A new strategy for the synthesis of hydroxylated pyrrolizidinic alkaloids by highly stereoselective indium-mediated allylation of pyrrolidinic aldehydes

Article abstract of DOI:10.1016/j.tetasy.2005.10.010

Indium-mediated allylation of N-Cbz-L-prolinal 3, under Grignard conditions, was carried out with high yield and stereoselectivity (de = 90%) to afford intermediate (2S,1′R)-N-benzyloxycarbonyl-2-(1′-hydroxybut- 3′-en-1′-yl)pyrrolidine 4, which was transf

Full text of DOI:10.1016/j.tetasy.2005.10.010

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3887–3891
A new strategy for the synthesis of hydroxylated
pyrrolizidinic alkaloids by highly stereoselective indium-mediated
allylation of pyrrolidinic aldehydes
*
´
´
´
Isidoro Izquierdo, Marıa T. Plaza and Vıctor Yanez
˜
Department of Medicinal and Organic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Received 23 September 2005; accepted 3 October 2005
Available online 11 November 2005
Abstract—Indium-mediated allylation of N-Cbz-L-prolinal 3, under Grignard conditions, was carried out with high yield and ste-
reoselectivity (de = 90%) to afford intermediate (2S,10R)-N-benzyloxycarbonyl-2-(10-hydroxybut-30-en-10-yl)pyrrolidine 4, which
was transformed in two steps into (1R,3R,7aS)-1-hydroxy-3-hydroxymethylpyrrolizidine 9. Commercial Cbz-L-proline was a source
of functionalization and chirality.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
functional groups to the final compound, whereas the
B ring, with the appropriate stereochemistry and func-
tionalization, can be built up following a synthetic strat-
egy similar to that outlined in Scheme 1, where the
retrosynthesis for less elaborated 3-hydroxymethyl A,
1-hydroxy-B and 1-hydroxy-3-methyl- or 1-hydroxy-3-
hydroxymethylpyrrolizidine (C), with chiralities match-
ing those in the target molecules is displayed, and
consists of a stereocontrolled carbon-chain lengthening
and subsequent cyclization. Accordingly, N-Cbz-L-
prolinal 3, easily prepared4 from commercially available
N-benzyloxycarbonyl-L-proline, would be an excellent
starting material for these purposes in order to investi-
gate not only the suitability of the synthetic proposal,
but also controlling its stereochemical outcomes, and
consequently application of those results to the prepara-
tion of more complex targets 1 and 2.
Continuing with our most recent efforts1 on the synthe-
sis of polyhydroxylated pyrrolizidinic alkaloids
(PHPAs), we were interested in exploring the possibility
of preparing those with higher and a more diverse
degree of functionalization in the B-ring, such as the
hyacinthacines2 shown in Figure 1, and other analogues
of interest for SAR studies as glycosidase inhibitors.
According to Figure 1, the preparation of the target
PHPAs can be accomplished as follows: ring A comes
from a suitable and orthogonally protected polyhydr-
oxypyrrolidine,3 which will transfer its chirality and
Ring A furnished by the
appropriated pyrrolidine
Ring B built up according to
the retrosynthesis in Scheme 1
HO
R
H
N
R
H
HO
A
B
H
B
CHO
R1
N
N
N
HO
Cbz
Cbz
OH
hyacinthacine B2 1 (R = H; R1 = CH2OH)
hyacinthacine B5 2 (R = OH; R1 = CH3)
R1
3
A R = H; R1 = CH2OH
B R = OH; R1 = H
Figure 1. Hyacinthacine B2 1 and B5 2.
C R = OH; R1 = CH3, CH2OH
Cbz -L-Proline
*
Scheme 1. Retrosynthesis of pyrrolizidines A, B and C from Cbz-L-
Corresponding author. Tel.: +34 958 249583; fax: +34 958 243845;
proline.
e-mail: isidoro@ugr.es
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.10.010

