Asymmetric Evans syn-Aldol Reactions of Terpene-Derived Enals: Scope and Limitations

Article abstract of DOI:10.1002/ejoc.201402736

The (E)- and (Z)-terpene-based aldehydes 6b and 6c with a silyl ether function in the γ-position were prepared and investigated in boron-mediated asymmetric Evans aldol reactions. Screening experiments of chiral N-acylated oxazolidinones 7, which are conveniently accessible from 5-methyl-5-hexenoic acid and Evans oxazolidinone auxiliaries, with various boron triflates and terpenoid neral (Z)-6a as aldehyde component, provided conditions in which highly selective formation of syn-aldol adduct 5a occurred and competing C=C double bond isomerization to 10 was completely suppressed. Applying the optimized conditions to O-silylated aldehydes 6b and 6c and N-acyloxazolidinone derivative (R)-7a confirmed the syn-selectivity and gave the appropriate products syn-5b,c and syn-21b,c in good yields. In the case of neral-derived syn adduct 5a, the configuration of the new stereogenic centers C-2/C-3 could be assigned as (2R,3S). The asymmetric Evans aldol reaction could be successfully applied to terpene-based (E)- and (Z)-aldehydes and N-acyloxazolidinones, giving syn-aldol adducts with high selectivity. Isomerization at the double bond was not observed.

Full text of DOI:10.1002/ejoc.201402736

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
FULL PAPER
DOI: 10.1002/ejoc.201402736
Asymmetric Evans syn-Aldol Reactions of Terpene-Derived Enals: Scope and
Limitations
[a]
[a]
[a]
[a]
Sebastian Kriening, Athanasios Evagelou, Birgit Claasen, Angelika Baro, and
Sabine Laschat*[
a]
Keywords: Aldol reactions / Terpenoids / Boron / C–C coupling / Configuration determination
The (E)- and (Z)-terpene-based aldehydes 6b and 6c with a
silyl ether function in the γ-position were prepared and in-
vestigated in boron-mediated asymmetric Evans aldol reac-
tions. Screening experiments of chiral N-acylated oxazol-
idinones 7, which are conveniently accessible from 5-methyl-
formation of syn-aldol adduct 5a occurred and competing
C=C double bond isomerization to 10 was completely sup-
pressed. Applying the optimized conditions to O-silylated
aldehydes 6b and 6c and N-acyloxazolidinone derivative
(R)-7a confirmed the syn-selectivity and gave the appropriate
products syn-5b,c and syn-21b,c in good yields. In the case
of neral-derived syn adduct 5a, the configuration of the new
stereogenic centers C-2/C-3 could be assigned as (2R,3S).
5-hexenoic acid and Evans oxazolidinone auxiliaries, with
various boron triflates and terpenoid neral (Z)-6a as aldehyde
component, provided conditions in which highly selective
Eunicea tourneforti in 1977 by Weinheimer.[10] The natural
product 1 and its closely related analogues knightol (2a),
knightol acetate (2b), and knightal (3) (Figure 1), which
were isolated in 2009 by Tello from the Caribbean sea whip
Introduction
The discovery of boron enolates[1] and silyl enol ethers[2]
and their use in stereocontrolled aldol reactions 40 years
ago by Mukaiyama opened a plethora of possibilities in
asymmetric C–C coupling reactions and has been success-
fully implemented as key steps in numerous total syntheses
of natural products.[ In particular, the combination of the
Mukaiyama aldol reaction with Evans oxazolidinone auxil-
iary led to a highly reliable and robust methodology even
for complex target molecules.[
[
11]
Eunicea knighti,
have received increasing interest due to
their promising cytotoxic and antimicrobial activity.
3]
4]
[
5]
Although asymmetric aldol reactions with either enals
or aldehydes carrying alkenes[
6,5a,5b]
are known to proceed
with a high degree of stereoselectivity, surprisingly little is
known about enals derived from terpenes.[ For these sub-
strates one might worry about competing C=C double bond
isomerization. anti-Aldol products from acrolein are not ac-
cessible through an anti-Evans protocol, but recently a
7]
Figure 1. Asperdiol (1a), its analogue knightol (2a), their acetates
1b, 2b and knightal (3).
[
8]
method to overcome these difficulties was reported. Dur-
ing our studies on gephyronic acid, we observed that
Five total syntheses of asperdiol (1a) have been reported
[
12]
[13]
[14]
by Still,
Marshall,
and Tius
utilizing a Nozaki–
2,3,5,6-dienals are particularly sensitive towards double
Hiyami–Kishi reaction, sulfone alkylation,[13b] [2,3]-Wit-
tig rearrangements
HWE) olefinations as key steps for the ring closure. To
[
12]
bond isomerization but they could be cleanly converted into
the anti-Evans aldol products without any formation of the
[
13a]
or Horner–Wadsworth–Emmons
[
14]
(
[
9]
conjugated dienes. Hence, we intended to install an asym-
metric Evans aldol addition as key step in the synthesis of
asperdiol precursors. Asperdiol (1a) is a 14-membered
macrocyclic diterpene that was isolated together with
acetate 1b from the soft corals Eunicea asperula and
gain access to potential asperdiol precursors 4, we envis-
aged a synthetic strategy that was based on an Evans aldol
reaction between terpene-based enals 6 and N-acyloxazol-
idinone derivatives 7. Variation at the double bond in 6 (E
or Z) and at the stereocenter in 7 (R or S) should provide
different stereoisomers, also those with unnatural configu-
ration, for structure–activity relationship (SAR) studies. A
methodological study was therefore undertaken to explore
the synthesis of 5 starting from enals 6 and N-acyloxazol-
idinones 7 (Scheme 1). The results are discussed below.
[
a] Institut für Organische Chemie, Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
E-mail: sabine.laschat@oc.uni-stuttgart.de
http://www.laschat.oc.uni-stuttgart.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402736.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

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Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
The N-acyloxazolidines (S)-7 were first coupled with the
terpenoid neral (Z)-6a in boron-mediated aldol reac-
[
3a,17]
tions.
To find optimal conditions, a series of screening
experiments were undertaken; the results thereof are sum-
marized in Table 1. Reactions of oxazolidinone (S)-7b with
Bu BOTf and (Z)-6a at –78 °C provided the aldol addition
2
product 5d as an almost equimolar mixture of syn- and
anti-diastereomers, and the yield could be improved from
3
9 to 70% by replacing Et N with Hünig’s base (iPr NEt;
3
2
Scheme 1. Evans aldol products 5 based on fragments 6 und 7.
Results and Discussion
The required chiral N-acylated oxazolidin-2-one deriva-
tives 7 were accessible from 5-methylhex-5-enoic acid
8)[
15]
by conversion with pivaloyl chloride
[16]
and sub-
(
sequent reaction with auxiliaries (R)-9a, (S)-9a, or (S)-9b
to yield the target products (R)-7a, (S)-7a, and (S)-7b in 76,
80, and 77%, respectively (Scheme 2).
It should be noted that the use of thionyl chloride instead
of pivaloyl chloride resulted in the formation of undesired
byproducts (see the Supporting Information).
Scheme 2. Synthesis of N-acyloxazolidinones 7. Reagents and con-
ditions: (a) 1. PivCl, Et N, THF, 0 °C, 30 min; 2. BuLi, 9; 3. –78 °C,
1 h; 0 °C, 1 h. Numbering for NMR assignment.
3
Table 1. Asymmetric aldol reactions of N-acyloxazolidinones (S)-7a or (S)-7b with neral (Z)-6a under various conditions.[a,b]
Product
Ratio
Yield [%]
Entry Method (S)-7
R
2
BOTf
t
1
[min]
Enal
T [°C]
t
2
[h]
5
syn/anti Yield [%]
5a/10
5a+10[c]
1
2
3
4
5
6
7
8
9
1
1
A[d]
A
A
A
A
A
B
B
B
C
C
7b
7b
7a
7a
7a
7a
7a
7a
7a
7a
7a
Bu
Bu
Bu
Bu
Bu
Cy
BBNOTf
BBNOTf
BBNOTf
BBNOTf
2
2
2
2
2
2
BOTf
BOTf
BOTf
BOTf
BOTf
BOTf
60
30
5
5
5
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
–78
–78
–78
–15
0
–100
0
0
0
0
0
2
5d
5d
5a
5a
5a
5a
5a
5a
5a
5a
5a
47:53
52:48
100:0
100:0
100:0
100:0
Ͼ95:5
Ͼ95:5
Ͼ95:5
100:0
100:0
39
70
69
70
72
–
–
–
–
86
48
–
–
–
–
–
–
–
–
–
–
14
62
51
59
–
20
5.5
5.5
15
21
21
21
21
17
19
5
71:29
30:70
20:80
6:94
–
30
45
120
90
90
0
1
Cy
2
BOTf
–
–
1
[
a] Formation of boron enolate (time t
1
), aldol addition (time t
2
). [b] The syn/anti and isomeric ratios 5a/10 were determined by H NMR
spectroscopic analysis. [c] Compound 10 could not be separated by chromatography and was analyzed as 1,3-diol after removal of the
auxiliary (see the Supporting Information). [d] Et N was used as base.
3
2
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Asymmetric Evans syn-Aldol Reactions
entries 1 and 2, method A). In contrast, oxazolidinone (S)-
7
a in combination with Bu BOTf/Hünig’s base underwent
2
a stereoselective aldol reaction with (Z)-6a affording exclu-
sively the syn-aldol product 5a in 69–72% yield regardless
of the reaction temperature (entries 3–5). The use of
BBNOTf, however, resulted in the formation of a 20:80
mixture of aldol product 5a (syn/anti = 95:5) and byproduct
10 in which isomerization of the terminal double bond had
taken place (entry 8, method B). This C=C double bond
isomerization could be slightly suppressed by shortening
the reaction time of (S)-7a with the boron reagent BBNOTf
(entry 7), whereas reaction time extension promoted isom-
erization, providing a mixture of 5a/10 in a ratio of 6:94,
which was isolated in 59% yield (entry 9). The ratio 5a/10
could be shifted in favor of 5a by reacting (S)-7a with boron
triflate Cy BOTf at –100 °C for 5 min (entry 6). By using
2
an inverse addition protocol, i.e., first addition of Hünig
base to oxazolidinone (S)-7a followed by addition of the
boron reagent BBNOTf (Method C), not only avoided by-
product formation but also led to the selective formation of
syn-aldol adduct 5a in 86% yield (entry 10); thus Method C
was clearly superior to Method A. Use of the inverse reac-
tion conditions with dicyclohexylboron triflate Cy BOTf
2
also gave clean adduct syn-5a, albeit with a poorer yield of
48% (entry 11).
To check the enantiomeric purity, aldol adduct syn-5a
was converted into the respective TBS ether 11 (Scheme 3),
which was submitted to capillary GC analysis with an achi-
ral nonpolar stationary phase. Only a single peak was de-
Scheme 3. Assignment of the relative and absolute configuration of
aldol product 5a. Reagents and conditions: (a) TBSCl, Et N,
3
tected and the diastereoselectivity was determined to be DMAP, DMF, room temp., 21 h; (b) (R)- or (S)-MTPACl, py,
DMAP, CH
2
Cl
2
, room temp., 17 h; (c) 5a, LiBH
CMe , PPTS, acetone, room temp.,
h. (R)- and (S)-12 denotes the MTPA configuration; the Δδ values
4
, THF/MeOH
96% de (see the Supporting Information).
(
100:1), 0 °C, 6 h; (d) (MeO)
2
2
All attempts to determine the configuration of aldol
product 5a by X-ray single-crystal structure analysis failed
3
–1
are given in units of 10 ppm. Numbering in 5a and 14 for NMR
(
see the Supporting Information). Therefore, Mosher’s assignment.
[
18]
method was applied to determine the absolute configura-
tion at carbon atom C-3. For this purpose, syn-5a was ester-
ified with Mosher acid chloride (R)- and (S)-MTPA chlor- uration of the stereogenic centers C-2/C-3. Consequently, a
ide to furnish the corresponding (S)- and (R)-MTPA esters (2S,3R)-configuration was assumed for syn-5a.
1
(
S)- and (R)-12, respectively (Scheme 3). Analysis of the H
The γ-substituted terpene-based aldehydes (E)-6b,c, with
[18]
NMR shift differences indicated the absolute configura- oxy functionality, and their corresponding (Z)-isomers (Z)-
tion at C-3 as R (see the Supporting Information for de- 6b,c were obtained starting from phosphonate 15, which
tails).
was α-alkylated with 5-iodo-2-methyl-2-pentene as shown
The resulting phosphonate 16 was submitted to a HWE
To simplify the assignment of the relative configuration in Scheme 4.
at C-3/C-2, product syn-5a was converted into the confor-
mationally fixed cyclic acetal 14. First, 5a was treated with olefination with {[tert-butyl(dimethyl)silyl]oxy}acetalde-
[5a]
LiBH to remove the auxiliary and the resulting syn diol hyde in the presence of KOtBu to yield methacrylate 17 as
4
13 was isolated in 70% yield. Subsequent reaction with 2,2- a 70:30 mixture of E/Z isomers (see Table S1 in the Sup-
dimethoxypropane in the presence of PPTS in acetone af- porting Information for studies on E/Z selectivity control).
forded acetal 14 in 89% yield (Scheme 3). Coupling con- Chromatographic separation followed by DIBAL-mediated
stants and NOESY correlations secured the relative stereo- reduction provided (E)-allylic alcohol (E)-18 or its (Z)-ana-
chemical assignment. A syn-configured position of the pro- logue (Z)-18, which were protected with TBDPSCl
tons H-2 and Hax of the adjacent CH group is indicated (Method A) or with PMBBr (Method B) to give derivatives
2
by the small coupling constant (J = 2.9 Hz). NOEs of H-2 (E)-19a,b and (Z)-19a,b, respectively. Deprotection of the
with both Hax and Heq of the CH group can be found. TBS ether in 19 with TsOH gave allylic alcohols (E)- and
2
Furthermore, a NOE of the axial methyl group with Hax (Z)-20a,b, respectively. Compounds (E)-20a and (Z)-20a
but not Heq of the CH group was observed. A second NOE were finally submitted to Dess–Martin periodinane oxi-
2
of the axial CH group with H-3 brings the alkyl chain at dation to give (E)- and (Z)-enals 6b in 91 and 86% yield,
3
C-3 in an equatorial position, thus confirming a syn-config- respectively. The corresponding PMB derivatives (E)- and
Eur. J. Org. Chem. 0000, 0–0
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Job/Unit: O42736
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Date: 03-09-14 19:44:18
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S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
Scheme 5. Aldol reaction of N-acyloxazolidinone (R)-7a with (E)-
and (Z)-enals 6 by following Method C.
Table 2. Boron (BBNOTf)-mediated aldol reactions of N-acylox-
azolidinone (R)-7a with enals (E)- and (Z)-6a–c in the presence of
NEt according to Method C.[
2
a]
Hünigs base iPr
Entry Enal T [°C] t [h] Product
syn/anti[b] Yield [%]
1
2
3
4
5
6
(Z)-6a
(E)-6a
(E)-6b
(Z)-6b
(E)-6c
(Z)-6c
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
22 (2R,3S)-5a
22 (2R,3S)-21a
22 (2R,3S)-5b
22 (2R,3S)-21b
22 (2R,3S)-5c
22 (2R,3S)-21c
100:0
100:0
100:0
73
73
64
45
70
70
85:15[
100:0
100:0
c]
Scheme 4. Preparation of enals (E)- and (Z)-6b,c. Reagents and con-
ditions: Method A: imidazole, TBDPSCl, DMF, room temp., 18 h;
[a] For details see Scheme 5 and Table 1. [b] For entries 1–3 and 5,
Method B: NaH, CH
2
Cl
2
, 0 °C, (E)- or (Z)-18, room temp., 1 h,
Cl , 0 °C, 1.5 h (20a);
, room temp., 4 h (20b). Number-
1
6
no trace of anti product was detected by H NMR spectroscopic
PMBBr, 16 h; Method C: DMP, CH
2
2
analysis. [c] The syn/anti or (2R,3S)/(2S,3S)-ratio of 21b was deter-
mined by H NMR spectroscopic analysis.
Method D: NMO, TPAP, CH
ing for NMR assignment.
2 2
Cl
1
was the anti-configured aldol adduct (2S,3S)-21b detected
(
(
Z)-20b were oxidized with N-methylmorpholine N-oxide
NMO) and tetrapropylammonium perruthenate (TPAP) to
(syn/anti ratio = 85:15) (entry 4), whereas the reaction of
oxazolidinone (R)-7a with the other silylated enals (E)-6b,c
and (Z)-6c proceeded syn-selectively and afforded the corre-
sponding (2R,3S)-aldol products 5b,c and 21c in moderate
to good yields (entries 3, 5, and 6).
give substituted enals (E)- and (Z)-6c in 77 and 80%,
respectively (Scheme 4).
With fragments 6b,c in hand, we applied the conditions
of boron-mediated aldol reaction (Method C) to the N-
acylated oxazolidinone (R)-7a in the presence of Hünigs
base. For comparison, neral (Z)-6a and geranial (E)-6a
were also converted (Scheme 5). The results are summarized
in Table 2.
Conclusions
We have documented a directed aldol reaction employing
Under these conditions, aldol coupling occurred between chiral Evans N-acyloxazolidinone derivatives (S)- and (R)-
the boron enolate of oxazolidinone (R)-7a and both terpen- 7 and boron triflates in the presence of iPr NEt as the base.
