Synthesis of functionalized pyrrolidines by a highly stereoselective [3+2]-annulation reaction of N-tosyl-α-amino aldehydes and 1,3-bis(silyl)propenes

Article abstract of DOI:10.1055/s-2007-966046

An efficient protocol for stereoselective construction of densely functionalized pyrrolidines by a [3+2]-annulation reaction of N-tosyl-α-amino aldehydes and 1,3-bis(silyl)propenes is described. This methodology is also applied as a key step in the synthe

Full text of DOI:10.1055/s-2007-966046

1576
FEATURE ARTICLE
Synthesis of Functionalized Pyrrolidines by a Highly Stereoselective
[3+2]-Annulation Reaction of N-Tosyl-a-Amino Aldehydes and
1,3-Bis(silyl)propenes
Synthesis of
F
e
unctionalize
r
d PyrrolidinesRestorp, Martina Dressel, Peter Somfai*
Organic Chemistry, KTH Chemical Science and Engineering, 10044 Stockholm, Sweden
Fax +46(8)7912333; E-mail: somfai@kth.se
Received 26 January 2007; revised 12 April 2007
activated aldehydes,4 imines,5 and chlorosulfonyl iso-
Abstract: An efficient protocol for stereoselective construction of
densely functionalized pyrrolidines by a [3+2]-annulation reaction
of N-tosyl-a-amino aldehydes and 1,3-bis(silyl)propenes is de-
scribed. This methodology is also applied as a key step in the syn-
cyanate6 by intramolecular nucleophilic interception of b-
silyl cation intermediate A. These approaches have been
particularly well studied and provide efficient entries to
thesis of the polyhydroxylated pyrrolidine alkaloid 2,5-dideoxy- five-membered heterocyclic ring systems, mainly func-
tionalized tetrahydrofuran4 and pyrrolid-2-one6 (g-lac-
2,5-imino-D-glucitol (DGDP).
tam) subunits, and have recently been implemented in
complex natural product synthesis.7 In contrast, the corre-
sponding [3+2]-annulation reaction to afford pyrrolidines
has received scant attention.5,8 Recently, we reported that
highly functionalized pyrrolidines 1, containing four con-
tiguous stereocenters can be prepared by a [3+2]-annula-
tion reaction of protected a-amino aldehydes 2 and 1,3-
bis(silyl)propenes 3 (Scheme 2).9 Herein, we report our
full investigation of this [3+2]-annulation methodology
for the synthesis of pyrrolidine-based alkaloids.
Key words: a-amino aldehyde, allylsilane, [3+2] annulation, pyr-
rolidine, alkaloid
Allylsilanes are versatile reagents in organic synthesis for
stereoselective C–C bond construction.1 A prominent fea-
ture of the reactivity of allylsilanes is the ability of C–Si
bonds to stabilize adjacent carbocations.2 This s → p hy-
perconjugative stabilization of b-carbocations is often re-
ferred to as the silicon b-effect and is responsible for the
regioselectivity and nucleophilicity of allylsilanes toward
electrophiles. Specifically, the Lewis acid promoted addi-
tion of allylsilanes to activated C=X p-bonds (Sakurai–
Hosomi allylation) is an important transformation in or-
ganic synthesis (Scheme 1). From a mechanistic point of
view, the allylsilane attacks the activated C=X p-bond
(X = O, NR3) to transiently form b-silyl cation intermedi-
ate A. This is followed by elimination of the silyl group to
afford the corresponding homoallylic alcohol or second-
ary amine. Due to the low Lewis acidity of allylsilanes, an
external activation is generally needed and efficient asym-
metric induction has been realized by employing chiral
Lewis acids or Lewis bases.3
R23Si
SiR2
3
LA
O
O
3
H
R1HN
SiR2
3
LA
NHR1
+
a
2
b
R23Si
a
b
SiR2
3
SiR2
HO
3
HO
SiR2
3
N
N
R1
SiR2
R1
3
not observed
1
LA
X
SiR2
X
XH
3
Scheme 2 Pathway for the synthesis of functionalized pyrrolidines
SiR2
3
R1
H
R1
R1
1
LA
Initial focus was directed towards investigating the effects
of different silicon substituents and a-amino aldehyde N-
Scheme 1 Addition of allylsilanes to activated C=X p-bonds protecting groups on the annulation reaction. Treatment of
(X = O, NR3)
N-tosyl-a-amino aldehyde 2a10 and silane 3a11
(SiR2 = SiMe3) with boron trifluoride–diethyl ether com-
3
plex at –78 °C afforded pyrrolidine 1a as a single diaste-
reomer in 77% isolated yield (Table 1, entry 1). In this
reaction, silane 3 functions only as a 1,2-dipole equivalent
since pyrrolidine 1a was formed exclusively (Scheme 2,
path a) and no piperidine formation derived from a 1,2-si-
lyl shift of the terminal silyl moiety could be detected
Allylsilanes can also function as synthetic equivalents of
1,2- or 1,3-dipoles in [3+2]-annulation reactions with
SYNTHESIS 2007, No. 10, pp 1576–1583
x
x.
x
x
.
2
0
0
7
Advanced online publication: 02.05.2007
DOI: 10.1055/s-2007-966046; Art ID: T01607SS
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Synthesis of Functionalized Pyrrolidines
1577
(path b). Consequently, in this approach silane 3 functions mands, silanes 3c–e were synthesized and subjected to the
only as a 1,2-dipole equivalent4c,8 in contrast to most pre- same reaction conditions. Disappointingly, treatment of
vious reports in which the allylsilane acts as a 1,3-dipole silane
3c
(SiR2 = SiCl3)15
or
silane
3d
3
equivalent with concomitant 1,2-silyl shift.4a,b,5,6 Silane [SiR2 = Si(OEt)3]16 at –78 °C resulted in no addition
3
3b [SiR23 = Si(i-Pr)3]11 failed to participate in the [3+2]- product; successive increase of the temperature to 0 °C re-
annulation reaction probably due to increased steric hin- sulted in decomposition of aldehyde 2a with no sign of
drance. Instead, after prolonged stirring at –78 °C com- product formation (Table 1, entries 3, 4). The lack of re-
pound 4 was isolated as a single diastereomer in excellent activity can be explained by the lower nucleophilicity of
yield (Table 1, entry 2). This kind of a-amino aldehyde 3c and 3d bearing more electron-withdrawing substitu-
dimerization is to the best of our knowledge unprecedent- ents.17 Treatment of silane 3e18 and aldehyde 2a with bo-
ed, but reflects the nucleophilic character of the sulfon- ron trifluoride–diethyl ether complex afforded pyrrolidine
amide nitrogen which is an important feature of the [3+2] 5, lacking the dimethylphenylsilyl group at C4, in 39%
annulation.12
yield along with the desired pyrrolidine 1b in 15% yield
both as single detectable stereoisomers (Table 1, entry 5).
