Polyfunctional β-dicarbonyl compounds by michael addition reactions of ester enolates to α-benzylidene and α-alkylidene-β-dicarbonyl compounds

Article abstract of DOI:10.1002/ejoc.201200077

The scope and stereoselectivity of the Michael addition of ester enolates to α-benzylidene and α-alkylidene β-dicarbonyl compounds was studied. Most substrates reacted in good to excellent yields. Michael acceptors bearing carboxylic functionalities reacted directly in the β-position, whereas aldol and Michael addition competed with unsaturated ketones. The diastereoselectivity of the process is dependent on the substitution pattern of the Michael acceptor and the geometry of the enolate. (Z)-Enolates add to unsaturated malonates or dibenzoylmethane derivatives with good anti-selectivity, whereas (E)-enolates afforded the syn-diastereomers predominately. Unsaturated nitriles and Meldrum's acid derivatives reacted with low diastereoselectivity. A stereochemical model is proposed that accounts for all experimental results and allows the stereochemical outcome to be predicted. Michael addition reactions of ester enolates with various unsaturated β-dicarbonyl compounds are presented. The diastereoselectivity of the addition can be controlled by employing enolates with defined geometry.The scope and limitations of the methodology are discussed.

Full text of DOI:10.1002/ejoc.201200077

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FULL PAPER
DOI: 10.1002/ejoc.201200077
Polyfunctional β-Dicarbonyl Compounds by Michael Addition Reactions of
Ester Enolates to α-Benzylidene and α-Alkylidene-β-dicarbonyl Compounds
[a]
[a]
[b]
[a]
ˇ
Martin Holan, Radek Pohl, Ivana Císarová, and Ullrich Jahn*
Keywords: Michael addition / Diastereoselectivity / Regioselectivity / Enols / Dicarbonyl compounds
The scope and stereoselectivity of the Michael addition of
ester enolates to α-benzylidene and α-alkylidene β-dicarb-
onyl compounds was studied. Most substrates reacted in
good to excellent yields. Michael acceptors bearing carbox-
ylic functionalities reacted directly in the β-position, whereas
aldol and Michael addition competed with unsaturated
ketones. The diastereoselectivity of the process is dependent
on the substitution pattern of the Michael acceptor and the
geometry of the enolate. (Z)-Enolates add to unsaturated ma-
lonates or dibenzoylmethane derivatives with good anti-
selectivity, whereas (E)-enolates afforded the syn-dia-
stereomers predominately. Unsaturated nitriles and Meld-
rum’s acid derivatives reacted with low diastereoselectivity.
A stereochemical model is proposed that accounts for all ex-
perimental results and allows the stereochemical outcome to
be predicted.
Introduction
The Michael addition reaction is likely the most valuable
synthetic methodology available to approach the synthesis
of 1,5-dicarbonyl compounds.[1] Initial investigations relied
heavily on β-dicarbonyl compounds as Michael donors and
a number of α,β-unsaturated carbonyl compounds.[1a] With
the advent of modern enolate chemistry, the focus shifted
more to the use of preformed enolates II derived from carb-
onyl compounds
I
in Michael addition reactions
(Scheme 1). Thanks to the ground-breaking studies by
Heathcock and colleagues, a stereochemical model for the
addition reactions of lithium ester or ketone enolates II to
α,β-unsaturated ketones III was developed,[2,3] which is sup-
ported by a recent computational study using simplified
model compounds.[4] This type of Michael addition is
thought to proceed through an initial reversible aldol ad-
dition step, from which the Michael adduct forms via an
eight-membered transition state. Subsequent investigations
extended the scope of the approach to include titanate enol-
ates II (M = Ti).[5]
Scheme 1. Michael addition reactions.
In parallel, Mukaiyama and colleagues introduced silyl
enol ethers II (M = SiR3) as stable isolated nucleophiles in
Michael additions.[6] These addition reactions proceed
mostly via open transition states and usually require activa-
ting agents. Recently, Michael addition reactions that are
catalytic in the metal ion were developed.[7] These reactions
are, however, limited to the most highly acidic Michael do-
nors. Michael addition reactions of enols (II, M = H) were
rare until recently. With the establishment of asymmetric
organocatalysis, this reaction type became more impor-
tant.[8] Dual modes, in which both the electrophile and nu-
cleophile are activated by the catalyst, were also tested.[9]
Despite controlling stereochemistry efficiently, a major
limitation of this methodology remains its substrate scope,
which, is by nature, is restricted to the most enolizable
Michael donors and most electron-deficient Michael ac-
ceptors.
[a] Institute of Organic Chemistry and Biochemistry, Academy of
Sciences of the Czech Republic,
Flemingovo námeˇstí 2, 16610 Prague 6, Czech Republic
E-mail: jahn@uochb.cas.cz
[b] Department of Inorganic Chemistry, Faculty of Science,
Charles University in Prague,
Albertov 6, 12840 Prague 2, Czech Republic
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200077.
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M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
The enolate Michael addition is a very attractive reaction Table 1. Base and solvent screening in the Michael addition of 1a
to 2A.[a]
with respect to its potential in tandem processes because, at
the end of the reaction, another enolate is generated that
may enter additional reaction steps.[10] Several formally an-
ionic tandem Michael–Michael additions and related reac-
tions were also studied. We reported initial results on new
tandem enolate Michael addition/radical cyclization/oxy-
genation reactions some time ago.[11] However, to allow the
design of new applications, the scope and limitations of the
enolate Michael addition reaction must be better defined
and the validity of the stereochemical model put forward
must be proven. Although the Heathcock model holds for
Michael addition reactions to simple α,β-unsaturated
ketones, relatively little is known about the regio- and stereo-
selectivity using more complex and structurally diverse α-
alkylidene or arylidene β-dicarbonyl compounds.[12]
In this paper we report on Michael addition reactions
that involve lithium ester enolates II (X = OR3) as proto-
typical donors and diverse α-alkylidene or arylidene β-di-
carbonyl compounds V as acceptors. The substrate scope is
probed. Application of the starting enolates II, with defined
(Z)- or (E)-geometry, allows effective steering of the dia-
stereoselectivity of the Michael addition reaction with ester-
bearing Michael acceptors V giving either anti- or syn-VI
with good yield and diastereoselectivity. The reactivity of
ketone-derived Michael acceptors and nitriles, and combi-
nations thereof, and their influence on the outcome of the
Michael addition is presented. Based on these results, ste-
reochemical models for the reactions are derived that allow
the predictive use of Michael acceptors V.
Entry Enolate of 1a Base
Solvent
3Aa [%] anti/syn
1
(E)
(Z)
LDA
LDA
THF
THF/
HMPA
THF
THF
THF
92
1:7.7
15:1
2
79
3[b]
4
(E)
(Z)
(Z)
(E)
LiHMDS
NaHMDS
KHMDS
89[c]
83[d]
98
1:3
1:1.1
3.2:1
2:1
5
6[e]
LDA/Ti(OiPr)4 THF
99
[a] Reagents and conditions: 1a (1.25 mmol), solvent, base
(1.6 mmol), –78 °C, 30 min, then 2A (1.0 mmol), –78 °C for 30 min,
then warmed to –40 °C until complete. [b] Reagents and conditions:
1a (1.1 mmol), solvent, base (1.2 mmol), –78 °C, 30 min, then 2A
(1.0 mmol), –78 °C for 30 min, then warmed to –40 °C until com-
plete. [c] Compound 4 was isolated in 3% yield. [d] Compound 4
was isolated in 13% yield. [e] Reagents and conditions: 1a
(1.0 mmol), solvent, base (1.05 mmol), –78 °C, 20 min, then
Ti(OiPr)4 (1.0 mmol) added at –40 °C, 40 min, 2A (0.5 mmol),
–40 °C for 30 min, then warmed to –20 °C until complete.
Results
Initially, suitable conditions for the Michael addition re-
actions of enolates of tert-butyl 4-pentenoate (1a) to ac-
ceptor 2A were screened (Table 1 and Scheme 2). Using lith-
ium diisopropylamide (LDA) as the base for deprotonation
of 1a in tetrahydrofuran (THF) followed by addition of
benzylidenemalonate 2A at –78 °C provided addition prod-
uct 3Aa as the sole product with a 7.7:1 syn/anti-diastereo-
selectivity (Table 1, entry 1). When the solvent was changed
to THF/HMPA, a reversal of the diastereoselectivity was
Scheme 2. Screening of optimal conditions for the Michael ad-
dition of 1a to 2A.
The configuration of ester enolates 1– was probed by de-
observed and anti-3Aa formed as the major product in 79% protonation of 1a or 1b with LDA and subsequent trapping
yield and with a 15:1 diastereomeric ratio (Table 1, entry 2). as their silyl ketene acetals 5 (Scheme 3). tert-Butyl ester 1a
With lithium hexamethyldisilazide (LiHMDS), the yield did not afford a silyl ketene acetal 5a after deprotonation
was similar, but the diastereomeric ratio was significantly with LDA in THF and trapping with TBSCl. The desired
lower (Table 1, entry 3). Small amounts of product 4 re- silyl ketene acetal 5b formed in the reaction of 1a– with
sulting from conjugate addition of hexamethyldisilazide to TMSCl only in low yield and with unexpected (Z)-selectiv-
2A were also isolated. Sodium and potassium hexamethyl- ity. C-Silylated ester 6b was the main product of the sil-
disilazide gave also good yields of Michael addition prod- ylation,[14] thus precluding access to crucial information on
ucts 3Aa, but the diastereoselectivity was low (Table 1, en- the enolate configuration. Less bulky ester 1b gave the re-
tries 4 and 5).[13] A good yield of 3Aa was observed when quired silyl ketene acetal 5c upon treatment with TMSCl in
the corresponding titanate enolate was applied in the high yield and a 6.6:1 (E)-diastereoselectivity, which was
Michael addition reaction. The diastereoselectivity was low, established by NOE measurements of the resulting crude
but reversed compared to the products obtained from lith- mixture. In the presence of HMPA, the enolate of tert-butyl
ium enolates (Table 1, entry 6).
ester 1a reacted with TBSCl providing the corresponding
2
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Polyfunctional β-Dicarbonyl Compounds
(Z)-silyl ketene acetal (Z)-5a with good diastereoselectivity.
The sodium enolate of 1b generated with NaHMDS gave a
mixture of products upon trapping with TMSCl, in which
silyl ketene acetal 5c was observed as a 3:1 mixture of (Z)-
and (E)-isomers. The potassium enolate resulting from de-
protonation with KHMDS furnished silyl ketene acetal 5c
cleanly as a 8:1 mixture of (Z)- and (E)-isomers in 78%
yield (data not shown).
Scheme 4. Michael addition reactions of 4-pentenoates 1a–e to
ylidenemalonates 2A–C.
Table 2. Results of the Michael addition reactions of 1a–e to
malonate acceptors 2A–C.
Entry Enolate
2
Solvent
T [°C]
3 [%]
anti/syn[a]
1
2
3
4
5
6
7
8
(Z)-1b
(E)-1b
(E)-1b
(Z)-1c
(Z)-1d
(E)-1d
(Z)-1e
(E)-1e
(E)-1a
(Z)-1a
(Z)-1a
(Z)-1e
(Z)-1a
(E)-1a
A
A
A
A
A
A
A
A
B
B
B
B
C
C
THF/HMPA –78 to –40 Ab 96
6.6:1
1:2.8
1:4
8.9:1
11.8:1
1:2.2
11:1
1:11
1:5
THF
–78 to –40 Ab 60
–78 to –40 Ab 76
THF/LiCl[b]
THF/HMPA –78 to –40 Ac 95
THF/HMPA –78 to –40 Ad 77
THF
–78 to –40 Ad 90
Scheme 3. Silyl ketene acetals 5 by reaction of 1a and 1b with LDA
and TBSCl or TMSCl.
THF/HMPA –78 to –30 Ae 93
THF
THF
–78 to –30 Ae 85
–78 to –40 Ba 95
9
10[c]
11[e]
12
13[e]
14[e]
THF/HMPA –78 to –30 Ba 60[d] 5:1
With optimal conditions for the stereoselective genera-
tion of lithium enolates of 1 and their subsequent Michael
addition in hand, the scope of the methodology was deter-
mined. Ester enolates 1b–e underwent the Michael addition
reaction with benzylidenemalonate 2A and alkylidenemal-
onates 2B and 2C reliably with moderate to good yields
(Scheme 4, Table 2). (Z)-Enolates 1b–e– provided the corre-
sponding anti adducts 3Ab–Ae with good diastereoselecti-
vity (Table 2, entries 1, 4, 5, and 7). The diastereoselectivity
of the addition of (E)-enolates 1b–e– varied depending on
the size of the ester substituent. Those with methyl esters
THF/HMPA –78
Ba 80[f] 4:1
Be 92 4.6:1
THF/HMPA –78 to 0
THF/HMPA –78 to –40 Ca 40[g]
–
–
THF
–78 to –40 Ca 75[h]
[a] Assignment based on cyclization products (vide infra). [b]
7.5 equiv. anhydrous LiCl added from the beginning. [c] Reagents
and conditions: 1 (1.25 equiv.), LDA (1.25 equiv.), 2 (1.0 equiv.). [d]
15% 2B recovered. [e] Reagents and conditions: 1 (1.4 equiv.), LDA
(1.2 equiv.), 2B (1.0 equiv.). [f] 5% 2B recovered. [g] 20% 2C reco-
vered, 30% 7 formed. [h] 4% 2C recovered, 2% 7 formed.
(1b or 1d) proceeded with a low syn-diastereoselectivity these reactions an excess of LDA over esters 1 should be
(Table 2, entries 2 and 6), which was improved by addition avoided. This led to an increase in the yield from 60 to 80%
of lithium chloride to the reaction mixture (Table 2, en- and only 5% recovery of starting malonate 2B (Table 2, en-
try 3). Better syn-selectivity was achieved by application of try 10 vs. 11). Diethyl isopropylidenemalonate (2C) gave
tert-butyl esters 1a and 1e (Table 1, entry 1, and Table 2, Michael adduct 3Ca via the (Z)-enolate of 1a in only 40%
entry 8).
yield as an inseparable mixture with 20% recovered starting
Ethylidene malonate 2B reacted with the (E)-enolate of malonate 2C and 30% isomerized malonate 7 (Table 2, en-
1a to give Michael addition product 3Ba in 95% yield as a try 13). The result was much improved when less basic con-
1:5 anti/syn diastereomeric mixture (Table 2, entry 9). The ditions for the formation of the (E)-enolate were applied.
(Z)-enolates of 1a and 1e reacted with 2B to generate prod- The yield of 3Ca increased to 75% and 2C and 7 were
ucts anti-3Ba or 3Be in 60–92% yield with approximately formed in only 4 and 2% yield, respectively (Table 2, en-
4–5:1 anti-selectivity (Table 2, entries 10–12). Variable try 14).
amounts of starting material 2B were recovered from the
Michael acceptors 2D–H also reacted in good to excel-
reactions in the presence of HMPA, which was due to the lent yield with (E)- and (Z)-enolates of 1 (Scheme 5 and
occurrence of competing γ-deprotonation. Therefore, in Table 3). However, replacement of the ester groups in 2A–
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FULL PAPER
C by those acceptors led to a sharp decrease in diastereo- der the reaction conditions, leading to a mixture of crude
selectivity, irrespective of the geometry of enolates 1. The acids, which was esterified using trimethylsilyldiazome-
benzylidene derivative of Meldrum’s acid 2D, as an example thane. The relative configuration of the resulting cyclization
of a conformationally locked ester derivative, gave, in con- products 8Ab was established as trans between the 2- and
trast to related 2A, lower yields and diastereoselectivities 3-positions by NOE experiments (see the Supporting Infor-
in the Michael addition with 1a (Table 3, entries 1 and 2). mation). The major product has an α-orientation of the
Reaction mixtures containing 3Da must be quenched with iodomethyl group. The configuration of the other products
acid to avoid losses due to incomplete protonation, but 3Ab–Ca were assigned on the basis of the similarity of their
workup and isolation should be performed quickly because 1H NMR spectroscopic data (see the Supporting Infor-
adducts 3Da are also very acid-sensitive.[15] Benzylidene- mation). The anti-diastereomers of 3Aa–Ae display a
cyanoacetate 2E and propylidenecyanoacetate 2F reacted in 0.2 ppm downfield shift of their malonyl proton compared
good yields, providing four diastereomers of the adducts to the syn-isomers. A similar trend, but with 0.1 ppm, some-
3Ea and 3Fa due to the creation of the additional stereocen- what less pronounced, holds for the diastereomers of 3Ba
ter on protonation (Table 3, entries 3–6). Malononitriles 2G and 3Be.
and 2H afforded the products in good yields (Table 3, en-
tries 7–11), however, the diastereoselectivity was low irre-
spective of the enolate geometry (Table 3, entries 7–10).
Scheme 5. Michael addition reactions of 4-pentenoates 1a and 1b
Scheme 6. Iodocarbocyclization of 3Aa and 3Fa.
to β-dicarbonyl compounds 2D–H.
The syn-diastereomer of 3Ga gave crystals that were suit-
Table 3. Results of the Michael addition reactions of 1a and 1b to
able for obtaining an X-ray crystal structure (Figure 1).[17]
acceptors 2D–H.
The bulky tert-butyl ester group and the phenyl ring are
oriented antiperiplanar to each other in the crystal. The
cyano groups also point away from the ester function. The
compound displays a characteristic chemical shift of the
tert-butyl group at δ = 1.51 ppm, whereas the correspond-
ing anti-diastereomer has an upfield-shifted value of δ =
1.20 ppm. This shift difference of the tert-butyl resonances
is characteristic for all derivatives 3Da, 3Ea, and 3Ga. The
anti-isomers have chemical shifts at δ = 1.01–1.20 ppm for
the tert-butyl group, whereas the resonances of syn-isomers
were found at δ = 1.41–1.51 ppm. The resonances of the
OMe groups in the diastereomers of 3Gb show a similar
difference of their chemical shifts. Because derivatives 3Ea
and 3Fa have a second stereocenter at the cyanoacetate
group formed on protonation of the prochiral adduct enol-
ate, the determination of the addition diastereoselectivity
Entry Enolate
2
Solvent
T [°C]
3 [%]
anti/syn[a]
1
2
3
4
5
6
7
8
(Z)-1a
(E)-1a
(Z)-1a
(E)-1a
(Z)-1a
(E)-1a
(Z)-1a
(E)-1a
(Z)-1b
(E)-1b
(E)-1a
D
D
E
E
F
THF/HMPA
THF
THF/HMPA
THF
THF/HMPA
THF
THF/HMPA
THF
–78 to –50
–78 to –50
–78 to –35
–78 to –35
–78
Da 57[b] 1:1
Da 76[c] 1:1.5
Ea 87
Ea 76
Fa 84
Fa 89
Ga 76
Ga 84
Gb 78
Gb 78
Ha 97
(1.5:4.2):(3.2:1)[d]
(1:3.2):(4.2:1)[d]
(1.4:2.0):(3.4:1)[d]
F
–78
(1.4:2.1):(3.5:1)[d]
G
G
G
G
H
–78 to –50
–78 to –50
–78
–78
–78
1:1
1.6:1
2.4:1
1.2:1
–
9
10
11
THF/HMPA
THF
THF
[a] Assignment based on comparison of NMR shifts. [b] 3% of 5-
benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione formed as a side prod-
uct. [c] 10% of 5-benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione formed
as a side product. [d] Values in first parentheses are for anti- and
in second for syn-diastereomers.
