On the enantioselectivity of transition metal-catalyzed 1,3-cycloadditions of 2-diazocyclohexane-1,3-diones

Article abstract of DOI:10.1002/hlca.200390257

The formal 1,3-cycloaddition of 2-diazocyclohexane-1,3-diones 1a-1d to acyclic and cyclic enol ethers in the presence of Rh^II-catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of 1-ethoxyprop-1-ene (13a)

Full text of DOI:10.1002/hlca.200390257

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Helvetica Chimica Acta ± Vol. 86 (2003)
On the Enantioselectivity of Transition Metal-Catalyzed 1,3-Cycloadditions
of 2-Diazocyclohexane-1,3-diones
by Paul M¸ller*, Yves F. Allenbach, and G e¬ rald Bernardinelli
Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, CH-1211 Geneva,
(
Phone: ‡41223796527, fax: ‡41223793215, e-mail: paul.muller@chiorg.unige.ch)
The formal 1,3-cycloaddition of 2-diazocyclohexane-1,3-diones 1a ±1d to acyclic and cyclic enol ethers in
II
the presence of Rh -catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of
1
-ethoxyprop-1-ene (13a) yielded the dihydrofuran 14a with a cis/trans ratio of 85 :15, while that with (Z)-1-
ethoxy-3,3,3-trifluoroprop-1-ene (13b) gave the cis-product 14b exclusively. The stereochemical outcome of the
reaction is consistent with a concerted rather than stepwise mechanism for cycloaddition. The asymmetric
cycloaddition of 2-diazocyclohexane-1,3-dione (1a) or 2-diazodimedone (ˆ2-diazo-5,5-dimethylcyclohexane-
1
,3-dione; 1b) to furan and dihydrofuran was investigated with a representative selection of chiral, nonracemic
II
Rh catalysts, but no significant enantioselectivity was observed, and the reported enantioselective cyclo-
additions of these diazo compounds could not be reproduced. The absence of enantioselectivity in the
cycloadditions of 2-diazocyclohexane-1,3-diones is tentatively explained in terms of the Hammond postulate.
The transition state for the cycloaddition occurs early on the reaction coordinate owing to the high reactivity of
the intermediate metallocarbene. An early transition state is associated with low selectivity. In contrast, the
transition state for transfer of stabilized metallocarbenes occurs later, and the reactions exhibit higher
selectivity.
Introduction. ± The desymmetrization of meso-compounds offers an attractive
entry towards the synthesis of enantiomerically pure compounds, and a large number of
approaches by enzymatic or chemical methods have been developed to this end. In the
field of asymmetric carbene transfer, desymmetrization has been successfully applied
towards inter-[1] and intramolecular cyclopropanations [2], and to intramolecular CH
insertions of diazoacetate esters [3][4] and amides [5]. Cyclopropanation of olefins or
acetylenes [6] is the most common pathway for transition metal-catalyzed decom-
position of diazo compounds [7]. However, an alternative reaction consisting of formal
1,3-cycloadditions to olefins is available. It occurs with diazo esters or diazo ketones,
which carry additional electron-attracting groups such as ethyl diazoacetoacetate [8],
ethyl diazopyruvate [9], or 2-diazocyclohexane-1,3-dione [10], and it is favored with
polar or polarizable olefins such as enol ethers and furans. Cycloadditions are also
observed upon reaction of such diazo compounds or the corresponding phenyl-
iodonium ylides with acetylenes [11][12], ketenes [13], nitriles [14], isocyanates [15],
thioisocyanates [16], thiones [17], and heterocyclopentadienes [18]. Formal 1,3-dipolar
cycloadditions have been reported upon photochemical decomposition of phenyl-
iodonium ylides derived from dimedone (ˆ 5,5-dimethylcyclohexane-1,3-dione) and
1,3-cyclohexane-1,3-dione [19], and upon reaction of 2,2-dibromo 1,3-diketones with
olefins in the presence of metallic Cu [20].
The 1,3-dipolar cycloaddition of 2-diazocyclohexane-1,3-diones to polar olefins
leads to the formation of stereogenic centers and, therefore, is potentially enantiose-

Helvetica Chimica Acta ± Vol. 86 (2003)
3165
lective. If the diketone carries a single substituent at C(5), C(5) becomes a stereogenic
center in the product. Cycloaddition of 1 to an acetylene results in formation of a
benzofuran derivative 2 with a single stereogenic center, while addition to an olefin
leads to the creation of up to three stereogenic centers in the product 3, as exemplified
in Scheme 1. Since 1 is a meso-compound, the enantioselective cycloaddion to
acetylenes or olefins constitutes a desymmetrization.
Scheme 1
The feasibility of this approach may be illustrated by enantioselective cyclo-
additions with 2-diazo diones reported in the literature(Scheme 2). Thus, Pirrung and
Zhang achieved enantioselectivities in the range of 44 ± 50% upon decomposition of 2-
diazocyclohexane-1,3-dione (1a) or 2-diazodimedone (ˆ2-diazo-5,5-dimethylcyclo-
II
hexane-1,3-dione; 1b) to furan and 2,3-dihydrofuran with a chiral Rh catalyst based on
binol phosphate ([Rh {(R)-bnp} ], bnp ˆ binolphosphate) [21]. More recently, Ishitani
2
4
and Achiwa reported enantioselectivities of up to 93% for the addition of 1a to 2,3-
II
dihydrofuran with a Rh catalyst having a benzoylated proline ligand, [Rh {(S)-bzp} ],
2
4
and even 98% ee with 4-methoxybenzoylproline as ligand [22]. In view of the large
I
II
structural variability of Cu and Rh catalysts, which are now available for
enantioselective carbene transfer, it appeared possible to develop and generalize the
enantioselective cycloadditions of 2-diazocyclohexane-1,3-diones.
This positive appreciation of the situation is, however, attenuated by the absence of
any follow-up subsequent to the original reports on enantioselective cycloadditions
[
23]. Furthermore, the large majority of successful enantioselective carbene-transfer
reactions uses diazo esters or diazo amides. Enantioselective carbene transfer with
diazo ketones is, for unknown reasons, much less advanced [24], although some
selective catalysts have been developed for this purpose [25][26].
As will be described below, this original approach could not be realized. All
cycloadditions tried afforded products without any significant enantioselectivity. This
II
failure led us to investigate the Rh -catalyzed decomposition of 2-diazocyclohexane-
1,3-diones in more detail, in the hope of finding its underlying reasons.

