEt 9:1); 1H NMR (300 MHz, CDCl3): d=0.89 (t, J=6.9 Hz,
3H), 1.08 1.34 (m, 4H), 2.00 2.08 (m, 2H), 3.19 (s, 3H), 3.79 (s, 3H),
6.39 (dd, J=1.8, 0.8 Hz, 1H), 7.40 (dd, J=1.8, 1.7 Hz, 1H), 7.54 ppm (dd,
(2S,3R)-[3-Methyl-2-[(E)-2-phenylethenyl]-2,3-dihydro-3-furyl]methanol
[(E)-5 f]: Colorless oil; [a]2D0 =ꢀ31.5 (c=0.12 in CH2Cl2); 1H NMR
5734
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5725 5736

Furan Dearomatization
5725 5736
J=1.3, 1.0 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=13.9, 22.6, 25.4,
36.6, 52.1, 52.3, 80.8, 109.1, 124.5, 141.1, 143.0, 172.7 ppm; LRMS (FAB+
): m/z (%): 227 (10) [M ++H], 207 (41), 193 (24), 183 (23), 167 (100), 154
(14); HRMS (FAB+): m/z: calcd for C12H19O4 [M ++H]: 227.1283;
found: 227.1287.
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44)1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgement
Methoxy (2S*,3S*)-2-tert-butyl-3-methyl-2,3-dihydrofuran-3-carboxylate
(11a): This product was prepared in 72% yield by following the above
general procedure for the preparation of esters 4. Colorless oil; Rf =0.37
(hexane/AcOEt 9:1); 1H NMR (300 MHz, CDCl3): d=1.01 (s, 9H), 1.49
(s, 3H), 3.69 (s, 3H), 3.91 (s, 1H), 4.90 (d, J=2.8 Hz, 1H), 6.51 ppm (d,
J=2.8 Hz, 1H); 13C NMR (75.5 MHz, CDCl3): d=26.2 (3C), 26.4, 33.9,
52.0, 53.5, 99.5, 108.5, 146.4, 175.2 ppm; LRMS (FAB+): m/z (%): 199
(62) [M ++H], 194 (67), 167 (68), 165 (100); HRMS (FAB+) m/z: calcd
for C11H19O3 [M ++H]: 199.1334; found: 199.1343.
This work was financially supported by the DGICYT (grants PB97-1271
and PB00-0219). S.K.N. and Y.R.S.L. thank the Ministerio de EducaciÛn,
Cultura y Deporte of Spain for a postdoctoral fellowship.
[1] a) T. Bach, Angew. Chem. 1996, 108, 795; Angew. Chem. Int. Ed.
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Xiong, R. P. Hsung, C. R. Berry, C. Rameshkumar, J. Am. Chem.
Soc. 2001, 123, 7174.
(2S,3R)-3-Methyl-2-[(Z)-2-phenylethenyl]-2,3-dihydro-3-furylmethyl
(1S)-camphanoate (12): Et3N (0.09 mL, 0.65 mmol), 4-dimethylaminopyr-
idine (DMAP, 100 mg, 0.82 mmol), and then (1S)-(ꢀ)-camphanoyl chlo-
ride (107 mg, 0.50 mmol) were added to a solution of (Z)-5 f (90.0 mg,
0.416 mmol) in CH2Cl2 (2 mL) at 08C. The mixture was stirred at room
temperature for 3 h. Water was then added (5 mL), and the mixture was
extracted with Et2O (3î10 mL). The organic layer was dried over
Na2SO4 and the solvent was removed under reduced pressure. The crude
compound was purified by column chromatography (silica gel, hexane/
AcOEt 9:1) to give compound 12 (148.3 mg, 90%) as a white solid. Rf =
0.52 (hexane/AcOEt 9:1); [a]2D0 =+13.2 (c=0.95 in CH2Cl2); 1H NMR
(300 MHz, CDCl3): d=0.95 (s, 3H), 1.06 (s, 3H), 1.11 (s, 3H), 1.15 (s,
3H), 1.61 1.72 (m, 1H), 1.86 1.72 (m, 1H), 2.42 (ddd, J=14.1, 9.8,
4.3 Hz, 1H), 4.03 (d, J=11.1 Hz, 1H), 4.32 (d, J=11.1 Hz, 1H), 4.84 (d,
J=2.9 Hz, 1H), 5.00 (d, J=10.2 Hz, 1H), 5.85 (dd, J=11.5, 10.3 Hz, 1H),
6.37 (d, J=2.9 Hz, 1H), 6.84 (d, J=11.7 Hz, 1H), 7.26 7.38 ppm (m,
5H); 13C NMR (75.5 MHz, CDCl3): d=9.6, 16.6, 16.7, 22.9, 28.8, 30.5,
48.9, 53.9, 54.7, 68.1, 84.7, 91.1, 106.9, 125.4, 127.5, 128.2 (2C), 128.5
(2C), 135.5, 135.6, 145.9, 167.2, 177.9 ppm; LRMS (70 eV, EI): m/z (%):
396 (10) [M +], 367 (18), 170 (89), 169 (100), 155 (80), 91 (31); HRMS
(70 eV, EI): m/z: calcd for C24H28O5 [M +]: 396.1937; found: 396.1936.