The configuration of the major anti Michael adduct 3Aa was challenging. For 3Ea, the shift differences of the tert-
was determined by applying Taguchi’s iodocarbocyclization butyl ester units could be used to assign the relative config-
reaction using TiCl4 in the presence of NEt3 and iodine uration of the Michael adducts. The relative configuration
(Scheme 6).[16] The reaction of a 5:1 anti/syn mixture of 3Aa of 3Fa could not be established with certainty by the Tagu-
proceeded cleanly with anti-3Aa, while the syn-isomer re- chi cyclization, because four diastereomers of products 8Fb
mained unaffected. The tert-butyl ester unit was cleaved un- were formed in almost equal proportions (Scheme 6, see the
4
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Polyfunctional β-Dicarbonyl Compounds
Supporting Information).[18] The configuration of the car- 1f afforded, in contrast to all other Michael acceptors, aldol
bon atom bearing the cyano and ester functions could not addition products 9Ia, and 9Ie–If in good yields and only
be determined.
small amounts of 3Ia, 3Ie–If with reasonable syn-selectivity
after short reaction times at low temperature (Table 4, en-
tries 2, 6, and 9).
Figure 1. View of one of the two symmetrically independent mole-
cules of syn-3Ga with atom numbering scheme. The displacement
ellipsoids are drawn at 30% probability level. Selected bond lengths
(Å) and angles (°): C(7)–O(1) 1.2049 (15), C(7)–O(2) 1.3305 (15),
C(18)–N(1) 1.138 (2), C(19)–N(2) 1.141 (2); C(1)–C(2)–C(3)–C(7)
57.29 (14); C(12)–C(2)–C(3)–C(7) 177.71 (11).
Scheme 7. Michael addition reactions of 4-pentenoates 1 to 2I or
2K.
The reactions of the enolates of 1a, 1e, and 1f with
ketone-derived Michael acceptors differ from acceptors
bearing carboxylic acid functionalities (Scheme 7 and
Because it is known that aldol additions to enones are
Table 4). The (Z)-enolates of 1a and 1f reacted with benzyl- reversible and that aldol adducts convert into Michael ad-
idenedibenzoylmethane 2I providing the expected Michael ducts upon warming,[19] the product and temperature pro-
addition products 3Ia and 3If, respectively, in reasonable file of the reaction was investigated briefly. When the reac-
yield and good anti-diastereoselectivities; the reactions were tion mixture formed from the (Z)-enolate of 1f was warmed
accompanied by the unexpected formation of small to room temperature with extension of the time, the amount
amounts of the β-keto esters 10Ia and 10If, chalcone iso- of 3If did not increase, but the amounts of 10If, 11I, and
mers 11I and trione 12I (Table 4, entries 1 and 5) or aldol 12I increased corresponding to the disappearance of 9If
adduct 9If (Table 4, entry 4). The (E)-enolates of 1a, 1e,and (Table 4, entries 4 vs. 5). The product mixture of 3Ia, 3Ie–
Table 4. Divergent Michael vs. aldol addition reactivity in the reaction of 1 with 2I or 2K.
Entry Enolate
2
Additive T [°C]
3 [%] (anti/syn) 9 [%] (anti/syn) 10I/K [%]
11I [%]
12I/13K [%]
1
2
3
4
5
6
7
8
(Z)-1a
(E)-1a
(E)-1a
(Z)-1f
(Z)-1f
(E)-1f
(E)-1f
(E)-1f
(E)-1e
(E)-1e
(Z)-1a
(Z)-1a
(E)-1a
(E)-1a
I
I
HMPA
–
–
HMPA
HMPA
–78 to –40
–78
–78 to room temp.
–78 to –60
–78 to room temp.
–78 to –60
–78 to room temp.
–78 to room temp.
–78
–78 to room temp.
–78
–78 to room temp.
–78
–78 to room temp.
Ia 71 (8.8:1)
Ia 33 (1:4.2)
Ia 23 (1:5)
If 61 (5.9:1)
If 50 (5.9:1)
If 10 (1.3:1)
If 17 (1:3.1)
If 26 (1:4.2)
Ie 18 (1:4.2)
Ie 15 (1:4)
Ka 19 (1:0)
Ka 10 (1:0)
–
–
11
–
57
–
15
–
68
52
–
62
–
–
–
–
trace
–
trace
–
11
–
10
–
trace
19
–
11
30
64
–
Ia 65 (1:12)
–
If 22 (1:1.6)
–
If 67 (1:5.7)
–
–
Ie 73 (1:5)
–
Ka 34 (4.9:1)
–
Ka 82 (1:7)
–
I
28[a]
–
I
I
5[b,c]
–
I
–
–
I
27[d]
36[f]
–
I
LiCl[e]
9
I
–
–
10
11
12
13
14
I
26[g]
–
K
K
K
K
HMPA
HMPA
–
–
–
–
–
Ka 3 (1.9:1)
30
[a] E/Z ratio 10:1. [b] (E)-Isomer. [c] 33% of starting ester recovered. [d] E/Z ratio 1.8:1. [e] 0.01 equiv. anhydrous LiCl added from the
beginning. [f] E/Z ratio 2.4:1. [g] E/Z ratio 3.8:1.
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Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
If and 9Ia, 9Ie–If resulting from (E)-enolates of 1a, 1e, and
1f furnished, on warming, unchanged Michael adducts 3Ia,
3Ie–If and a mixture of products 10Ia, 10Ie–If, 11I, and 12I
(Table 4, entries 3, 7, 8, and 10). This indicated that aldol
adducts 9I rearranged completely to 10–12I. Similar results
were obtained with benzylideneacetylacetone 2K, although
the reactions were less clean. The (Z)-enolate of 1a gave
Michael adduct 3Ka in low yield as a single diastereomer;
the major products proved to be aldol adduct 9Ka and di-
mer 13K resulting from self-condensation of 2K (Table 4,
entry 11). Use of the (E)-enolate of 1a led exclusively to
the formation of aldol adduct 9Ka in high yield (Table 4,
entry 13). Warming of the reaction mixtures to room tem-
perature was not beneficial; dimer 13K was the major prod-
uct under these conditions (Table 4, entries 12 and 14).
The dibenzoylmethane derivatives 3Ia–If displayed sim-
ilar NMR spectral properties to those of malonates 3Aa–
Ca. The resonances of the hydrogen atom at the dibenzo-
ylmethane units in the anti-diastereomers are downfield-
shifted by 0.2–0.29 ppm compared to those in the syn-dia-
stereomers (see the Supporting Information). Moreover, the
hydrogen atom at the ester-bearing position is ca. 0.2 ppm
downfield-shifted in all syn-isomers compared to the anti-
isomers. The major syn-diastereomer of the aldol adduct
9Ie crystallized and its structure was determined by X-ray
crystallography (Figure 2). It was confirmed that aldol ad-
dition occurred at the (E)-benzoyl group. The (Z)-config-
ured alkene unit is twisted by 7.4° from planarity. The
phenyl and ester groups are located antiperiplanar to each
other, a conformation that is enforced by a hydrogen bond
(2.0 Å) between the OH and COOtBu groups.
Discussion
Heathcock and co-workers found, in seminal contri-
butions, that Michael addition reactions of lithium ester
enolates to simple unsaturated ketones often take place with
good diastereoselectivity.[2] It was firmly established that
most Michael additions to ketones proceed through an ini-
tial reversible aldol addition reaction at low temperature,
which is followed by a rearrangement to the thermo-
dynamic Michael addition product on warming (Scheme 8,
Path BǞC).[19] The Michael addition reactions of ester
enolates 1a–f to benzylidene or alkylidenedicarboxylic acid
derivatives 2A–H presented herein, in contrast, most likely
proceed by a direct addition process according to Path A,
because aldol or Claisen type adducts were never detected
even at early stages of the Michael addition with acceptors
2A–H. Diketones 2I and 2K behave differently. The reac-
tions proceed with competing Michael and aldol addition
reactions. In the presence of HMPA, Michael addition
(Path A) is preferred with reasonable chemo- and stereose-
lectivity. Aldol adducts 9Ia–, 9Ie–, or 9If– form only to a
small extent at low temperature. They are, however, the pre-
dominant products in THF, where precoordination of enol-
ates 1– to 2I is expected to be stronger. However, in contrast
to the aldol adducts studied by Heathcock and Schultz,[2,19]
9Ia,Ie, and If do not undergo the retro-aldol reaction on the
same pathway they formed. Instead a retro-aldol process
(Path D) leading to β-keto esters 10, an E,Z mixture of
chalcones 11I and Michael adduct 12I, resulting from the
allenolate 11I–, is the exclusive pathway. (Benzylidene)-
acetylacetone 2K reacted similarly, however, the formation
Figure 2. View of aldol adduct syn-9Ie with atom numbering
scheme. The displacement ellipsoids are drawn at 30% probability
level. Selected bond lengths (Å) and angles (°): C(3)–O(1) 1.4259
(17), C(2)–C(27) 1.338 (2), C(6)–C(7) 1.328 (2), C(10)–O(3) 1.2147
(18), C(10)–O(4) 1.3323 (18); O(2)–C(1)–C(2)–C(3) 52.81 (19),
C(1)–C(2)–C(27)–C(28) 7.4 (2), O(2)–C(1)–C(2)–C(3) 52.81 (19),
C(5)–C(6)–C(7)–C(8) –176.57 (15), C(10)–C(4)–C(5)–C(6) 74.20
(16). Intramolecular hydrogen bond: O(1)–H(1)···O(3): O(1)–H(1)
0.93, H(1)···O(3) 2.00, O(1)···O(3) 2.8036 (15); O(1)–H(1)···O(3)
143.
Scheme 8. Michael versus aldol addition.
6
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Polyfunctional β-Dicarbonyl Compounds
of the Michael adduct 3 was even less favored. On warming sible for product formation. The situation is, however, con-
of the reaction mixture, dimerization product 13K became siderably more complex with acceptors 2 than with simple
predominant.
enones,[2] because both carbonyl groups can coordinate the
The diastereoselectivity of the Michael addition is good lithium ion of enolates 1 and s-trans as well as s-cis orienta-
to excellent for enolates of tert-butyl esters 1a or 1e and tions of the Michael acceptors are possible, thus the reac-
conformationally flexible malonate or dibenzoylmethane- tion can proceed via transition states 14–17 with (Z)-enol-
derived Michael acceptors 2A–C and 2I (Scheme 9). Ester ates of 1, or 18–21 with (E)-enolates of 1. Based on the
enolates (Z)-1– provide the adduct enolates anti-3– predomi- differential diastereoselectivity observed for substrates 2A–
nately, whereas (E)-1– leads to syn-3– in accord with the C,I vs. 2D–H, it can be concluded that the Michael addition
model put forward by Heathcock.[2] (Z)-Enolates of methyl step probably proceeds in the former by initial coordination
esters 1b and 1d tend to also give high anti-diastereoselec- to both carbonyl groups. This seems to be very important
tivity with 2A, whereas the corresponding (E)-enolates react for obtaining good diastereoselectivity, because nitrile-bear-
only with moderate syn-selectivity. Thus, it can be assumed ing 2E–G gave, in contrast to oxygen-containing com-
that an eight-membered chelated transition state is respon- pounds, no diastereoselectivity. It seems, however, that only
coordination to the (Z)-oriented carbonyl group leads to
good diastereoselectivity in the Michael addition via transi-
tion states 14, 15, 18, or 19. This is based on the fact that
cyanoacetates 2E and 2F, which have only (E)-oriented ester
groups, undergo the Michael addition with (E)- and (Z)-1–
with almost no diastereoselectivity. Thus, it is unlikely that
diastereoselective Michael addition reactions proceed
through transition states 16, 17, 20, or 21.
The preferred orientation of the carbonyl group in the
transition state is apparently s-trans, as in transition states
14 or 18, because Meldrum’s acid-derived acceptor 2D, in
which the conformation is fixed to s-cis, also undergoes the
addition only with very low diastereoselectivity. Thus, che-
lated transition states 15 and 19 seem to be less favored. It
must be noted that steric interactions between R2 and R3
are present on all possible trajectories of (Z)-1– to Michael
acceptors 2. The coordination of the HMPA additive to the
lithium ion (S = HMPA) also seems to play a role. Inspec-
tion of molecular models indicated that 1,3-diaxial interac-
tions are minimized in transition state 14 compared to 15
and 16. In the reaction of (E)-1–, transition state 18 is free
of steric interactions between the substituents, whereas in-
teractions of R1 and R3 in TS 19 or of R2 and R3 in 20 and
21 may disfavor them.
Potential triple-chelated transition states 22 and 23 might
also be responsible for the observed diastereoselectivity
(Scheme 10). However, to attain those transition states the
Scheme 9. Transition states for the Michael addition of ester enol-
ates to Michael acceptors 2A–C and 2I.
Scheme 10. Potential triple-chelated transition states.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
lithium cation would need to bend strongly out of the plane ates of 1 give the syn-diastereomers with moderate to good
of 2, reducing conjugation and, consequently, the resonance diastereoselectivity via chelated transition states. Michael
stabilization.
addition reactions with acceptors bearing only (E)-carbonyl
A sharp drop in the diastereoselectivity was observed groups, carbonyl groups fixed in s-cis-conformation, or ni-
when the ester groups in 2 were successively replaced by trile groups, apparently proceed through open transition
nitrile groups, as in 2E–G. The linear cyano group cannot states with low diastereoselectivity. The results presented
compete for coordination with THF or HMPA at the lith- herein form the basis for the design of anionic-radical reac-
ium cation of 1– and even if coordination would occur, en- tion sequences consisting of Michael addition coupled to
ergetically feasible chelated transition states, such as 14–21, radical 5-exo cyclizations or new tandem Michael additions.
could not be reached. Therefore, the Michael addition reac- Research along these lines is underway and will be reported
tion most likely proceeds through open transition states 24– in due course.
27 (Scheme 11). Steric interactions between the incoming
enolate 1– and the Michael acceptor 2E–G dominate on
Experimental Section
antiperiplanar or gauche (not shown) trajectories, thus, low
diastereoselectivity was observed for the addition. A similar
rationale may also hold for the addition reactions to Meld-
rum’s acid 2D, in which the carbonyl groups are fixed in an
s-cis-arrangement that precludes productive chelated transi-
tion states.
General: All reactions were conducted in flame- or oven-dried
glassware under a nitrogen atmosphere. THF and CH2Cl2 were
dried following standard methods under an argon atmosphere.
TLC plates POLYGRAM SIL G/UV254 (Macherey–Nagel) were
used to monitor reactions. Flash column chromatographic separa-
tions were performed on silica gel 60 (Fluka, 230–400 mesh). IR
spectra were recorded with a Bruker ALPHA FTIR spectrometer
as neat samples using an ATR device. 1H and 13C NMR spectra
were recorded, unless otherwise noted, in CDCl3 with Bruker Av-
ance 500 or 400 spectrometers (500.0 and 400.1 MHz for 1H NMR
or 125.7 and 100.6 MHz for 13C NMR), or with a Bruker AC-
200 spectrometer (200.1 MHz for H NMR and 50.1 MHz for 13C
1
NMR). Connectivity was determined by 1H-1H COSY experi-
ments. Relative configurations were determined by NOE or
NOESY experiments. 13C NMR assignments were obtained from
DEPT and HSQC experiments. EI-MS were recorded with a
Waters GCT Premier spectrometer operating at 70 eV. ESI-MS
were obtained with a Thermo Fisher Scientific LCQ Fleet spec-
trometer (sample concentration approx. 1 μg/mL, spray voltage
pos. mode: 3.3 kV). HRMS spectra were measured with a Waters
Q-Tof micro spectrometer (resolution: 100000). Combustion analy-
ses were performed at the Microanalytical Laboratories of the
IOCB ASCR Prague. Melting points are uncorrected. Esters 1a,[20]
1b,[21] 1c,[22] 1d,[23] 1e,[24] 1f,[22] and Michael acceptors 2D,[25] 2E,[26]
2F,[27] 2H,[28] and 2I[29] were prepared according to literature pro-
cedures.
syn-Selective Michael Addition of 1 to 2; General Procedure: To a
solution of iPr2NH (210 μL, 1.6 mmol) in anhydrous THF (13 mL)
was added nBuLi (1.6 m in hexane, 1.0 mL, 1.6 mmol) at –78 °C
under a N2 atmosphere. After stirring for 30 min, a solution of ester
1 (1.25 mmol) in anhydrous THF (0.5 mL) was added by using a
syringe. The reaction mixture was stirred at –78 °C for 30 min and
2 (1 mmol) was added either neat (2A–C, 2F, 2H, or 2K) or as a
solution in THF (0.5 mL, 2D, 2E, 2G, or 2I). The mixture was
warmed slowly from –78 to –40 °C until the reaction was complete
(reaction monitored by TLC; ca 2 h). The reaction mixture was
quenched by addition of either four drops of water (2A–C, 2E, and
2F) or HCOOH (130 μL; 2D, 2G–K), stirred for 5 min, diluted with
diethyl ether to double volume and filtered through a plug of silica
gel. The solvent was evaporated and the thick oil was purified by
column chromatography (silica gel; hexane/EtOAc, 20:1 to 10:1) to
give some β-keto ester resulting from self-condensation of excess
ester enolate, followed by a syn/anti mixture of Michael adducts 3.
Scheme 11. Open transition states for Michael addition reactions
of enolates 1 to acceptors 2E–G.
Conclusions
Michael addition reactions of ester enolates to α-benzyl-
idene and α-alkylidene β-dicarbonyl compounds proceed in
good yields with all acceptors except those bearing acidic
αЈ-protons, such as benzylideneacetylacetone. The Michael
addition proceeds directly at the β-position with carboxylic
acceptors. Michael acceptors bearing keto groups undergo
competing irreversible Michael and reversible aldol ad-
ditions. The former reaction is strongly predominant in the
presence of THF/HMPA, whereas the aldol process prevails
in THF alone. (Z)-Enolates of esters 1 react with good anti-
diastereoselectivity with Michael acceptors bearing confor-
anti-Selective Michael Addition of 1 to 2; General Procedure: To a
solution of iPr2NH (210 μL, 1.6 mmol) in anhydrous THF (10 mL)
was added nBuLi (1.6 m in hexane, 1.0 mL, 1.6 mmol) at –78 °C
mationally flexible (Z)-carbonyl groups, whereas (E)-enol- under a N2 atmosphere. After stirring for 30 min, anhydrous
8
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Polyfunctional β-Dicarbonyl Compounds
HMPA (2.5 mL) was added by using a syringe. A solution of 1
(1.25 mmol) in anhydrous THF (0.5 mL) was added by using a sy-
ringe. The reaction mixture was stirred at –78 °C for 30 min and 2
(1 mmol) was added either neat (2A–C, 2F, 2H, 2K) or as a solution
in THF (0.5 mL; 2D, 2E, 2G, 2I). The mixture was warmed slowly
from –78 to –40 °C until the reaction was complete (reaction moni-
tored by TLC; ca 2 h). The reaction mixture was quenched by the
addition of either four drops of water (2A–C, 2E, 2F) or HCOOH
(130 μL; 2D, 2G–K), stirred for 5 min, diluted with diethyl ether to
double volume, and filtered through a plug of silica gel. The solvent
was evaporated and the thick oil was purified by column
chromatography (silica gel; hexane/EtOAc, 20:1 to 10:1) to give the
β-keto ester resulting from self-condensation of excess ester enolate,
followed by an anti/syn mixture of Michael adducts 3.