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Scheme 2
Results and Discussion. ± 1. Decomposition of 2-Diazocyclohexane-1,3-dione (1a)
and 2-Diazodimedone (1b) in CH Cl . The decomposition of 2-diazocyclohexane-1,3-
2
2
dione (1a) or 2-diazodimedone (1b) in the presence of [Rh (OAc) ] in CH Cl affords
2
4
2
2
2-chloro-3-(chloromethoxy)cyclohex-2-en-1-ones 7a and 7b in 87 and 88% yields,
respectively (Scheme 3). Evidence for the structures of 7a and 7b is provided by the 2-
1
13
H singlet at 5.83 ppm in the H-NMR and the CH signal in the C-NMR at 74.3 ppm.
2
Compound 7 originates probably from the ylide 6, which, in turn, results from reaction
of the intermediate metallocarbene with the solvent. Ylide formation between 1,3-
dioxocarbenes and benzyl or acyl halides to afford the corresponding haloenones is well
documented, and has been preparatively exploited [27].
Scheme 3
Our observations contrast with those of Pirrung et al. [10], who reported formation
of 2-chlorocyclohexane-1,3-dione (8a, 80%) and 2-(dichloromethyl)cyclohexane-1,3-

Helvetica Chimica Acta ± Vol. 86 (2003)
3167
dione (9a) upon decomposition of 1a in CH Cl although the latter product was not
2
2
fully characterized. The formation of ylide 6a was also invoked to account for the
formation of 8a and 9a. However, in our experiments, 8a and 9a could not be detected.
When the decomposition of 1a and 1b was carried out with the N-proline benzoate
catalyst [Rh {(S)-bzp} ] in the presence of 2,3-dihydrofuran in CH Cl , the chloro-
2
4
2
2
enones 7a and 7b were formed in 70 and 80% yields, respectively, while the expected
cycloadducts were formed in yields of only 14 and 15% (see below).
To prevent formation of these secondary products, the cycloadditions were carried
out either with the substrate as solvent, or in trifluorotoluene, which does not react with
the carbenes. Pirrung et al. have used fluorobenzene for such cycloadditions [18].
2
. Cycloaddition of 5-phenylcyclohexane-1,3-dione (1c) to phenylacetylene. 2-
Diazo-5-phenylcyclohexane-1,3-dione (1c) [28] underwent cycloaddition to phenyl-
acetylene to afford a single product 10 in 84% yield (Scheme 4). The structure of 10,
unequivocally established by X-ray crystallography (Fig.), has the Ph substituent at
C(2), and is consistent with that reported by Pirrung et al. for addition of 1a to other
acetylenes [11].
Scheme 4
Figure. Perspective view of the crystalstructure of 10 with atom numbering. Ellipsoids are represented with 40%
probability.

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The reaction was carried out with three chiral catalysts, [Rh {(S)-ptpa} ], [Rh {(S)-
2
4
2
phsp} ], and [Rh {(S)-bnp} ], with yields of 75, 68, and 73%, respectively. In all
4
2
4
reactions, no enantioselectivity had been observed within experimental error.
Among the possible sources for the absence of enantioselectivity in these reactions,
the possible intermediacy of a spirocyclic cyclopropene derivative 11 as proposed by
Pirrung et al. [11] must be considered. The formation of cyclopropenes upon addition of
carbenes to acetylenes is well-known [6], and thermal or transition metal catalyzed
rearrangements of cycloprop-2-ene-1-carboxylates to furans [29][30] via intermediate
vinylcarbenes [31][32] have been reported. In the present case, the postulated
intermediate 11 may represent a trans/cis mixture of meso-compounds and the
vinylcarbene 12 derived thereof via thermal rearrangement is necessarily racemic, so
that the final product 10 is a racemate. We have recently shown that the products
II
resulting from Rh -catalyzed rearrangement of achiral cycloprop-2-ene-1-carboxylates
II
in the presence of chiral Rh catalysts may be enantiomerically enriched [33].
Therefore, the absence of enantioselectivity in our experiments does not constitute
conclusive evidence for a cyclopropene intermediate and could as well be due to an
inappropriate choice of catalyst. Concievably, a concerted or stepwise cycloaddition
could also proceed without enantioselectivity. To avoid possible ambiguities, the
cycloaddition to acetylenes was not pursued, and the effort was concentrated on
cycloadditions to olefins. In these latter reactions, the putative cyclopropane
intermediates, if appropriately substituted, are chiral.
3
. Cycloaddition to Acyclic Polar Olefins. The [Rh (OAc) ]-catalyzed decomposi-
2 4
tion of 2-diazodimedone (1b) in the presence of 1-ethoxyprop-1-ene (13a; 65 :35 (Z)/
E)-mixture) afforded the cycloadduct 14a in 70% yield as an unseparable 85 :15 cis/
(
trans mixture (Scheme 5). The relative configuration of the major component, cis-14a,
follows from the vicinal coupling constant of 7.6 Hz of H-C(2)/H-C(3), while the
vicinal coupling constant of the trans-isomer (trans-14a) was 2.8 Hz. The value for cis-
1
4a agrees well with that of 7.3 Hz in the adduct 5b of 2-diazodimedone (1b) to 2,3-
dihydrofuran (see below). The preferential formation of cis-14a from from the (Z)/
E)-mixture of the dipolarophile indicates kinetic discrimination against the (E)-
(
isomer of 13a in the cycloaddition step, and is consistent with a concerted mechanism.
For a stepwise cycloaddition, or for a process involving an intermediate cyclopropane,
or for a thermodynamically controlled process, preferential formation of trans-14a
would be expected. An analogous preference for the cycloaddition of cis-propenyl
acetate has been reported by Pirrung and Lee [34]. Similarily, 2-diazo-5-methylcyclo-
hexane-1,3-dione (1d) underwent preferential cis-cycloaddition to 13a ((Z)/(E) 65 :35)
to afford 14b as a 1:1 mixture of stereoisomers (with respect to the Me group at C(6))
3
3
and a cis/trans ratio of 91:9 (cis-14b: J(H,H) ˆ 7.5 Hz, trans-14b: J(H,H) ˆ 2.7 Hz).
Thus, our expectation of stereochemical control by substituents at C(5) of the diazo
compound could not be realized. To confirm the stereochemical course of the
cycloaddition, 1b was reacted with (Z)-1-ethoxy-3,3,3-trifluoropropene (13b) [35]. The
cycloadduct cis-14c was isolated in 75% yield, with a cis/trans ratio > 99 :1. The cis-
configuration of 14c was assigned again on the grounds of the vicinal coupling constant
of 7.3 Hz of the dihydrofuran moiety. Although cycloaddition with the (E)-isomer of
13b, which is not readily accessible [36], was not examined, the exclusive formation of
cis-14c from 13b supports the hypothesis of a concerted and stereospecific cyclo-

Helvetica Chimica Acta ± Vol. 86 (2003)
3169
addition of 1 to polar olefins. A concerted cycloaddition mechanism has also been
proposed for the stereospecific addition of diazopyruvate to (E)-and ( Z)-dimethoxy-
ethylene [9]. However, concertedness may not be general in these reactions, and, in
other cases, a two-step mechanism involving either a cyclopropane intermediate, which
subsequently rearranges, or a dipolar intermedate may take place.
Scheme 5
The cycloadducts cis-14a and cis-14c were isolated with ee values of 8 and 10%,
respectively, when reactions were carried out with [Rh {(S)-nttl} ] (Table 1). 1,2-
2
4
Dichloroethylene, in turn, failed to undergo cycloaddition to 1b.
Table 1. Cycloaddition of 2-Diazocyclohexane-1,3-diones 1b and 1d to Acyclic Olefins (Scheme 5)a)
Diazo compound
Olefin
No.
Catalyst
Adduct (Yield)
cis/transb)
ee (cis)c)
No.
R
R'
1b
1b
1d
1b
1b
Me
Me
H
Me
Me
13a
13a
13a
13b
13b
Me
Me
Me
CF
CF
[Rh
[Rh
[Rh
[Rh
[Rh
2
2
2
2
2
(OAc)
{(S)-nttl}
(OAc)
(OAc)
{(S)-nttl}
4
]
14a (70%)
14a (65%)
14b (56%) )
14c (75%)
14c (85%)
85 : 15
85 : 15
98 : 2
> 99 : 1
> 99 : 1
±
8%
±
±
10%
4
4
]
]
d
4
4
]
]
3
3
a) Conditions: neat, at r.t. in the presence of 0.60 mol-% of Rh catalyst. b) With respect to C(2)/C(3). ) The ee
II
c
d
value of trans-isomer not determined. ) 1 : 1 Mixture of stereoisomers with respect to Me group at C(6).

