Stereoselective synthesis of β-proline derivatives from allylamines via domino hydroformylation/wittig olefination and aza-michael addition

Article abstract of DOI:10.1002/adsc.201000016

Under appropriate reaction conditions, a domino hydroformylation/Wittig olefination can be accomplished with derivatives of allylamines and stabilized Wittig ylides. A further highly diastereoselective aza-Michael reaction yields β-proline derivatives. These are, for example, useful as building blocks for alkaloid syntheses.

Full text of DOI:10.1002/adsc.201000016

FULL PAPERS
DOI: 10.1002/adsc.201000016
Stereoselective Synthesis of b-Proline Derivatives from
Allylamines via Domino Hydroformylation/Wittig Olefination
and Aza-Michael Addition
Andreas Farwicka and Gꢀnter Helmchena,*
a
Organisch-Chemisches Institut der Ruprecht-Karls-Universitꢁt Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,
Germany
Fax : (+49)-6221-54-4205; phone: (+49)-6221-54-8401; e-mail: g.helmchen@oci.uni-heidelberg.de
Received: January 6, 2010; Published online: March 23, 2010
Abstract: Under appropriate reaction conditions, a These are, for example, useful as building blocks for
domino hydroformylation/Wittig olefination can be alkaloid syntheses.
accomplished with derivatives of allylamines and sta-
bilized Wittig ylides. A further highly diastereoselec- Keywords: asymmetric synthesis; catalysis; domino
tive aza-Michael reaction yields b-proline derivatives. reactions; hydroformylation; Wittig olefination
Introduction
hydrogenated under the conditions of the hydrofor-
mylation, except in the case of disubstituted stabilized
The hydroformylation of allyl- and homoallylamines Wittig ylides leading to a-substituted a,b-unsaturated
yields g- and d-amino aldehydes, respectively, which carboxylic acid derivatives.[12,13] We are pleased to
can undergo domino-type[1,2] cyclizations and hydroge- report that we have found conditions allowing the
nations to furnish medicinally interesting pyrrolidine direct preparation of a,b-unsaturated carbonyl com-
or piperidine derivatives.[3,4] These procedures often pounds C under hydroformylation conditions for the
proceed with higher yield than conventional sequen- first time (Scheme 1).
tial syntheses, because side reactions of the hydrofor-
The intramolecular aza-Michael reaction usually
mylation, for example, aldol reaction and reduction of proceeds with high cis-diastereoelectivity if 2,6-substi-
the aldehyde,[5] are suppressed because of the low tuted piperidines are formed.[11,14] The analogous for-
concentration of the aldehyde.
mation of 2,5-substituted pyrrolidines has often been
Recently we have reported very efficient syntheses conducted in a domino manner in combination with a
of chiral pyrrolidines via the combination of an Ir-cat- Wittig or Wadsworth–Emmons olefination.[15] The
alyzed allylic substitution[6,7] and a hydroformylation/ trans-configuration of the products is generally pre-
reduction.[8] Other groups have developed corre- ferred. The diastereoselectivity is usually high for re-
sponding syntheses of piperidines.[9,10] The success of actions of compounds C with R=CO2R’, while it is
this approach was an incentive to try further combina- less predictable for cases with R=alkyl.[15d] In our
tions of the allylic substitution and the hydroformyla-
tion reaction. Herein we report syntheses of pyrroli-
dine derivatives by a domino hydroformylation/Wittig
olefination, applied to allylamine derivatives, followed
by a separate aza-Michael addition (Scheme 1). Re-
cently, Breit, Mann and co-workers have carried out
corresponding experiments with homoallylamine de-
rivatives. However, in these examples the Wittig reac-
tion was conducted sequentially after the hydroformy-
lation step, although in one pot.[11]
In pioneering studies, Breit et al. have shown that
the combination of a hydroformylation reaction with
a Wittig olefination, using stabilized ylides A, is a reli-
able method for the formation of carbon-carbon
bonds.[12] Unfortunately, the resultant enoates were Scheme 1. Access to b-proline derivatives.
Adv. Synth. Catal. 2010, 352, 1023 – 1032
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Table 1. Domino hydroformylation/Wittig olefination with the N,N-diacylamine 1a as test substrate.
Entry
Ligand
H2/CO
p [bar]
T [8C]
Time [h]
3a[a] [%]
4a[a] [%]
Conversion[a] [%]
1
2
3
4
5
6
7
XP
XP
BP
BP
BP
BP
BP
1:3
1:1
1:1
1:1
1:1
1:1
1:1
10
5
5
5
5
60
70
50
50
50
50
50
11
10
10
8
6
5
38
84.5
85
0
38
15.5
15
13
7.5
5.5
5
100
100
100
100
100
100
87
92.5
94.5
95
5
1
31
[a]
Determined by GC after removal of the formyl group to give 5a (cf. Table 3).
group, it was found that the cyclization of urethanes,
Early experiments were carried out with Xantphos
e.g., PG1 =Boc or Cbz, generally proceeds with as ligand. A synthesis gas pressure of 10 bar with a
almost perfect trans-diastereoselectivity at a reaction low partial pressure of H2 (H2/CO 1:3) was chosen in
temperature of ꢀ788C upon use of KO-t-Bu as order keep the level of hydrogenation low (Table 1,
base.[15a,16]
entry 1). At a reaction temperature of 608C conver-
sion was low after 11 h. Full conversion was reached
by increase of the reaction temperature to 708C with
a ratio H2/CO=1:1 (5 bar). Under these conditions
the reaction was complete after 10 h, and 15.5% of
Results and Discussion
The requisite chiral allylamine derivatives were pre- the hydrogenated product 4a were formed (Table 1,
pared with high enantiomeric excess using the estab- entry 2).
lished asymmetric Ir-catalyzed allylic amination.[17]
It was possible to lower the reaction temperature to
The N,N-diacylamine 1a[18] served as test substrate 508C when Biphephos was the ligand. However, the
(Table 1). For the hydroformylation reaction, the li- ratio 3a/4a=85:15 was essentially unchanged
gands Xantphos[19] and Biphephos[20] (Figure 1) were (Table 1, entries 3 and 4). Improvement was obtained
used; a ratio ligand/Rh=5:1 was chosen in order to by lowering the reaction time to 5 h. This sufficed to
ensure a high degree of n/iso-selectivity. In prior tests get full conversion, with a ratio 3a/4a=94.5:5.5
toluene was found to be the solvent of choice. For the (Table 1, entry 6). Finally, it turned out that full con-
1
analytical evaluation (GC, H NMR) of the hydrofor- version could be achieved at atmospheric pressure of
mylation/Wittig olefination, it was necessary to synthesis gas (H2/CO 1:1) (Table 1, entry 7). Thus, it
remove the formyl protecting group and produce was not necessary to run the reaction in an autoclave;
compound 5a (cf. Table 3), which could be analyzed. this rendered analytical monitoring convenient.
The results are summarized in Table 1.
The graph in Figure 2, describing conversion vs. re-
action time, shows that the reaction proceeds without
an induction period under the conditions according to
entry 7 of Table 1. The precise data allowed us to es-
tablish optimal reaction conditions for the reaction of
the allylamine 1a, i.e., reaction time 7.5 h, conversion
99%, selectivity of 3a/4a=97:3.
The above very user-friendly reaction conditions
were used to assess the scope of the domino reaction
with a variety of allylamine derivatives and represen-
tative stabilized Wittig ylides (Table 2). TLC was used
for monitoring of the conversion. The products 3/4
were obtained in 72–95% yield. In order to determine
the content of the saturated products 4 precisely, sam-
ples of these were prepared by catalytic hydrogena-
tion of the products 3/4 under standard conditions.[21]
Figure 1. Ligands used for rhodium-catalyzed hydroformyla-
tion reactions.
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Adv. Synth. Catal. 2010, 352, 1023 – 1032

Stereoselective Synthesis of b-Proline Derivatives from Allylamines
amines are used as starting materials. The key step is
a domino hydroformylation/Wittig olefination. Condi-
tions were found that avoid hydrogenation of the
double bond created in the Wittig reaction. A subse-
quent intramolecular aza-Michael addition can be
controlled to give trans-2,5-disubstituted pyrrolidines
with excellent diastereoselectivity.
Experimental Section
General Methods
All reactions were carried out under an atmosphere of
argon with dry solvents. TLC: Macherey & Nagel Polygram
Sil G/UV precoated sheets, visualization of spots by treat-
ment with aqueous KMnO4 or a solution of ninhydrin in
EtOH (1%). Flash column chromatography: Fluka silica gel
60 (0.032–0.062 mm). 1H and 13C NMR spectra: Bruker
DRX 200, DRX 300 or a DRX 500; chemical shifts relative
to residual non-deuterated solvent peaks (1H NMR: CDCl3
d=7.26, toluene-d8 d=2.09; 13C NMR: CDCl3 d=77.2, tolu-
ene-d8 d=20.4). HR-MS: JEOL JMS-700 (FAB+) or FT-
ICR-MS (ESI+). HPLC: Hewlett Packard 1090 or 1100
equipped with columns Chiralcel OD-H (25 cmꢃ0.46 cm)
with precolumn OD-H (5 cmꢃ0.46 cm) or Chiralpak AD-H
(25 cmꢃ0.46 cm) with precolumn AD-H (5 cmꢃ0.46 cm)].
GC: Hewlett Packard 5890 series II equipped with columns
HP-1 cross-linked methylsilicone gum (25 mꢃ0.2 mm,
0.33 mm film thickness) or Chrompack Chirasil-Dex perme-
thyl b-cyclodextrin (50 mꢃ0.25 mm, 25 mm film thickness).