2
oids neral [(Z)-6a] and geranial [(E)-6a] with high selectivity The aldol reaction was based on a methodological screen-
to give the respective (2R,3S)-aldol products 5a and 21a ing with the aldehyde component neral (Z)-6a. In addition
(Table 2, entries 1 and 2). The absolute and relative stereo- to neral, its (E)-analogue geranial (E)-6a and the structur-
chemistry of the two stereocenters in ent-5a was assigned ally related aldehydes (E)- and (Z)-6b,c with O-silyl func-
as described for its (2S,3R)-congener 5a (see the Supporting tion in the γ-position were studied. The synthesis of the
Information). In the case of carbonyl components 6b,c, the latter was realized by a sequence of alkylation/HWE ole-
method was modified by slightly changing the proportion fination starting from the commercially available di-
of reactants 6b,c, 7a, and BBNOTf as compared with those isopropyl (ethoxycarbonylmethyl)phosphonate 15 to give
in Table 1. Only in the case of TBDPS silyl ether (Z)-6b, E/Z-methacrylate 17. Chromatographic separation of the
4
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Asymmetric Evans syn-Aldol Reactions
isomers allowed a systematic preparation of both O-sil- under vacuum. The residue was purified by chromatography on
SiO
2 f
(hexanes/EtOAc, 10:1; R = 0.26) to give (R)-7a (4.30 g,
ylated (E)- and (Z)-enals 6b,c. The aldol coupling between
the boron enolate of 7 and terpene-based enals 6 proceeded
with high selectivity to afford the appropriate syn-aldol ad-
ducts 5 and 21. Under the optimized reaction conditions,
the boron enolate of (R)-7a coupled with (E)-6b,c and (Z)-
2
0
1
8.0 mmol, 76%, GC purity 98%) as a colorless oil. [α]
D
= –72.0
): δ = 0.88 and
], 1.73 (dd, J = 1.3, 1.2 Hz,
), 2.09 (td, J = 7.6, 1.3 Hz, 2
), 2.38 [qqd, J = 7.0, 7.0, 3.9 Hz, 1 H, CH(CH ], 2.87
ddd, J = 16.9, 8.3, 6.6 Hz, 1 H, 2-H ), 2.98 (ddd, J = 16.9, 8.4,
), 4.21 (dd, J = 9.1, 3.0 Hz, 1 H, 5Ј-H ), 4.27 (dd,
1
(
0
3
c = 1.00, CH
2
Cl
.92 [each d, J = 7.0 Hz, 3 H, CH(CH
H, CH ), 1.75–1.88 (m, 2 H, CH
2 3
). H NMR (500 MHz, CDCl
3 2
)
3
2
H, CH
(
2
3 2
)
6c syn-selectively to give the respective aldol adducts. The
a
aldol reaction between (R)-7a and (Z)-6b, however, also
6.5 Hz, 1 H, 2-H
b
a
produced the anti adduct 21b, with a low syn/anti ratio J = 9.1, 8.2 Hz, 1 H, 5Ј-H ), 4.44 (ddd, J = 8.2, 3.9, 3.0 Hz, 1 H,
b
(
85:15). The absolute and relative configuration of the 4ЈH), 4.69–4.71 (m,
1
H, =CH
) ppm. C NMR (125 MHz, CDCl
], 22.38 (CH ), 22.39 (CH ), 28.5 [CH(CH
), 37.2 (CH ), 58.5 (C-4Ј), 63.5 (C-5Ј), 110.7 (=CH ), 145.1 (C=),
a
H
b
), 4.72–4.74 (m,
): δ = 14.8, 18.1
], 35.1 (C-
1 H,
1
3
newly formed stereocenters at C-2/C-3 was established for =CH
a
H
b
3
[
CH(CH
3
)
2
2
3
3 2
)
syn-5a to be (2S,3R) by the Mosher method and conversion
into the conformationally rigid acetal 14. The results dem-
onstrate that terpene-derived enals can be submitted to
boron-mediated Evans aldol reactions without any compet-
ing double bond isomerization or conjugate additions.
Thus, the scope of the Evans methodology has been further
extended. The obtained aldol addition products 5a–c and
2
1
1
2
2
54.2 (CO), 173.3 (C-1) ppm. FTIR (ATR): ν˜ = 2964 (w), 2876 (w),
772 (vs), 1698 (s), 1649 (w), 1486 (w), 1450 (w), 1385 (s), 1339
(
w), 1301 (m), 1243 (m), 1201 (vs), 1165 (m), 1140 (w), 1121 (w),
1
7
103 (m), 1070 (m), 1020 (m), 972 (w), 888 (m), 816 (w), 774 (w),
–1
+
54 (w), 693 (w) cm . MS (ESI): m/z = 262.1 [M + Na] , 240.2
+
+
3
[M + H] . HRMS (ESI): m/z calcd. for C13H21NO Na [M + Na]
2
1a–c will be further utilized for the synthesis of unnatural 262.1414; found 262.1419. C H NO (239.3): calcd. C 65.25, H
13 21 3
asperdiol derivatives. Work towards this goal is in progress 8.84, N 5.85; found C 65.24, H 8.91, N 5.72.
in our laboratory.
(
4S)-Isopropyl-3-(5-methylhex-5-enoyl)-1,3-oxazolidin-2-one
[(S)-
7a]: As described above for (R)-7a, from (S)-9a (1.01 g, 7.80 mmol)
in anhydrous THF (40 mL), BuLi (1.6 m in hexane, 4.68 mL,
Experimental Section
480 mg, 7.49 mmol), 8 (1.00 g, 7.80 mmol) in anhydrous Et O
2
(
(
(
(
40 mL), Et
0.96 mL, 0.94 g, 7.80 mmol), saturated solution of Na
50 mL), extraction with EtOAc (4ϫ 30 mL) and chromatography
= 0.26) gave (S)-7a (1.26 g, 5.28 mmol, 70%, GC purity 98%)
3
N (1.09 mL, 0.79 g, 7.80 mmol), pivaloyl chloride
General: NMR spectra were recorded with a Bruker Avance 500
spectrometer with TMS as internal standard. IR spectra were re-
corded with a Bruker FTIR Vektor 22 spectrometer equipped with
an MKII golden gate single reflection Diamant ATR system. Mass
spectra were recorded with a Finnigan MAT 95 spectrometer (CI,
APCI) with ammonia as carrier gas, a Varian MAT 711 (EI, 70 eV),
and a Bruker Daltonics micrOTOF_Q (ESI) with nitrogen as car-
rier gas. Optical rotations were measured with a Perkin–Elmer 241
polarimeter at 20 °C. Diastereoselectivities were determined by GC
with a Trace GC Ultra (Thermo Electron Corporation) using an
achiral stationary phase Trace TR-5MS (55 mϫ 0.32 mm, film
thickness 0.25 μm, Thermo Scientific) with hydrogen as carrier gas.
Chromatography was performed on silica gel (grain size 40–63 μm,
Fluka).
2
CO
3
R
f
2
0
1
as a colorless oil. [α]
500 MHz, CDCl ): δ = 0.88 and 0.92 [each d, J = 7.1 Hz, 3 H,
CH(CH ], 1.73 (d, J = 0.6 Hz, 3 H, CH ), 1.75–1.88 (m, 2 H,
CH ), 2.09 (td, J = 7.6, 1.2 Hz, 2 H, CH ), 2.38 [qqd, J = 7.1, 7.1,
.0 Hz, 1 H, CH(CH ], 2.87 (ddd, J = 16.9, 8.3, 6.6 Hz, 1 H, 2-
), 2.98 (ddd, J = 16.9, 8.4, 6.4 Hz, 1 H, 2-H ), 4.21 (dd, J = 9.1,
.0 Hz, 1 H, 5Ј-H ), 4.27 (dd, J = 9.1, 8.3 Hz, 1 H, 5Ј-H ), 4.44
ddd, J = 8.3, 4.0, 3.0 Hz, 1 H, 4Ј-H), 4.69–4.71 (m, 1 H, =CH
D 2 2
= +71.8 (c = 1.03, CH Cl ). H NMR
(
3
3
)
2
3
2
2
4
H
3
(
3 2
)
a
b
a
b
a
H
b
),
):
1
3
4
.73–4.74 (m, 1 H, =CH
a
H
b
) ppm. C NMR (125 MHz, CDCl
], 22.38 (CH ), 22.40 (CH
], 35.1 (C-2), 37.2 (CH ), 58.5 (C-4Ј), 63.5 (C-5Ј), 110.7
3
δ = 14.8, 18.1 [CH(CH
CH(CH
3
)
2
2
3
), 28.5
[
3
)
2
2
All reactions were performed under nitrogen in oven-dried glass-
ware. All reagents were used as purchased unless otherwise noted.
Solvents for chromatography were distilled prior to use. THF and
(=CH ), 145.1 (C=), 154.2 (CO), 173.3 (C-1) ppm. FTIR (ATR): ν˜
= 2964 (w), 2937 (w), 2877 (w), 1776 (vs), 1699 (s), 1650 (w), 1606
2
(w), 1487 (w), 1450 (w), 1385 (s), 1339 (w), 1301 (m), 1249 (m),
1204 (s), 1167 (m), 1141 (w), 1120 (w), 1103 (w), 1069 (w), 1020
Et
2
O were distilled from sodium/benzophenone, CH
2 2 3
Cl , Et N,
–
1
DMF, and pyridine from CaH
2
, and MeOH from magnesium. The
(w), 973 (w), 889 (w), 773 (w), 756 (w) cm . MS (ESI): m/z = 262.1
+
+
+
reactions were monitored by TLC (Macherey–Nagel 60 F254 plates)
and visualized with an ethanolic solution of p-anisaldehyde and
sulfuric acid.
[M + Na] , 240.2 [M + H] , 130.1 [AuxH ] . HRMS (ESI): calcd.
2
+
for C H NO Na [M
1
3
21
3
+
Na] 262.1414; found 262.1417.
C H NO (239.3): calcd. C 65.25, H 8.84, N 5.85; found C 65.03,
1
3
21
3
H 8.83, N 5.86.
a]: To a solution of (R)-9a (3.06 g, 23.7 mmol) in THF (60 mL) (4S)-4-Benzyl-3-(5-methylhex-5-enoyl)-1,3-oxazolidin-2-one [(S)-7b]:
To a solution of 8 (240 mg, 1.87 mmol) in anhydrous THF (5 mL)
at 0 °C were successively added dropwise anhydrous Et
(0.26 mL, 189 mg, 1.87 mmol) and pivaloyl chloride (0.23 mL,
.40 g, 23.7 mmol) and pivaloyl chloride (2.92 mL, 2.86 g, 226 mg, 1.87 mmol), and the resulting suspension was stirred at
(
7
4R)-Isopropyl-3-(5-methylhex-5-enoyl)-1,3-oxazolidin-2-one [(R)-
at –70 °C was added dropwise a solution of nBuLi (1.6 m in hexane,
1
–
2
2
4.8 mL, 1.52 g, 23.7 mmol), and the reaction mixture stirred at
70 °C for 30 min. In a second flask, anhydrous Et N (3.31 mL,
3
N
3
3.7 mmol) were successively added dropwise to a solution of 8
O (60 mL) at 0 °C and the
resulting suspension was stirred at 0 °C for 50 min. After cooling
0 °C for 1 h. In a second flask, a solution of nBuLi (1.6 m in hexane,
1.17 mL, 120 mg, 1.87 mmol) was added dropwise to a solution of
(S)-9b (332 mg, 1.87 mmol) in THF (10 mL) at –78 °C, and the
reaction mixture was stirred at –78 °C for 20 min prior to dropwise
addition to the suspension of 8. The reaction mixture was stirred
at –78 °C for 1 h and at 0 °C for a further 1.5 h. A solution of
(
3.04 g, 23.7 mmol) in anhydrous Et
2
to –78 °C, the suspension of 9a/BuLi was added dropwise and the
reaction mixture stirred for 4.5 h. A saturated solution of Na
100 mL) was added and the layers were separated. The aqueous
layer was extracted with EtOAc (4ϫ 100 mL) and the combined
2 3
CO
(
Na
2 3
CO (50 mL) was then added and the layers were separated.
4
organic layers were dried (MgSO ), and the solvent was removed
The aqueous layer was extracted with EtOAc (4ϫ 50 mL). The
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
combined organic layers were dried (MgSO
+
+
+
4
), and the solvent was
(21) [M] , 292.2 (7) [M – iPr] , 275.2 (5) [M–OiPr] , 250.1 (27)
+
removed under vacuum. The residue was purified by chromatog-
[M–Me
(10), 168.0 (100) [M–PO(OiPr)
109.0 (6), 96.0 (15), 82.1 (17) [Me
(6), 41.0 (10). MS (ESI): m/z (%) = 357.2 [M + Na] , 335.2 [M +
2 2 2
CCHCH CH ] , 233.1 (18), 211.1 (28), 205.1 (22), 181.0
+
raphy on SiO
2
(hexanes/EtOAc, 10:1) to give (S)-7b (415 mg,
2
] , 141.0 (9), 135.0 (3), 123.0 (13),
1
+
1
0
.14 mmol, 77%, H NMR purity 95%) as a colorless solid. R
f
=
2 2 2
CCHCH CH ] , 67.1 (5), 55.0
2
0
+
.21 (hexanes/EtOAc, 20:1); m.p. 46 °C; [α]
D
= +63.9 (c = 1.06,
), H] , 251.1 (27) [M–Me
), 2.77 (dd, m/z calcd. for C16
), 2.90 (ddd, J = 17.2, 8.1, 6.8 Hz, 1
), 2.98 (ddd, J = 17.2, 8.3, 6.6 Hz, 1 H, 2-H ), 3.30 (dd, J
13.4, 3.3 Hz, 1 H, 5Ј-H ), 4.17 (dd, J = 9.1, 3.0 Hz, 1 H,
CH Ph), 4.20 (dd, J = 9.1, 7.5 Hz, 1 H, CH Ph), 4.68 (dddd,
J = 9.7, 7.5, 3.3, 3.0 Hz, 1 H, 4Ј-H), 4.72 (br. s, 1 H, =CH ),
), 7.19–7.23 (m, 2 H, o-H), 7.25–7.31 (m,
1
+
+
CH
2
Cl
2
). H NMR (500 MHz, CDCl
3
): δ = 1.75 (s, 3 H, CH
), 2.12 (t, J = 7.6 Hz, 2 H, CH
J = 13.4, 6.7 Hz, 1 H, 5Ј-H
H, 2-H
3
2
CCHCH
2 2
CH – H] , 205.1. HRMS (ESI):
1.80–1.92 (m, 2 H, CH
2
2
32 5
H O
P [M + H]+ 335.1975; found 335.1969.
a
Ethyl
(2E,Z)-2-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethylidene)-6-
a
b
methylhept-5-enoate (17): A solution of 16 (9.58 g, 28.6 mmol) in
anhydrous THF (20 mL) was added dropwise to a solution of
freshly sublimated KOtBu (3.51 g, 31.2 mmol) in anhydrous THF
=
b
a
H
b
a b
H
a
H
b
(
60 mL) at 0 °C in a Schlenk flask, and the reaction mixture was
4
1
.75 (br. s, 1 H, =CH
H, p-H), 7.31–7.36 (m, 2 H, m-H) ppm. 1 C NMR (125 MHz,
): δ = 22.2 (CH ), 22.4 (CH ), 35.1 (C-2), 37.2 (CH ), 38.1
C-5Ј), 55.3 (C-4Ј), 66.3 (CH Ph), 110.8 (=CH ), 127.5 (C-p), 129.1
C-m), 129.6 (C-o), 135.4 (C-i), 145.1 (C=), 153.6 (CO), 173.4 (C-
a b
H
stirred at room temp. for 19 h. After cooling to –78 °C, a solution
of {[tert-butyl(dimethyl)silyl]oxy}acetaldehyde (4.54 g, 26.0 mmol)
in anhydrous THF (20 mL) was added dropwise and the reaction
mixture was stirred at –78 °C for 23 h. A saturated solution of
3
CDCl
(
(
3
2
3
2
2
2
NH
aqueous layer was extracted with Et
organic layers were dried (MgSO ) and the solvent was removed
under vacuum. The residue was purified by flash chromatography
on SiO (hexanes/CH Cl , 5:1Ǟ1:1) to give in a first fraction (Z)-
7 (2.05 g, 6.29 mmol, 24%, H NMR purity Ͼ95%) and in a sec-
4
Cl (40 mL) was then added, the layers were separated, and the
1) ppm. FTIR (ATR): ν˜ = 3069 (w), 3029 (w), 2933 (w), 2362 (w),
2
O (5ϫ 30 mL). The combined
1781 (vs), 1699 (m), 1649 (w), 1497 (w), 1454 (w), 1386 (m), 1352
4
(
(
m), 1210 (m), 1110 (w), 1076 (w), 1052 (w), 997 (w), 890 (w), 762
–1
w), 740 (w), 703 (w), 521 (w) cm . MS (EI): m/z (%) = 287.1 (100)
+
+
2
2
2
[M] , 269.1 (3), 256.2 (3), 232.1 (21) [M–Me
2
CCH
2
] , 219.1 (32)
1
1
+
+
[M–C
5
H
8
] , 204.1 (1), 190.1 (7), 178.1 (65) [AuxH
2
] , 160.1 (4),
1
ond fraction (E)-17 (4.79 g, 14.7 mmol, 56%, H NMR purity
Ͼ95%) as colorless oils.
+
1
34.1 (35), 128.0 (26) [M–C
5
H
8
– Bn] , 117.1 (48), 111.1 (100) [M–
+
+
+
Aux] , 91.0 (37) [Bn] , 69.0 (19), 55.0 (80) [Me
2
CCH
] . HRMS (ESI): m/z calcd. for C17
Na] 310.1414; found 310.1417. C17 21NO (287.35): calcd. C
1.06, H 7.37, N 4.87; found C 70.95, H 7.36, N 4.90.
2
] , 41.0 (21)
+
, 2:1). 1H NMR (500 MHz,
], 1.30
),
[CH
2
CCCH
2
H21NO
3
Na [M +
(Z)-17: R
CDCl ): δ = 0.07 [s, 6 H, Si(CH
(t, J = 7.1 Hz, 3 H, OCH CH ), 1.58 (d, J = 1.1 Hz, 3 H, 6-CH
.68 (d, J = 1.3 Hz, 3 H, 7-H), 2.09–2.15 (m, 2 H, 4-H), 2.25–2.29
(m, 2 H, 3-H), 4.19 (q, J = 7.1 Hz, 2 H, OCH CH ), 4.59 (dt, J =
f
= 0.31 (hexanes/CH
2
Cl
2
+
H
3
3
3
)
2
], 0.91 [s, 9 H, SiC(CH
3 3
)
7
2
3
3
1
Ethyl 2-(Diisopropoxyphosphoryl)-6-methylhept-5-enoate (16): In a
Schlenk flask, NaH (60% suspension, 1.27 g, 52.8 mmol) was
washed with n-hexane (2ϫ 10 mL) and the overlaying solvent was
removed by using a pipette. After removal of trace amounts of
solvent under vacuum, the solid was suspended in anhydrous DMF
2
3
4.7, 1.4 Hz, 2 H, 2Ј-H), 5.10 (tqq, J = 7.2, 1.4, 1.4 Hz, 1 H, 5-H),
1
3
6.04 (tt, J = 4.7, 1.2 Hz, 1 H, 1Ј-H) ppm. C NMR (125 MHz,
CDCl ): δ = –5.1 [Si(CH ) ], 14.4 (OCH CH ), 17.8 (Me-6), 18.5
3
3 2
2
3
[SiC(CH ) ], 25.8 (C-7), 26.1 [SiC(CH ) ], 27.8 (C-4), 33.9 (C-3),
3
3
3 3
(20 mL) and cooled to 0 °C. A solution of 15 (14.6 g, 57.9 mmol)
2 3
60.4 (OCH CH ), 62.4 (C-2Ј), 123.6 (C-5), 130.2 (C-2), 132.4 (C-
in anhydrous DMF (20 mL) was added dropwise (low levels of gas
formation), and the reaction mixture was stirred at room temp. for
6), 145.6 (C-1Ј), 167.4 (C-1) ppm. FTIR (ATR): ν˜ = 2959 (m), 2930
(s), 2858 (m), 2360 (m), 2342 (m), 1714 (vs), 1645 (w), 1463 (w),
1376 (w), 1255 (m), 1221 (m), 1160 (w), 1100 (s), 1061 (w), 836
1
.5 h. After addition of a solution of 5-iodo-2-methyl-2-pentene
9.64 g, 45.9 mmol) in anhydrous DMF (10 mL), the reaction mix-
ture was stirred at 60 °C for 18 h and taken up in a mixture of
Et O (200 mL) and H O (100 mL) at room temp. The layers were
separated and the aqueous layer was extracted with Et O (4ϫ
00 mL). The combined organic layers were successively washed
with H O and brine (200 mL each), dried (MgSO ), and the solvent
was removed under vacuum. The residue was purified by
chromatography on SiO (hexanes/EtOAc, 2:1; R = 0.20) to give
6 (12.0 g, 35.8 mmol, 78%, GC purity 96%) as a colorless oil. H
–
1
+
(
(vs), 777 (m), 668 (w) cm . MS (ESI): m/z = 349.2 [M + Na] ,
+
+
195.1 [M–OTBS] , 167.1 [C H O ] , 102.1. HRMS (ESI): m/z
1
0
15
2
+
2
2
18 34 3
calcd. for C H O SiNa [M + Na] 349.2169; found 349.2167.