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The cycloaddition of 1c to 1-ethoxyethene (15a) in the presence of [Rh (OAc) ]
2
4
produced an unseparable cis/trans-mixture of 16a in a 1:1 ratio in quantitative yield,
while ethenyl acetate (15b) afforded a 2 :1 mixture of stereoisomers 16b in 43% yield
(
Scheme 5). Heating 16b in refluxing toluene in the presence of TsOH [37] afforded
the benzofuran 17. Attempts to eliminate EtOH from 16a under a variety of conditions
were not successful, however. No chiral catalysts were tested with 15a and 15b owing to
the possibility of epimerization at the acetal function in the products 16a and 16b,
respectively.
4
. Cycloaddition to Furan and Dihydrofuran (Scheme 6). The original procedure for
addition of 2-diazocyclohexane-1,3-dione (1a) or 2-diazodimedone (1b) to furan uses
the substrate as solvent and [Rh {(S)-bnp} ] as catalyst. Decomposition of 1a takes
2
4
place at room temperature in 12 h. In our hands, these reaction conditions applied to 1b
produced only an insignificant ee value of the adduct 4b (Table 2). Similarily, addition
of 1a, to 2,3-dihydrofuran in the presence of [Rh {(S)-bnp} ] afforded only the racemic
2
4
adduct 5a (Table 3). The method of preparation and the quality of the catalyst seem not
responsible for this failure, since its optical rotation was found identical with that
reported in the literature, and since we have used [Rh {(S)-bnp} ] in the past with
2
4
success for other reactions [38]. Subsequently, the [Rh {(S)-bzp} ]-catalyst was
2
4
synthesized as described by Ishitani and Achiwa, and tested for the addition of 1a to
,3-dihydrofuran in CH Cl . However, the enantioselectivity of the reaction leading to
2
2
2
the adduct 5a was 0% rather than the reported 93%. In addition, 5a was isolated in only
2% yield. The major reaction product was 7a derived from reaction of the
1
intermediate carbene with the solvent. The yield could be increased to 66% when
the reaction was carried out in neat 2,3-dihydrofuran, but with only an insignificant ee
value of 5%.
Table 2. Cycloaddition of 2-Diazodimedone (1b) to Furana)
Catalyst
Adduct (4b) [%]
ee [%]
Remark
[21]
[
[
[
[
[
[
[
[
[
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
2
2
2
2
(OAc)
{(S)-bnp}
{(S)-bnp}
{(S)-phsp}
{(S)-ptpa}
{(S)-nttl}
{(R)-camph}]
{(4S)-bnaz}
{(4S)-bnaz}
4
]
34
24
50
42
36
36
46
0
±
6
49
9
9
8
2
±
0
4
4
]
]
4
]
4
]
4
]
4
]
]
b
4
8 )
a) In neat furan, 258. b) With phenyliodonium ylide 18 as substrate.
Some other catalysts of a different type were also tested for cycloaddition of 1a and
b to furan and 2,3-dihydrofuran, and the results are summarized in Tables 2 and 3. The
1
catalysts are representative for the various structural types, which have been
successfully used in enantioselective carbene transfer with diazo compounds. They
II
were prepared according to published procedures. The Rh carboxamidate catalysts of
Doyle, such as [Rh {2S)-mepy} ] or [Rh {4S)-bnaz} ] failed to decompose the diazo
2
4
2
4
compounds 1a and 1b, but reacted with the corresponding phenyliodonium ylide 18

Helvetica Chimica Acta ± Vol. 86 (2003)
3171
Table 3. Cycloaddition of 2-Diazocyclohexane-1,3-diones 1a, 1b, and 1d and Phenyliodonium Ylide 18 to
Dihydrofuran (Scheme 6)
Compound R, R'
X
Catalyst
Solvent Adduct (yield) ee [%] Remarks
1a
1a
1a
1a
1a
1a
1b
1d
18
18
18
18
18
18
H
H
H
H
H
H
Me
Me, H
Me
Me
Me
Me
Me
Me
N
N
N
N
N
N
N
N
2
2
2
2
2
2
2
2
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
[Rh
2
2
2
2
2
2
2
2
2
2
2
2
2
(S)-bnp}
(S)-bnp}
4
4
]
]
]
]
]
Neat
Neat
5a (67%)
5a (60%)
5a (36%)
5a (12%)
5a (66%)
5a (8%)
5b (14%)
5c (80%)
5b (26%)
5b (26%)
5b (60%)
5b (75%)
5b (69%)
5b (82%)
44
0
93
0
5
2
0
0
0
0
[21]
This work
[22]
(S)-bzp}
(S)-bzp}
(S)-bzp}
4
CH
CH
2
Cl
Cl
2
4
4
2
2
This work
Neat
PhCF
(S)-tbsp}
(S)-phsp}
(OAc)
(S)-nttl
(2S)-mepy}
(S)-bnp}
(O CF
(OAc)
4
]
3
4
]
CH
2
Cl
2
4
]
Neat
PhCF
PhCF
PhCF
PhCF
IPh [Rh
IPh [Rh
IPh [Rh
IPh [Rh
IPh [Rh
4
]
3
4
]
3
3
3
3
3
4
]
0
2
3
)
2
(pc)
(pc) ] (23)
CF (pc)
2
] (22)
±
±
0
2
2
PhCF
IPh (P)-[Rh
2
(O
2
3
)
2
2
] (24) PhCF
Scheme 6
[
39]. However, despite large structural variations in the catalysts, no significant
enantioselectivities were reached (Scheme 6). This failure is even more surprising
considering the analogous carbene transfer with the phenyliodonium ylide derived
from Meldrum×s acid, where we have observed ee values of up to 59% for
intermolecular cyclopropanations of olefins [40].
The addition of 2-diazo-5-methylcyclohexane-1,3-dione (1d) to 2,3-dihydrofuran
afforded 5c as a 1:1 mixture of stereoisomers (with respect to the Me group at C(6)).
No chiral catalysts were tested with 1d, however.

