Cross-metathesis reactions of homoallyl methyl malonates with sterically hindered allylic esters

Article abstract of DOI:10.1002/ejoc.201100916

The methyl malonate esters of 3-buten-1-ol and 2-methyl-3-buten-1-ol can be coupled efficiently to different methallylic esters in the presence of the second-generation Grubbs catalyst to yield trisubstituted olefins by the cross-metathesis reaction. Product selectivity and yields depend on the relative amounts of reagents and to a minor extent on the methallylic ester functional group. Alkyl substituents at either the allylic or the geminal positions significantly affect the product yields and the E/Z stereoselectivity. The cross-metathesis reactions of homoallyl malonates with allylic esters featuring a variety of alkyl substituents at the vinylic and/or allylic positions afford trisubstituted olefins. Copyright

Full text of DOI:10.1002/ejoc.201100916

FULL PAPER
DOI: 10.1002/ejoc.201100916
Cross-Metathesis Reactions of Homoallyl Methyl Malonates with Sterically
Hindered Allylic Esters
Fabio Barile,[a] Mauro Bassetti,*[b] Andrea D’Annibale,*[a] Renzo Gerometta,[a] and
Michele Palazzi[a]
Keywords: Metathesis / Alkenes / Cross-coupling / Ruthenium / Homogeneous catalysis
The methyl malonate esters of 3-buten-1-ol and 2-methyl-3-
buten-1-ol can be coupled efficiently to different methallylic
amounts of reagents and to a minor extent on the methallylic
ester functional group. Alkyl substituents at either the allylic
esters in the presence of the second-generation Grubbs cata- or the geminal positions significantly affect the product
lyst to yield trisubstituted olefins by the cross-metathesis re-
action. Product selectivity and yields depend on the relative
yields and the E/Z stereoselectivity.
thetic analysis carried out on compounds A, and the re-
sulting disconnection of their trisubstituted double bond,
clearly indicate CM of homoallyl malonate 1 and allyl es-
ters B as a convenient approach for their preparation.
Whereas allylic esters are known to react efficiently in CM
reactions,[3,7] the use of an olefin bearing a malonate group
as CM partner is rare. The reported cases include the reac-
tion between acrylonitrile and diethyl 2-allylmalonate,
CH2=CHCH2CH(CO2Et)2, which afforded the desired CM
product in good yield,[8] and the incorporation of diallyl
Introduction
Among the various olefin metathesis processes,[1] cross
metathesis (CM) has gained increasing relevance as a con-
venient synthetic tool in organic chemistry.[1,2] This is the
result of the evolution of new catalysts and the advance-
ments in the efficiency, selectivity, and functional group
compatibility of the process. The continuous expansion of
literature data has even led to a general model for predic-
ting the product and stereoselectivity of a cross-metathesis
reaction, depending on the type of catalyst and olefin func-
tionalization.[3] As a consequence, the installation of struc-
tural elements within complex natural products or the syn-
thesis of intermediates for further synthetic transformations
are currently the most significant expressions of olefin CM.
In recent years, our group has focused on the synthesis of
γ- and δ-lactones by different synthetic methodologies, in-
cluding ring-closing metathesis.[4] The development of this
research enhanced our interest in the synthesis of intermedi-
ates of general structure A containing a trisubstituted
double bond (Scheme 1). Taking aside the importance of
trisubstituted double bond subunits in natural products,[2e]
such intermediates could be subsequently transformed into
lactone skeletons, either by an intramolecular metal-cata-
lyzed allylic alkylation (Scheme 1, path a)[5] or by oxidative
radical cyclization (Scheme 1, path b).[6] A concise retrosyn-
[a] Dipartimento di Chimica, Università degli Studi
“La Sapienza”,
P.le Aldo Moro 5, 00185 Roma, Italy
Fax: +39-0649913628
E-mail: andrea.dannibale@uniroma1.it
[b] Istituto di Metodologie Chimiche del CNR, Sezione
Meccanismi di Reazione, and Dipartimento di Chimica,
Università degli Studi “La Sapienza”,
P.le Aldo Moro 5, 00185 Roma, Italy
E-mail: mauro.bassetti@uniroma1.it
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100916.
Scheme 1. Retrosynthetic analysis of bifunctional trisubstituted
olefins as potential precursors of lactone skeletons.
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F. Barile, M. Bassetti, A. D’Annibale, R. Gerometta, M. Palazzi
FULL PAPER
malonate into the backbone of polycyclooctene by a combi-
In the presence of I (5 mol-%), the desired CM product
nation of ring-opening metathesis polymerization (ROMP) 3 was isolated in 56% yield with an E/Z ratio of 9. Al-
and acyclic diene metathesis (ADMET) processes.[9]
though the stereoselectivity is remarkably high, the moder-
These examples indicate that the C–H acidity and the ate yield of the CM derivative may reflect a mild deactivat-
chelating ability of the malonate group are not detrimental ing effect of the malonate group; yields of up to 80% are
to the metathetic process catalyzed by carbene–ruthenium not uncommon for CM reactions involving two monosub-
complexes.[10] However, the reactivity of linear allyl or stituted terminal olefins. Once the compatibility of the β-
homoallyl malonate esters in CM reactions can be regarded diester function in the metathetic process had been verified,
at present as virtually unknown. By contrast, the access to we studied the reactivity of 1a with methallylic esters for
malonate-substituted olefins by CM and therefore to valu- the synthesis of trisubstituted olefins (Scheme 3). When
able intermediates for subsequent transformations would be homoallyl malonate was treated with methallyl acetate
highly desirable, the malonate moiety being one of the most (3.3 equiv. 4a, 3 mol-% I), the CM product 5a was obtained
versatile functional groups for C–C or C–O bond formation with 28% yield with a stereoisomeric ratio E/Z of 3.4. The
in organic synthesis.[11]
result was encouraging and indicated the ability of an olefin
Herein we report on the CM reactions between the bearing a malonate moiety to cross-react with a gem-disub-
methyl homoallyl malonate derivatives of general formula stituted olefin partner, in spite of the increased steric hin-
CH2=CH(CHR)CH2OCOCH2CO2Me [R = H (1a); Me drance of the allylic ester, in the presence of a relatively low
(1b)] and allylic partners with different electronic and steric catalyst load. The reaction between the same partners in
properties. In particular, we have addressed the effect of the a 4:1 molar ratio in the presence of the second-generation
position and steric hindrance of alkyl groups in the allylic Hoveyda–Grubbs catalyst (4 mol-%) afforded the product
moieties on the reaction, which is a key factor in the con- 5a in 21% yield, which indicates a higher activity of the
struction of alkyl-functionalized trisubstituted olefins.
Grubbs catalyst. Therefore the reaction of 1a with methal-
lylic partners 4 in the presence of complex I was investi-
gated more systematically by varying the ester functionali-
ties and the reaction conditions in an attempt to improve
the yields of the trisubstituted olefins. The reactions were
performed with an excess of either the methallyl substrate
or the terminal olefin. Both conditions should assist selec-
tive cross metathesis.[3] The gem-disusbstituted ester, unre-
active towards homodimerization due to the sterically hin-
dered double bond, is expected to undergo the desired reac-
tion with a terminal olefin. Conversely, a monosubstituted
olefin used in excess can undergo both CM with the allylic
ester and homodimerization by self-metathesis. The homo-
dimer can react further with the methallyl ester in a second-
ary metathesis process, thus increasing the conversion into
the desired heterodimer (Scheme 3). The products and
yields obtained under the different conditions are presented
in Table 1.