Elemental analysis: Microanalytical Laboratory of the Or-
ganisch-Chemisches Institut, Universitꢁt Heidelberg.
Figure 2. Domino hydroformylation/Wittig olefination under
conditions according to Table 1, entry 7.
E/Z-Selectivity was typical for the Wittig olefination
with stabilized ylids, ca. 97:3; as its quantitative evalu-
1
ation by H NMR was not very precise because of
fairly broad signals, typical for carbamates, we present
conservative values in Table 2.
The N,N-diacylamines 3 were converted to the
mono-protected amides 5 (Table 3), which were the
starting materials of the aza-Michael reaction. The se-
lective deprotection of the formyl or the Boc group
was effected with KOH (cat.)/methanol or with TFA/
CH2Cl2, respectively (yields: 50–99%).
The aza-Michael reactions to yield the pyrrolidines
6 were effected with KO-t-Bu (0.8 equiv.) as base at a
reaction temperature of ꢀ788C in THF as solvent. A
reaction time of 20 min sufficed, and this ensured ki-
netic control of the reaction according to control ex-
periments with the ester 5b. The trans-diastereoiso-
mers 6a–6e were obtained in good to excellent yields
General Procedure 1: Domino Hydroformylation/
Wittig Olefination
In a Schlenk-tube flushed with argon, a solution of allyl-
A
1
(1.0 equiv.), ylide
2
(1.5 equiv.),
AHCTUNGTRENNUNG
toluene (0.06M) was stirred for 5 min at room temperature.
Argon was exchanged for synthesis gas and a balloon filled
with H2/CO 1:1 was added, keeping the apparatus essentially
at atmospheric pressure. The mixture was heated at 508C
until TLC monitoring showed full consumption of the start-
ing material. The crude product was directly subjected to
column chromatography on silica gel (petroleum ether/ethyl
acetate).
1
(68–97%). No cis-isomers were detected by H NMR
under the reaction conditions stated in Table 3. Ac-
cordingly, the diastereoselectivity of the reaction is
almost perfect.
The enantiomeric excess was determined for three
of the 2,5-disubstituted pyrrolidines 6 (Table 3, en-
tries 3, 5 and 7). It was found to be equal to that of
the chiral allylamine derivatives 1. Therefore, no race-
mization had occurred in the hydroformylation reac-
tion. This is remarkable, because olefins with a chiral-
ity center in an allylic position are prone to partial
racemization or epimerization in transition metal-cat-
alyzed reactions.[22]
General Procedure 2: Cleavage of the N-Formyl
Group (Deprotection Procedure a of Table 3)
A solution of a formyl-protected ester 3 (a, c, f, g)
(1.0 equiv.) and KOH (20–40 mol%) in methanol (0.2M)
was stirred until TLC monitoring showed full conversion of
the starting material. The solvent was removed under re-
duced pressure, and the residue was subjected to column
chromatography on silica gel (petroleum ether/ethyl ace-
tate).
Conclusions
In summary, we are describing a short route to chiral
b-proline derivatives, in which N-protected allyl-
Adv. Synth. Catal. 2010, 352, 1023 – 1032
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Table 2. Domino hydroformylation/Wittig olefination under optimized conditions.
Entry
1
Product
Time [h]
9
Ratio 3/4[a]
Ratio E/Z[a]
>91:09[d]
Yield of 3[b,c] [%]
3a
3b
3c
95:05
91
2
3
5
95:05
94:06
>95:05
>95:05
87
94
12
4
5
3d
3e
6
97:03
98:02
>95:05
>95:05
92
92
5.5
6
7
3f
3g
5.5
9
91:09
95:05
>95:05
>95:05
72
95
8
3h
3i
13
81:19
91:09
>95:05
>95:05
77
90
9
5.5
10
3j
12.5
5
84:16
93:07
>95:05
>95:05
75
87
11
3k
[a]
1
Determined by H NMR of the crude product.
Isolated yield.
[b]
[c]
[d]
1
Purity >95%, determined by H NMR.
Determined by GC [HP-1 cross-linked methylsilicon gum (25 mꢃ0.2 mm, 0.33 mm film thickness), temperature program:
508C (1 min), 208Cminꢀ1, 2508C (12 min): tR (5a)=13.3 min, tR (dihydro-5a)=13.8 min] after cleavage of the formyl
group. The formulae of 5a and 5b are given in Table 3.
General Procedure 3: Cleavage of the N-Boc Group
(Deprotection Procedure b of Table 3)
at room temperature. The mixture was stirred until TLC
monitoring showed complete conversion of the starting ma-
terial. NaOH solution (3M) was added, the layers were sep-
arated, and the aqueous phase was extracted with CH2Cl2.
An N,N-diboc-amide 3 (d, b, e) (1.0 equiv.) was dissolved in
CH2Cl2 (0.05M) and TFA (1.4 equiv.) was added dropwise
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Stereoselective Synthesis of b-Proline Derivatives from Allylamines
Table 3. Selective deprotection and intramolecular aza-Michael reaction.
Entry
3
R1
R2
R3
Deprotonation method Yield of 5 [%] Yield of 6 [%] ee[a] [%] of 6
1
2
3
4
5
6
7
a
b
c
d
e
f
n-Pr
Ph
Ph
n-Pr
Boc CHO
Boc Boc
Boc CHO
Boc Boc
Boc Boc
Boc CHO
a
b
a
b
b
a
a
89 (5a)
99 (5b)
93 (5b)
81 (5a)
81 (5c)
68 (5d)
71 (5e)
77 (6a)
80 (6b)
96
97
94
n-Hept
CH2OCPh3
CH2OSiACTHUNGTERN(UNG t-Bu)Ph2 Boc CHO
97 (6c)
86 (6d)
91 (6e)
g
[a]
Determined by chiral HPLC.
The combined organic layers were dried over Na2SO4, fil-
tered and concentrated under vacuum. The crude product
was purified by column chromatography on silica gel (petro-
leum ether/ethyl acetate).
7.3 Hz, 3H), 1.15–1.28 (m, 4H), 1.45–1.69 (m, 4H), 1.52 (s,
9H), 1.79–1.94 (m, 2H), 2.27 (t, J=7.5 Hz, 3H), 3.64 (s,
3H), 4.30–4.40 (m, 1H), 9.23 (s, 1H); 13C NMR (CDCl3,
75 MHz): d=14.0, 19.8, 24.8, 26.2, 28.2, 32.3, 34.0, 34.8, 51.6,
52.6, 83.9, 153.1, 164.2, 174.1; HR-MS (ESI+): m/z=
316.2123 [M+H]+, calcd. for C16H30NO5: 316.2119.
General Procedure 4: Diastereoselective
Intramolecular Aza-Michael Addition
Methyl (2E,6S)-6-[Bis(tert-butoxycarbonyl)amino]-6-phe-
nylhex-2-enoate (3b) (Table 2, entry 2): GP1 was carried out
Under an atmosphere of argon in a Schlenk tube, a solution
of an a,b-unsaturated carbonyl compound 5 (1.0 equiv.) in
dry THF (0.09M) was cooled to ꢀ788C. Then KO-t-Bu
(0.8 equiv.) was added, and the mixture was stirred at this
temperature for 20 min, when TLC monitoring showed full
conversion. Saturated aqueous NH4Cl was added, and the
mixture was allowed to reach room temperature. It was then
extracted three times with Et2O. The combined organic
layers were washed with brine, dried over Na2SO4, filtered
and concentrated under vacuum. The crude product was pu-
rified by column chromatography on silica gel (petroleum
ether/ethyl acetate).
with RhACHTUNTRGNE(UNG acac)(CO)2 (0.8mg, 3.2 mmol), Biphephos (12.5mg,
15.9 mmol), Ph3P=CHCO2Me (160mg, 0.478mmol), amide
1b (105mg, 0.319mmol) and toluene (5.3mL); reaction
time: 5 h; ratio 3b:4b=95:05 (1H NMR). Column chroma-
tography on silica gel (petroleum ether/ethyl acetate 4:1) af-
forded 3b (yield: 116mg, 0.277mmol, 87%) as a colourless
oil. TLC (petroleum ether/ethyl acetate 4:1, KMnO4): Rf
(2b)=0.52, Rf (3b)=0.38; [a]2D0: ꢀ40.3 (c 0.93, CHCl3);
1H NMR (CDCl3, 300 MHz): d=1.38 (s, 18H), 2.17–2.50 (m,
4H), 3.72 (s, 3H), 5.36 (dd, J=9.5 Hz, J=5.6 Hz, 1H), 5.88
(dt, J=15.7 Hz, J=1.3 Hz, 1H), 7.02 (dt, J=15.6 Hz, J=
6.6 Hz, 1H), 7.21–7.37 (m, 5H); 13C NMR (CDCl3,
75 MHz): d=28.0, 29.4, 30.3, 51.6, 58.3, 82.5, 121.6, 127.3,
127.4, 128.3, 140.4, 148.5, 153.2, 167.1; HR-MS (FAB+):
m/z=420.2418 [M+H]+, calcd. for C23H34NO6: 420.2386;
elem. anal. calcd. for C23H33NO6: C 65.85, H 7.93, N 3.34;
found: C 65.62, H 7.82, N 3.41.