Crystals of 12 suitable for X-ray diffraction studies were grown by cool-
ing (in a refrigerator) a solution of the compound in dry pentane contain-
ing a few drops of CH2Cl2.
[8] H. M. L. Davies, G. Ahmed, M. R. Churchill, J. Am. Chem. Soc.
1996, 118, 10774.
[9] A. Vasella, R. Voeffray, Helv. Chim. Acta 1982, 65, 1134.
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M¸ller, E. F. Paulus, Tetrahedron Lett. 1985, 26, 2997.
[11] a) H.-S. Ryang, K. Shima, H. Sakurai, J. Org. Chem. 1973, 38, 2860;
b) C. Rivas, R. A. BolÌvar, M. Cucarella, J. Heterocycl. Chem. 1982,
19, 529; c) J. A. Porco, Jr., S. L. Schreiber in Comprehensive Organic
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gamon, Oxford, 1991, p. 151.
[12] a) J. Adams, J. Rokach, Tetrahedron Lett. 1984, 25, 35; b) R. B.
Chhor, B. Nosse, S. Sˆrgel, C. Bˆhm, M. Seitz, O. Reiser, Chem.
Eur. J. 2003, 9, 260, and references therein.
Pentacarbonyl-[1-methoxy-1-[(2S*,3S*)-3-methyl-2-[(E)-2-phenylethen-
yl]-2,3-dihydro-3-furyl]methylidene]chromium (13): Data taken from the
7:1 mixture of E:Z isomers: red oil; Rf =0.35 (hexane/AcOEt 9:1);
1H NMR (300 MHz, CDCl3): d=1.35 (s, 3H), 4.75 4.80 (m with s at 4.79,
4H), 5.89 (d, J=2.9 Hz, 1H), 6.00 (dd, J=15.7, 8.4 Hz, 1H), 6.48 (d, J=
2.9 Hz, 1H), 6.51 (d, J=15.7 Hz, 1H), 7.22 7.43 ppm (m, 5H); 13C NMR
(75.5 MHz, CDCl3): d=27.3, 67.2, 76.9, 91.2, 110.4, 124.9, 126.2 (2C),
127.9, 128.4 (2C), 132.8, 135.8, 145.7, 216.1 (4C), 223.1, 369.6 ppm;
LRMS (FAB+): m/z (%): 420 (6) [M +], 336 (32), 309 (32), 308 (100),
248 (57), 237 (36); HRMS (FAB+): m/z: calcd for C20H17CrO7 [M ++H]:
421.0379; found: 421.0395. Resolvable resonances of minor Z isomer:
1H NMR (300 MHz, CDCl3): d=1.30 (s, 3H), 4.69 (s, 3H), 5.23 (d, J=
10.5 Hz, 1H), 5.56 ppm (apparent t, J=11.2 Hz, 1H).
[13] B. H. Lipshutz, Chem. Rev. 1986, 86, 795.
X-ray crystal structure determinations: Data for the X-ray structure anal-
ysis of compounds minor-3a, minor-4e, and 12 were collected on a
Nonius Kappa CCD single-crystal diffractometer by using f and w scans
(qmax =708) with CuKa radiation (graphite crystal monochromator, l=
1.54184 ä). Crystal detector distance was fixed at 29 mm with 28 oscilla-
tion and 40 s exposure time per image. Data collection strategy was cal-
culated with the program Collect (Collect, Nonius BV, 1997 2000). Data
reduction and cell refinement were performed with the programs
DENZO and SCALEPACK.[46] Lorentz, polarization, and empirical
XABS2[47] absorption corrections were performed. The crystal structure
was solved with direct methods by using the program SHELXS-97.[48]
Anisotropic least-squares refinement was carried out with SHELXL-
97.[49] Atomic scattering factors were taken from the International Tables
for Crystallography (Vol. C). Geometrical calculations were made with
PARST.[50] The crystallographic plots were made with ORTEP3.[51]
[14] a) J. D. Elliott, M. Hetmanski, R. J. Stoodley, M. N. Palfreyman, J.
