Application of a metathesis reaction in the synthesis of sterically congested medium-sized rings. A direct ring closing versus a double bond migration-ring closing process

Article abstract of DOI:10.1039/c1ob05086a

An efficient double bond migration-ring closing metathesis reaction leading to cycloheptene derivatives is observed when specific sterically congested 1,9-dienes are treated with the Grubbs' imidazolidene ruthenium catalyst. The simultaneous use of the Grubbs' catalyst and RuClH(CO)(PPh₃) ₃ facilitates the tandem bond migration-metathesis process. RuClH(CO)(PPh₃)₃ alone is capable of triggering an unactivated double bond migration that may have preparative applications.

Full text of DOI:10.1039/c1ob05086a

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PAPER
Application of a metathesis reaction in the synthesis of sterically congested
medium-sized rings. A direct ring closing versus a double bond migration–ring
closing process†
Michał Michalak and Jerzy Wicha*
Received 17th January 2011, Accepted 28th February 2011
DOI: 10.1039/c1ob05086a
An efficient double bond migration–ring closing metathesis reaction leading to cycloheptene derivatives
is observed when specific sterically congested 1,9-dienes are treated with the Grubbs’ imidazolidene
ruthenium catalyst. The simultaneous use of the Grubbs’ catalyst and RuClH(CO)(PPh
3
3
) facilitates the
tandem bond migration–metathesis process. RuClH(CO)(PPh alone is capable of triggering an
3 3
)
unactivated double bond migration that may have preparative applications.
Introduction
In a work directed at the total synthesis of diterpenoids with
the dicyclopenta[a,d]cyclooctane carbon skeleton (5-8-5), such
as in cycloaraneozene and epoxydictymene (Fig. 1, 1 and 2,
respectively), we envisaged the construction of key cyclopenta-
cyclooctane intermediate 4 by a ring closing metathesis (RCM)
reaction with diene 3. A mono- and a di-substituted double bond
in a relative 1,9-position would be involved in this process. The
closing of an eight-membered ring was, generally, considered to be
1–6
a difficult reaction. However, some encouraging examples of the
application of metathesis in the synthesis of complex cyclooctene
7
–16
derivatives have been reported
are also noteworthy
(more recent related examples
17–20
). The distinctive feature of substrate 3
was the l,l relative configuration around C-2,C-1¢ and C-1¢,C-2¢
as well as the presence of a bulky S-tert-butylthiocarbonyl group
in a position adjacent to the cyclopentane ring. The ring closing
process would place this group in a pseudo-axial position and
create considerable steric congestion.
Fig. 1 The target natural products (1, 2), intermediate diene 3, the
expected RCM product, 4, and obtained hydroazulene derivative 5.
Diene 3 exposed to the Grubbs’ imidazolidene ruthenium
catalyst (7, Fig. 2) in refluxing benzene afforded a RCM reaction
product in a 60–70% yield. Surprisingly, the product was not the
expected cyclooctacyclopentane 4 but the hydroazulene derivative
Tandem double bond migration–RCM reactions have been
scarcely reported in the literature (the previously reported ob-
servations on a double bond migration related to a metathesis will
be discussed later). In order to clarify the structural features that
may be promoting the tandem process, selected dienes analogous
to 3 were synthesized and their transformation with Grubbs’
ruthenium catalysts were studied. Additionally, a simultaneous
5. In an alternative attempt, the treatment of 3 with Grubbs’
benzylidene catalyst 6 in refluxing dichloromethane led to a
mixture of bimolecular cross metathesis products (“dimers”,
8
7%), which on heating with 7 in dichloroethane generated the
action of catalyst 7 and known ruthenium double bond migration
same product, 5 (49%). It was evident that the propene was the
complementary product of the formation of 5 from 3 and that a
double bond migration preceded the metathesis.
21–22
catalyst
9 was scrutinized. A preliminary communication on
23–24
our findings was previously published.
complete account of the work.
Herein, we present a
Institute of Organic Chemistry of the Polish Academy of Sciences,
Kasprzaka, 44/52, 01-224, Warsaw, Poland. E-mail: jwicha@icho.edu.pl;
Fax: 48 22 632 6681
Results
The metathesis of 3 and four related 1,9-dienes, 10–13, (Fig. 3),
with a di-substituted double bond in the “lower” side chain, was
examined using catalyst 7 alone or a mixture of catalysts 7 and
†
Electronic supplementary information (ESI) available: Experimental
procedures and characterisation data for new compounds. See DOI:
0.1039/c1ob05086a
1
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Fig. 2 The catalysts used in the present work.
