Combination of rearrangement with metallic and organic catalyses - A step- and atom-economical approach to α-spiroactones and -lactams

Article abstract of DOI:10.1002/ejoc.201100734

A general synthetic route to α-spirolactones and -lactams from 2-diazo-1,3-dicarbonyl compounds, (homo)allylic alcohols or amines and acrylic derivatives, involving a single consecutive reaction consisting of a Wolff rearrangement/α-oxo ketene trapping/cr

Full text of DOI:10.1002/ejoc.201100734

FULL PAPER
DOI: 10.1002/ejoc.201100734
Combination of Rearrangement with Metallic and Organic Catalyses –
a Step- and Atom-Economical Approach to α-Spirolactones and -lactams
Thomas Boddaert,[a] Yoann Coquerel,*[a] and Jean Rodriguez*[a]
Keywords: Microwave chemistry / Spiro compounds / Rearrangement / Olefin metathesis / Michael addition
A general synthetic route to α-spirolactones and -lactams
from 2-diazo-1,3-dicarbonyl compounds, (homo)allylic
alcohols or amines and acrylic derivatives, involving a single
consecutive reaction consisting of a Wolff rearrangement/α-
oxo ketene trapping/cross metathesis/Michael addition se-
quence is described. During the consecutive reaction optimi-
zation, the organocatalytic activity of N,N-diaryl-1,3-imid-
Michael addition of 1,3-dicarbonyl compounds was discov-
ered. A conceptually attractive version of the consecutive re-
action was then developed, involving the Grubbs–Hoveyda
ruthenium-based precatalyst containing the SIMes [1,3-
bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene] NHC ligand
as the source of both the organometallic catalyst of the cross
metathesis and the organic catalyst of the intramolecular
azol(in)-2-ylidene N-heterocyclic carbenes (NHCs) in the Michael addition.
the development of multiple-bond-forming transformations
(MBFTs)[4] and catalytic chemical processes[5] for the simple
Introduction
Spiro compounds form a class of molecules with unique creation of molecular complexity and functional diversity.
chemical and conformational features often associated with It is now recognized that the step count is one of the most
important biological properties. They have attracted con- important criteria when evaluating the efficiency of a syn-
siderable attention from the synthetic community and still thesis.
constitute an active domain of research.[1] In complex bi-
In this context, and in connection with our interest in
oactive molecules containing a spiro moiety, it often occurs the applications of 1,3-dicarbonyl compounds in MBFTs[6]
that simplified analogs retaining the spiro structural do- and the construction of functionalized spirocyclic scaf-
main exhibit a biological profile comparable to that of the folds,[7] we present a new synthetic approach to α-spiro-
parent compounds.[2] Therefore, original stereoselective syn- lactones and -lactams 1. Retrosynthetic analysis involves a
thetic strategies targeting spiro compounds are of impor- catalytic Michael-based spirocyclization of substrates 2,
tance for the development of new medicinally relevant scaf- which should be available by olefin cross metathesis (CM)
folds. An important focus for contemporary organic synthe- between acrylic derivatives and the terminal olefin in esters
sis is economy.[3] Indeed, the efficiency of a synthetic se- (or amides) 3,[8] obtained from 4a by transesterification (or
quence is determined by issues of brevity and sustainability, transamidation), or alternatively from the 2-diazo-1,3-diket-
as witnessed by the tremendous efforts currently directed at ones 4b following a Wolff rearrangement and trapping of
Scheme 1. Retrosynthetic analysis for α-spirolactones and -lactams (n = 1, 2; m = 0, 1).
[a] Institut des Sciences Moléculaires de Marseille, iSm2 – UMR
CNRS 6263, Aix-Marseille Université, Centre Saint Jérôme, the resultant α-oxo ketene (Scheme 1). Ideally, all of these
Service 531
transformations should be conducted in a single consecu-
13397 Marseille cedex 20, France
tive reaction.[4]
Fax: +33-4-91289187
E-mail: yoann.coquerel@univ-cezanne.fr
In this article, we report our efforts to develop a general
synthetic route to the spiro compounds 1 in a single consec-
utive reaction, and how this work has led to the discovery
jean.rodriguez@univ-cezanne.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100734.
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T. Boddaert, Y. Coquerel, J. Rodriguez
FULL PAPER
of the excellent organocatalytic activity of N,N-diaryl-1,3- Table 2. Wolff rearrangement/α-oxo ketene trapping reactions.[a]
imidazol(in)-2-ylidenes in the Michael addition of 1,3-di-
carbonyl compounds.
Results and Discussion
The study started with the preparation of 1,3-dicarbonyl
compounds of type 3 in the five- to seven-membered ring
series either by transesterification and transamidation reac-
tions from 4a (Table 1),[9] or by our recently developed mi-
crowave-assisted Wolff rearrangement/α-oxo ketene trap-
ping reaction from 4b (Table 2).[10] It must be highlighted
that, although the transesterification (and transamidation)
strategy is quite general, it requires an excess of nucleophile
and additives, prolonged reaction times to proceed ef-
ficiently and a final purification step. Conversely, when ap-
plicable, the Wolff rearrangement/α-oxo ketene trapping re-
actions require no excess of substrate or additive, the reac-
tions are efficient and require no purification (only nitrogen
gas was produced as byproduct), the reaction times were
short, and the sequence required a minimum of energy.
[a] Results of Entries 5 and 6 are reproduced from ref.[10] for com-
parison. [b] Yields for isolated clean crude products.
Table 1. Transesterification and transamidation reactions.[a]
With a series of olefinic substrates 3 in hand, we turned
our attention to their required CM reactions with a variety
of acrylic derivatives, keeping in mind our objective of a
single consecutive reaction for the sequence 4 Ǟ 1. Thus,
we optimized the CM reactions on a few substrates 3 con-
sidering only reaction conditions involving a single equiva-
lent of the acrylic derivative reaction partners. This should
secure a subsequent Michael-based spirocyclization in a
consecutive manner without competition with intermo-
lecular processes with the excess of acrylic reagent. Based
on our previous work with the microwave-assisted CM of
olefins,[11] and owing to the efficiency and cleanliness of
the metathesis reactions under these conditions,[12] we only
considered dielectric heating as the activation mode. After
a short optimization study, we found that these CM reac-
tions were best performed in dichloromethane with the
Grubbs–Hoveyda precatalyst 5 introduced in two portions
(3 then 1 mol-%) at 100 °C. These reaction conditions
proved quite general (see Table 3 and below), and few
limitations were encountered. Among these, substrate 3d
containing a basic nitrogen atom was recovered unchanged
probably due to catalyst deactivation.[13] From the results
reported in Table 3, it also appears that allylic esters (or
amides, see below) are less reactive than their homoallylic
counterparts (Entries 1 and 2 vs. 3–6). This is most likely
due to the formation of stabilized six-membered-ring ruthe-
nium chelate complexes with allylic esters (or amides),
which inhibit the reactions.[14] It must be mentioned here
[a] Products of Entries 1–6 were obtained from the corresponding
methyl esters and those of Entries 7–9 were obtained from the cor-
responding ethyl esters; see Supporting Information for the prepa-
any case, indicating that 5 and the ruthenium species de-
ration of substrates 4a for Entries 4–7. [b] Yields for isolated prod-
ucts after flash chromatography. DMAP = 4-(dimethylamino)pyr-
idine, MMP = 3-methoxyphenyl.
that the spiro product 1 was not detected after the CM in
rived from 5 do not catalyze the Michael-induced spirocy-
clization (see below).