Analytical Data for Methyl (6S)-6-[Bis(tert-butoxycarbo-
nyl)amino]-6-phenylhexanoate (4b): Colourless oil. [a]2D0:
ꢀ39.3 (c 0.88, CHCl3); 1H NMR (CDCl3, 300 MHz): d=
1.33–1.48 (m, 2H, 4-H), 1.38 (s, 18H), 1.67–1.78 (m, 2H),
2.04–2.15 (m, 1H), 2.18–2.29 (m, 1H), 2.34 (t, J=7.6 Hz,
2H), 3.66 (s, 3H), 5.33 (dd, J=9.4 Hz, J=6.2 Hz, 1H), 7.19–
7.37 (m, 5H); 13C NMR (CDCl3, 75 MHz): d=25.0, 26.3,
28.0, 31.5, 34.2, 51.6, 58.8, 82.3, 127.1, 127.4, 128.2, 140.9,
153.3, 174.1; HR-MS (ESI+): m/z=422.2548 [M+H]+, calcd.
for C23H36NO6: 422.2548.
Methyl
non-2-enoate (3a) (Table 2, entry 1): GP1 was carried out
with Rh(acac)(CO)2 (0.7 mg, 2.6 mmol), Biphephos (10.4 mg,
(2E,6S)-6-[Acetyl(tert-butoxycarbonyl)amino]-
ACHTUNGTRENNUNG
13.2 mmol), Ph3P=CHCO2Me (132 mg, 0.396 mmol), amide
1a (60 mg, 0.264 mmol) and toluene (4.5 mL); reaction time:
9 h; ratio 3a:4a=95:05 (1H NMR). Column chromatography
on silica gel (petroleum ether/ethyl acetate 4:1) afforded 3a
(yield: 75 mg, 0.239 mmol, 91%) as a yellowish oil. TLC (pe-
troleum ether/ethyl acetate 4:1, KMnO4): Rf (1a)=0.63, Rf
(3a)=0.35; [a]2D0: ꢀ6.7 (c 0.57, CHCl3); 1H NMR (CDCl3,
300 MHz): d=0.88 (t, J=7.3 Hz, 3H), 1.16–1.28 (m, 2H),
1.46–1.58 (m, 1H), 1.53 (s, 9H), 1.64–1.73 (m, 1H), 1.82–
1.95 (m, 1H), 2.03–2.16 (m, 3H), 3.71 (s, 3H), 4.37 (bs, 1H),
5.79 (dt, J=15.7 Hz, J=1.4 Hz, 1H), 6.91 (dt, J=15.6 Hz,
J=6.7 Hz, 1H), 9.22 (s, 1H, CHO); 13C NMR (CDCl3,
75 MHz): d=14.0, 19.7, 28.2, 29.5, 31.0, 34.7, 51.6, 52.3, 84.2,
121.5, 148.4, 152.9, 164.2, 167.0; HR-MS (FAB+): m/z=
314.1989 [M+H]+, calcd. for C16H28NO5: 314.1968; elem.
anal. calcd. for C16H27NO5: C 61.32, H 8.68, N 4.47; found:
C 61.29, H 8.72, N 4.52.
Methyl (2E,6R)-6-[Acetyl(tert-butoxycarbonyl)amino]-6-
phenylhex-2-enoate (3c) (Table 2, entry 3): GP1 was carried
out with Rh
ACHTUNGTRENNUNG
(212 mg, 0.27 mmol),
8.065 mmol), amide 1c (1.405 g, 5.377 mmol) and toluene
(90 mL); reaction time: 12 h; ratio 3c:4c=94:06 (1H NMR).
Column chromatography on silica gel (petroleum ether/
Analytical Data for Methyl (6S)-6-[Acetyl(tert-butoxycar-
bonyl)amino]nonanoate (4a): Colourless oil. [a]2D0: +1.1 (c
1
0.72, CHCl3); H NMR (CDCl3, 300 MHz): d=0.87 (t, J=
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Andreas Farwick and Gꢀnter Helmchen
FULL PAPERS
ethyl acetate 4:1) afforded 3c (yield: 1.748 g, 5.032 mmol,
94%) as a colourless oil, which crystallized on standing; mp
100–1018C; TLC (petroleum ether/ethyl acetate 4:1,
KMnO4): Rf (1c)=0.47, Rf (3c)=0.31; [a]2D0: +74.4 (c 0.51,
KMnO4): Rf (1e)=0.62, Rf (3e)=0.49; [a]2D0: +5.7 (c 1.37,
CHCl3); H NMR (CDCl3, 300 MHz): d=0.86 (t, J=6.7 Hz,
1
3H), 1.25 (bs, 10H), 1.48 (s, 19H), 1.56–1.69 (m, 1H), 1.74–
1.83 (m, 1H), 1.92–2.05 (m, 1H), 2.17–2.25 (m, 2H), 3.71 (s,
3H), 4.09 (tt, J=10.0 Hz, J=5.2 Hz, 1H), 5.81 (dt, J=
15.6 Hz, J=1.5 Hz, 1H), 6.95 (dt, J=15.6 Hz, J=6.9 Hz,
1H); 13C NMR (CDCl3, 75 MHz): d=14.2, 22.8, 26.6, 28.2,
29.4, 29.5, 29.5, 31.9, 32.1, 33.6, 51.5, 57.3, 82.1, 121.3, 149.0,
153.6, 167.2; HR-MS (FAB+): m/z=442.3159 [M+H]+,
calcd. for C24H44NO6: 442.3169; elem. anal. calcd. for
C24H43NO6: C 65.28, H 9.81, N 3.17; found: C 65.48, H 9.67,
N 3.24.
1
CHCl3); H NMR (CDCl3, 300 MHz): d=1.37 (s, 9H), 2.17–
2.29 (m, 2H), 2.31–2.53 (m, 2H), 3.73 (s, 3H), 5.59 (dd, J=
9.6 Hz, J=6.0 Hz, 1H), 5.86 (dt, J=15.7 Hz, J=1.3 Hz,
1H), 6.99 (dt, J=15.6 Hz, J=6.7 Hz, 1H), 7.23–7.33 (m,
5H), 9.31 (s, 1H); 13C NMR (CDCl3, 75 MHz): d=28.0,
29.0, 29.5, 51.6, 53.7, 84.6, 121.8, 127.6, 127.6, 128.4, 139.4,
148.0, 152.6, 163.9, 167.0; HR-MS (FAB+): m/z=348.1809
[M+H]+, calcd. for C19H26NO6: 348.1811; elem. anal. calcd.
for C19H25NO5: C 65.69, H 7.25, N 4.03; found: C 65.50, H
7.31, N 4.03.
Analytical Data for Methyl (6R)-6-[Acetyl(tert-butoxycar-
bonyl)amino]-6-phenylhexanoate (4c): Colourless oil. [a]2D0:
+85.4 (c 0.80, CHCl3); 1H NMR (CDCl3, 300 MHz): d=
1.33–1.41 (m, 2H), 1.37 (s, 9H), 1.63–1.77 (m, 2H), 2.12–
2.31 (m, 2H), 2.33 (t, J=7.5 Hz, 2H), 3.66 (s, 3H), 5.58 (dd,
J=9.5 Hz, J=6.4 Hz, 1H), 7.21–7.34 (m, 5H), 9.31 (s, 1H);
13C NMR (CDCl3, 75 MHz): d=24.9, 26.3, 28.0, 30.2, 34.0,
51.6, 53.8, 84.3, 127.4, 127.6, 128.3, 139.9, 152.8, 163.9, 174.0;
HR-MS (ESI+): m/z=350.1970 [M+H]+, calcd. for
C19H28NO5: 350.1962.
Analytical Data for Methyl (6S)-6-[Bis(tert-butoxycarbo-
nyl)amino]tridecanoate (4e): Colourless oil. [a]2D0: ꢀ0.1 (c
1
0.74, MeOH); H NMR (CDCl3, 300 MHz): d=0.86 (t, J=
6.7 Hz, 3H), 1.25–1.36 (m, 12H), 1.43–1.53 (m, 2H), 1.48 (s,
18H), 1.58–1.65 (m, 2H), 1.72–1.86 (m, 2H), 2.29 (t, J=
7.6 Hz, 2H), 3.65 (s, 3H), 4.01–4.11 (m, 1H); 13C NMR
(CDCl3, 75 MHz): d=14.2, 22.8, 25.0, 26.3, 26.7, 28.2, 29.4,
29.5, 31.9, 33.4, 33.6, 34.2, 51.6, 57.7, 81.8, 153.8, 174.2; HR-
MS (ESI+): m/z=444.3329 [M+H]+, calcd. for C14H45NO6:
444.3320.