9. Additionally, the metathesis of diene 14, devoid of the angular
methyl and differing from 3 by the relative configuration, was
tested (for the synthesis of substrates vide infra).
Heating of 3 in benzene, at reflux, in the presence of catalyst
Fig. 3 The metathesis of dienes with a di-substituted double bond in the
lower side chain, bearing a S-tert-butylthiocarbonyl group: substrates and
products.
7
(5 mol%), for 16–72 h afforded azulene derivative 5 in 49–56%
yield (Table 1, entry 1). The outcome of the reaction was not
affected by additives that were reported to inhibit double bond
2
5
migration, such as tricyclohexylphosphine oxide, (5 mol%), or
products that were separated by column chromatography. The
product isolated in a 34% yield was identified as the hydroazulene
derivative 5. The HRMS, H, and C NMR spectra of the second
product (40% yield) unambiguously pointed to the cyclooctene
structure 4 (entry 8). Heating of 11 with the catalysts 7 and 9
(5 mol% each) exclusively provided 5 (86%, entry 9).
26
1
,4-benzoquinone, (10 mol%) or by using 1,2-dichloroethane
25
27
1
13
as the solvent (entry 2). The catalyst 8 was found to be less
effective, although some migration–metathesis product was also
formed (entry 3). The reaction carried out in the presence of 7
(
5 mol%) with ruthenium hydride catalyst 9 (1 mol%) subsequently
added, afforded product 5 in 84% yield (entry 4). The increase in
the amount of catalyst 9 to 5 mol% resulted in a quantitative
conversion of the substrate to product 5 (entry 5). Interestingly,
briefly preheating catalysts 7 and 9 (5 mol% each), before the
substrate was added, had a negative effect on the product yield
1,10-Diene 12 and the catalyst 7 afforded a small amount of
5 (17% yield) with dimers prevailing (66% yield; entry 10). The
reaction of substrate 12 with the mixture of catalysts 7 and 9
(5 mol% each) afforded 5 in a substantially higher yield (64%),
along with dimers, 30% yield (entry 11).
(
65%, entry 6).
The 6-membered ring substrate 13, under the standard metathe-
sis conditions with the catalyst 7 (5 mol%), gave the corresponding
cycloheptene derivative 15, in 57% yield (entry 12). Finally, heating
of 14 and the catalyst 7 in benzene at reflux for 16 h gave a single
product that was identified as the cyclooctene derivative 16 (58%
yield; entry 13).
As anticipated, 1,8-diene 10, with the double bond in the C-4,C-
5
position, in the presence of the catalyst 7, in refluxing benzene,
smoothly afforded product 5 (98% yield, entry 7). The substrate
1, with the upper side chain extended by a methylene group,
and catalyst 7, heated in benzene, afforded a mixture of two
1
Table 1 The metathesis of dienes with one di-substituted double bond and a S-tert-butylthiocarbonyl group
Products, yield (%)
a
Entry
Diene
Catalyst (5 mol%)
Catalyst 9, (mol%)
Solvent
Time, h
7-memb.
8-memb.
dimers
b
1
2
3
4
5
6
7
8
9
1
1
1
1
3
7
—
—
—
1
5
5
—
—
5
—
5
—
—
C
(CH
6
H
6
2
6
6
6
6
6
6
6
6
6
6
6
16–72
72
24
6
6
6
5, 49–56
5, 67
3
7
8
7
7
Cl)
2
3
C
C
C
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
H
H
H
5, 15
3
5, 84
3
5, 100
5, 65
c
3
7
10
11
11
12
12
13
14
7
7
7
7
7
7
7
2
5, 98
72
24
72
24
16
16
5, 34
4, 40
5, 86
0
1
2
3
5, 17
66
30
5, 64
15, 57
16, 58
a
b
c
All reactions were carried out at reflux temperature. Addition of Cy
3
PO or 1,4-benzoquinone didn’t change the reaction outcome. A mixture of the
catalysts was preheated (30 min) before the substrate was added.
3
440 | Org. Biomol. Chem., 2011, 9, 3439–3446
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Table 2 The metathesis of 1,9-dienes with two mono-substituted double bonds and a S-tert-butylthiocarbonyl group (in benzene at reflux temperature)
Products, yield (%)
Entry
Diene
Catalyst (5 mol%)
Catalyst 9, (mol%)
Time, h
7-memb.