Previous work has shown that protodesilylation of unacti-
vated C(sp3)–SiMe2R2 moieties (R2 = Me or Ph) as in 1 re-
quires harsh basic conditions at elevated temperatures.19
Accordingly, it is more likely that the loss of the silyl
group at C4 in 5 is due to a protodesilylation of the vinyl-
silane moiety in silane 3e,20 followed by nucleophilic at-
tack of the monodesilylated nucleophile to aldehyde 2a,
which would, in agreement with literature precedence, ac-
count for the formation of pyrrolidine 5.8
Since we were primarily interested in developing new and
efficient methods to access polyhydroxylated pyrrolidine
and pyrrolizidine alkaloids, the synthetic utility of the
[3+2] annulation would be greatly increased if the silyl
moieties in 1 could be oxidized to hydroxy groups via a
stereospecific Tamao–Fleming oxidation.13 Alkylsilane
moieties can generally not be transformed to hydroxy
groups. In contrast, the dimethylphenylsilyl group14 or
heteroatom-substituted silanes13 are known hydroxy
group synthons in organic synthesis. To meet these de-
Biographical Sketches
Per Restorp was born in 2001. Currently he is carry- nology, Stockholm. His re-
Göteborg, Sweden in 1976. ing out his PhD studies out search projects focuses on
He studied chemistry and within the research group of the exploration of stereo-
biology at Lund University Professor Peter Somfai at selective nucleophilic addi-
to earn a M.Sc. degree in the Royal Institute of Tech- tions to a-amino aldehydes.
Martina Dressel was born nical University of Munich in 2006 and is currently car-
1977 in Lichtenfels, Germa- under the supervision of rying out postdoctoral re-
ny. She received her diplo- Prof. Thorsten Bach, which search with Prof. Peter
ma in 2002 from the focused on hydrogen bond Somfai at the Royal Institute
Technical University of mediated
stereoselective of Technology.
Munich. She performed her radical cyclization reac-
graduate studies at the Tech- tions. She received her PhD
Peter Somfai was born in After a postdoctoral stay at nology (KTH) in 1999. In
1960 in Göteborg, Sweden, MIT, with Prof. S. Masam- 2001 he was appointed
and received his MSc in une, he returned to Sweden Head of the Department of
chemistry and PhD in or- and was appointed Profes- Chemistry and in 2005 Dean
ganic chemistry at Chalmers sor in Organic Chemistry at of the School of Chemical
University of Technology. the Royal Institute of Tech- Science and Engineering.
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

1578
P. Restorp et al.
FEATURE ARTICLE
Table 1 Optimization of the [3+2]-Annulation Reactiona
2
R23Si
O
SiR2
3
SiR2
HO
HO
OH
3
O
3a–c
H
Lewis acid
N
N
NHR1
SiR2 TsHN
Ts
Ts
CH2Cl2
3
2a–c
1a,b
4
–78 °C
N
NHTs
6
Ts
SiMe2Ph
5
Entry
2
3
Lewis acid
Product
Yieldb (%)
drc
R1
Ts
Ts
Ts
Ts
Ts
SiR2
3
1
a
a
a
a
a
a
b
c
SiMe3
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
1a
4
77
95
–
>98:2
2
Si(i-Pr)3
SiCl3
>98:2
3d
4d
5e
–
–
–
d
e
Si(OEt)3
SiMe2Ph
–
–
1b
5
15
39
>98:2
>98:2
6
7
a
a
Ts
Ts
e
e
SiMe2Ph
SiMe2Ph
Me2AlCl
MeAlCl2
1b
25
>98:2
1b
6
67
18
>98:2
E/Z >98:2
8
9
b
c
Cbz
Bz
e
e
SiMe2Ph
SiMe2Ph
MeAlCl2
MeAlCl2
–
–
–
–
–
–
a For experimental details, see the experimental section.
b Isolated yield.
c Determined by 1H NMR analysis of the crude reaction mixture.
d No reaction was observed until aldehyde 2a decomposed at 0 °C.
e The reaction temperature was –60 °C.
To circumvent this problem a variety of monodentate and lane 3e proceeded with excellent levels of
chelating Lewis acids were screened, none of which pro- diastereoselection and in each case only the formation of
1
moted the formation of 1b. However, the aluminum-based a single diastereomer was detected by H NMR analysis
Lewis acids afforded pyrrolidine 1b with no sign of the of the crude reaction mixtures (Table 1, entries 1–6).
desilylated pyrrolidine 5 (Table 1, entries 6, 7) and the
best result was obtained using dichloro(methyl)aluminum
as Lewis acid furnishing pyrrolidine 1b in 67% yield as a
Consequently, this approach provides ready access to
densely functionalized pyrrolidines 1b,d–h containing
four contiguous stereocenters and derivatizable functional
single detected isomer along with the formation of diene
groups with complete diastereoselectivity. In addition,
6 (Table 1, entry 7). Finally, the effect of nitrogen protect-
chiral HPLC analysis showed no sign of racemization of
ing groups was studied, but when using benzyloxycarbo-
nyl or benzoyl groups no sign of pyrrolidine formation
aldehydes 2 during either the oxidation or the [3+2]-annu-
lation reaction.21
was observed. Instead, only unidentified elimination
As noted previously, no 1,2-silyl shift was observed in the
products were detected (Table 1, entries 8, 9). It is specu-
[3+2]-annulation reaction (Scheme 1, path b) and conse-
lated that this difference in reactivity between sulfon-
quently, this is not a viable route to functionalized pipe-
amide, carbamate, and amide moieties in the [3+2]
ridines. An alternative approach to gain access to
annulation is due to the lower nucleophilicity of the nitro-
piperidines would be to use silane 3 and an N-tosyl-a-ami-
gen atom in the two latter functional groups, which favors
no aldehyde in a mechanistically related [4+2]-annulation
elimination over annulation.
reaction.22 However, subjecting aldehyde 723 to the opti-
With optimized conditions at hand, we turned our atten-
mized reaction conditions for the [3+2]-annulation reac-
tion to the nature of the N-tosyl-a-amino aldehydes and
tion resulted in no piperidine formation. Instead, diene 8
was isolated in 51% yield as a single detected geometrical
2a,d–h10 having different R groups were selected for fur-
ther investigation (Table 2). The [3+2] annulation with si-
isomer (Scheme 3).