Methyl (2E,6S)-6-[Acetyl(tert-butoxycarbonyl)amino]-7-
(trityloxy)hept-2-enoate (3f) (Table 2, entry 6): GP1 was
Methyl (2E,6S)-6-[Bis(tert-butoxycarbonyl)amino]non-2-
enoate (3d) (Table 2, entry 4): GP1 was carried out with
RhACHTUNGTRENNUNG(acac)(CO)2 (1.4 mg, 5.3 mmol), Biphephos (21.0 mg,
carried out with RhACTHUNGTERN(NUG acac)(CO)2 (1.0 mg, 3.9 mmol), Biphe-
phos (15.3 mg, 19.4 mmol), Ph3P=CHCO2Me (197 mg,
0.584 mmol), amide 1f (178 mg, 0.389 mmol) and toluene
(6.5 mL); reaction time: 5.5 h; ratio 3f:4f=91:09
(1H NMR). Column chromatography on silica gel (petro-
leum ether/ethyl acetate 4:1) afforded 3f (yield: 152 mg,
0.280 mmol, 72%) as a colourless oil which crystallized on
standing; mp 98–1008C; TLC (petroleum ether/ethyl acetate
4:1, KMnO4): Rf (1f)=0.48, Rf (3f)=0.28; [a]2D0: +25.7 (c
26.7 mmol), Ph3P=CHCO2Me (268 mg, 0.802 mmol), amide
1d (160 mg, 0.534 mmol) and toluene (9 mL); reaction time:
6 h; ratio 3d:4d=97:03 (1H NMR). Column chromatography
on silica gel (petroleum ether/ethyl acetate 30:1!9:1) af-
forded 3d (yield: 189 mg, 0.490 mmol, 92%) as a colourless
oil. TLC (petroleum ether/ethyl acetate 4:1, KMnO4): Rf
(1d)=0.64, Rf (3d)=0.54; [a]2D0: +7.3 (c 1.07, CHCl3);
1H NMR (CDCl3, 300 MHz): d=0.88 (t, J=7.3 Hz, 3H),
1.23–1.37 (m, 2H), 1.42–1.47 (m, 1H), 1.47 (s, 18H), 1.57–
1.64 (m, 1H), 1.75–1.83 (m, 1H), 1.95–2.02 (m, 1H), 2.16–
2.26 (m, 2H), 3.70 (s, 3H), 4.07–4.15 (m, 1H), 5.80 (dt, J=
15.6 Hz, J=1.5 Hz, 1H), 6.94 (dt, J=15.6 Hz, J=6.9 Hz,
1H); 13C NMR (CDCl3, 75 MHz): d=14.0, 19.8, 28.1, 29.5,
32.0, 35.8, 51.5, 57.0, 82.1, 121.3, 149.0, 153.6, 167.1; HR-MS
(FAB+): m/z=386.2558 [M+H]+, calcd. for C20H36NO6:
386.2543; elem. anal. calcd. for C20H35NO6: C 62.31, H 9.15,
N 3.63; found: C 62.48, H 9.29, N 3.61.
1
1.01, CHCl3); H NMR (CDCl3, 300 MHz): d=1.46 (s, 9H),
1.62–1.73 (m, 1H), 1.90–2.02 (m, 1H), 2.11–2.18 (m, 2H),
3.23 (dd, J=9.1 Hz, J=5.4 Hz, 1H), 3.44 (dd, J=9.0 Hz, J=
8.7 Hz, 1H), 3.74 (s, 3H), 4.79 (bs, 1H), 5.80 (dt, J=
15.7 Hz, J=1.4 Hz, 1H), 6.90 (dt, J=15.6 Hz, J=6.8 Hz,
1H), 7.22–7.42 (m, 15H), 9.31 (s, 1H); 13C NMR (CDCl3,
75 MHz): d=27.7, 28.1, 29.1, 51.6, 52.4, 63.5, 84.2, 86.6,
121.7, 127.1, 127.9, 128.7, 143.9, 148.0, 152.8, 164.0, 166.9;
HR-MS (FAB+): m/z=566.2470 [M+Na]+, calcd. for
C33H37NO6Na: 566.2519; elem. anal. calcd. for C33H37NO6: C
72.91, H 6.86, N 2.58; found: C 72.90, H 7.11, N 2.46.
Analytical Data for Methyl (6S)-6-[Bis(tert-butoxycarbo-
Analytical Data for Methyl (6S)-6-[Acetyl(tert-butoxycar-
bonyl)amino]-7-(trityloxy)heptanoate (4f): Colourless oil.
nyl)amino]nonanoate (4d): Colourless oil. [a]2D0: +3.8 (c
1
1
0.80, CHCl3); H NMR (CDCl3, 300 MHz): d=0.88 (t, J=
[a]2D0: +27.9 (c 1.30, CHCl3); H NMR (CDCl3, 300 MHz):
7.2 Hz, 3H), 1.23–1.38 (m, 4H, 4-H), 1.40–1.56 (m, 2H),
1.47 (s, 18H), 1.58–1.68 (m, 2H), 1.71–1.86 (m, 2H), 2.28 (t,
J=7.6 Hz, 2H), 3.64 (s, 3H), 4.03–4.13 (m, 1H); 13C NMR
(CDCl3, 75 MHz): d=14.1, 19.8, 25.0, 26.3, 28.1, 33.3, 34.2,
35.8, 51.6, 57.4, 81.8, 153.7, 174.2; HR-MS (ESI+): m/z=
388.2697 [M+H]+, calcd. for C20H38NO6: 388.2694.
d=1.21 (m, 2H), 1.47 (s, 9H), 1.54–1.68 (m, 3H), 1.73–1.85
(m, 1H), 2.30 (t, J=7.5 Hz, 2H), 3.23 (dd, J=9.1 Hz, J=
5.2 Hz, 1H), 3.43 (dd, J=8.9 Hz, J=8.9 Hz, 1H), 3.68 (s,
3H), 4.80 (bs, 1H), 7.23–7.45 (m, 15H), 9.35 (s, 1H);
13C NMR (CDCl3, 75 MHz): d=24.7, 25.8, 28.1, 28.9, 33.9,
51.6, 52.4, 63.7, 83.9, 86.5, 127.1, 127.3, 127.9, 128.0, 128.0,
128.7, 144.0, 153.0, 164.1, 175.0; HR-MS (ESI+): m/z=
546.2850 [M+H]+, calcd. for C33H40NO6: 546.2878.
Methyl (2E,6S)-6-[Bis(tert-butoxycarbonyl)amino]tridec-
2-enoate (3e) (Table 2, entry 5): GP1 was carried out with
Rh
G
Methyl (2E,6S)-6-[Acetyl(tert-butoxycarbonyl)amino]-7-
35.2 mmol), Ph3P=CHCO2Me (353 mg, 1.055 mmol), amide
1e (250 mg, 0.703 mmol) and toluene (12 mL); reaction
time: 5.5 h; ratio 3e:4e=98:02 (1H NMR). Column chroma-
tography on silica gel (petroleum ether/ethyl acetate 30:1!
9:1) afforded 3e (yield: 286 mg, 0.648 mmol, 92%) as a col-
ourless oil. TLC (petroleum ether/ethyl acetate 4:1,
{[tert-butyl
entry 7): GP1 was carried out with Rh
3.3 mmol), Biphephos (13.0 mg,
CHCO2Me (166 mg, 0.496 mmol), amide 1g (150 mg,
0.330 mmol) and toluene (5.5 mL); reaction time: 9 h; ratio
3g:4g=95:05 (1H NMR). Column chromatography on silica
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1028
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1023 – 1032

Stereoselective Synthesis of b-Proline Derivatives from Allylamines
gel (petroleum ether/ethyl acetate 4:1) afforded 3g (yield:
170 mg, 0.315 mmol, 95%) as a yellowish oil. TLC (petro-
leum ether/ethyl acetate 4:1, KMnO4): Rf (1g)=0.52, Rf
Benzyl AcetylACTHUNGRTENNU[G (1S,4E)-1-({[tert-butylACHTUNGTRENNUNG
methyl)-6-oxohept-4-en-1-yl]carbamate
entry 9): GP1 was carried out with RhACTHUNGTRENNNUG
1
(3g)=0.35, [a]2D0: +15.3 (c 0.50, CHCl3); H NMR (CDCl3,
8.5 mmol),
Biphephos
(33.5 mg,
300 MHz): d=1.00 (s, 9H), 1.50 (s, 9H), 1.61–1.72 (m, 1H),
1.91–2.04 (m, 1H), 2.09–2.17 (m, 2H), 3.68 (dd, J=10.2 Hz,
J=6.3 Hz, 1H), 3.72 (s, 3H), 4.01 (dd, J=9.4 Hz, J=9.4 Hz,
1H), 4.58–4.67 (m, 1H), 5.78 (dt, J=15.6 Hz, J=1.4 Hz,
1H), 6.89 (dt, J=15.6 Hz, J=6.8 Hz, 1H), 7.35–7.45 (m,
6H), 7.60–7.65 (m, 4H), 9.26 (s, 1H); 13C NMR (CDCl3,
75 MHz): d=19.3, 26.9, 27.1, 28.2, 29.2, 51.6, 54.3, 63.5, 84.3,
121.6, 127.9, 129.9, 129.9, 133.4, 133.4, 135.7, 135.7, 148.1,
152.8, 164.1, 167.0; HR-MS (ESI+): m/z=562.2601 [M+
Na]+, calcd. for C30H41NO5SiNa: 562.2595; elem. anal. calcd.
for C30H41NO6Si: C 66.76, H 7.66, N 2.60; found: C 66.75, H
7.76, N 2.59.