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Discussion. ± Two conclusions may be drawn from the present investigation: i) We
were unable to reproduce the results of two independent reports on asymmetric
cycloadditions of 2-diazocyclohexane-1,3-dione (1a) and 2-diazodimedone (1b) under
the conditions applied by the authors, and ii) the cycloaddition of these diazo
compounds or those of the corresponding phenyliodonium ylide 18 with catalysts that,
in the past, have been successfully employed in asymmetric carbene transfer, are not
enantioselective. While we cannot comment on the research of the other authors, we
note that they have not followed up with applications on their original results. In
addition, we have recently reinvestigated the cyclopropanation of styrene with 2-
diazodimedone (1b) in the presence of [Cu{(‡)-facam} ] [41] and were unable to
2
reproduce the high enantioselectivity reported by the authors. Other chiral RhII
catalysts were equally unselective [42]. In contrast, we have observed enantioselective
cyclopropanations with the ylide 19 derived from Meldrum×s acid, which may be
considered the dioxygen analogue of that derived from dimedone 18 [40], while some,
although modest, enantioselectivity for cycloaddition to furan and 2,3-dihydrofuran
was observed with the substituted ylides 20 and 21 [42].
The trend for enantioselective carbene transfer increases in the series 18 < 20 ꢀ
2
1 < 19 is analogous to that in going from diazo ketones to diazo esters and diazo
amides. Enantioselectivity is very difficult to control in reactions of diazo ketones, while
numerous efficient systems for diazo esters and amides are known. We have recently
argued that the reduced selectivity of diazo ketones may be ascribed to an early
transition state in the carbene transfer step, which, in turn, is due to the higher reactivity
of the intermediate carbene [24]. The same argument may be advanced for carbenes
derived from 1,3-diones. The carbene derived from 2-diazodimedone (1b) is extremely
reactive. As mentioned above, it reacts with CH Cl via ylide formation, and with
2
2
fluorobenzene via aromatic substitution or cycloaddition [10]. A Hammett study of
Davies revealed that carbenes stabilized by electron-donating substituents are more
susceptible towards electronic effects of the olefin than the more-electron-deficient
counterparts. The stabilized carbenes exhibit larger negative 1 values for cyclo-
propanations of substituted styrenes with [Rh {(S)-dosp} ] [43]. Thus, with ethyl
2
4
diazoacetate, the styrenes showed no significant variation in reactivity upon changing
the substituent. With diazomalonate, the 1 value was À0.2, with diazoglutaconate À0.7,
with phenyldiazoacetate and and vinyldiazoacetate À1.0, and with 4-methoxyphenyl
acetate À1.3. The 1 value for diazomalonate compares well with our previously
reported value of À 0.49 using [Rh (OAc) ] [44]. Davies observed that the carbenes
2
4
with higher negative 1 values are not only more susceptible to electronic effects in the
olefin, but, at the same time, exhibit higher enantioselectivities. This trend may be
interpreted in terms of the Hammond postulate: the more-stabilized metallocarbenes
pass through a later transition state, as evidenced by the higher 1 value, and their
selectivities increase. In contrast, for the carbenes derived from diazo ketones, and even
more so from 2-diazo 1,3-diones, we expect an early transition state and, consequently,
lower selectivity.
This work was supported by the Swiss NationalScience Foundation (Projects No. 20-52581.97 and 2027-
0
48156) and by the European Commission for Science, Research and Development (COST Action D12). The
authors are indebted to A. Pinto and J.-P. Saulnier for the NMR spectra, and D. Klink for the mass spectra.
Samples of the o-metallated catalysts 22 ± 24 were generously provided by J. P e¬ rez-Prieto.

Helvetica Chimica Acta ± Vol. 86 (2003)
3173
Experimental Part
1
. General: See [45]. The chiral catalysts were synthesized according to literature procedures: [Rh
mepy} ]: [46]; [Rh {(4S)-bnaz} ]: [47]; [Rh {(R)-campha} ], [Rh {(S)-phsp} ], and [Rh {(S)-tbsp}
Rh {(S)-bnp} ]: [21]; [Rh {(S)-nttl} ]: [42], [Rh {(S)-ptpa} ]: [49].
. Synthesis of [Rh {(S)-bzp} ] (Tetrakis-N-benzoyl-l-prolinate dirhodium(II)) [22]. To NaHCO
.0 mmol) in H O (33 ml)/EtOH (2.0 ml) was added N-benzoyl-l-proline [50] (657 mmg, 3.00 mmol), followed
by RhCl (263 mg, 1.00 mmol). The soln. was heated to reflux for 1 h. The solvent was evaporated, and the
residue was purified by FC (Alox basic; Et O/EtOH 4 :1). The eluates were concentrated, and the residue was
treated with MeCN to afford a violet solid (220 mg, 38%). An anal. sample was dissolved in CHCl (30 ml),
washed with 5% NaHCO SO ), and concentrated almost to dryness. The product was
2
{(2S)-
4
]: [48];
4
2
4
2
4
2
4
2
[
2
4
2
4
2
4
2
2
4
3
(253 mg,
3
2
3
2
3
3
(2 Â 10 ml), dried (Na
2
4
2
0
then precipitated with an excess of hexane and filtered. [a]
595s, 1402s, 1300w. H-NMR (500 MHz, CDCl
.20 ± 3.38 (m, 2 H); 4.33 (br. t, J ˆ 8.7, 1 H); 7.43 (s, 5 H). C-NMR (125 MHz, CDCl
D
ˆ À237 (c ˆ 0.04, CHCl
3
). IR (film): 2928w, 1729w,
1
1
3
3
): 1.49 ± 1.54 (m, 1 H); 1.65 ± 1.75 (m, 1 H); 1.89 ± 2.00 (m, 2 H);
1
3
3
): 25.9 (t); 30.1 (t); 50.4 (t);