Results and Discussion
The olefin metathesis experiments were performed with
the second-generation Grubbs catalyst I due to its tolerance
towards polar functional groups and the recognized activity
of the 1,3-disubstituted 4,5-dihydroimidazol-2-ylidene–ru-
thenium complexes in the formation of trisubstituted al-
kenes by CM.[3,12] Homoallyl methyl malonate 1a was pre-
pared by the reaction of 3-buten-1-ol with methyl malonyl
chloride in the presence of NEt3 and obtained as a light-
yellow oil after column chromatography in 70% yield. The
methyl-substituted analogue 1b was obtained similarly from
2-methyl-3-buten-1-ol in 35% yield. To test the compatibil-
ity of the malonate moiety in the CM process, ester 1a was
treated with the monosubstituted allyl acetate (2;
Scheme 2). Olefin 2 was used in 5 equiv. molar excess; in
fact, the reaction between two terminal olefins, expected to
exhibit fast homodimerization rates and similar reactivity
of the homodimers and of the cross-products, requires the
use of one of them in excess to avoid nonselective product
mixtures.[3]
Scheme 3. Primary and secondary cross-metathesis processes in the
reactions between methallylic esters 4 and homoallyl methyl malon-
ate 1a.
Scheme 2. CM reaction between homoallyl methyl malonate 1a and
allyl acetate (2).
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Cross-Metathesis Reactions of Malonates with Allylic Esters
Table 1. Cross-metathesis reactions of homoallyl methyl malonate
1a with methallyl esters 4.
Table 2. Cross-metathesis reactions of homoallyl methyl malonate
1a with tertiary allylic esters 7.[a]
Entry
R
4/1a
Product
Yield
[%][a]
E/Z
Yield of 6
[%][a]
1[b]
2[c]
Me
Me
Me
OEt
OEt
Ph
Ph
Ph
OBn
3.3:1
4:1
1:2
3.1:1
4:1
3.4:1
1:2.5
1:2.5
1:2
5a
5a
5a
5b
5b
5c
5c
5c
5d
28
78
28
24
58
20
43
57
40
3.4
5.0
3.4
3.7
3.7
3.4
3.9
3.4
3.7
–
trace
57
–
3[c]
4[b,d]
5[c]
15
–
6[b]
7[c]
[e]
–
Entry
R1
R2
Product
Yield
[%][b]
E/Z
Yield of 6
8[c,f]
9[c]
–
[e]
[%]
42
1
2
3
4
5
6
Me
Me
Me
OBn
Me
Me
Et
nBu
nC10H21
nBu
8a
8b
8c
8d
8e
8f
31
38
38
34
11
7
20
21
20
24
all E
18
39
42
30
44
74
80
[a] Isolated yield. [b] 3 mol-% I. [c] 4 mol-% I. [d] 22 h. [e] Not de-
termined. [f] Addition of I over 6 h through a syringe pump.
When the methallyl ester was used in about a three-fold
molar excess with respect to 1a, the yields remained in the
range of 20–30%, irrespective of the nature of the ester moi-
ety, which was changed from acetate (Table 1, Entry 1) to
ethyl carbonate (Table 1, Entry 4) to benzoate (Table 1, En-
try 6). The CM efficiency improved appreciably by using
4 mol-% of catalyst I and a four-fold molar excess of the
methallyl substrate (Table 1, Entries 2 and 5), the best yield
and stereoselectivity being obtained in the case of the acet-
ate (78%). In contrast, when using 2 equiv. of homoallyl
methyl malonate, the yield of 5a was the same (28%;
Table 1, Entry 3) as that obtained under the conditions of
Entry 1 (Table 1) and it was accompanied by a significant
amount of the homodimer 6, whereas the yield of the ben-
zoate derivative 5c was appreciably higher (Table 1, En-
try 7). With the same molar ratio, the slow and constant
addition of complex I in dichloromethane (0.015 m) to the
reaction solution of 4c (0.38 m) and 1a over 6 h led to a
significant increase in the amount of CM product (57%;
Table 1, Entry 8).[13,14] In an attempt to reduce the interac-
tions of the coordinating malonate group with the catalyst
and so the presence of an inactive ruthenium species, the
reactions of Entries 1 and 6 (Table 1) were repeated in the
presence of Ti(OiPr)4. Indeed, Ti(OiPr)4 has proved to be a
useful additive in RCM reactions of substrates with oxygen
donor functional groups, in particular olefinic esters, due
to their affinity for the electrophilic metal center.[15] How-
ever, in our case the addition of this Lewis acid led to the
complete inhibition of the reaction when an equimolar
amount with respect to 1 was used under the conditions of
Entry 1 (Table 1), or a 25% yield of 5c when a catalytic
amount was used under the conditions of Entry 7 (Table 1).
We then investigated the influence of increased steric hin-
iPr
cPn[c]
[a] Molar ratio of 7/1a = 4:1. [b] Isolated yield. [c] cPn = cyclo-
pentyl.
The malonate derivatives 8 were prepared with excellent
stereoselectivity; similar features were observed in the CM
products of quaternary allylic olefins.[3] Although the yields
remained low, the involvement of olefins with alkyl substit-
uents at both the geminal and the allylic carbon atoms in
CM reactions is not common. The length of the linear alkyl
chain did not affect the actual outcomes (Table 2, En-
tries 1–3), but greater steric congestion at the allylic carbon
due to the presence of secondary isopropyl or cyclopentyl
groups reduced the CM product yield to around 10%
(Table 2, Entries 5 and 6). In spite of the molar excess of
esters 7, consistent amounts of the homodimer 6 were reco-
vered from these reactions.
The influence of alkyl groups R other than methyl at the
quaternary sp2 carbon in the allylic partner was studied by
treating olefin 1a with acetate esters of general formula
CH2=C(R)CH2OAc (10). These compounds were easily
prepared starting from the corresponding alcohols 9, ac-
cessible by literature procedures (Scheme 4).[16] Esters 10
were then treated with malonate 1a and the results are
shown in Table 3.
drance at the allylic carbon in the CM reaction with homo- Scheme 4. Preparation of compounds 10 (R = Et, Bu, cPn).
allyl methyl malonate. To choose the correct molar ratio
between the two olefin types, the homodimer 6 was treated
When comparing the reactivity of the ethyl-substituted
with ester 7b. No products were observed from the reaction, ester 10a with that of its methyl analogue 4a under identical
which indicates the inability of the internal olefin to partici- reaction conditions (78%; Table 1, Entry 2), it is evident
pate in CM with this ester. Therefore tertiary methallylic that a secondary carbon group causes a significant re-
acetates 7 bearing alkyl groups R2 of increasing steric bulk duction in the yield of the CM product (Table 3, Entry 1),
at the allylic carbon were treated with a four-fold molar which decreases further in the presence of the butyl group
excess of 1a. These conditions resulted in productive CM (Table 3, Entry 2). The CM reaction is suppressed for R =
(Table 2).
cyclopentyl. In addition, there is a complete loss of stereo-
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FULL PAPER
Table 3. Cross-metathesis reactions of homoallyl methyl malonate alized with both the malonate and the allylic ester moieties.
1a with gem-disubstituted allylic acetates 10.[a]
Thus, we have shown that homoallyl malonate derivatives
are reactive CM partners for mono- and 1,1-disubstituted
allylic esters. In the presence of alkyl groups at the allylic
position, the CM products are formed with high E/Z stereo-
selectivity, which is important for the synthesis of naturally
occurring compounds.
Experimental Section
General Methods: 1H and 13C NMR spectra were recorded in
CDCl3 with a 300 MHz Mercury Varian spectrometer. The cali-
bration of spectra was carried out by using solvent signals (CDCl3:
δH = 7.25, δC = 77.0 ppm). The E/Z ratios were determined by
NMR and GC–MS analysis, and the major isomer was deduced by
the NOESY correlation of selected compounds (see the Supporting
Information). IR spectra were recorded with a Shimadzu IR 470
spectrometer in CHCl3 using NaCl cells. GC–MS analyses were
performed with an HP 5890 gas chromatograph linked to an HP
5791 mass spectrometer. HRMS (ESI) spectra were recorded with
a QTOF Micro spectrometer (Waters) operating in positive ion
mode. Chemicals were commercially available and used without
further purification. Dichloromethane was dried by distillation
over P2O5. All the reactions were analyzed by TLC on silica gel
plates (60 F254). Column chromatography was performed on silica
gel 60 (Merck, 70–230 mesh). The CM reactions were performed
under Ar using standard Schlenk techniques. 2-Methyl-2-propenyl
acetate (4a)[17a] and 2-methyl-2-propenyl benzoate (4c)[17b] were
prepared as described in the literature.