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Functionalized Pyrrolidines
1579
activation and by invoking a hydrogen bond between the
a-NHTs and C=O moieties.24 This is followed by nucleo-
philic attack on the least hindered Si face, which accounts
for the cis C2–C3 relative stereochemistry in pyrrolidine
1b. Attack of silane 3 to aldehyde 2 in a Felkin–Anh sense
(not shown) would result in the formation of the C3
epimeric pyrrolidine. Keck and co-workers have studied
transition state geometries in boron trifluoride–diethyl
ether complex promoted crotylstannane additions to alde-
hydes. They concluded that syn-synclinal transition states,
in which the silyl methylene moiety is oriented gauche to
the aldehyde C=O, are the lowest energy pathways due to
the presence of favorable secondary orbital interactions.25
It has also been argued that the most sterically demanding
quadrant of space in these structures is that occupied by
the carbonyl complexed Lewis acid.4a In order to mini-
mize these unfavorable steric interactions with the ap-
proaching nucleophile, we propose that the reactions
proceed through syn-synclinal transition state B that ac-
counts for the observed C4 selectivity. The alternative
syn-synclinal transition state C suffers from unfavorable
steric interactions between the carbonyl complexed Lewis
acid and silane 3 and predicts the formation of the C4
epimeric pyrrolidine. The transiently formed b-silyl cat-
ion D is then trapped by the NHTs moiety. It should be
noted that the observed C5 stereochemistry indicates that
the nucleophilic attack of the sulfonamide on the b-silyl
cation is faster than C4–C5 bond rotation.
Table 2 Stereoselective [3+2] Annulation of Silane 3e and
N-Tosyl-a-amino Aldehydes 2a,d–ha
SiMe2Ph
HO
O
3e
R
H
MeAlCl2
CH2Cl2
–78 °C
R
N
NHTs
Ts
1b,d–h
SiMe2Ph
2a,d–h
Entry
2
a
d
e
f
R
Product
1b
Yieldb (%) drc
1
2
3
4
5
6
i-Pr
Me
Ph
67
>98:2
1d
33d
69
>98:2
>98:2
>98:2
>98:2
>98:2
1e
CH2OTBS
1f
57
g
CH2CH=CH2
(CH2)3OTBDPS
1g
35d
61
h
1h
a For experimental details, see the experimental section.
b Isolated yield.
c Determined by 1H NMR analysis of the crude reaction mixture.
d Low yield due to low stability of the aldehyde.
TsHN
O
TsHN
3e
H
MeAlCl2
CH2Cl2
–78 °C
51%
7
8
As shown in Scheme 4, silane 3 reacts through an open
transition state and altering the alkene geometry of the si-
lane from E to Z is not expected to influence the overall
C3–C4 relative stereochemistry of pyrrolidine 1.26 How-
ever, we reasoned that if the nucleophilic attack by the
sulfonamide is indeed faster than C4–C5 bond rotation,
changing the alkene geometry of 3e could provide an en-
try to the C5 epimeric pyrrolidine. To test this notion, al-
dehyde 2a was treated with silane 927 under the optimized
reaction conditions for the [3+2] annulation but, some-
what disappointingly, this resulted in no pyrrolidine for-
mation (Scheme 5). Instead, diene 6 was isolated as the
major product in 54% yield as a single stereoisomer.
Scheme 3 Attempted [4+2]-annulation reaction
Pyrrolidine 1b was crystalline and its relative configura-
tion was determined by X-ray crystallographic analysis to
be (2S*,3R*,4R*,5R*) (Figure 1).9 The relative configura-
tion of pyrrolidines 1a,d–h was assigned in analogy with
this result.
Functionalized pyrrolidines are common substructures in
a variety of natural products, including polyhydroxylated
pyrrolidine and pyrrolizidine alkaloids.28 Many of these
compounds display powerful glycosidase inhibitory prop-
erties and anticancer and antiviral activities and they have
received considerable attention from the synthetic com-
munity. To demonstrate the utility of the developed [3+2]-
annulation methodology for the synthesis of polyhydrox-
ylated alkaloids, we report a straightforward synthesis of
the monocyclic glucosidase inhibitor DGDP (11),29 which
is also a substructure of the more complex pyrrolizidine
alkaloid (+)-alexine.
Figure 1 Crystal structure of pyrrolidine 1b
To account for the observed stereochemical outcome of
the [3+2] annulations, the diastereofacial bias imposed on
the aldehyde C=O by the a-NHTs substituent (C3 selec-
tivity) and the orientation of silane 3 in the transition state
(C4 selectivity) have to be considered (Scheme 4). The C3
selectivity can be rationalized by a chelation-controlled
mechanism proceeding via a monodentate Lewis acidic
The synthesis of DGDP (11) started from aldehyde 2f and
silane 3e, which smoothly underwent a highly stereoselec-
tive [3+2]-annulation reaction to afford pyrrolidine 1f as a
single diastereomer (Scheme 6). Desilylation of pyrroli-
dine 3f under acidic conditions followed by stereospecific
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

1580
P. Restorp et al.
FEATURE ARTICLE
LA
R23Si
H
O
SiR2
SiR2
4
HO
3
3
3
LAO
R1
H
SiR2
TsN
R1
3
O
NH
Ts
R1
H
5
2
SiR2
N
3
H
H
R1
SiR2
3M
Ts
H
1
A
C
LA
NHTs
2
LA
SiR2
3
O
R23Si
SiR2
3
H
3
TsN
R1
C4-epimer
H
SiR2
3
H
B
Scheme 4 Rationalization of the stereoselectivity
SiMe2Ph
able functional groups by [3+2] annulation of N-tosyl-a-
amino aldehydes and 1,3-bis(silyl)propenes. In this ap-
proach, silane 3 functions only as a 1,2-dipole equivalent
and no 1,2-silyl migration was observed. The further util-
ity of the [3+2]-annulation methodology in natural prod-
uct synthesis is underway in our laboratory and will be
reported in due course.