3
174
Helvetica Chimica Acta ± Vol. 86 (2003)
‡
6
1.1 (d); 127.8 (d); 129.2 (d); 130.7 (d); 138.3 (s); 169.4 (s); 193.4 (s). ES-MS: 1183.1 (C52
H
54
N
6
NaO12Rh
2
‡
‡
‡
(
[Rh
2
L
4
(MeCN)
] )), 1101.0 (C48H N NaO12, [Rh L Na] ).
2 48 4 2 4
3. Synthesis of Diazo Ketones 1a ± 1d and Phenyliodonium ylide 18. The 2-diazocyclohexane-1,3-diones 1a ±
1
d were prepared via diazo transfer with 4-acetamidobenzenesulfonyl azide to the appropriate dione in the
N [51], and the ylide 18 via reaction of dimedone with diacetoxyiodobenzene, according to
Schank and Lick [52].
. Decomposition of 1a in CH
clohexane-1,3-dione (1a; 72.2 mg, 0.52 mmol) in CH
Rh (OAc) ] (5.3 mg, 0.01 mmol) in CH Cl (1.0 ml) dropwise. The mixture was stirred at r.t. during 1 h. The
solvent was evaporated, and the residue was purified by flash chromatography (FC; SiO , AcOEt/pentane 3 :7)
presence of Et
3
4
2
Cl
2
. 2-Chloro-3-(chloromethoxy)cyclohex-2-en-1-one (6a). To 2-diazocy-
Cl (4.0 ml) was added activated (by heating in vacuo)
2
2
[
2
4
2
2
2
to afford 6a. Yellow oil (90.0 mg, 88%). IR (film): 3320w, 3067w, 3001w, 1960w, 2929w, 1655s, 1597s, 1425m,
1
1
370m, 1292m, 1279m, 1182s, 1074s, 1043s, 1015s. H-NMR (300 MHz, CDCl
3
): 2.14 (quint., J ˆ 6.2, 2 H); 2.69 (t,
1
3
J ˆ 7.0, 2 H); 2.89 (t, J ˆ 6.2, 2 H); 5.87 (s, 2 H). C-NMR (75 MHz, CDCl
3
): 20.1 (t); 25.9 (t); 36.9 (t); 74.5 (t);
‡
1
16.0 (s); 167.0 (s); 191.1 (s). MS: 195 (9, M ), 194 (100), 170 (10), 168 (61), 166 (94), 161 (21), 160 (10), 159
(164), 158 (16), 148 (13), 146 (42), 138 (29), 133 (16), 131 (64), 130 (14), 129 (63), 128 (16), 123 (16), 120 (28),
1
7
18 (80), 110 (22), 108 (29), 105 (14), 104 (24), 103 (31), 102 (47), 101 (18), 100 (12), 95 (16), 91 (13), 89 (44),
6 (11), 75 (29), 74 (11), 73 (35), 67 (33), 66 (20), 65 (50), 63 (11), 61 (19), 55 (65), 54 (26), 53 (31), 49 (39). HR
3
5
‡
37
37
‡
MS: 193.9942 (C
7
H
8
O
2
Cl
2
; calc. 193.9901); 195.9879 (C
7
H
8
Cl ClO
2
; calc. 195.9872).
2
-Chloro-3-(chloromethoxy)-5,5-dimethylcyclohex-2-en-1-one (6b). Same procedure. Yield 87%. IR (film):
1
13
1
(
680s, 1613s, 1067s. H-NMR (500 MHz, CDCl
125 MHz, CDCl
3
): 1.14 (s, 6 H); 2.42 (s, 2 H); 2.69 (s, 2 H); 5.83 (s, 2 H). C-NMR
): 28.0 (q); 32.2 (s); 39.3 (t); 50.5 (t); 74.3 (t); 115.0 (s); 165.1 (s); 190.0 (s). MS: 222 (52, M ),
‡
3
1
96 (18), 194 (28), 170 (11), 169 (10), 168 (64), 167 (18), 166 (100), 157 (17), 138 (24), 136 (37), 110 (11), 108
(
(
18), 104 (10), 103 (15), 102 (32), 101 (11), 83 (17), 77 (10), 73 (11), 67 (18), 55 (14). HR MS: 222.0217
3
5
‡
C
9
H
12 Cl
2
O
2
; calc. 222.0214).
5. Cycloaddition of 2-Diazocyclohexane-1,3-diones 1 and Phenyliodonium ylide 18.
5.1. Addition of 2-Diazo-5-phenylcyclohexane-2,5-dione (1c) to Phenylacetylene. 4,5,6,7-Tetrahydro-2,6-
diphenylbenzofuran-4-one (10). Composing 1c (214 mg, 1.00 mmol) in phenylacetylene (10 ml) was stirred at r.t.
under N with [Rh (OAc) ] (4.8 mg, 0.01 mol) for 6 h. After evaporation of the solvent, the residue was purified
by FC (SiO ; Et
2
2
4
2
2
O/pentane 35 :65) to afford pure 10 (243 mg, 84%). Solid. M.p. 1108. IR (CHCl
3
): 3026w,
1
3
015m, 2875w, 1673s, 1456m, 1438m, 1221m, 1213m. H-NMR (400 MHz, CDCl
3
): 2.78 ± 2.88 (m, 2 H); 3.16 (dd,
J ˆ 11.1, 17.4, 1 H); 3.29 (dd, J ˆ 5.3, 17.4, 1 H); 3.59 ± 3.70 (m, 1 H); 6.94 (s, 1 H); 6.29 ± 7.35 (m, 4 H); 7.38 ± 7.44
1
3
(
(
2
m, 4 H); 7.67 ± 7.70 (m, 2 H). C-NMR (100 MHz, CDCl
3
): 31.2 (t); 41.2 (d); 44.9 (t); 100.8 (d); 122.8 (s); 123.9
‡
d); 126.7 (d); 127.2 (d); 128.2 (d); 128.9 (d); 129.7 (s); 142.4 (s); 154.7 (s); 165.7 (s); 193.0 (s). MS: 288 (58, M ),
89 (13), 185 (13), 184 (98), 156 (53), 105 (100), 77 (34). HR-MS: 288.1159 (C20
‡
H
16
O
2
; calc. 288.1150).
Enantiomer separation by HPLC (OD-H column, i-PrOH/hexane 1:9, 0.5 ml/min; t
1
ˆ 32.6, t
2
ˆ 37.3 min).
À1
À3
Crystal-Structure Analysis of 10. C20
H
16
O
2
; M
r
288.4; m ˆ 0.08 mm , d
x
ˆ 1.256 g ¥ cm , monoclinic, C2/c,
3
Z ˆ 8, a ˆ 19.5015(10), b ˆ 6.3772(3), c ˆ 24.6135(13) ä, b ˆ 94.810(6)8, Vˆ 3050.3(3) ä . Crystal size: 0.076 Â
0
.21 Â 0.24 mm. Cell dimensions and intensities were measured at 200 K on a Stoe IPDS diffractometer with
graphite-monochromated MoK
radiation (l ˆ 0.71073 ä), 10962 measured reflections, 2962 unique reflections
)); Rint for 7446 equivalent reflections 0.059. Data were corrected
a
of wich 1387 were observables (j F
o
j> 4s (F
o
for Lorentz and polarization effects and for absorption (Tmin,max ˆ 0.9790, 0.9943). The structure was solved by
direct method (SIR97) [53], all other calculations were performed with XTAL system [54]. Full-matrix least-
2
2
squares refinement based on F using weight of 1/(s (F
o
) ‡ 0.0002(F
o
)) gave final values R ˆ 0.046, wR ˆ 0.045,
À3
and S ˆ 1.76(4). The maximum shift/error on the last cycle was 0.35 ¥ 10 . H-Atoms were observed and refined
with a fixed value of their isotropic displacement parameters. The final difference electron-density map showed
À3
a maximum of ‡ 0.76 and a minimum of À 0.34 eä . CCDC-205856 contains supplementary crystallographic
data for this paper. These data can be obtained, free of charge, via http://www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ,
UK (fax: Int. ‡441223336033; e-mail: deposit@ccdc.cam.ac.uk)).
5.2. Addition to Acyclic Vinyl Ethers. cis-2-Ethoxy-2,3,4,5,6,7-hexahydro-3,6,6-trimethylbenzofuran-4-one
(
14a). To 2-diazo-5,5-dimethylcyclohexane-1,3-dione (1b, 360 mg, 2.16 mmol) in 1-ethoxyprop-1-ene (13a;
5
1
.0 ml, 85 :15 (Z)/(E) mixture) was added [Rh
2
(OAc)
4
] (6.6 mg, 0.014 mmol), and the mixture was stirred for
; AcOEt/pentane 2 :3)
): 2959w, 1638s, 1401m,
h at r.t. under N . The solvent was evaporated, and the residue was purified by FC (SiO
2
2
to afford 14a (341 mg, 70%) as a 17:3 mixture of unseparable stereoisomers. IR (CHCl
1
3
3
1
169w, 1137w, 1032w. H-NMR 500 MHz, CDCl
3
): 1.07 (s, 3 H); 1.11 (s, 3 H); 1.19 (d, J ˆ 7.3, 3 H); 1.26 (t, J ˆ 7.3,
13
H); 2.15 ± 2.14 (m, 4 H); 3.19 ± 3.26 (m, 2 H); 3.58 ± 3.95 (m, 2 H); 5.65 (d, J ˆ 7.6, 1 H). C-NMR (125 MHz,