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Combination of Rearrangement with Metallic and Organic Catalyses
Table 3. CM reactions of 3 with 1 equiv. of acrylic derivatives.
amount of tributylphosphane was used for the spirocycliza-
tion step of the consecutive reaction, no methanol was re-
quired, and spiro compounds 1c and 1f were obtained in
moderate yields from 3e and 3f, respectively (Scheme 2).
At this point, we surmised that the entire sequence Wolff
rearrangement/α-oxo ketene trapping/CM/Michael reaction
corresponding to the desired transformation 4b Ǟ 1 could
be performed in a single consecutive reaction, provided that
the Wolff rearrangement could be performed in the CM
reaction solvent (i.e. dichloromethane) rather than toluene.
Accordingly, we briefly examined the microwave-assisted
Wolff rearrangement in dichloromethane, and not surpris-
ingly (both solvents have similar loss tangent, tan δ ≈
0.04[18]) the reaction was found to be equally efficient and
clean as in toluene, although somewhat slower. Thus, the
consecutive reaction leading to 1 from 4b was attempted
as follows: microwave-assisted Wolff rearrangement/α-oxo
ketene trapping in dichloromethane for 15 min (300 W), ad-
dition of the acrylic derivative (1 equiv.) and the CM precat-
alyst 5 (3 + 1 mol-%) to the reaction mixture followed by
microwave irradiation at 100 °C, and finally addition of tri-
butylphosphane (20 mol-%) and microwave irradiation at
100 °C. Rewardingly, a variety of α-spirolactones and
-lactams 1 were obtained under these conditions involving
a single consecutive reaction, and the products were all ob-
tained in good yields considering that four chemical bonds
are created (and one broken) in the transformation. The
results are presented in Table 4. A single diastereomer of α-
spiro-δ-lactones 1i and 1j was obtained (Entries 4 and 5,
respectively), probably due to the existence of a well-defined
six-membered chair-like transition state in these cases with
both (E) and (Z) CM products 2, whereas the formation of
α-spiro-γ-lactones and -γ-lactams 1a, 1g and 1h was found
to be poorly diastereoselective (Entries 1–3). With the in
situ formed CM product 2 derived from the chiral α-oxo
ketene obtained from 4b (X = CHMe), homoallyl alcohol
and acrylonitrile (Entry 6), a modest but effective chiral in-
duction was observed, the Michael-based spirocyclization
[a] Yields for isolated products after silica gel flash chromatog-
raphy. The diastereomeric ratios were determined from 1H and 13
NMR spectroscopy of the crude material.
C
When the CM reactions were performed under the above occurring preferentially anti to the methyl group on the cy-
conditions, relatively clean final reaction mixtures were ob- clopentane ring. The structures of spiro compounds 1j and
tained (essentially dichloromethane solutions of 2), which 1k (major diastereomer) have been obtained by X-ray dif-
were used directly in the next transformation. Therefore, fraction analysis (Figure 1).[19] Finally, it is important to
our early attempts for the consecutive reaction of 3 Ǟ 1 note that, quite surprisingly, no α-spiro-δ-lactams (e.g. 1e)
were realized with various known catalysts for the Michael were obtained under these conditions leaving the corre-
addition. Among these, we have successfully examined basic sponding monocyclic intermediates 2 unchanged (see be-
alumina,[15] Dowex 550A resin[16] and tributylphosphane.[17] low).
Practically, basic alumina or Dowex resin and methanol
In order to better evaluate the efficiency (as defined in
were added directly to the cooled CM reaction mixture to the Introduction) of the consecutive reaction 4b Ǟ 1 vs.
afford the expected spiro compounds 1 upon heating in the three-step sequence 4b Ǟ 3 Ǟ 2 Ǟ 1, the yield of the
good yields for the consecutive CM/Michael reaction tributylphosphane-promoted spirocyclization step was
(Scheme 2). However, basic alumina was found to be inef- needed starting from pure compound 2. We chose the trans-
fective for the formation of δ-latones and δ-lactams, and formation 2c Ǟ 1i for this purpose. Thus, in separate ex-
the Dowex resin promoted only the spirocyclization of β- periments, a dichloromethane solution of pure β-oxo ester
keto amide substrates. This first set of experiments also re- 2c was treated with up to 1 equiv. of tributylphosphane and
vealed an excellent diastereoselectivity for the spiro[4,5] irradiated with microwaves at 100 °C, according to the con-
series (e.g. δ-lactams 1e), a feature later found to be general ditions developed for the last elemental transformation of
regardless of the nature of the catalyst used to promote the the consecutive reactions presented in Scheme 2 and
Michael-based spirocyclization. Finally, when a catalytic Table 4. To our great surprise, substrate 2c was totally inert
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T. Boddaert, Y. Coquerel, J. Rodriguez
FULL PAPER
Scheme 2. Consecutive CM/Michael reactions.
Table 4. Consecutive Wolff rearrangement/α-oxo ketene trapping/
CM/Michael reactions.
Figure 1. ORTEP diagrams of 1j (left) and 1k (major diastereomer,
right) displayed at 50% probability.[19]
under these conditions and was recovered quantitatively
(Scheme 3, left). From these results, we concluded that, al-
though tributylphosphane is an excellent promoter of the
transformation 2 Ǟ 1 under the consecutive reaction condi-
tions, it is not a catalyst for this transformation. Logically,
we searched for the actual catalyst of the Michael-based
spirocyclization. The most reasonable hypothesis was that
tributylphosphane was acting as a competing ligand at the
ruthenium centre in 5, or more likely in the other ruthenium
complexes formed during the CM reaction. Several control
experiments were conducted with the three metathesis pre-
catalysts 5–7 and tributylphosphane (Table 5). From this set
of experiments it was concluded that (1) only 5 and 6 con-
taining a SIMes NHC ligand led to the catalyst for the
Michael addition (compare Entries 2, 4, 6 and 7 with 8),
and (2) this catalyst is generated only when the reactions
are performed under ethylene (Entries 2, 4, 6, 7). Related
domino CM/Michael addition reactions have been reported
in the past few years, invoking the Lewis acidity of either
the (methylidene)ruthenium 14-electron complex [(SI-
Mes)(Cl)2Ru=CH2] generated during the metathesis cata-
lytic cycle or the ruthenium hydride species derived from
degradation of the latter[20] as the activation mode of the
Michael addition.[8b,21] However, in this case, the Lewis
acidity of the ruthenium species formed during the reaction
should be quenched by the excess phosphane (relative to
the ruthenium), and thus, such an activation mode for the
[a] Yields for isolated products after flash chromatography. The
1
diastereomeric ratios were determined by H and 13C NMR spec-
troscopy of the crude material. [b] Conditions for the last step:
nBu3P (10 mol-%), microwaves, 100 °C, 10 min.
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Combination of Rearrangement with Metallic and Organic Catalyses
Scheme 3. NHC-catalyzed Michael-induced spirocyclization. Mes = mesityl = 2,4,6-trimethylphenyl.