Z/E 11:1
SiMe2Ph
O
9
H
MeAlCl2, CH2Cl2
–78 °C, 54%
NHTs
NHTs
2a
6
Scheme 5 Addition of (Z)-silane 9 to aldehyde 2a
1H and 13C NMR spectra were recorded in CDCl3, CD3OD, or D2O
using the residual peak of CHCl3 (1H: d 7.26; 13C: d 77.0), MeOH
(1H: d 3.31; 13C: d 49.0), or D2O (1H: d 4.79, 13C: trace amounts of
MeOH d 49.5) as internal standard. Only the strongest/structurally
most important peaks (cm–1), in the IR spectra, are listed. Analytical
TLC plates were visualized with UV light and phosphomolybdic
Tamao–Fleming oxidation furnished the polyhydroxylat-
ed pyrrolidine 10 in 50% yield over two steps. Attempts
to detosylate 10 using sodium naphthalenide at –78 °C in
tetrahydrofuran resulted in no reaction and recovered
starting material only was isolated. Instead, detosylation acid/cerium sulfate staining reagent. Air and moisture sensitive re-
actions were carried out in flame-dried, septum-capped flasks under
an atmospheric pressure of N2. All liquid reagents were transferred
via oven-dried syringes. THF and CH2Cl2 were dried using a Glass-
contour solvent dispensing system.
was realized by treatment with lithium amide in tetrahy-
drofuran at –78 °C, which afforded DGDP (11) in only
three steps from 3f.
SiMe2Ph
HO
O
(2S,3R,4R,5R)-2-Isopropyl-4-(trimethylsilyl)-5[(trimethyl-
silyl)methyl]-1-tosylpyrrolidin-3-ol (1a)
3e
TBSO
H
MeAlCl2
CH2Cl2
To a stirred soln of aldehyde 2a (25 mg, 98 mmol) in CH2Cl2 (1 mL)
cooled to –78 °C was added BF3·OEt2 (43 mL, 343 mmol) with a sy-
ringe followed by addition of silane 3a (75 mL, 290 mmol) and the
resulting mixture was stirred at –78 °C for 2 h. After 2 h, more si-
lane 3a (25 mL, 98 mmol) was added and the stirring was continued
for an additional 1 h. The reaction was quenched by addition of sat.
aq NH4Cl (5 mL) and extracted with CH2Cl2 (3 × 5 mL). The com-
bined organic phases were dried (MgSO4), filtered, and evaporated
to give a colorless oil. Flash chromatography (silica gel, CH2Cl2) of
the residue yielded 1a as a white solid (33 mg, 77%).
N
NHTs
Ts
SiMe2Ph
TBSO
–78 °C
57%, >40:1
2f
1f
1. AcOH–THF–H2O, r.t.
2. KBr, AcOOH, r.t.
50% (2 steps)
HO
OH
HO
OH
[a]D25 –25.8 (c 1.2, CH2Cl2).
Li/NH3(l)
IR (neat): 3520, 2950, 1330, 1160 cm–1.
N
H
N
THF
–78 °C
65%
1H NMR (500 MHz, CDCl3): d = 7.71 (d, J = 8.1 Hz, 2 H), 7.30 (d,
J = 8.1 Hz, 2 H), 3.72 (ddd, J = 8.7, 7.9, 4.0 Hz, 1 H), 3.48 (td,
J = 9.7, 6.5 Hz, 1 H), 3.29 (dd, J = 8.7, 6.3 Hz, 1 H), 2.39 (s, 3 H),
2.03–1.99 (m, 1 H), 1.18–1.07 (m, 8 H), 0.88 (dd, J = 15.6, 3.9 Hz,
1 H), 0.14 (s, 9 H), –0.14 (s, 9 H).
Ts
HO
OH
HO
OH
11
10
Scheme 6 Synthesis of DGDP
13C NMR (125 MHz, CDCl3): d = 145.5, 138.4, 131.9, 129.9, 77.1,
In conclusion, we have developed a protocol for the stereo-
selective synthesis of densely functionalized pyrrolidines
containing four contiguous stereocenters and derivatiz-
70.5, 60.6, 44.9, 33.0, 30.2, 23.6, 23.4, 23.0, 1.7, 0.1.
MS (ESI): m/z (%) = 464 (100) [M + Na]+.
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Functionalized Pyrrolidines
1581
HRMS (ESI): m/z [M + Na]+ calcd for C21H39NNaO3SSi2:
HRMS (ESI): m/z [M + Na]+ calcd for C34H41NNaO3SSi2:
464.2081; found: 464.2078.
622.2238; found: 622.2230.
(2S,3R,4R,5R)-2-Isopropyl-4-(dimethylphenylsilyl)-5-[(dimeth-
ylphenylsilyl)methyl]-1-tosylpyrrolidin-3-ol (1b); Typical Pro-
cedure
(2S,3R,4R,5R)-2-[(tert-Butyldimethylsiloxy)methyl]-4-(dimeth-
ylphenylsilyl)-5-[(dimethylphenylsilyl)methyl]-1-tosylpyrroli-
din-3-ol (1f)
To a stirred soln of aldehyde 2a (45 mg, 176 mmol) in CH2Cl2 (3.5
mL) cooled to –78 °C was added 1 M MeAlCl2 in hexanes (360 mL)
with a syringe followed by addition of 3e (115 mL, 0.35 mmol). The
resulting mixture was stirred at –78 °C for 2 h. The reaction was
quenched by addition of sat. aq soln NH4Cl (5 mL) and extracted
with CH2Cl2 (3 × 5 mL). The combined organic phases were dried
(MgSO4), filtered and evaporated to give a colorless oil. Flash chro-
matography (silica gel, pentane–EtOAc, 5:1) of the residue yielded
1b as a white solid (66 mg, 67%).
[a]D25 –3.4 (c 0.55, CH2Cl2).