Entry
10
R
Product Yield
[%][b]
E/Z
Yield of 6
[%][b]
1
10a
10b
10c
Et
Bu
cPn
11a
11b
n.r.
59
36
–
1:1
1:1
–
–
51
63
2
3[c]
[a] Molar ratio of 10/1a = 4:1. [b] Isolated yield. [c] cPn = cyclo-
pentyl.
selectivity as a result of the comparable steric bulk of the
gem substituents in esters 10.
The methyl-substituted homoallyl methyl malonate 1b
was allowed to react with selected methallylic esters (4a, 7b,
7f) in order to evaluate the effect of steric hindrance on the
malonate partner. The results are shown in Table 4.
Table 4. Cross-metathesis reactions of homoallyl methyl malonate
1b with selected allylic esters 4 and 7.[a]
Homoallyl Methyl Malonates 1a and 1b: Triethylamine (28 mL) was
added to a solution of 3-buten-1-ol (2.03 g, 28 mmol) or 2-methyl-
3-buten-1-ol (2.40 g, 28 mmol) in CH2Cl2 (25 mL) under argon.
The resulting mixture was cooled in an ice bath and then a solution
of methyl 3-chloro-3-oxopropionate (4.9 g, 36 mmol) in CH2Cl2
(15 mL) was added dropwise whilst stirring. The reaction was com-
plete after 3 h (TLC). After addition of aq. 2 n HCl (6 mL), the
reaction mixture was extracted with CH2Cl2 and the organic phase
was washed with aq. sat. NaHCO3 and then with water until neu-
trality. The organic phase was dried (Na2SO4) and the solvent evap-
orated under reduced pressure to give an oily residue, which was
purified by column chromatography (silica gel, light petroleum
ether/Et2O, 7:3) to afford pure compounds 1 as colorless oils
(3.37 g, 70% for 1a; 1.82 g, 35% for 1b). A previous report of 1a
did not report analytical and characterization data.[18]
Entry
Ester
R
Product
Yield
[%][b]
E/Z
Yield of 13
[%]
1
2
3
4a
7b
7f
H
nBu
cPn
12a
12b
n.r.
43
28
–
4
all E
–
45
68
53
[a] Molar ratio of 7/1b = 4:1. [b] Isolated yield.
The presence of the methyl group in 1b resulted in a sig-
nificant decrease in yield with respect to the analogous reac-
tions carried out with malonate 1a. This effect is particu-
larly evident in the case of the methallylic partner 4a (see
for comparison Table 1, Entry 2; 78%) and becomes even
Compound 1a: Colorless oil. IR (CHCl3): ν = 1737, 1462,
˜
1281 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.36 (qt, J = 6.7,
1.5 Hz, 2 H, CH2C=), 3.35 [s, 2 H, CH2(C=O)2], 3.70 (s, 3 H,
OCH3), 4.16 (t, J = 6.7 Hz, 3 H, CH2O), 5.07 (m, 2 H, CH2=), 5.69
larger for esters bearing an alkyl substituent at the allylic (ddt, J = 17.0, 10.3, 6.8 Hz, 1 H, CH=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 31.7, 41.3, 52.4, 64.7, 117.4, 133.5, 166.3, 166.8 ppm.
GC–MS (EI, 70 eV): m/z (%) = 101 (100), 59 (40), 55 (30), 54 (84).
position. In fact, the presence of a secondary cyclopentyl
group inhibits the CM reaction. In all cases, the homodimer
13 from the self-metathesis of 1b was obtained. Note that
only the E isomer was isolated from the reaction with 7b.
Compound 1b: Colorless oil. IR (CHCl3): ν = 2950, 1750,
˜
1
1326 cm–1. H NMR (300 MHz, CDCl3): δ = 1.00 (d, J = 6.6 Hz,
3 H, CH3CH), 2.50 (sext., J = 6.6 Hz, 1 H, CHCH3), 3.34 [s, 2 H,
CH2(C=O)2], 3.70 (s, 3 H, OCH3), 3.99 (m, 2 H, CH2O), 5.03 (m,
2 H, CH2=), 5.69 (ddd, J = 17.6, 10.3, 7.3 Hz, CH=) ppm. 13C
NMR (75 MHz, CDCl3): δ = 16.2, 36.7, 41.2, 52.2, 69.1, 115.0,
139.5, 166.3, 166.8 ppm. HRMS (ESI): calcd. for C9H14O4+Na [M
+ Na]+ 209.0790; found 209.0794.
Conclusions
The cross-metathesis reactions of malonate esters
CH2=CHCH(R)CH2OCOCH2CO2Me (R = H, Me) with
methallyl esters CH2=C(R3)CH(OCOR1)R2 featuring dif-
1-Acetoxy-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-pentene (3): Allyl
ferent alkyl groups afforded trisubstituted olefins function- acetate 2 (1.32 g, 13.2 mmol) and ester 1a (419 mg, 2.4 mmol) were
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Cross-Metathesis Reactions of Malonates with Allylic Esters
added whilst stirring to a CH2Cl2 solution (20 mL) of catalyst I = 140 (40), 98 (100), 80 (96), 81 (64), 59 (36). HRMS (ESI): calcd.
(78 mg, 0.092 mmol). After 22 h at reflux, the solvent was removed
under reduced pressure and the oily residue was purified by column
chromatography (silica gel, light petroleum ether/Et2O, 7:3) to af-
for C12H18O6Na [M + Na]+ 281.1001; found 281.1005.
Ethyl 2Ј-Methyl-5Ј-(3ЈЈ-methoxy-3ЈЈ-oxopropionyloxy)pent-2Ј-enyl
Carbonate (5b, Table 1, Entries 4 and 5): Colorless oil; E/Z = 3.7:1.
ford pure compound 3 as a colorless oil (0.33 g, 56%). IR (CHCl3):
IR (CHCl ): ν = 2934, 1748, 1716, 1420, 1362, 1232 cm–1. 1H NMR
˜
3
1
ν = 3010, 1735, 1430, 1240, 1100, 1020 cm–1. H NMR (300 MHz,
˜
(300 MHz, CDCl3): δ = 1.27 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.66
(s, 3 H, E isomer, CH3C=), 1.76 (s, 3 H, Z isomer, CH3C=), 2.40
(m, 2 H, CH2CH2CH=), 3.33 [s, 2 H, CH2(C=O)2], 3.70 (s, 3 H,
OCH3), 4.13 (m, 4 H, CH3CH2O), 4.47 (s, 2 H, E isomer,
CH2OC=O), 4.59 (s, 2 H, Z isomer, CH2OC=O), 5.36 (m, 1 H, E
isomer, CH=), 5.44 (m, 1 H, Z isomer) ppm. 13C NMR (75 MHz,
CDCl3): δ = 13.9, 14.2, 21.3, 27.0, 27.1, 41.2, 52.4, 63.9, 64.4, 65.9,
72.7, 124.1, 125.6, 132.7 ppm. GC–MS (EI, 70 eV): m/z (%) = 170
(23), 101 (50), 81 (88), 80 (100), 79 (53), 69 (33), 59 (35). HRMS
(ESI): calcd. for C13H20O7Na [M + Na]+ 311.1107; found 311.1112.