Michael addition is unlikely. The fact that the NHC-free silyl)amide]} at room temperature, and the spiro product 1i
7 combined with tributylphosphane and ethylene did not was obtained in 85% yield with excellent diastereoselectiv-
promote the Michael addition (Entry 8) brought the hy- ity, demonstrating the organocatalytic activity of NHCs in
pothesis that the SIMes NHC in 5 and 6 is responsible for the Michael addition of 1,3-dicarbonyl compounds
the observed catalytic activity. Yet another set of control (Scheme 3, right).[23] With the commercially available stable
experiments allowed us to confirm this hypothesis: to a NHC IPr [9, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylid-
dichloromethane solution of 5 under ethylene was added ene], the same reaction afforded a 97% yield of the spiro
5 equiv. of tributylphosphane, the mixture was irradiated product 1i. It was concluded that, under the conditions of
with microwaves at 100 °C for 20 min, and a preparative the consecutive reactions involving a tributylphosphane-
TLC of the concentrated product mixture allowed the isola- promoted spirocyclization (Table 4 and in part Scheme 2),
tion of the chlorohydrate of the NHC SIMes (8, confirmed the actual catalyst of the intramolecular Michael addition
1
by comparison of H NMR spectroscopic data with those step is the NHC SIMes originally present as an ancillary
of an authentic sample) together with unidentified ruthe- ligand on 5.[24] These reactions represent examples of a par-
nium species. This experiment indicated that a NHC/tribu-
tylphosphane exchange occurred at the metal centre, pre-
sumably involving the 14-electron complex [(SIMes)(Cl)2-
Ru=CH2]. Such NHC/phosphane ligand exchange reac-
Table 6. Modified consecutive Wolff rearrangement/α-oxo ketene
trapping/CM/Michael reactions.
tions are rare due to the strong NHC–metal interaction,
and the tributylphosphane analogue of 6 [(SIMes)(Cl)2-
(nBu3P)Ru=CHPh] was reported to be stable in the pres-
ence of an excess of tributylphosphane at room tempera-
ture.[22] Finally, we examined the intramolecular Michael
addition of β-oxo ester 2c with 20 mol-% of SIMes
{generated from 8 and KHMDS [potassium bis(trimethyl-
Table 5. Control experiments with metathesis precatalysts and tri-
butylphophane.
Entry
Conditions
nBu3P
Spirocyclization[a]
1
2
3
4
5
6
7
8
5 under argon
5 under ethylene
5 under argon
5 under ethylene
5 under argon
5 under ethylene
6 under ethylene
7 under ethylene
10 mol-%
10 mol-%
50 mol-%
50 mol-%
100 mol-%
100 mol-%
100 mol-%
100 mol-%
no
yes
no
yes
no
yes
yes
no
[a] Yields for isolated products after flash chromatography. The
1
[a] These qualitative experiments were analyzed by TLC, and full
conversion was not achieved when spirocyclization occurred.
diastereomeric ratios were determined by H and 13C NMR spec-
troscopy of the crude material.
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T. Boddaert, Y. Coquerel, J. Rodriguez
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ring bar in anhydrous solvents under argon. Reactions under mi-
crowave irradiation were performed in oven-dried 10 mL sealable
Pyrex tubes equipped with a Teflon-coated stirring bar (obtained
from CEM). All reactions under microwave irradiation (ν =
2.45 GHz) were performed in a CEM Discover 1–300 W system
equipped with build-in pressure measurement sensor and a verti-
cally focused IR temperature sensor. All reagents were obtained
from commercial sources and used as supplied unless otherwise
stated. Anhydrous CH2Cl2 and toluene were obtained from an
MBraun SPS-800 solvent purification system. MeOH was dried by
ticularly attractive concept of consecutive reactions involv-
ing the same organometallic precatalyst as the successive
source of both metallic and organic catalysts.
Having demonstrated that the Michael addition elemen-
tal step could be efficiently catalyzed by the NHC 9, we
briefly explored a modified version of the consecutive Wolff
rearrangement/α-oxo ketene trapping/CM/Michael reaction
involving a catalytic amount of 9 instead of tributylphos-
phane (Table 6). These modified conditions proved equally
efficient and general, leading to the same observations, with heating to reflux with magnesium turnings and then distilled under
argon. All acrylic derivatives were distilled prior use. Petroleum
ether refers to the fraction distilled between 40 °C and 65 °C. The
reactions were monitored by TLC, which was performed with
Merck 60F254 plates and visualized with an ethanolic solution of
p-anisaldehyde and sulfuric acid or an ethanolic solution of molyb-
dophosphoric acid. Flash chromatography was performed with
Merck 230–400 mesh silica gel. NMR spectroscopic data were re-
corded with a Bruker Avance 300 spectrometer in CDCl3, and
chemical shifts (δ) are given in ppm relative to the residual nondeu-
terated solvent signal for 1H (CHCl3: δ = 7.26 ppm) and relative to
the deuterated solvent signal for 13C (CDCl3: δ = 77.0 ppm); cou-
pling constants (J) are in Hz. Mass spectra were recorded with a
Bruker Esquire 6000 spectrometer equipped with an electrospray
ionization source and an ion trap detector. Melting points were
measured with a Büchi B-540 apparatus and are uncorrected. High-
resolution mass spectra were obtained from Spectropole (http://
www.spectropole.u-3mrs.fr/).
the advantage of generalizing the method to the preparation
of α-spiro-δ-lactams (1m and 1n, Entries 6 and 7, respec-
tively) unavailable under the previous conditions (see
Table 4).
Conclusions
A general stereoselective synthetic route to α-spirolac-
tones and -lactams from 2-diazo-1,3-dicarbonyl com-
pounds, (homo)allylic alcohols or amines, and acrylic deriv-
atives, involving a single consecutive reaction consisting of
a Wolff rearrangement/α-oxo ketene trapping/CM/Michael
addition sequence is described in full. The yields are typi-
cally in the 40–60% range (up to 77%), but the simplicity
and cleanliness of the reactions, combined with the chemi-
cal diversity accessible and the rapid increase in molecular
complexity largely make up for this small limitation. In the
course of this work, the superiority of the microwave-as-
sisted Wolff rearrangement/α-oxo ketene trapping reaction
Compounds of Tables 1 and 2: The substrates of Entries 4,[25] 5,[26]
6[27] and 7[28] in Table 1, the diazo substrates[29] and the nucleophile
of Entry 6[30] in Table 2 were prepared according to literature pro-
over the classical transesterification/transamidation strategy cedures.
was confirmed for the preparation of β-oxo esters and β-
General Procedure for the Preparation of Compounds in Table 1: To
oxo amides where applicable. Thanks to microwave technol-
ogy, we have developed “clean” conditions for the CM of
terminal olefins with acrylic derivatives using only 1 equiv.