IR (neat): 3490, 2950, 1350, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.56 (d, J = 8.2 Hz, 2 H), 7.45–
7.23 (m, 12 H), 3.99 (dd, J = 10.1, 4.7 Hz, 1 H), 3.88–3.86 (m, 2 H),
3.80 (ddd, J = 8.8, 5.9, 3.1 Hz, 1 H), 3.54–3.51 (m, 1 H), 3.45 (d,
J = 3.3 Hz, 1 H), 2.42 (s, 3 H), 1.69 (dd, J = 15.7, 8.8 Hz, 1 H), 1.47
(t, J = 5.7 Hz, 1 H), 1.18 (dd, J = 15.7, 3.1 Hz, 1 H), 0.89 (s, 9 H),
0.27 (s, 3 H), 0.26 (s, 3 H), 0.10 (s, 6 H), 0.06 (s, 3 H), 0.05 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 143.4, 139.2, 136.6, 135.4, 134.0,
133.9, 129.6, 129.3, 128.8, 127.9, 127.7, 127.6, 75.1, 64.1, 62.8,
60.3, 39.6, 26.7, 25.8, 21.5, 18.0, –1.5, –1.8, –4.0, –4.2, –5.4, –5.5.
MS (ESI): m/z (%) = 690 (100) [M + Na]+.
HRMS (FAB): m/z [M + Na]+ calcd for C35H53NNaO4SSi3:
[a]D25 –55.8 (c 1.0, CH2Cl2).
IR (neat): 3510, 2920, 1330, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.56 (d, J = 8.1 Hz, 2 H), 7.42–
7.26 (m, 12 H), 3.80 (dt, J = 8.8, 3.5 Hz, 1 H), 3.53–3.48 (m, 1 H),
3.30 (dd, J = 8.7, 6.6 Hz, 1 H), 2.47–2.43 (m, 4 H), 2.05–1.90 (m, 1
H), 1.33 (dd, J = 9.6, 8.0 Hz, 1 H), 1.23 (dd, J = 15.1, 9.1 Hz, 1 H),
1.09 (d, J = 6.6 Hz, 3 H), 1.07 (d, J = 6.6 Hz, 3 H), 1.00 (dd,
J = 15.1, 3.5 Hz, 1 H), 0.45 (s, 3 H), 0.39 (s, 3 H), 0.10 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 143.2, 140.3, 136.7, 136.1, 133.9,
133.7, 129.7, 129.6, 128.6, 128.2, 127.7, 127.6, 74.5, 68.1, 58.2,
42.5, 29.5, 27.9, 21.5, 21.2, 20.8, –1.9, –3.0, –4.1, –4.3.
690.2895; found: 690.2899.
(2S*,3R*,4R*,5R*)-2-Allyl-4-(dimethylphenylsilyl)-5-[(dimeth-
ylphenylsilyl)methyl]-1-tosylpyrrolidin-3-ol (1g)
IR (neat): 3510, 2950, 1340, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.63–7.60 (m, 2 H), 7.46–7.26 (m,
12 H), 5.86–5.83 (m, 1 H), 5.08 (d, J = 17.2 Hz, 1 H), 5.06 (d,
J = 10.2 Hz, 1 H), 3.93 (dt, J = 8.1, 5.3 Hz, 1 H), 3.73 (q, J = 5.4 Hz,
1 H), 3.55 (dt, J = 8.1, 6.0 Hz, 1 H), 2.65–2.61 (m, 1 H), 2.46–2.42
(m, 4 H), 1.52 (dd, J = 14.8, 7.8 Hz, 1 H), 1.46 (d, J = 4.6 Hz, 1 H),
1.39 (t, J = 5.7 Hz, 1 H), 1.29–1.25 (m, 2 H), 0.32 (s, 3 H), 0.30 (s,
3 H), 0.10 (s, 3 H), 0.05 (s, 3 H).
MS (ESI): m/z (%) = 588 (100) [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H44NO3SSi2: 566.2575;
found: 566.2561.
(2S,3R,4R,5R)-4-(Dimethylphenylsilyl)-5-[(dimethylphenyl-
silyl)methyl]-2-methyl-1-tosylpyrrolidin-3-ol (1d)
[a]D25 –35.8 (c 0.65, CH2Cl2).
IR (neat): 3500, 2930, 1340, 1160 cm–1.
13C NMR (125 MHz, CDCl3): d = 143.3, 139.4, 136.5, 136.2, 135.4,
133.9, 133.8, 129.6, 129.5, 128.8, 128.0, 127.72, 127.68, 117.1,
74.3, 63.7, 59.4, 40.3, 35.2, 28.2, 21.5, –1.8, –2.4, –3.8, –4.5.
1H NMR (500 MHz, CDCl3): d = 7.61 (d, J = 8.4 Hz, 2 H), 7.51–
7.48 (m, 2 H), 7.40–7.24 (m, 10 H), 3.82 (dt, J = 7.4, 4.1 Hz, 1 H),
3.58 (p, J = 6.7 Hz, 1 H), 3.48 (dd, J = 12.2, 6.7 Hz, 1 H), 2.43 (s, 3
H), 1.62 (dd, J = 14.8, 7.4 Hz, 1 H), 1.37 (t, J = 7.5 Hz, 1 H), 1.27
(dd, J = 14.8, 4.2 Hz, 1 H), 1.23 (d, J = 6.6 Hz, 1 H), 1.12 (d, J = 5.4
Hz, 1 H), 0.88 (d, J = 6.5 Hz, 1 H), 0.40 (s, 3 H), 0.33 (s, 3 H), 0.12
(s, 3 H), 0.08 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 143.2, 139.7, 136.4, 135.5, 133.9,
133.8, 129.6, 129.5, 128.8, 128.1, 127.7, 127.6, 74.1, 59.5, 59.2,
39.4, 27.1, 21.5, 16.6, –1.5, –1.8, –3.7, –4.5.
MS (ESI): m/z (%) = 586 (100) [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H42NO3SSi2: 564.2418;
found: 564.2409.
(2S,3R,4R,5R)-2-[3-(tert-Butyldiphenylsiloxy)propyl]-4-(di-
methylphenylsilyl)-5-[(dimethylphenylsilyl)methyl]-1-tosyl-
pyrrolidin-3-ol (1h)
[a]D25 –19.0 (c 1.0, CH2Cl2).