8-memb.
other
1
2
3
4
5
6
17
17
18
18
19
20
6, 10
7, 5
7, 10
7, 5
7, 5
7, 5
—
5
—
5
—
—
72
2
72
16
16
15
21, 40–49
21, 38
22, ca.15
23, 52
23, 15
24, 34
25, 42
26, 30
After establishing that the tandem reaction is not a one-
substrate artefact, we turned our attention to the dienes in which
both double bonds are mono-substituted. Heating of diene 17
derivative 23 in 52% yield, along with some dimeric products (entry
3). It should be noted that placing one of the double bonds in
a neopentyl position considerably slows the reaction down (the
respective derivative of 3 did not cyclize at a reasonable rate).
On heating of 18 in the presence of both catalysts (7 and 9) the
derivative 23 (15% yield) and diene 24 (34% yield), were obtained
(entry 4). The latter product results from the migration of the
double bond in the lower side chain.
Diene 19 and catalyst 7 afforded a product with cyclohexacyclo-
heptene rings (6,7), 25 (42% yield; Table 2, entry 5). This product
was somewhat easier to purify than its hydroazulene analogue,
as discussed earlier. The reaction of the gem-dimethyl diene 20
afforded 26 in 30% yield (Table 2, entry 6).
(
Fig. 4) in benzene in the presence of the catalyst 7 (10 mol%) led
to at least five products, with one dominating the mixture. None
of these products could be isolated in a pure form by column
chromatography. However, HPLC-MS analysis of the mixture and
1
13
the H and C NMR spectra of the mixture enriched with the main
product (column chromatography) pointed to the hydroazulene
structure 21. The yield of this product was estimated to be 40–
4
9%. Another product was identified by HPLC-MS analysis as
cyclopentacyclooctene 22 and its content was estimated to be 15%
Table 2, entry 1).
(
Substrates with a methoxycarbonyl group instead of a S-tert-
butylthiocarbonyl group were examined next (Fig. 5). Diene 27
with the l,l relative configuration and with one di- and one mono-
substituted double bond, with catalyst 7, in refluxing benzene,
underwent a bond migration–RCM reaction to afford the azulene
derivative 32 in 85% yield (Table 3, entry 1). An analogous
experiment with olefin isomerization catalyst 9 (5 mol%) added
afforded the same product, but the yield was higher and the
substrate was consumed in a shorter time (entry 2). Curiously,
when 1 mol% of catalyst 9 was added, 32 was accompanied by the
eight-membered ring product 33 (entry 3). The substrate with the
blocked allylic position in the upper side chain (28) only afforded
dimers (entry 4).
Diene 29, with the u,l relative configuration, smoothly under-
went ring closing to afford the cyclooctene derivative 34 in 96%
yield (entry 5).
Diene 30, with two mono-substituted double bonds (l,l relative
configuration), on treatment with catalyst 6 in benzene afforded
the product of an isomerization–RCM reaction, 35 (56% yield;
entry 6). When both metathesis (7) and isomerization (9) catalysts
were present, the substrate was consumed in a markedly shorter
time, but the product yield was lower (entry 7).
Finally, diene 31, with two mono-substituted double bonds
and the u,l relative configuration, in the presence of catalyst 6
in dichloromethane smoothly afforded the cyclooctene product 36
(
94% yield, entry 8).
In the concluding part of our studies, we examined di-mono-
Fig. 4 The metathesis of dienes with a mono-substituted double bond in
the lower side chain, bearing a S-tert-butylthiocarbonyl group: substrates
and products.
substituted 1,9-dienes with a hydroxymethyl group instead of an
ester group. Since the literature data concerning the effect of a
free hydroxy group on the metathetic formation of medium-size
rings appeared contradictory, with both the enhancement as well
as the inhibition of the reaction rate reported,
benzoates were also examined.
The consumption of 17 in the presence of the both catalysts, 7
and 9, was relatively fast. However, no improvement in the product
yield was noted (entry 2).
28–30
the respective
The diene with the blocked allylic position in the upper side
chain (18), under analogous conditions, afforded the cyclooctene
Alcohol 37 and catalyst 6 (3 mol%) afforded cyclooctene
derivative 41 in 47% yield (Fig. 6, Table 4, entry 1). The
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Table 3 Metathesis of 1,9-dienes bearing a methoxycarbonyl group
Products, yield (%)
7-memb.