2
, 2:1). 1H NMR (500 MHz,
], 1.30
),
(
E)-17: R
CDCl ): δ = 0.08 [s, 6 H, Si(CH
t, J = 7.1 Hz, 3 H, OCH CH ), 1.58 (d, J = 1.3 Hz, 3 H, 6-CH
.68 (d, J = 1.3 Hz, 3 H, 7-H), 2.05–2.11 (m, 2 H, 4-H), 2.26–2.29
CH ), 4.34 (d, J =
.8 Hz, 2 H, 2Ј-H), 5.10 (tqq, J = 7.4, 1.4, 1.4 Hz, 1 H, 5-H), 6.77
f
= 0.21 (hexanes/CH
2
Cl
2
1
3
3
)
2
], 0.91 [s, 9 H, SiC(CH
3 3
)
2
4
(
1
(
5
2
3
3
2
f
m, 2 H, 3-H), 4.20 (q, J = 7.1 Hz, 2 H, OCH
2
3
1
1
NMR (500 MHz, CDCl
3
): δ = 1.29 (t, J = 7.1 Hz, 3 H, OCH
], 1.34 [d, J = 6.2 Hz, 6 H,
], 1.58 (d, J = 1.3 Hz, 3 H, 6-CH ), 1.68 (d, J = 1.1 Hz,
H, 7-H), 1.79–2.09 (m, 4 H, 3-H, 4-H), 2.88 (ddd, J = 22.6, 10.7,
.2 Hz, 1 H, 2-H), 4.20 (q, J = 7.1 Hz, 2 H, OCH CH ), 4.71 [dqq,
], 4.72 [dqq, J = 12.3, 6.2,
], 5.04–5.08 (m, 1 H, 5-H) ppm. 13C NMR
): δ = 14.3 (OCH CH ), 17.8 (6-CH ), 23.9 [d, J
)], 24.0 [d, J = 5.2 Hz, CH(CH )], 24.2 [d, J =
)], 25.9 (C-7), 26.8
d, J = 15.7 Hz, C-3), 27.4 (d, J = 4.7 Hz, C-4), 46.0 (d, J =
2 3
CH ),
1
3
(
t, J = 5.8 Hz, 1 H, 1Ј-H) ppm. C NMR (125 MHz, CDCl
3
): δ =
), 18.5 [SiC(CH ],
], 27.61 (C-4), 27.65 (C-3), 60.5 (C-2Ј),
), 123.5 (C-5), 131.8 (C-6), 132.7 (C-2), 142.1 (C-
Ј), 167.6 (C-8) ppm. FTIR (ATR): ν˜ = 2956 (m), 2929 (m), 2858
1.32 [d, J = 6.2 Hz, 6 H, CH(CH
3 2
)
–
2
6
1
5.1 [Si(CH
5.9 (C-7), 26.1 [SiC(CH
0.7 (OCH CH
3
)
2
], 14.4 (OCH
2
CH
3
), 17.7 (6-CH
3
3 3
)
CH(CH
3
)
2
3
3 3
)
3
3
2
3
2
3
J = 12.3, 6.2, 6.2 Hz, 1 H, CH(CH
.2 Hz, 1 H, CH(CH
3 2
)
(
1
m), 1713 (vs), 1650 (w), 1463 (m), 1365 (m), 1253 (s), 1165 (m),
096 (s), 1052 (s), 1006 (w), 939 (w), 835 (vs), 776 (s), 738 (m), 672
6
3 2
)
(125 MHz, CDCl
3
2
3
3
–
1
+
+
(w) cm . MS (ESI): m/z = 349.2 [M + Na] , 195.1 [M–OTBS] ,
=
5.3 Hz, CH(CH
3
3
+
1
67.1 [C10
15 2
H O ] , 139.1, 121.1. HRMS (ESI): m/z calcd. for
3 3
3.7 Hz, CH(CH )], 24.3 [d, J = 3.5 Hz, CH(CH
+
18 34 3
C H O
SiNa [M + Na] 349.2169; found 349.2162.
(
1
32.0 Hz, C-2), 61.3 (OCH
2
CH
3
), 71.2 [d, J = 6.8 Hz, CH(CH
3
)
2
],
(2Z)-2-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethylidene)-6-methylhept-
5-en-1-ol [(Z)-18]: To a solution of (Z)-17 (801 mg, 2.48 mmol) in
71.4 [d, J = 6.8 Hz, CH(CH )
3 2
1
], 122.9 (C-5), 133.4 (C-6), 169.6 (d,
3
J = 5.0 Hz, C-1) ppm. P NMR (200 MHz, CDCl
0.97 ppm. FTIR (ATR): ν˜ = 2979 (w), 2934 (w), 1734 (m), 1451 tion of DIBAL (1.2 m in toluene, 4.55 mL, 778 mg, 5.45 mmol) and
w), 1374 (w), 1332 (w), 1255 (m), 1178 (w), 1143 (m), 1107 (m), the reaction mixture was stirred for 2 h. A saturated solution of
3 2 2
): δ = anhydrous CH Cl (20 mL) at –78 °C was added dropwise a solu-
2
(
–1
984 (vs), 888 (w), 835 (w), 771 (w) cm . MS (EI): m/z (%) = 334.2
Na/K tartrate (20 mL) was added, the layers were separated, and
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
Asymmetric Evans syn-Aldol Reactions
the aqueous layer was extracted with Et
bined organic layers were dried (MgSO
2
O (3ϫ 50 mL). The com-
) and the solvent was re-
moved under vacuum. The residue was purified by chromatography
on SiO (hexanes/EtOAc, 15:1) to give (Z)-18 (536 mg, 1.88 mmol,
CDCl
(CH
27.0 [Ph
(CH O), 124.1 (C-6), 124.9 (C-2), 127.8 (C-m), 129.7 (C-p), 132.1
(C-7), 133.8 (C-i), 135.7 (C-o), 139.2 (C-3) ppm. FTIR (ATR): ν˜ =
): δ = 0.08 [s, 6 H, 3071 (w), 2955 (m), 2929 (m), 2856 (m), 2361 (w), 1590 (w), 1472
], 1.60 (d, J = 1.4 Hz, 3 H, 7- (w), 1462 (w), 1428 (m), 1389 (w), 1362 (w), 1253 (m), 1189 (w),
), 1.68 (d, J = 1.4 Hz, 3 H, 8-H), 2.09–2.17 (m, 4 H, 4-H, 5- 1105 (s), 1053 (s), 1007 (m), 938 (w), 834 (vs), 775 (s), 739 (m), 701
H), 2.25 (t, J = 4.9 Hz, 1 H, OH), 4.11 (dt, J = 4.9, 0.7 Hz, 2 H,
CH OH), 4.24 (d, J = 6.4 Hz, 2 H, 1-H), 5.11 (tqq, J = 6.7, 1.4,
.4 Hz, 1 H, 6-H), 5.52 (tt, J = 6.4, 0.7 Hz, 1 H, 2-H) ppm.
NMR (125 MHz, CDCl ): δ = –5.0 [Si(CH ], 17.9 (7-CH ), 18.4
SiC(CH ], 25.8 (C-8), 26.1 [SiC(CH ], 26.8, 36.0 (C-4, C-5), 545.3227.
9.6 (C-1), 61.3 (CH OH), 124.0 (C-6), 126.9 (C-2), 132.1 (C-7),
42.7 (C-3) ppm. FTIR (ATR): ν˜ = 3379 (br w), 2955 (m), 2928
3
): δ = –4.9 [Si(CH
], 19.4 [Ph SiC(CH
SiC(CH ], 27.4 (C-5), 28.6 (C-4), 60.0 (C-1), 66.9
3
)
2
], 17.8 (7-CH
3
), 18.5 [(CH
3
)
2
SiC-
4
3
)
3
2
3
)
3
], 25.8 (C-8), 26.1 [(CH
3
)
2
SiC(CH
3
)
3
],
2
3 3
)
2
2
1
7
f
6%, H NMR purity 95%) as a colorless oil. R = 0.58 (hexanes/
1
EtOAc, 10:1). H NMR (500 MHz, CDCl
Si(CH ], 0.90 [s, 9 H, SiC(CH
CH
3
3
)
2
3 3
)
3
–
1
+
(vs), 666 (w), 614 (w) cm . MS (ESI): m/z = 561.3 [M + K] ,
+
+
2
545.3 [M + Na] , 391.2 [M–OTBS] , 313.2, 281.1, 267.2 [M–
OTBDPS] , 211.2, 135.1 [M–OTBS–OTBDPS] , 107.1. HRMS
1
3
+
+
1
C
)
2
3
(ESI): m/z calcd. for C32 Si
H
50
O
2
2
Na [M + Na]+ 545.3242; found
3
3
[
3
)
3
3 3
)
5
1
2
(
6Z)-2,2,10,10,11,11-Hexamethyl-6-(4-methylpent-3-enyl)-3,3-di-
phenyl-4,9-dioxa-3,10-disiladodec-6-ene [(Z)-19a]: As described
above for (E)-19a, from (Z)-18 (483 mg, 1.70 mmol) in anhydrous
DMF (10 mL), imidazole (254 mg, 3.73 mmol) and TBDPSCl
(m), 2856 (m), 1666 (w), 1462 (m), 1378 (m), 1361 (w), 1254 (m),
1
099 (m), 1062 (s), 1006 (m), 939 (w), 833 (vs), 775 (s), 666
–1
+
+
(w) cm . MS (ESI): m/z = 323.2 [M + K] , 307.2 [M + Na] , 265.1
(
0.49 mL, 513 mg, 1.87 mmol), stirring for 14 h; a saturated solu-
tion of NaHCO (15 mL), extraction with CH Cl (3ϫ 20 mL),
and chromatography gave (Z)-19a (865 mg, 1.65 mmol, 97%,
NMR purity 95%) as a colorless oil. R = 0.88 (hexanes/EtOAc,
): δ = –0.01 [s, 6 H, Si(CH ],
], 1.04 [s, 9 H, Ph SiC(CH ], 1.59 (d,
), 1.68 (d, J = 1.2 Hz, 3 H, 8-H), 2.10–2.16
(10 mL), a solution of (m, 2 H, 5-H), 2.17–2.22 (m, 2 H, 4-H), 4.05 (dt, J = 6.2, 0.9 Hz,
+
+
[M – H
2
O – H] , 209.1 [M – H
2
O – tBu] , 193.1, 167.1, 151.1 [M –
O – OTBS] , 123.1, 107.1. HRMS
3
2
2
+
+
H
2
O – TBS] , 135.1 [M – H
2
1
H
+
(ESI): m/z calcd. for C16
32 2
H O SiNa [M + Na] 307.2064; found
f
307.2062.
1
1
0:1). H NMR (500 MHz, CDCl
0.85 [s, 9 H, Me SiC(CH
J = 1.1 Hz, 3 H, 7-CH
3
3 2
)
(
2E)-2-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethylidene)-6-methylhept-5-
en-1-ol [(E)-18]: As described above for (Z)-18, from (E)-17
309 mg, 0.95 mmol) in anhydrous CH Cl
2
3
)
3
2
3 3
)
3
(
2
2
DIBAL (1.2 m in toluene, 1.70 mL, 292 mg, 2.05 mmol), a satu-
rated solution of Na/K tartrate (10 mL); chromatography gave (E)-
2 H, 1-H), 4.15 (d, J = 1.0 Hz, 2 H, CH
1.4, 1.4 Hz, 1 H, 6-H), 5.36 (tt, J = 6.2, 1.0 Hz, 1 H, 2-H), 7.36–
2
OSi), 5.11 (tqq, J = 6.9,
1
3
1
R
=
6
1
1
5
1
1
8 (202 mg, 0.71 mmol, 76%, GC purity 98%) as a colorless oil.
7.45 (m, 6 H, m-H, p-H), 7.65–7.70 (m, 4 H, o-H) ppm. C NMR
(125 MHz, CDCl ): δ = –5.0 [Si(CH ], 17.9 (7-CH ), 18.5 [Me
], 1.33 (t, J = SiC(CH ], 19.4 [Ph SiC(CH ], 25.9 (C-8), 26.1 [Me SiC(CH
), 1.68 (d, J = 26.8 (C-5), 26.9 [Ph SiC(CH ], 34.7 (C-4), 59.9 (C-1), 61.8
(CH OSi), 124.5 (C-6), 126.7 (C-2), 127.8 (C-m), 129.8 (C-p), 131.6
1
f
= 0.52 (hexanes/EtOAc, 10:1). H NMR (500 MHz, CDCl
3
): δ
3
3
)
2
3
2
-
0.08 [s, 6 H, Si(CH
3
)
2
], 0.91 [s, 9 H, SiC(CH
3
)
3
3
)
3
2
3
)
3
2
3 3
) ],
.3 Hz, 1 H, OH), 1.60 (d, J = 1.4 Hz, 3 H, 7-CH
3
2
3 3
)
.4 Hz, 3 H, 8-H), 2.04–2.15 (m, 4 H, 4-H, 5-H), 4.06 (dtt, J = 6.3,
.4, 1.1 Hz, 2 H, CH OH), 4.24 (dt, J = 6.3, 1.1 Hz, 2 H, 1-H),
.10 (tqq, J = 7.0, 1.4, 1.4 Hz, 1 H, 6-H), 5.58 (tt, J = 6.3, 1.4 Hz,
H, 2-H) ppm. 13C NMR (125 MHz, CDCl
): δ = –5.0 [Si(CH ],
7.8 (7-CH ), 18.6 [SiC(CH ], 25.9 (C-8), 26.1 [SiC(CH ], 27.3
OH), 123.8 (C-6), 126.3 (C-
), 132.5 (C-7), 140.3 (C-3) ppm. FTIR (ATR): ν˜ = 3350 (br w),
2
2
(C-7), 133.7 (C-i), 135.5 (C-o), 139.4 (C-3) ppm. FTIR (ATR): ν˜ =
2929 (m), 2856 (m), 2360 (w), 1471 (w), 1428 (w), 1388 (w), 1361
(w), 1253 (w), 1106 (m), 1058 (s), 1006 (w), 938 (w), 833 (s), 775
3
3 2
)
–
1
3
3
)
3
3
)
3
(m), 738 (m), 700 (vs), 667 (w), 614 (m) cm . MS (ESI): m/z =
+
+
+
(C-4), 28.6 (C-5), 59.9 (C-1), 66.8 (CH
2
545.3 [M + Na] , 391.3 [M–OTBS] , 313.2 [M–OTBS–Ph] , 281.2,
+
2
2
257.1, 135.1 [M–OTBS–OTBDPS] , 119.1. HRMS (ESI): m/z
954 (m), 2928 (m), 2856 (m), 1462 (m), 1377 (w), 1361 (w), 1254 calcd. for C32
H
50
O
2
Si
tert-Butyl[((2E)-3-{[(4-methoxybenzyl)oxy]-methyl}-7-methylocta-
,6-dienyl)oxy]dimethylsilane [(E)-19b]: In a Schlenk flask, NaH
Na [M + Na]+ 545.3242; found 545.3240.
2
(
(
m), 1093 (s), 1062 (s), 1005 (m), 939 (w), 834 (vs), 775 (s), 665
–1
+
+
w) cm . MS (ESI): m/z = 323.2 [M + K] , 307.2 [M + Na] , 265.1
2
+
+
[
[
M – H
M – H
2
O – H] , 193.1, 169.1, 151.1 [M – H
2
O – TBS] , 135.1
(
(
60% suspension, 70.4 mg, 1.76 mmol) was washed with n-hexane
2ϫ 4 mL) and the overlaying solvent was removed by using a pi-
+
2
O – OTBS] , 107.1. HRMS (ESI): m/z calcd. for C16
H
32
O
2
-
+
SiNa [M + Na] 307.2064; found 307.2054.
pette. After careful removal of trace amounts of solvent under vac-
6E)-2,2,10,10,11,11-Hexamethyl-6-(4-methylpent-3-enyl)-3,3-di- uum, the solid was suspended in anhydrous THF (5 mL) and
(
phenyl-4,9-dioxa-3,10-disiladodec-6-ene [(E)-19a]: To a solution of
E)-18 (197 mg, 0.69 mmol) in anhydrous DMF (10 mL) at 0 °C
were successively added imidazole (104 mg, 1.52 mmol) and
TBDPSCl (0.20 mL, 209 mg, 0.76 mmol), and the reaction mixture
was stirred at room temp. for 18 h. A saturated solution of
cooled to 0 °C. A solution of (E)-18 (251 mg, 0.88 mmol) in anhy-
drous THF (10 mL) was added dropwise (low levels of gas forma-
tion), and the reaction mixture stirred at room temp. for 1 h. After
addition of a solution of p-methoxybenzylbromide (355 mg,
1.76 mmol) in anhydrous THF (5 mL), the reaction mixture was
stirred for a further 16 h. Water (30 mL) was added and the layers
were separated. The aqueous layer was salted out with NaCl and
(
NaHCO
CH Cl
MgSO
3
(20 mL) was added and the mixture was extracted with
(3 ϫ 30 mL). The combined organic layers were dried
) and the solvent was removed under vacuum. The residue
2
2
(
4
extracted with Et
were dried (MgSO
The residue was purified by chromatography on SiO
EtOAc, 30:1) to give (E)-19b (284 mg, 0.70 mmol, 80%, GC purity
2
O (3ϫ 30 mL). The combined organic layers
) and the solvent was removed under vacuum.