IR (neat): 2950, 1160, 1110 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.61–7.58 (m, 4 H), 7.49–7.45 (m,
2 H), 7.34–7.12 (m, 18 H), 3.75 (q, J = 6.8 Hz, 1 H), 3.64–3.58 (m,
2 H), 3.44–3.40 (m, 2 H), 2.34 (s, 3 H), 1.68–1.49 (m, 3 H), 1.41 (d,
J = 5.4 Hz, 1 H), 1.28–1.22 (m, 2 H), 1.10 (dd, J = 14.9, 5.5 Hz, 1
H), 0.97 (s, 9 H), 0.29 (s, 3 H), 0.25 (s, 3 H), 0.04 (s, 3 H), 0.03 (s,
3 H).
13C NMR (125 MHz, CDCl3): d = 143.1, 139.8, 136.6, 135.9, 135.6,
135.5, 133.9, 133.82, 133.80, 133.77, 129.6, 129.4, 128.7, 128.1,
127.7, 127.6, 73.5, 63.8, 63.7, 58.9, 40.7, 31.9, 28.9, 28.6, 26.9,
25.9, 22.7, 21.4, 19.2, 14.1, –1.8, –2.3, –4.1.
MS (ESI): m/z (%) = 560 (100) [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C29H40NO3SSi2: 538.2267;
found: 538.2240.
(2S,3R,4R,5R)-4-(Dimethylphenylsilyl)-5-[(dimethylphenyl-
silyl)methyl]-2-phenyl-1-tosylpyrrolidin-3-ol (1e)
[a]D25 +18.9 (c 0.93, CH2Cl2).
IR (neat): 3520, 3070, 2950, 1330, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.47–7.08 (m, 19 H), 4.55 (d,
J = 4.7 Hz, 1 H), 4.35 (dt, J = 11.7, 0.8 Hz, 1 H), 3.98 (d, J = 4.4 Hz,
1 H), 2.33 (s, 3 H), 1.92 (dd, J = 14.2, 11.7 Hz, 1 H), 1.53–1.50 (m,
2 H), 1.08 (br s, 1 H), 0.23 (s, 3 H), 0.17 (s, 3 H), 0.08 (s, 3 H), 0.03
(s, 3 H).
MS (ESI): m/z (%) = 842 (100) [M + Na]+.
HRMS (FAB): m/z [M + Na]+ calcd for C47H61NNaO4SSi3:
842.3521; found: 842.3528.
13C NMR (125 MHz, CDCl3): d = 143.0, 138.6, 136.8, 136.5, 136.3,
134.0, 133.9, 129.4, 129.2, 129.0, 128.5, 128.1, 127.9, 127.8, 70.1,
60.4, 39.9, 28.2, 21.4, –1.9, –2.6, –3.3, –4.8.
(E)-1,3-Bis(trichlorosilyl)prop-1-ene (3c)
IR (neat): 1610, 1390, 1090 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.60 (dt, J = 17.9, 7.6 Hz, 1 H),
5.99–5.95 (m, 1 H), 2.59 (dd, J = 7.9, 1.3 Hz, 2 H).
MS (ESI): m/z (%) = 622 (100) [M + Na]+.
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

1582
P. Restorp et al.
FEATURE ARTICLE
13C NMR (125 MHz, CDCl3): d = 145.0, 127.3, 33.5.
HRMS (TOF Cl+): m/z [M]+ calcd for C3H4Cl6Si2: 305.7983; found:
H), 3.40–3.33 (m, 1 H), 2.44 (s, 3 H), 2.19–2.14 (m, 2 H), 1.09 (d,
J = 6.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 143.2, 137.8, 136.4, 134.6, 129.6,
128.8, 127.1, 116.5, 49.4, 40.0, 21.5, 21.4.
305.7986.
(4S*)-4-Isopropyl-2-[(S*)-2-methyl-1-(tosylamino)propyl]-3-
tosyloxazolidin-5-ol (4)
HRMS (FAB): m/z [M + H]+ calcd for C14H20NO2S: 266.1209;
found: 266.1209.
IR (neat): 2960, 1340, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.81 (d, J = 8.3 Hz, 2 H), 7.78 (d,
J = 8.3 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2 H), 7.29 (d, J = 8.1 Hz, 2 H),
5.26 (d, J = 2.3 Hz, 1 H), 5.17 (s, 1 H), 4.79 (d, J = 10.0 Hz, 1 H),
3.69 (ddd, J = 9.9, 4.1, 2.3 Hz, 1 H), 3.21 (d, J = 10.0 Hz, 1 H), 2.84
(s, 1 H), 2.45 (s, 3 H), 2.42 (s, 3 H), 1.85–1.82 (m, 1 H), 1.66–1.63
(m, 1 H), 0.89 (d, J = 6.6 Hz, 3 H), 0.87 (d, J = 6.6 Hz, 3 H), 0.81–
0.75 (m, 6 H).
13C NMR (125 MHz, CDCl3): d = 144.8, 143.0, 139.1, 133.5, 129.6,
129.5, 129.1, 126.9, 98.3, 89.6, 71.9, 60.7, 30.6, 29.9, 21.6, 21.5,
19.8, 19.4, 19.2, 18.3.
(Z)-1,3-Bis(dimethylphenylsilyl)propene (9)27
IR (neat): 2881, 2390, 1704, 1603, 1246, 1147, 858, 765.
1H NMR (500 MHz, CDCl3, E/Z 1:11): d = 7.46–7.24 (m, 10 Hmaj
10 Hmin), 6.39–6.31 (m, 1 Hmaj), 6.03–5.92 (m, 1 Hmin), 5.49–5.44
(m, 1 Hmin), 5.44–5.40 (m, 1 Hmaj), 1.86–1.83 (m, 2 Hmin), 1.78–1.74
(m, 2 Hmaj), 0.27–0.24 (m, 6 Hmaj), 0.23–0.19 (m, 12 Hmin), 0.17–
0.12 (m, 6 Hmaj).
13C NMR (125 MHz, CDCl3): d = 146.1, 145.2, 139.9, 138.4, 133.7,
133.6, 133.5, 133.5, 132.9, 129.2, 129.0, 128.7, 127.7, 127.6, 127.6,
126.4, 124.7, 27.6, 24.5, 20.1, 18.3, 12.7, 0.8, –0.7, –2.3, –2.9, –3.3,
–3.4.