CHC(O)Me (406 mg, 1.277 mmol), amide 1i (415 mg,
0.851 mmol) and toluene (14 mL); reaction time: 5.5 h; ratio
3i:4i=91:09 (1H NMR). Column chromatography on silica
gel (petroleum ether/ethyl acetate 4:1) afforded 3i (yield:
429 mg, 0.769 mmol, 90%) as a yellowish oil. TLC (petro-
leum ether/ethyl acetate 9:1, KMnO4): Rf (1i)=0.48, Rf
1
(3i)=0.15; [a]2D0: +13.3 (c 0.68, CHCl3); H NMR (CDCl3,
300 MHz): d=0.98 (s, 9H), 1.59–1.70 (m, 1H), 1.92–2.04 (m,
1H), 2.08–2.15 (m, 2H), 2.18 (s, 3H), 3.70 (dd, J=10.2 Hz,
J=5.8 Hz, 1H), 4.01 (dd, J=9.5 Hz, J=9.5 Hz, 1H), 4.59–
4.71 (m, 1H), 5.19 (d, J=12.1 Hz, 1H), 5.25 (d, J=12.1 Hz,
1H), 5.97 (dt, J=15.8 Hz, J=1.3 Hz, 1H), 6.65 (dt, J=
16.0 Hz, J=6.7 Hz, 1H), 7.30–7.45 (m, 11H), 7.57–7.62 (m,
4H), 9.32 (s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.3,
26.8, 27.1, 27.1, 29.3, 54.8, 63.3, 69.1, 127.9, 128.6, 129.0,
129.0, 129.9, 130.0, 131.9, 133.3, 134.6, 135.7, 146.5, 154.1,
163.7, 198.4; HR-MS (ESI+): m/z=580.2489 [M+Na]+,
calcd. for C33H39NO5SiNa: 580.2490; elem. anal. calcd. for
C33H39NO5Si: C 71.06, H 7.05, N 2.51; found: C 71.25, H
7.12, N 2.51.
Analytical Data for Methyl (6S)-6-[Acetyl(tert-butoxycar-
bonyl)amino]-7-{[tert-butylACHTNUTRGNE(UNG diphenyl)silyl]oxy}heptanoate
(4g): Colourless oil. [a]2D0: +7.8 (c 1.06, CHCl3); 1H NMR
(CDCl3, 300 MHz): d=1.00 (s, 9H), 1.18–1.30 (m, 2H),
1.47–1.64 (m, 3H, 3-H), 1.50 (s, 9H), 1.69–1.85 (m, 1H),
2.26 (t, J=7.5 Hz, 2H), 3.64 (s, 3H), 3.56 (dd, J=9.8 Hz, J=
5.5 Hz, 1H), 4.01 (dd, J=9.6 Hz, J=9.6 Hz, 1H), 4.57–4.66
(m, 1H), 7.34–7.45 (m, 6H), 7.61–7.66 (m, 4H), 9.29 (s,
1H); 13C NMR (CDCl3, 75 MHz): d=19.3, 24.8, 25.9, 26.8,
28.2, 28.3, 34.0, 51.6, 54.4, 63.6, 83.9, 127.8, 129.8, 129.8,
133.5, 133.5, 135.6, 135.7, 153.0, 164.2, 174.0; HR-MS
(ESI+): m/z=564.2755 [M+Na]+, calcd. for C30H43NO6SiNa:
564.2752.
Analytical Data for Benzyl Acetyl[(1S)-1-({[tert-butyl-
AHCTUNGERTG(NNUN diphenyl)silyl]oxy}methyl)-6-oxoheptyl]carbamate (4i): Col-
ourless oil. [a]D20: +7.8 (c 0.63, CHCl3); 1H NMR (CDCl3,
300 MHz): d=0.98 (s, 9H), 1.10–1.20 (m, 2H), 1.40–1.52 (m,
3H), 1.70–1.83 (m, 1H), 2.08 (s, 3H), 2.31 (t, J=7.3 Hz,
2H), 3.66 (dd, J=10.2 Hz, J=5.6 Hz, 1H), 4.00 (t, J=
9.8 Hz, 1H), 4.59–4.69 (m, 1H), 5.18 (d, J=12.1 Hz, 1H),
5.24 (d, J=12.0 Hz, 1H), 7.28–7.45 (m, 11H), 7.57–7.62 (m,
4H), 9.33 (s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.2,
23.5, 25.9, 26.8, 28.3, 30.0, 43.5, 55.1, 63.4, 68.9, 127.4, 127.8,
128.1, 128.6, 128.9, 128.9, 129.9, 133.4, 134.8, 135.7, 135.7,
154.3, 163.6, 208.8; HR-MS (ESI+): m/z=582.2647 [M+
Na]+, calcd. for C33H41NO5SiNa: 582.2646.
tert-Butyl Acetyl
4-en-1-yl}carbamate (3h) (Table 2, entry 8): GP1 was carried
out with Rh(acac)(CO)2 (1.9 mg, 7.4 mmol), Biphephos
(29.2 mg, 37.1 mmol), Ph3P=CHC(O)Me (355 mg,
ACHTUNGTRENNUNG{(1S,4E)-6-oxo-1-[(trityloxy)methyl]hept-
ACHTUNGTRENNUNG
1.115 mmol), amide 1h (340 mg, 0.743 mmol) and toluene
(12.4 mL); reaction time: 13 h; ratio 3h:4h=81:19
(1H NMR). Column chromatography on silica gel (petro-
leum ether/ethyl acetate 4:1) afforded 3h (yield: 301 mg,
0.571 mmol, 77%) as a colourless foam. TLC (petroleum
ether/ethyl acetate 4:1, KMnO4): Rf (1h)=0.49, Rf (3h)=
0.15; [a]2D0: +21.0 (c 0.79, CHCl3); 1H NMR (CDCl3,
500 MHz): d=1.47 (s, 9H), 1.70 (ddt, J=13.5 Hz, J=7.8 Hz,
J=5.7 Hz, 1H), 1.98 (bs, 1H), 2.18 (dt, J=7.2 Hz, J=
7.2 Hz, 2H), 2.25 (s, 3H), 3.25 (dd, J=9.1 Hz, J=5.4 Hz,
1H), 3.45–3.48 (m, 1H), 4.79 (bs, 1H), 6.05 (d, J=15.9 Hz,
1H), 6.73 (dt, J=15.9 Hz, J=6.8 Hz, 1H), 7.25–7.33 (m,
9H), 7.40–7.42 (m, 6H), 9.31 (s, 1H); 13C NMR (CDCl3,
125 MHz): d=27.1, 27.9, 28.1, 29.3, 52.2, 63.6, 84.3, 86.7,
127.2, 128.0, 128.7, 131.9, 143.9, 146.7, 152.8, 164.0, 198.5;
HR-MS (ESI+): m/z=550.2565 [M+Na]+, calcd. for
C33H37NO5Na: 550.2564; elem. anal. calcd. for C33H37NO5: C
75.12, H 7.07, N 2.65; found: C 74.97, H 7.37, N 2.57.
Benzyl
methyl)-6-[methoxy
(3j) (Table 2, entry 10): GP1 was carried out with
Rh(acac)(CO)2 (0.6 mg, 2.3 mmol), Biphephos (9.0 mg,
11.4 mmol), Ph3P=CHC(O)N(OMe)Me (125 mg,
Acetyl{(1S)-1-({[tert-butylACHTNUGTREN(NUNG diphenyl)silyl]oxy}-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
0.345 mmol), amide 1j (112 mg, 0.230 mmol) and toluene
(3.8 mL); reaction time: 12.5 h; ratio 3j:4j=84:16
(1H NMR). Column chromatography on silica gel (petro-
leum ether/ethyl acetate 1:1) afforded 3j (yield: 130 mg,
0.216 mmol, 94%) as a yellow oil. TLC (petroleum ether/
ethyl acetate 4:1, KMnO4): Rf (1j)=0.52, Rf (3j)=0.05;
1
[a]2D0: +11.1 (c 1.34, CHCl3); H NMR (CDCl3, 300 MHz):
d=0.97 (s, 9H), 1.59–1.70 (m, 1H), 1.92–2.02 (m, 1H), 2.14
(dt, J=7.4 Hz, J=7.4 Hz, 1H), 3.22 (s, 3H), 3.67 (s, 3H),
3.69 (dd, J=10.2 Hz, J=5.7 Hz, 1H), 4.01 (dd, J=9.7 Hz,
J=9.7 Hz, 1H), 4.69 (bs, 1H), 5.18 (d, J=12.1 Hz, 1H), 5.25
(d, J=12.0 Hz, 1H), 6.33 (d, J=15.4 Hz, 1H), 6.85 (dt, J=
15.1 Hz, J=6.7 Hz, 1H), 7.29–7.45 (m, 11H), 7.57–7.62 (m,
4H), 9.34 (s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.2,
26.8, 27.1, 29.4, 32.5, 54.9, 61.8, 63.3, 69.0, 119.5, 127.9, 128.6,
128.9, 128.9, 129.9, 129.9, 133.3, 133.3, 134.7, 135.7, 146.0,
154.2, 163.8, 166.7; HR-MS (ESI+): m/z=603.2886 [M+H]+,
calcd. for C34H43N2O6Si: 603.2885; elem. anal. calcd. for
C34H42N2O6Si: C 67.75, H 7.02, N 4.65; found: C 67.74, H
7.22, N 4.46.
Analytical Data for tert-Butyl Acetyl{(1S)-6-oxo-1-
[(trityloxy)methyl]heptyl}carbamate (4h): Colourless oil.
1
[a]2D0: ꢀ6.2 (c 0.57, CHCl3); H NMR (CDCl3, 300 MHz): d=
1.17–1.28 (m, 2H,), 1.47 (s, 9H), 1.51–1.62 (m, 3H), 1.72–
1.88 (m, 1H), 2.14 (s, 3H), 2.41 (t, J=7.4 Hz, 2H), 3.22 (dd,
J=9.1 Hz, J=5.2 Hz, 1H), 3.43 (t, J=8.7 Hz, 1H), 4.79 (bs,
1H), 7.24–7.5 (m, 15H), 9.34 (s, 1H); 13C NMR (CDCl3,
75 MHz): d=23.5, 25.8, 28.1, 28.5, 30.0, 43.6, 52.5, 63.7, 84.0,
86.5, 127.1, 127.39, 127.9, 128.1, 128.8, 144.0, 152.7, 164.1,
208.8; HR-MS (ESI+): m/z=552.2722 [M+Na]+, calcd. for
C33H39NO5Na: 552.2720.