Entry
Diene
Catalyst (mol%)
Catalyst 9, (mol%)
Solvent
Time, h
8-memb.
other
1
2
3
4
5
6
7
8
27
27
27
28
29
30
30
31
7(5)
7(5)
7(5)
7(10)
7(3)
6(3)
7(5)
6(3)
—
5
1
—
—
—
5
C
C
C
C
CH
C
C
6
6
6
6
H
H
H
H
6
6
6
16
0.5
6
72
6
72
6
16
32, 85
32, 94
32, 38
33, 36
6
dimer, 83
2
Cl
6
2
34, 96
6
H
H
35, 56
35, 28
6
6
—
CH
2
Cl
2
36, 94
Table 4 The metathesis of 1,9-dienes bearing a hydroxymethyl or ben-
zoxymethyl group using catalyst 6 (3 mol%)
Entry
Diene
Solvent
Time, h
Product, yield (%)
1
2
3
4
37
38
39
40
C
C
CH
CH
6
6
H
H
6
72
72
16
16
41, 47
42, 18
43, 99
44, 99
6
2
Cl
Cl
2
2
2
l,u configuration, underwent the RCM reaction in refluxing
dichloromethane to afford cyclooctene derivative 43 in a 99% yield
(
entry 3). Analogously, benzoate 40 was transformed into 44 in a
virtually quantitative yield (entry 4).
The metathesis reaction: discussion
The ruthenium metathesis catalysts and related ruthenium-
containing species are capable of triggering the migration of
unactivated double bonds, either during the reaction, or during
31–35
the product isolation procedure (for example, distillation).
The double bond migration that occurs prior to the metathesis
was observed during metathetic macrocyclization with use of the
Fig. 5 The metathesis of dienes bearing a methoxycarbonyl group:
substrates and products.
36–38
Nolan–Grubbs catalyst
(an analogous process was observed
8
in the presence of a molybdenum catalyst ). A linear 1,9-diene
bearing free hydroxy groups, in the presence of catalyst 6, afforded
a mixture of eight- and seven-membered ring products, the
latter arising from a double bond migration–metathesis process.
More recently, the cyclization of complex 1,9-dienes to form a
14
20,39
“
contracted” 7-membered ring has also been reported.
The transformation of an allylic alcohol into a ketone with one
fewer carbons, under the conditions of metathesis in the presence
40
of catalyst 6, was noted. In some specific cases, the attempted
RCM reaction was hampered by a double bond shift, leading to
18,20,41
the product being resistant to further changes.
In a broadly accepted explanation of the double bond migration
35,42
mechanism,
the ruthenium hydride species, contaminating the
catalyst or generated from the catalyst in the reaction mixture,
brings about the successive hydroruthenation–ruthenium hydride
elimination sequences.
In contrast to the esoteric ruthenium hydrides that possibly
accompany the metathesis catalysts, the well-defined, easily ac-
cessible, ruthenium hydride complexes are used to isomerize allyl
ethers into vinyl ethers or allyl amines into vinyl amines under
Fig. 6 The metathesis of 1,9-dienes with di-mono-substituted double
bonds, bearing no ester function: substrates and products.
21,43–45
mild conditions.
Ruthenium hydride 9 is one of the most
corresponding benzoate 38, under analogous reaction conditions
gave 42 in 18% yield (entry 2). Hydroxy diene 39, with the
efficient and convenient isomerization catalysts. A consecutive,
but separate use of metathesis catalyst 6 and then catalyst 9,
3
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4
6,47
provided an efficient route to various benzo-fused heterocycles.
Catalyst 7 was modified by treatment with a mixture of H –N
the tandem metathesis–double bond migration process leading to
Table 5 Bond migration–metathesis of dienes with catalyst 7 alone or
with a mixture of catalysts 7 and 9 (products, % yields)
2
2
for
Catalyst
Substrate
48,49
cyclic enol ethers.
However, the simultaneous use of metathesis
and isomerization catalysts has not been reported in the literature,
to the best of our knowledge.
We found that all three ruthenium metathesis catalysts (6, 7,
3
11
5, 34
5, 86
12
5, 17
5, 64
27
32, 85
32, 94
17
21, 49
21, 38
50
7
7
5, 67
5, 100
and 9
8) were capable of initiating the bond migration–metathesis of a
series of 1,9-dienes related to 1-allyl-2-(pent-4-enyl)cyclopentane,
although catalyst 8 gave a low yield of products. The catalyst 7 was
the most efficient for both types of dienes, with one di-substituted
double bond and two-mono-substituted double bonds.