3888
I. Izquierdo et al. / Tetrahedron: Asymmetry 16 (2005) 3887–3891
C-Allylation of 3 with TiCl4-mediated allylsilane,5 or
instead that of its N-trityl-derivative with the same
organometallic reagent and BF3:Et2O-mediated or
allylmagnesium bromide6 has previously been reported.
Even though moderate to good yields, as well as high
stereoselectivities resulted in some cases, we were inter-
ested in exploring the same C-alkylation but using
indium7 as a metal promoter.
Thus, the J1 ,2 ꢀ 0 Hz value in 3 is compatible with con-
formations 3a and 3b, where an orthogonal disposition
for the formyl and H(2) protons is present. Of both con-
formations, only 3a could account for the chelated mod-
el proposed by Singh et al.,8 where in the transition
state, the metal promoter interacts with both formyl
oxygen and the heterocyclic nitrogen atoms TS1à and
TS2à. It is easy to conclude that in TS1à, which leads
to diastereomer 4, attack of the nucleophile on the top
face would be favoured due to a less crowding than that
showed by TS2à.
0
2. Results and discussion
Indium-mediated reaction of 3 under Grignard condi-
tions7d (Scheme 2), gave, after column chromatography,
(2S,10R)-N-benzyloxycarbonyl-2-(10-hydroxybut-30-
en-10-yl)pyrrolidine 4 (tR 7.65 min) in 78% yield, although
GLC analysis of the reaction mixture, before work-up
and column chromatography, seemed to indicate the
presence of a small amount (ꢀ5%) of the corresponding
(2S,10S)-epimer 5 (tR 7.80 min), which could not be iso-
lated. Although a synthesis of 4 and 5 has been previ-
ously published,5 data on their optical spectroscopic
properties that would allow the determination of the
configuration of our compounds, were not included in
that report. Thus, upon treatment of 4 with aq KOH,
bicyclic carbamate 6 was isolated showing identical
spectroscopic data to that previously reported5,6 for
(1R,7S)-tetrahydro-1-(2-propenyl)-1H,3H-pyrrolo[1,2-
c]oxazol-3-one, indicating a cis-configuration for H(1,7)
and hence an (R)-configuration at C(10) in 4.
Surprisingly, when compound 4 was epoxidized with
MCPBA (see Fig. 3 and Scheme 3) only one compound,
which was identified as (2S,10R,30S)-N-benzyloxycar-
bonyl-2-(30,40-epoxi-10-hydroxybut-10-yl)pyrrolidine 7,
was isolated. Due to the presence of typical carbamate
rotamers in 7, scarce structural and stereochemical
information could be obtained from its spectroscopic
data, nevertheless its HRMS-spectrum was consistent
with the proposed structure. The high stereoselectivity
found in this reaction, is noteworthy and can be justified
on the basis of the transition state (Aà) displayed in Fig-
ure 3, where according to an extension of HenbestÕs
statement,9 the peroxyacid is tethered by the hydroxyl
group at C(10) through a hydrogen bond in such a
way that epoxidation took place on the si-face affording
7.
Catalytic hydrogenation of 7 (see Scheme 3) caused a
tandem process consisting on its N-deprotection to the
intermediate pyrrolidine 8, followed by a spontaneous
and highly favoured 5-exo-tet10 intramolecular cycliza-
tion to afford (1R,3R,7aS)-1-hydroxy-3-hydroxymethyl-
pyrrolizidine 9 isolated as its di-O-acetate 10 after
conventional acetylation of the reaction mixture. A pro-
cedure similar to this, but with a different open-chain
c,d-epoxiamine leading to polyhydroxylated pyrrolidine
derivatives, have previously been reported by others.11
J = 7.3 Hz
H
H
H
(i)
(ii)
7
N
1
3
N
R1
O
Cbz R
O
4 R= OH; R1 = H
6
5 R= H; R1 = OH
Scheme 2. Reagents and conditions: (i) H2C@CHCH2InBr/THF/
ꢁ78 ꢁC; (ii) aq KOH/THF/rt.
The structure of 10 was determined on the basis of its 1H
1
and 13C NMR spectroscopic data. In addition, H–1H
The transition states displayed in Figure 2, account for
the the high stereoselectivity found in the above process.
and 1H–13C COSY and extensive NOE-difference experi-
H
δ−
R
N
H
N
δ+
H
Cbz
In
H
N
OH
Cbz
O
O
J ~ 0
~90o
Cbz
H
TS1‡
(Re face)
major 4
3a
H
O
N
H
N
δ+
N
Cbz
In
H
H
Cbz
H
O
OH
)
(
δ−
Cbz
R
J ~ 0
~90o
TS2‡
(Si face)
minor 5
(not isolated)
3b
Figure 2. Conformations 3a and 3b accounting for the J1 ,2 value and transition states TS1à and TS2à leading to homoallylic alcohols 4 and 5,
0
respectively.