5.00 (m, 2 H, =CH2), 5.68 (m, 1 H, =CH), 7.04 (m, 2 H, Ph), 7.16
(m, 3 H, Ph) ppm. 13C NMR (100 MHz): δ = 13.50 (q, OCH2CH3),
14.0 (q, OCH2CH3), 34.0 (t, =CHCH2), 46.4 (d, PhCH), 47.1 (d,
MeOOCCH), 51.3 (q, OCH3), 55.3 [d, (EtOOC)2CH], 61.2 (t,
OCH2), 61.6 (t, OCH2), 117.2 (t, =CH2), 127.40 (d, p-Ph), 128.0
(d, Ph), 129.0 (d, Ph), 135.3 (d, =CH), 136.9 (s, ipso-Ph), 167.6 (s,
COOEt), 168.1 (s, COOEt), 173.1 (s, COOMe) ppm.
syn-3Ab: 1H NMR (400 MHz): δ = 0.89 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.14 (t, J = 7.0 Hz, 3 H, OCH2CH3), 1.96 (m, 1 H,
=CHCH2), 2.09 (m, 1 H, =CHCH2), 2.90 (ddd, J = 8.6, 6.9, 3.5 Hz,
1 H, MeOOCCH), 3.56 (s, 3 H, OCH3), 3.73 (dd, J = 9.4, 8.6 Hz,
1 H, PhCH), 3.81 (q, J = 7.1 Hz, 2 H, OCH2), 3.85 [d, J = 9.4 Hz,
1 H, (EtOOC)2CH], 4.07 (q, J = 7.0 Hz, 2 H, OCH2), 4.84 (m, 2
H, =CH2), 5.55 (m, 1 H, =CH), 7.16 (m, 5 H, Ph) ppm. 13C NMR
(100 MHz): δ = 13.55 (q, OCH2CH3), 13.8 (q, OCH2CH3), 33.5 (t,
=CHCH2), 46.6 (d, PhCH), 48.7 (d, MeOOCCH), 51.4 (q, OCH3),
55.8 [d, (EtOOC)2CH], 61.1 (t, OCH2), 61.5 (t, OCH2), 116.8 (t,
=CH2), 127.35 (d, p-Ph), 128.2 (d, Ph), 129.0 (d, Ph), 135.0 (d,
anti/syn-3-tert-Butyl 1,1-Diethyl 2-Phenylhex-5-ene-1,1,3-tricarb-
oxylates (3Aa): Colorless oil; R = 0.51 (hexane/EtOAc, 5:1). IR: ν
˜
f
= 2979, 1728, 1367, 1147, 1031, 701 cm–1. MS (ESI+): m/z (%) =
443 (9) [M + K+], 427 (100) [M + Na+], 371 (82) [M + Na+
–
H2C=C(CH3)2], 331 (21) [M+ – COOEt]. C23H32O6 (404.50): calcd. =CH), 137.8 (s, ipso-Ph), 167.3 (s, COOEt), 167.8 (s, COOEt),
C 68.29, H 7.97; found C 68.07, H 8.15. 173.7 (s, COOMe) ppm.
anti-3Aa: 1H NMR (400 MHz): δ = 0.83 (t, J = 7.1 Hz, 3 H, anti/syn-(E)-1,1,3-Triethyl 2,6-Diphenylhex-5-ene-1,1,3-tricarboxy-
OCH2CH3), 1.20 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.25 [s, 9 H, lates (3Ac): Colorless oil. IR: ν = 3062, 3030, 2983, 2938, 1751,
˜
C(CH3)3], 2.00–2.20 (m, 2 H, =CHCH2), 2.89 (dt, J = 9.1, 6.3 Hz,
1 H, tBuOOCCH), 3.58 (dd, J = 10.5, 6.3 Hz, 1 H, PhCH), 3.79
(q, J = 7.1 Hz, 2 H, OCH2), 4.06 [d, J = 10.5 Hz, 1 H, (EtOOC)2-
1733, 1496, 1455, 1370, 1302, 1260, 1212, 1177, 1097, 1031, 745,
702 cm–1. MS (EI): m/z (%) = 452 (17) [M+], 407 (14), 378 (34),
361 (17), 332 (24), 304 (15), 287 (13), 250 (100), 219 (46), 203 (87),
CH], 4.16 (dq, J = 10.8, 7.1 Hz, 1 H, OCH2), 4.17 (dq, J = 10.8, 176 (29), 157 (49), 131 (43), 117 (58), 103 (24), 91 (52), 77 (14).
7.1 Hz, 1 H, OCH2), 4.97 (m, 2 H, =CH2), 5.68 (ddt, J = 17.0,
10.2, 6.8 Hz, 1 H, =CH), 7.15 (m, 5 H, PhH) ppm. 13C NMR
(100 MHz): δ = 13.6 (q, OCH2CH3), 14.0 (q, OCH2CH3), 27.9 [q,
C(CH3)3], 34.7 (t, =CHCH2), 46.7 (d, PhCH), 48.1 (d,
tBuOOCCH), 55.6 [d, (EtOOC)2CH], 61.2 (t, OCH2), 61.5 (t,
OCH2), 80.8 [s, C(CH3)3], 116.8 (t, =CH2), 127.3 (d, p-Ph), 127.8
(d, Ph), 129.6 (d, Ph), 135.5 (d, =CH), 137.3 (s, ipso-Ph), 167.8 (s,
COOEt), 168.2 (s, COOEt), 171.9 (s, COOtBu) ppm.
C27H32O6 (452.55): calcd. C 71.66, H 7.13; found C 71.56, H 7.17.
(E)-anti-3Ac: 1H NMR (400 MHz): δ = 0.84 (t, J = 7.2 Hz, 3 H,
OCH2CH3), 1.11 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.24 (t, J =
7.1 Hz, 3 H, OCH2CH3), 2.26 (m, 1 H, =CHCH2), 2.40 (m, 1 H,
=CHCH2), 3.10 (dt, J = 8.7, 5.7 Hz, 1 H, EtOOCCH), 3.71 (dd, J
= 11.2, 5.4 Hz, 1 H, PhCH), 3.81 (2 ϫ q, J = 7.1 Hz, 2 H, OCH2),
4.01 (dq, J = 10.8, 7.2 Hz, 2 H, OCH2), 4.14 [d, J = 11.1 Hz, 1 H,
(EtOOC)2CH], 4.20 (q, J = 7.2 Hz, 2 H, OCH2), 6.09 (dt, J = 15.7,
7.1 Hz, 1 H, =CH), 6.35 (d, J = 15.8 Hz, 1 H, =CHPh), 7.11–7.29
syn-3Aa: 1H NMR (400 MHz): δ = 0.97 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.12 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.35 [s, 9 H, (m, 10 H, Ph) ppm. 13C NMR (100 MHz): δ = 13.6 (q, OCH2CH3),
C(CH3)3], 1.99–2.11 (m, 2 H, =CHCH2), 2.86 (ddd, J = 9.6, 8.4,
4.2 Hz, 1 H, tBuOOCCH), 3.68 (t, J = 8.4 Hz, 1 H, PhCH), 3.86
14.0 (q, 2 C, OCH2CH3), 33.6 (t, =CHCH2), 46.8 (d, PhCH), 47.6
(d, EtOOCCH), 55.5 [d, (EtOOC)2CH], 60.4 (t, OCH2), 61.23 (t,
[d, J = 8.4 Hz, 1 H, (EtOOC)2CH], 3.87 (dq, J = 10.2, 7.1 Hz, 1 OCH2), 61.6 (t, OCH2), 126.1 (d, Ph), 127.1 (d, 2 C, 2 Ph or
H, OCH2), 3.90 (dq, J = 10.2, 7.1 Hz, 1 H, OCH2), 4.05 (dq, J =
10.7, 7.1 Hz, 1 H, OCH2), 4.06 (dq, J = 10.7, 7.1 Hz, 1 H, OCH2),
Ph+CH=), 127.5 (d, Ph or CH=), 128.0 (d, Ph), 128.42 (d, Ph),
129.2 (d, Ph), 132.3 (d, =CH), 137.0 (s, ipso-Ph), 137.4 (s, ipso-Ph),
4.87 (m, 2 H, =CH2), 5.59 (m, 1 H, =CH), 7.15 (m, 5 H, Ph) ppm. 167.7 (s, COOEt), 168.2 (s, COOEt), 172.7 (s, COOEt) ppm.
13C NMR (100 MHz):
δ = 13.7 (q, OCH2CH3), 13.9 (q,
(E)-syn-3Ac: 1H NMR (400 MHz): δ = 0.95 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.18 (t, J = 7.1 Hz, 6 H, OCH2CH3), 2.33 (m, 2 H,
=CHCH2), 3.02 (m, 1 H, EtOOCCH), 3.71 (m, 1 H, PhCH), 3.88
(q, J = 7.1 Hz, 2 H, OCH2), 3.92 [d, J = 9.3 Hz, 1 H, (EtOOC)2-
CH], 3.94–4.11 (m, 4 H, OCH2), 5.98 (ddd, J = 15.7, 7.4, 6.8 Hz,
1 H, =CH), 6.22 (d, J = 15.8 Hz, 1 H, =CHPh), 7.03–7.29 (m, 10
H, Ph) ppm. 13C NMR (100 MHz): δ = 13.7 (q, OCH2CH3), 13.9
(q, OCH2CH3), 14.2 (q, OCH2CH3), 33.0 (t, =CHCH2), 46.7 (d,
PhCH), 49.0 (d, EtOOCCH), 55.8 [d, (EtOOC)2CH], 60.6 (t,
OCH2), 61.19 (t, OCH2), 61.6 (t, OCH2), 126.0 (d, Ph), 127.8 (d,
Ph or CH=), 128.1 (d, Ph or CH=), 128.2 (d, Ph or CH=), 128.39
(d, Ph), 128.7 (d, Ph), 129.1 (d, Ph), 132.1 (d, PhCH=), 137.3 (s,
ipso-Ph), 137.9 (s, ipso-Ph), 167.5 (s, COOEt), 168.0 (s, COOEt),
173.4 (s, COOEt) ppm.
OCH2CH3), 28.0 [q, C(CH3)3], 33.9 (t, =CHCH2), 46.6 (d, PhCH),
48.9 (d, tBuOOCCH), 55.3 [d, (EtOOC)2CH], 61.1 (t, OCH2), 61.4
(t, OCH2), 81.0 [s, C(CH3)3], 116.6 (t, =CH2), 127.2 (d, p-Ph), 128.0
(d, Ph), 129.5 (d, Ph), 135.2 (d, =CH), 137.8 (s, ipso-Ph), 167.6 (s,
COOEt), 168.0 (s, COOEt), 172.7 (s, COOtBu) ppm.
anti/syn 1,1-Diethyl 3-Methyl 2-Phenylhex-5-ene-1,1,3-tricarb-
oxylates (3Ab): Colorless oil; R = 0.28 (hexane/EtOAc, 5:1). IR: ν
˜
f
= 3065, 3032, 2983, 2952, 1736, 1455, 1370, 1258, 1242, 1220, 1196,
1175, 1032, 704 cm–1. MS (EI): m/z (%) = 362 (6) [M+], 331 (12),
321 (25), 302 (94), 289 (48), 256 (41), 250 (52), 229 (70), 210 (28),
203 (44), 182 (38), 176 (37), 155 (65), 143 (66), 131 (100), 103 (48),
91 (31), 77 (22). C20H26O6 (362.43): calcd. C 66.28, H 7.23; found
C 66.34, H 7.36.
anti-3Ab: 1H NMR (400 MHz): δ = 0.80 (t, J = 7.1 Hz, 3 H, anti/syn-1,1-Diethyl 3-Methyl 6-Methyl-2-phenylhept-5-ene-1,1,3-
OCH2CH3), 1.21 (t, J = 7.1 Hz, 3 H, OCH2CH3), 2.06 (m, 1 H, tricarboxylates (3Ad): Colorless oil. IR: ν = 3063, 3031, 2952, 2935,
˜
=CHCH2), 2.22 (m, 1 H, =CHCH2), 2.98 (ddd, J = 8.3, 6.6, 4.9 Hz,
1 H, MeOOCCH), 3.54 (s, 3 H, OCH3), 3.64 (dd, J = 11.3, 4.9 Hz,
1 H, PhCH), 3.77 (2 ϫ q, J = 7.1 Hz, 2 H, OCH2), 4.11 [d, J =
11.3 Hz, 1 H, (EtOOC)2CH], 4.17 (2 ϫ q, J = 7.1 Hz, 2 H, OCH2),
1736, 1454, 1370, 1302, 1256, 1247, 1201, 1174, 1157, 1097 cm–1.
MS (EI): m/z (%) = 390 (4) [M+], 359 (4), 345 (8), 330 (39), 313
(9), 299 (13), 284 (8), 256 (24), 250 (100), 176 (40), 171 (54), 141
(43), 131 (55), 109 (31), 103 (24), 81 (15), 69 (14). C22H30O6
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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9

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
(390.48): calcd. C 67.67, H 7.74; found (anti) C 67.47, H 7.85; (syn) OCH2CH3), 13.9 (q, OCH2CH3), 17.6 [q, (Z)- =CCH3], 25.67 [q,
FULL PAPER
C 67.72, H 7.85.
(E)- =CCH3], 27.9 [q, C(CH3)3], 28.8 (t, =CHCH2), 46.7 (d,
PhCH), 49.5 (d, tBuOOCCH), 55.4 [d, (EtOOC)2CH], 61.0 (t,
OCH2), 61.3 (t, OCH2), 80.6 [s, C(CH3)3], 121.0 (d, =CH), 127.2
(d, Ph), 127.9 (d, Ph), 129.6 (d, Ph), 133.1 [s, =C(CH3)2], 138.0 (s,
ipso-Ph), 167.7 (s, COOEt), 168.1 (s, COOEt), 173.4 (s, CO-
OtBu) ppm.
anti-3Ad: 1H NMR (400 MHz): δ = 0.85 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.25 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.50 (s, 3 H,
=CCH3), 1.65 (s, 3 H, =CCH3), 2.05 (m, 1 H, =CHCH2), 2.17 (m,
1 H, =CHCH2), 2.93 (ddd, J = 8.3, 6.8, 5.1 Hz, 1 H, MeOOCCH),
3.54 (s, 3 H, OCH3), 3.67 (dd, J = 11.3, 5.1 Hz, 1 H, PhCH), 3.81
(q, J = 7.1 Hz, 1 H, OCH2), 3.82 (q, J = 7.1 Hz, 1 H, OCH2), 4.12
[d, J = 11.3 Hz, 1 H, (EtOOC)2CH], 4.200 (q, J = 7.1 Hz, 1 H,
OCH2), 4.205 (q, J = 7.1 Hz, 1 H, OCH2), 5.05 (ddt, J = 7.6, 6.3,
1.3 Hz, 1 H, =CH), 7.06 (m, 2 H, Ph), 7.18 (m, 3 H, Ph) ppm. 13C
NMR (100 MHz): δ = 13.5 (q, OCH2CH3), 14.0 (q, OCH2CH3),
17.8 [q, (Z)- =CCH3], 25.7 [q, (E)- =CCH3], 28.4 (t, =CHCH2),
46.6 (d, PhCH), 47.9 (d, MeOOCCH), 51.2 (q, OCH3), 55.4 [d,
(EtOOC)2CH], 61.1 (t, OCH2), 61.6 (t, OCH2), 121.0 (d, =CH),
127.3 (d, p-Ph), 127.9 (d, Ph), 129.0 (d, Ph), 133.9 [s, =C(CH3)2],
137.2 (s, ipso-Ph), 167.7 (s, COOEt), 168.2 (s, COOEt), 173.5 (s,
COOMe) ppm.
syn-3Ad: 1H NMR (400 MHz): δ = 0.90 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.16 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.34 (s, 3 H,
=CCH3), 1.54 (s, 3 H, =CCH3), 1.88 (m, 1 H, =CHCH2), 2.03 (m,
1 H, =CHCH2), 2.83 (ddd, J = 10.3, 8.8, 3.8 Hz, 1 H, MeOOCCH),
3.58 (s, 3 H, OCH3), 3.71 (dd, J = 9.3, 8.8 Hz, 1 H, PhCH), 3.82
(q, J = 7.2 Hz, 2 H, OCH2), 3.84 [d, J = 9.3 Hz, 1 H, (EtOOC)2-
CH], 4.07 (q, J = 7.2 Hz, 2 H, OCH2), 4.87 (t, J = 7.2 Hz, 1 H,
=CH), 7.16 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 13.6 (q,
OCH2CH3), 13.9 (q, OCH2CH3), 17.5 [q, (Z)- =CCH3], 25.6 [q,
(E)- =CCH3], 28.1 (t, =CHCH2), 46.7 (d, PhCH), 49.3 (d,
MeOOCCH), 51.5 (q, OCH3), 56.0 [d, (EtOOC)2CH], 61.1 (t,
OCH2), 61.5 (t, OCH2), 120.6 (d, =CH), 127.3 (d, p-Ph), 128.1 (d,
Ph), 129.1 (d, Ph), 133.8 [s, =C(CH3)2], 138.1 (s, ipso-Ph), 167.5 (s,
COOEt), 168.0 (s, COOEt), 174.3 (s, COOMe) ppm.
anti/syn-3-tert-Butyl 1,1-Diethyl 2-Methylhex-5-ene-1,1,3-tricarb-
oxylates (3Ba): Colorless liquid; Rf = 0.5 (hexane/EtOAc, 5:1). IR:
ν = 2979, 1751, 1726, 1678, 1367, 1149, 1029 cm–1. MS (ESI+): m/z
˜
(%) = 381 (14) [M + K+], 365 (100) [M + Na+], 309 (45) [M +
Na+ – H2C=C(CH3)2]. C18H30O6 (342.43): calcd. C 63.14, H 8.83;
found C 63.19, H 8.98.
anti-3Ba: 1H NMR (400 MHz): δ = 0.90 (d, J = 6.8 Hz, 3 H,
CH3CH), 1.20 (t, J = 7.2 Hz, 6 H, OCH2CH3), 1.38 [s, 9 H,
C(CH3)3], 2.13 (m, 1 H, =CHCH2), 2.36 (m, 1 H, =CHCH2), 2.42
(m, 1 H, CH3CH), 2.45 (m, 1 H, tBuOOCCH), 3.48 [d, J = 8.9 Hz,
1 H, (EtOOC)2CH], 4.14 (m, 4 H, OCH2), 4.96 (dd, J = 10.1,
1.7 Hz, 1 H, cis =CH2), 5.01 (dd, J = 17.1, 1.7 Hz, 1 H, trans
=CH2), 5.68 (ddt, J = 16.9, 10.1, 6.8 Hz, 1 H, =CH) ppm. 13C
NMR (100 MHz): δ = 13.3 (q, CH3CH), 14.25 (q, OCH2CH3),
14.30 (q, OCH2CH3), 28.4 [q, C(CH3)3], 34.7 (t, =CHCH2), 35.0
(d, CH3CH), 48.0 (d, tBuOOCCH), 55.9 [d, (EtOOC)2CH], 61.4 (t,
OCH2), 61.5 (t, OCH2), 81.0 [s, C(CH3)3], 116.9 (t, =CH2), 135.6
(d, =CH), 168.69 (s, COOEt), 168.71 (s, COOEt), 172.8 (s, CO-
OtBu) ppm.
syn-3Ba: 1H NMR (400 MHz): δ = 0.98 (d, J = 7.0 Hz, 3 H,
CH3CH), 1.20 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.21 (t, J = 7.1 Hz,
3 H, OCH2CH3), 1.37 [s, 9 H, C(CH3)3], 2.10–2.30 (m, 2 H,
=CHCH2), 2.36 (ddd, J = 9.6, 7.4, 4.2 Hz, 1 H, tBuOOCCH), 2.52
(sext, J = 6.9 Hz, 1 H, CH3CH), 3.38 [d, J = 6.8 Hz, 1 H, (EtOOC)2-
CH], 4.14 (m, 4 H, OCH2), 4.93 (d, J = 10.1 Hz, 1 H, cis =CH2),
4.99 (d, J = 17.1 Hz, 1 H, trans =CH2), 5.67 (ddt, J = 17.1, 10.2,
6.8 Hz, 1 H, =CH) ppm. 13C NMR (100 MHz): δ = 13.6 (q,
CH3CH), 14.27 (q, OCH2CH3), 14.30 (q, OCH2CH3), 28.3 [q,
C(CH3)3], 32.7 (t, =CHCH2), 35.1 (d, CH3CH), 49.0 (d,
tBuOOCCH), 55.1 [d, (EtOOC)2CH], 61.3 (t, OCH2), 61.6 (t,
OCH2), 80.9 [s, C(CH3)3], 116.8 (t, =CH2), 135.7 (d, =CH), 168.5
(s, COOEt), 168.9 (s, COOEt), 173.6 (s, COOtBu) ppm.
anti/syn-3-tert-Butyl 1,1-Diethyl 6-Methyl-2-phenylhept-5-ene-1,1,3-
tricarboxylates (3Ae): Colorless oil; Rf = 0.4 (hexane/EtOAc, 5:1).