of each olefinic substrate and 4 mol-% of metallic precata-
lyst in reduced reaction times. The organocatalytic activity
of N,N-diaryl-1,3-imidazol(in)-2-ylidene NHCs in the
Michael addition of 1,3-dicarbonyl compounds and ana-
logues was discovered and exploited in the consecutive reac-
tion leading to α-spirolactones and -lactams. A conceptu-
ally attractive version of this consecutive reaction was de-
veloped, which involved the Grubbs–Hoveyda precatalyst 5
containing the SIMes NHC ligand as the successive source
of both the organometallic CM catalyst and the organic
catalyst for the intramolecular Michael addition when the
last step is promoted by a catalytic amount of tributylphos-
phane to release the NHC from the ruthenium centre. Over-
all, it can be emphasized that the consecutive reaction de-
a solution of β-oxo ester 4a (1.0 mmol) in anhydrous toluene (0–
5 mL) were successively added the nucleophile (3.0 equiv. to sol-
vent), DMAP (1.5 mmol) and molecular sieves (3 Å) (0.5 g). The
reaction mixture was stirred with heating to reflux for 6–120 h with
periodic monitoring by TLC. When full conversion was reached,
the reaction was quenched with an aqueous solution of hydrochlo-
ric acid (1 m). The resulting acidic aqueous medium was washed
three times with ethyl acetate, the combined organic layers were
washed with water then brine, dried with anhydrous sodium sulfate,
filtered and concentrated under vacuum to give the crude product,
which was purified by silica gel flash chromatography with EtOAc/
petroleum ether to afford pure 3.
General Procedure for the Preparation of Compounds in Table 2:[10]
A solution of 2-diazo-1,3-diketone 4b (1.0 mmol) and nucleophile
(1.0 mmol) in toluene (2 mL) in a 10 mL sealed tube equipped with
a Teflon-coated stirring bar was irradiated with microwaves at
300 W until the temperature reached 180 °C, the pressure reached
17 bars or for a maximum time of 3 min, whereupon the reaction
scribed here has allowed the preparation of the target α- mixture was cooled to 40 °C with an air flow. Concentration of
the reaction mixture followed by high-vacuum removal of volatiles
afforded the clean crude product 3 without need for purification.
Compounds 3b,[31] 3c,[32] 3j[10] and 3k[10] exhibited physical and
spectroscopic properties identical to previously reported data.
spirolactones and -lactams by using only a single equivalent
of each of the three reaction partners and a catalytic
amount of additives, which was designed to produce only
nitrogen and ethylene gases as byproducts, and required
minimum energy thanks to microwave technology.
Compound 3a: According to the general procedure, 3a was obtained
as a colourless oil (144 mg, 79% for Table 1, and 180 mg, 99% for
Table 2). Rf (50% EtOAc in petroleum ether) = 0.75. 13C NMR
(75 MHz, CDCl3): δ = 212.2 (C), 169.3 (C), 133.7 (CH), 117.3
(CH2), 64.2 (CH2), 54.7 (CH), 38.0 (CH2), 33.0 (CH2), 27.4 (CH2),
Experimental Section
General Remarks: Reactions were generally performed in oven-
1
dried round-bottomed flasks equipped with a Teflon-coated stir-
20.9 (CH2) ppm. H NMR (300 MHz, CDCl3): δ = 5.77 (dddd, J
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Combination of Rearrangement with Metallic and Organic Catalyses
= 6.7, 6.9, 10.2, 17.0 Hz, 1 H), 5.16–5.01 (m, 2 H), 4.17 (dd, J = (CH), 117.2 (CH2), 97.7 (C), 63.1 (CH2), 33.0 (CH2), 29.9 (CH2),
6.7, 6.8 Hz, 2 H), 3.13 (dd, J = 8.8, 9.0 Hz, 1 H), 2.53–2.01 (m, 6
27.0 (CH2), 22.3 (CH2), 21.9 (CH2) ppm. 1H NMR (300 MHz,
H), 1.93–1.77 (m, 2 H) ppm. MS (ESI+): m/z = 183 [M + H]+, 205 CDCl3): δ = 12.16 (s, 0.9 H), 5.80 (dddd, J = 6.8, 6.9, 10.2, 17.0 Hz,
[M + Na]+, 221 [M + K]+.
0.9 H), 5.71 (dddd, J = 6.7, 6.9, 10.2, 17.1 Hz, 0.1 H), 5.16–4.98
(m, 2 H), 4.18 (dd, J = 6.7, 6.7 Hz, 1.8 H), 4.14–4.10 (m, 0.2 H),
3.38–3.33 (m, 0.1 H), 2.41 (dddd, J = 1.2, 1.3, 6.8, 13.4 Hz, 2 H),
2.28–2.16 (m, 4 H), 1.72–1.54 (m, 4 H) ppm. MS (ESI+): m/z =
197 [M + H]+, 219 [M + Na]+, 235 [M + K]+.
Compound 3d: According to the general procedure, 3d was obtained
as a colourless oil (167 mg, 58%). Rf (30% EtOAc in petroleum
ether) = 0.42. 13C NMR (75 MHz, CDCl3): δ = 207.0 (C), 206.8
(C), 166.3 (C), 165.8 (C), 160.8 (2 C), 148.6 (C), 148.6 (C), 132.6
(CH), 132.2 (CH), 130.1 (2CH), 117.5 (CH2), 116.9 (CH2), 105.8
(2 CH), 103.3 (2 CH), 99.3 (2 CH), 55.8 (CH2), 55.7 (CH2), 55.1
Compound 3i: According to the general procedure, 3i was obtained
as a colourless oil (135 mg, 74% for Table 1, and 171 mg, 94% for
(2 CH3), 52.3 (CH2), 51.6 (CH2), 51.3 (CH), 50.6 (CH), 49.0 (CH2), Table 2). Rf (20% EtOAc in petroleum ether) = 0.57–0.86. 13C
48.7 (CH2), 35.2 (CH3), 34.3 (CH3) ppm. 1H NMR (300 MHz,
CDCl3): δ = 7.19 (dd, J = 8.2, 8.2 Hz, 2 H), 6.40 (dd, J = 2.3, (C), 131.7 (CH), 118.4 (CH2), 65.6 (CH2), 57.1 (CH), 41.4 (CH2),
NMR (75 MHz, CDCl3): keto form (ca. 30%): δ = 206.0 (C), 169.6
8.0 Hz, 2 H), 6.29 (ddd, J = 2.3, 2.6, 7.9 Hz, 2 H), 6.25–6.20 (m, 2
H), 5.93–5.69 (m, 2 H), 5.30–5.14 (m, 4 H), 4.14–3.70 (m, 14 H),
3.8 (s, 6 H), 3.15 (s, 3 H), 3.0 (s, 3 H) ppm. MS (ESI+): m/z = 289
[M + H]+, 311 [M + Na]+, 227 [M + K]+.
29.9 (CH2), 27.0 (CH2), 23.2 (CH2); enol form (ca. 70%): δ = 172.4
(C), 172.2 (C), 132.2 (CH), 117.7 (CH2), 97.5 (C), 64.6 (CH2), 29.0
(CH2), 22.3 (CH2), 22.3 (CH2), 21.8 (CH2) ppm. 1H NMR
(300 MHz, CDCl3): δ = 12.13 (s, 0.7 H), 5.95 (dddd, J = 5.5, 6.7,
10.5, 17.2 Hz, 0.7 H), 5.91 (dddd, J = 5.8, 6.0, 10.5, 17.2 Hz, 0.3
H), 5.27 (dddd, J = 1.4, 1.5, 10.5, 17.2 Hz, 1.4 H), 5.40–5.10 (m,
0.6 H), 4.65 (ddd, J = 1.4, 1.5, 5.5 Hz, 1.4 H), 4.75–4.55 (m, 0.6
H), 3.41 (m, 0.3 H), 2.56–2.45 (m, 0.3 H), 2.42–2.10 (m, 3.7 H),
1.94–1.77 (m, 0.3 H), 1.72–1.56 (m, 3.7 H) ppm. MS (ESI+): m/z
= 197 [M + H]+, 219 [M + Na]+, 235 [M + K]+.