(hexanes/
was purified by chromatography on SiO
2
(hexanes/EtOAc, 50:1) to
4
give (E)-19a (354 mg, 0.68 mmol, 98%, GC purity 97%) as a color-
2
1
less oil. R
CDCl ): δ = 0.09 [s, 6 H, Si(CH
.06 [s, 9 H, Ph SiC(CH ], 1.54 (d, J = 1.4 Hz, 3 H, 7-CH
d, J = 1.4 Hz, 3 H, 8-H), 1.94–2.01 (m, 2 H, 5-H), 2.01–2.06 (m,
f
= 0.89 (hexanes/EtOAc, 20:1). H NMR (500 MHz,
], 0.92 [s, 9 H, (CH SiC(CH ], 98%) as a colorless oil. R
), 1.65 (500 MHz, CDCl ): δ = 0.08 [s, 6 H, Si(CH
SiC(CH ], 1.58 (d, J = 1.4 Hz, 3 H, 7-CH ), 1.67 (d, J = 1.4 Hz,
3 H, 8-H), 2.03–2.13 (m, 4 H, 4-H, 5-H), 3.80 (s, 3 H, OMe), 3.92
(dt, J = 1.2, 1.0 Hz, 2 H, CH O), 4.26 (tt, J = 6.2, 1.0 Hz, 2 H, 1-
1
3
3
)
2
3
)
2
3
)
3
f
= 0.35 (hexanes/EtOAc, 10:1). H NMR
], 0.91 [s, 9 H,
1
(
2
1
2
3
)
3
3
3
3 2
)
3
)
3
3
H, 4-H), 4.09 (dt, J = 1.6, 1.5 Hz, 2 H, CH
.4 Hz, 2 H, 1-H), 5.03 (tqq, J = 7.1, 1.4, 1.4 Hz, 1 H, 6-H), 5.68
2
O), 4.27 (dt, J = 6.3,
2
(
(
tt, J = 6.3, 1.6 Hz, 1 H, 2-H), 7.35–7.70 (m, 4 H, m-H), 7.40–7.44
m, 2 H, p-H), 7.67–7.70 (m, 4 H, o-H) ppm. C NMR (125 MHz,
H), 4.40 (s, 2 H, 1Ј-H), 5.09 (tqq, J = 7.0, 1.4, 1.4 Hz, 1 H, 6-H),
5.59 (tt, J = 6.1, 1.2 Hz, 1 H, 2-H), 6.86–6.89 (m, 2 H, 4Ј-H), 7.24–
13
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
7
[
[
.28 (m, 2 H, 3Ј-H) ppm. 13C NMR (125 MHz, CDCl
Si(CH ], 17.8 (7-CH ), 18.5 [SiC(CH ], 25.9 (C-8), 26.1
36 2
SiC(CH ], 27.1 (C-4), 28.7 (C-5), 55.4 (OMe), 59.9 (C-1), 71.5 Na] , 135.1. HRMS (ESI): m/z calcd. for C26H O SiNa [M +
3
): δ = –4.9
1376 (w), 1361 (w), 1188 (w), 1107 (vs), 1090 (s), 999 (m), 822 (m),
–
1
3
)
2
3
3
)
3
739 (m), 700 (vs), 613 (w) cm . MS (ESI): m/z = 431.2 [M +
+
3
)
3
+
(C-1Ј), 73.7 (CH
2
O), 113.9 (C-4Ј), 124.0 (C-6), 128.6 (C-2), 129.5 Na] 431.2377; found 431.2375.
(
C-3Ј), 130.7 (C-2Ј), 132.1 (C-7), 137.3 (C-3), 159.3 (C-5Ј) ppm.
(
2E)-3-{[(4-Methoxybenzyl)oxy]methyl}-7-methylocta-2,6-dien-1-ol
FTIR (ATR): ν˜ = 2956 (w), 2928 (m), 2855 (m), 1613 (w), 1513
m), 1470 (w), 1378 (w), 1360 (w), 1301 (w), 1248 (s), 1172 (w),
[
(
(E)-20b]: From (E)-19b (277 mg, 0.68 mmol) in anhydrous MeOH
10 mL) and pTsOH·H O (9.11 mg, 0.05 mmol), reaction time 23 h,
Et N (0.4 mL); chromatography (hexanes/EtOAc, 2:1; R = 0.26)
gave (E)-20b (11.0 mg, 0.04 mmol, 95%, GC purity 98%) as a col-
(
1
3
2
097 (m), 1060 (m), 1037 (m), 1006 (w), 835 (s), 776 (m), 693 (w),
–
1
+
3
f
47 (w) cm . MS (ESI): m/z = 443.2 [M + K] , 427.3 [M +
+
+
Na] , 255.2, 121.1 [MeOPhCH
C H O SiNa [M + Na] 427.2639; found 427.2631.
2
] . HRMS (ESI): m/z calcd. for
1
+
orless oil. H NMR (500 MHz, CDCl
H, OH), 1.58 (d, J = 1.4 Hz, 3 H, 7-CH
H, 8-H), 2.04–2.10 (m, 2 H, 5-H), 2.14–2.18 (m, 2 H, 4-H), 3.81 (s,
3 H, OMe), 3.94 (s, 2 H, CH O), 4.20 (dd, J = 7.0, 5.4 Hz, 2 H, 1-
H), 4.42 (s, 2 H, 1Ј-H), 5.09 (tqq, J = 7.2, 1.4, 1.4 Hz, 1 H, 6-H),
5.71 (t, J = 7.0 Hz, 1 H, 2-H), 6.86–6.90 (m, 2 H, 4Ј-H), 7.25–7.28
(m, 2 H, 3Ј-H) ppm. C NMR (125 MHz, CDCl
CH ), 25.8 (C-8), 27.1 (C-5), 28.4 (C-4), 55.4 (OMe), 59.0 (C-1),
71.9 (C-1Ј), 73.4 (CH O), 113.9 (C-4Ј), 123.9 (C-6), 126.9 (C-2),
129.5 (C-3Ј), 130.5 (C-2Ј), 132.7 (C-7), 139.7 (C-3), 159.3 (C-
5Ј) ppm. FTIR (ATR): ν˜ = 3382 (br w), 2964 (m), 2928 (m), 2854
3
): δ = 1.25 (t, J = 5.4 Hz, 1
24 40 3
3
), 1.68 (d, J = 1.4 Hz, 3
tert-Butyl[((2Z)-3-{[(4-methoxybenzyl)oxy]-methyl}-7-methylocta-
2
1
,6-dienyl)oxy]dimethylsilane [(Z)-19b]: As described above for (E)-
9b, from NaH (60% suspension, 182 mg, 4.54 mmol) in anhydrous
2
THF (5 mL), (Z)-18 (542 mg, 1.91 mmol) in anhydrous THF
10 mL) and p-methoxybenzylbromide (913 mg, 4.54 mmol) in an-
hydrous THF (5 mL); chromatography on SiO (hexanes/EtOAc,
0:1) gave (Z)-19b (378 mg, 0.93 mmol, 49%, GC purity: 95%) as
1
3
(
3
): δ = 17.8 (7-
2
3
3
2
a colorless oil. R
(
f
= 0.37 (hexanes/EtOAc, 10:1). 1H NMR
): δ = 0.05 [s, 6 H, Si(CH ], 0.89 [s, 9 H,
500 MHz, CDCl
3
3 2
)
SiC(CH ], 1.59 (d, J = 1.4 Hz, 3 H, 7-CH
3
)
3
3
), 1.67 (d, J = 1.4 Hz, (m), 2358 (w), 1671 (w), 1612 (m), 1586 (w), 1513 (vs), 1466 (m),
3
H, 8-H), 2.08–2.15 (m, 4 H, 4-H, 5-H), 3.81 (s, 3 H, OMe), 3.96 1441 (m), 1377 (w), 1302 (m), 1248 (vs), 1174 (m), 1091 (m), 1066
–
1
(d, J = 0.9 Hz, 2 H, CH
2
O), 4.21 (d, J = 6.3 Hz, 2 H, 1-H), 4.38
(m), 1036 (s), 923 (w), 820 (m), 759 (w) cm . MS (ESI): m/z =
+
+
+
(
s, 2 H, 1Ј-H), 5.10 (tqq, J = 6.8, 1.4, 1.4 Hz, 1 H, 6-H), 5.52 (tt,
329.2 [M + K] , 313.2 [M + Na] , 121.1 [MeOPhCH
(ESI): m/z calcd. for C18
Na [M + Na]+ 313.1774; found
): δ = –4.9 313.1766.
], 25.8 (C-8), 26.1
], 26.7 (C-5), 35.4 (C-4), 55.4 (OMe), 59.9 (C-1), 67.3
O), 71.8 (C-1Ј), 113.9 (C-4Ј), 124.2 (C-6), 129.1 (C-2), 129.5
C-3Ј), 130.6 (C-2Ј), 131.8 (C-7), 137.4 (C-3), 159.3 (C-5Ј) ppm.
2
] . HRMS
J = 6.3, 0.9 Hz, 1 H, 2-H), 6.86–6.90 (m, 2 H, 4Ј-H), 7.24–7.27
(
[
26 3
H O
m, 2 H, 3Ј-H) ppm. 13C NMR (125 MHz, CDCl
Si(CH ], 17.9 (7-CH ), 18.5 [SiC(CH
3
3
)
2
3
3 3
)
(
2Z)-3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-7-methylocta-2,6-
dien-1-ol [(Z)-20a]: From (Z)-19a (134 mg, 0.26 mmol) in anhy-
drous MeOH (10 mL) and pTsOH·H O (3.41 mg, 0.02 mmol), re-
3 3
[SiC(CH )
(CH
2
2
(
action time 23 h; chromatography (hexanes/EtOAc, 20:1Ǟ10:1)
FTIR (ATR): ν˜ = 2955 (m), 2928 (m), 2855 (m), 1669 (w), 1612
w), 1586 (w), 1513 (m), 1462 (w), 1441 (w), 1379 (w), 1360 (w),
302 (w), 1248 (s), 01173 (w), 1099 (m), 1063 (s), 1037 (m), 1006
gave (Z)-19a (82.0 mg, 0.20 mmol, 76%, GC purity 98%) as a col-
(
1
1
orless oil. R
CDCl ): δ = 1.05 [s, 9 H, SiC(CH
(d, J = 1.4 Hz, 3 H, 7-CH ), 1.68 (d, J = 1.4 Hz, 3 H, 8-H), 2.07–
2.13 (m, 2 H, 5-H), 2.15–2.20 (m, 2 H, 4-H), 3.96 (d, J = 6.9 Hz,
2 H, 1-H), 4.19 (d, J = 1.0 Hz, 2 H, CH OSi), 5.09 (tqq, J = 6.9,
.4, 1.4 Hz, 1 H, 6-H), 5.46 (tt, J = 6.9, 1.0 Hz, 1 H, 2-H), 7.37–
7.41 (m, 4 H, m-H), 7.42–7.46 (m, 2 H, p-H), 7.67–7.70 (m, 4 H,
f
= 0.29 (hexanes/EtOAc, 20:1). H NMR (500 MHz,
–
1
3
3 3
) ], 1.33 (br. s, 1 H, OH), 1.58
(w), 835 (s), 776 (m), 666 (w) cm . MS (ESI): m/z = 443.2 [M
+
+
+
3
+
K] , 427.3 [M + Na] , 371.3, 273.2 [M–OTBS] , 255.2, 121.1
+
[MeOPhCH
2
] . HRMS (ESI): m/z calcd. for C24
40 3
H O SiNa [M +
+
2
Na] 427.2639; found 427.2625.
1
General Procedure for the Deprotection of the TBS Ethers: To a
solution of the respective silyl ether 19 (1.0 equiv.) in anhydrous
MeOH at –10°C was added pTsOH·H
1
3
o-H) ppm. C NMR (125 MHz, CDCl
[SiC(CH ], 25.8 (C-8), 26.8 (C-5), 26.9 [SiC(CH
58.9 (C-1), 61.8 (CH OSi), 124.1 (C-6), 125.8 (C-2), 127.9 (C-m),
3
): δ = 17.9 (7-CH
3
), 19.3
2
O (0.08 equiv.) and the reac-
N (0.2 mL) was
3
)
3
3 3
)
], 35.0 (C-4),
tion mixture was stirred for 14–23 h. Anhydrous Et
3
2
then added and the reaction mixture was stirred for 5 min. The
solvent was removed under vacuum and the residue was purified
129.9 (C-p), 131.9 (C-7), 133.5 (C-i), 135.8 (C-o), 142.1 (C-3) ppm.
FTIR (ATR): ν˜ = 3323 (br w), 2959 (w), 2929 (m), 2856 (m), 2360
(w), 1589 (w), 1472 (w), 1427 (m), 1389 (w), 1361 (w), 1188 (w),
2
by chromatography on SiO to give products 20.
1
110 (s), 1071 (s), 1007 (m), 823 (m), 740 (m), 701 (vs), 615
(
2E)-3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-7-methylocta-2,6-
–1
+
+
(m) cm . MS (ESI): m/z = 447.2 [M + K] , 431.2 [M + Na] ,
dien-1-ol [(E)-20a]: From (E)-19a (390 mg, 0.76 mmol) in anhy-
drous MeOH (5 mL) and pTsOH·H O (11.4 mg, 0.06 mmol), reac-
tion time 14 h; chromatography (hexanes/EtOAc, 6:1) gave (E)-20a
313 mg, 0.76 mmol, quant., GC purity 98%) as a colorless oil. R
+
391.2 [M–OH] , 313.2, 135.1, 119.1. HRMS (ESI): m/z calcd. for
2
SiNa [M + Na]+ 431.2377; found 431.2367.
26 36 2
C H O
(
=
f
(2Z)-3-{[(4-Methoxybenzyl)oxy]methyl}-7-methylocta-2,6-dien-1-ol
[(Z)-20b]: From (Z)-19b (17.0 mg, 0.04 mmol) in anhydrous MeOH
1
0.33 (hexanes/EtOAc, 4:1). H NMR (500 MHz, CDCl
3
): δ =
1
=
.07 [s, 9 H, SiC(CH
1.3 Hz, 3 H, 7-CH
3
)
3
], 1.11 (t, J = 5.8 Hz, 1 H, OH), 1.53 (d, J (3 mL) and pTsOH·H
2
O (0.56 mg, 0.03 mmol), reaction time 23 h;
= 0.31) gave (Z)-20b
3
), 1.65 (d, J = 1.3 Hz, 3 H, 8-H), 1.95–2.01 chromatography (hexanes/EtOAc, 2:1; R
f
1
(
m, 2 H, 5-H), 2.05–2.11 (m, 2 H, 4-H), 4.12 (d, J = 1.5 Hz, 2 H, (11.0 mg, 0.04 mmol, 95%, GC purity: 97%) as a colorless oil. H
CH O), 4.18 (1-H), 4.18 (dt, J = 7.1, 5.8 Hz, 2 H, 1-H), 5.03 (tqq, NMR (500 MHz, CDCl ): δ = 1.59 (d, J = 1.4 Hz, 3 H, 7-CH ),
J = 7.2, 1.3, 1.3 Hz, 1 H, 6-H), 5.74–5.79 (m, 1 H, 2-H), 7.35–7.40 1.68 (d, J = 1.4 Hz, 3 H, 8-H), 1.78 (br. s, 1 H, OH), 2.07–2.16 (m,
m, 4 H, m-H), 7.40–7.45 (m, 2 H, p-H), 7.66–7.70 (m, 4 H, 4 H, 4-H, 5-H), 3.81 (s, 3 H, OMe), 3.99 (s, 2 H, CH O), 4.11–4.15
), 19.4 (m, 2 H, 1-H), 4.43 (s, 2 H, 1Ј-H), 5.10 (tqq, J = 6.9, 1.4, 1.4 Hz,
], 27.4 (C-5), 28.2 (C-4), 1 H, 6-H), 5.67 (d, J = 7.0 Hz, 1 H, 2-H), 6.86–6.90 (m, 2 H, 4Ј-
O), 123.5 (C-2), 123.9 (C-6), 127.8 (C-m),
29.8 (C-p), 132.6 (C-7), 133.7 (C-i), 135.7 (C-o), 141.9 (C-3) ppm.
2
3
3
(
2
13
o-H) ppm. C NMR (125 MHz, CDCl
SiC(CH ], 25.8 (C-8), 26.9 [SiC(CH
9.0 (C-1), 66.7 (CH
3 3
): δ = 17.8 (7-CH
)
3 3
[
5
1
3
)
3
1
3
2
H), 7.24–7.28 (m, 2 H, 3Ј-H) ppm. C NMR (125 MHz, CDCl
δ = 17.9 (7-CH ), 25.8 (C-8), 26.8 (C-5), 36.1 (C-4), 55.4 (OMe),
O), 72.3 (C-1Ј), 114.0 (C-4Ј), 123.9 (C-6),
128.2 (C-2), 129.6 (C-3Ј), 130.2 (C-2Ј), 132.1 (C-7), 140.4 (C-3),
3
):
3
FTIR (ATR): ν˜ = 3320 (br w), 3071 (w), 3049 (w), 2959 (w), 2929 58.9 (C-1), 67.7 (CH
w), 2856 (m), 1672 (w), 1589 (w), 1472 (w), 1461 (w), 1427 (m),
2
(
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
Asymmetric Evans syn-Aldol Reactions
1
(
1
59.4 (C-5Ј) ppm. FTIR (ATR): ν˜ = 3395 (br w), 2964 (m), 2926
m), 2854 (m), 2359 (w), 1736 (w), 1670 (w), 1612 (m), 1585 (w),
513 (s), 1440 (m), 1377 (w), 1302 (m), 1248 (vs), 1173 (m), 1071 (d, J = 1.6 Hz, 2 H, CH
3
3 H, 7-CH ), 1.67 (dt, J = 1.4, 1.4 Hz, 3 H, 8-H), 2.18–2.24 (m, 2
H, 5-H), 2.54 (t, J = 7.4 Hz, 2 H, 4-H), 3.81 (s, 3 H, OMe), 4.07
O), 4.48 (s, 2 H, 1Ј-H), 5.09 (tqq, J = 7.4,
2
–1
(m), 1035 (s), 923 (w), 820 (m) cm . MS (ESI): m/z = 329.2 [M +
1.4, 1.4 Hz, 1 H, 6-H), 6.17 (dt, J = 8.0, 1.6 Hz, 1 H, 2-H), 6.88–
+
+
+
K] , 313.2 [M + Na] , 121.1 [MeOPhCH
calcd. for C18
2
] . HRMS (ESI): m/z
6.91 (m, 2 H, 4Ј-H), 7.25–7.28 (m, 2 H, 3Ј-H), 9.99 (d, J = 8.0 Hz,
+
13
H
26
O
3
Na [M + Na] 313.1774; found 313.1788.
1 H, 1-H) ppm. C NMR (125 MHz, CDCl
3
): δ = 17.9 (7-CH
3
),
2
5.8 (C-8), 28.1 (C-5), 28.8 (C-4), 55.4 (OMe), 72.0 (CH O), 72.6
2
(
2E)-3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-7-methylocta-2,6-di-
enal [(E)-6b]: To a solution of (E)-20a (335 mg, 0.82 mmol) in anhy-
drous CH Cl (10 mL) at 0 °C was added DMP (522 mg,
.23 mmol) and the reaction mixture was stirred for 1.5 h. The sol-
vent was removed under vacuum and the residue was purified by
chromatography on SiO (hexanes/EtOAc, 4:1; R = 0.71) to give
E)-6b (303 mg, 0.75 mmol, 91%, H NMR purity 95%) as a light-
(
(
C-1Ј), 114.0 (C-4Ј), 122.3 (C-6), 126.3 (C-2), 129.5 (C-3Ј), 129.7
C-2Ј), 134.1 (C-7), 159.5 (C-5Ј), 162.3 (C-3), 191.0 (C-1) ppm.