The gem-dimethyl derivatives 18 and 20, for which the upper side
chain double bond migration is blocked, underwent metathesis
with catalyst 7 to give cyclooctene derivatives, 23 and 26,
respectively (52% and 30% yield) along with the corresponding
dimers. The diene 28 gave only a mixture of dimers. The high
degree of steric congestion of the formed cyclooctane derivatives
is noteworthy.
substituted double bond, in general, afforded products that were
more difficult to purify and in lower yields. The difference likely
reflects the possibility of further involvement of the initially formed
bicyclic products with disubstituted double bonds (as in 21) in
the metathesis and/or double bond migration processes, whereas
products with trisubstituted double bonds (as 5) are removed from
the reaction cycle.
Some additional comments on the simultaneous use of metathe-
sis and isomerization catalysts are in order. A joint application
of catalysts 7 and 9 was effective in generating contracted ring
products with respect to substrates 3, 11, 12, 27 with a di-
substituted double bond. However, no positive effect was observed
with diene 17 (mono-substituted double bond) (Table 5).
It should be noted that the formation of hydroazulene 5
from 11 occurred through the migration of an “internal” double
bond. 1,10-diene 12 underwent “two-fold” double bond migration,
presumably via 11.
The “normal” RCM leading to the cyclooctane derivatives, as
the major product or a side product, was observed for the following
1
,9-dienes: 11, 14, 17, 18, 20, 29, 31, 37–40. Tandem double bond
migration–metathesis reactions occurred when the following eight
substrates were used: 3, 11–13, 17, 19, 27 and 30.
In the bond migration–metathesis process, the formation of
seven-membered ring derivatives appears to be favoured, since
product 5 is formed from the various substrates: 3 (single migration
of the double bond), 10 (“direct”), and 12 (two-fold migration
of the double bond). No annulation with formation of a six-
membered ring was recorded.
Analysis of the structural features of the substrates leads to
the generalizations illustrated in Scheme 1. The tandem bond
migration–rearrangement was only observed for substrates bear-
ing an alkylthio- or alkoxycarbonyl group [–C(O)X] attached at
position 2.
The use of catalysts 7 and 9 with diene 18 afforded a product of
double bond migration in the lower side chain. Another example
of unactivated bond migration induced by catalyst 9 is discussed
in the section devoted to the preparation of substrates (compound
1
0), possibly indicating a broader synthetic application of this
catalyst.
Various aspects of non-bonding interactions were considered
for both the reaction products as well as the intermediates in
an effort to explain the noted preference of the isomerization–
cyclization reaction. A comparison of the molecular models of the
seven- and eight-membered ring products, for example 5 and 4,
suggested only a minor difference in their steric strain.
Inspection of molecular models of the reaction intermediates
with a ruthenium-containing four membered ring suggested that
the formation of a seven-membered ring requires less non-bonding
interactions, but no conclusive prediction could be made.
The synthesis of dienes for metathesis studies
The substrates with a l,l configuration were prepared by
starting from 2-methylcyclopent-2-en-1-one (49, Scheme 2), 2-
methylcyclohex-2-en-1-one (50), or methylcyclopent-2-en-1-one
(
2
54), the respective ketene acetals (45–48) and allyl (2-methylprop-
-enyl) methyl carbonates (52 and 53, respectively), using the
Scheme
1
The structural features relevant to the bond migra-
tion–metathesis or “direct” metathesis induced by catalyst 7.
tandem Mukaiyama–Michael addition and Tsuji alkylation re-
actions. The unsaturated ketone was first treated with ketene
acetal in dichloromethane (DCM), at -78 C, in the presence of
◦
The stereogenic centers in a l,l relative configuration (sub-
stituent at C-2 in a pro-axial orientation) are essential for the
tandem migration–metathesis sequence. The relative configuration
effect is particularly revealing when the reaction outcomes for
epimer pairs 27–29 and 30, 31 are compared.
The bond migration–metathesis process was observed for
substrates with both di- and mono-substituted double bonds
in the lower side chain. However, substrates with a mono-
trimethylsilyl triflate (5 mol%), to afford trimethylsilyl enol ethers
51. These intermediates were isolated by a quick filtration of the
reaction mixture through a pad of silica gel and evaporation. The
NMR analysis of these products indicated that the virtually pure
(like) diastereomers were formed. Trimethylsilyl triflate was found
to be the catalyst of choice for this reaction, since it could be easily
51,52
removed from the reaction mixture before the subsequent step.
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Scheme 2 Syntheses of dienes 3, 11–13 and 17–20.