CDCl3): δ = 1.97 (s, 3 H, CH3CO), 2.37 (m, 2 H, CH2CH2CH=),
3.30 [s, 2 H, CH2(C=O)2], 3.65 (s, 3 H, OCH3), 4.09 (t, J = 6.7 Hz,
2 H, Z isomer, CH2CH2O), 4.10 (t, J = 6.7 Hz, 2 H, E isomer,
CH2CH2O), 4.43 (d, J = 5.4 Hz, 2 H=, E isomer, OCH2CH), 4.53
(d, J = 5.4 Hz, 2 H, Z isomer, OCH2CH=), 5.60 (m, 2 H,
CH=CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.7, 26.7, 31.2,
41.0, 52.3, 59.9, 64.1, 64.2, 64.5, 126.3, 126.8, 129.3, 130.3, 166.2,
166.7, 170.5 ppm. HRMS (ESI): calcd. for C11H16O6Na [M +
Na]+ 267.0845; found 267.0847.
General Procedure for Preparation of Methallyl Carbonates 4b and
4d: A solution of 2-methyl-2-propen-1-ol (1.17 mL, 13.9 mmol) and
the desired ethyl or benzyl chloroformate (20 mmol) in CH2Cl2
(36 mL) was cooled to 0 °C. Pyridine (1.61 mL, 20 mmol) was
added dropwise over 45 min. After 12 h, the reaction mixture was
diluted with additional CH2Cl2 (10 mL), washed with 2 n HCl
(2ϫ10 mL), then with aq. sat. NaHCO3 (3ϫ5 mL). The organic
phase was dried with Na2SO4 and the solvent removed under re-
duced pressure. The resulting oily residue was purified by column
chromatography (silica gel, light petroleum ether/Et2O, 95:5) to af-
ford pure 4.
1-Benzoyloxy-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-methyl-2-
pentene (5c, Table 1, Entries 6–8): Colorless oil. IR (CHCl ): ν =
˜
3
2950, 1718, 1452, 1386, 1315, 1274, 1177, 1070 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 1.74 (s, 3 H, E isomer, CH3C=), 1.85 (s, 3
H, Z isomer, CH3C=), 2.44 (m, 2 H, CH2CH2CH=), 3.35 [s, 2 H,
CH2(C=O)2], 3.72 (s, 3 H, OCH3), 4.07 (t, J = 6.9 Hz, 2 H, Z
isomer, OCH2CH2), 4.09 (t, J = 6.9 Hz, 2 H, E isomer, OCH2CH2),
4.71 (s, 2 H, E isomer, CH2OBz), 4.83 (s, 2 H, Z isomer, CH2OBz),
5.36 (m, 1 H, Z isomer, CH=), 5.53 (m, 1 H, E isomer, CH=), 7.43
(m, 2 H, Ar), 7.55 (tt, J = 7.4, 1.3 Hz, 1 H, Ar), 8.03 (m, 2 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.5, 15.6, 21.3, 21.9,
27.6, 27.7, 63.9, 64.1, 66.2, 70.4, 124.4, 125.9, 128.7, 130.0, 130.6,
133.3, 133.5, 166.7, 171.4 ppm. GC–MS (EI, 70 eV): m/z (%) = 105
Ethyl 2-Methyl-2-propenyl Carbonate (4b): Colorless oil; yield:
77%. IR (CHCl ): ν = 2980, 1740, 1480, 1400, 1290 cm–1. 1H NMR
˜
3
(300 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 3 H, CH3CH2), 1.73 (100), 77 (18). HRMS (ESI): calcd. for C17H20O6Na [M + Na]+
(s, 3 H, CH3C=), 4.16 (q, J = 7.1 Hz, 2 H, CH3CH2O), 4.49 (s, 2 H,
CH2O), 4.94 (m, 2 H, CH2=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 14.2, 19.3, 63.9, 70.9, 113.3, 139.4, 155.0 ppm. HRMS (ESI):
calcd. for C7H12O3Na [M + Na]+ 167.0684; found 167.0690.
343.1158; found 343.1156.
Benzyl 2Ј-Methyl-5Ј-(3ЈЈ-methoxy-3ЈЈ-oxopropionyloxy)pent-2Ј-enyl
Carbonate (5d, Table 1, Entry 9): Colorless oil; yield: 40%; E/Z =
3.7:1. IR (CHCl ): ν = 2910, 1750, 1722, 1453, 1390, 1265 cm–1.
˜
3
Benzyl 2-Methyl-2-propenyl Carbonate (4d): Colorless oil; yield: 1H NMR (300 MHz, CDCl3): δ = 1.68 (s, 3 H, E isomer, CH3C=),
41%. IR (CHCl ): ν = 2965, 1742, 1398, 1282 cm–1. 1H NMR
1.78 (s, 3 H, Z isomer, CH3C=), 2.40 (q, J = 7.3 Hz, 2 H,
OCH2CH2CH=), 3.36 [s, 3 H, CH2(C=O)2], 3.73 (s, 3 H, OCH3),
4.14 (t, J = 6.6 Hz, 2 H, OCH2CH2), 4.53 (s, 2 H, E isomer,
PhCH2), 4.64 (s, 2 H, PhCH2), 5.46 (t, J = 7.3 Hz, 1 H, CH=), 7.36
˜
3
(300 MHz, CDCl3): δ = 1.77 (s, 3 H, CH3C=), 4.56 (s, 2 H, CH2O),
4.97 (m, 2 H, CH2=), 5.17 (s, 2 H, OCH2Ph), 7.37 (m, 5 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.2, 69.5, 71.1, 113.5,
128.2, 128.4, 128.5, 135.3, 139.3, 155.0 ppm. GC–MS (EI, 70 eV): (m, 5 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.8, 27.0,
m/z (%) = 151 (16), 107 (14), 91 (100). HRMS (ESI): calcd. for
41.2, 52.3, 64.3, 69.6, 73.0, 124.2, 132.6, 135.2, 154.9, 166.3,
166.7 ppm. GC–MS (EI, 70 eV): m/z (%) = 170 (7), 101 (10),97
(24), 91 (100), 81 (16). HRMS (ESI): calcd. for C18H22O7Na [M +
Na]+ 373.1263; found 373.1265.
C12H14O3Na [M + Na]+ 229.0841; found 229.0834.
General CM Procedure for the Synthesis of Compounds 5: Homoal-
lyl malonate 1a (0.5 mmol) and up to 4 equiv. of ester 4 (2.0 mmol)
were dissolved in CH2Cl2 (10 mL). The mixture was heated at re-
flux and a solution of catalyst I (0.015 or 0.02 mmol) in CH2Cl2
(6 mL) was added dropwise through a syringe pump over 45 min.
The mixture was heated at reflux for 15 h. Removal of solvent un-
der reduced pressure afforded an oily residue that was purified by
column chromatography (silica gel, light petroleum ether/Et2O, 8:2)
to afford pure compound 5 and homodimer 6, both as colorless
oils. Reaction yields are reported in Table 1.
1,5-Bis(3Ј-methoxy-3Ј-oxopropionyloxy)-3-pentene (6, Table 1, En-
tries 3, 5, 9, Table 2, Table 3): Colorless oil; E/Z mixture. IR
(CHCl ): ν = 2974, 1725, 1489, 1358, 1249 cm–1. 1H NMR
˜
3
(300 MHz, CDCl3): δ = 2.33 (m, 4 H, OCH2CH2CH=), 3.38 [s, 4
H, CH2(C=O)2], 3.74 (s, 6 H, OCH3), 4.15 (t, J = 7.3 Hz, 4 H,
OCH2CH2), 5.49 (m, 2 H, CH=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 31.7, 41.2, 52.3, 64.7, 128.1, 166.3, 166.8 ppm. HRMS
(ESI): calcd. for C14H20O8Na [M + Na]+ 339.1056; found 339.1049.