2
2
FTIR (ATR): ν˜ = 2965 (w), 2933 (w), 2911 (w), 2856 (w), 2835 (w),
744 (w), 2361 (w), 1668 (vs), 1636 (w), 1612 (m), 1585 (w), 1512
s), 1441 (m), 1404 (m), 1378 (w), 1363 (w), 1302 (m), 1246 (vs),
1
2
(
1
8
2
f
174 (m), 1149 (m), 1102 (vs), 1034 (s), 951 (w), 886 (w), 850 (m),
1
(
–1
18 (s), 759 (w), 576 (w), 522 (w) cm . MS (ESI): m/z = 311.2 [M
1
yellow oil. H NMR (500 MHz, CDCl
3
): δ = 1.08 [s, 9 H, SiC(CH
), 1.63 (d, J = 1.4 Hz, 3 H, 8-H),
.10 (td, J = 7.4, 7.4 Hz, 2 H, 5-H), 2.42 (t, J = 7.4 Hz, 2 H, 4-H),
.24 (d, J = 1.9 Hz, 2 H, CH O), 5.01 (tqq, J = 7.4, 1.4, 1.4 Hz, 1
3
)
3
],
+
+
+
2 2 2
Na] , 281.3 [M + Na – CHO] , 227.0 [M – Me CCHCH CH +
1
2
4
.50 (d, J = 1.4 Hz, 3 H, 7-CH
3
+
+
Na] , 159.0, 121.1 [PMB] . HRMS (ESI): m/z calcd. for
C H O
18 24 3
Na [M + Na]+ 311.1618; found 311.1636.
2
H, 6-H), 6.38 (dt, J = 8.4, 1.9 Hz, 1 H, 2-H), 7.37–7.41 (m, 4 H, (2Z)-3-{[(4-Methoxybenzyl)oxy]methyl}-7-methylocta-2,6-dienal
m-H), 7.43–7.47 (m, 2 H, p-H), 7.63–7.67 (m, 4 H, o-H), 10.01 (d, [(Z)-6c]: As described above for (E)-6c, from (Z)-20b (254 mg,
J = 8.4 Hz, 1 H, 1-H) ppm. 13C NMR (125 MHz, CDCl
): δ = 17.9 0.87 mmol) in anhydrous CH
], 28.5 (C- 1.31 mmol) and TPAP (15.4 mg, 0.04 mmol); chromatography on
O), 122.3 (C-6), 124.7 (C-2), 128.0 (C-m), SiO (hexanes/EtOAc, 10:1; R = 0.19) gave (Z)-6c (202 mg,
30.1 (C-p), 132.9 (C-i), 134.1 (C-7), 135.6 (C-o), 164.8 (C-3), 191.2 0.70 mmol, 80%, H NMR purity 95%) as a yellow oil. H NMR
(500 MHz, CDCl ): δ = 1.59 (d, J = 1.4 Hz, 3 H, 7-CH ), 1.68 (dt,
m), 2740 (w), 1678 (s), 1472 (w), 1428 (m), 1378 (w), 1190 (w), J = 1.4, 1.4 Hz, 3 H, 8-H), 2.16–2.21 (m, 2 H, 5-H), 2.30–2.35 (m,
151 (w), 1112 (vs), 938 (w), 854 (w), 824 (m), 804 (w), 741 2 H, 4-H), 3.81 (s, 3 H, OMe), 4.39 (d, J = 1.2 Hz, 2 H, CH O),
w), 703 (m), 622 (w) cm . MS (ESI): m/z = 445.2 [M + K] , 4.49 (s, 2 H, 1Ј-H), 5.07 (tqq, J = 7.1, 1.4, 1.4 Hz, 1 H, 6-H), 5.95
3
2 2
Cl (5 mL), NMO (154 mg,
(
7-CH
3
), 19.4 [SiC(CH
3 3 3 3
) ], 25.7 (C-8), 26.9 [SiC(CH )
5
1
), 28.6 (C-4), 66.1 (CH
2
2
f
1
1
(C-1) ppm. FTIR (ATR): ν˜ = 3072 (w), 2962 (w), 2930 (w), 2857
3
3
(
1
(
2
–
1
+
+
+
429.2 [M + Na] , 389.2 [M–OH] . HRMS (ESI): m/z calcd. for
(dt, J = 7.7, 1.2 Hz, 1 H, 2-H), 6.88–6.91 (m, 2 H, 4Ј-H), 7.25–7.27
+
13
C
26
H
34
O
2
SiNa [M + Na] 429.2220; found 429.2211.
(m, 2 H, 3Ј-H), 10.05 (d, J = 7.7 Hz, 1 H, 1-H) ppm. C NMR
(
(
(
(
2
(
125 MHz, CDCl
C-4), 55.4 (OMe), 67.6 (CH
C-6), 129.1 (C-2), 129.55 (C-2Ј), 129.63 (C-3Ј), 133.1 (C-7), 159.6
C-5Ј), 161.8 (C-3), 191.4 (C-1) ppm. FTIR (ATR): ν˜ = 2966 (w),
912 (w), 2856 (w), 1721 (w), 1674 (vs), 1612 (m), 1513 (s), 1441
3
): δ = 17.9 (7-CH
3
), 25.8 (C-8), 26.2 (C-5), 36.0
(
2Z)-3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-7-methylocta-2,6-di-
2
O), 72.7 (C-1Ј), 114.1 (C-4Ј), 122.8
enal [(Z)-6b]: As described above for (E)-6b, from (Z)-20a (481 mg,
.18 mmol) and DMP (749 mg, 1.77 mmol); chromatography on
SiO (hexanes/EtOAc, 4:1; R = 0.71) gave (Z)-6b (414 mg,
.02 mmol, 86%, H NMR purity 95%) as a light-yellow oil. H
NMR (500 MHz, CDCl ): δ = 1.06 [s, 9 H, SiC(CH ], 1.58 (d, J
1.4 Hz, 3 H, 7-CH ), 1.67 (d, J = 1.4 Hz, 3 H, 8-H), 2.15–2.21
m, 2 H, 5-H), 2.32–2.36 (m, 2 H, 4-H), 4.59 (d, J = 1.2 Hz, 2 H,
CH O), 5.06 (tqq, J = 7.1, 1.4, 1.4 Hz, 1 H, 6-H), 5.85 (dtt, J =
.8, 1.2, 1.2 Hz, 1 H, 2-H), 7.37–7.42 (m, 4 H, m-H), 7.43–7.47 (m,
1
2
f
1
1
1
w), 1377 (w), 1362 (w), 1302 (w), 1247 (vs), 1174 (m), 1113 (m),
078 (m), 1034 (m), 820 (m), 756 (w), 575 (w), 520 (w) cm . MS
3
3
)
3
–1
1
=
(
3
+
+
(
ESI): m/z = 311.2 [M + Na] , 285.3, 225.1, 209.1, 121.1 [PMB] .
Na [M + Na]+ 311.1618;
HRMS (ESI): m/z calcd. for C18H O
found 311.1634.
24 3
2
7
2
1
H, p-H), 7.64–7.69 (m, 4 H, o-H), 9.87 (d, J = 7.8 Hz, 1 H, General Procedure for the Aldol Reaction of N-Acyloxazolidinones
-H) ppm. 13C NMR (125 MHz, CDCl
): δ = 17.9 (7-CH ), 19.3 7 with Enals 6. Method A: To a solution of (S)- or (R)-7 (1 equiv.)
], 25.8 (C-8), 26.3 (C-5), 26.9 [SiC(CH ], 35.3 (C-4), in anhydrous CH Cl at –78 °C was added dropwise Bu BOTf (1 m
O), 122.9 (C-6), 127.7 (C-2), 128.1 (C-m), 130.2 (C-p), in CH Cl , 1.25 equiv.) followed by addition of iPr NEt (1.5 equiv.)
after the time given in Table 1. The reaction mixture was stirred at
3
3
[SiC(CH
3
)
3
3
)
3
2
2
2
6
1
2.4 (CH
2
2
2
2
32.8 (C-i), 133.0 (C-7), 135.7 (C-o), 163.9 (C-3), 191.2 (C-1) ppm.
FTIR (ATR): ν˜ = 3072 (w), 3050 (w), 2961 (w), 2930 (m), 2857 –78 °C for 1 h and at 0 °C for a further 15 min. Then a solution of
w), 1722 (w), 1678 (m), 1589 (w), 1472 (w), 1428 (m), 1378 (w), enal 6 (1.25 equiv.) in anhydrous CH Cl was added dropwise, and
the reaction mixture was stirred (temperature and time are given in
Table 1). A mixture of pH 7 buffer and aqueous H (30%, 2:1)
(
2
2
1
7
4
262 (w), 1190 (w), 1169 (w), 1113 (s), 1079 (m), 998 (w), 823 (m),
–1
+
41 (m), 702 (s), 612 (w) cm . MS (ESI): m/z = 445.2 [M + K] ,
2 2
O
+
+
+
29.2 [M + Na] , 407.2 [M + H] , 389.2 [M–OH] , 327.3. HRMS
was added at 0 °C, the mixture was stirred for 1 h, and then the
layers were separated. The organic layer was washed with a satu-
+
34 2
(ESI): m/z calcd. for C26H O SiNa [M + Na] 429.2220; found
4
29.2202.
rated solution of NaHCO
with CH Cl . The combined organic layers were dried (MgSO
and the solvent was removed under vacuum. The crude products
were purified by column chromatography on SiO (hexanes/EtOAc,
:1).
3
and the aqueous layer was extracted
2
2
4
)
(
2E)-3-{[(4-Methoxybenzyl)oxy]methyl}-7-methylocta-2,6-dienal
(E)-6c]: To dried and ground (pestle and mortar) molecular sieves
Å (500 mg) was added a solution of (E)-20b (183 mg, 0.63 mmol)
in anhydrous CH Cl (5 mL) followed by addition of NMO
111 mg, 0.95 mmol) and TPAP (11.1 mg, 0.03 mmol). The suspen-
sion was stirred for 4 h and then filtered through Celite. The filter
residue was washed with CH Cl (200 mL) and the combined fil-
trates were concentrated under vacuum. The residue was purified
by chromatography on SiO (hexanes/EtOAc, 10:1; R = 0.19) to
give (E)-6c (138 mg, 0.48 mmol, 77%, H NMR purity 95%) as a
[
4
2
6
2
2
(
Method B: To a solution of (S)-7a (1 equiv.) in anhydrous CH
at 0 °C was added dropwise BBNOTf (0.5 m in CH Cl , 1.25 equiv.)
followed by addition of iPr NEt (1.5 equiv.) after the time given in
Table 1. The reaction mixture was stirred at 0 °C for 2 h. Then a
solution of enal 6 (1.25 equiv.) in anhydrous CH Cl was added
dropwise and the reaction mixture was stirred (temperature and
3
): δ = 1.56 (d, J = 1.4 Hz, time are given in Table 1). A mixture of pH 7 buffer and aqueous
2 2
Cl
2
2
2
2
2
2
f
2
2
1
1
yellow oil. H NMR (500 MHz, CDCl
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
H
2
O
2
(30%, 2:1) was added at 0 °C, the mixture was stirred for 2 h,
and then the layers were separated. The organic layer was washed
with a saturated solution of NaHCO and the aqueous layer was
extracted with CH Cl . The combined organic layers were dried
MgSO ) and the solvent was removed under vacuum. The crude
= 9.1, 4.2 Hz, 1 H, 3Ј-H
4.42 (ddd, J = 6.9, 4.2, 3.8 Hz, 1 H, 4Ј-H), 4.55 (dd, J = 8.9, 6.1 Hz,
1 H, 3-H), 4.66–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–4.71 (m, 1 H, 1ЈЈ-H ),
5.09 (ddqq, J = 6.9, 6.9, 1.5, 1.5 Hz, 1 H, 8-H), 5.24 (dq, J = 8.9,
a b
), 4.20 (dd, J = 9.1, 6.9 Hz, 1 H, 3Ј-H ),
3
b
a
2
2
1
3
(
4
1.4 Hz, 1 H, 4-H) ppm. C NMR (125 MHz, CD
18.2 [CH(CH ], 16.9 (5-CH ), 17.8 (9-CH ), 22.4 (2ЈЈ-CH
(C-10), 26.9 (C-7), 27.0 (C-4ЈЈ), 28.9 (C-5Ј), 35.9 (C-3ЈЈ), 40.1 (C-
2
Cl
2
): δ = 14.9,
products were purified by column chromatography on SiO
anes/EtOAc, 6:1).
2
(hex-
3
)
2
3
3
3
), 25.8
6
1
1
), 48.6 (C-2), 59.2 (C-4Ј), 63.6 (C-3Ј), 69.9 (C-3), 110.4 (C-1ЈЈ),
24.2 (C-8), 124.9 (C-4), 132.1 (C-9), 140.2 (C-5), 145.8 (C-2ЈЈ),
54.5 (C-2Ј), 175.0 (C-1) ppm. FTIR (ATR): ν˜ = 3492 (br w), 2965
Method C: To a solution of (S)- or (R)-7a (1 equiv.) in anhydrous
CH Cl at 0 °C was added dropwise iPr NEt (1.5 equiv.) and the
mixture was stirred for 10 min. Then BBNOTf (0.5 m in hexane,
.25 equiv.) was added dropwise at 0 °C. After stirring for 1.5 h, a
solution of 6 (1.25 equiv.) in CH Cl was added dropwise [in the
case of enals (E)- and (Z)-6b,c, 1.2 equiv. of (R)-7a, 1.2 equiv. of
BBNOTf and 1 equiv. of the enal was used]. The reaction mixture
was stirred (temperature and time are given in Table 1 and Table 2)
2
2
2
(
1
m), 2922 (m), 1779 (vs), 1695 (m), 1486 (w), 1449 (w), 1384 (s),
300 (m), 1201 (s), 1141 (w), 1120 (w), 1096 (w), 1056 (w), 1020
1
2
2
–1
(
m), 984 (w), 888 (w), 705 (w) cm . MS (ESI): m/z = 414.26 [M +
+
+
+
2
Na] , 393.3 [M + 2H] , 374.3 [M – H O] , 250.1. HRMS (ESI):
+
m/z calcd. for C23
4R)-3-[(2R,3S,4Z)-3-Hydroxy-5,9-dimethyl-2-(3-methylbut-3-enyl)-
deca-4,8-dienoyl]-4-isopropyl-1,3-oxazolidin-2-one [ent- or (2R,3S)-
4
H37NO Na [M + Na] 414.2615; found 414.2614.
(
2 2
then a mixture of pH 7 buffer and aqueous H O (30%, 2:1) was
added at 0 °C. The reaction mixture was stirred for 2 h, then the
layers were separated. The organic layer was washed with a satu-
2
0
5
=
[
a]: Colorless oil. R
f
= 0.33 (hexanes/EtOAc, 4:1). [α]
). H NMR (500 MHz, CD Cl ): δ = 0.87 and 0.91
each d, J = 7.0 Hz, 3 H, CH(CH ], 1.61 (d, J = 1.4 Hz, 3 H, 9-
CH ), 1.69 (d, J = 1.4 Hz, 3 H, 10-H), 1.70 (dd, J = 1.4, 0.8 Hz, 3
H, 2ЈЈ-CH ), 1.72 (d, J = 1.4 Hz, 3 H, 5-CH ), 1.78–1.86 (m, 1 H,
), 1.88–1.97 (m, 2 H, 4ЈЈ-H , OH), 1.97–2.18 (m, 6 H, 3ЈЈ-H,
-H, 7-H), 2.32 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H, CH(CH ], 4.11
D
= –19.2 (c
1
1.00, CH
2
Cl
2
2
2
rated solution of NaHCO
with CH Cl . The combined organic layers were dried (MgSO
and the solvent was removed under vacuum. The crude products
were purified by column chromatography on SiO (hexanes/EtOAc,
:1).
3
and the aqueous layer was extracted
3 2
)
2
2
4
)
3
3
3
2
4
6
ЈЈ-H
a
b
6
3 2
)
(
4S)-3-[(2S,3R,4Z)-3-Hydroxy-5,9-dimethyl-2-(3-methylbut-3-enyl)-
deca-4,8-dienoyl]-4-isopropyl-1,3-oxazolidin-2-one [syn- or (2S,3R)-
a]: According to Method A, chromatography gave syn-5a (63%,
(ddd, J = 9.5, 6.3, 3.9 Hz, 1 H, 2-H), 4.17–4.22 (m, 2 H, 3Ј-H),
4.41 (ddd, J = 6.6, 4.6, 3.8 Hz, 1 H, 4Ј-H), 4.52 (ddd, J = 9.2, 6.3,
3.1 Hz, 1 H, 3-H), 4.66–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–4.71 (m, 1 H,
1ЈЈ-H ), 5.12 (ddqq, J = 7.0, 7.0, 1.4, 1.4 Hz, 1 H, 8-H), 5.26 (dq,
5
b
1
f
H NMR purity 95%) as a yellow oil; R = 0.26 (hexanes/EtOAc,
a
0
1
4
:1). [α]2
CD Cl ): δ = 0.87 and 0.91 [each d, J = 7.0 Hz, 3 H, CH(CH
.61 (d, J = 1.5 Hz, 3 H, 9-CH ), 1.69 (d, J = 1.5 Hz, 3 H, 10-H),
.70 (dd, J = 1.5, 0.9 Hz, 3 H, 2ЈЈ-CH ), 1.72 (d, J = 1.5 Hz, 3 H,
-CH ), 1.81 (dddd, J = 13.3, 9.3, 7.2, 4.0 Hz, 1 H, 4ЈЈ-H ), 1.92
), 1.88–2.17 (m, 7 H,
ЈЈ-H, 6-H, 7-H, OH), 2.32 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H,
CH(CH ], 4.12 (ddd, J = 9.5, 6.4, 4.0 Hz, 1 H, 2-H), 4.17–4.22
m, 2 H, 3Ј-H), 4.41 (ddd, J = 6.6, 4.4, 3.8 Hz, 1 H, 4Ј-H), 4.52
dd, J = 9.1, 6.4 Hz, 1 H, 3-H), 4.66–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–
.71 (m, 1 H, 1ЈЈ-H ), 5.12 (ddqq, J = 6.9, 6.9, 1.5, 1.5 Hz, 1 H, 8-
H), 5.26 (dq, J = 9.1, 1.5 Hz, 1 H, 4-H) ppm. C NMR (125 MHz,
CD Cl ): δ = 15.0 [CH(CH ], 17.8 (9-CH ), 18.2 [CH(CH ], 22.4
2ЈЈ-CH ), 23.6 (5-CH ), 25.8 (C-10), 27.0 (C-7), 27.1 (C-4ЈЈ), 29.0
CH(CH ], 32.6 (C-6), 35.8 (C-3ЈЈ), 48.4 (C-2), 59.2 (C-4Ј), 63.7
C-3Ј), 69.4 (C-3), 110.4 (C-1ЈЈ), 124.3 (C-8), 125.5 (C-4), 132.5 (C-
), 140.8 (C-5), 145.9 (C-2ЈЈ), 154.5 (C-2Ј), 174.9 (C-1) ppm. FTIR
ATR): ν˜ = 3495 (br w), 2965 (m), 2929 (w), 1779 (vs), 1695 (s),
486 (w), 1449 (w), 1384 (s), 1300 (m), 1226 (m), 1201 (s), 1141
D
= +18.1 (c = 1.05, CH
2
Cl
2
). H NMR (500 MHz,
],
13
J = 9.2, 1.4 Hz, 1 H, 4-H) ppm. C NMR (125 MHz, CD
15.0, 18.2 [CH(CH ], 17.8 (9-CH ), 22.4 (2ЈЈ-CH ), 23.6 (5-
CH ), 25.8 (C-10), 27.0 (C-7), 27.1 (C-4ЈЈ), 29.0 [CH(CH ], 32.6
C-6), 35.8 (C-3ЈЈ), 48.4 (C-2), 59.2 (C-4Ј), 63.6 (C-3Ј), 69.4 (C-3),
2 2
Cl ): δ
2
2
3 2
)
=
)
2
3
3
3
1
1
5
3
3
3 2
)
3
(
3
a
110.4 (C-1ЈЈ), 124.3 (C-8), 125.5 (C-4), 132.6 (C-9), 140.8 (C-5),
145.9 (C-2ЈЈ), 154.5 (C-2Ј), 174.9 (C-1) ppm. FTIR (ATR): ν˜ =
3495 (br w), 2965 (m), 2933 (w), 1779 (vs), 1695 (s), 1486 (w), 1450
(dddd, J = 13.3, 9.5, 9.5, 5.8 Hz, 1 H, 4ЈЈ-H
b
3
3 2
)
(
w), 1385 (s), 1300 (m), 1226 (m), 1200 (vs), 1141 (w), 1120 (w),
(
(
4
1
7
095 (m), 1056 (w), 1018 (m), 983 (m), 887 (m), 774 (w), 756 (w),
–1
+
b
05 (w) cm . MS (ESI): m/z = 430.2 [M + K] , 414.26 [M +
+
+
a
Na] , 374.3 [M – H
C H37NO
23 4
2
O] , 250.1. HRMS (ESI): m/z calcd. for
13
Na [M + Na]+ 414.2615; found 414.2626.