Table 6 Synthesis of dienes 3, 11–13 and 17–20
Allylation reaction
Table 7 The preparation of methyl esters 27–31
Product, yield (%)
Product,
yield (%)
1
2
Entry Substrates, n, R
R , catalysts
1
2
Entry
R
R
Thioester
u,l
l,l
1
2
3
4
5
6
7
8
1, –CH
1, –CMe
2, –CH CH CH
2, –CMe CH CH
CH CH
CH
2
CH CH
2
(45)
2
H, A
H, A
H, A
H, A
17, 68
18, 69
19, 69
20, 62
3, 86
12, 39
11, 64
13, 22
1
2
3
CH
H
H
3
H
H
CH
3
17
18
29, 45–49
31, 46
27, 40–42
30, 42
2
CH CH
(46)
2
2
(45)
(46)
3
28, 82
2
2
1, –CH
1, –CH
1, –CH
2, –CH
2
2
2
2
2
(45)
CH
(47) CH
(48) CH
CH
3
3
3
3
, B
, B
, B
, B
2
CH CH
2
CH CH
CH CH
2
CH
(45)
3
2
Upon the use of trityl hexachloroantimonate (TrSbCl
6
), which is
53
the generally preferred catalyst for the Mukaiyama addition, the
reproducibility of the tandem process yield was problematic.
The silyl enol ethers were, without purification, subjected to the
reaction with allyl methyl carbonate (52) or methyl 2-methylprop-
2
-enyl (methallyl) carbonate (53) and a suitable palladium catalyst.
With the former, the classic palladium dibenzylacetone complex
54,55
[
Pd
2
(dba) ]-1,2-(diphenylphosphine)ethane (dppe) was used.
3
The reaction with methallyl methyl carbonate (53) was carried
out in the presence of a modified catalyst consisting of palladium
acetate and 1,4-(diphenylphosphine)butane (dppb). The results of
these reactions are summarized in Table 6.
The synthesis of thioester 14 was accomplished essentially using
the reported procedures for the conjugate addition step and the
procedure developed earlier for the allylation step (Scheme 3). It
is well-documented that when cyclopent-2-en-1-one (54) is used
as the acceptor in the Mukaiyama–Michael addition, products
with a u,l configuration are formed, in contrast to the reactions
discussed earlier involving 2-methyl-cyclopent-2-en-1-one (49).
Diene 10 was prepared by treatment of 3 with the ruthenium
hydride catalyst 9 (1 mol%) in benzene at reflux temperature for
Scheme 3 The synthesis of diene 14.
53
1
0 min, followed by chromatography. The product was isolated in
a 87% yield as a mixture of E and Z isomers, ca. 3 : 1 (Scheme 4).
Methyl esters of both of the series, with methallyl or allyl
substituents, 27–31, were prepared from the respective thioesters
by methanolysis using potassium methoxide in methanol (Scheme
Scheme 4 The synthesis of diene 10.
Thioester 17 and ester 31 were transformed into their respective
derivatives 37, 38, 39, and 40, as indicated in Scheme 6. Two
issues related to these transformations should be singled out
for comment. Since the hydrolysis of benzoate 38 with KOH in
MeOH was slow, the MeOK/MeOH system was used. In the
NMR spectrum of hydroxy ketone 39 (in CDCl ) no carbonyl
5
, Table 7). Under these conditions, the respective products were
formed as mixtures of epimers, l,l (27 and 30) and u,l (29 and
1), in a ratio of ca. 1 : 1. The epimers were separated by flash
3
1
3
chromatography. It is noteworthy that methanolysis of the very
sterically congested thioester 18 gave a single epimer of the
product, 28.
C
3
signal appeared, which might be indicative of the intramolecular
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one, or 2-methylcyclohept-2-en-1-one, the suitable S-tert-butyl
alkenylthiocarboxylates and alkyl allyl carbonates, using tandem
Mukaiyama–Michael addition and Tsuji alkylation reactions.
A modified catalyst, consisting of palladium acetate and 1,4-
(
diphenylphosphine)butane (dppb), permitted the application of
sterically demanding alkyl 2-methylprop-2-enyl carbonates in the
alkylation step.
Acknowledgements
We thank Prof. Karol Grela and Prof. Stanisław Krompiec for
samples of catalysts 8 and 9, respectively. The Ministry of Sciences
and Higher Education, grant for M.M. is gratefully acknowledged.
Scheme 5 The preparation of methyl esters 27–31 from their respective
thioesters.
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