1-Acetoxy-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-methyl-2-pentene
General Procedure for the Synthesis of Esters 7: A solution of meth-
(5a, Table 1, Entries 1–3): Colorless oil. IR (CHCl ): ν = 3010, acrolein (3.0 mmol) was cooled in an ice bath under argon and the
˜
3
1743, 1446, 1390, 1345, 1291 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 1.64 (s, 3 H, E isomer, CH3C=), 1.74 (s, 3 H, Z isomer,
CH3C=), 2.04 (s, 3 H, Z isomer, CH3CO), 2.05 (s, 3 H, E isomer,
appropriate Grignard reagent (BrMgR2; R2 = Et, Bu, nC10H11, iPr,
or cPn; 4.5 mmol, 2 m solution in THF) was added dropwise whilst
stirring. After 4 h, the reaction mixture was poured into water
CH3CO), 2.40 (m, 2 H, CH2CH2CH=), 3.35 [s, 2 H, CH2(C=O)2], (10 mL) and aq. 6 n HCl was added dropwise until the solid dis-
3.71 (s, 3 H, OCH3), 4.12 (t, J = 6.6 Hz, 2 H, OCH2CH2), 4.42 (s, solved completely. After addition of CH2Cl2 (30 mL), the separated
2 H, E isomer, CH2OAc), 4.54 (s, 2 H, Z isomer, CH2OAc), 5.38
organic phase was washed with aq. sat. NaHCO3, then with water,
and finally dried (Na2SO4). Removal of solvent under reduced pres-
(m, 1 H, CH=) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.9, 20.7,
20.8, 21.4, 26.9, 27.0, 41.2, 52.4, 64.4, 64.6, 68.2, 123.4, 124.9, sure afforded the desired crude methallyl alcohols as oils. Acetates
133.1, 166.3, 166.8, 170.7, 170.8 ppm. GC–MS (EI, 70 eV): m/z (%) 7a–c,e,f were obtained by reaction of the methallyl alcohol
Eur. J. Org. Chem. 2011, 6519–6526
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6523

F. Barile, M. Bassetti, A. D’Annibale, R. Gerometta, M. Palazzi
FULL PAPER
CH2=C(Me)CH(R2)OH with acetic anhydride in pyridine, whereas
carbonate 7d was obtained by reaction of CH2=C(Me)CH(Bu)OH
with benzoyl chloride in dichloromethane. The products were puri-
fied by column chromatography.
tion flask at 40 °C, a solution of catalyst I (4 mol-%) in CH2Cl2
(6 mL) was added dropwise over 45 min. The reaction was kept at
reflux for 15 h and then the solvent was removed under reduced
pressure. The oily residue was purified by column chromatography
(silica gel, light petroleum ether/Et2O, 8:2) to afford pure products
8 or 11 and homodimer 6.
3-Acetoxy-2-methyl-1-pentene (7a): Colorless oil; obtained from
CH =C(Me)CH(Et)OH; yield: 92%. IR (CHCl ): ν = 2945, 1723,
˜
2
3
1462, 1383, 1278, 1018 cm–1. 1H NMR (300 MHz, CDCl3): δ =
0.85 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.63 (quint., J = 7.3 Hz, 2 H,
CH3CH2), 1.69 (s, 3 H, CH3C=), 2.04 (s, 3 H, CH3CO), 4.88 (m,
2 H, CH2=), 5.07 (t, J = 7.3 Hz, 1 H, CHO) ppm. 13C NMR
(75 MHz, CDCl3): δ = 9.6, 18.0, 21.1, 25.5, 78.5, 108.3, 112.6,
170.1 ppm. HRMS (ESI): calcd. for C8H14O2Na [M + Na]+
165.0891; found 165.0895.
1-(3Ј-Methoxy-3Ј-oxopropionyloxy)-5-acetoxy-4-methyl-3-heptene
(8a): Colorless oil; yield: 31%; E/Z = 20. IR (CHCl ): ν = 2970,
˜
3
1730, 1463, 1382, 1284, 1148, 1021 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 0.80 (t, J = 7.3 Hz, 3 H, CH2CH3), 1.60 (s, 3 H,
CH3C=), 1.65 (m, 2 H, CH2CH3), 2.03 (s, 3 H, CH3CO), 2.36 (q,
J = 7.3 Hz, 2 H, CH2CH=), 3.35 [s, 2 H, CH2(C=O)2], 3.72 (s, 3
H, OCH3), 4.12 (t, J = 7.0 Hz, 2 H, CH2CH2O), 5.01 (t, J = 7.3 Hz,
1 H, CHO), 5.37 (t, J = 7.3 Hz, 1 H, E isomer, CH=), 5.59 (t, J =
7.3 Hz, 1 H, Z isomer, CH=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 9.7, 11.9, 21.1, 25.5, 27.0, 41.2, 52.4, 64.6, 80.1, 122.5, 136.1,
166.4, 166.8, 170.2 ppm. GC–MS (EI, 70 eV): m/z (%) = 126 (45),
109 (36), 108 (52), 101 (25), 97 (100), 93 (71), 59 (28), 57 (34).
HRMS (ESI): calcd. for C14H22O6Na [M + Na]+ 309.1314; found
309.1310.
3-Acetoxy-2-methyl-1-heptene (7b): Colorless oil; obtained from
CH =C(Me)CH(Bu)OH; yield: 79%. IR (CHCl ): ν = 3060, 1727,
˜
2
3
1446, 1260, 1021 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.96 [t, J
= 6.6 Hz, 3 H, (CH2)3CH3], 1.43 (m, 6 H, CH2CH2CH2), 1.71 (s,
3 H, CH3C=), 2.01 (s, 3 H, CH3CO), 4.90 (m, 2 H, CH2=), 5.12
(t, J = 6.6 Hz, 1 H, CHO) ppm. 13C NMR (75 MHz, CDCl3): δ =
13.9, 17.4, 17.7, 23.2, 26.9, 31.5, 83.2, 107.2, 150.0, 171.5 ppm.
HRMS (ESI): calcd. for C10H18O2Na [M + Na]+ 193.1204; found
193.1200.
1-(3Ј-Methoxy-3Ј-oxopropionyloxy)-5-acetoxy-4-methyl-3-nonene
(8b): Colorless oil; yield: 38%; E/Z = 21. IR (CHCl ): ν = 2965,
˜
3
1730, 1464, 1383, 1150, 1016 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 0.87 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.23 (m, 4 H, CH2CH2),
1.57 (m, 2 H, CH2), 1.60 (s, 3 H, CH3C=), 2.01 (s, 3 H, CH3CO),
2.36 (q, J = 7.3 Hz, 2 H, CH2CH=), 3.35 [s, 2 H, CH2(C=O)2],
3.73 (s, 3 H, OCH3), 4.12 (t, J = 7.3 Hz, 2 H, CH2O), 5.08 (t, J =
7.3 Hz, 1 H, CHO), 5.37 (t, J = 7.3 Hz, 1 H, E isomer, CH=), 5.55
(t, J = 7.3 Hz, 1 H, Z isomer, CH=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 12.0, 13.9, 21.7, 22.3, 27.0, 27.6, 32.3, 41.2, 52.4, 64.5,
78.9, 122.3, 136.5, 166.4, 166.8, 170.2 ppm. GC–MS (EI, 70 eV):
m/z (%) = 154 (37), 136 (31), 101 (24), 97 (100), 93 (63), 81 (26),
59 (24), 57 (25). HRMS (ESI): calcd. for C16H26O6Na [M + Na]+
337.1627; found 337.1625.
3-Acetoxy-2-methyl-1-tridecene (7c): Colorless oil; obtained from
CH =C(Me)CH(nC H )OH; yield: 66%. IR (CHCl ): ν = 2925,
˜
2
10 11
3
1736, 1471, 1386, 1078 cm–1. 1H NMR (300 MHz, CDCl3): δ =
0.86 [t, J = 6.6 Hz, 3 H, (CH2)9CH3], 1.42 [m, 18 H, (CH2)9], 1.71
(s, 3 H, CH3C=), 2.01 (s, 3 H, CH3CO), 4.90 (m, 2 H, CH2=), 5.13
(t, J = 6.6 Hz, 1 H, CHO) ppm. 13C NMR (75 MHz, CDCl3): δ =
14.1, 18.1, 21.2, 22.7, 25.4, 25.5, 29.4, 29.6, 29.7, 32.0, 77.5, 112.6,
143.4, 170.3 ppm. HRMS (ESI): calcd. for C16H30O2Na [M +
Na]+ 277.2143; found 277.2145.