2
2
3
)
2
3
3 2
)
(
4R)-3-[(2R,3S,4E)-5-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-3-
hydroxy-9-methyl-2-(3-methylbut-3-enyl)deca-4,8-dienoyl]-4-iso-
propyl-1,3-oxazolidin-2-one [(2R,3S)-5b]: Light-yellow oil; R
(
[
(
9
(
1
3
3
3 2
)
f
=
2
0
1
0
.24. [α]
CD Cl ): δ = 0.87 and 0.91 [each d, J = 7.1 Hz, 3 H, CH(CH
.06 [s, 9 H, SiC(CH ], 1.54 (d, J = 1.4 Hz, 3 H, 9-CH ), 1.65 (d,
J = 1.4 Hz, 3 H, 10-H), 1.70 (dd, J = 1.4, 1.0 Hz, 3 H, 2ЈЈ-CH ),
1.82–1.89 (m, 1 H, 4ЈЈ-H ), 1.93–2.08 (m, 7 H, 3ЈЈ-H, 4ЈЈ-H , 6-H
7-H, OH), 2.11–2.18 (m, 1 H, 6-H ), 2.34 [qqd, J = 7.1, 7.1, 3.7 Hz,
], 4.11 (dd, J = 9.2, 3.7 Hz, 1 H, 3Ј-H ), 4.12 (d, J
1.7 Hz, 1 H, CH O), 4.14 (dd, J = 9.1, 3.7 Hz, 1 H, 3Ј-H ), 4.18
D
= –22.9 (c = 0.99, CH
2
Cl
2
). H NMR (500 MHz,
2
2
3 2
)
],
1
3
)
3
3
–
1
3
(w), 1095 (w), 1056 (w), 1019 (m), 984 (w), 888 (w), 705 (w) cm .
+
+
a
b
a
,
2
MS (ESI): m/z = 414.26 [M + Na] , 374.3 [M – H O] , 250.1.
HRMS (ESI): m/z calcd. for C23H37NO Na [M + Na] 414.2615;
4
+
b
1
=
H, CH(CH
3
)
2
a
found 414.2626.
2
b
(
4S)-3-[(2R,3R,4Z)-3-Hydroxy-5,9-dimethyl-2-(3-methylbut-3-enyl)-
(ddd, J = 9.4, 6.0, 3.9 Hz, 1 H, 2-H), 4.39 (ddd, J = 7.5, 3.7, 3.7 Hz,
1 H, 4Ј-H), 4.62 (d, J = 9.3, 6.0, 3.4 Hz, 1 H, 3-H), 4.66–4.68 (m,
deca-4,8-dienoyl]-4-isopropyl-1,3-oxazolidin-2-one [anti- or (2R,3R)-
5
9
4
CD
1
1
CH
(
3
a]: According to Method A, chromatography gave anti-5a (21%,
a b
1 H, 1ЈЈ-H ), 4.69–4.71 (m, 1 H, 1ЈЈ-H ), 5.06 (ddqq, J = 7.0, 7.0,
1
5% H NMR purity) as a yellow oil; R
f
= 0.23 (hexanes/EtOAc,
). H NMR (500 MHz,
1.4, 1.4 Hz, 1 H, 8-H), 5.67 (dt, J = 9.3, 1.7 Hz, 1 H, 4-H), 7.37–
:1). [α]2
Cl ): δ = 0.87 and 0.91 [each d, J = 7.0 Hz, 3 H, CH(CH
.61 (d, J = 1.5 Hz, 3 H, 9-CH ), 1.66 (d, J = 1.4 Hz, 3 H, 5-CH
.68 (d, J = 1.5 Hz, 3 H, 10-H), 1.70 (dd, J = 1.5, 0.8 Hz, 3 H, 2ЈЈ-
), 1.82 (dddd, J = 13.3, 9.5, 7.0, 4.0 Hz, 1 H, 4ЈЈ-H ), 1.93 (C-4Ј), 63.5 (C-3Ј), 66.9 (CH
dddd, J = 13.3, 9.5, 9.5, 5.4 Hz, 1 H, 4ЈЈ-H ), 1.98–2.16 (m, 7 H,
ЈЈ-H, 6-H, 7-H, OH), 2.33 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H,
0
= +25.3 (c = 1.06, CH
Cl
1
7.45 (m, 6 H, m-H, p-H), 7.65–7.69 (m, 4 H, o-H) ppm. C NMR
13
D
2
2
2
2
3
)
2
], (125 MHz, CD
), [SiC(CH ], 22.5 (2ЈЈ-CH
(C-7), 28.6 (C-6), 29.0 [CH(CH
O), 69.1 (C-3), 110.4 (C-1ЈЈ), 124.2
2
Cl
2
): δ = 14.9, 18.2 [CH(CH
), 25.7 (C-10), 27.0 [SiC(CH
], 35.8 (C-3ЈЈ), 48.4 (C-2), 59.2
3
)
2
], 17.8 (9-CH
3
), 19.5
3
3
3
)
3
3
) ], 27.6
3 3
3 2
)
3
a
2
b
(C-4), 124.3 (C-8), 128.1 (C-m), 130.08 (C-p), 130.10 (C-p), 132.6
(C-9), 133.97 (C-i), 134.04 (C-i), 135.91 (C-o),135.92 (C-o), 143.1
(C-5), 145.8 (C-2ЈЈ), 154.5 (C-2Ј), 174.8 (C-1) ppm. FTIR (ATR):
CH(CH
3
)
2
], 4.12 (ddd, J = 9.5, 6.1, 4.0 Hz, 1 H, 2-H), 4.18 (dd, J
10
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
Asymmetric Evans syn-Aldol Reactions
ν˜ = 3500 (br w), 3072 (w), 2963 (w), 2930 (w), 2856 (w), 2359 (w),
(4R)-3-[(2R,3S,4Z)-5-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-3-
1781 (s), 1695 (m), 1649 (w), 1589 (w), 1448 (w), 1427 (w), 1385 hydroxy-9-methyl-2-(3-methylbut-3-enyl)deca-4,8-dienoyl]-4-iso-
(
1
m), 1299 (w), 1226 (m), 1201 (m), 1140 (w), 1110 (s), 1055 (m), propyl-1,3-oxazolidin-2-one [syn-(2R,3S)-21b]: Colorless oil. R =
f
1
020 (m), 983 (w), 888 (w), 823 (m), 741 (m), 703 (vs), 611 (w), 503 0.21 (hexanes/Et
2
O, 2:1). H NMR (500 MHz, CD
and 0.88 [each d, J = 7.0 Hz, 3 H, CH(CH ], 1.04 [s, 9 H,
SiC(CH ], 1.58 (d, J = 1.4 Hz, 3 H, 9-CH ), 1.665 (dd, J = 1.5,
1.0 Hz, 3 H, 2ЈЈ-CH ), 1.672 (d, J = 1.4 Hz, 3 H, 10-H), 1.69–1.75
m, 1 H, 4ЈЈ-H ), 1.84 (dddd, J = 13.5, 9.5, 9.5, 5.9 Hz, 1 H, 4ЈЈ-
), 1.92–1.97 (m, 2 H, 3ЈЈ-H), 1.95 (d, J = 3.4 Hz, 1 H, OH),
.01–2.19 (m, 3 H, 6-H , 7-H), 2.21–2.27 (m, 1 H, 6-H ), 2.29 [qqd,
J = 7.0, 7.0, 3.8 Hz, 1 H, CH(CH ], 4.02 (ddd, J = 9.5, 6.4,
.0 Hz, 1 H, 2-H), 4.11 (dd, J = 12.6, 1.1 Hz, 1 H, 5-CH O),
.12–4.16 (m, 2 H, 3Ј-H), 4.29 (dd, J = 12.6, 1.1 Hz, 1 H, 5-
O), 4.33–4.38 (m, 2 H, 4Ј-H, 3-H), 4.61–4.63 (m, 1 H, 1ЈЈ-
), 4.65–4.68 (m, 1 H, 1ЈЈ-H ), 5.10 (ddqq, J = 6.9, 6.9, 1.4,
.4 Hz, 1 H, 8-H), 5.31 (ddd, J = 8.9, 1.1, 1.1 Hz, 1 H, 4-H), 7.38–
2 2
Cl ): δ = 0.84
–1
+
+
(m) cm . MS (ESI): m/z = 668.4 [M + Na] , 628.4 [M – H
2
O] ,
3 2
)
+
3
72.3, 243.2 [C15
H
19OSi] . HRMS (ESI): m/z calcd. for C39
H
55
-
3
)
3
3
+
NO SiNa [M + Na] 668.3742; found 668.3721.
5
3
(
H
2
a
(
9
4R)-3-((2R,3S,4E)-3-Hydroxy-5-{[(4-methoxybenzyl)oxy]methyl}-
-methyl-2-(3-methylbut-3-enyl)-deca-4,8-dienoyl)-4-isopropyl-1,3-
b
a
b
oxazolidin-2-one [(2R,3S)-5c]: Colorless oil. R
f
= 0.21 (hexanes/
). H NMR (500 MHz,
],
), 1.68 (d, J = 1.4 Hz, 3 H, 10-H),
.70 (dd, J = 1.4, 0.9 Hz, 3 H, 2ЈЈ-CH ), 1.82–1.89 (m, 1 H, 4ЈЈ-
), 1.90–2.22 (m, 8 H, 3ЈЈ-H, 4ЈЈ-H , 6-H, 7-H, OH), 2.31 [qqd,
J = 6.9, 6.9, 3.8 Hz, 1 H, CH(CH ], 3.79 (s, 3 H, OMe), 3.86 (dd,
J = 12.2, 1.3 Hz, 1 H, CH O), 3.93 (dd, J = 12.2, 1.3 Hz, 1 H,
CH O), 4.09 (dd, J = 9.1, 3.5 Hz, 1 H, 3Ј-H ), 4.12 (dd, J = 9.1,
), 4.16 (ddd, J = 9.5, 6.6, 3.9 Hz, 1 H, 2-H),
EtOAc, 3:1). [α]2
0
1
3 2
)
D
2 2
= –21.1 (c = 1.00, CH Cl
4
4
a b
H
CD
1
1
2
Cl
2 3 2
): δ = 0.85 and 0.88 [each d, J = 6.9 Hz, 3 H, CH(CH )
.59 (d, J = 1.4 Hz, 3 H, 9-CH
3
a b
CH H
H
3
a
b
H
a
b
1
7
3 2
)
1
3
.47 (m, 6 H, m-H, p-H), 7.66–7.71 (m, 4 H, o-H) ppm. C NMR
Cl ): δ = 14.9, 18.1 [CH(CH ], 17.8 (9-CH ), 19.5
], 22.4 (2ЈЈ-CH ), 25.8 (C-10), 26.7 (C-4ЈЈ), 27.0
], 27.3 (C-7), 28.9 [CH(CH ], 35.0 (C-6), 35.7 (C-3ЈЈ),
8.3 (C-2), 59.1 (C-4Ј), 61.8 (CH O), 63.5 (C-3Ј), 68.9 (C-3), 110.4
a
H
b
(
[
125 MHz, CD
SiC(CH
2
2
3
)
2
3
a
H
b
a
3
)
3
3
7
4
1
=
.6 Hz, 1 H, 3Ј-H
.361 (ddd, J = 7.6, 3.8, 3.5 Hz, 1 H, 4Ј-H), 4.362 (d, J = 11.1 Hz,
b
[SiC(CH
3
)
3
3 2
)
4
2
H, OCH
9.2, 6.6, 3.6 Hz, 1 H, 3-H), 4.66–4.68 (m, 1 H, 1ЈЈ-H
), 5. 12 (ddqq, J = 7.0, 7.0, 1.4, 1.4 Hz, 1 H, 8-H),
.52 (ddd, J = 9.2, 1.3, 1.3 Hz, 1 H, 4-H), 6.85–6.89 (m, 2 H, Ph),
.24–7.27 (m, 2 H, Ph) ppm. 13C NMR (125 MHz, CD
Cl ): δ =
4.9, 18.2 [CH(CH ], 17.8 (9-CH ), 22.5 (2ЈЈ-CH ), 25.8 (C-10),
7.2 (C-4ЈЈ), 27.3 (C-7), 28.8 [CH(CH ], 29.0 (C-6), 35.8 (C-3ЈЈ),
8.5 (C-2), 55.6 (OMe), 59.3 (C-4Ј), 63.6 (C-3Ј), 69.3 (C-3), 72.2
), 73.7 (CH O), 110.5 (C-1ЈЈ), 114.0 (Ph), 124.3 (C-8), 127.5
C-4), 129.7 (Ph), 131.0 (Ph), 132.7 (C-9), 141.0 (C-5), 145.8 (C-
ЈЈ), 154.6 (C-2Ј), 159.7 (C-OMe), 174.7 (C-1) ppm. FTIR (ATR):
ν˜ = 3477 (br w), 2965 (w), 2913 (w), 2854 (w), 1778 (vs), 1694 (m),
649 (w), 1612 (w), 1586 (w), 1513 (m), 1443 (w), 1385 (s), 1300
a
H
b
), 4.39 (d, J = 11.1 Hz, 1 H, OCH
a
H
b
), 4.58 (ddd, J
(
(
C-1ЈЈ), 124.3 (C-8), 126.6 (C-4), 128.08 (C-m), 128.13 (C-m), 130.1
C-p), 130.2 (C-p), 132.1 (C-9), 133.88 (C-i), 133.89 (C-i), 136.0 (C-
a
), 4.69–4.71
(
m, 1 H, 1ЈЈ-H
b
o), 136.1 (C-o), 142.8 (C-5), 145.7 (C-2ЈЈ), 154.4 (C-2Ј), 174.6 (C-
5
7
1
2
4
(
(
2
1) ppm.
2
2
3
)
2
3
3
(
4R)-3-[(2S,3S,4Z)-5-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-3-
hydroxy-9-methyl-2-(3-methylbut-3-enyl)deca-4,8-dienoyl]-4-iso-
propyl-1,3-oxazolidin-2-one [anti-(2S,3S)-21b]: R = 0.21 (hexanes/
): δ = 0.86 and 0.91 [each
], 1.07 [s, 9 H, SiC(CH ], 1.64 (d,
), 1.66 (dd, J = 1.4, 1.0 Hz, 3 H, 2ЈЈ-CH ),
.70 (d, J = 1.4 Hz, 3 H, 10-H), 1.69–1.75 (m, 1 H, 4ЈЈ-H ), 1.84
dddd, J = 13.5, 9.5, 9.5, 5.9 Hz, 1 H, 4ЈЈ-H ), 1.92–1.97 (m, 2 H,
ЈЈ-H), 1.95 (d, J = 3.4 Hz, 1 H, OH), 2.01–2.19 (m, 3 H, 6-H , 7-
), 2.29 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H,
3 2
)
f
OCH
2
2
1
Et
d, J = 7.0 Hz, 3 H, CH(CH
J = 1.4 Hz, 3 H, 9-CH
1
(
2 2 2
O, 2:1). H NMR (500 MHz, CD Cl
3
)
2
3 3
)
3
3
a
1
b
(
(
(
m), 1247 (vs), 1173 (m), 1141 (w), 1097 (s), 1056 (m), 1034 (s), 983
m), 888 (m), 820 (m), 774 (w), 756 (w), 705 (w), 637 (w), 569
3
a
H), 2.21–2.27 (m, 1 H, 6-H
b
–
1
+
w) cm . MS (ESI): m/z = 550.3 [M + Na] . HRMS (ESI): m/z
CH(CH
dd, J = 9.2, 2.7 Hz, 1 H, 3Ј-H
3Ј-H ), 4.11 (dd, J = 12.6, 1.1 Hz, 1 H, 5-CH H O), 4.29 (dd, J =
3
)
2
], 3.84–3.89 (m, 1 H, 3-H), 3.96–4.01 (m, 1 H, 2-H), 4.17
+
calcd. for C31
4R)-3-[(2R,3S,4E)-3-Hydroxy-5,9-dimethyl-2-(3-methylbut-3-enyl)-
deca-4,8-dienoyl]-4-isopropyl-1,3-oxazolidin-2-one [(2R,3S)-21a]: 12.6, 1.1 Hz, 1 H, 5-CH H O), 4.44 (ddd, J = 6.8, 3.83, 3.1 Hz, 1
6
H45NO Na [M + Na] 550.3139; found 550.3142.
(
a
), 4.21 (dd, J = 9.2, 7.9 Hz, 1 H,
(
b
a
b
a
b
= 0.43 (hexanes/EtOAc, 2:1). [α]2
0
= –40.8 (c =
): δ = 0.87 and 0.92
3 2
) ], 1.61 (d, J = 1.4 Hz, 3 H, 9- H), 7.38–7.47 (m, 6 H, m-H, p-H), 7.66–7.71 (m, 4 H, o-H) ppm.