I. Izquierdo et al. / Tetrahedron: Asymmetry 16 (2005) 3887–3891
3889
R
Platform II and VG Autospec-Q mass spectrometers.
Optical rotations were measured in solutions of CHCl3
(1-dm tube) with a Jasco DIP-370 polarimeter. GLC
was performed on a Hewlett–Packard 6890 gas chro-
matograph equipped with split/splitless injector, a
flame-ionization detector and a capillary HP-5 column
(30 m · 0.25 mm i.d. · 0.25 lm film thickness) at
10 min at 230 ꢁC program to 250 ꢁC, 20 ꢁC/min; the
He flow rate was 0.7 ml/min and the injection port
and the zone-detector temperatures were 250 ꢁC. TLC
was performed on precoated silica gel 60 F254 alumin-
ium sheets and detection by employing a mixture of
10% ammonium molybdate (w/v) in 10% aqueous sulfu-
ric acid containing 0.8% cerium sulfate and heating. Col-
umn chromatography was performed on silica gel
(Merck, 7734). The non-crystalline compounds, whose
elemental analyses are not include, were shown to be
homogeneous by chromatographic methods and charac-
terized by NMR, MS and HRMS.
OH
H
O
O
O
O
4
H
O
N
H
Cbz
N
H
Cbz
7
‡
A
Figure 3. Epoxidation of 4 according to the Henbest model.
OR
OH
H
N
H
(ii)
(i)
(ii)
4
7
3
NH
O
OR
8
9 R = H
10 R = Ac
(iii)
(iv)
Scheme 3. Reagents and conditions: (i) MCPBA/Cl2CH2, rt; (ii) 10%
Pd–C/H2; (iii) Ac2O/py, rt; (iv) MeONa (cat.)/MeOH, rt.
4.1. Indium-mediated allylation reaction of N-Cbz-L-
prolinal 3
ments (see Fig. 4) allowed the assignment of its
1H and 13C NMR signals as well as the configuration
of the stereogenic centre at C(3). In this context, the
definitive NOE interaction between H(1)–H(3) was
crucial in order to achieve such an assignment not only
in 10, but also that at C(30) in 7. Finally, conventional
Zemplen de-O-acetylation of 10 afforded the required
target molecule 9.
To a vigorously stirred suspension of indium metal (1 g,
8.7 mmol) in anhydrous THF (10 ml), allyl bromide
(1.1 ml, 12.6 mmol) was added and the mixture refluxed
until most of the metal had disappeared (1 h). The mix-
ture was then cooled to ꢁ78 ꢁC, and a solution of 34b
(1 g, 4.2 mmol) in the same solvent (5 ml) added drop-
wise. After 15 min, GLC revealed the absence of 3 and
the presence of two new products (tR 7.65 and
7.80 min) in a 95:5 ratio, respectively. The reaction
mixture was concentrated and the residue subjected to
column chromatography (Et2O–hexane 1:2 ! Et2O !
Et2O–MeOH, 15:1) to yield (2S,10R)-N-benzyloxycar-
H7β
H1
H7a
N
OAc
H2β
bonyl-2-(10-hydroxybut-30-en-10-yl)pyrrolidine 4 (900 mg,
H2α
H3
26
H5β
78%) as
a
colourless syrup; ½aꢂD ¼ ꢁ56 (c 1,
H5α
10
CHCl3). IR (neat): 3450 (OH) and 1681 cmꢁ1 (C@O).
NMR data (300 MHz): H, d 7.35 (m, 5H, Ph), 5.88
OAc
1
(m, 1H, H-30), 5.17–4.98 (m, 4H, CH2Ph, H-
40cis,40trans), 3.98–3.29 (m, 5H, H-10,2,5a,5b,OH) and
2.17–1.71 (m, 4H, H-3a,3b,4a,4b); 13C (75 MHz, inter
alia): d 136.70, 128.58, 128.12 and 127.98 (Ph), 135.39
(C-30), 117.22 (C-4Õ), 72.09 (C-10), 67.20 (CH2Ph), 63.12
(C-2), 47.84 (C-5), 37.46 (C-20), 26.89 and 24.40 (C-
3,4). Mass spectrum (LSIMS): m/z: 298.1418 [M++Na]
for C16H21NO3Na 298.1419 (deviation +0.5 ppm).
Figure 4. Main NOE interactions in 10.
3. Conclusions
We have developed a new strategy for the preparation of
the B ring in natural, densely polyhydroxylated, pyrrol-
izidinic alkaloids with a high degree of stereocontrol via
C-allylation and tandem allylic epoxidation–intramole-
cular cyclization reactions. These results will be extended
to the synthesis of more complex molecules in due
course.
4.2. (1R,7S)-Tetrahydro-1-(2-propenyl)-1H,3H-
pyrrolo-[1,2-c]oxazol-3-one 6
To a solution of 4 (168 mg, 0.61 mmol) in THF (3 ml) an
aqueous solution of KOH (100 mg) in water (5 ml) was
added and the mixture left at rt for two weeks. GLC
analysis then revealed the absence of 4 and the appear-
ance of a new product (tR = 2.98 min). The reaction
mixture was concentrated and the residue dissolved in
Cl2CH2, washed with brine, supported on silica gel
and then chromatographed (Et2O–hexane 2:1) to yield
4. Experimental
Solutions were dried over MgSO4 before concentration
1
under reduced pressure. The H and 13C NMR spec-
tra were recorded with Bruker AMX-300, AM-300 and
ARX-400 spectrometers for solutions in CDCl3 (internal
Me4Si). IR spectra were recorded with a Perkin–Elmer
FT-IR Spectrum One instrument and mass spectra
with a Hewlett–Packard HP-5988-A and Fisons mod.
6 (20 mg, 20%) with spectroscopic data in accordance
26
with those previously reported6 ½aꢂD ¼ ꢁ20 (c 0.6,
CHCl3). IR (neat) 3079 (C@CH), 1755 (C@O) and
1
1643 cmꢁ1 (C@C). NMR data (300 MHz): H, d 5.79