Chem. Soc. Perkin Trans. 1 1981, 1782; b) B. P. Gunn, Tetrahedron
Lett. 1985, 26, 2869.
[15] a) T. Shono, Y. Matsumura, S. Yamane, Tetrahedron Lett. 1981, 22,
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1981, 1121; c) J. M. J. Verlaak, A. J. H. Klunder, B. Zwanenburg,Tet-
rahedron Lett. 1982, 23, 5463.
[16] In addition, reaction of furan with radical species produced a stereo-
isomeric mixture of 1,4-addition products (2,5-dialkyl/aryl-2,5-dihy-
drofurans): a) L. Benati, N. La Barba, M. Tiecco, A. Tundo, J.
Chem. Soc. B 1969, 1253; b) M. Janda, J. Srogl, I. Stibor, M. Nemec,
P. Vopatrnµ, Tetrahedron Lett. 1973, 637.
[17] a) I. Kuwajima, H. Urabe, Tetrahedron Lett. 1981, 22, 5191; b) D.
Goldsmith, D. Liotta, M. Saindane, L. Waykole, P. Bowen, Tetrahe-
dron Lett. 1983, 24, 5835; c) A. G. Schultz, L. A. Motyka, M.
Plummer, J. Am. Chem. Soc. 1986, 108, 1056. See also: d) M.
Asaoka, N. Yanagida, K. Ishibashi, H. Takei, Tetrahedron Lett. 1981,
22, 4269; e) C. W. Jefford, P.-Z. Huang, J.-C. Rossier, A. W. Sledeski,
J. Boukouvalas, Synlett 1990, 745.
CCDC-210973 (minor-3a), -210974 (minor-4e), and -210975 (12) contain
the supplementary crystallographic data for the structures reported in
this paper. These data can be obtained free of charge via www.ccdc.ca-
m.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic
5735
Chem. Eur. J. 2003, 9, 5725 5736
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
[18] a) H. Chen, L. M. Hodges, R. Liu, W. C. Stevens, Jr., M. Sabat,
W. D. Harman, J. Am. Chem. Soc. 1994, 116, 5499; b) H. Chen, R.
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Smith, M. D. Chordia, W. D. Harman, Tetrahedron 2001, 57, 8203.
[19] Complexes of the type: [tpRe(CO)(L)(h2-furan)] tp=hydridotris-
(pyrazolyl)borate, L=tBuNC, PMe3, pyridine, 1-methylimidazole.
[20] L. A. Friedman, W. D. Harman, J. Am. Chem. Soc. 2001, 123, 8967.
[21] J. Barluenga, A. A. Trabanco, J. FlÛrez, S. GarcÌa-Granda, E.
MartÌn, J. Am. Chem. Soc. 1996, 118, 13099.
[31] In this experiment we also observed a mixture of unidentified prod-
ucts.
[32] The scope and limitations of this latter reaction are currently being
studied in our laboratory. These results will be reported separately.
[33] The NMR spectra measured included 1H, 13C, DEPT, gHMQC,
gHMBC, gCOSY, and NOESY.
[34] Crystal data for minor-4e: C22H30O3, Mr =342.48, crystal size 0.32î
0.25î0.25 mm, orthorhombic, space group P212121, a=9.3736(1),
b=11.0456(2),
c=18.6432(3) ä,
V=1930.26(5) ä3,
1calcd =
1.178 Mgmꢀ3, T=200(2) K. 3615 independent and 3339 (I>2s(I)),
m=0.603 mmꢀ1, Tmin =0.817 and Tmax =0.865. All hydrogen atoms
were treated by a mixture of independent and constrained refine-
ment. Final conventional R=0.0468, wR2=0.1093 for 307 parame-
ters refined on F2. Final residual electron density 0.262 and
ꢀ0.340 eäꢀ3. Absolute configuration Flack parameter, 0.00(3).
[35] J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34, 2543.
[36] Prepared from commercially available b-bromostyrene (E:Z 90:10)
by bromine lithium exchange reaction with tBuLi.
[22] a) E. O. Fischer, T. Selmayr, F. R. Kreissl, Chem. Ber. 1977, 110,
2947; b) M. F. Semmelhack, J. J. Bozell, Tetrahedron Lett. 1982, 23,
2931; c) B. C. Sˆderberg, L. S. Hegedus, M. A. Sierra, J. Am. Chem.
Soc. 1990, 112, 4364.