Compound 3e: According to the general procedure, 3e was obtained
as a colourless oil (134 mg, 63%). Rf (60% EtOAc in petroleum
ether) = 0.65. 13C NMR (75 MHz, CDCl3): δ = 204.6 (C), 204.3
(C), 168.7 (C), 168.4 (C), 132.7 (CH), 132.4 (CH), 117.3 (CH2),
117.1 (CH2), 57.2 (CH), 56.8 (CH), 52.2 (CH2), 50.2 (CH2), 44.3
(CH2), 44.0 (CH2), 34.6 (CH3), 33.7 (CH3), 32.9 (CH2), 32.8 (CH2),
30.2 (CH2), 30.0 (CH2) ppm. 1H NMR (300 MHz, CDCl3): δ = General Procedure for the Preparation of Compounds in Table 3: To
5.84–5.69 (m, 2 H), 5.29–5.10 (m, 4 H), 4.17–3.65 (m, 6 H), 3.48–
3.33 (m, 2 H), 3.11–2.63 (m, 10 H), 2.97 (s, 3 H), 2.83 (s, 3 H) ppm.
MS (ESI+): m/z = 214 [M + H]+, 236 [M + Na]+, 252 [M + K]+.
a solution of 3 (0.50 mmol) in anhydrous dichloromethane (5 mL)
were successively added the acrylic derivative (0.50 mmol) and 5 in
two portions (0.015 mmol at the start, and 0.005 mmol after
20 min). The reaction vessel was sealed and irradiated with micro-
waves at 100 °C for 30 min (20, then 10 min). The solvent and vola-
tiles were removed under vacuum, and the resulting crude product
was purified by silica gel flash chromatography with EtOAc/petro-
leum ether to afford pure 2. Compounds 2b,[11b] 2c[11a] and 2f[23a]
exhibited physical and spectroscopic properties identical to pre-
viously reported data.
Compound 3f: According to the general procedure, 3f was obtained
as a colourless oil (159 mg, 65%). Rf (10% EtOAc in petroleum
ether) = 0.63. 13C NMR (75 MHz, CDCl3): keto form (ca. 30%):
δ = 200.4 (C), 170.0 (C), 141.2 (C), 138.0 (C), 132.4 (CH), 131.8
(CH), 129.8 (CH), 129.1 (CH), 126.7 (CH), 118.4 (CH2), 65.7
(CH2), 56.6 (CH), 32.8 (CH2), 25.3 (CH2), 24.3 (CH2); enol form
(ca. 70%): δ = 172.6 (C), 170.7 (C), 141.0 (C), 135.6 (C), 132.2
(CH), 130.1 (CH), 128.9 (CH), 127.1 (CH), 126.3 (CH), 117.9
Compound 2a: According to the general procedure, 2a was obtained
(CH2), 100.1 (C), 65.0 (CH2), 33.5 (CH2), 31.7 (CH2), 21.7 (CH2) as a brown oil (60 mg, 53%). Rf (25% EtOAc in petroleum ether)
1
ppm. H NMR (300 MHz, CDCl3): δ = 12.61 (s, 0.7 H), 7.78–7.59
(m, 1 H), 7.47–7.27 (m, 2 H), 7.25–7.17 (m, 1 H), 6.00 (dddd, J =
= 0.33. 13C NMR (75 MHz, CDCl3): δ = 211.7 (C), 168.6 (C), 166.2
(C), 140.8 (CH), 122.0 (CH), 63.2 (CH2), 54.6 (CH), 51.7 (CH3),
5.5, 6.7, 10.5, 16.0 Hz, 0.7 H), 5.91 (dddd, J = 5.8, 6.8, 10.5, 38.0 (CH2), 27.3 (CH2), 20.9 (CH2) ppm. 1H NMR (300 MHz,
16.1 Hz, 0.3 H), 5.41–5.22 (m, 2 H), 4.77–4.73 (m, 1.4 H), 4.70–
CDCl3): δ = 6.97–6.87 (m, 1 H), 6.12–6.05 (m, 1 H), 4.84–4.77 (m,
4.64 (m, 0.6 H), 3.89–3.82 (m, 0.3 H), 2.98–2.92 (m, 0.6 H), 2.65 2 H), 3.74 (s, 3 H), 3.22 (dd, J = 9.2, 9.0 Hz, 1 H), 2.44–2.24 (m,
(dd, J = 6.9, 6.5 Hz, 1.4 H), 2.27–2.01 (m, 3.7 H), 1.94–1.76 (m, 4 H), 2.20–2.08 (m, 1 H), 1.94–1.79 (m, 1 H) ppm. HRMS (ESI+):
+
0.3 H) ppm. MS (ESI+): m/z = 245 [M + H]+, 267 [M + Na]+, 283
m/z [M + H]+: calcd. for C11H15O5 227.0916, obsd 227.0920.
[M + K]+.
Compound 2d: According to the general procedure, 2d was obtained
as a brown oil (74 mg, 66%). Rf (30% EtOAc in petroleum ether)
= 0.45. 13C NMR (75 MHz, CDCl3): δ = 211.9 (C), 198.2 (C), 169.1
Compound 3g: According to the general procedure, 3g was obtained
as a colourless oil (186 mg, 63%). Rf (40% EtOAc in petroleum
ether) = 0.50. 13C NMR (75 MHz, CDCl3): δ = 203.9 (C), 203.6 (C), 142.7 (CH), 133.1 (CH), 62.9 (CH2), 54.6 (CH), 37.8 (CH2),
(C), 167.6 (C), 167.3 (C), 154.4 (2 C), 132.6 (CH), 132.3 (CH),
117.3 (2CH2), 80.7 (C), 80.6 (C), 53.6 (2 CH), 52.2 (2 CH2), 50.1
(2 CH2), 40.9 (2 CH2), 40.7 (2 CH2), 34.7 (2 CH3), 28.3 (6 CH3)
31.5 (CH2), 27.1 (CH2), 26.7 (CH3), 20.8 (CH2) ppm. 1H NMR
(300 MHz, CDCl3): δ = 6.73 (ddd, J = 6.8, 6.9, 16.0 Hz, 1 H), 6.09
(ddd, J = 1.3, 1.4, 16.0 Hz, 1 H), 4.32–4.16 (m, 2 H), 3.12 (dd, J =
9.2, 9.1 Hz, 1 H), 2.59–2.50 (m, 2 H), 2.30–2.01 (m, 5 H), 2.23 (s,
3 H), 1.90–1.74 (m, 1 H) ppm. MS (ESI+): m/z = 225 [M + H]+,
247 [M + Na]+, 263 [M + K]+.