IR: ν = 3090, 3064, 3033, 2980, 2933, 2878, 1754, 1733, 1455, 1392,
˜
1368, 1257, 1249, 1217, 1174, 1148, 1032, 701 cm–1. MS (EI): m/z
(%) = 432 (5) [M+], 376 (20) [M+ – H2C=C(CH3)2], 359 (7), 330
(29), 284 (7), 250 (100), 203 (9), 176 (31), 171 (23), 131 (23), 91 (6),
57 (19). C25H36O6 (432.55): calcd. C 69.42, H 8.39; found C 69.31,
H 8.53.
anti/syn-3-tert-Butyl 1,1-Diethyl 2,6-Dimethylhept-5-ene-1,1,3-tri-
anti-3Ae: 1H NMR (200 MHz): δ = 0.88 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.23 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.25 [s, 9 H,
C(CH3)3], 1.51 (s, 3 H, =CCH3), 1.64 (s, 3 H, =CCH3), 1.94–2.21
(m, 2 H, =CHCH2), 2.86 (m, 1 H, tBuOOCCH), 3.62 (dd, J = 10.2,
6.9 Hz, 1 H, PhCH), 3.83 (q, J = 7.1 Hz, 2 H, OCH2), 4.02 [d, J
= 10.2 Hz, 1 H, (EtOOC)2CH], 4.17 (q, J = 7.1 Hz, 1 H, OCH2),
4.18 (q, J = 7.2 Hz, 1 H, OCH2), 5.05 (t, J = 7.1 Hz, 1 H, =CH),
7.18 (m, 5 H, Ph) ppm. 13C NMR (50 MHz): δ = 13.6 (q,
OCH2CH3), 14.0 (q, OCH2CH3), 17.8 [q, (Z)- =CCH3], 25.71 [q,
(E)- =CCH3], 27.8 [q, C(CH3)3], 29.2 (t, =CHCH2), 46.9 (d,
PhCH), 49.1 (d, MeOOCCH), 55.6 [d, (EtOOC)2CH], 61.1 (t,
OCH2), 61.5 (t, OCH2), 80.4 [s, C(CH3)3], 121.2 (d, =CH), 127.2
(d, p-Ph), 127.7 (d, Ph), 129.6 (d, Ph), 133.4 [s, =C(CH3)2], 137.6
(s, ipso-Ph), 167.8 (s, COOEt), 168.3 (s, COOEt), 172.4 (s, CO-
OtBu) ppm.
carboxylates (3Be): Colorless oil. IR: ν = 2980, 2952, 2935, 1754,
˜
1732, 1456, 1392, 1368, 1302, 1251, 1223, 1215, 1176, 1150, 1032,
849 cm–1. MS (EI): m/z (%) = 370 (0.5) [M+], 314 (13) [M+
–
H2C=C(CH3)2], 297 (8), 268 (100), 251 (17), 222 (14), 194 (69), 187
(14), 121 (34), 109 (27), 69 (7), 57 (35). C20H34O6 (370.48): calcd.
C 64.84, H 9.25; found C 64.83, H 9.56.
anti-3Be: 1H NMR (200 MHz): δ = 0.95 (d, J = 6.7 Hz, 3 H,
CH3CH), 1.24 (t, J = 7.1 Hz, 6 H, OCH2CH3), 1.40 [s, 9 H,
C(CH3)3], 1.58 (s, 3 H, =CCH3), 1.64 (s, 3 H, =CCH3), 2.10–2.54
(m, 4 H, =CHCH2, CH3CH, tBuOOCCH), 3.50 [d, J = 8.4 Hz, 1
H, (EtOOC)2CH], 4.16 (q, J = 7.1 Hz, 4 H, OCH2), 5.03 (m, 1 H,
=CH) ppm. 13C NMR (50 MHz): δ = 13.3 (q, CH3CH), 14.04 (q,
OCH2CH3), 17.7 [q, (Z)- =CCH3], 25.7 [q, (E)- =CCH3], 28.0 [q,
C(CH3)3], 28.9 (t, =CHCH2), 34.96 (d, CH3CH), 48.6 (d,
tBuOOCCH), 55.4 [d, (EtOOC)2CH], 61.16 (t, OCH2), 61.22 (t,
OCH2), 80.5 [s, C(CH3)3], 121.1 (d, =CH), 133.4 [s, =C(CH3)2],
168.53 (s, COOEt), 168.55 (s, COOEt), 173.1 (s, COOtBu) ppm.
syn-3Ae: 1H NMR (200 MHz): δ = 1.00 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.14 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.37 [s, 9 H,
C(CH3)3], 1.39 (s, 3 H, =CCH3), 1.58 (s, 3 H, =CCH3), 1.94–2.21
(m, 2 H, =CHCH2), 2.86 (m, 1 H, tBuOOCCH), 3.67 (m, 1 H,
syn-3Be: 1H NMR (200 MHz): δ = 1.02 (d, J = 6.9 Hz, 3 H,
PhCH), 3.88 [d, J = 8.2 Hz, 1 H, (EtOOC)2CH], 3.92 (q, J = CH3CH), 1.25 (t, J = 7.1 Hz, 6 H, OCH2CH3), 1.39 [s, 9 H,
7.2 Hz, 2 H, OCH2), 4.06 (m, 2 H, OCH2), 4.95 (m, 1 H, =CH), C(CH3)3], 1.58 (s, 3 H, =CCH3), 1.64 (s, 3 H, =CCH3), 2.10–2.54
7.18 (m, 5 H, Ph) ppm. 13C NMR (50 MHz): δ = 13.7 (q,
(m, 4 H, =CHCH2, CH3CH, tBuOOCCH), 3.42 [d, J = 6.4 Hz, 1
10
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Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
Polyfunctional β-Dicarbonyl Compounds
H, (EtOOC)2CH], 4.17 (q, J = 7.2 Hz, 4 H, OCH2), 5.03 (m, 1 H, 699 cm–1. MS (ESI+): m/z (%) = 380 (58) [M + Na+], 324 [M +
=CH) ppm. 13C NMR (50 MHz): δ = 13.4 (q, CH3CH), 13.96 (q, Na+ – H2C=C(CH3)2]. C21H27NO4 (357.44): calcd. C 70.56, H
OCH2CH3), 17.7 [q, (Z)- =CCH3], 25.7 [q, (E)- =CCH3], 27.2 (t, 7.61, N 3.92; found C 70.70, H 7.88, N 3.78.
=CHCH2), 27.9 [q, C(CH3)3], 35.00 (d, CH3CH), 49.3 (d,
1
anti-3Ea (Diastereomer 1): H NMR (400 MHz): δ = 1.07 (t, J =
tBuOOCCH), 54.8 [d, (EtOOC)2CH], 61.0 (t, OCH2), 61.22 (t,
OCH2), 80.3 [s, C(CH3)3], 121.2 (d, =CH), 133.2 [s, =C(CH3)2],
168.3 (s, COOEt), 168.7 (s, COOEt), 173.9 (s, COOtBu) ppm.
7.1 Hz, 3 H, OCH2CH3), 1.14 [s, 9 H, C(CH3)3], 2.26 (m, 2 H,
=CHCH2), 3.12 (dt, J = 8.7, 6.0 Hz, 1 H, tBuOOCCH), 3.50 (dd,
J = 8.8, 6.4 Hz, 1 H, PhCH), 3.98 [d, J = 6.4 Hz, 1 H,
(EtOOC)(NC)CH], 4.05 (q, J = 7.1 Hz, 2 H, OCH2), 5.04 (m, 2 H,
=CH2), 5.70 (m, 1 H, =CH), 7.16–7.28 (m, 5 H, Ph) ppm. 13C
NMR (100 MHz): δ = 14.3 (q, OCH2CH3), 27.9 [q, C(CH3)3], 34.8
(t, =CHCH2), 42.4 [d, (EtOOC)(NC)CH], 47.7 (d, PhCH), 48.6 (d,
tBuOOCCH), 63.0 (t, OCH2), 81.5 [s, C(CH3)3], 115.86 (s, CN),
117.9 (t, =CH2), 128.3 (d, p-Ph), 128.66 (d, Ph), 128.73 (d, Ph),
134.5 (d, =CH), 137.3 (s, ipso-Ph), 165.2 (s, COOEt), 171.4 (s, CO-
OtBu) ppm.
3-tert-Butyl 1,1-Diethyl 2,2-Dimethylhex-5-ene-1,1,3-tricarboxylate
(3Ca): Colorless liquid. R = 0.55 (hexane/EtOAc, 5:1). IR: ν =
˜
f
2979, 1755, 1723, 1466, 1366, 1145, 1035 cm–1. MS (ESI+): m/z (%)
= 379 (100) [M + Na+], 323 (60) [M + Na+ – H2C=C(CH3)2].
C19H32O6 (356.45): calcd. C 64.02, H 9.05; found C 64.04, H 9.07.
1H NMR (400 MHz): δ = 1.13 (s, 3 H, CH3C), 1.19 (s, 3 H, CH3C),
1.23 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.24 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.39 [s, 9 H, C(CH3)3], 2.19 (m, 1 H, =CHCH2), 2.31
(m, 1 H, =CHCH2), 2.68 (dd, J = 11.8, 3.1 Hz, 1 H, tBuOOCCH),
3.45 [s, 1 H, (EtOOC)2CH], 4.15 (m, 4 H, OCH2), 4.95 (d, J =
10.1 Hz, 1 H, cis =CH2), 5.03 (ddd, J = 17.1, 3.0, 1.6 Hz, 1 H, trans
1
anti-3Ea (Diastereomer 2): H NMR (400 MHz): δ = 0.94 (t, J =
7.1 Hz, 3 H, OCH2CH3), 1.01 [s, 9 H, C(CH3)3], 2.39 (m, 2 H,
=CHCH2), 3.05 (ddd, J = 11.4, 9.4, 4.6 Hz, 1 H, tBuOOCCH),
3.46 (dd, J = 11.4, 5.3 Hz, 1 H, PhCH), 3.93 (m, 2 H, OCH2), 3.98
[d, J = 5.3 Hz, 1 H, (EtOOC)(NC)CH], 5.06 (d, J = 10.1 Hz, 1 H,
cis =CH2), 5.11 (d, J = 17.1 Hz, 1 H, trans =CH2), 5.78 (m, 1 H,
=CH), 7.16–7.28 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 13.8
(q, OCH2CH3), 27.7 [q, C(CH3)3], 35.12 (t, =CHCH2), 41.5 [d,
(EtOOC)(NC)CH], 47.2 (d, PhCH), 49.0 (d, tBuOOCCH), 62.84
(t, OCH2), 81.2 [s, C(CH3)3], 115.1 (s, CN), 118.2 (t, =CH2), 128.43
(d, p-Ph), 128.48 (d, Ph), 129.2 (d, Ph), 133.86 (d, =CH), 136.6 (s,
ipso-Ph), 165.0 (s, COOEt), 171.5 (s, COOtBu) ppm.
=CH2), 5.66 (dddd, J = 17.1, 10.1, 7.6, 6.0 Hz, 1 H, =CH) ppm. 13
C
NMR (100 MHz): δ = 14.2 (q, OCH2CH3), 14.3 (q, OCH2CH3),
21.9 (q, CH3C), 22.6 (q, CH3C), 28.2 [q, C(CH3)3], 31.9 (t,
=CHCH2), 38.3 [s, (CH3)2C], 53.0 (d, tBuOOCCH), 58.7 [d,
(EtOOC)2CH], 80.9 [s, C(CH3)3], 116.7 (t, =CH2), 136.0 (d, =CH),
168.0 (s, COOEt), 168.3 (s, COOEt), 173.1 (s, COOtBu) ppm.
anti/syn-5-[2-(tert-Butoxycarbonyl)-1-phenylpent-4-en-1-yl]-2,2-di-
methyl-1,3-dioxan-4,6-diones (3Da): Colorless oil; Rf = 0.55 (anti),
0.5 (syn) (hexane/EtOAc, 5:1). IR: ν = 2977, 2918, 1718, 1368,
˜
1149, 701 cm–1. MS (ESI+): m/z (%) = 427 (20) [M + K+], 411 (35)
[M + Na+], 353 (52) [M + Na+ – CH3COCH3], 297 (100) [M +
Na+ – H2C=C(CH3)2 – CH3COCH3]. C22H28O6 (388.45): calcd. C
68.02, H 7.27; found (anti) C 67.96, H 7.40; (syn) C 67.77, H 7.25.
syn-3Ea (Diastereomer 3): 1H NMR (400 MHz): δ = 0.94 (t, J =
7.1 Hz, 3 H, OCH2CH3), 1.44 [s, 9 H, C(CH3)3], 2.02 (m, 2 H,
=CHCH2), 3.04 (ddd, J = 11.8, 8.4, 4.1 Hz, 1 H, tBuOOCCH),
3.48 (dd, J = 11.9, 5.0 Hz, 1 H, PhCH), 3.88 (dq, J = 10.7, 7.1 Hz,
1 H, OCH2), 3.92 (dq, J = 10.7, 7.2 Hz, 1 H, OCH2), 4.04 [d, J =
5.0 Hz, 1 H, (EtOOC)(NC)CH], 4.83 (d, J = 17.0 Hz, 1 H, trans
=CH2), 4.92 (d, J = 10.1 Hz, 1 H, cis =CH2), 5.57 (m, 1 H, =CH),
7.10–7.30 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 13.9 (q,
OCH2CH3), 28.3 [q, C(CH3)3], 35.19 (t, =CHCH2), 42.6 [d,
(EtOOC)(NC)CH], 46.4 (d, PhCH), 48.3 (d, tBuOOCCH), 62.6 (t,
OCH2), 82.1 [s, C(CH3)3], 115.4 (s, CN), 117.8 (t, =CH2), 128.54
(d, p-Ph), 128.94 (d, Ph), 128.95 (d, Ph), 133.76 (d, =CH), 136.0 (s,
ipso-Ph), 164.9 (s, COOEt), 173.0 (s, COOtBu) ppm.
1
anti-3Da: H NMR (400 MHz, C6D6): δ = 0.59 (s, 3 H, OCCH3),
1.01 (s, 3 H, OCCH3), 1.05 [s, 9 H, C(CH3)3], 2.54 (m, 2 H,
=CHCH2), 3.61 [d, J = 3.3 Hz, 1 H, (OOC)2CH], 4.03 (ddd, J =
12.0, 9.4, 4.5 Hz, 1 H, tBuOOCCH), 4.26 (dd, J = 12.0, 3.3 Hz, 1
H, PhCH), 5.04 (d, J = 10.1 Hz, 1 H, cis =CH2), 5.16 (d, J =
17.0 Hz, 1 H, trans =CH2), 6.00 (dddd, J = 17.0, 10.1, 8.0, 6.1 Hz,
1 H, =CH), 6.93 (m, 1 H, p-Ph), 6.99 (m, 2 H, m-Ph), 7.52 (m, 2
H, o-Ph) ppm. 13C NMR (100 MHz, C6D6): δ = 27.8 (q, OCCH3),
28.0 [q, C(CH3)3], 28.2 (q, OCCH3), 36.2 (t, =CHCH2), 48.3 [d,
(OOC)2CH], 48.66 (d, PhCH or tBuOOCCH), 48.72 (d, PhCH or
tBuOOCCH), 80.5 [s, C(CH3)3], 105.4 [s, C(CH3)2], 117.9 (t,
=CH2), 128.41 (d, p-Ph), 129.0 (d, m-Ph), 130.8 (d, o-Ph), 135.4 (d,
=CH), 139.4 (s, ipso-Ph), 165.1 (s, COO), 165.8 (s, COO), 172.8 (s,
COOtBu) ppm.
syn-3Ea (Diastereomer 4): 1H NMR (400 MHz): δ = 1.13 (t, J =
7.1 Hz, 3 H, OCH2CH3), 1.41 [s, 9 H, C(CH3)3], 2.00–2.20 (m, 2
H, =CHCH2), 3.13 (ddd, J = 10.8, 8.2, 4.2 Hz, 1 H, tBuOOCCH),
3.52 (dd, J = 10.8, 4.4 Hz, 1 H, PhCH), 3.97 [d, J = 4.4 Hz, 1 H,
(EtOOC)(NC)CH], 4.09 (q, J = 7.1 Hz, 2 H, OCH2), 4.83 (d, J =
17.0 Hz, 1 H, trans =CH2), 4.92 (d, J = 10.1 Hz, 1 H, cis =CH2),
5.57 (m, 1 H, =CH), 7.10–7.30 (m, 5 H, Ph) ppm. 13C NMR
(100 MHz): δ = 14.0 (q, OCH2CH3), 28.2 [q, C(CH3)3], 35.23 (t,
=CHCH2), 41.6 [d, (EtOOC)(NC)CH], 46.9 (d, PhCH), 47.6 (d,
tBuOOCCH), 62.76 (t, OCH2), 81.9 [s, C(CH3)3], 115.89 (s, CN),
118.4 (t, =CH2), 128.48 (d, p-Ph), 128.59 (d, Ph), 129.05 (d, Ph),
133.88 (d, =CH), 137.5 (s, ipso-Ph), 165.1 (s, COOEt), 172.9 (s,
COOtBu) ppm.
1
syn-3Da: H NMR (400 MHz, C6D6): δ = 0.78 (s, 3 H, OCCH3),
0.85 (s, 3 H, OCCH3), 1.43 [s, 9 H, C(CH3)3], 2.07 (m, 1 H,
=CHCH2), 2.33 (m, 1 H, =CHCH2), 3.95 (ddd, J = 11.8, 7.4,
4.0 Hz, 1 H, tBuOOCCH), 4.33 (dd, J = 11.8, 3.3 Hz, 1 H, PhCH),
4.41 [d, J = 3.3 Hz, 1 H, (OOC)2CH], 4.87 (d, J = 16.9 Hz, 1 H,
trans =CH2), 4.94 (d, J = 10.1 Hz, 1 H, cis =CH2), 5.77 (dddd, J
= 16.9, 10.1, 8.4, 5.9 Hz, 1 H, =CH), 7.07 (m, 1 H, p-Ph), 7.15 (m,
2 H, m-Ph), 7.58 (m, 2 H, o-Ph) ppm. 13C NMR (100 MHz, C6D6):
δ = 27.6 (q, OCCH3), 28.1 (q, OCCH3), 28.5 [q, C(CH3)3], 36.0 (t,
=CHCH2), 46.6 (d, PhCH), 47.3 (d, tBuOOCCH), 50.2 [d,
(OOC)2CH], 81.3 [s, C(CH3)3], 105.2 [s, C(CH3)2], 116.8 (t, =CH2),
128.38 (d, p-Ph), 129.4 (d, m-Ph), 130.5 (d, o-Ph), 134.8 (d, =CH),
139.5 (s, ipso-Ph), 165.6 (s, COO), 165.7 (s, COO), 174.5 (s, CO-
OtBu) ppm.
anti/syn-3-tert-Butyl 1-Ethyl 1-Cyano-2-ethylhex-5-ene-1,3-dicarb-
oxylates (3Fa): Colorless oil; R = 0.4 (hexane/EtOAc, 5:1). IR: ν
= 2977, 2937, 1743, 1721, 1459, 1392, 1367, 1244, 1201, 1149, 1027,
994, 918, 845 cm–1. MS (ESI+): m/z (%) = 332 (78) [M + Na+], 276
(100) [M + Na+ – CH2=C(CH3)2]. C17H27NO4 (309.40): calcd. C
65.99, H 8.80, N 4.53; found C 66.27, H 8.95, N 4.40.