[23] Crystal data for minor-3a: C24H34CrO6, Mr =470.51, crystal size
0.17î0.15î0.10 mm, orthorhombic, space group P212121, a=
10.9770(8), b=14.9881(9), c=15.3515(16) ä, V=2525.7(4) ä3,
1calcd =1.237 Mgmꢀ3, T=200(2) K. 11974 reflections were measured,
4722 independent and 4167 (I>2s(I)), with m=4.007 mmꢀ1, Tmin
=
[37] Prepared from diastereomerically pure (Z)-b-bromostyrene which
was synthesized according to: C. Kuang, H. Senboku, M. Tokuda,
Tetrahedron Lett. 2001, 42, 3893.
0.466 and Tmax =0.670. All hydrogen atoms were treated by a mix-
ture of independent and constrained refinement. Final conventional
R=0.0417, wR2=0.1019 for 280 parameters refined on F2. Final re-
sidual electron density 0.196 and ꢀ0.298 eäꢀ3. Absolute configura-
tion Flack parameter, 0.009(5).
[38] Crystal data for 12: C24H28O5, Mr =396.49, crystal size 0.40î0.20î
0.08 mm, monoclinic, space group P21, a=16.4134(3), b=6.1783(1),
c=21.1099(4) ä, V=2054.25(6) ä3, 1calcd =1.282 Mgmꢀ3
,
T=
[24] The size of the chelate ring has been defined by taking the center of
the coordinated double bond as one ring member.
120(2) K. 23416 reflections were measured, 7564 independent and
7071 (I>2s(I)). m=0.720 mmꢀ1, Tmin =0.764 and Tmax =0.954. All
hydrogen atoms were treated by a mixture of independent and con-
strained refinement. Final conventional R=0.0576, wR2=0.1960 for
520 parameters refined on F2. Final residual electron density 0.417
and ꢀ0.401 eäꢀ3. Absolute configuration Flack parameter, ꢀ0.2(2).
[39] Indeed the analogous reaction of methoxycarbene complex 7 with
(E)-2-phenylethenyllithium afforded only pentacarbonylcarbene
complex 13 with mainly a trans configuration of the exocyclic C=C
bond. The observed 7:1 mixture of E:Z isomers of 13 is close to the
E:Z mixture of the starting b-bromostyrene.
[25] For related h2-alkene(tetracarbonyl)carbene complexes of Group 6
metals with either a three-, five-, or six-membered chelate structure
and which have been characterized by X-ray crystallography, see: Cr
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Commun. 1984, 576; j) C. Alvarez, A. Pacreau, A. Parlier, H.
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S. Ricart, J. Veciana, K. H. Dˆtz, J. M. MoretÛ, J. Am. Chem. Soc.
1998, 120, 2283; m) J. Barluenga, F. Aznar, I. Gutiÿrrez, A. MartÌn,
S. GarcÌa-Granda, M. A. Llorca-BaragaÊo, J. Am. Chem. Soc. 2000,
122, 1314.
[40] A competing intramolecular displacement by one of the p systems
of a CO ligand at the level of intermediate D, which will certainly
reduce the steric strain, could account for the finally observed 1:1
ratio of E:Z isomers.
[41] For other recent asymmetric synthesis of 2,3-dihydrofurans, see:
a) F. E. McDonald, M. M. Gleason, J. Am. Chem. Soc. 1996, 118,
6648; b) D. A. Evans, Z. K. Sweeney, T. Rovis, J. S. Tedrow, J. Am.
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[26] N. H. T. Huy, L. Ricard, F. Mathey, Polyhedron 1990, 9, 2193.
[27] Intermediate A reacts also with other electrophilic reagents; for ex-
ample with benzaldehyde a different regioisomer was obtained cor-
responding to electrophile addition to C5. Further work on this sub-
ject is underway.
[28] a) U. Schubert, W. Hepp, J. M¸ller, Organometallics 1986, 5, 173;
b) W. Hepp, U. Schubert, J. Organomet. Chem. 1990, 385, 221. See
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[42] H. Gilman, J. W. Morton, Org. React. 1954, 8, 286.
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[44] D. E. Applequist, D. F. O×Brien, J. Am. Chem. Soc. 1963, 85, 743.
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Structures, University of Gˆttingen, Gˆttingen (Germany), 1997.
[49] G. M. Sheldrick, SHELXL-97, Program for the Refinement of Crys-
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[50] M. Nardelli, Comput. Chem. 1983, 7, 95.
[51] ORTEP3 for Windows, L. J. Farrugia, J. Appl. Crystallogr. 1997, 30,
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[30] C. P. Casey, M. C. Cesa, Organometallics 1982, 1, 87.
Received: June 17, 2003 [F5241]
5736
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5725 5736