,
HRMS (ESI): m/z [M + H]+ calcd for C24H35N2O6S2: 511.1931;
found: 511.1930.
HRMS (FAB): m/z [M + H]+ calcd for C19H27Si2: 311.1646; found:
311.1641.
(2S*,3S*,5R*)-5-[(Dimethylphenylsilyl)methyl]-2-isopropyl-1-
tosylpyrrolidin-3-ol (5)
(2S,3R,4R,5R)-2,5-Bis(hydroxymethyl)-1-tosylpyrrolidine-3,4-
diol (10)
IR (neat): 2960, 1340, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.51–7.47 (m, 2 H), 7.43–7.39 (m,
2 H), 7.36–7.32 (m, 3 H), 7.14–7.09 (m, 2 H), 3.42–3.38 (m, 1 H),
3.33–3.28 (m, 2 H), 2.31 (s, 3 H), 1.86–1.82 (m, 3 H), 1.36–1.30 (m,
1 H), 1.09–1.03 (m, 7 H), 0.14 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 142.3, 137.3, 134.2, 132.9, 128.8,
128.4, 127.2, 126.6, 71.1, 66.2, 54.9, 39.2, 27.7, 25.7, 20.7, 20.6,
19.8, –3.0, –3.4.
Pyrrolidine 1f (180 mg, 0.27 mmol) was dissolved in AcOH–THF–
H2O (3:1:1, 5 mL) and stirred at r.t. for 18 h. The solvents were re-
moved in vacuo and the crude oil was filtered through a short plug
of silica gel (pentane–EtOAc, 2:1) to give the desilylated adduct as
a colorless oil (151 mg, 92%). The product obtained in the previous
step (19 mg, 34 mmol), KBr (11 mg, 92 mmol), and NaOAc (15 mg,
185 mmol) were dissolved in glacial AcOH and cooled on an ice-
water bath before addition of 32% AcOOH in AcOH (1 mL). After
20 min the ice-water bath was removed and the soln was stirred at
r.t. for 15 h and heated to 40 °C for 1 h. The reaction was quenched
with 20% aq Na2S2O3 soln (0.5 mL), diluted with brine (10 mL), and
extracted with EtOAc (4 × 10 mL). The combined organic phases
were dried (Na2SO4), filtered, and evaporated to give a clear oil.
Flash chromatography (EtOAc–MeOH 98:2) of the residue yielded
pyrrolidine 10 (5.8 mg, 54%) as a clear oil.
[a]D25 –11.0 (c 0.58, MeOH).
IR (neat): 3350, 1340, 1160 cm–1.
1H NMR (500 MHz, CD3OD): d = 7.76 (d, J = 8.4 Hz, 2 H), 7.42 (d,
J = 8.4 Hz, 2 H), 4.16–4.13 (m, 1 H), 3.98 (dd, J = 11.3, 5.1 Hz, 1
H), 3.89 (dd, J = 11.3, 4.3 Hz, 1 H), 3.83 (dd, J = 11.3, 5.8 Hz, 1 H),
3.78 (dd, J = 11.3, 2.8 Hz, 1 H), 3.67–3.63 (m, 1 H), 3.57 (dd,
J = 6.8, 5.8 Hz, 1 H), 3.35 (dt, J = 4.9, 3.1 Hz, 1 H), 2.44 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C23H34NO3SSi: 432.2023;
found: 432.2020.
rac-(E)-2-Methyl-N-tosylhepta-4,6-dien-3-amine (6)
IR (neat): 1723, 1501, 1070 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.71 (d, J = 8.1 Hz, 2 H), 7.26 (d,
J = 8.1 Hz, 2 H), 6.09 (dt, J = 17.3, 10.5 Hz, 1 H), 5.78 (dd,
J = 15.2, 10.3 Hz, 1 H), 5.29 (dd, J = 15.3, 7.5 Hz, 1 H), 5.10–5.01
(m, 2 H), 4.34 (d, J = 8.3 Hz, 1 H), 3.65–3.62 (m, 1 H), 2.40 (s, 3
H), 1.77–1.72 (m, 1 H), 0.86 (d, J = 6.8 Hz, 3 H), 0.84 (d, J = 5.8
Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 143.6, 138.4, 136.3, 133.5, 131.3,
129.9, 127.7, 118.0, 61.6, 33.5, 21.9, 18.7.
HRMS (FAB): m/z [M + Na]+ calcd for C15H21NNaO2S: 302.1185;
found: 302.1182.
13C NMR (125 MHz, CD3OD): d = 146.39, 135.9, 131.7, 129.9,
77.5, 77.4, 69.7, 65.4, 64.2, 63.1, 22.4.
MS (ESI): m/z (%) = 340 (100) [M + Na]+.
rac-3-(Tosylamino)butanal (7)23
IR (neat): 1720, 1305, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.66 (s, 1 H), 7.77 (d, J = 8.2 Hz,
2 H), 7.33 (d, J = 8.2 Hz, 2 H), 4.91 (d, J = 8.3 Hz, 1 H), 3.79–3.72
(m, 1 H), 2.76 (dd, J = 17.9, 5.2 Hz, 1 H), 2.62 (dd, J = 17.9, 6.2 Hz,
1 H), 2.45 (s, 3 H), 1.14 (d, J = 6.8 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 200.3, 143.6, 137.6, 129.8, 127.1,
50.1, 45.5, 21.5, 21.3.
HRMS (ESI): m/z [M + H]+ calcd for C13H20NO6S: 318.1006;
found: 318.0993.