Benzyl 2Ј-Methylhept-1Ј-en-3Ј-yl Carbonate (7d): Colorless oil; ob-
tained from CH =C(Me)CH(Bu)OH; yield: 35%. IR (CHCl ): ν =
˜
2
3
2965, 1735, 1462, 1394, 1200 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 0.98 [t, J = 7.3 Hz, 3 H, (CH2)3CH3], 1.32 (m, 4 H, CH2CH2),
1.70 (m, 2 H, CH2), 1.75 (s, 3 H, CH3C=), 4.60 (s, 2 H, CH2Ph),
5.00 (m, 3 H, CHO, CH2=), 7.38 (m, 5 H, Ar) ppm. 13C NMR
(75 MHz, CDCl3): δ = 13.8, 17.7, 22.3, 27.3, 32.3, 69.3, 81.8, 113.3,
128.2, 128.3, 128.5, 135.5, 142.7, 154.7 ppm. HRMS (ESI): calcd.
for C16H22O3Na [M + Na]+ 285.1467; found 285.1473.
1-(3Ј-Methoxy-3Ј-oxopropionyloxy)-5-acetoxy-4-methyl-3-penta-
decene (8c): Colorless oil; yield: 38%; E/Z = 20. IR (CHCl ): ν =
˜
3
2953, 1750, 1480, 1290, 1200 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 0.86 (t, J = 7.3 Hz, 3 H, CH2CH3), 1.23 [m, 18 H, CH2-
(CH2)8], 1.59 (s, 3 H, CH3C=), 2.02 (s, 3 H, CH3CO), 2.38 (q, J =
7.3 Hz, 2 H, CH2CH=), 3.35 [s, 2 H, CH2(C=O)2], 3.73 (s, 3 H,
OCH3), 4.12 (t, J = 7.3 Hz, 2 H, CH2CH2O), 5.08 (m, 1 H,
CHOAc), 5.37 (t, J = 7.3 Hz, 1 H, E isomer, CH=), 5.54 (t, J =
7.3 Hz, 1 H, Z isomer, CH=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 12.1, 14.2, 15.3, 15.8, 15.9, 16.0, 17.5, 18.2, 18.6, 29.4, 29.6, 32.0,
32.7, 41.4, 52.5, 64.7, 76.5, 122.4, 136.7, 166.5, 167.0, 170.3 ppm.
HRMS (ESI): calcd. for C22H38O6Na [M + Na]+ 421.2566; found
421.2571.
3-Acetoxy-2,4-dimethyl-1-pentene (7e): Colorless oil; obtained from
CH =C(Me)CH(iPr)OH; yield: 55%. IR (CHCl ): ν = 2965, 1735,
˜
2
3
1462, 1394, 1200 cm–1. 1H NMR (300 MHz, CDCl3): δ = 085 (d, J
= 6.6 Hz, 3 H, CH3CH), 0.89 (d, J = 6.6 Hz, 3 H, CH3CH), 1.68
(s, 3 H, CH3C=), 1.90 [m, 1 H, CH(CH3)2], 2.05 (s, 3 H, CH3CO),
4.89 (m, 3 H, CHO, CH2=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 17.9, 18.3, 19.0, 21.0, 29.7, 82.4, 113.6, 142.4, 170.3 ppm. HRMS
(ESI): calcd. for C9H16O2Na [M + Na]+ 179.1048; found 179.1044.
Benzyl 1Ј-(3ЈЈ-Methoxy-3ЈЈ-oxopropionyloxy)-4Ј-methylnon-3Ј-ene-
5Ј-yl Carbonate (8d): Colorless oil; yield: 34 %; E/Z = 24. IR
3-Acetoxy-3-cyclopentyl-2-methyl-1-propene (7f): Colorless oil; ob-
(CHCl ): ν = 3160, 1783, 1432, 1325, 1169, 1043 cm–1. 1H NMR
˜
3
tained from CH =C(Me)CH(cPn)OH; yield: 78%. IR (CHCl ): ν
˜
2
3
(300 MHz, CDCl3): δ = 0.91 (t, J = 7.3 Hz, 3 H, CH2CH3), 1.31
(m, 4 H, CH2CH2), 1.65 (s, 3 H, overlapped, CH3C=), 1.67 (m, 2
H, CH2), 2.42 (q, J = 7.3 Hz, 2 H, CH2CH=), 3.40 [s, 2 H,
CH2(C=O)2], 3.76 (s, 3 H, OCH3), 4.16 (t, J = 7.0 Hz, 2 H,
CH2CH2O), 4.99 (t, J = 7.3 Hz, 1 H, CHO), 5.16 (s, 2 H, OCH2Ph),
5.47 (t, J = 7.0 Hz, 1 H, E isomer, CH=), 5.65 (t, J = 7.0 Hz, 1 H,
Z isomer, CH=), 7.34 (m, 5 H, Ar) ppm. 13C NMR (75 MHz,
CDCl3): δ = 11.7, 13.8, 22.3, 26.9, 27.4, 32.2, 41.5, 52.3, 64.4, 69.3,
83.4, 123.2 ppm. GC–MS (EI, 70 eV): m/z (%) = 136 (15), 107 (13),
94 (30), 93 (100), 81 (16), 79 (22), 59 (15). HRMS (ESI): calcd. for
C22H30O7Na [M + Na]+ 429.1889; found 429.1891.
= 2944, 1738, 1423, 1372, 1225 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 1.38 (m, 8 H, CH2CH2CH2CH2), 1.71 (s, 3 H, CH3C=), 1.97
(m, 1 H, CH2CHCH2), 2.06 (s, 3 H, CH3CO), 4.53 (d, J = 7.2 Hz,
1 H, CHO), 4.96 (m, 2 H, CH2=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.0, 23.8, 25.0, 31.4, 32.7, 43.5, 66.8, 110.0, 147.4,
170.7 ppm. HRMS (ESI): calcd. for C11H18O2Na [M + Na]+
205.1204; found 205.1206.
General Procedure for the Synthesis of Esters 8, 11, and 12: Com-
pound 1 (0.5 mmol) and methallyl esters 7 or 10 (2 mmol) were
dissolved in CH2Cl2 (10 mL) under argon. While keeping the reac-
6524
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6519–6526

Cross-Metathesis Reactions of Malonates with Allylic Esters
1-(3Ј-Methoxy-3Ј-oxopropionyloxy)-5-acetoxy-4,6-dimethyl-3- a 2 m solution of an appropriate Grignard reagent (16 mL,
heptene (8e): Colorless oil; yield: 11%; E isomer. IR (CHCl ): ν =
32.0 mmol) was added dropwise over a period of 45 min. After 6 h,
satd. aq. NH4Cl (15 mL) was added to the reaction mixture while
˜
3
2970, 1740, 1422, 1311, 1198 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 0.81 (d, J = 7.0 Hz, 3 H, CH3CH), 0.90 (d, J = 7.0 Hz, 3 H, keeping the flask at 0 °C. The biphasic mixture was then separated
CH3CH), 1.61 (s, 3 H, overlapped, CH3C=), 1.68 (m, 2 H, over-
lapped, CH2CH=), 2.07 (s, 3 H, CH3CO), 2.42 [m, 1 H, CH-
(CH3)2], 3.40 [s, 2 H, CH2(C=O)2], 3.76 (s, 3 H, OCH3), 4.17 (m,
and the aqueous phase was extracted with Et2O (2ϫ20 mL). The
combined organic phases were washed with water and dried
(Na2SO4). Removal of the solvent under reduced pressure afforded
2 H, CH2O), 4.81 (m, 1 H, CHO), 5.39 (m, 1 H, CH=) ppm. 13C an oily residue, which was purified by column chromatography (sil-
NMR (75 MHz, CDCl3): δ = 18.5, 19.0, 20.3, 26.5, 29.8, 41.4, 52.6, ica gel, light petroleum ether/Et2O, 9:1) to give pure alcohols 9.