˜
f
anti/syn-3-tert-Butyl 1-Ethyl 1-Cyano-2-phenylhex-5-ene-1,3-dicarb-
oxylates (3Ea): Colorless oil; Rf = 0.6 (syn), 0.55 (anti) (hexane/
anti-3Fa (Diastereomer 1): 1H NMR (400 MHz): δ = 0.98 (t, J =
7.4 Hz, 3 H, CH2CH3) or 0.99 (t, J = 7.1 Hz, 3 H, CH2CH3), 1.335
EtOAc, 5:1). IR: ν = 2979, 1724, 1367, 1249, 1148, 1027, 919, 846,
˜
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
11

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
or 1.344 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.448 or 1.458 [s, 9 H, C(CH3)3], 111.7 (s, CN), 112.0 (s, CN), 118.9 (t, =CH2), 128.83 (d,
C(CH3)3], 1.62–1.68 (m, 2 H, CH2CH3), 2.15–2.50 (m, 2 H, Ph), 129.2 (d, Ph), 129.40 (d, p-Ph), 133.7 (d, =CH), 135.0 (s, ipso-
=CHCH2), 2.41 (m, 1 H, CH3CH2CH), 2.50–2.65 (m, 1 H, Ph), 170.7 (s, COOtBu) ppm.
tBuOOCCH), 3.750 [d, J = 5.1 Hz, 1 H, (EtOOC)(NC)CH], 4.23–
syn-3Ga: 1H NMR (400 MHz): δ = 1.51 [s, 9 H, C(CH3)3], 2.08 (m,
4.32 (m, 2 H, OCH2), 5.09 (m, 2 H, =CH2), 5.74 (m, 1 H,
1 H, =CHCH2), 2.28 (m, 1 H, =CHCH2), 3.12 (ddd, J = 11.6, 7.6,
CH=) ppm. 13C NMR (100 MHz): δ = 11.83 (q, CH2CH3), 14.08
4.0 Hz, 1 H, tBuOOCCH), 3.39 (dd, J = 11.6, 4.8 Hz, 1 H, PhCH),
or 14.10 (q, OCH2CH3), 22.6 (t, CH2CH3), 28.16 or 28.19 [q,
4.53 [d, J = 4.8 Hz, 1 H, (NC)2CH], 4.90 (dd, J = 17.0, 1.2 Hz, 1
C(CH3)3], 32.84 (t, =CHCH2), 40.2 [d, (EtOOC)(NC)CH], 41.9 (d,
H, trans =CH2), 5.04 (d, J = 10.1 Hz, 1 H, cis =CH2), 5.60 (dddd,
CH3CH2CH), 47.3 (d, tBuOOCCH), 62.8 or 63.02 (t, OCH2), 81.4
J = 17.0, 10.1, 8.4, 6.0 Hz, 1 H, =CH), 7.35–7.47 (m, 5 H, Ph) ppm.
or 81.61 [s, C(CH3)3], 116.1 (s, CN), 117.4 (t, =CH2), 135.0 (d,
CH=), 166.0 (s, COOEt), 172.8 (s, COOtBu) ppm.
13C NMR (100 MHz): δ = 28.1 [d, (NC)2CH], 28.2 [q, C(CH3)3],
35.0 (t, =CHCH2), 46.5 (d, PhCH), 47.0 (d, tBuOOCCH), 83.0 [s,
C(CH3)3], 111.6 (s, CN), 111.8 (s, CN), 118.8 (t, =CH2), 128.80 (d,
Ph), 129.49 (d, p-Ph), 129.54 (d, Ph), 132.7 (d, =CH), 134.7 (s, ipso-
Ph), 172.7 (s, COOtBu) ppm.
anti-3Fa (Diastereomer 2): 1H NMR (400 MHz): δ = 0.97 (t, J =
7.2 Hz, 3 H, CH2CH3), 1.327 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.455
[s, 9 H, C(CH3)3], 1.62–1.68 (m, 2 H, CH2CH3), 2.15–2.50 (m, 2
H, =CHCH2), 2.41 (m, 1 H, CH3CH2CH), 2.50–2.65 (m, 1 H,
tBuOOCCH), 3.92 [d, J = 3.1 Hz, 1 H, (EtOOC)(NC)CH], 4.23–
4.32 (m, 2 H, OCH2), 5.09 (m, 2 H, =CH2), 5.74 (m, 1 H,
CH=) ppm. 13C NMR (100 MHz): δ = 11.76 (q, CH2CH3), 14.08
(q, OCH2CH3), 23.6 (t, CH2CH3), 28.16 [q, C(CH3)3], 32.85 (t,
=CHCH2), 39.4 [d, (EtOOC)(NC)CH], 41.7 (d, CH3CH2CH), 48.2
(d, tBuOOCCH), 63.02 (t, OCH2), 81.63 [s, C(CH3)3], 115.7 (s,
CN), 117.5 (t, =CH2), 134.8 (d, =CH), 166.4 (s, COOEt), 173.0 (s,
COOtBu) ppm.
syn-3Fa (Diastereomer 3): 1H NMR (400 MHz): δ = 0.99 (t, J =
7.1 Hz, 3 H, CH2CH3), 1.331 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.47
[s, 9 H, C(CH3)3], 1.62–1.68 (m, 2 H, CH2CH3), 2.15–2.50 (m, 2
H, =CHCH2), 2.41 (m, 1 H, CH3CH2CH), 2.50–2.65 (m, 1 H,
tBuOOCCH), 3.80 [d, J = 3.0 Hz, 1 H, (EtOOC)(NC)CH], 4.23–
4.32 (m, 2 H, OCH2), 5.09 (m, 2 H, =CH2), 5.74 (m, 1 H,
=CH) ppm. 13C NMR (100 MHz): δ = 11.7 (q, CH2CH3), 14.08
(q, OCH2CH3), 23.4 (t, CH2CH3), 28.19 [q, C(CH3)3], 34.5 (t,
=CHCH2), 40.0 [d, (EtOOC)(NC)CH], 41.4 (d, CH3CH2CH), 48.0
(d, tBuOOCCH), 62.99 (t, OCH2), 81.9 [s, C(CH3)3], 115.4 (s, CN),
117.7 (t, =CH2), 134.4 (d, =CH), 166.5 (s, COOEt), 172.7 (s, CO-
OtBu) ppm.
syn-3Fa (Diastereomer 4): 1H NMR (400 MHz): δ = 0.98 (t, J =
7.4 Hz, 3 H, CH2CH3) or 0.99 (t, J = 7.1 Hz, 3 H, CH2CH3), 1.335
or 1.344 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.448 or 1.458 [s, 9 H,
C(CH3)3], 1.62–1.68 (m, 2 H, CH2CH3), 2.15–2.50 (m, 2 H,
=CHCH2), 2.41 (m, 1 H, CH3CH2CH), 2.50–2.65 (m, 1 H,
tBuOOCCH), 3.752 [d, J = 4.6 Hz, 1 H, (EtOOC)(NC)CH], 4.23–
4.32 (m, 2 H, OCH2), 5.09 (m, 2 H, =CH2), 5.74 (m, 1 H,
CH=) ppm. 13C NMR (100 MHz): δ = 12.0 (q, CH2CH3), 14.08 or
14.10 (q, OCH2CH3), 23.7 (t, CH2CH3), 28.16 or 28.19 [q,
C(CH3)3], 34.8 (t, =CHCH2), 40.1 [d, (EtOOC)(NC)CH], 42.5 (d,
CH3CH2CH), 48.6 (d, tBuOOCCH), 62.8 or 63.02 (t, OCH2), 81.4
or 81.61 [s, C(CH3)3], 115.5 (s, CN), 117.6 (t, =CH2), 134.7 (d,
CH=), 166.2 (s, COOEt), 172.3 (s, COOtBu) ppm.
anti/syn-Methyl 1,1-Dicyano-2-phenylhex-5-en-3-oates (3Gb): Col-
orless oil; R = 0.48 (hexane/EtOAc, 5:1). IR: ν = 2953, 2916, 1731,
˜
f
1437, 1198, 1168, 922, 700 cm–1. MS (EI): m/z (%) = 268 (6) [M+],
237 (8), 227 (17), 209 (9), 195 (14), 155 (23), 143 (100), 128 (46),
113 (98), 91 (33), 77 (20). C16H16N2O2 (268.31): calcd. C 71.62, H
6.01, N 10.44; found C 71.49, H 5.96, N 10.23.
1
anti-3Gb: H NMR (400 MHz): δ = 2.39 (m, 2 H, =CHCH2), 3.24
(m, 1 H, MeOOCCH), 3.50 (t, J = 7.9 Hz, 1 H, PhCH), 3.53 (s, 3
H, OCH3), 4.53 [d, J = 7.8 Hz, 1 H, (NC)2CH], 5.16 (m, 2 H,
=CH2), 5.78 (ddt, J = 17.7, 10.8, 7.0 Hz, 1 H, =CH), 7.22–7.47 (m,
5 H, Ph) ppm. 13C NMR (100 MHz): δ = 27.5 [d, (NC)2CH], 34.0
(t, =CHCH2), 47.0 (d, PhCH or MeOOCCH), 47.3 (d, PhCH or
MeOOCCH), 52.1 (q, OCH3), 111.8 (s, CN), 112.1 (s, CN), 119.0
(t, =CH2), 128.4 (d, Ph), 129.3 (d, Ph), 129.4 (d, p-Ph), 133.6 (d,
=CH), 134.5 (s, ipso-Ph), 172.0 (s, COOMe) ppm.
1
syn-3Gb: H NMR (400 MHz): δ = 2.18 (m, 2 H, =CHCH2), 3.24
(m, 1 H, MeOOCCH), 3.49 (dd, J = 7.3, 4.8 Hz, 1 H, PhCH), 3.77
(s, 3 H, OCH3), 4.46 [d, J = 4.8 Hz, 1 H, (NC)2CH], 4.88 (dd, J =
17.0, 1.2 Hz, 1 H, trans =CH2), 5.02 (d, J = 10.1 Hz, 1 H, cis
=CH2), 5.78 (dddd, J = 17.0, 10.1, 8.2, 6.2 Hz, 1 H, =CH), 7.22–
7.47 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 28.3 [d, (NC)2-
CH], 34.7 (t, =CHCH2), 46.5 (d, 2 C, PhCH, MeOOCCH), 52.5
(q, OCH3), 111.6 (s, CN), 111.7 (s, CN), 118.8 (t, =CH2), 128.6 (d,
Ph), 129.49 (d, p-Ph), 129.53 (d, Ph), 132.5 (d, =CH), 134.4 (s, ipso-
Ph), 173.6 (s, COOMe) ppm.
tert-Butyl 2-Allyl-2-[1-(dicyanomethyl)cyclohexyl]acetate (3Ha):
Colorless liquid; R = 0.63 (hexane/EtOAc, 5:1). IR: ν = 2933, 1711,
˜
f
1459, 1368, 1238, 1144, 990, 918, 841 cm–1. MS (ESI+): m/z (%) =
325 (56) [M + Na+], 269 (100) [M + Na+ – H2C=C(CH3)2].
C18H26N2O2 (302.41): calcd. C 71.49, H 8.67, N 9.26; found C
1
71.25, H 8.79, N 9.08. H NMR (400 MHz): δ = 1.20–1.75 (m, 9
H, cyclohexane), 1.41 [s, 9 H, C(CH3)3], 2.02 (m, 1 H, cyclohexane),
2.38 (m, 1 H, =CHCH2), 2.47 (m, 1 H, =CHCH2), 2.89 (dd, J =
12.2, 3.3 Hz, 1 H, tBuOOCCH), 4.73 [s, 1 H, (NC)2CH], 5.02 (d,
J = 10.1 Hz, 1 H, cis =CH2), 5.08 (ddd, J = 17.0, 2.7, 1.4 Hz, 1 H,
trans =CH2), 5.64 (dddd, J = 17.0, 10.1, 7.8, 5.9 Hz, 1 H,
=CH) ppm. 13C NMR (100 MHz): δ = 20.96 (t, cyclohexane), 21.01
(t, cyclohexane), 24.9 (t, cyclohexane), 28.3 [q, C(CH3)3], 30.1 [d,
(NC)2CH], 30.8 (t, cyclohexane), 32.0 (t, =CHCH2), 33.5 (t, cyclo-
hexane), 41.4 [s, (CH2)5C], 48.1 (d, tBuOOCCH), 82.6 [s,
C(CH3)3], 112.6 (s, CN), 112.9 (s, CN), 118.0 (t, =CH2), 134.7 (d,
=CH), 173.3 (s, COOtBu) ppm.
anti/syn-tert-Butyl 1,1-Dicyano-2-phenylhex-5-en-3-oates (3Ga):
anti-Isomer: Colorless oil; Rf = 0.27 (hexane/EtOAc, 5:1). syn-Iso-
mer: Colorless solid; m.p. 76–78 °C; Rf = 0.4 (hexane/EtOAc, 5:1).
IR: ν = 2979, 1716, 1369, 1150, 706 cm–1. MS (ESI+): m/z (%) =
˜
333 (15) [M + Na+], 312 (37), 277 (100) [M + Na+ – H2C=C-
(CH3)2], 180 (19). C19H22N2O2 (310.39): calcd. C 73.52, H 7.14, N
9.03; found C 73.45, H 7.04, N 8.88.
1
anti-3Ga: H NMR (400 MHz): δ = 1.20 [s, 9 H, C(CH3)3], 2.32–
2.48 (m, 2 H, =CHCH2), 3.12 (ddd, J = 9.2, 8.1, 5.8 Hz, 1 H,
anti/syn-tert-Butyl 1,1-Dibenzoyl-2-phenylhex-5-en-3-oates (3Ia):
tBuOOCCH), 3.41 (dd, J = 9.2, 6.6 Hz, 1 H, PhCH), 4.42 [d, J = Colorless oil; R = 0.5 (hexane/EtOAc, 5:1). IR: ν = 2977, 1723,
˜
f
6.6 Hz, 1 H, (NC)2CH], 5.19 (m, 2 H, =CH2), 5.81 (ddt, J = 16.9,
1699, 1665, 1448, 1367, 1259, 1149, 975, 758, 701, 689 cm–1. MS
9.7, 7.0 Hz, 1 H, =CH), 7.32–7.44 (m, 5 H, Ph) ppm. 13C NMR (ESI+): m/z (%) = 959 (20) [2M + Na+], 507 (15) [M + K+], 491
(100 MHz): δ = 27.6 [d, (NC)2CH], 27.8 [q, C(CH3)3], 34.7 (t,
=CHCH2), 47.7 (d, PhCH), 47.8 (d, tBuOOCCH), 82.2 [s,
(100) [M + Na+], 435 (17) [M + Na+ – H2C=C(CH3)2]. C31H32O4
(468.58): calcd. C 79.46, H 6.88; found C 79.24, H 7.00.
12
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
Polyfunctional β-Dicarbonyl Compounds
anti-3Ia: 1H NMR (400 MHz): δ = 1.19 [s, 9 H, C(CH3)3], 2.01 (m, (CH3)2]. C37H36O4 (544.68): calcd. C 81.59, H 6.66; found C 81.50,
1 H, =CHCH2), 2.18 (m, 1 H, =CHCH2), 2.87 (dt, J = 8.6, 5.6 Hz, H 6.60.
1 H, tBuOOCCH), 4.14 (dd, J = 10.8, 5.4 Hz, 1 H, PhCH), 4.92–
anti-3If: 1H NMR (400 MHz): δ = 1.20 [s, 9 H, C(CH3)3], 2.23 (m,
4.95 (m, 2 H, =CH2), 5.67 (m, 1 H, =CH), 6.25 [d, J = 10.8 Hz, 1
1 H, =CHCH2), 2.36 (m, 1 H, =CHCH2), 3.02 (dt, J = 8.9, 5.8 Hz,
H, (PhOC)2CH], 6.90–7.50 (m, 11 H, ArH), 7.53 (m, 2 H, o-COPh),
1 H, tBuOOCCH), 4.21 (dd, J = 10.6, 5.7 Hz, 1 H, PhCH), 6.09
8.04 (m, 2 H, o-COPh) ppm. 13C NMR (100 MHz): δ = 28.0 [q,
(dt, J = 15.7, 7.0 Hz, 1 H, =CH), 6.27 [d, J = 10.8 Hz, 1 H, (PhOC)2-
C(CH3)3], 35.2 (t, =CHCH2), 48.31 (d, PhCH), 48.33 (d,
CH], 6.30 (d, J = 16.0 Hz, 1 H, =CHPh), 7.04 (m, 3 H, Ar), 7.15
tBuOOCCH), 61.6 [d, (PhOC)2CH], 81.1 [s, C(CH3)3], 117.0 (t,
(m, 3 H, Ar), 7.24 (m, 6 H, Ar), 7.37 (m, 3 H, Ar), 7.49 (t, J =
=CH2), 127.2 (d, p-Ar), 127.9 (d, Ar), 128.46 (d, Ar), 128.7 (d, Ar),
7.4 Hz, 1 H, Ar), 7.69 (m, 2 H, o-COPh), 8.08 (m, 2 H, o-
128.8 (d, Ar), 129.1 (d, o-COPh), 130.2 (d, o-COPh), 133.0 (d, p-
Ar), 133.6 (d, p-Ar), 135.9 (d, =CH), 137.3 (s, ipso-Ar), 137.37 (s,
ipso-Ar), 137.44 (s, ipso-Ar), 172.7 (s, COOtBu), 194.89 (s, COPh),
194.92 (s, COPh) ppm.
COPh) ppm. 13C NMR (100 MHz): δ = 28.12 [q, C(CH3)3], 34.7
(t, =CHCH2), 48.6 (d, PhCH), 48.8 (d, tBuOOCCH), 61.8 [d,
(PhOC)2CH], 81.23 [s, C(CH3)3], 126.3 (d, Ar), 127.2 (d, p-Ar or
=CH), 127.3 (d, p-Ar or =CH), 127.7 (d, p-Ar or =CH), 128.0 (d,
Ar), 128.56 (d, Ar), 128.7 (d, Ar), 128.82 (d, Ar), 129.0 (d, Ar),
129.3 (d, Ar), 130.4 (d, Ar), 132.4 (d, PhCH=), 133.2 (d, p-Ar),
133.7 (d, p-Ar), 137.36 (s, ipso-Ar), 137.40 (s, ipso-Ar), 137.56 (s,
ipso-Ar), 137.7 (s, ipso-Ar), 172.8 (s, COOtBu), 195.01 (s, COPh),
195.03 (s, COPh) ppm.
syn-3Ia: 1H NMR (400 MHz): δ = 1.19 [s, 9 H, C(CH3)3], 2.01 (m,
1 H, =CHCH2), 2.18 (m, 1 H, =CHCH2), 3.09 (dt, J = 9.7, 4.0 Hz,
1 H, tBuOOCCH), 4.04 (dd, J = 9.4, 7.5 Hz, 1 H, PhCH), 4.80–
4.84 (m, 2 H, =CH2), 5.55 (m, 1 H, =CH), 5.96 [d, J = 7.4 Hz, 1
H, (PhOC)2CH], 6.90–7.50 (m, 11 H, Ar), 7.70 (m, 2 H, o-COPh),
7.93 (m, 2 H, o-COPh) ppm. 13C NMR (100 MHz): δ = 28.0 [q,
C(CH3)3], 35.4 (t, =CHCH2), 48.28 (d, PhCH), 49.9 (d,
tBuOOCCH), 60.2 [d, (PhOC)2CH], 81.3 [s, C(CH3)3], 116.8 (t,
=CH2), 127.3 (d, p-Ar), 128.2 (d, Ar), 128.53 (d, Ar), 128.6 (d, Ar),
128.97 (d, Ar), 129.01 (d, o-COPh), 130.1 (d, o-COPh), 132.6 (d,
p-Ar), 133.1 (d, p-Ar), 135.4 (d, =CH), 136.6 (s, ipso-Ar), 137.44
(s, ipso-Ar), 138.2 (s, ipso-Ar), 173.9 (s, COOtBu), 195.0 (s, COPh),
195.1 (s, COPh) ppm.