1
ppm. H NMR (300 MHz, CDCl3): δ = 5.77 (dddd, J = 6.7, 6.9,
10.2, 17.2 Hz, 1 H), 5.75 (dddd, J = 6.7, 6.9, 10.2, 17.2 Hz, 1 H),
5.30–5.14 (m, 4 H), 4.30–3.83 (m, 6 H), 3.79–3.47 (m, 6 H), 3.40–
3.25 (m, 2 H), 2.95 (s, 3 H), 2.87 (s, 3 H), 2.64–2.39 (m, 4 H), 1.47
(s, 9 H), 1.46 (s, 9 H) ppm. MS (ESI+): m/z = 297 [M + H]+, 320
[M + Na]+, 336 [M + K]+.
Compound 2e: According to the general procedure, 2e was obtained
as a brown oil (104 mg, 78%). Rf (30% EtOAc in petroleum ether)
= 0.63. 13C NMR (75 MHz, CDCl3): δ = 211.1 (C), 169.2 (C), 166.4
(C), 143.8 (CH), 123.2 (CH), 62.9 (CH2), 54.0 (CH), 52.8 (CH2),
Compound 3h: According to the general procedure, 3h was obtained
as a colourless oil (151 mg, 77%). Rf (20% EtOAc in petroleum 51.4 (CH3), 40.6 (CH2), 34.3 (C), 31.2 (CH2), 28.8 (CH3), 27.5
1
ether) = 0.56–0.78. 13C NMR (75 MHz, CDCl3): keto form (ca.
40%): δ = 206.1 (C), 169.9 (C), 133.8 (CH), 117.2 (CH2), 64.0
(CH3) ppm. H NMR (300 MHz, CDCl3): δ = 6.9 (ddd, J = 6.9,
7.0, 15.8 Hz, 1 H), 5.90 (ddd, J = 1.2, 1.5, 15.8 Hz, 1 H), 4.35–4.15
(CH2), 57.1 (CH), 41.5 (CH2), 32.9 (CH2), 29.0 (CH2), 23.2 (CH2), (m, 2 H), 3.72 (s, 3 H), 3.36 (dd, J = 9.0, 11.0 Hz, 1 H), 2.64–2.28
22.3 (CH2); enol form (ca. 60%): δ = 172.5 (C), 172.1 (C), 133.9 (m, 3 H), 2.18 (s, 2 H), 2.21–1.97 (m, 1 H), 1.21 (s, 3 H), 1.04 (s, 3
Eur. J. Org. Chem. 2011, 5061–5070
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5067

T. Boddaert, Y. Coquerel, J. Rodriguez
FULL PAPER
H) ppm. MS (ESI+): m/z = 269 [M + H]+, 291 [M + Na]+, 307 [M
15.9 Hz, 1 H), 2.76–2.62 (m, 1 H), 2.40–2.20 (m, 2 H), 2.23–2.08
(m, 1 H), 2.07–1.96 (m, 1 H), 1.80–1.60 (m, 3 H) ppm.
+ K]+.
Procedure for 1e: To a solution of 3l (0.50 mmol) in anhydrous
dichloromethane (5 mL) were successively added methyl acrylate
(0.50 mmol) and 5 in two portions (0.015 mmol at the start and
0.005 mmol after 20 min), and the reaction vessel was sealed and
irradiated with microwaves at 100 °C for 30 min (20, then 10 min).
To the cooled reaction mixture was added Dowex 550A resin
(230 mg), and the resulting mixture was irradiated with microwaves
at 100 °C for 20 min, and the product 1e was isolated as above.
Compound 1e exhibited physical and spectroscopic properties iden-
tical to previously reported data.[23a]
General Procedure for the Preparation of Compounds 1a–1d in
Scheme 2: To a solution of 3 (0.50 mmol) in anhydrous dichloro-
methane (5 mL) were successively added the acrylic derivative
(0.50 mmol) and 5 in two portions (0.015 mmol at the start and
0.005 mmol after 20 min), and the reaction vessel was sealed and
irradiated with microwaves at 100 °C for 30 min (20, then 10 min).
To the cooled reaction mixture was added basic alumina (0.8 g)
and methanol (0.7 mL), and the resulting mixture was heated at
50 °C for 24 h. The reaction mixture was filtered through a pad of
Celite and concentrated under vacuum to give the crude product,
which was purified by silica gel flash chromatography with EtOAc/
petroleum ether to afford pure 1a–d. Compound 1a[8a] exhibited
physical and spectroscopic properties identical to previously re-
ported data.
General Procedure for 1c and 1f: To a solution of 3e or 3f, respec-
tively, (0.50 mmol) in anhydrous dichloromethane (5 mL) were suc-
cessively added the acrylic derivative (0.50 mmol) and 5 in two por-
tions (0.015 mmol at the start and 0.005 mmol after 20 min), and
the reaction vessel was sealed and irradiated with microwaves at
100 °C for 30 min (20, then 10 min). To the cooled reaction mixture
was added tributylphosphane (0.10 mmol), and the resulting mix-
ture was irradiated with microwaves at 100 °C for 20 min. The
products 1c and 1f were isolated as above.
Compound 1b (dr = 1.3:1): According to the general procedure, 1b
was obtained as a brown oil (67 mg, 56%). Minor diastereomer
(isolated): Rf (60% EtOAc in petroleum ether) = 0.22. 13C NMR
(75 MHz, CDCl3): δ = 216.9 (C), 172.4 (C), 172.1 (C), 60.9 (C),
52.6 (CH2), 51.8 (CH3), 39.4 (CH2), 38.6 (CH), 32.9 (CH2), 32.6
(CH2), 29.9 (CH3), 20.1 (CH2) ppm. 1H NMR (300 MHz, CDCl3):
δ = 3.66 (s, 3 H), 3.47 (dd, J = 8.5, 9.2 Hz, 1 H), 3.36 (dd, J =
10.0, 9.2 Hz, 1 H), 2.86 (s, 3 H), 2.72–260 (m, 1 H), 2.58–2.45 (m,
3 H), 2.41–2.11 (m, 3 H), 1.97–1.82 (m, 2 H) ppm. HRMS (ESI+):
m/z [M + H]+: calcd. for [C12H18NO4]+ 240.1230, found 240.1228.
Major diastereomer: Rf (60% EtOAc in petroleum ether) = 0.27.