Helvetica Chimica Acta ± Vol. 86 (2003)
3175
CDCl
3
): 11.3 (q); 14.9 (q); 28.5 (q); 28.8 (q); 33.9 (s); 37.4 (d); 37.8 (t); 51.3 (t); 66.1 (t); 110.5 (d); 115.6 (s); 173.8
‡
(
s); 194.7 (s). MS: 225 (16), 224 (100, M ), 196 (11), 195 (69), 180 (26), 179 (96), 178 (51), 177 (10), 168 (13),
1
67 (24), 165 (21), 153 (20), 140 (17), 139 (17), 137 (13), 135 (14), 125 (20), 123 (14), 122 (36), 112 (19), 111
(
(
47), 107 (22), 98 (15), 97 (52), 96 (10), 95 (17), 94 (12), 93 (11), 84 (13), 83 (62), 69 (33), 67 (19), 66 (17), 65
‡
14), 57 (15), 55 (34), 53 (15). HR-MS: 224.1404 (C13
ˆ 18.1, t ˆ 19.1 min).
-Ethoxy-2,3,4,5,6,7-hexahydro-3,6-dimethylbenzofuran-4-one (14b). To 2-diazo-5-methylcyclohexane-1,3-
dione (1d; 152 mg, 1.00 mmol) in 13a (2.5 ml, (E)/(Z) mixture) was added [Rh (OAc) ] (3.3 mg, 0.0069 mmol),
and the mixture was stirred for 1 h at r.t. under N . The solvent was evaporated, and the residue was purified by
FC (SiO ; AcOEt/pentane 3 :7) to afford 14b (118 mg, 56%) as 11.2 :1 mixture of cis/trans isomers with respect
to C(2)/C(3). Colorless oil. IR (CHCl
isomer at C(2)/C(3)): 1.01 ± 1.04 (m, 3 H); 1.12 ± 1.14 (m, 3 H); 1.16 ± 1.21 (m, 3 H); 1.94 ± 2.45 (m, 5 H); 3.11 ±
H
20
O
3
; calc. 224.1413). Enantiomer separation by GC (g-
Dex, isothermal at 1508, t
1
2
2
2
4
2
2
1
3
3
): 2983w, 1628s, 1455w, 1403m, 1380w. H-NMR (500 MHz, CDCl , cis-
1
3
3
.19 (m, 1 H); 3.51 ± 3.60 (m, 1 H); 3.76 ± 3.89 (m, 1 H); 5.56 (d, J ˆ 7.3, 0.5 H); 5.59 (d, J ˆ 7.3, 0.5 H). C NMR
(
(
(
125 MHz, CDCl ): [10.9 (q), 11.6 (q)]; 14.9 (q); [20.9 (d), 21.1 (d)]; [29.5 (q), 29.9 (q)]; [31.9 (t), 32.1 (t)]; 37.4
3
d), 37.6 (d)]; [45.3 (t), 45.7 (t)]; 65.9 (t), 66.1 (t)]; [110.3 (d), 110.5 (d)]; [116.2 (s); 116.9 (s)]; [174.4 (s), 174.6
‡
s)]; [194.9 (s); 195.1 (s). MS: 210 (100, M ), 181 (66), 165 (88), 164 (46), 163 (15), 154 (10), 153 (36), 151 (20),
1
9
40 (13), 136 (10), 135 (11), 125 (11), 122 (28), 122 (28), 121 (12), 112 (17), 111 (21), 109 (10), 98 (10), 97 (27),
5 (15), 94 (10), 93 (33), 85 (12), 84 (13), 83 (15), 79 (11), 69 (66), 67 (22), 65 (12), 57 (10), 55 (25), 53 (16), 45
‡
(10). HR MS: 210.1306 (C12
H
18
O
3
; calc. 210.1256).
cis-2-Ethoxy-2,3,4,5,6,7-hexahydro-6,6-dimethyl-3-(trifluoromethyl)benzofuran-4-one (14c). To 1b (86 mg,
.52 mmol) in (Z)-1-ethoxy-3,3,3-trifluoroprop-1-ene [25] (13b; 1.0 ml) was added [Rh (OAc) ] (9.2 mg,
.019 mmol), and the mixture was stirred under N for 4 h at r.t. After evaporation of the solvent, the residue
0
0
2
4
2
was purified by FC (SiO
2
; AcOEt/pentane 3 :7) to afford 14c. Yellow solid (109 mg, 75%). IR (CHCl
3
): 2963w,
1
1
659s, 1630s, 1400m, 1259m, 1195m, 1137m. H-NMR (500 MHz, CDCl
3
): 1.10 (s, 3 H); 1.14 (s, 3 H); 1.31 (t, J ˆ
7
.3, 3 H); 2.23 (d, J ˆ 16, 1 H); 2.29 (d, J ˆ 18, 1 H); 2.23 (d, J ˆ 16, 1 H); 2.42 (d, J ˆ 18, 1 H); 3.75 (dq, J ˆ 8.5,
1
3
9
.6, 1 H); 3.80 (quint., J ˆ 7.6, 1 H); 5.83 (d, J ˆ 7.3, 1 H). C-NMR (125 MHz, CDCl
3
): 14.8 (q); 28.1 (q); 28.8
(
(
(
q); 33.5 (s); 33.5 (s); 37.9 (t); 46.3 (d); 51.1 (t); 67.7 (t); 107.8 (s); 108.2 (d); 124.3 (s); 177.5 (s); 192.1 (s). MS: 278
‡