1
syn-3If: H NMR (400 MHz): δ = 1.19 [s, 9 H, C(CH3)3], 2.24 (m,
2 H, =CHCH2), 3.21 (dt, J = 9.6, 4.2 Hz, 1 H, tBuOOCCH), 4.12
(dd, J = 9.4, 7.5 Hz, 1 H, PhCH), 5.98 (ddd, J = 15.7, 7.9, 6.3 Hz,
1 H, =CH), 6.02 [d, J = 7.4 Hz, 1 H, (PhOC)2CH], 6.18 (d, J =
15.9 Hz, 1 H, =CHPh), 7.00–7.55 (m, 16 H, Ar), 7.75 (m, 2 H, o-
COPh), 7.99 (m, 2 H, o-COPh) ppm. 13C NMR (100 MHz): δ =
28.09 [q, C(CH3)3], 34.9 (t, =CHCH2), 48.5 (d, PhCH), 50.4 (d,
tBuOOCCH), 60.3 [d, (PhOC)2CH], 81.17 [s, C(CH3)3], 126.2 (d,
Ar), 127.9 (d, =CH), 128.4 (d, Ar), 128.5 (d, Ar), 128.62 (d, Ar),
128.65 (d, Ar), 128.76 (d, Ar), 129.1 (d, Ar), 130.20 (d, Ar), 130.24
(d, Ar), 131.0 (d, Ar), 132.1 (d, PhCH=), 133.1 (d, Ar), 133.6 (d,
Ar), 136.6 (s, ipso-Ar), 137.42 (s, ipso-Ar), 137.55 (s, ipso-Ar), 138.2
(s, ipso-Ar), 174.0 (s, COOtBu), 195.03 (s, COPh), 195.2 (s,
COPh) ppm.
anti/syn-tert-Butyl
1,1-Dibenzoyl-2-phenyl-6-methylhept-5-en-3-
oates (3Ie): Colorless oil; R = 0.35 (hexane/EtOAc, 5:1). IR: ν =
˜
f
2975, 2927, 1699, 1675, 1596, 1447, 1366, 1256, 1146, 845, 757,
690 cm–1. MS (ESI+): m/z (%) = 1015 (3) [2M + Na+], 535 (8) [M
+ K+], 519 (100) [M + Na+], 463 (49) [M + Na+ – H2C=C-
(CH3)2]. C33H36O4 (496.26): calcd. C 79.81, H 7.31; found C 79.98;
H 7.57.
anti-3Ie: 1H NMR (400 MHz): δ = 1.19 [s, 9 H, C(CH3)3], 1.42 (br.
s, 3 H, CH3), 1.61 (br. s, 3 H, CH3), 2.00 (m, 1 H, =CHCH2), 2.14
(m, 1 H, =CHCH2), 2.87 (dt, J = 8.9, 6.3 Hz, 1 H, tBuOOCCH),
4.17 (dd, J = 10.5, 6.1 Hz, 1 H, PhCH), 5.03 (t, J = 7.0 Hz, 1 H,
=CH), 6.20 [d, J = 10.5 Hz, 1 H, (PhOC)2CH], 6.95–7.55 (m, 11
H, Ar), 7.69 (m, 2 H, o-Ar), 8.06 (m, 2 H, o-Ar) ppm. 13C NMR
(100 MHz, detectable resonances): δ = 25.9 [q, (E)- =CCH3], 28.01
[q, C(CH3)3], 29.8 (t, =CHCH2), 48.51 (d, PhCH), 49.5 (d,
tBuOOCCH), 61.8 [d, (PhOC)2CH], 80.8 [s, C(CH3)3], 121.7 (d,
=CH), 127.07 (d, p-Ar), 127.9 (d, Ar), 128.5 (d, Ar), 128.8 (d, Ar),
128.9 (d, Ar), 129.2 (d, Ar), 130.3 (d, Ar), 133.07 (d, p-Ar) ppm.
anti/syn-tert-Butyl 1,1-Diacetyl-2-phenylhex-5-en-3-oates (3Ka):
Colorless solid; m.p. 80–82 °C; Rf = 0.45 (hexane/EtOAc, 5:1). IR:
ν = 2977, 1720, 1697, 1355, 1249, 1144, 916, 845, 743, 702 cm–1.
˜
MS (ESI+): m/z (%) = 711 (10) [2M + Na+], 367 (100) [M + Na+],
311 (15) [M + Na+ – H2C=C(CH3)2]. C21H28O4 (344.44): calcd. C
73.23 H 8.19; found C 73.19, H 8.27.
anti-3Ka: 1H NMR (400 MHz): δ = 1.37 [s, 9 H, C(CH3)3], 1.81 (s,
3 H, COCH3), 2.04 (m, 1 H, =CHCH2), 2.17 (m, 1 H, =CHCH2),
2.37 (s, 3 H, COCH3), 2.59 (ddd, J = 9.1, 5.9, 4.6 Hz, 1 H,
tBuOOCCH), 3.77 (dd, J = 12.0, 4.6 Hz, 1 H, PhCH), 4.71 [d, J =
11.9 Hz, 1 H, (CH3OC)2CH], 5.05 (m, 2 H, =CH2), 5.71 (m, 1 H,
=CH), 7.10–7.30 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 27.9
(q, COCH3), 28.1 [q, C(CH3)3], 31.0 (q, COCH3), 34.7 (t,
=CHCH2), 46.3 (d, PhCH), 48.2 (d, tBuOOCCH), 73.0 [d,
(CH3OC)2CH], 81.3 [s, C(CH3)3], 117.1 (t, =CH2), 127.64 (d, p-
Ph), 128.3 (d, Ph), 129.6 (d, Ph), 135.6 (d, =CH), 137.0 (s, ipso-
Ph), 171.8 (s, COOtBu), 202.8 (s, COCH3), 203.3 (s, COCH3) ppm.
1
syn-3Ie: H NMR (400 MHz): δ = 1.21 [s, 9 H, C(CH3)3], 1.35 (br.
s, 3 H, CH3), 1.54 (br. s, 3 H, CH3), 1.90 (m, 1 H, =CHCH2), 2.10
(m, 1 H, =CHCH2), 3.06 (dt, J = 9.8, 3.9 Hz, 1 H, tBuOOCCH),
4.06 (dd, J = 9.6, 7.3 Hz, 1 H, PhCH), 4.94 (m, 1 H, =CH), 6.00
[d, J = 7.5 Hz, 1 H, (PhOC)2CH], 6.95–7.55 (m, 11 H, Ar), 7.74
(m, 2 H, o-Ar), 7.99 (m, 2 H, o-Ar) ppm. 13C NMR (100 MHz): δ
= 17.8 [q, (Z)- =CCH3], 25.8 [q, (E)- =CCH3], 27.98 [q, C(CH3)3],
30.3 (t, =CHCH2), 48.51 (d, PhCH), 50.8 (d, tBuOOCCH), 60.3
[d, (PhOC)2CH], 81.0 [s, C(CH3)3], 121.4 (d, =CH), 127.10 (d, p-
Ar), 128.2 (d, Ar), 128.61 (d, Ar), 128.63 (d, Ar), 129.0 (d, Ar),
129.1 (d, Ar), 130.2 (d, Ar), 133.09 (d, p-Ar), 133.4 [s, =C(CH3)2],
133.6 (d, p-Ar), 136.7 (s, ipso-Ar), 137.5 (s, ipso-Ar), 138.5 (s, ipso-
Ar), 174.6 (s, COOtBu), 195.1 (s, COPh), 195.3 (s, COPh) ppm.
1
syn-3Ka: H NMR (400 MHz): δ = 1.40 [s, 9 H, C(CH3)3], 1.80 (s,
3 H, COCH3), 1.94 (m, 1 H, =CHCH2), 2.08 (m, 1 H, =CHCH2),
2.27 (s, 3 H, COCH3), 2.55 (m, 1 H, tBuOOCCH), 3.89 (dd, J =
10.6, 7.4 Hz, 1 H, PhCH), 4.44 [d, J = 10.6 Hz, 1 H, (CH3OC)2-
CH], 4.94 (m, 2 H, =CH2), 5.60 (m, 1 H, =CH), 7.10–7.30 (m, 5
H, Ph) ppm. 13C NMR (100 MHz): δ = 28.1 [q, C(CH3)3], 29.2 (q,
COCH3), 29.9 (q, COCH3), 34.1 (t, =CHCH2), 46.8 (d, PhCH),
51.0 (d, tBuOOCCH), 73.8 [d, (CH3OC)2CH], 81.5 [s, C(CH3)3],
117.0 (t, =CH2), 127.61 (d, p-Ph), 128.8 (d, Ph), 129.1 (d, Ph), 135.4
(d, =CH), 138.6 (s, ipso-Ph), 172.8 (s, COOtBu), 202.9 (s, COCH3),
203.1 (s, COCH3) ppm.
anti/syn-(E)-tert-Butyl 1,1-Dibenzoyl-2,6-diphenylhex-5-en-3-oates
(3If): Colorless crystals; m.p. 164–165 °C; Rf = 0.3 (hexane/EtOAc,
5:1). IR: ν = 2976, 2928, 1700, 1698, 1664, 1596, 1447, 1366, 1258,
˜
1146, 966, 846, 758, 690 cm–1. MS (ESI+): m/z (%) = 583 (12) [M
Diethyl 2-{[Bis(trimethylsilyl)amino](phenyl)methyl}malonate (4):
+ K+], 567 (100) [M + Na+], 511 (56) [M + Na+ – H2C=C-
Colorless oil; R = 0.6 (hexane/EtOAc, 5:1). IR: ν = 2955, 1757,
˜
f
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
13

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
1732, 1248, 1186, 1138, 1047, 1027, 902, 834, 759, 696, 678 cm–1. NMR (125.7 MHz, C6D6): δ = –0.25 [q, Si(CH3)3], 29.4 (t, CH2),
FULL PAPER
MS (ESI+): m/z (%) = 432 (12) [M + Na+], 376 (10), 371 (13), 250
54.3 (q, OCH3), 82.0 [d, CH=C(OMe)], 113.5 (t, =CH2), 139.2 (d,
=CHCH2), 154.7 [s, CH=C(OMe)] ppm.
(100) [M
+ – N(SiMe3)2]. HRMS (ESI+): calcd. for
H+
C20H35NO4Si2Na+ 432.1997; found 432.1998. C20H35NO4Si2
(409.67): calcd. C 58.64 H 8.61 N 3.42 Si 13.71; found C 59.04 H
(Z)-5c: 1H NMR (500 MHz, C6D6): δ = 0.18 [s, 9 H, Si(CH3)3],
2.89 (ddt, J = 7.1, 6.2, 1.6 Hz, 2 H, CH2), 3.13 (s, 3 H, OCH3),
3.45 [t, J = 7.1 Hz, 1 H, CH=C(OMe)], 4.98 (ddt, J = 10.0, 2.0,
1.5 Hz, 1 H, cis =CH2), 5.12 (dq, J = 17.0, 2.0 Hz, 1 H, trans
1
8.66 N 3.32 Si 13.50. H NMR (400 MHz, C6D6): δ = 0.02 [br. s,
9 H, Si(CH3)3], 0.43 [br. s, 9 H, Si(CH3)3], 0.77 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 0.98 (t, J = 7.2 Hz, 3 H, OCH2CH3), 3.81 (q, J =
7.1 Hz, 2 H, OCH2), 4.02 (dq, J = 10.8, 7.1 Hz, 1 H, OCH2), 4.10
(dq, J = 10.8, 7.1 Hz, 1 H, OCH2), 4.67 [d, J = 11.8 Hz, 1 H,
(EtOOC)2CH], 5.66 (d, J = 11.8 Hz, 1 H, PhCH), 7.00 (m, 1 H, p-
Ph), 7.09 (m, 2 H, m-Ph), 7.39 (m, 2 H, o-Ph) ppm. 13C NMR
(100 MHz, C6D6): δ = 3.88 [q, Si(CH3)3], 4.09 [q, Si(CH3)3], 13.9
(q, OCH2CH3), 14.1 (q, OCH2CH3), 57.8 [d, (EtOOC)2CH], 59.1
(d, PhCH), 61.3 (t, OCH2), 61.4 (t, OCH2), 127.4 (d, p-Ph), 128.1
(d, Ph), 128.5 (d, Ph), 143.0 (s, ipso-Ph), 167.5 (s, COOEt), 168.4
(s, COOEt) ppm.
=CH2), 5.92 (ddt, J = 17.0, 10.0, 6.1 Hz, 1 H, CH=CH2) ppm. 13
C
NMR (125.7 MHz, C6D6): δ = 0.5 [q, Si(CH3)3], 29.8 (t, CH2),
54.3 (q, OCH3), 73.5 [d, CH=C(OMe)], 113.4 (t, =CH2), 139.4 (d,
=CHCH2), 157.6 [s, (MeO)C=] ppm.
tert-Butyl 2-(Trimethylsilyl)pent-4-enoate 6b by Trapping of the
Enolate Resulting from 1a: To a stirred solution of iPr2NH (210 μL,
1.6 mmol) in anhydrous THF (13 mL) was added nBuLi (1.6 m in
hexane, 1.0 mL, 1.6 mmol) at –78 °C under a N2 atmosphere. A
solution of 1a (195 mg, 1.25 mmol) in anhydrous THF (0.5 mL)
was added by using a syringe. The reaction mixture was stirred at
–78 °C for 30 min and TMSCl (205 μL, 1.6 mmol) was added by
using a syringe. The reaction mixture was kept at –78 °C for 1.5 h,
then the solvent was carefully removed in high vacuum at 0 °C. The
solid white residue was washed with anhydrous pentane (5ϫ 5 mL)
and filtered under inert conditions. The solvent was removed in
high vacuum and the remaining sensitive colorless oil (270 mg) was
(Z)-1-tert-Butoxy-1-(tert-butyldimethylsilyloxy)penta-1,4-diene (Z)-
5a by Trapping of the Enolate Resulting from 1a: To a stirred solu-
tion of iPr2NH (210 μL, 1.6 mmol) in anhydrous THF (10 mL) was
added nBuLi (1.6 m in hexane, 1.0 mL, 1.6 mmol) at –78 °C under
a N2 atmosphere. Anhydrous HMPA (2.5 mL) was added by using
a syringe. A solution of 1a (195 mg, 1.25 mmol) in anhydrous THF
(0.5 mL) was added by using a syringe. The reaction mixture was
stirred at –78 °C for 30 min and TBDMSCl (241 mg, 1.6 mmol) in
anhydrous THF (0.5 mL) was added by using a syringe. The reac-
tion mixture was kept at –78 °C for 2 h, then the solvent was care-
fully removed in high vacuum at 0 °C. The yellow liquid residue
was washed with anhydrous pentane (5ϫ 5 mL) and filtered under
inert conditions through a plug of LiCl that was dried directly be-
fore use. The solvent was removed in high vacuum and the remain-
ing sensitive colorless oil (281 mg) was dissolved in C6D6, transfer-
1
dissolved in C6D6, transferred to an NMR tube and analyzed. H
NMR (500 MHz, C6D6): δ = 0.02 [s, 9 H, Si(CH3)3], 1.36 [s, 9 H,
C(CH3)3], 1.96 [dd, J = 11.6, 3.2 Hz, 1 H, (CH3)3SiCH], 2.01 (m,
1 H, CH2), 2.54 (dddt, J = 14.6, 11.5, 6.3, 1.3 Hz, 1 H, CH2), 4.94
(m, 1 H, cis =CH2), 5.06 (m, 1 H, trans =CH2), 5.85 (m, 1 H,
CH=CH2) ppm. 13C NMR (125.7 MHz, C6D6): δ = –2.5 [q,
Si(CH3)3], 28.4 [q, C(CH3)3], 31.4 (t, CH2), 38.1 [d, (CH3)3SiCH],
79.1 [s, C(CH3)3], 114.8 (t, =CH2), 138.6 (d, =CHCH2), 173.3 (s,
COOtBu) ppm.
1
red to an NMR tube and analyzed. H NMR (500 MHz, C6D6): δ
(2S*,3S*,5R*)/(2S*,3S*,5S*)-1,1-Diethyl 3-Methyl 5-(Iodomethyl)-
2-phenylcyclopentane-1,1,3-tricarboxylates (8Ab): To a solution of
anti/syn-3Aa (101 mg, 0.25 mmol, 5:1 anti/syn) in anhydrous
CH2Cl2 (2 mL) was added anhydrous Et3N (42 μL, 0.3 mmol) at
room temperature under a N2 atmosphere, followed by TiCl4 (1 m
in CH2Cl2, 450 μL, 0.45 mmol) by using a syringe. After stirring at
room temp. for 10 min, I2 (95 mg, 0.38 mmol) was added in one
portion. The intensely purple reaction mixture was stirred at room
temp. in the dark for 2 h, poured into 2% HCl solution (10 mL)
and washed with diethyl ether. The layers were separated, the or-
ganic fractions were washed with 10% Na2S2O3 solution, dried
with MgSO4 and the solvents evaporated. The crude product was
dissolved in anhydrous THF (2 mL) and anhydrous MeOH
(0.2 mL) and a solution of TMSCHN2 (2 m in Et2O, 125 μL,
0.25 mmol) was added by using a syringe. The pale-yellow clear
reaction mixture was stirred at room temp. under N2 in the dark
for 2 h. The solvent was evaporated and the thick oil was purified
by column chromatography (silica gel; hexane/EtOAc, 20:1 to 10:1)
= 0.15 [s, 6 H, Si(CH3)2], 0.93 [s, 9 H, SiC(CH3)3], 1.19 [s, 9 H,
C(CH3)3], 2.85 (ddt, J = 7.3, 6.0, 1.7 Hz, 2 H, CH2), 3.97 [t, J =
7.3 Hz, 1 H, CH=C(OtBu)], 4.93 (ddt, J = 10.1, 2.2, 1.7 Hz, 1 H,
cis =CH2), 5.08 (ddt, J = 17.1, 2.2, 1.8 Hz, 1 H, trans =CH2), 5.84
(ddt, J = 17.1, 10.1, 6.0 Hz, 1 H, CH=CH2) ppm. 13C NMR
(125.7 MHz, C6D6): δ = –3.9 [q, Si(CH3)2], 18.1 [s, SiC(CH3)3], 25.9
[q, SiC(CH3)3], 28.5 [q, C(CH3)3], 30.3 (t, CH2), 78.2 [s, C(CH3)3],
88.6 [d, CH=C(OtBu)], 113.7 (t, =CH2), 138.6 (d, =CHCH2), 152.3
[s, CH=C(OtBu)] ppm.