13C NMR (75 MHz, CDCl3): δ = 216.5 (C), 172.5 (C), 171.8 (C),
61.2 (C), 52.6 (CH2), 51.9 (CH3), 38.7 (CH), 37.3 (CH2), 34.6
(CH2), 29.8 (CH3), 28.5 (CH2), 19.4 (CH2) ppm. 1H NMR
(300 MHz, CDCl3): δ = 3.67 (s, 3 H), 3.05–2.93 (m, 2 H), 2.83 (s,
3 H), 2.59–2.12 (m, 7 H), 1.98–1.82 (m, 2 H) ppm.
Compound 1f (dr = 1.2:1): According to the general procedure, 1f
was obtained as a brown oil (40 mg, 30%). Rf (10% EtOAc in pe-
troleum ether) = 0.47. 13C NMR (75 MHz, CDCl3): δ = 205.5 (C),
204.2 (C), 174.0 (C), 172.9 (C), 138.7 (C), 138.3 (C), 138.3 (C),
137.9 (C), 133.2 (CH), 132.7 (CH), 129.1 (CH), 129.0 (CH), 128.7
(CH), 127.6 (CH), 127.4 (CH), 127.1 (CH), 116.8 (C), 116.4 (C),
69.7 (CH2), 68.4 (CH2), 60.6 (C), 59.5 (C), 43.4 (CH), 41.8 (CH),
32.0 (CH2), 30.9 (CH2), 30.4 (CH2), 25.4 (CH2), 22.8 (CH2), 21.5
(CH2), 17.0 (CH2), 16.0 (CH2) ppm. 1H NMR (300 MHz, CDCl3):
δ = 7.52–7.29 (m, 6 H), 7.18 (d, J = 7.4 Hz, 2 H), 4.56 (dd, J =
7.8, 9.0 Hz, 1 H), 4.53 (dd, J = 6.9, 9.0 Hz, 1 H), 4.34 (dd, J = 8.2,
9.0 Hz, 1 H), 4.09 (dd, J = 7.2, 9.0 Hz, 1 H), 3.47 (ddd, J = 6.9,
8.3, 13.8 Hz, 1 H), 3.32 (ddd, J = 5.4, 9.6, 15.0 Hz, 1 H), 3.09 (ddd,
J = 7.2, 7.3, 14.6 Hz, 1 H), 3.92 (dt, J = 1.3, 7.8 Hz, 1 H), 2.88–
2.73 (m, 2 H), 2.71–2.51 (m, 6 H), 2.20–1.81 (m, 6 H) ppm. MS
(ESI+): m/z = 270 [M + H]+, 292 [M + Na]+, 308 [M + K]+.
Compound 1c (dr = 1.3:1 with Al2O3 or dr = 1.2:1 with nBu3P):
According to the general procedures, 1c was obtained as a brown
oil (58 mg, 43% with Al2O3, and 47 mg, 35% with nBu3P). Rf (60%
EtOAc in petroleum ether) = 0.13. 13C NMR (75 MHz, CDCl3): δ
= 206.2 (C), 205.3 (C), 171.9 (C), 171.9 (C), 171.2 (C), 170.8 (C),
60.1 (C), 61.8 (C), 52.4 (CH2), 51.9 (CH3), 51.8 (CH3), 51.1 (CH2),
41.5 (CH2), 41.4 (CH), 40.6 (CH2), 36.6 (CH2), 35.1 (CH), 34.8
(CH2), 33.0 (CH2), 31.5 (CH2), 29.9 (2CH3), 28.5 (CH2), 26.7
General Procedure for the Preparation of Compounds in Table 4: A
solution of 2-diazo-1,3-diketone 4b (0.50 mmol) and allyl alcohol,
homoallyl alcohol or allyl(methyl)amine (0.50 mmol) in dichloro-
methane (5 mL) in a 10 mL sealed tube equipped with a Teflon-
coated stirring bar was irradiated with microwaves at 300 W for
15 min, whereupon the reaction mixture was cooled to 40 °C with
an air flow. To the resulting solution were added the acrylic deriva-
tive (0.50 mmol) and 5 in two portions (0.015 mmol at the start
and 0.005 mmol after 20 min), and the reaction vessel was sealed
and irradiated with microwaves at 100 °C for 30 min (20, then
10 min). To the cooled reaction mixture was added tributylphos-
phane (0.10 mmol), and the resulting mixture was irradiated with
microwaves at 100 °C for 20 min. The cooled reaction mixture was
filtered through a pad of Celite and concentrated under vacuum
to give the crude product, which was purified by silica gel flash
chromatography with EtOAc/petroleum ether to afford pure 1a and
1g–k. Compounds 1h–k exhibited physical and spectroscopic prop-
erties identical to previously reported data.[8a] Compounds 1j and
1k (major diastereomer) were obtained as white needles suitable for
X-ray diffraction analysis.[19]
1
(CH2) ppm. H NMR (300 MHz, CDCl3): δ = 3.67 (s, 3 H), 3.66
(s, 3 H), 3.77–3.44 (m, 4 H), 3.28–2.66 (m, 16 H), 2.85 (s, 3 H),
2.84 (s, 3 H), 2.55–2.22 (m, 2 H) ppm. HRMS (ESI+): m/z [M +
H]+: calcd. for [C12H18NO4S]+ 272.0951, found 272.0953.
Compound 1d (dr = 1:1): According to the general procedure, 1d
was obtained as a brown oil (63 mg, 52%). First diastereomer
eluted (isolated): Rf (30% EtOAc in petroleum ether) = 0.54. 13C
NMR (75 MHz, CDCl3): δ = 205.9 (C), 174.7 (C), 172.0 (C), 71.1
(CH2), 59.2 (C), 52.0 (CH3), 42.9 (CH), 40.8 (CH2), 34.6 (CH2),
31.6 (CH2), 24.8 (CH2), 20.6 (CH2) ppm. 1H NMR (300 MHz,
CDCl3): δ = 4.52 (dd, J = 8.5, 9.2 Hz, 1 H), 4.16 (dd, J = 8.7,
9.2 Hz, 1 H), 3.68 (s, 3 H), 2.86 (dd, J = 10.0, 16.1 Hz, 1 H), 2.57
(dd, J = 3.8, 16.1 Hz, 1 H), 2.76–2.59 (m, 2 H), 2.42–2.27 (m, 2
H), 2.24–2.14 (m, 1 H), 2.07–1.96 (m, 1 H), 1.91–1.60 (m, 3 H)
ppm. HRMS (ESI+): m/z [M + H]+: calcd. for [C12H17O5]+
241.1071, found 241.1074. Second diastereomer eluted: Rf (30%
EtOAc in petroleum ether) = 0.50. 13C NMR (75 MHz, CDCl3): δ
= 204.7 (C), 174.1 (C), 171.5 (C), 69.9 (CH2), 59.1 (C), 52.0 (CH3),
Compound 1g (dr = 1.2:1): According to the general procedure, 1g
39.5 (CH2), 36.2 (CH), 34.6 (CH2), 30.2 (CH2), 26.6 (CH2), 20.2 was obtained as a brown oil (35 mg, 34%). Rf (50% EtOAc in pe-
(CH2) ppm. 1H NMR (300 MHz, CDCl3): δ = 4.53 (dd, J = 7.4, troleum ether) = 0.27. 13C NMR (75 MHz, CDCl3): δ = 216.5 (C),
9.2 Hz, 1 H), 3.93 (dd, J = 8.7, 9.2 Hz, 1 H), 3.70 (s, 3 H), 3.10– 215.4 (C), 171.8 (C), 171.0 (C), 117.4 (C), 117.3 (C), 61.3 (C), 60.6
2.98 (m, 1 H), 2.51 (dd, J = 4.9, 15.9 Hz, 1 H), 2.28 (dd, J = 10.5,
(C), 52.0 (CH2), 51.9 (CH2), 39.3 (CH2), 38.2 (CH), 37.1 (CH2),
5068
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 5061–5070

Combination of Rearrangement with Metallic and Organic Catalyses
34.9 (CH), 30.0 (CH3), 30.0 (CH3), 29.7 (CH2), 28.4 (CH2), 19.9
(CH2), 19.3 (CH2), 19.0 (CH2), 16.3 (CH2) ppm. 1H NMR
(300 MHz, CDCl3): δ = 3.86 (dd, J = 7.2, 10.0 Hz, 1 H), 3.50–3.36
(m, 1 H), 3.44 (dd, J = 7.9, 10.0 Hz, 1 H), 3.15 (dd, J = 4.1,
10.0 Hz, 1 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 2.69–2.52 (m, 4 H), 2.51–
2.23 (m, 9 H), 2.16–1.86 (m, 5 H) ppm. MS (ESI+): m/z = 207 [M
+ H]+, 229 [M + Na]+, 245 [M + K]+.