64.4, 123.1, 136.7, 123.8, 133.2, 166.4, 166.8, 170.5 ppm. HRMS
The alcohols were subsequently converted into esters 10 by reaction
with acetyl chloride/Et3N in CH2Cl2. The esters 10 were purified
by distillation at atmospheric pressure.
(ESI): calcd. for C15H24O6Na [M + Na]+ 323.1471; found 323.1475.
1-Acetoxy-1-cyclopentyl-2-methyl-5-(3Ј-methoxy-3Ј-oxopropion-
yloxy)-2-pentene (8f): Colorless oil; yield: 7 %; E/Z = 18. IR
2-Ethyl-2-propen-1-ol (9a): Colorless oil; yield: 55%. IR (CHCl3):
1
ν = 3625, 2946, 1465, 1029 cm–1. H NMR (300 MHz, CDCl ): δ
(CHCl ): ν = 2934, 1725, 1430, 1350, 1250 cm–1 1H NMR
.
˜
˜
3
3
= 1.04 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.94 (q, J = 7.3 Hz, 2 H,
CH3CH2), 2.05 (br. s, 1 H, OH), 4.05 (s, 2 H, CH2O), 4.88 (m, 1 H,
CHA=), 4.99 (m, 1 H, CHB=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 12.2, 25.8, 66.0, 108.1, 150.8 ppm. Spectral data are in agreement
with those reported in the literature.[19a]
(300 MHz, CDCl3): δ = 1.53 [m, 8 H, overlapped, CH2(CH2)2CH2],
1.59 (s, 3 H overlapped, CH3C=), 1.67 (m, 2 H, CH2CH=), 2.01 (s,
3 H, E isomer, CH3CO), 2.02 (s, 3 H, Z isomer, CH3CO), 2.35 (m,
1 H, CH of cyclopentyl), 3.35 [s, 2 H, CH2(C=O)2], 3.72 (s, 3 H,
OCH3), 4.11 (d, J = 7.3 Hz, 1 H, E isomer, CHO), 4.14 (d, J =
7.3 Hz, 1 H, Z isomer, CHO), 5.38 (m, 1 H, E isomer, CH=), 5.56
(m, 1 H, Z isomer, CH=) ppm. 13C NMR (75 MHz, CDCl3): δ =
17.3, 25.4, 27.0, 27.1, 29.1, 41.4, 41.8, 52.5, 64.7, 83.3, 123.5,
139.2 ppm. HRMS (ESI): calcd. for C17H26O6Na [M + Na]+
349.1627; found 349.1629.
2-n-Butyl-2-propen-1-ol (9b): Colorless oil; yield: 24%. IR (CHCl3):
1
ν = 3630, 2935, 1239, 1043 cm–1. H NMR (300 MHz, CDCl ): δ
˜
3
= 0.87 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.34 (m, 4 H, CH3CH2CH2),
2.02 [t, J = 7.3 Hz, 2 H, CH3(CH2)2CH2C =], 2.21 (t, J = 5.8 Hz,
1 H, OH), 4.02 (d, J = 5.8 Hz, 2 H, CH2O), 4.83 (m, 1 H, CHA=),
4.98 (m, 1 H, CHB=) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.0,
22.6, 30.0, 32.8, 65.9, 109.0, 149.3 ppm. Spectral data are in agree-
ment with those reported in the literature.[19b]
1-Acetoxy-2-ethyl-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-pentene
(11a): Colorless oil; yield: 59%; E/Z = 1. IR (CHCl ): ν = 2970,
˜
3
1730, 1423, 1382, 1284, 1148, 1021 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 0.98 (t, J = 7.3 Hz, 3 H, E isomer, CH3CH2), 1.00 (t,
J = 7.3 Hz, 3 H, Z isomer, CH3CH2), 2.04 (s, 3 H, E isomer, over-
lapped, CH3CO), 2.05 (s, 3 H, Z isomer, overlapped, CH3CO), 2.06
(m, 2 H, CH3CH2), 2.40 (q, J = 7.3 Hz, 2 H, E isomer, OCH2CH2),
2.44 (q, J = 7.3 Hz, 2 H, Z isomer, OCH2CH2), 3.37 [s, 2 H,
CH2(C=O)2], 3.73 (s, 3 H, OCH3), 4.13 (t, J = 6.6 Hz, 2 H, E
isomer, OCH2CH2), 4.14 (t, J = 6.6 Hz, 2 H, Z isomer, OCH2CH2),
4.48 (s, 2 H, E isomer, CH2OAc), 4.58 (s, 2 H, Z isomer, CH2OAc),
5.32 (t, J = 6.6 Hz, 1 H, E isomer, CH=), 5.40 (t, J = 6.6 Hz, 1 H,
Z isomer, CH=) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.0, 21.5,
26.7, 41.4, 52.6, 61.9, 64.8, 67.7, 123.5, 139.1, 166.5, 167.0,
170.9 ppm. GC–MS (EI, 70 eV): m/z (%) = 126 (45), 109 (36), 108
(52), 101, (25), 97 (100), 93 (71), 59 (28), 57 (34). HRMS (ESI):
calcd. for C13H20O6Na [M + Na]+ 295.1158; found 295.1162.
2-Cyclopentyl-2-propen-1-ol (9c): Colorless oil; yield: 24 %. IR
(CHCl ): ν = 3628, 2972, 1198, 1030 cm–1. 1H NMR (300 MHz,
˜
3
CDCl3): δ = 1.15–1.82 [m, 8 H, CH2(CH2)2CH2], 2.42 (quint., J =
8.3 Hz, 1 H, CH of cyclopentyl), 4.10 (s, 2 H, CH2O), 4.88 (m, 1 H,
CHA=), 4.94 (m, 2 H, CHB=) ppm. 13C NMR (75 MHz, CDCl3): δ
= 24.9, 31.5, 43.1, 65.7, 106.9, 150.2 ppm. Spectral data are in
agreement with those reported in the literature.[19c]
2-Ethylallyl Acetate (10a): Colorless oil; yield: 64%. IR (CHCl ): ν
˜
3
= 2980, 1741, 1582, 1425, 1312, 1193 cm–1 1H NMR (300 Hz,
.
CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3 H, CH3CH2), 2.01 (q, J = 7.3 Hz,
2 H, CH3CH2), 2.07 (s, 3 H, CH3CO), 4.51 (s, 2 H, CH2O), 4.89
(m, 1 H, CHA=), 5.00 (m, 1 H, CHB=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 12.0, 21.0, 26.1, 67.0, 111.1, 145.7, 170.8 ppm. HRMS
(ESI): calcd. for C7H12O2Na [M + Na]+ 151.0735; found 151.0734.
1-Acetoxy-2-butyl-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-pentene
2-Butylallyl Acetate (10b): Colorless oil; yield: 53%. IR (CHCl ): ν
˜
3
(11b): Colorless oil; yield: 36%; E/Z = 1. IR (CHCl ): ν = 2990,
˜
3
= 2950, 1733, 1462, 1391, 1295, 1037 cm–1 1H NMR (300 Hz,
.