Adv. Synth. Catal. 2010, 352, 1023 – 1032
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1029

Andreas Farwick and Gꢀnter Helmchen
FULL PAPERS
Analytical Data for Benzyl Acetyl
ACHTUNGTRENNUNG(diphenyl)silyl]oxy}methyl)-6-[methoxyACHTUGNTRENNNUG
N
column chromatography on silica gel (petroleum ether/ethyl
acetate 4:1) to afford 5a (yield: 376 mg, 1.32 mmol, 81%) as
a colourless oil. [a]2D0: ꢀ8.6 (c 1.00, CHCl3); 1H NMR
(CDCl3, 300 MHz): d=0.88 (t, J=6.8 Hz, 3H), 1.23–1.50
(m, 5H), 1.41 (s, 9H), 1.55–1.66 (m, 1H), 2.17–2.30 (m, 2H),
3.56 (bs, 1H), 3.69 (s, 3H), 4.27 (d, J=8.6 Hz, 1H), 5.81 (dt,
J=15.7 Hz, J=1.4 Hz, 1H), 6.94 (dt, J=15.6 Hz, J=6.9 Hz,
1H); 13C NMR (CDCl3, 75 MHz): d=14.1, 19.2, 28.5, 29.0,
34.3, 37.9, 50.3, 51.5, 79.1, 121.2, 149.0, 155.8, 167.1; HR-MS
(FAB+): m/z=286.1978 [M+H]+, calcd. for C15H28NO4:
286.2018; elem. anal. calcd. for C15H27NO4: C 63.13, H 9.54,
N 4.91; found: C 63.02, H 9.62, N 4.92.
Methyl (2E,6R)-6-[(tert-Butoxycarbonyl)amino]-6-phenyl-
hex-2-enoate (5b) (Table 3, entries 2 and 3): Method A:
GP2 was carried out with KOH (54.6 mg, 0.973 mmol),
amide 3c (1.690 g, 4.864 mmol) and MeOH (25 mL). TLC
monitoring [petroleum ether/ethyl acetate 4:1, KMnO4): Rf
(3c)=0.33, Rf (5b)=0.26] showed full conversion of the
starting material after 18 h. Column chromatography on
silica gel (petroleum ether/ethyl acetate 4:1) afforded 5b
(yield: 1.442 g, 4.515 mmol, 93%) as a white, waxy solid.
Method B: GP3 was carried out with TFA (4.5 mL,
0.06 mmol), amide 3b (18 mg, 0.043 mmol) and CH2Cl2
(1.0 mL). TLC monitoring [petroleum ether/ethyl acetate
4:1, KMnO4: Rf (3b)=0.57, Rf (5b)=0.37] showed full con-
version of the starting material after 7 h. The solvent was re-
moved under vacuum to afford 5b (yield: 15 mg, 0.43 mmol,
100%) as a colourless oil which crystallized on standing; mp
68–698C; [a]2D0: +23.5 (c 0.90, CHCl3); 1H NMR (CDCl3,
300 MHz): d=1.41 (s, 9H), 1.81–2.01 (m, 2H), 2.09–2.27 (m,
2H), 3.71 (s, 3H), 4.62 (bs, 1H), 4.82 (d, J=6.5 Hz, 1H),
5.80 (dt, J=15.6 Hz, J=1.3 Hz, 1H), 6.93 (dt, J=15.6 Hz,
J=6.8 Hz, 1H), 7.23–7.36 (m, 5H); 13C NMR (CDCl3,
75 MHz): d=28.5, 29.1, 35.2, 51.6, 54.7, 79.8, 121.6, 126.5,
127.6, 128.9, 142.2, 148.2, 155.3, 167.0; HR-MS (FAB+):
m/z=320.1844 [M+H]+, calcd. for C18H26NO4: 320.1862;
elem. anal. calcd. for C18H25NO4: C 67.69, H 7.89, N 4.39;
found: C 67.89, H 7.94, N 4.34.
Methyl (2E,6S)-6-[(tert-Butoxycarbonyl)amino]tridec-2-
enoate (5c) (Table 3, entry 5): GP3 was carried out with
TFA (56 mL, 0.761 mmol), amide 3e (240 mg, 0.543 mmol)
and CH2Cl2 (11.0 mL). TLC monitoring [petroleum ether/
ethyl acetate 9:1, KMnO4: Rf (3e)=0.40, Rf (5c)=0.18]
showed full conversion of the starting material after 18 h.
After work-up the crude product was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate
9:1) to afford 5c (yield: 150 mg, 0.439 mmol, 81%) as a col-
ourless oil. [a]D20: ꢀ1.5 (c 0.40, CHCl3); 1H NMR (CDCl3,
300 MHz): d=0.87 (t, J=6.7 Hz, 3H), 1.23–1.32 (m, 11H),
1.39–1.51 (m, 2H), 1.44 (s, 9H), 1.57–1.68 (m, 1H), 2.18–
2.33 (m, 2H), 3.56 (bs, 1H), 3.72 (s, 3H), 4.22 (d, J=9.2 Hz,
1H), 5.83 (dt, J=15.6 Hz, J=1.5 Hz, 1H), 6.96 (dt, J=
15.7 Hz, J=6.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=
14.2, 22.8, 26.0, 28.6, 29.0, 29.4, 31.9, 34.4, 35.8, 50.6, 51.5,
79.2, 121.3, 149.0, 155.8, 167.2; HR-MS (FAB+): m/z=
342.2632 [M+H]+, calcd. for C19H36NO4: 342.2644; elem.
anal. calcd. for C19H35NO4: C 66.83, H 10.33, N 4.10; found:
C 67.06, H 10.46, N 4.00.
oxohex-4-en-1-yl}carbamate (4j): Colourless oil. [a]2D0: +6.4
(c 0.51, CHCl3); 1H NMR (CDCl3, 300 MHz): d=0.97 (s,
9H), 1.19–1.26 (m, 2H), 1.44–1.59 (m, 3H), 1.70–1.85 (m,
1H), 2.32 (t, J=7.5 Hz, 2H), 3.15 (s, 3H), 3.64 (s, 3H), 3.67
(dd, J=9.6 Hz, J=5.0 Hz, 1H), 4.01 (t, J=9.9 Hz, 1H),
4.61–4.70 (m, 1H), 5.18 (d, J=12.1 Hz, 1H), 5.24 (d, J=
12.0 Hz, 1H), 7.28–7.45 (m, 11H), 7.57–7.63 (m, 4H), 9.34
(s, 1H); 13C NMR (CDCl3, 75 MHz): d=19.3, 24.4, 26.2,
26.8, 28.4, 31.8, 32.3, 54.9, 61.3, 63.4, 68.9, 127.8, 128.6, 128.9,
129.8, 133.4, 133.5, 134.8, 135.7, 154.4, 163.8, 166.2; HR-MS
(ESI+): m/z=605.3049 [M+H]+, calcd. for C34H45N2O6Si:
605.3041.
Methyl (2E,6S)-6-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-
yl)-6-phenylhex-2-enoate (3k) (Table 2, entry 11): GP1 was
carried out with RhACHTNUTRGNE(NUG acac)(CO)2 (1.7 mg, 6.6 mmol), Biphe-
phos (26.1 mg, 33.7 mmol), Ph3P=CHCO2Me (333 mg,
0.997 mmol), amide 1k (175 mg, 0.664 mmol) and toluene
(11 mL); reaction time: 5 h; ratio 3k:4k=93:07 (1H NMR).
Column chromatography on silica gel (petroleum ether/
ethyl acetate 4:1) afforded 3k (202 mg, 0.575 mmol, 87%) as
a colourless oil. TLC (petroleum ether/ethyl acetate 4:1,
KMnO4): Rf (1k)=0.38, Rf (3k)=0.19; [a]2D0: ꢀ22.5 (c 0.97,
1
CHCl3); H NMR (CDCl3, 300 MHz): d=2.22–2.23 (m, 2H),
2.47 (ddt, J=13.5 Hz, J=8.4 Hz, J=6.6 Hz, 1H), 2.78 (ddt,
J=13.9 Hz, J=9.6 Hz, J=7.5 Hz, 1H), 3.67 (s, 3H), 5.32
(dd, J=9.6 Hz, J=6.6 Hz, 1H), 5.80 (dt, J=15.7 Hz, J=
1.5 Hz, 1H), 6.95 (dt, J=15.7 Hz, J=6.9 Hz, 1H), 7.24–7.36
(m, 3H), 7.52–7.55 (m, 2H), 7.66–7.72 (m, 2H), 7.77–7.83
(m, 2H); 13C NMR (CDCl3, 75 MHz): d=29.5, 29.9, 51.5,
54.6, 121.9, 123.4, 128.2, 128.2, 128.8, 131.9, 134.1, 139.2,
147.6, 166.8, 168.4; HR-MS (FAB+): m/z=350.1389 [M+
H]+, calcd. for C21H20NO4: 350.1392; elem. anal. calcd. for
C21H19NO4: C 72.19, H 5.48, N 4.01; found: C 72.41, H 5.63,
N 4.11.
Analytical Data for Methyl (6S)-6-(1,3-Dioxo-1,3-dihydro-
2H-isoindol-2-yl)-6-phenylhexanoate (4k): Yellowish oil.