(2S,3R,4R,5R)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol (11)
To a deep blue soln of Li (20 mg) in liquid NH3 (3 mL) at –78 °C
was added pyrrolidine 10 (4 mg, 13 mmol) in THF (1 mL) and the
soln was stirred at –78 °C for 90 min. The reaction was quenched
by addition of benzene until the blue color disappeared followed by
addition of H2O (5 mL). The crude mixture was allowed to slowly
reach r.t. and evaporated to dryness. The residue was filtered
through a plug of deactivated silica gel (MeOH) to remove exces-
sive salts. Flash chromatography (EtOAc–MeOH, 1:1) of the resi-
due on deactivated silica yielded DGDP (11) (1.3 mg, 65%) with
spectral data characterizations in accordance with those previously
reported in the literature.26
rac-(E)-N-Tosylhepta-4,6-dien-2-amine (8)
IR (neat): 1430, 1320, 1160 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.74 (d, J = 8.2 Hz, 2 H), 7.30 (d,
J = 8.1 Hz, 2 H), 6.18 (dt, J = 17.0, 10.3 Hz, 1 H), 5.98 (dd,
J = 15.1, 10.5 Hz, 1 H), 5.38 (dt, J = 15.1, 7.4 Hz, 1 H), 5.11 (d,
J = 16.8 Hz, 1 H), 5.03 (d, J = 10.2 Hz, 1 H), 4.33 (d, J = 7.4 Hz, 1
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Functionalized Pyrrolidines
1583
[a]D25 + 23.9 (c 0.13, MeOH).
1H NMR (500 MHz, D2O): d = 4.14 (dd, J = 4.9, 3.0 Hz, 1 H), 3.87
(dd, J = 5.2, 3.0 Hz, 1 H), 3.79–3.63 (m, 4 H), 3.31 (app q, J = 5.5
Hz, 1 H), 2.99 (app q, J = 5.2 Hz, 1 H).
(11) Guijarro, A.; Yus, M. Tetrahedron 1994, 50, 13269. Silane
3b was prepared by the same procedure as 3a.
(12) For a recent example of a related dimerization of aziridine
aldehydes, see: Hili, R.; Yudin, A. K. J. Am. Chem. Soc.
2006, 128, 14772.
(13) Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
(14) Fleming, I.; Henning, R.; Parker, D. C.; Plaut, H. E.;
Sanderson, P. E. J. J. Chem. Soc., Perkin Trans. 1 1995, 317.
(15) Silane 3c was prepared by the same method as 3d.
(16) Pietraszuk, C.; Fischer, H.; Kujawa, M.; Marciniec, B.
Tetrahedron Lett. 2001, 42, 1175.
(17) Hagen, G.; Mayr, H. J. Am. Chem. Soc. 1991, 113, 4954.
(18) de Dios, M. A. C.; Fleming, I.; Friedhoff, W.; Woode, P. D.
W. J. Organomet. Chem. 2001, 624, 69.
(19) Heitzman, C. L.; Lambert, W. T.; Mertz, E.; Shotwell, J. B.;
Tinsley, J. M.; Va, P.; Roush, W. R. Org. Lett. 2005, 7, 2405;
and references cited therein.
13C NMR (125 MHz, D2O): d = 79.9, 78.2, 65.5, 63.1, 61.5, 61.2.
Acknowledgment
Financial support from the Royal Institute of Technology, the Swe-
dish Research Council and the Knut and Alice Wallenberg founda-
tion is gratefully acknowledged. Martina Dressel thanks the
Wenner-Gren foundation for a grant. The authors thank Dr. Andreas
Fischer for his help with the X-ray crystal structure of pyrrolidine
1b.
(20) Fleming, I.; Langley, J. A. J. Chem. Soc., Perkin Trans. 1
1981, 1421.
(21) The [3+2] annulation of (S)-2a and 3e afforded 1b with
>97% ee according to chiral HPLC analysis (Chiracel OD-
H, hexane–i-PrOH, 99:1, 1 mL/min).
(22) For a related [4+2]-annulation reaction to afford THP rings,
see: Angle, S. R.; Belanger, D. S.; El-Said, N. A. J. Org.
Chem. 2002, 67, 7699.
(23) Aldehyde 7 was prepared from the N-tosylated b-amino-
ethyl ester according to: Davis, F. A.; Song, M.; Augustine,
A. J. Org. Chem. 2006, 71, 2779.
(24) (a) Restorp, P.; Somfai, P. Org. Lett. 2005, 7, 893.
(b) Yamada, Y.; Shirakawa, E.; Ando, K.; Shibata, S.;
Uchida, I. Tetrahedron: Asymmetry 1999, 10, 3443.
(25) Keck, G. E.; Savin, K. A.; Cressman, E. N. K.; Abbott, D. E.
J. Org. Chem. 1994, 59, 7889.
(26) Addition of (E)- or (Z)-crotylsilanes to aldehydes give
predominantly syn selectivity, although the selectivity is
generally higher for (E)-crotylsilanes, see: Hayashi, T.;
Kabeta, K.; Hamachi, I.; Kumada, M. Tetrahedron Lett.
1983, 24, 2865.
(27) The Z-silane 9 was obtained as a side product in the synthesis
of silane 3e (see ref. 18).
(28) (a) Liddell, J. R. Nat. Prod. Rep. 1999, 16, 499. (b) Liddell,
J. R. Nat. Prod. Rep. 2000, 17, 455. (c) O’Hagan, D. Nat.
Prod. Rep. 2000, 17, 435.
References
(1) (a) Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95, 1293.
(b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(c) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem.
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(2) Lambert, J. B. Tetrahedron 1990, 46, 2677.
(3) Denmark, S. E.; Fu, J. P. Chem. Rev. 2003, 103, 2763.
(4) (a) Micalizio, G. C.; Roush, W. R. Org. Lett. 2000, 2, 461.
(b) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113,
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(5) Panek, J. S.; Jain, N. F. J. Org. Chem. 1994, 59, 2674.
(6) (a) Romero, A.; Woerpel, K. A. Org. Lett. 2006, 8, 2127.
(b) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999,
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(7) Tinsley, J. M.; Roush, W. R. J. Am. Chem. Soc. 2005, 127,
10818; and references cited therein.
(8) Kiyooka, S.; Shiomi, Y.; Kira, H.; Kaneko, Y.; Tanimori, S.
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(9) Restorp, P.; Fischer, A.; Somfai, P. J. Am. Chem. Soc. 2006,
128, 12646.
(10) Aldehydes 2d–f,h were prepared from the corresponding
enantiopure a-amino alcohols under conditions known to
prevent racemization, see: Ocejo, M.; Vicario, J. L.; Badia,
D.; Carrillo, L.; Reyes, E. Synlett 2005, 2110. Aldehydes
2a–c,g were prepared from racemic a-amino alcohols by the
same method.
(29) Baxter, E. W.; Reitz, A. B. J. Org. Chem. 1994, 59, 3175.
Synthesis 2007, No. 10, 1576–1583 © Thieme Stuttgart · New York