[1]
For reviews, see: a) M. Sannigrahi, Tetrahedron 1999, 55, 9007–
9071; b) R. Pradhan, M. Patra, A. K. Behera, B. K. Mishra,
R. K. Behera, Tetrahedron 2006, 62, 779–828; c) M.-E. Sinib-
aldi, I. Canet, Eur. J. Org. Chem. 2008, 4391–4399; d) B. R.
Raju, A. K. Saikia, Molecules 2008, 13, 1942–2038; e) S. Ko-
tha, A. C. Deb, K. Lahiri, E. Manivannan, Synthesis 2009,
165–193; f) A. Bartoli, F. Rodier, L. Commeiras, J.-L. Parrain,
G. Chouraqui, Nat. Prod. Rep. 2011, 28, 763–782.
General Procedure for the Preparation of Compounds in Scheme 3:
To a suspension of SIMes chlorohydrate 8 (17 mg, 0.05 mmol) in
anhydrous toluene (0.5 mL) was added a 0.05 m solution of
KHMDS in toluene (1 mL, 0.05 mmol), and the resulting mixture
was stirred at room temperature for 30 min. To the reaction mixture
was added a solution of pure 2c (52 mg, 0.25 mmol) in anhydrous
dichloromethane (2.5 mL), and the reaction mixture was stirred at
24 °C for 20 h. The solvent was removed under vacuum, and the
resulting crude product was purified by silica gel flash chromatog-
raphy with EtOAc/petroleum ether to afford 44 mg (85%) of pure
1i as a colourless oil. Alternatively, to a solution of 2c (104 mg,
0.50 mmol) in dichloromethane (5 mL) was added 9 (38 mg,
0.10 mmol), and the reaction mixture was stirred at 24 °C for 20 h.
The solvent was removed under vacuum, and the resulting crude
product was purified by silica gel flash chromatography with
EtOAc/petroleum ether to afford 100 mg (97%) of pure 1i as a
colourless oil.
[2]
[3]
For an illustrative example, see: K. C. Nicolaou, T. R. Wu, D.
Sarlah, D. M. Shaw, E. Rowcliffe, D. R. Burton, J. Am. Chem.
Soc. 2008, 130, 11114–11121.
Step economy: a) P. A. Wender, V. A. Verma, T. J. Paxton, T. H.
Pillow, Acc. Chem. Res. 2008, 41, 40–49 and references cited
therein. Atom economy: b) B. M. Trost, Acc. Chem. Res. 2002,
35, 695–705 and references cited therein. Redox economy: c)
N. Z. Burns, P. S. Baran, R. W. Hoffmann, Angew. Chem. 2009,
121, 2896; Angew. Chem. Int. Ed. 2009, 48, 2854–2867. For a
discussion using case-studies from complex-molecules synthe-
sis, see: d) T. Newhouse, P. S. Baran, R. W. Hoffmann, Chem.
Soc. Rev. 2009, 38, 3010–3021.
For discussions on terminologies of multiple-bond-forming
transformations, see: a) L. F. Tietze, U. Beifuss, Angew. Chem.
1993, 105, 137; Angew. Chem. Int. Ed. Engl. 1993, 32, 131–
163; b) Y. Coquerel, T. Boddaert, M. Presset, D. Mailhol, J.
Rodriguez, in Ideas in Chemistry and Molecular Sciences: Ad-
vances in Synthetic Chemistry (Ed.: B. Pignataro), Wiley-VCH,
Weinheim, Germany, 2010, chapter 9, pp. 187–202.
[4]
General Procedure for the Preparation of Compounds in Table 6: A
solution of 2-diazo-1,3-diketone 4b (0.50 mmol) and allyl alcohol,
homoallyl alcohol or benzyl homoallylamine (0.50 mmol) in
dichloromethane (5 mL) in a 10 mL sealed tube equipped with a
Teflon-coated stirring bar was irradiated with microwaves at 300 W
for 15 min, whereupon the reaction mixture was cooled to 40 °C
with an air flow. To the resulting solution were added the acrylic
derivative (0.50 mmol) and 5 in two portions (0.015 mmol at the
start and 0.005 mmol after 20 min), and the reaction vessel was
sealed and irradiated with microwaves at 100 °C for 30 min (20,
then 10 min). To the cooled reaction mixture was added 9
(0.10 mmol), and the resulting mixture was stirred at 24 °C for 20 h.
The reaction mixture was filtered through a pad of Celite and con-
centrated under vacuum to give the crude product, which was puri-
fied by silica gel flash chromatography with EtOAc/petroleum ether
to afford pure 1h–o. Compounds 1l–n exhibited physical and spec-
troscopic properties identical to previously reported data.[8a]
[5]
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[7]
Compound 1o: According to the general procedure, 1o was obtained
as a brown oil (95 mg, 71%). Rf (40% EtOAc in petroleum ether)
= 0.27. 13C NMR (75 MHz, CDCl3): δ = 212.8 (C), 171.5 (C), 171.5
(C), 68.0 (CH2), 61.0 (C), 53.5 (CH2), 52.0 (CH3), 44.7 (CH2), 35.2
(CH2), 34.4 (CH), 32.8 (C), 31.1 (CH3), 30.0 (CH3), 24.6 (CH2)
[8]
[9]
1
ppm. H NMR (300 MHz, CDCl3): δ = 4.48–4.40 (m, 2 H), 3.68
(s, 3 H), 2.82–2.73 (m, 1 H), 2.64 (d, J = 17.7 Hz, 1 H), 2.37–2.21
(m, 5 H), 1.87 (d, J = 14.2 Hz, 1 H), 1.71–1.59 (m, 1 H), 1.13 (s, 3
H), 1.24 (s, 3 H) ppm. HRMS (ESI+): m/z [M + H]+ calcd. for
+
C14H21O5 269.1384, obsd 269.1385.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of NMR spectra of all new compounds.
[10]
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a) A. Michaut, T. Boddaert, Y. Coquerel, J. Rodriguez, Synthe-
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C. R. Chim. 2009, 12, 872–875.
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Chem. 2008, 1125–1132; b) F. Nicks, Y. Borguet, S. Delfosse,
D. Bicchielli, L. Delaude, X. Sauvage, A. Demonceau, Aust. J.
We thank Dr. M. Giorgi (Aix-Marseille Université) for X-ray dif-
fraction analyses. Financial support from the French Research
Ministry, Aix-Marseille Université and the Centre National de la
Recherche Scientifique (CNRS) is gratefully acknowledged.
[12]
Eur. J. Org. Chem. 2011, 5061–5070
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Received: May 25, 2011
Published Online: July 26, 2011
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Eur. J. Org. Chem. 2011, 5061–5070