[a]2D0: ꢀ27.7 (c 0.99, CHCl3); 1H NMR (CDCl3, 300 MHz):
d=1.31–1.41 (m, 2H), 1.63–1.79 (m, 2H), 2.24–2.36 (m,
1H), 2.29 (t, J=7.4 Hz), 2.54–2.66 (m, 1H), 3.62 (s, 3H),
5.32 (dd, J=9.6 Hz, J=6.7 Hz, 1H), 7.23–7.35 (m, 3H),
7.52–7.55 (m, 2H), 7.65–7.71 (m, 2H), 7.76–7.83 (m, 2H);
13C NMR (CDCl3, 75 MHz): d=24.6, 26.7, 30.8, 34.0, 51.6,
55.0, 123.3, 128.0, 128.3, 128.7, 132.0, 134.1, 139.7, 168.5,
174.0; HR-MS (ESI+): m/z=352.1548 [M+H]+, calcd. for
C21H22NO4: 352.1543.
Methyl (2E,6S)-6-[(tert-Butoxycarbonyl)amino]non-2-en-
oate (5a) (Table 3, entries 1 and 4): Method A: GP2 was car-
ried out with KOH (0.8 mg, 0.014 mmol), amide 3a (21 mg,
0.067 mmol) and MeOH (335 mL). TLC monitoring [petro-
leum ether/ethyl acetate 9:1, KMnO4: Rf (3a)=0.26, Rf
(5a)=0.23] showed full conversion of the starting material
after 24 h. Column chromatography on silica gel (petroleum
ether/ethyl acetate 9:1) afforded 5a (yield: 17 mg,
0.060 mmol, 89%) as a colourless oil.
Method B: GP3 was carried out with TFA (175 mL,
2.29 mmol), amide 3d (630 mg, 1.634 mmol) and CH2Cl2
(33.0 mL). TLC monitoring [petroleum ether/ethyl acetate
9:1, KMnO4: Rf (3d)=0.23, Rf (5a)=0.08] showed full con-
version of the starting material after 20 h. After work-up as
described in GP3 the crude product was subjected to
Methyl (2E,6S)-6-[(tert-Butoxycarbonyl)amino]-7-(trityl-
oxy)hept-2-enoate (5d) (Table 3, entry 6): GP2 was carried
out with KOH (3.0 mg, 0.050 mmol), amide 3f (125 mg,
0.230 mmol) and MeOH (1.2 mL). TLC monitoring [petro-
1030
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1023 – 1032

Stereoselective Synthesis of b-Proline Derivatives from Allylamines
leum ether/ethyl acetate 4:1, KMnO4: Rf (3f)=0.69, Rf
(5d)=0.63] showed full conversion of the starting material
after 4 h. Column chromatography on silica gel (petroleum
ether/ethyl acetate 4:1) afforded 5d (yield: 81 mg,
0.157 mmol, 68%) as a colourless foam. [a]2D0: ꢀ12.8 (c 0.61,
stirred for 20 min at ꢀ788C until TLC monitoring [petro-
leum ether/ethyl acetate 4:1, ninhydrin: Rf (5b)=0.29, Rf
(6b)=0.42] showed full conversion of the starting material.
After work-up the crude product was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate
4:1) to afford 6b (yield: 1.141 g, 3.572 mmol, 80%) as a col-
ourless oil, which crystallized on standing as colourless
square crystals; mp 60–618C. [a]20: +84.6 (c 0.98, CHCl3);
GC [Chrompack Permethyl b-CyDclodextrin column (50 mꢃ
0.25 mm), injector temperature 2008C, temperature pro-
gram: 1508C isothermal]: tR [(ꢀ)-(2S,5S)-6b]=103.2 min, tR
1
CHCl3); H NMR (CDCl3, 300 MHz): d=1.37 (s, 9H), 1.59–
1.66 (m, 2H), 1.98–2.15 (m, 2H), 2.97 (dd, J=9.2 Hz, J=
4.0 Hz, 1H), 3.14 (dd, J=9.0 Hz, J=3.2 Hz, 1H), 3.62–3.71
(m, 4H), 4.63 (d, J=9.1 Hz, 1H), 5.70 (d, J=15.5 Hz, 1H),
6.85 (dt, J=15.5 Hz, J=6.9 Hz, 1H), 7.14–7.25 (m, 9H),
7.33–7.36 (m, 6H); 13C NMR (CDCl3, 75 MHz): d=28.6,
29.1, 31.0, 50.5, 51.6, 65.1, 79.5, 86.5, 121.4, 127.2, 128.0,
128.8, 143.9, 148.7, 155.6, 167.1; HR-MS (ESI+): m/z=
538.2570 [M+Na]+, calcd. for C32H37NO5Na: 538.2564;
elem. anal. calcd. for C32H37NO5: C 74.54, H 7.23, N 2.72;
found: C 74.45, H 7.29, N 2.61.
[(+)-(2R,5R)-6b]=106.1 min;
1H NMR
(toluene-d8,
300 MHz, 908C): d=1.28 (s, 9H), 1.49–1.55 (m, 1H), 1.60–
1.65 (m, 1H), 1.98–2.20 (m, 2H), 2.38 (dd, J=14.8 Hz, J=
9.4 Hz, 1H), 3.12–3.17 (m, 1H), 3.49 (s, 3H), 4.57 (bs, 1H),
4.79 (d, J=6.9 Hz, 1H), 7.03–7.20 (m, 5H); 13C NMR (tolu-
ene-d8, 75 MHz, 908C): d=28.3, 28.5, 32.9, 38.7, 50.8, 56.0,
62.5, 79.3, 125.9, 126.8, 128.6, 146.0, 153.9, 171.5; HR-MS
(FAB+): m/z=320.1854 [M+H]+, calcd. for C18H26NO4:
320.1862; elem. anal. calcd. for C18H25NO4: C 67.69, H 7.89,
N 4.39; found: C 67.45, H 7.91, N 4.31.
Methyl (2E,6S)-6-[(tert-Butoxycarbonyl)amino]-7-{[tert-
butyl
(diphenyl)silyl]oxy}hept-2-enoate
(5e)
(Table 3,
entry 7): GP2 was carried out with KOH (4.4 mg,
0.078 mmol), amide 3g (214 mg, 0.396 mmol) and MeOH
(2.0 mL). TLC monitoring [petroleum ether/ethyl acetate
4:1, KMnO4: Rf (3g)=0.36, Rf (5e)=0.34] showed full con-
version of the starting material after 24 h. Column chroma-
tography on silica gel (petroleum ether/ethyl acetate 9:1) af-
forded 5e (yield: 143 mg, 0.279 mmol, 71%) as a colourless
oil. [a]2D0: ꢀ13.7 (c 0.63, CHCl3); 1H NMR (CDCl3,
500 MHz): d=1.07 (s, 9H), 1.44 (s, 9H), 1.62–1.73 (m, 2H),
2.14–2.28 (m, 2H), 3.58–3.61 (m, 1H), 3.66–3.70 (m, 2H),
3.73 (s, 3H), 4.68 (br d, J=9.9 Hz, 1H), 5.80 (dt, J=15.6 Hz,
J=1.4 Hz, 1H), 6.94 (dt, J=15.6 Hz, J=6.9 Hz, 1H), 7.37–
7.45 (m, 6H), 7.62–7.64 (m, 4H); 13C NMR (CDCl3,
125 MHz): d=19.5, 27.1, 28.6, 29.1, 30.6, 51.6, 51.7, 65.8,
79.4, 121.3, 127.9, 127.9, 130.0, 130.0, 133.3, 133.3, 135.7,
135.7, 148.8, 155.7, 167.2; HR-MS (FAB+): m/z=512.2853
[M+H]+, calcd. for C29H42NO5Si: 512.2832; elem. anal.
calcd. for C29H41NO5Si: C 68.07, H 8.08, N 2.74; found: C
67.96, H 8.21, N 2.68.
tert-Butyl (2R,5S)-2-(2-Methoxy-2-oxoethyl)-5-heptylpyr-
rolidine-1-carboxylate (6c) (Table 3, entry 5): GP4 was car-
ried out with KO-t-Bu (16 mg, 0.141 mmol), amide 5c
(60 mg, 0.176 mmol) and THF (2.9 mL). The mixture was
stirred for 20 min at ꢀ788C until TLC monitoring [petro-
leum ether/ethyl acetate 4:1, ninhydrin: Rf (5c)=0.52, Rf
(6c)=0.63] showed full conversion of the starting material.