1742, 1462, 1310, 1258, 1040 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 0.87 (t, J = 7.3 Hz, 3 H, E isomer, CH3CH2), 0.89 (t, J =
7.3 Hz, 3 H, Z isomer, CH3CH2), 1.32 (m, 4 H, CH3CH2CH2), 2.04
(s, 3 H, E isomer, overlapped, CH3CO), 2.06 (s, 3 H, Z isomer,
overlapped, CH3CO), 2.07 (m, 2 H, CH2CH2C=), 2.40 (q, J =
7.3 Hz, 2 H, E isomer, OCH2CH2CH=), 2.43 (q, J = 7.3 Hz, 2 H,
Z isomer, OCH2CH2CH=), 3.36 [s, 2 H, E isomer, CH2(C=O)2],
3.37 [s, 2 H, Z isomer, CH2(C=O)2], 3.72, (s, 3 H, OCH3), 4.10 (t,
J = 6.6 Hz, 2 H, E isomer, OCH2CH2), 4.11 (t, J = 6.6 Hz, 2 H, Z
isomer, OCH2CH2), 4.47 (s, 2 H, E isomer, CH2OAc), 4.56 (s, 2 H,
Z isomer, CH2OAc), 5.36 (t, J = 7.3 Hz, 1 H, E isomer, CH=), 5.40
(t, J = 7.3 Hz, 1 H, Z isomer, CH=) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.0, 22.8, 27.1, 28.2, 30.52, 41.4, 52.5, 61.8, 64.8,
68.0, 123.9, 125.0, 137.7, 166.9, 167.0, 170.8 ppm. HRMS (ESI):
calcd. for C15H24O6Na [M + Na]+ 323.1471; found 323.1465.
CDCl3): δ = 0.88 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.38 (m, 4 H,
CH3CH2CH2), 2.04 [q, J = 7.3 Hz, 2 H, CH3(CH2)2CH2C=], 2.06
(s, 3 H, CH3CO), 4.49 (s, 2 H, CH2O), 4.90 (m, 1 H, CHA=), 4.98
(m, 1 H, CHB=) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.9, 20.9,
22.4, 29.8, 33.0, 66.9, 112.0, 144.2, 170.7 ppm. HRMS (ESI): calcd.
for C9H16O2Na [M + Na]+ 179.1048; found 179.1040.
2-Cyclopentylallyl Acetate (10c): Colorless oil; yield: 28 %. IR
(CHCl ): ν = 2936, 1742, 1444, 1319, 1040 cm–1 1H NMR
.
˜
3
(300 MHz, CDCl3): δ = 1.15–1.64 [m, 8 H, CH2(CH2)2CH2], 2.06
(s, 3 H, CH3CO), 2.46 (m, 1 H, CH of cyclopentyl), 4.53 (s, 2 H,
CH2O), 4.88 (m, 1 H, CHA=), 4.98 (m, 1 H, CHB=) ppm. 13C
NMR (75 MHz, CDCl3): δ = 21.0, 23.8, 25.0, 31.4, 32.7, 43.5, 66.8,
110.0, 147.4, 170.7 ppm. HRMS (ESI): calcd. for C10H16O2Na [M
+ Na]+ 191.1048; found 191.1052.
General Procedure for the Synthesis of Alcohols 9 and Acetates 10:
General Procedure for the Synthesis of Esters 12: Compound 1b
CuI (300 mg, 1.6 mmol) was added to a solution of prop-2-yn-1-ol (0.5 mmol) and methallyl esters 4 or 7 (2 mmol) were dissolved in
(1.0 mL, 16.0 mmol) in anhyd. Et2O (30 mL) whilst stirring at room CH2Cl2 (10 mL) under argon. While keeping the reaction flask at
temp. under argon. The reaction mixture was cooled to –10 °C and
40 °C, a solution of catalyst I (4 mol-%) in CH2Cl2 (6 mL) was
Eur. J. Org. Chem. 2011, 6519–6526
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6525

F. Barile, M. Bassetti, A. D’Annibale, R. Gerometta, M. Palazzi
FULL PAPER
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added dropwise over 45 min. The reaction was kept at reflux for
15 h and then the solvent was removed under reduced pressure. The
oily residue was purified by column chromatography (silica gel,
light petroleum ether/Et2O, 8:2) to afford pure products 12 and
homodimer 13.
[3] A. K. Chatterjee, T.-L. Choi, D. P. Sanders, R. H. Grubbs, J.
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1-Acetoxy-2,4-dimethyl-5-(3Ј-methoxy-3Ј-oxopropionyloxy)-2-
pentene (12a): Colorless oil; yield 43%. IR (CHCl ): ν = 2980, 1756,
˜
3
1425, 1385, 1250 cm–1. H NMR (300 MHz, CDCl3): δ = 0.94 (d,
1
J = 6.6 Hz, 3 H, CH3CH), 1.64 (s, 3 H, CH3C=), 2.03 (s, 3 H,
CH3CO), 2.78 (m, 1 H, CHCH3), 3.34 [s, 2 H, CH2(C=O)2], 3.72
(s, 3 H, OCH3), 3.94 [m, 2 H, CH(CH3)CH2O], 4.40 (s, 2 H,
CH2OAc), 5.17 (m, 1 H, CH=) ppm. 13C NMR (75 MHz, CDCl3):
δ = 14.2, 17.0, 20.9, 31.9, 41.4, 52.4, 63.2, 69.3, 130.1, 132.0, 166.4,
166.8, 170.8 ppm. HRMS (ESI): calcd. for C13H20O6Na [M +
Na]+ 295.1158; found 295.1152.
[7] S. BouzBouz, R. Simmons, J. Cossy, Org. Lett. 2004, 6, 3465–
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1-(3Ј-Methoxy-3Ј-oxopropionyloxy)-2,4-dimethyl-5-acetoxy-3-
[8] S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001,
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nonene (12b): Colorless oil; yield 28%. IR (CHCl ): ν = 2965, 1732,
˜
3
1411, 1323, 1190 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.88 [t, J
= 7.3 Hz, 3 H, (CH2)2CH3], 0.97 (dd, J = 7.3, 6.6 Hz, 3 H,
CH3 C H) , 1 . 24 (m , 4 H , C H3 CH2 CH2 ) , 1 . 6 0 ( m , 2 H ,
CH3CH2CH2CH2), 1.61 (s, 3 H, CH3C=), 2.02 (s, 3 H, CH3CO),
2.77 (m, 1 H, CHCH3), 3.36 and 3.37 [s, 2 H, CH2(C=O)2], 3.74
(s, 3 H, OCH3), 3.94 [m, 2 H, CH(CH3)CH2O], 5.06 (t, J = 7.3 Hz,
1 H, CHOAc), 5.16 (d, J = 9.5 Hz, 1 H, CH=) ppm. 13C NMR
(75 MHz, CDCl3): δ = 12.3, 14.0, 17.2, 21.3, 22.5, 27.7, 31.7, 32.4,
41.4, 52.5, 69.4, 79.0, 129.1, 135.0, 166.5, 166.9, 170.2 ppm. HRMS
(ESI): calcd. for C17H28O6Na [M + Na]+ 351.1784; found 351.1781.
[9] G. S. Constable, A. J. Lesser, E. B. Coughlin, Polym. Prepr.
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gem-methyl-substituted derivatives are used as model sub-
strates to test the catalyst activity in ring-closing metathesis
reactions: a) M. Scholl, T. M. Trnka, J. P. Morgan, R. H.
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1,5-Bis(3Ј-methoxy-3Ј-oxopropionyloxy)-2,4-dimethyl-3-pentene
(13): Colorless oil. IR (CHCl ): ν = 2977, 1741, 1467, 1348,
˜
3
1210 cm–1. H NMR (300 MHz, CDCl3): δ = 1.00 (d, J = 6.6 Hz,
1
6 H, CH3CH), 2.35 (m, 2 H, CHCH3), 3.34 [s, 4 H, CH2(C=O)2],
3.70 (s, 6 H, OCH3), 4.02 (m, 4 H, CH2O), 5.31 (m, 2 H,
CH=) ppm. 13C NMR (75 MHz, CDCl3): δ = 16.7, 35.9, 41.2, 52.3,
69.4, 132.1, 166.2, 166.8 ppm. HRMS (ESI): calcd. for
C16H24O8Na [M + Na]+ 367.1369; found 367.1365.
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Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of compounds 1, 5–8, and 10–13;
NOESY spectra for compounds 5b and 5c.
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Received: June 23, 2011
Published Online: September 16, 2011
6526
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6519–6526