1-Methoxy-1-(trimethylsilyloxy)penta-1,4-dienes (Z/E)-5c by Trap-
ping of the Enolate Resulting from 1b: To a stirred solution of
iPr2NH (210 μL, 1.6 mmol) in anhydrous THF (13 mL) was added
nBuLi (1.6 m in hexane, 1.0 mL, 1.6 mmol) at –78 °C under a N2
atmosphere. Alternatively NaHMDS or KHMDS (1 m in THF,
1.6 mL, 1.6 mmol) were used instead of LDA. A solution of 1b
(143 mg, 1.25 mmol) in anhydrous THF (0.5 mL) was added by
using a syringe. The reaction mixture was stirred at –78 °C for
30 min and TMSCl (205 μL, 1.6 mmol) was added by using a sy-
ringe. The reaction mixture was kept at –78 °C for 2 h, then the
solvent was carefully removed in high vacuum at 0 °C. The solid
white residue was washed with anhydrous pentane (5ϫ 5 mL) and
filtered under inert conditions. The solvent was carefully removed
in high vacuum and the remaining sensitive colorless volatile liquid
was dissolved in C6D6, transferred to an NMR tube and analyzed.
to give
a partly separable 3.5:1 mixture of (2S*,3S*,5R*)/
(2S*,3S*,5S*)-8Ab (81 mg, 66%) followed by syn-3Ab (9 mg, 10%).
Colorless oil; R = 0.35 (hexane/EtOAc, 5:1). IR: ν = 2980, 1720,
˜
f
1454, 1367, 1254, 1202, 1174, 1096, 1020, 911, 868, 729, 699 cm–1.
MS (ESI+): m/z (%) = 527 (15) [M + K+], 511 (100) [M + Na+],
489 (8) [M + H+], 361 (20) [M + H+ – HI]. HRMS (ESI+): calcd.
for C20H25IO6Na+ 511.0588; found 511.0590.
(E)-5c: 1H NMR (500 MHz, C6D6): δ = 0.12 [br. s, 9 H, (2S*,3S*,5R*)-8Ab (major diastereomer): 1H NMR (400 MHz): δ
Si(CH3)3], 2.89 (ddt, J = 7.5, 6.0, 1.7 Hz, 2 H, CH2), 3.32 (s, 3 H,
OCH3), 3.79 [t, J = 7.3 Hz, 1 H, CH=C(OMe)], 4.97 (ddt, J = 10.1,
= 0.77 (t, J = 7.2 Hz, 3 H, OCH2CH3), 1.25 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.87 (ddd, J = 12.9, 12.3, 10.6 Hz, 1 H, α-CH2), 2.77
2.1, 1.5 Hz, 1 H, cis =CH2), 5.12 (dq, J = 17.1, 1.8 Hz, 1 H, trans (ddd, J = 13.0, 7.7, 7.0 Hz, 1 H, β-CH2), 2.87 (dd, J = 11.4, 9.5 Hz,
=CH2), 5.90 (ddt, J = 17.1, 10.1, 6.0 Hz, 1 H, CH=CH2) ppm. 13C
1 H, CH2I), 3.21 (dt, J = 10.6, 8.1 Hz, 1 H, MeOOCCH), 3.33 (m,
14
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
Polyfunctional β-Dicarbonyl Compounds
1
1 H, ICH2CH), 3.40 (dq, J = 10.7, 7.1 Hz, 1 H, OCH2), 3.58 (dd,
syn-9Ie: H NMR (400 MHz): δ = 1.41 (s, 3 H, CH3), 1.48 [s, 9 H,
J = 9.5, 3.4 Hz, 1 H, CH2I), 3.65 (s, 3 H, OCH3), 3.76 (dq, J = C(CH3)3], 1.60 (s, 3 H, CH3), 1.81 (m, 1 H, =CHCH2), 2.46 (ddd,
10.7, 7.1 Hz, 1 H, OCH2), 4.16 (dq, J = 10.8, 7.2 Hz, 1 H, OCH2),
4.28 (dq, J = 10.7, 7.2 Hz, 1 H, OCH2), 4.50 (d, J = 8.4 Hz, 1 H,
PhCH), 7.15–7.30 (m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ =
5.9 (t, CH2I), 13.4 (q, OCH2CH3), 14.2 (q, OCH2CH3), 35.7 (t,
J = 14.3, 11.1, 9.5 Hz, 1 H, =CHCH2), 3.46 (dd, J = 11.3, 4.0 Hz,
1 H, tBuOOCCH), 5.04 (m, 1 H, =CHCH2), 5.27 (s, 1 H, OH),
6.95–7.20 (m, 12 H, Ar, PhCH=), 7.42 (br. d, J = 7.1 Hz, 2 H, o-
Ar), 7.49 (m, 2 H, o-Ar) ppm. 13C NMR (100 MHz): δ = 17.7 [q,
CHCH2CH), 48.4 (d, ICH2CH), 48.9 (d, MeOOCCH), 52.1 (q, (Z)- =CCH3], 25.9 [q, (E)- =CCH3], 26.9 (t, =CHCH2), 28.3 [q,
OCH3), 54.7 (d, PhCH), 61.31 (t, OCH2), 62.0 (t, OCH2), 68.1 [s,
(EtOOC)2C], 127.5 (d, p-Ph), 128.4 (d, Ph), 128.8 (d, Ph), 140.5 (s,
ipso-Ph), 169.1 (s, COOEt), 169.6 (s, COOEt), 173.8 (s, CO-
OMe) ppm.
C(CH3)3], 52.7 (d, tBuOOCCH), 79.3 (s, COH), 82.3 [s, C(CH3)3],
121.2 (d, =CHCH2), 125.7 (d, Ar), 127.1 (d, p-Ar or PhCH=),
127.71 (d, p-Ar or PhCH=), 127.9 (d, p-Ar or PhCH=), 128.0 (d,
Ar), 128.2 (d, Ar), 128.3 (d, Ar), 128.9 (d, Ar), 129.25 (d, Ar),
132.7 (d, p-Ar), 133.5 [s, =C(CH3)2], 135.3 (s, ipso-Ar), 137.0 (s,
ipso-Ar), 141.6 (s, ipso-Ar), 146.3 (s, PhCH=C), 176.6 (s, COOtBu),
198.9 (s, COPh) ppm.
(2S*,3S*,5S*)-8Ab (minor diastereomer): 1H NMR (400 MHz): δ =
0.95 (t, J = 7.2 Hz, 3 H, OCH2CH3), 1.26 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 2.47 (ddd, J = 13.4, 11.2, 10.4 Hz, 1 H, β-CH2), 2.55
(ddd, J = 13.4, 9.3, 5.6 Hz, 1 H, α-CH2), 2.92 (m, 1 H, ICH2CH),
3.38 (dd, J = 11.8, 9.3 Hz, 1 H, CH2I), 3.60 (dt, J = 11.3, 5.7 Hz,
1 H, MeOOCCH), 3.63 (s, 3 H, OCH3), 3.75 (dd, J = 9.3, 3.1 Hz,
1 H, CH2I), 3.80 (dq, J = 10.7, 7.1 Hz, 1 H, OCH2), 4.03 (dq, J =
10.7, 7.1 Hz, 1 H, OCH2), 4.24 (m, 2 H, OCH2), 4.29 (d, J =
11.0 Hz, 1 H, PhCH), 7.20–7.35 (m, 5 H, Ph) ppm. 13C NMR
(100 MHz): δ = 5.6 (t, CH2I), 13.7 (q, OCH2CH3), 14.1 (q,
OCH2CH3), 35.9 (t, CHCH2CH), 45.9 (d, MeOOCCH), 50.3 (d,
ICH2CH), 52.2 (q, OCH3), 55.6 (d, PhCH), 61.27 (t, OCH2), 61.7
(t, OCH2), 68.5 [s, (EtOOC)2C], 127.6 (d, p-Ph), 128.1 (d, Ph),
129.1 (d, Ph), 137.6 (s, ipso-Ph), 168.4 (s, COOEt), 169.9 (s, CO-
OEt), 175.2 (s, COOMe) ppm.
1
anti-9Ie: H NMR (400 MHz): δ = 1.10 [s, 9 H, C(CH3)3], 1.64 (s,
3 H, CH3), 1.69 (s, 3 H, CH3), 2.69 (t, J = 7.8 Hz, 2 H, =CHCH2),
3.78 (t, J = 7.7 Hz, 1 H, tBuOOCCH), 5.07 (s, 1 H, OH), 5.29 (t,
J = 7.6 Hz, 1 H, =CHCH2), 6.90–7.10 (m, 11 H, Ar, PhCH=), 7.30
(m, 2 H, Ar), 7.42 (m, 3 H, Ar) ppm. 13C NMR (100 MHz): δ =
17.9 [q, (Z)- =CCH3], 26.0 [q, (E)- =CCH3], 26.8 (t, =CHCH2),
27.7 [q, C(CH3)3], 51.4 (d, tBuOOCCH), 78.4 (s, COH), 81.6 [s,
C(CH3)3], 121.6 (d, =CHCH2), 126.3 (d, Ar), 127.2 (d, p-Ar or
PhCH=), 127.68 (d, Ar), 127.70 (d, p-Ar or PhCH=), 127.8 (d, Ar),
128.1 (d, Ar), 129.0 (d, Ar), 129.22 (d, p-Ar or PhCH=), 129.3 (d,
Ar), 132.6 (d, p-Ar), 133.4 [s, =C(CH3)2], 135.7 (s, ipso-Ar), 136.7
(s, ipso-Ar), 141.2 (s, ipso-Ar), 143.7 (s, PhCH=C), 176.4 (s, CO-
OtBu), 199.8 (s, COPh) ppm.
syn/anti-(Z)-tert-Butyl 2-Benzoyl-3-hydroxy-1,3-diphenylhepta-1,6-
dien-4-oates (9Ia): Colorless viscous oil; Rf = 0.51 (hexane/EtOAc,
anti/syn-(1Z,6E)-tert-Butyl
2-Benzoyl-3-hydroxy-1,3,7-triphenyl-
5:1). IR: ν = 3442, 2978, 1697, 1668, 1447, 1366, 1227, 1149, 911,
˜
hepta-1,6-dien-4-oates (9If): Colorless solid; m.p. 156–157 °C; Rf =
729, 695 cm–1. MS (ESI+): m/z (%) = 507 (11) [M + K+], 491 (100)
[M + Na+], 435 (20) [M + Na+ – H2C=C(CH3)2], 395 (18) [M +
H+ – H2C=C(CH3)2 – H2O], 377 (25) [M + H+ – H2C=C(CH3)2 –
2H2O]. HRMS (ESI+): calcd. for C31H32O4Na+ 491.2193; found
491.2193.
0.5 (hexane/EtOAc, 5:1). IR: ν = 3426, 2977, 1694, 1688, 1448,
˜
1367, 1228, 1149, 743, 694 cm–1. MS (ESI+): m/z (%) = 583 (12)
[M + K+], 567 (100) [M + Na+], 511 (20) [M + Na+ – H2C=C-
(CH3)2]. C37H36O4 (544.68): calcd. C 81.59, H 6.66; found C 81.45,
H 6.82.
syn-9Ia: 1H NMR (400 MHz): δ = 1.49 [s, 9 H, C(CH3)3], 2.00 (m,
1 H, =CHCH2), 2.40 (ddd, J = 14.3, 11.2, 8.6 Hz, 1 H, =CHCH2),
3.53 (dd, J = 11.3, 3.7 Hz, 1 H, tBuOOCCH), 4.91 (d, J = 9.7 Hz,
1 H, cis =CH2), 4.94 (d, J = 17.0 Hz, 1 H, trans =CH2), 5.24 (s, 1
H, OH), 5.68 (dddd, J = 16.8, 10.1, 8.6, 5.8 Hz, 1 H, =CHCH2),
6.95–7.20 (m, 12 H, Ar, PhCH=), 7.41 (br. d, J = 7.4 Hz, 2 H, o-
Ar), 7.47 (m, 2 H, o-Ar) ppm. 13C NMR (100 MHz): δ = 28.4 [q,
C(CH3)3], 32.8 (t, =CHCH2), 52.2 (d, tBuOOCCH), 79.3 (s, COH),
82.9 [s, C(CH3)3], 117.0 (t, =CH2), 125.7 (d, 2 C, p-Ar), 127.2 (d,
PhCH=), 128.0 (d, 2 C, Ar), 128.2 (d, Ar), 128.3 (d, Ar), 128.9 (d,
Ar), 129.3 (d, Ar), 132.7 (d, p-Ar), 135.2 (s, ipso-Ar), 135.3 (d,
=CHCH2), 136.9 (s, ipso-Ar), 141.4 (s, ipso-Ar), 146.2 (s, =C), 176.0
(s, COOtBu), 198.9 (s, COPh) ppm.
anti-9Ia: 1H NMR (400 MHz): δ = 1.11 [s, 9 H, C(CH3)3], 2.62 (m,
1 H, =CHCH2), 2.84 (m, 1 H, =CHCH2), 3.85 (dd, J = 11.2,
3.8 Hz, 1 H, tBuOOCCH), 5.02 (s, 1 H, OH), 5.04 (d, J = 17.1 Hz,
1 H, trans =CH2), 5.13 (d, J = 10.0 Hz, 1 H, cis =CH2), 5.96 (dddd,
J = 17.1, 10.1, 8.6, 5.6 Hz, 1 H, =CH), 6.85–7.10 (m, 11 H, Ar,
PhCH=), 7.30 (m, 2 H, Ar), 7.43 (m, 3 H, Ar) ppm. Due to the
low content an assignment of the 13C NMR spectroscopic data was
not possible.
1
syn-9If: H NMR (400 MHz): δ = 1.40 [s, 9 H, C(CH3)3], 2.15 (m,
1 H, =CHCH2), 2.55 (ddd, J = 14.1, 10.9, 9.3 Hz, 1 H, =CHCH2),
3.63 (dd, J = 11.2, 3.9 Hz, 1 H, tBuOOCCH), 5.34 (s, 1 H, OH),
6.06 (ddd, J = 15.5, 9.2, 5.8 Hz, 1 H, PhCH=CH), 6.26 (d, J =
15.8 Hz,
1
H, HC=CHPh), 6.90–7.50 (m, 21 H, Ar,
PhCH=C) ppm. 13C NMR (100 MHz): δ = 28.3 [q, C(CH3)3], 31.9
(t, =CHCH2), 52.6 (d, tBuOOCCH), 79.3 (s, COH), 82.8 [s,
C(CH3)3], 125.7 (d, Ar), 126.1 (d, 2 C, p-Ar), 127.0 (d, =CH), 127.2
(d, 2 C, p-Ar, =CH), 127.94 (d, 2 C, Ar), 128.26 (d, Ar), 128.29 (d,
Ar), 128.58 (d, Ar), 128.9 (d, Ar), 129.2 (d, Ar), 132.1 (d,
PhCH=CHCH2), 132.71 (d, p-Ar), 135.2 (s, ipso-Ar), 136.9 (s, ipso-
Ar), 137.4 (s, ipso-Ar), 141.4 (s, ipso-Ar), 146.1 (s, =C), 176.1 (s,
COOtBu), 198.9 (s, COPh) ppm.
anti-9If: 1H NMR (400 MHz): δ = 1.04 [s, 9 H, C(CH3)3], 2.79
(ddd, J = 13.8, 11.2, 8.6 Hz, 1 H, =CHCH2), 3.02 (m, 1 H,
=CHCH2), 3.97 (dd, J = 11.2, 3.9 Hz, 1 H, tBuOOCCH), 5.14 (s,
1 H, OH), 6.37 (ddd, J = 15.6, 8.5, 5.3 Hz, 1 H, PhCH=CH), 6.46
(d, J = 15.9 Hz, 1 H, HC=CHPh), 6.85–7.50 (m, 21 H, Ar,
PhCH=C) ppm. 13C NMR (100 MHz): δ = 27.8 [q, C(CH3)3], 32.0
(t, =CHCH2), 51.2 (d, tBuOOCCH), 78.4 (s, COH), 82.1 [s,
syn/anti-(Z)-tert-Butyl 2-Benzoyl-3-hydroxy-7-methyl-1,3-diphenyl- C(CH3)3], 126.17 (d, Ar), 126.21 (d, Ar), 127.1 (d, p-Ar or =CH),
octa-1,6-dien-4-oates (9Ie): Colorless solid; m.p. 128–130 °C; Rf =
0.48 (hexane/EtOAc, 5:1). IR: ν = 3429, 3027, 2975, 1692, 1668,
127.4 (d, p-Ar or =CH), 127.7 (d, 2 C, Ar, p-Ar or =CH), 127.8
(d, p-Ar or =CH), 127.95 (d, Ar), 128.2 (d, Ar), 128.60 (d, Ar),
˜
1447, 1366, 1227, 1147, 696 cm–1. MS (ESI+): m/z (%) = 519 (100) 129.1 (d, Ar), 129.3 (d, Ar), 129.5 (d, p-Ar), 132.0 (d,
[M + Na+], 463 (34) [M + Na+ – H2C=C(CH3)2], 401 (32) [M +
Na+ – H2C=C(CH3)2 – H2O – CO2]. C33H36O4 (496.64): calcd. C
79.81, H 7.31; found C 79.82, H 7.33.
PhCH=CHCH2), 132.69 (d, p-Ar), 135.5 (s, ipso-Ar), 136.6 (s, ipso-
Ar), 137.8 (s, ipso-Ar), 140.9 (s, ipso-Ar), 143.6 (s, =C), 176.0 (s,
COOtBu), 200.0 (s, COPh) ppm.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
15

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
anti/syn-(Z)-tert-Butyl 2-Acetyl-3-hydroxy-3-methyl-1-phenylhepta- (E)-tert-Butyl 2-Benzoyl-5-phenylpent-4-enoate (10If): Yellow vis-
1,6-dien-4-oates (9Ka): Colorless oil; Rf = 0.63 (hexane/EtOAc, cous liquid as an inseparable mixture with chalcone (10If/11I, 4:1).
5:1). IR: ν = 3447, 2979, 1693, 1365, 1234, 1148, 916, 750,
R = 0.4 (hexane/EtOAc, 5:1). IR: ν = 2977, 1726, 1685, 1597, 1448,
˜
˜
f
698 cm–1. MS (ESI+): m/z (%) = 367 (100) [M + Na+], 311 (52) [M
1368, 1231, 1141, 964, 745, 689 cm–1. MS (ESI+): m/z (%) = 359
(100) [M + Na+], 303 (58) [M + Na+ – H2C=C(CH3)2], 259 (25)
[M + Na+ – CO2 – H2C=C(CH3)2]. HRMS (ESI+): calcd. for
C22H24O3Na+ 359.1618; found 359.1616. 1H NMR (400 MHz): δ
= 1.29 [s, 9 H, C(CH3)3], 2.84 (m, 2 H, CH2CH=), 4.29 (t, J =
7.2 Hz, 1 H, tBuOOCCH), 6.18 (dt, J = 15.7, 7.2 Hz, 1 H,
CH2CH=), 6.44 (d, J = 15.8 Hz, 1 H, =CHPh), 7.10–7.55 (m, 8 H,
Ar), 7.96 (m, 2 H, o-COPh) ppm. 13C NMR (100 MHz): δ = 28.0
[q, C(CH3)3], 32.4 (t, =CHCH2), 55.8 (d, tBuOOCCH), 82.3 [s,
C(CH3)3], 126.4 (d, Ar), 126.7 (d, p-Ar or =CH), 127.4 (d, p-Ar or
=CH), 128.7 (d, Ar), 128.78 (d, Ar), 128.82 (d, Ar), 132.6 (d, =CH),
133.4 (d, p-Ar), 136.8 (s, ipso-Ar), 137.5 (s, ipso-Ar), 168.7 (s, CO-
OtBu), 195.0 (s, COPh) ppm.