After work-up the crude product was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate
9:1) to afford 6c (yield: 58 mg, 0.170 mmol, 97%) as a col-
ourless oil. [a]20: +50.9 (c 1.05, CHCl3); HPLC [Daicel Chir-
alpak AD-H 4D.6ꢃ250 mm with precolumn AD-H 10ꢃ4 mm,
n-hexane/i-PrOH 98:2, flow=0.5 mLminꢀ1, l=210 nm]: tR
[(+)-(2R,5S)-6c]=10.5 min, tR [(ꢀ)-(2S,5R)-6c]=11.9 min;
1H NMR (toluene-d8, 300 MHz, 908C): d=0.87 (t, J=
6.1 Hz, 3H), 1.19–1.29 (m, 11H), 1.35–1.58 (m, 1H), 1.43 (s,
9H), 1.58 (dd, J=11.8 Hz, J=6.6 Hz, 1H), 1.65–1.94 (m,
3H), 2.20 (dd, J=14.8 Hz, J=9.5 Hz, 1H), 2.94 (d, J=
14.5 Hz, 1H), 3.38 (s, 3H), 3.65–3.70 (m, 1H), 4.15–4.21 (m,
1H); 13C NMR (toluene-d8, 75 MHz, 908C): d=14.2, 23.1,
27.1, 27.8, 28.9, 29.0, 29.8, 30.2, 32.4, 34.4, 38.7, 50.8, 55.1,
58.6, 79.1, 153.7, 171.6; HR-MS (FAB+): m/z=342.2629
[M+H]+, calcd. for C19H36NO4: 342.2644; elem. anal. calcd.
for C19H35NO4: C 66.83, H 10.33, N 4.10; found: C 66.81, H
10.34, N 4.10.
tert-Butyl (2S,5S)-2-(2-Methoxy-2-oxoethyl)-5-[(trityloxy)-
methyl]pyrrolidine-1-carboxylate (6d) (Table 3, entry 6):
GP4 was carried out with KO-t-Bu (13.9 mg, 0.124 mmol),
amide 5d (80 mg, 0.155 mmol) and THF (2.6 mL). The mix-
ture was stirred for 20 min at ꢀ788C until TLC monitoring
[petroleum ether/ethyl acetate 4:1, ninhydrin: Rf (5d)=0.27,
Rf (6d)=0.36] showed full conversion of the starting materi-
al. After work-up the crude product was subjected to
column chromatography on silica gel (petroleum ether/ethyl
acetate 4:1) to furnish 6d (yield: 76 mg, 0.147 mmol, 95%)
as a colourless oil. [a]2D0: ꢀ43.16 (c 0.80, CHCl3); HPLC
[Daicel Chiralpak AD-H 4.6ꢃ250 mm with precolumn AD-
H 10ꢃ4 mm, n-hexane/i-PrOH 90:10, flow=0.5 mLminꢀ1,
l=220 nm]: tR [(+)-(2R,5R)-6d]=9.1 min, tR [(ꢀ)-(2S,5S)-
6d]=13.6 min; 1H NMR (toluene-d8, 500 MHz, 908C): d=
1.33 (s, 9H), 1.58 (dd, J=12.5 Hz, J=6.9 Hz, 1H), 1.74–1.91
tert-Butyl (2R,5S)-2-(2-Methoxy-2-oxoethyl)-5-propylpyr-
rolidine-1-carboxylate (6a) (Table 3, entry 1): GP4 was car-
ried out with KO-t-Bu (81 mg, 0.723 mmol), amide 5a
(258 mg, 0.904 mmol) and THF (15 mL). The mixture was
stirred for 20 min at ꢀ788C until TLC monitoring [petro-
leum ether/ethyl acetate 4:1, ninhydrin: Rf (5a)=0.34, Rf
(6a)=0.44] showed full conversion of the starting material.
After work-up the crude product was subjected to column
chromatography on silica gel (petroleum ether/ethyl acetate
9:1) to afford 6a (yield: 198 mg, 0.694 mmol, 77%) as a col-
1
ourless oil. [a]2D0: +57.2 (c 1.26, CHCl3); H NMR (toluene-
d8, 300 MHz, 908C): d=0.85 (t, J=7.1 Hz, 3H), 1.11–1.24
(m, 3H), 1.32 (dd, J=11.9 Hz, J=7.1 Hz, 1H), 1.42 (s, 9H),
1.56 (dd, J=11.8 Hz, J=6.6 Hz, 1H), 1.61–1.90 (m, 3H),
2.17 (dd, J=14.9 Hz, J=9.6 Hz, 1H), 2.94 (d, J=14.0 Hz,
1H), 3.37 (s, 3H), 3.62–3.67 (m, 1H), 4.14–4.20 (m, 1H);
13C NMR (toluene-d8, 75 MHz, 908C): d=14.2, 20.1, 27.7,
28.7, 28.8, 36.6, 38.5, 50.8, 55.0, 58.2, 79.0, 153.6, 171.6; HR-
MS (FAB+): m/z=286.2010 [M+H]+, calcd. for C15H28NO4:
512.2018; elem. anal. calcd. for C15H27NO4: C 63.13, H 9.54,
N 4.91; found: C 63.41, H 9.54, N 4.96.
tert-Butyl (2R,5R)-2-(2-Methoxy-2-oxoethyl)-5-phenylpyr-
rolidine-1-carboxylate (6b) (Table 3, entry 3): GP4 was car-
ried out with KO-t-Bu (399 mg, 3.557 mmol), amide 5b
(1.420 g, 4.446 mmol) and THF (40 mL). The mixture was
Adv. Synth. Catal. 2010, 352, 1023 – 1032
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1031

Andreas Farwick and Gꢀnter Helmchen
FULL PAPERS
(m, 2H), 1.98–2.05 (m, 1H), 2.23 (dd, J=14.8 Hz, J=9.4 Hz,
1H), 2.89–2.97 (m, 1H), 3.14–3.23 (m, 1H), 3.36 (s, 3H),
3.36–3.38 (m, 1H), 3.92–3.96 (m, 1H), 4.19–4.23 (m, 1H),
6.96–7.03 (m, 4H), 7.09–7.12 (m, 6H), 7.44–7.46 (m, 5H);
13C NMR (toluene-d8, 125 MHz, 908C): d=26.6, 28.8, 29.0,
38.5, 50.8, 55.5, 58.2, 64.6, 79.3, 87.5, 127.3, 128.2, 129.4,
145.1, 153.6, 171.5; HR-MS (ESI+): m/z=538.2570 [M+
H]+, calcd. for C32H37NO5Na: 538.2564.
[4] A. M. Schmidt, P. Eilbracht, Org. Biomol. Chem. 2005,
3, 2333–2343.
[5] L. Diab, T. Smejkal, J. Geier, B. Breit, Angew. Chem.
2009, 121, 8166–8170; Angew. Chem. Int. Ed. 2009, 48,
8022–8026.
[6] G. Helmchen, A. Dahnz, P. Dꢀbon, M. Schelwies, R.
Weihofen, Chem. Commun. 2007, 675–691.
[7] R. Takeuchi, S. Kezuka, Synthesis 2006, 3349–3366.
[8] P. Dꢀbon, A. Farwick, G. Helmchen, Synlett 2009,
1413–1416.
tert-Butyl
(2S,5S)-2-({[tert-ButylACTHNGUTERNNU(G diphenyl)silyl]oxy}-
methyl)-5-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate
(6e) (Table 3, entry 7): GP4 was carried out with KO-t-Bu
(18 mg, 0.161 mmol), amide 5e (103 mg, 0.201 mmol) and
THF (3.4 mL). The mixture was stirred for 20 min at ꢀ788C
until TLC monitoring [petroleum ether/ethyl acetate 4:1,
ninhydrin: Rf (5e)=0.48, Rf (6e)=0.54] showed full conver-
sion of the starting material. After work-up the crude prod-
uct was subjected to column chromatography on silica gel
(petroleum ether/ethyl acetate 4:1) to afford 6e (yield:
94 mg, 0.184 mmol, 91%) as a colourless oil. [a]2D0: ꢀ38.5 (c
0.68, CHCl3); HPLC [Daicel Chiralcel OD-H 4.6ꢃ250 mm
with precolumn OD-H 10ꢃ4 mm, n-hexane/i-PrOH 99:1,
flow=0.5 mLminꢀ1, l=220 nm]: tR [(ꢀ)-(2S,5S)-6e]=
[9] I. Ojima, E. S. Vidal, J. Org. Chem. 1998, 63, 7999–
8003.
[10] T. Oshitari, T. Mandai, Synlett 2006, 3395–3398.
[11] a) T. Spangenberg, B. Breit, A. Mann, Org. Lett. 2009,
11, 261–264; b) T. Spangenberg, E. Airiau, M. B. T.
Thuong, M. Donnard, M. Billet, A. Mann, Synlett 2008,
2859–2863.
[12] B. Breit, S. K. Zahn, Angew. Chem. 1999, 111, 1022–
1024; Angew. Chem. Int. Ed. 1999, 38, 969–971.
[13] Analogous combinations with a Knoevenagel reaction:
a) B. Breit, S. K. Zahn, Angew. Chem. 2001, 113, 1964–
1967; Angew. Chem. Int. Ed. 2001, 40, 1910–1913;
1
13.2 min, tR [(+)-(2R,5R)-6e]=14.5 min; H NMR (toluene-
ˆ
b) S. T. Kemme, T. Smejkal, B. Breit, Adv. Synth. Catal.
d8, 500 MHz, 908C): d=1.12 (s, 9H), 1.35 (s, 9H), 1.59 (dd,
J=12.5 Hz, J=7.1 Hz, 1H), 1.75–1.83 (m, 1H), 1.92–1.96
(m, 1H), 2.01–2.06 (m, 1H), 2.23 (dd, J=14.8 Hz, J=9.5 Hz,
1H), 2.84–2.98 (m, 1H), 3.36 (s, 3H), 3.62–3.74 (m, 1H),
3.85–3.88 (m, 2H), 4.19–4.24 (m, 1H), 7.18–7.23 (m, 6H),
7.68–7.71 (m, 4H); 13C NMR (toluene-d8, 125 MHz, 908C):
d=19.7, 26.3, 27.5, 28.8, 29.1, 38.5, 50.8, 55.7, 59.6, 65.0,
79.3, 128.2, 130.1, 134.7, 136.2, 153.7, 171.5; HR-MS (FAB+):
m/z=512.2868 [M+H]+, calcd. for C29H42NO5Si: 512.2832;
elem. anal. calcd. for C29H41NO5Si: C 68.07, H 8.08, N 2.74;
found: C 67.80, H 8.13, N 2.67.
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