54, M ), 258 (10), 234 (10), 233 (17), 230 (25), 229 (11), 215 (34), 213 (39), 202 (45), 196 (55), 194 (23), 179
19), 177 (18), 176 (18), 176 (16), 174 (75), 166 (16), 165 (100), 159 (16), 154 (16), 162 (32), 151 (12), 148 (14),
‡
1
46 (38), 140 (20), 86 (41), 84 (68), 83 (33), 69 (32). HR MS: 278.1120 (C13
Enantiomer separation by GC (g-Dex, isothermal, at 1608, t ˆ 16.8 min).
ˆ 15.9, t
-Ethoxy-2,3,4,5,6,7-hexahydro-6-phenylbenzofuran-4-one (16a). Same procedure with 1c and 1-ethoxy-
ethene (15a) as solvent. FC (SiO ; hexane/AcOEt 60 :40) afforded 16a as a 1 :1 mixture of cis/trans isomers.
): 3024w, 3015m, 2984w, 2938m, 1632s, 1405m, 1347m, 1257m, 1189m, 1108m.
): 1.28 ± 1.32 (m, 3 H); 2.61 ± 2.81 (m, 4 H); 2.99 ± 3.06 (m, 1 H); 3.42 ± 3.48 (m, 1 H);
.51 ± 3.57 (m, 1 H); 3.66 ± 3.73 (m, 1 H); 3.91 ± 3.99 (m, 1 H); 5.81 ± 5.84 (m, 1 H); 7.28 ± 7.41 (m, 5 H). 13C-NMR
125 MHz, CDCl ): 15.0 (q); [31.4 (t), 31.6 (t)]; 38.2 (t); [40.1 (d), 40.5 (d)]; [43.6 (t), 44.0 (t)]; [65.1 (t), 65.3
H
17
O
3
F
3
; calc. 278.1129).
1
2
2
2
Yield 100%, oil. IR (CHCl
3
1
H-NMR (500 MHz, CDCl
3
3
(
(
3
t)]; [108.9 (d), 109.2 (d)]; [112.2(s), 112.5 (s)]; 126.7 (d); [127.0 (d), 127.1 (d)]; [128.8 (d), 128.8 (d)]; [142.6 (s);
‡
1
42.7 (s)]; [174.8 (s), 174.9 (s)]; [193.7 (s), 193.8 (s)]. MS: 258 (100, M ), 213 (19), 154 (26), 126 (50, 125 (23),
1
11 (10), 108 (17), 104 820), 103 (15), 98 (38), 97 (39), 91 (16), 84 (23), 83 (15), 82 (14), 81 (10), 77 (14), 70
‡
(11), 69 (32), 55 (21), 53 (13), 51 (12). HR MS: 258.1235 (C16
H
18
O
3
; calc. 258.1256).
2-Acetoxy-2,3,4,5,6,7-hexahydro-6-phenylbenzofuran-4-one (16b). Same procedure with 1c in vinyl acetate.
Purification by FC (SiO
2
; AcOEt/cyclohexane 35 :65) gave a 2 :1 mixture of cis/trans stereoisomers of 16b in
1
4
3% yield as colorless solid. IR (CHCl
3
): 3028w, 3015m, 1759s, 1644s, 1404m. H-NMR (500 MHz, CDCl
3
): 2.06
(
s, 1 H); 2.08 (s, 2 H); 2.60 ± 2.80 (m, 5 H); 3.03 ± 3.09 (m, 1 H); 3.34 ± 3.48 (m, 1 H); 7.17 ± 7.31 (m, 5 H).
C-NMR (125 MHz, CDCl ): [21.0 (q), 21.0 (q)]; [31.0 (t), 31.2 (t)]; [32.0 (t), 32.0 (t)]; [40.2 (d), 40.5 (d)]; [43.8
3
1
3
(
t), 44.1 (t)]; [98.9 (d), 99.1 (d)]; [112.3 (s), 112.5 (s)]; [126.7 (d), 126.7 (d)]; [127.3 (d), 127.3 (d)]; [128.9 (d)];
‡
[142.2 (s);, 142.3 (s)]; [169.4 (s), 169.5 (s)]; [174.5 (s), 174.6 (s)]; [193.7 (s); 193.7 (s)]. MS: 272 (<1, M ), 244
(
(
10), 213 (20), 212 (55), 203 (10), 202 (72), 108 (28), 104 (14), 98 (100), 97 (21), 69 (16). HR MS: 272.1062
‡
C
16
H
16
O
4
; calc. 272.1049).
4
,5,6,7-Tetrahydro-6-phenylbenzofuran-4-one (17). The acetate 16b (200 mg, 0.7 mmol) and TsOH (18 mg)
were heated to reflux in toluene under N for 3 h. The solvent was evaporated in vacuo, and the residue was
purified by FC (SiO , EtO /pentane 35 :65) to afford 17 (120 mg, 77%). Colorless liquid. IR (CHCl
2
2
2
3
): 3030m,
1
3
022m, 2957w, 2908w, 1674s, 1601m, 1516m, 1498m, 1450s, 1413m, 1120m, 1039m, 996m, 908s. H-NMR
(
500 MHz, CDCl
3
): 2.77 ± 2.84 (m, 2 H); 3.08 (ddd, J ˆ 0.6, 11.1, 17.1, 1 H); 3.21 (dd, J ˆ 5.1, 17.1, 1 H); 6.73 (d,
13
J ˆ 1.9, 1 H); 7.28 ± 7.40 (m, 6 H). C-NMR (125 MHz, CDCl
3
): 31.2 (t); 41.3 (d); 45.0 (t); 106.5 (d); 121.0 (s);