Colorless oil. R
f
1
D
a b
H, 4Ј-H), 4.61–4.63 (m, 1 H, 1ЈЈ-H ), 4.65–4.68 (m, 1 H, 1ЈЈ-H ),
0
[
.98, CH
each d, J = 7.0 Hz, 3 H, CH(CH
CH ), 1.66 (d, J = 1.4 Hz, 3 H, 5-CH
0-H), 1.70 (dd, J = 1.4, 0.9 Hz, 3 H, 2ЈЈ-CH
ЈЈ-H ), 1.89–1.98 (m, 1 H, 4ЈЈ-H ), 1.98–2.13 (m, 7 H, 3ЈЈ-H, 6-H,
-H, OH), 2.33 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H, CH(CH ], 4.12 3ЈЈ), 47.5 (C-2), 59.1 (C-4Ј), 61.8 (CH O), 63.5 (C-3Ј), 69.6 (C-3),
2
Cl
2
). H NMR (500 MHz, CD
2
Cl
2
5.19–5.24 (m, 1 H, 8-H), 5.31 (ddd, J = 8.9, 1.1, 1.1 Hz, 1 H, 4-
1
3
3
3
), 1.68 (d, J = 1.4 Hz, 3 H,
), 1.79–1.86 (m, 1 H,
2 2 3 2
C NMR (125 MHz, CD Cl ): δ = 14.9, 18.1 [CH(CH ) ], 17.8 (9-
CH ), 19.5 [SiC(CH ) ], 22.4 (2ЈЈ-CH ), 25.8 (C-10), 26.7 (C-4ЈЈ),
3 3 3 3
1
4
7
3
a
b
3 3 3 2
27.0 [SiC(CH ) ], 27.3 (C-7), 28.9 [CH(CH ) ], 35.0 (C-6), 35.7 (C-
3 2
)
2
(
ddd, J = 9.4, 6.2, 4.1 Hz, 1 H, 2-H), 4.18 (dd, J = 9.1, 3.8 Hz, 1
H, 3Ј-H ), 4.20 (dd, J = 9.1, 6.9 Hz, 1 H, 3Ј-H ), 4.43 (ddd, J =
.9, 3.8, 3.8 Hz, 1 H, 4Ј-H), 4.55 (ddd, J = 9.0, 6.2, 3.6 Hz, 1 H, 3-
H), 4.66–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–4.71 (m, 1 H, 1ЈЈ-H ), 5.09
ddqq, J = 7.0, 7.0, 1.4, 1.4 Hz, 1 H, 8-H), 5.24 (dt, J = 9.0, 1.4 Hz,
110.4 (C-1ЈЈ), 124.9 (C-8), 126.6 (C-4), 128.21 (C-m), 128.25 (C-m),
130.1 (C-p), 130.2 (C-p), 132.0 (C-9), 133.88 (C-i), 133.89 (C-i),
135.7 (C-o), 135.8 (C-o), 142.8 (C-5), 145.9 (C-2ЈЈ), 154.4 (C-2Ј),
174.6 (C-1) ppm.
a
b
6
a
b
(
H, 4-H) ppm. 13C NMR (125 MHz, CD
], 16.9 (5-CH ), 17.8 (9-CH ), 22.4 (2ЈЈ-CH
0), 26.9 (C-7), 27.0 (C-4ЈЈ), 29.0 [CH(CH ], 35.9 (C-3ЈЈ), 40.1 1695 (m), 1448 (w), 1427 (w), 1385 (m), 1300 (w), 1261 (w), 1202
2 2
Cl
2 2
): δ = 14.9, 18.2 syn/anti-21b (85:15): [α] 2D 0 = –17.4 (c = 1.00, CH Cl ). FTIR (ATR):
1
[CH(CH
3
)
2
3
3
3
), 25.8 (C- ν˜ = 3495 (br w), 3072 (w), 2963 (w), 2930 (m), 2856 (w), 1782 (s),
1
3 2
)
(
1
1
C-6), 48.5 (C-2), 59.2 (C-4Ј), 63.6 (C-3Ј), 69.9 (C-3), 110.4 (C-1ЈЈ), (m), 1141 (w), 1111 (s), 1056 (s), 1018 (s), 983 (m), 888 (w), 822
–
1
24.2 (C-8), 124.9 (C-4), 132.1 (C-9), 140.2 (C-5), 145.9 (C-2ЈЈ), (m), 798 (m), 740 (m), 702 (vs), 613 (w), 503 (s) cm . MS (ESI):
+
+
54.5 (C-2Ј), 175.0 (C-1) ppm. FTIR (ATR): ν˜ = 3498 (br w), 3073
2 2
m/z = 668.4 [M + Na] , 628.4 [M – H O] , 561.4, 372.3 [M – H O –
+
(w), 2965 (m), 2926 (m), 2854 (w), 1779 (vs), 1696 (s), 1486 (w), OTBDPS] . HRMS (ESI): m/z calcd. for C H NO SiNa [M +
39 55 5
+
1
450 (m), 1385 (vs), 1300 (m), 1227 (m), 1201 (vs), 1141 (w), 1121 Na] 668.3742; found 668.3731.
(
(
H
w), 1096 (m), 1056 (m), 1019 (m), 983 (m), 887 (m), 774 (w), 756
–1
+
w), 705 (w) cm . MS (ESI): m/z = 414.3 [M + Na] , 374.3 [M –
(4R)-3-((2R,3S,4Z)-3-Hydroxy-5-{[(4-methoxybenzyl)oxy]methyl}-
9-methyl-2-(3-methylbut-3-enyl)deca-4,8-dienoyl)-4-isopropyl-1,3-ox-
+
2
O] , 250.1. HRMS (ESI): m/z calcd. for C23
H37NO
4
Na [M +
+
Na] 414.2615; found 414.2615.
azolidin-2-one [(2R,3S)-21c]: Colorless oil. R
f
= 0.23 (hexanes/
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org 11

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
EtOAc, 3:1). [α]20
CD Cl
.59 (d, J = 1.4 Hz, 3 H, 9-CH
.70 (dd, J = 1.4, 0.8 Hz, 3 H, 2ЈЈ-CH
), 1.88–1.96 (m, 1 H, 4ЈЈ-H ), 1.96–2.02 (m, 2 H, 3ЈЈ-H), 2.04–
.14 (m, 4 H, 6-H, 7-H), 2.28 [qqd, J = 7.0, 7.0, 3.9 Hz, 1 H,
CH(CH ], 2.35 (d, J = 3.5 Hz, 1 H, OH), 3.79 (s, 3 H, OMe),
.89 (dd, J = 11.3, 1.0 Hz, 1 H, CH O), 4.06 (dd, J = 11.3,
.0 Hz, 1 H, CH O), 4.11 (ddd, J = 9.5, 6.5, 3.9 Hz, 1 H, 2-H),
.13 (dd, J = 9.2, 4.0 Hz, 1 H, 3Ј-H ), 4.15 (dd, J = 9.2, 6.9 Hz, 1
), 4.37 (ddd, J = 6.9, 4.0, 3.9 Hz, 1 H, 4Ј-H), 4.38 (d, J =
1.3 Hz, 1 H, OCH ), 4.41 (d, J = 11.3 Hz, 1 H, OCH ), 4.57
ddd, J = 8.7, 6.5, 3.5 Hz, 1 H, 3-H), 4.65–4.67 (m, 1 H, 1ЈЈ-H ),
), 5.07–5.12 (m, 1 H, 8-H), 5.46 (dt, J =
.7, 1.0 Hz, 1 H, 4-H), 6.85–6.89 (m, 2 H, Ph), 7.24–7.28 (m, 2 H,
= –33.0 (c = 0.98, CH
Cl
). H NMR (500 MHz,
1
250.1. HRMS (ESI): m/z calcd. for C29
], 528.3480; found 528.3462.
), 1.67 (d, J = 1.4 Hz, 3 H, 10-H),
), 1.77–1.84 (m, 1 H, 4ЈЈ-
H51NO
4
SiNa [M + Na]+
D
2
2
2
2 3 2
): δ = 0.85 and 0.87 [each d, J = 7.0 Hz, 3 H, CH(CH )
1
1
3
(
1R,2Z)-1-((1S)-1-{[(4S)-4-Isopropyl-2-oxo-1,3-oxazolidin-3-
yl]carbonyl}-4-methylpent-4-enyl)-3,7-dimethylocta-2,6-dienyl (2S)-
,3,3-Trifluoro-2-methoxy-2-phenylpropanoate [(S)-12]: To a solu-
tion of syn-5a (25.0 mg, 0.06 mmol) in anhydrous CH Cl (2 mL)
at 0 °C were successively added anhydrous pyridine (0.01 mL,
3
H
a
b
3
2
2
2
3 2
)
3
1
4
a b
H
1
0
0
0.1 mg, 0.13 mmol), a solution of (R)-MTPACl (20.2 mg,
.08 mmol) in anhydrous CH Cl (1 mL) and DMAP (3.90 mg,
.03 mmol). The reaction mixture was warmed to room temp.
a
H
b
2
2
a
H, 3Ј-H
b
within 2 h and stirred for a further 15 h. A saturated solution of
NaHCO (10 mL) was then added, the layers were separated, and
the aqueous layer was extracted with CH Cl (3ϫ 10 mL). The
combined organic layers were dried (MgSO ) and the solvent was
removed under vacuum. The residue was purified by chromatog-
1
a
H
b
a b
H
3
(
a
2
2
4.69–4.71 (m, 1 H, 1ЈЈ-H
b
4
8
1
3
Ph) ppm. C NMR (125 MHz, CD
2
Cl
), 25.8 (C-10), 26.9 (C-4ЈЈ), 27.1 (C-7),
], 35.8 (C-3ЈЈ), 36.0 (C-6), 48.4 (C-2), 55.6 (OMe),
9.1 (C-4Ј), 63.6 (C-3Ј), 67.9 (CH O), 69.2 (C-3), 72.6 (OCH ),
10.4 (C-1ЈЈ), 114.0 (Ph), 124.2 (C-8), 129.0 (C-4), 129.8 (Ph), 130.9
2 3 2
): δ = 15.0, 18.1 [CH(CH ) ],
raphy on SiO
2
(hexanes/EtOAc, 10:1; R
f
= 0.27) to give (S)-12
1
2
5
1
7.8 (9-CH
9.0 [CH(CH
3
), 22.4 (2ЈЈ-CH
3
1
(
34.0 mg, 0.06 mmol, 88%, H NMR purity 95%) as a yellow oil.
3
)
2
20
1
[α]
D
= +29.3 (c = 1.01, CH
2
Cl
2
). H NMR (500 MHz, CDCl
], 1.55–1.61
), 1.66 (d, J = 1.4 Hz, 3 H, 10-H),
), 1.80–1.90 (m, 1 H, 4ЈЈ-H ), 1.90–
.96 (m, 2 H, 3ЈЈ-H), 2.01–2.14 (m, 2 H, 7-H), 2.19–2.25 (m, 2 H,
-H), 2.33 [qqd, J = 7.0, 7.0, 3.8 Hz, 1 H, CH(CH ], 3.54 (s, 3 H,
), 4.13 (dd, J = 9.1, 7.7 Hz, 1 H, 3Ј-H ), 4.16 (dd, J = 9.1,
.1 Hz, 1 H, 3Ј-H ), 4.34 (ddd, J = 7.7, 3.8, 3.1 Hz, 1 H, 4Ј-H),
.38 (ddd, J = 9.7, 7.6, 3.8 Hz, 1 H, 2-H), 4.56–4.58 (m, 1 H, 1ЈЈ-
), 4.65–4.67 (m, 1 H, 1ЈЈ-H ), 5.13 (ddqq, J = 7.1, 7.1, 1.4,
.4 Hz, 1 H, 8-H), 5.34 (dq, J = 10.0, 1.6 Hz, 1 H, 4-H), 5.97 (dd,
J = 10.0, 7.6 Hz, 1 H, 3-H), 7.33–7.38 (m, 3 H, m-H, p-H), 7.48–
3
): δ
2
2
=
(
1
1
6
OCH
3
4
H
1
0.86 and 0.91 [each d, J = 7.0 Hz, 3 H, CH(CH
, 9-CH , 4ЈЈ-H
.76 (d, J = 1.6 Hz, 3 H, 5-CH
3 2
)
m, 7 H, 2ЈЈ-CH
3
3
a
(
Ph), 132.2 (C-9), 140.7 (C-5), 145.8 (C-2ЈЈ), 154.5 (C-2Ј), 159.7 (C-
OMe), 174.7 (C-1) ppm. FTIR (ATR): ν˜ = 3485 (br w), 2965 (w),
933 (w), 291 (w), 2855 (w), 1778 (vs), 1694 (m), 1612 (w), 1586
3
b
2
3 2
)
(w), 1513 (m), 1486 (w), 1451 (w), 1385 (s), 1300 (m), 1248 (s), 1202
3
a
(s), 1174 (m), 1142 (w), 1095 (m), 1034 (m), 984 (w), 888 (w), 822
b
–1
(
=
w), 774 (w), 756 (w), 705 (w), 642 (w), 566 (w) cm . MS (ESI): m/z
550.3 [M + Na] , 510.3 [M – H O] , 492.3, 372.3 [M–AuxCO] .
2
+
+
+
b
a
+
6
HRMS (ESI): m/z calcd. for C31H45NO Na [M + Na] 550.3139;
found 550.3136.
1
3
7
1
.53 (m, 2 H, o-H) ppm. C NMR (75 MHz, CDCl
8.2 [CH(CH ], 17.7 (9-CH ), 22.3 (2ЈЈ-CH ), 23.5 (5-CH
], 32.6 (C-6), 34.9
), 59.1 (C-4Ј), 63.2
), 110.7 (C-1ЈЈ), 119.9
), 123.9 (C-8), 127.4 (C-o), 128.4
C-m), 129.6 (C-p), 132.2 (C-9), 132.7 (C-i), 144.65 (C-5), 144.69
3
): δ = 14.8,
(
4S)-3-((2S,3R,4Z)-3-{[tert-Butyl(dimethyl)silyl]oxy}-5,9-dimethyl-
3
)
2
3
3
3
), 25.8
2
2
-(3-methylbut-3-enyl)deca-4,8-dienoyl)-4-isopropyl-1,3-oxazolidin-
-one [(2S,3R)-11]: To a solution of syn-5a (38.0 mg, 0.10 mmol) in
(
(
(
(
(
(
(
C-10), 26.7 (C-7), 26.8 (C-4ЈЈ), 28.7 [CH(CH
C-3ЈЈ), 45.9 (C-2), 55.6 (q, J = 1.6 Hz, OCH
C-3Ј), 73.8 (C-3), 84.4 (q, J = 27.6 Hz, CCF
C-4), 123.5 (q, J = 288.3 Hz, CF
3 2
)
3
anhydrous DMF (2 mL) at 0 °C were successively added anhydrous
Et N (0.04 mL, 29.5 mg, 0.29 mmol) and a solution of TBSCl
29.3 mg, 0.19 mmol) in anhydrous DMF (1 mL). After stirring at
room temp. for 20 h, a saturated solution of NaHCO (10 mL) was
added, the layers were separated and the aqueous layer was ex-
tracted with CH Cl (3ϫ 10 mL). The combined organic layers
were dried (MgSO ) and the solvent was removed under vacuum.
The residue was purified by chromatography on SiO (hexanes/
EtOAc, 40:1; R = 0.27) to give 11 (36.0 mg, 0.07 mmol, 71%, H
NMR purity 95%) as a light-yellow oil. [α]
3
3
3
(
3
1
9
C-2ЈЈ), 153.8 (C-2Ј), 165.6 (CO), 172.7 (C-1) ppm. F NMR
235 MHz, CDCl ): δ = –71.32 ppm. FTIR (ATR): ν˜ = 2966 (w),
780 (vs), 1747 (m), 1697 (m), 1488 (w), 1451 (w), 1385 (m), 1299
m), 1269 (m), 1234 (s), 1169 (vs), 1121 (m), 1081 (m), 1056 (w),
1017 (m), 989 (m), 964 (w), 926 (w), 891 (w), 816 (w), 766 (w), 718
3
2
2
1
(
4
2
1
f
–
1
+
2
0
(m), 697 (w), 640 (w) cm . MS (ESI): m/z = 630.3 [M + Na] ,
D
= +27.4 (c = 1.01,
): δ = –0.41 [s, 3 H, Si(CH ],
], 0.82 [s, 9 H, SiC(CH ], 0.83 and 0.87 [d,
J = 7.1 Hz, 3 H, CH(CH ], 1.59 (d, J = 1.5 Hz, 3 H, 9-CH ), 1.65 (1R,2Z)-1-((1S)-1-{[(4S)-4-Isopropyl-2-oxo-1,3-oxazolidin-3-
d, J = 1.4 Hz, 3 H, 5-CH ), 1.66–1.67 (m, 6 H, 2ЈЈ-CH , 10-H), yl]carbonyl}-4-methylpent-4-enyl)-3,7-dimethylocta-2,6-dienyl (2R)-
.79–1.87 (m, 2 H, 4ЈЈ-H), 1.90–2.06 (m, 6 H, 3ЈЈ-H, 6-H, 7-H), 3,3,3-Trifluoro-2-methoxy-2-phenylpropanoate [(R)-12]: Obtained as
.27 [qqd, J = 7.1, 7.1, 3.9 Hz, 1 H, CH(CH ], 4.09 (ddd, J = 8.0, described above from syn-5a (25.0 mg, 0.06 mmol) in anhydrous
.2, 2.8 Hz, 1 H, 2-H), 4.05 (dd, J = 9.2, 8.1 Hz, 1 H, 3Ј-H ), 4.12 CH Cl (2 mL), anhydrous pyridine (0.01 mL, 10.1 mg,
), 4.28 (ddd, J = 8.1, 3.9, 2.4 Hz, 1 0.13 mmol), (S)-MTPACl (20.2 mg, 0.08 mmol) in anhydrous
H, 4Ј-H), 4.46 (dd, J = 9.4, 8.0 Hz, 1 H, 3-H), 4.60–4.62 (m, 1 H, CH Cl (1 mL) and DMAP (3.90 mg, 0.03 mmol) to give (R)-12
ЈЈ-H ), 4.63–4.65 (m, 1 H, 1ЈЈ-H ), 5.07–5.12 (m, 2 H, 4-H, 8- (32.0 mg, 0.05 mmol, 83%, H NMR purity 95%) as a yellow oil.
H) ppm. C NMR (125 MHz, CDCl ): δ = –4.7 [Si(CH ], –3.9
Si(CH ], 15.1, 18.2 [CH(CH ], 17.8 (9-CH ), 18.4 [SiC(CH ], CDCl
2.4 (2ЈЈ-CH ), 23.1 (5-CH ), 25.8 (C-10), 26.0 [SiC(CH ], 26.8 1.64 (d, J = 1.4 Hz, 3 H, 9-CH
C-7), 27.8 (C-4ЈЈ), 29.3 [CH(CH ], 32.8 (C-6), 35.7 (C-3ЈЈ), 49.6 CH
C-2), 59.4 (C-4Ј), 63.5 (C-3Ј), 71.0 (C-3), 110.2 (C-1ЈЈ), 124.5 (C- CH
+
1
396.3, 374.3 [M – MPTA] . HRMS (ESI): m/z calcd. for
CH
2
Cl
2
). H NMR (500 MHz, CDCl
3
3 2
)
33 44 3 6
C H F NO
Na [M + Na]+ 630.3013; found 630.3001.