+ Na+ – H2C=C(CH3)2], 249 (22) [M + Na+ – H2C=C(CH3)2
–
CO2 – H2O]. C18H30O6 (344.44): calcd. C 73.23, H 8.19; found C
73.28, H 8.21.
1
syn-9Ka: H NMR (400 MHz): δ = 1.39 [s, 9 H, C(CH3)3], 1.43 (s,
3 H, CH3), 2.02 (s, 3 H, COCH3), 2.45 (m, 2 H, =CHCH2), 2.99
(dd, J = 9.7, 5.8 Hz, 1 H, tBuOOCCH), 4.72 (s, 1 H, OH), 5.04 (d,
J = 10.0 Hz, 1 H, cis =CH2), 5.12 (d, J = 17.0 Hz, 1 H, trans
=CH2), 5.78 (m, 1 H, =CHCH2), 6.92 (s, 1 H, =CHPh), 7.20–7.40
(m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 24.6 (q, CH3), 28.2
[q, C(CH3)3], 32.0 (t, =CHCH2), 32.7 (q, CH3), 51.9 (d,
tBuOOCCH), 75.1 (s, COH), 82.4 [s, C(CH3)3], 117.2 (t, =CH2),
128.3 (d, p-Ph), 128.61 (d, Ph), 128.65 (d, Ph), 128.8 (d, =CHPh),
135.2 (d, =CHCH2), 135.8 (s, ipso-Ph), 149.6 (s, =C), 175.3 (s, CO-
OtBu), 207.9 (s, COCH3) ppm.
2-Benzoyl-4-benzylidene-1,3,5-triphenylpentane-1,5-dione (12I): Col-
orless solid; m.p. 195 °C; R = 0.2 (hexane/EtOAc, 5:1). IR: ν =
˜
f
3060, 3027, 1696, 1665, 1647, 1595, 1579, 1493, 1447, 1262, 1230,
anti-9Ka: H NMR (400 MHz): δ = 1.45 (s, 3 H, CH3), 1.47 [s, 9
1178, 973, 756, 732, 696 cm–1. MS (ESI+): m/z (%) = 543 (100) [M
1
H, C(CH3)3], 2.04 (s, 3 H, COCH3), 2.43 (m, 2 H, =CHCH2), 2.94 + Na+], 297 (10) [M+ – dibenzoylmethane]. HRMS (ESI+): calcd.
1
(dd, J = 10.7, 4.6 Hz, 1 H, tBuOOCCH), 4.44 (s, 1 H, OH), 5.00
for C37H28ONa+ 543.1931; found 543.1930. H NMR (400 MHz):
(d, J = 10.1 Hz, 1 H, cis =CH2), 5.06 (d, J = 17.1 Hz, 1 H, trans δ = 5.18 (d, J = 11.3 Hz, 1 H, PhCH), 6.82 (m, 2 H, Ar), 6.92 (m,
=CH2), 5.79 (m, 1 H, =CHCH2), 7.11 (s, 1 H, =CHPh), 7.20–7.40
3 H, Ar), 7.00 [m, 5 H, Ar, CH(COPh)2], 7.08 (s, 1 H, =CH), 7.16
(m, 5 H, Ph) ppm. 13C NMR (100 MHz): δ = 27.0 (q, CH3), 28.3 (m, 1 H, p-Ar), 7.30 (m, 5 H, Ar), 7.45 (m, 5 H, Ar), 7.53 (m, 1 H,
[q, C(CH3)3], 32.6 (q, CH3), 32.8 (t, =CHCH2), 52.5 (d,
p-Ar), 7.88 (m, 2 H, o-Ar), 8.29 (m, 2 H, o-Ar) ppm. 13C NMR
tBuOOCCH), 74.7 (s, COH), 82.3 [s, C(CH3)3], 116.7 (t, =CH2), (100 MHz): δ = 54.7 (d, PhCH), 60.1 [d, (PhOC)2CH], 127.0 (d, p-
128.4 (d, p-Ph), 128.64 (d, Ph), 128.67 (d, Ph), 130.1 (d, =CHPh), Ar or =CH), 127.86 (d, Ar), 127.88 (d, p-Ar or =CH), 127.94 (d,
135.5 (d, =CHCH2), 135.9 (s, ipso-Ph), 146.0 (s, =C), 175.5 (s, CO-
OtBu), 208.1 (s, COCH3) ppm.
Ar), 128.5 (d, Ar), 128.63 (d, Ar), 128.65 (d, Ar), 128.77 (d, Ar),
128.81 (d, Ar), 128.9 (d, Ar), 129.3 (d, Ar), 129.4 (d, Ar), 132.8 (d,
p-Ar), 133.3 (d, p-Ar), 133.4 (d, p-Ar), 134.2 (d, p-Ar), 135.4 (s,
ipso-Ar or =C), 136.6 (s, ipso-Ar or =C), 137.3 (s, ipso-Ar or =C),
137.6 (s, ipso-Ar or =C), 138.4 (s, ipso-Ar or =C), 139.4 (s, ipso-Ar
or =C), 193.7 (s, COPh), 194.8 (s, COPh), 200.7 (s, COPh) ppm.
tert-Butyl 2-Benzoylpent-4-enoate (10Ia): Colorless oil; Rf = 0.55
(hexane/EtOAc, 5:1). IR: ν = 2978, 1729, 1685, 1368, 1239, 1143,
˜
916, 689 cm–1. MS (ESI+): m/z (%) = 283 (100) [M + Na+], 227
(65) [M + Na+ – H2C=C(CH3)2], 205 (10) [M + H+ – H2C=C-
(CH3)2]. C16H20O3 (260.33): calcd. C 73.82, H 7.74; found C 73.94,
(3S*,5R*)-2,4,4-Triacetyl-3,5-diphenylcyclohex-1-en-1-ol
(13K):
Colorless solid; m.p. 185–186 °C; Rf = 0.28 (hexane/EtOAc, 5:1).
1
H 7.70. H NMR (400 MHz): δ = 1.30 [s, 9 H, C(CH3)3], 2.68 (tt,
IR: ν = 3029, 1690, 1596, 1410, 1354, 1266, 1238, 1217, 1172, 948,
˜
J = 7.1, 1.2 Hz, 2 H, =CHCH2), 4.23 (t, J = 7.2 Hz, 1 H,
tBuOOCCH), 5.00 (d, J = 10.2 Hz, 1 H, cis =CH2), 5.08 (dq, J =
17.1, 1.5 Hz, 1 H, trans =CH2), 5.79 (ddt, J = 17.0, 10.2, 6.9 Hz, 1
H, =CH), 7.43 (m, 2 H, m-COPh), 7.53 (m, 1 H, p-COPh), 7.95
(m, 2 H, o-COPh) ppm. 13C NMR (100 MHz): δ = 28.0 [q,
C(CH3)3], 33.0 (t, =CHCH2), 55.3 (d, tBuOOCCH), 82.1 [s,
C(CH3)3], 117.3 (t, =CH2), 128.7 (d, Ph), 128.8 (d, Ph), 133.4 (d,
p-Ph), 135.0 (d, =CH), 136.7 (s, ipso-Ph), 168.7 (s, COOtBu), 195.0
(s, COPh) ppm.
735, 700 cm–1. MS (ESI+): m/z (%) = 399 (100) [M + Na+], 357 (7)
[M + Na+ – O=C=CH2]. C24H24O4 (376.44): calcd. C 76.57, H
1
6.43; found C 76.55, H 6.50. H NMR (400 MHz): δ = 1.14 (s, 3
H, CH3), 1.96 (s, 3 H, CH3), 2.44 (s, 3 H, CH3), 2.99 [dd, J = 19.5,
9.5 Hz, 1 H, =C(OH)CH2], 3.03 [dd, J = 19.5, 8.4 Hz, 1 H,
=C(OH)CH2], 3.88 (dd, J = 9.5, 8.4 Hz, 1 H, PhCH), 4.69 (s, 1 H,
PhCH), 7.15–7.40 (m, 10 H, Ar), 15.98 (s, 1 H, OH) ppm. 13C
NMR (100 MHz): δ = 25.8 (q, CH3), 30.2 (q, CH3), 30.4 (q, CH3),
37.1 [t, =C(OH)CH2], 39.3 (d, PhCHCH2), 48.5 (d, PhCH), 71.9
[s, (CH3OC)2C], 108.8 [s, C(OH)=C], 127.1 (d, p-Ph), 128.3 (d, p-
Ph), 128.5 (d, Ph), 129.1 (d, Ph), 129.3 (d, Ph), 130.1 (d, Ph), 139.1
(s, ipso-Ph), 140.4 (s, ipso-Ph), 180.4 [d, (HO)C=], 200.5 (d,
COCH3), 205.9 (d, COCH3), 208.9 (d, COCH3) ppm.
tert-Butyl 2-Benzoyl-5-methylhex-4-enoate (10Ie): Colorless solid;
m.p. 33 °C; R = 0.55 (hexane/EtOAc, 5:1). IR: ν = 2976, 2929,
˜
f
1728, 1685, 1448, 1368, 1244, 1139, 844, 690 cm–1. MS (ESI+): m/z
(%) = 599 (18) [2M + Na+], 327 (3) [M + K+], 311 (100) [M +
Na+], 255 (3) [M + Na+ – H2C=C(CH3)2], 233 (15) [M + H+
–
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, analytical data, results of NOE ex-
periments, X-ray crystallographic data of syn-3Ga and syn-9Ie, and
copies of NMR spectra.
H2C=C(CH3)2]. HRMS (ESI+): calcd. for C18H24O3Na+ 311.1618;
found 311.1618. C18H24O3 (288.38): calcd. C 74.97, H 8.39; found
1
C 75.32, H 8.39. H NMR (400 MHz): δ = 1.30 [s, 9 H, C(CH3)3],
1.59 (br. s, 3 H, CH3), 1.62 (br. s, 3 H, CH3), 2.62 (m, 2 H,
=CHCH2), 4.14 (t, J = 7.3 Hz, 1 H, tBuOOCCH), 5.09 (t, J =
7.3 Hz, 1 H, =CH), 7.42 (t, J = 7.6 Hz, 2 H, m-COPh), 7.52 (tt, J
= 7.4, 1.9 Hz, 1 H, p-COPh), 7.94 (m, 2 H, o-COPh) ppm. 13C
Acknowledgments
NMR (100 MHz): δ = 18.0 [q, (Z)- =CCH3], 25.9 [q, (E)- =CCH3], Generous financial support by the Grant Agency of the Czech Re-
27.7 (t, =CHCH2), 27.9 [q, C(CH3)3], 55.9 (d, tBuOOCCH), 81.8 public (P203/09/1936) and the Institute of Organic Chemistry and
[s, C(CH3)3], 120.7 (d, =CH), 128.68 (d, Ph), 128.69 (d, Ph), 133.3 Biochemistry (Z4 055 0506) is gratefully acknowledged. I. C.
(d, p-Ph), 134.3 (s, =C), 136.9 (s, ipso-Ph), 169.1 (s, COOtBu), 195.5
(s, COPh) ppm.
thanks the Ministry of Education, Youth and Sports of the Czech
Republic (MSM0021620857) for financial support.
16
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
Polyfunctional β-Dicarbonyl Compounds
[12] a) O. Kaumanns, R. Lucius, H. Mayr, Chem. Eur. J. 2008, 14,
9675–9682 and references therein; b) S. Kanemasa, A. Tatsu-
kawa, E. Wada, J. Org. Chem. 1991, 56, 2875–2883; c) H.
Wang, R. Fan, J. Org. Chem. 2010, 75, 6994–6997; d) S. G.
Davies, P. M. Roberts, A. D. Smith, Org. Biomol. Chem. 2007,
5, 1405–1415; e) K. Yasuda, M. Shindo, K. Koga, Tetrahedron
Lett. 1996, 37, 6343–6346; f) K. Yasuda, M. Shindo, K. Koga,
Tetrahedron Lett. 1997, 38, 3531–3534; g) J. M. Betancort, K.
Sakthivel, R. Thayumanavan, C. F. Barbas III, Tetrahedron
Lett. 2001, 42, 4441–4444; h) H. Yang, X.-F. Lin, F. Padilla,
S. D. Gabriel, G. Heilek, C. Ji, S. Sankuratri, A. deRosier, P.
Berry, D. M. Rotstein, Bioorg. Med. Chem. Lett. 2009, 19, 209–
213.
[13] The geometry of a potassium enolate was assigned, see: J. Cor-
set, F. Froment, M. F. Lautie, N. Ratovelomanana, J. Seyden-
Penne, T. Strzalko, M. C. Roux-Schmitt, J. Am. Chem. Soc.
1993, 115, 1684–1694.
[14] M. W. Rathke, D. F. Sullivan, Synth. Commun. 1973, 3, 67–72.
It seems that the major (E)-enolate forms 6b, whereas the
minor (Z)-enolate affords silyl ketene acetal 5b.
[1]
a) For an overview on early work, see: E. D. Bergmann, D.
Ginsburg, R. Pappo, Org. React. 1959, 10, 179–555. For more
recent reviews, see: b) R. D. Little, M. R. Masjedizadeh, O.
Wallquist, J. I. McLoughlin, Org. React. 1995, 47, 315–552; c)
B. L. Feringa, J. F. G. A. Jansen, in: Methods of Organic Chem-
istry (Houben-Weyl) - Stereoselective Synthesis, vol. E21b, 4th
ed. (Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schau-
mann), Thieme, Stuttgart, Germany, 1995, pp. 2104–2155; d)
N. Krause, A. Hoffmann-Röder, Synthesis 2001, 171–196; e)
B. D. Mather, K. Viswanathan, K. M. Miller, T. E. Long, Prog.
Polym. Sci. 2006, 31, 487–531; f) J. Christoffers, G. Koripelly,
A. Rosiak, M. Rössle, Synthesis 2007, 1279–1300; g) S. Jautze,
R. Peters, Synthesis 2010, 365–388.
a) D. A. Oare, C. H. Heathcock, J. Org. Chem. 1990, 55, 157–
172; b) Review: D. A. Oare, C. H. Heathcock, Top. Stereochem.
1989, 19, 227–407.
To avoid confusion of stereochemical models, Heathcock’s
syn/anti-assignment of relative configuration is applied.[2] This
uses the extended 1,5-dicarbonyl chain as the central chain and
assigns all other groups as substituents irrespective of their
length. This is opposite to the common anti/syn assignment, in
which the longest chain is used as the basis.
[2]
[3]
[15] Yield losses can be traced to decomposition during purification
by silica gel flash chromatography.
[16] For a review, see: O. Kitagawa, T. Taguchi, Synlett 1999, 1191–
1199.
[4]
[5]
E. E. Kwan, D. A. Evans, Org. Lett. 2010, 12, 5124–5127.
[17] Full crystallographic details of the structures of syn-3Ga and
syn-9Ie were deposited at the Cambridge Crystallographic
Data Centre under the numbers CCDC-863379 and 863380,
respectively. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
a) A. Bernardi, Gazz. Chim. Ital. 1995, 125, 539–547; b) A.
Bernardi, P. Dotti, G. Poli, C. Scolastico, Tetrahedron 1992, 48,
5597–5606.
[6] D. C. Oare, C. H. Heathcock, Top. Stereochem. 1991, 20, 87–
170.
[7] For reviews, see: a) S. C. Jha, N. N. Joshi, ARKIVOC 2002, pt.
7, 167–196; b) J. Comelles, M. Moreno-Manas, A. Vallribera,
ARKIVOC 2005, pt. 9, 207–238; c) S. Kanemasa, M. Hase-
gawa, F. Ono, Chem. Rec. 2007, 7, 137–149.
[8] For selected reviews, see: a) J. L. Vicario, D. Badia, L. Carrillo,
Synthesis 2007, 2065–2092; b) H. Pellissier, Tetrahedron 2007,
63, 9267–9331; c) D. Roca-Lopez, D. Sadaba, I. Delso, R. P.
Herrera, T. Tejero, P. Merino, Tetrahedron: Asymmetry 2010,
21, 2561–2601; d) M. Thirumalaikumar, Org. Prep. Proced. Int.
2011, 43, 67–129.
[18] The relative configuration of 3Fa was confirmed by an oxidat-
ive cyclization; manuscript in preparation.
[19] A. G. Schultz, Y. K. Yee, J. Org. Chem. 1976, 41, 4044–4045.
[20] a) For the preparation of 4-pentenoyl chloride, see: B. T. Lotz,
M. J. Miller, J. Org. Chem. 1993, 58, 618–625; b) W. F. Beech,
H. A. Piggott, J. Chem. Soc. 1955, 423–429.
[21] J. R. Falck, P. S. Kumar, Y. K. Reddy, G. Zou, J. H. Capdevila,
Tetrahedron Lett. 2001, 42, 7211–7212.
[22] D. J. Fox, D. S. Pedersen, S. Warren, Org. Biomol. Chem. 2006,
4, 3113–3116.
[9] Reviews: a) D. Almasi, D. A. Alonso, C. Najera, Tetrahedron:
Asymmetry 2007, 18, 299–365; b) Y. Takemoto, Chem. Pharm.
Bull. 2010, 58, 593–601.
[23] P. A. Clarke, M. Grist, M. Ebden, C. Wilson, A. J. Blake, Tetra-
hedron 2005, 61, 353–363.
[24] E. G. Mata, E. J. Thomas, J. Chem. Soc. Perkin Trans. 1 1995,
[10] Selected reviews: a) M. Ihara, K. Fukumoto, Angew. Chem.
1993, 105, 1059–1071; Angew. Chem. Int. Ed. Engl. 1993, 32,
1010–1022; b) R. A. Bunce, Tetrahedron 1995, 51, 13103–
13159; c) E. V. Gorobets, M. S. Miftakhov, F. A. Valeev, Russ.
Chem. Rev. 2000, 69, 1001–1019; d) R. Ballini, A. Palmieri, L.
Barboni, Chem. Commun. 2008, 2975–2985; e) H. L. Cui, Y. C.
Chen, Chem. Commun. 2009, 4479–4486; f) M. Ruiz, P. Lopez-
Alvarado, G. Giorgi, J. C. Menendez, Chem. Soc. Rev. 2011,
40, 3445–3454.
785–799.
[25] O. Kaumanns, H. Mayr, J. Org. Chem. 2008, 73, 2738–2745.
[26] B. Siebenhaar, B. Casagrande, M. Studer, H.-U. Blaser, Can. J.
Chem. 2001, 79, 566–569.
[27] F. D. Popp, A. Catala, J. Org. Chem. 1961, 26, 2738–2740.
[28] A. C. Cope, K. E. Hoyle, J. Am. Chem. Soc. 1941, 63, 733–736.
[29] R. Antonioletti, P. Bovicelli, S. Malancona, Tetrahedron 2002,
58, 589–596.
Received: January 23, 2012
[11] U. Jahn, Chem. Commun. 2001, 1600–1601.
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
17

Job/Unit: O20077
/KAP1
Date: 09-05-12 10:26:24
Pages: 18
M. Holan, R. Pohl, I. Císarˇová, U. Jahn
FULL PAPER
Michael Addition
ˇ
M. Holan, R. Pohl, I. Císarová,
U. Jahn* ......................................... 1–18
Polyfunctional β-Dicarbonyl Compounds
by Michael Addition Reactions of Ester
Enolates to α-Benzylidene and α-Alkylid-
ene-β-dicarbonyl Compounds
Michael addition reactions of ester enolates
with various unsaturated β-dicarbonyl
compounds are presented. The diastereose-
lectivity of the addition can be controlled
by employing enolates with defined geometry.
The scope and limitations of the method-
ology are discussed.
Keywords: Michael addition / Diastereose-
lectivity / Regioselectivity / Enols / Dicarb-
onyl compounds
18
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Eur. J. Org. Chem. 0000, 0–0