3
1
176
Helvetica Chimica Acta ± Vol. 86 (2003)
‡
26.7 (d); 127.2 (d); 128.9 (d); 142.4 (s); 143.1 (d); 166.3 (s); 193.0 (s). MS: 212 (24, M ), 108 (100), 86 (14), 84
‡
(
32), 80 (32), 52 (14). HR MS: 212.0848 (C14
H
12
O
2
; calc. 212.0837).
5
.3. Cycloaddition of 1b to Furan. 4,5,6,7-Tetrahydro-6,6-dimethyl-3aH-furo[2,3-b]benzofuran-4-one (4b).
Compound 1b (396 mg, 2.38 mmol) was dissolved in furan (20 ml, freshly distilled over KOH). [Rh (OAc) .2
MeOH] (15.2 mg, 0.028 mmol) was added, and the mixture was stirred for 45 min under N . The solvent was
2
4
2
evaporated, and the residue was purified by FC (SiO
Yellowish oil. IR (CHCl
2
; AcOEt/pentane 2 :3) to afford 4b (171 mg, 34%).
1
3
): 3013m, 2963m, 2890w, 1640s, 1402s. H-NMR (500 MHz, CDCl
3
): 1.07 (s, 3 H); 1.11
(
s, 3 H); 2.19 (d, J ˆ 16.4, 1 H); 2.25 (d, J ˆ 16.4, 1 H); 2.33 ± 2.40 (m, 2 H); 5.38 (t, J ˆ 2.2, 1 H); 6.39 (d, J ˆ 2.2, 2
13
H); 6.60 (d, J ˆ 7.5, 1 H). C-NMR (125 MHz, CDCl
3
): 28.3 (q); 28.7 (q); 34.1 (s); 37.4 (t); 47.7 (d); 50.9 (t);
‡
1
03.4 (d); 112.7 (d); 114.8 (s); 144.2 (d); 174.9 (s); 194.1 (s). MS: 206 (25, M ), 178 (20), 150 (14), 123 (10), 122
‡
(
100), 121 (10), 94 (16), 66 (14), 55 (12), 52 (10). HR-MS: 206.0952 (C12
separation by GC (g-Dex, isothermal at 1508, t ˆ 26.2 min).
ˆ 25.2, t
.4. Cycloaddition of 1a and 1d to 2,3-Dihydrofuran. 2,3,4,5,6,7-Hexahydro-3H-3aH-furo[2,3-b]benzofur-
an-4-one (5a). To 2,3-dihydrofuran (2.5 ml) and 1a (139.6 mg, 1.01 mmol) was added activated [Rh (OAc)
18.5 mg, 0.039 mmol), and the mixture was stirred under N at r.t. for 16 h. The solvent was evaporated in
vacuo, and the residue was purified by distillation (1508/0.2 Torr) to afford 5a (137 mg, 75%). Colorless oil. IR
H
14
O
3
; calc. 206.0943). Enantiomer
1
2
5
2
4
]
(
2
(
film): 2946w, 2877w, 2358w, 1623s, 1450w, 1401m, 1364w, 1289w, 1240m, 1176w, 1079s, 1000w, 947s, 895s, 806s.
1
H-NMR (400 MHz, CDCl
4
(
1
3
): 2.00 ± 2.10 (m, 4 H); 2.32 ± 3.35 (m, 2 H); 2.39 ± 2.55 (m, 2 H); 3.60 ± 3.66 (m, 1 H);
1
3
.00 ± 4.10 (m, 1 H); 6.23 (d, J ˆ 5.9, 1 H). C-NMR (100 MHz, CDCl
3
): 21.6 (t); 23.7 (t); 30.3 (t); 36.6 (t); 43.8
‡
d); 67.9 (t); 112.8 (d); 113.7 (s); 177.5 (s); 195.2 (s). MS: 180 (86, M ), 165 (74), 152 (17), 151 (70), 137 (100),
35 (11), 134 (13), 124 (60), 123 (11), 110 (11), 109 (17), 96 (59), 95 (39), 91 (11), 82 (21), 81 (37), 79 (18), 78
(
13), 77 (16), 71 (13), 69 (14), 68 (34), 67 (26), 66 (17), 65 (13), 57 (10), 55 (73), 54 (18), 53 (57), 52 (18). HR
‡
MS: 180.0794 (C10
ˆ 27.6 min).
cis/trans-2,3,4,5,6,7-Hexahydro-6-methyl-3aH-furo[2,3-b]benzofuran-4-one (5c). The same procedure,
H
12
O
3
; calc. 180.0786). Enantiomer separation by GC (b-Dex, isothermal, at 1508, t
1
ˆ 26.0,
t
2
starting from 1d (304 mg, 2.00 mmol) afforded 5c as a 1:1 mixture of cis- and trans-stereoisomers (311 mg,
1
8
0%). Yellowish oil. IR (CHCl
3
): 2959w, 2247w, 1628s, 1421w, 1405w, 1363w. H-NMR (500 MHz, CDCl
3
): 1.09
(
4
2
d, J ˆ 8.2, 0.5 H); 1.10 (d, J ˆ 8.2, 0.5 H); 1.89 ± 2.57 (m, 7 H); 3.56 ± 3.65 (m, 1 H); 3.66 ± 3.72 (m, 1 H); 4.05 ±
13
.09 (m, 1 H); 6.22 (d, J ˆ 7.6, 0.5 H); 6.23 (d, J ˆ 7.3, 0.5 H). C-NMR (125 MHz, CDCl
3
): [20.8 (d), 20.9 (d)];
9.5 (q), 29.8 (q))]; [30.0 (t), 30.5 (t)]; [31.6 (t), 31.7 (t)]; [43.6 (d), 43.7 (d)]; 45.1 (t); [67.9 (t), 67.8 (t)]; [112.9
‡
(
(
(
(
d), 113.1 (d)]; [113.0 (s), 113.3 (s)]; [177.0 (s), 177.1 (s) ]; [194.7 (s), 1948 (s)]. MS: 194 (100, M ), 180 (10), 179
93), 166 (10), 165 (28), 153 (28), 152 (23), 151 (23), 151 (99), 133 (14), 124 (67), 123 (12), 109 (15), 96 (49), 95
28), 82 (19), 81 (25), 79 (12), 77 (11), 69 (42), 68 (19), 67 (16), 66 (10), 65 (10), 54 (11), 53 (42), 52 (12), 51
11). HR-MS: 194.0930 (C11
‡
H
14
O
3
; calc. 194.0943).
5.4. Cycloaddition of Ylide 18 to 2,3-Dihydrofuran. 2,3,4,5,6,7-Hexahydro-6,6-dimethyl-3aH-furo[2,3-
b]benzofuran-4-one (5b). The ylide 18 (342 mg, 1.00 mmol) was suspended in trifluorotoluene (3.0 ml)
containing 2,3-dihydrofuran (15 ± 20 equiv.). The catalyst (1.5 mol-%) in trifluorotoluene (2.0 ml) was added,
and the mixture was stirred at 30 ± 408 for 12 h, when all of the ylide was dissolved. The solvent was evaporated,
and the residue was purified by FC (SiO
2
; AcOEt/pentane 3 :7) to give 5b. Yellowish solid. M.p. 98 ± 998. IR
film): 2955w, 2866w, 1357m, 1650s, 1627s, 1403s, 1356m, 1221m, 1069s, 1035m, 943m, 922m, 881s. 1H-NMR
500 MHz, CDCl
): 1.08 (s, 3 H); 1.10 (s, 3 H); 2.10 ± 2.14 (m, 2 H); 2.19 (d, J ˆ 16.1, 1 H); 2.24 (d, J ˆ 16.1, 1 H);
(
(
3
2
4
.31 (dd, J ˆ 17.7, 2.3, 1 H); 2.36 (dd, J ˆ 17.1, 1.0, 1 H); 3.62 (ddd, J ˆ 12.0, 8.8, 5.1 1 H); 3.72 (br. t, J ˆ 7.0, 1 H);
13
.08 ± 4.12 (m, 1 H); 6.26 (d, J ˆ 5.7, 1 H). C-NMR (125 MHz, CDCl
3
): 28.2 (q); 28.8 (q); 30.4 (t); 33.9 (s); 37.5
‡
(
(
t); 43.7 (d); 51.0 (t); 67.8 (t); 112.1 (s); 113.0 (d); 176.2 (s); 194.4 (s). MS: 208 (85, M ), 194 (11), 193 (100), 180
15), 179 (35), 166 (13), 165 (100), 152 (19), 147 (17), 137 (15), 125 (11), 124 (87), 123 (16), 110 (13), 109 (20),
9
7 (11), 96 (75), 95 (32), 82 (28), 81 (29), 79 (12), 77 (19), 71 (10), 69 (30), 68 (22), 67 (20). HR MS: 208.1091
‡
(C
12
H
16
O
3
; calc. 208.1099). Enantiomer separation by GC, g-Dex, isothermal, at 1508, t
1
ˆ 26.7, t ˆ 27.3 min.
2
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