–
0.36 [s, 3 H, Si(CH
3
)
2
3 3
)
3
)
2
3
(
3
3
1
2
4
3 2
)
a
2
2
(dd, J = 9.2, 2.3 Hz, 1 H, 3Ј-H
b
2
2
1
1
b
a
13
20
1
3
3
)
2
R
f
= 0.27. [α]
): δ = 0.87 and 0.90 [each d, J = 7.0 Hz, 3 H, CH(CH
), 1.67 (d, J = 1.4 Hz, 3 H, 2ЈЈ-
), 1.69 (d, J = 1.4 Hz, 3 H, 10-H), 1.72 (d, J = 1.3 Hz, 3 H, 5-
), 1.70–1.75 (m, 1 H, 4ЈЈ-H ), 1.91–2.18 (m, 5 H, 3ЈЈ-H, 7-H,
), 2.19–2.27 (m, 2 H, 6-H), 2.33 [qqd, J = 7.0, 7.0, 3.8 Hz, 1
], 3.53 (s, 3 H, OCH ), 4.11 (dd, J = 9.1, 8.0 Hz, 1
), 4.15 (dd, J = 9.1, 2.7 Hz, 1 H, 3Ј-H ), 4.27 (ddd, J =
248 (m), 1229 (m), 1200 (m), 1057 (s), 985 (m), 940 (w), 887 (m), 8.0, 3.8, 2.7 Hz, 1 H, 4Ј-H), 4.40 (ddd, J = 9.6, 6.7, 3.7 Hz, 1 H, 2-
D
= +105.3 (c = 1.00, CH
2
Cl
2
). H NMR (500 MHz,
[
3
)
2
3
)
2
3
3
)
3
3
3 2
)
],
2
3
3
3
)
3
3
(
(
3
)
2
3
3
a
8), 127.5 (C-4), 132.1 (C-9), 137.4 (C-5), 145.9 (C-2ЈЈ), 154.2 (C- 4ЈЈ-H
b
2Ј), 174.2 (C-1) ppm. FTIR (ATR): ν˜ = 2960 (m), 2928 (m), 2856
H, CH(CH
3
)
2
3
(w), 1781 (s), 1694 (m), 1650 (w), 1449 (w), 1382 (m), 1299 (m), H, 3Ј-H
a
b
1
8
–
1
34 (vs), 774 (vs), 754 (m), 731 (w), 696 (w), 666 (w), 635 (w) cm .
b a
H), 4.63–4.65 (m, 1 H, 1ЈЈ-H ), 4.69–4.71 (m, 1 H, 1ЈЈ-H ), 5.13
+
+
MS (ESI): m/z = 528.4 [M + Na] , 374.3 [M–OTBS] ,
(dq, J = 9.8, 1.3 Hz, 1 H, 4-H), 5.16 (ddqq, J = 7.1, 7.1, 1.4, 1.4 Hz,
12
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
Asymmetric Evans syn-Aldol Reactions
H, 8-H), 5.94 (dd, J = 9.8, 6.9 Hz, 1 H, 3-H), 7.34–7.40 (m, 3 (C-3), 110.3 (C-1ЈЈ), 122.7 (C-8), 125.4 (C-4), 132.8 (C-9), 140.4
1
1
3
H, m-H, p-H), 7.44–7.48 (m, 2 H, o-H) ppm. C NMR (75 MHz,
CDCl ): δ = 14.9, 18.2 [CH(CH ], 17.8 (9-CH ), 22.3 (2ЈЈ-CH
3.4 (5-CH ), 25.8 (C-10), 26.6 (C-4ЈЈ), 26.7 (C-7), 28.7 [CH(CH
(C-5), 145.8 (C-2ЈЈ) ppm. FTIR (ATR): ν˜ = 3334 (br m), 3072 (w),
3
3
)
2
3
3
), 2965 (m), 2916 (s), 2359 (w), 1649 (w), 1446 (s), 1376 (s), 1274 (w),
–
1
2
3
5
1
3
3
)
2
], 1095 (w), 1031 (s), 885 (vs), 844 (w) cm .
2.6 (C-6), 35.1 (C-3ЈЈ), 45.8 (C-2), 55.7 (q, J = 1.5 Hz, OCH
9.1 (C-4Ј), 63.3 (C-3Ј), 74.1 (C-3), 84.8 (q, J = 27.6 Hz, CCF
3
),
),
4
3
-[(1Z)-2,6-Dimethylhepta-1,5-dienyl]-2,2-dimethyl-5-(3-methylbut-
3
-enyl)-1,3-dioxane (14): To a solution of 13 (71.0 mg, 0.27 mmol,
3
10.8 (C-1ЈЈ), 119.6 (C-4), 123.4 (q, J = 288.7 Hz, CF ), 124.0
1
syn/anti = 95:5 by H NMR) in anhydrous acetone (3 mL) at room
(
(
(
(
(
C-8), 127.6 (C-o), 128.4 (C-m), 129.7 (C-p), 132.1 (C-9), 132.4
temp. were added dimethoxypropane (0.30 mL, 250 mg,
C-i), 144.4 (C-5), 144.7 (C-2ЈЈ), 154.0 (C-2Ј), 165.7 (CO), 172.6
2
.40 mmol) and PPTS (3.35 mg, 0.01 mmol). After stirring for 2 h,
the solvent was removed under vacuum and the residue was puri-
fied by chromatography on SiO (hexanes/EtOAc, 4:1 and 2 vol.-%
Et N) to give a 95:5 syn/anti mixture of 14 (74.0 mg, 0.24 mmol,
1%, GC purity 98%) as a colorless oil.
C-1) ppm. 19F NMR (235 MHz, CDCl
): δ = –71.51 ppm. FTIR
3
ATR): ν˜ = 2966 (w), 1779 (vs), 1747 (m), 1697 (m), 1487 (w), 1451
m), 1385 (m), 1299 (m), 1237 (m), 1169 (vs), 1121 (m), 1082 (w),
2
3
1
6
3
056 (w), 1016 (m), 989 (m), 922 (w), 890 (w), 765 (w), 718 (m),
9
–
1
+
98 (w), 641 (w) cm . MS (ESI): m/z = 630.3 [M + Na] , 396.3,
+
20
74.3 [M–MPTA] . HRMS (ESI): m/z calcd. for C33
H
44
F
3
NO
6
Na
syn-14: R
f
1
= 0.85 (hexanes/EtOAc, 2:1). [α]
Cl ): δ = 1.22–1.28 (m, 1 H, 2-
-eq), 1.44 (q, J = 0.8 Hz, 3 H,
-ax), 1.61 (d, J = 1.4 Hz, 3 H, 9-CH ), 1.62–1.67 (m, 1 H, 4ЈЈ-
), 1.68 (d, J = 1.4 Hz, 3 H, 10-H), 1.71 (dd, J = 1.4, 0.8 Hz, 3
H, 2ЈЈ-CH ), 1.74 (dd, J = 1.5, 0.6 Hz, 3 H, 5-CH ), 1.82 (dddd, J
13.7, 9.4, 9.4, 5.3 Hz, 1 H, 4ЈЈ-H ), 1.95 (dddd, J = 14.5, 9.4, 6.7,
.5 Hz, 1 H, 3ЈЈ-H ), 2.00–2.16 (m, 5 H, 3ЈЈ-H , 6-H, 7-H), 3.72
dd, J = 11.8, 1.9 Hz, 1 H, CHeq axO), 3.98 (ddd, J = 11.8, 2.9,
axO), 4.67–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–4.70 (m,
), 4.75 (ddd, J = 8.0, 2.8, 0.6 Hz, 1 H, 3-H), 5.12 (ddqq,
D
= –15.3 (c = 1.03,
[
M + Na]+ 630.3013; found 630.3007.
CH Cl
2
2
). H NMR (500 MHz, CD
2
2
H), 1.32 (q, J = 0.8 Hz, 3 H, CH
CH
3
(
4Z)-5,9-Dimethyl-2-(3-methylbut-3-enyl)deca-4,8-diene-1,3-diol
13): To a solution of 5a (228 mg, 0.58 mmol, syn/anti = 95:5 by
3
3
(
H
a
1
H NMR) in anhydrous THF/anhydrous MeOH (10:0.1 mL) at
3
3
0
0
°C was added dropwise a solution of LiBH
.44 mL, 38.0 mg, 1.75 mmol) and the reaction mixture was stirred
(10 mL) was added, the
4
(4 m in THF,
=
1
(
b
a
b
for 3 h. A saturated solution of NaHCO
layers were separated, and the aqueous layer was extracted with
EtOAc (3 ϫ 30 mL). The combined organic layers were dried
3
H
1
1
.2 Hz, 1 H, CHeq
H, 1ЈЈ-H
H
b
a
(MgSO
4
) and the solvent was removed under vacuum. The residue
(hexanes/EtOAc, 4:1) to
J = 6.9, 6.9, 1.4, 1.4 Hz, 1 H, 8-H), 5.23 (dq, J = 8.0, 1.5 Hz, 1 H,
was purified by chromatography on SiO
give a 95:5 syn/anti mixture of 13 (108 mg, 0.41 mmol, 70%, GC
purity 98%) as a colorless oil.
2
13
4
(
2
(CH
-H) ppm. C NMR (125 MHz, CD
CH -ax), 22.3 (C-4ЈЈ), 22.5 (2ЈЈ-CH
7.0 (C-7), 29.9 (CH -eq), 33.0 (C-6), 36.1 (C-3ЈЈ), 38.5 (C-2), 63.2
O), 69.7 (C-3), 98.8 (Me C), 110.1 (C-1ЈЈ), 124.3 (C-8), 125.0
C-4), 132.2 (C-9), 138.7 (C-5), 146.5 (C-2ЈЈ) ppm. FTIR (ATR):
ν˜ = 3072 (w), 2991 (m), 2967 (m), 2936 (m), 2856 (m), 2359 (w),
670 (w), 1649 (w), 1452 (m), 1378 (s), 1274 (w), 1241 (m), 1196
vs), 1160 (s), 1129 (s), 1085 (m), 1064 (m), 1035 (w), 982 (m), 917
2
Cl
2
): δ = 17.8 (9-CH
3
), 19.5
3
3
), 23.5 (5-CH
3
), 25.8 (C-10),
3
= 0.24. [α]20 ). 1H NMR
D 2 2
= –10.8 (c = 0.99, CH Cl
2
2
syn-13: R
f
(
(
1
=
1
2
CH
4
H
1
500 MHz, CDCl
3
): δ = 1.49–1.55 (m, 2 H, 4ЈЈ-H), 1.61 (d, J =
.5 Hz, 3 H, 9-CH ), 1.69 (d, J = 1.5 Hz, 3 H, 10-H), 1.71 (dd, J
1.4, 0.9 Hz, 3 H, 2ЈЈ-CH ), 1.77 (d, J = 1.5 Hz, 3 H, 5-CH ),
.75–1.82 (m, 1 H, 2-H), 1.97–2.20 (m, 7 H, 3ЈЈ-H, 6-H, 7-H, OH),
.70–2.75 (m, 1 H, CH OH), 3.69 (ddd, J = 10.8, 4.9, 3.9 Hz, 1 H,
OH), 3.80 (ddd, J = 10.8, 7.7, 3.5 Hz, 1 H, CH OH),
.58 (ddd, J = 9.3, 4.2, 1.5 Hz, 1 H, 3-H), 4.68–4.70 (m, 1 H, 1ЈЈ-
), 4.70–4.73 (m, 1 H, 1ЈЈ-H ), 5.12 (ddqq, J = 7.3, 7.3, 1.5,
.5 Hz, 1 H, 8-H), 5.41 (dq, J = 9.4, 1.5 Hz, 1 H, 4-H) ppm.
NMR (125 MHz, CD Cl ): δ = 17.8 (9-CH ), 22.5 (2ЈЈ-CH ), 23.7
5-CH ), 24.3 (C-4ЈЈ), 25.8 (C-10), 26.5 (C-7), 32.4 (C-6), 35.7 (C-
ЈЈ), 44.5 (C-2), 64.3 (CH OH), 71.4 (C-3), 110.3 (C-1ЈЈ), 124.0 (C-
), 125.3 (C-4), 132.8 (C-9), 140.4 (C-5), 145.8 (C-2ЈЈ) ppm. FTIR
3
1
(
(
3
3
–
1
m), 885 (s), 839 (w), 741 (w) cm . MS (EI): m/z (%) = 306.2 (1)
2
+
+
+
[
M] , 291.2 (1) [M – Me] , 263.2 (1) [M–CMe
2
] , 248.2 (9) [M–
a
H
b
a b
H
+
+
Me
1
[C
2
COH] , 231.2 (4) [M–Me
2
CO
2
] , 205.2 (3), 194.2 (9), 178.1 (6),
+
+
68.1 (12), 153.1 (8) [nerol] , 135.1 (21) [C10
H
15] , 123.1 (11)
b
a
+
+
+
1
3
9
H
15] , 109.1 (31), 95.1 (100) [C
7
H
11] , 81.1 (74) [C
6
H
9
] , 69.1
C
+
+
+
(
86) [Me
2
CCHCH
2
] , 59.0 (49) [Me
2
COH] , 41.0 (40) [allyl] , 29.0
H O [M] 306.2559; found
34 2
2
2
3
3
+
(
3
6). HRMS (EI): m/z calcd. for C20
06.2562.
(
3
8
3
2
= 0.85 (hexanes/EtOAc, 2:1). 1H NMR (500 MHz,
): δ = 1.22–1.28 (m, 1 H, 2-H), 1.33 (q, J = 0.8 Hz, 3 H,
-eq), 1.44 (q, J = 0.8 Hz, 3 H, CH -ax), 1.64 (d, J = 1.2 Hz, 3
), 1.62–1.67 (m, 1 H, 4ЈЈ-H ), 1.69 (d, J = 1.4 Hz, 3 H,
0-H), 1.71 (dd, J = 1.4, 0.8 Hz, 3 H, 2ЈЈ-CH ), 1.74 (dd, J = 1.5,
.6 Hz, 3 H, 5-CH ), 1.82 (dddd, J = 13.7, 9.4, 9.4, 5.3 Hz, 1 H,
ЈЈ-H ), 1.95 (dddd, J = 14.5, 9.4, 6.7, 1.5 Hz, 1 H, 3ЈЈ-H ), 2.00–
.16 (m, 4 H, 3ЈЈ-H , 6-H, 7-H ), 2.44–2.48 (m, 1 H, 7-H ), 3.65
axO), 3.92 (ddd, J = 11.6, 2.9,
axO), 4.67–4.68 (m, 1 H, 1ЈЈ-H ), 4.69–4.70 (m,
), 4.77 (dd, J = 8.0, 2.8 Hz, 1 H, 3-H), 5.08 (ddqq, J =
.4, 7.4, 1.4, 1.4 Hz, 1 H, 8-H), 5.23 (dq, J = 8.0, 1.5 Hz, 1 H, 4-
anti-14: R
f
(
2
(
ATR): ν˜ = 3334 (br m), 3072 (w), 2967 (m), 2934 (m), 2912 (s),
881 (m), 2858 (m), 2359 (w), 1649 (w), 1451 (s), 1376 (s), 1109
w), 1094 (w), 1033 (s), 986 (s), 884 (vs), 846 (w), 817 (w), 763
CD
CH
2
Cl
2
3
3
H, 9-CH
3
a
–
1
+
+
(w) cm . MS (EI): m/z (%) = 266.1 (4) [M] , 248.2 (5) [M – H
2
O] ,
1
0
4
2
3
+
+
2
35.2 (5) [M – H
2
O (ϫ2)] , 217.2 (6) [M – H
2
O – CH
2
OH] , 194.2
3
+
+
(6), 179.1 (5), 153.1 (8) [C10
H
17O] , 135.1 (21), 128.1 (12) [C
9
H
15] ,
b
a
+
1
09.1 (24), 109.1 (24), 95.1 (66) [C
7
H
12] , 81.1 (32), 69.1 (100)
b
a
b
+
+
[
Me
2
CCHCH
2
] , 59.0 (30), 41.0 (38) [allyl] . HRMS (EI): m/z
O [M] 266.2246; found 266.2251.
30 2
(dd, J = 11.6, 1.8 Hz, 1 H, CHeqH
+
calcd. for C17
H
1
1
7
.3 Hz, 1 H, CHeq
H, 1ЈЈ-H
H
b
1
a
anti-13: R
f
= 0.24. H NMR (500 MHz, CDCl
H, 4ЈЈ-H), 1.60 (d, J = 1.1 Hz, 3 H, 9-CH ), 1.69 (d, J = 1.5 Hz,
H, 10-H), 1.71 (dd, J = 1.4, 0.9 Hz, 3 H, 2ЈЈ-CH ), 1.77 (d, J =
.5 Hz, 3 H, 5-CH ), 1.82–1.88 (m, 1 H, 2-H), 1.97–2.20 (m, 7 H,
ЈЈ-H, 6-H, 7-H, OH), 2.54–2.59 (m, 1 H, CH OH), 3.61–3.66 (m,
H, CH OH), 3.72–3.78 (m, 1 H, CH OH), 4.52–4.57 (m, 1
), 4.70–4.73 (m, 1 H, 1ЈЈ-H ),
.14 (ddqq, J = 7.4, 7.4, 1.4, 1.4 Hz, 1 H, 8-H), 5.41 (dq, J = 9.4,
3
): δ = 1.49–1.55 (m,
2
3
1
3
1
3
1
3
H) ppm. C NMR (125 MHz, CD
CH -ax), 22.3 (C-4ЈЈ), 22.5 (2ЈЈ-CH
7.0 (C-7), 30.0 (CH -eq), 33.0 (C-6), 36.1 (C-3ЈЈ), 39.5 (C-2), 62.9
CH O), 69.4 (C-3), 98.7 (Me C), 110.1 (C-1ЈЈ), 123.6 (C-8), 125.2
C-4), 133.4 (C-9), 138.6 (C-5), 146.6 (C-2ЈЈ) ppm.
2
Cl
2
): δ = 17.9 (9-CH
3
), 19.4
3
(
3
3
), 23.2 (5-CH
3
), 25.9 (C-10),
3
2
3
2
(
(
2
2
a
H
b
a b
H
H, 3-H), 4.68–4.70 (m, 1 H, 1ЈЈ-H
5
1
b
a
Supporting Information (see footnote on the first page of this arti-
): δ = 17.9 cle): Further experimental results, Mosher method, GC and
), 25.6 (C-4ЈЈ), 25.9 (C-10), NOESY spectra for configuration assignment as well as NMR
6.5 (C-7), 32.3 (C-6), 35.7 (C-3ЈЈ), 46.0 (C-2), 64.3 (CH OH), 71.0 spectra of all new compounds.
13
.5 Hz, 1 H, 4-H) ppm. C NMR (125 MHz, CD
), 22.5 (2ЈЈ-CH ), 23.7 (5-CH
2 2
Cl
(9-CH
3
3
3
2
2
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
13

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
S. Kriening, A. Evagelou, B. Claasen, A. Baro, S. Laschat
FULL PAPER
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Acknowledgments
Generous financial support by the German Ministerium für Wis-
senschaft, Forschung und Kunst des Landes Baden-Württemberg,
the Fonds der Chemischen Industrie and the Deutsche Forschungs-
gemeinschaft (DFG) is gratefully acknowledged.
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Received: June 11, 2014
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Published Online: ᭿
14
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42736
/KAP1
Date: 03-09-14 19:44:18
Pages: 15
Asymmetric Evans syn-Aldol Reactions
Asymmetric Aldol Reactions
The asymmetric Evans aldol reaction could
be successfully applied to terpene-based
S. Kriening, A. Evagelou, B. Claasen,
A. Baro, S. Laschat* ....................... 1–15
(E)- and (Z)-aldehydes and N-acyloxazol-
idinones, giving syn-aldol adducts with
high selectivity. Isomerization at the double
bond was not observed.
Asymmetric Evans syn-Aldol Reactions of
Terpene-Derived Enals: Scope and Limi-
tations
Keywords: Aldol reactions / Terpenoids /
Boron / C–C coupling / Configuration de-
termination
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
15