3890
I. Izquierdo et al. / Tetrahedron: Asymmetry 16 (2005) 3887–3891
0
0
0
0
0
0
0
0
(dddd, 1H, J1 a,2 6.1, J1 b,2 7.3, J2 ,3 cis 10.2, J2 ,3 trans
14.4 Hz, H-7a), 1.78–1.63 (m, 3H, H-2a,6a,6b) and
1.50 (ddt, 1H, H-7b); 13C (75 MHz): d 170.90 and
170.80 (CH3CO), 78.38 (C-1), 70.15 (C-7a), 68.09 (C-
8), 63.26 (C-3), 55.19 (C-5), 34.86 (C-2), 30.07 (C-7),
25.31 (C-6), 21.14 and 20.94 (2CH3CO).
17.3 Hz, H-20), 5.18 (dq, 1H, J3 cis,3 trans = J1 a,3 trans
=
=
=
0
0
0
0
J1 b,3 trans = 1.6 Hz, H-30trans), 5.15 (dq, 1H, J1 a,3 cis
0
0
0
0
J1 b,3 cis = 1.3 Hz, H-30cis), 4.69 (q, 1H, J1,1 a = J1,1 b
0
0
0
0
J1,7 = 7.3 Hz, H-1), 3.79 (ddd, 1H, J6a,7 5.2, J6b,7
10.9 Hz, H-7), 3.63 (dt, 1H, J4a,5a = J4a,5b = 8,
J4a,4b = 11.3 Hz, H-4a), 3.16 (ddd, 1H, J4b,5a 9.4, J4b,5b
3.3 Hz, H-4b), 2.58 (m, 1H, H-10a), 2.36 (m, 1H, H-
10b), 2.06 (m, 1H, H-5a), 1.86 (m, 1H, H-5b), 1.76 (m,
1H, H-6a) and 1.49 (dq, 1H, J5a,6b = J5b,6b = J6b,7 = 7.7,
J6a,6b 10.4 Hz, H-6b); 13C (75 MHz): d 161.59 (C-3),
132.33 (C-20), 118.70 (C-30), 75.39 (C-1), 63.24 (C-7),
45.78 (C-4), 34.91 (C-10), 25.18 (C-5) and 25.01 (C-6).
4.5. (1R,3R,7aS)-1-Hydroxy-3-hydroxymethyl-
pyrrolizidine (9)
To a solution of 10 (190 mg, 0.78 mmol) in anhydrous
MeOH (10 ml) was added MeONa/MeOH (2 M,
0.2 ml) and the mixture left at rt for 24 h. TLC (AcOEt)
then revealed the absence of 10 and the presence of a
slower-running compound. The reaction mixture was
concentrated and the residue chromatographed
(CH2Cl2–MeOH–NH4OH 6:2:0.5) to yield 9 as a syrup
4.3. (2S,10R,30S)-N-Benzyloxycarbonyl-2-(30,40-epoxi-10-
hydroxybut-10-yl)pyrrolidine 7
26
26
(100 mg, 82%); ½aꢂD ¼ þ1, ½aꢂ405 ¼ þ1:4 (c 0.8, MeOH).
To a stirred solution of 4 (1.13 g, 4.1 mmol) in anhy-
drous CH2Cl2 (5 ml) was added a solution of MCPBA
(2.12 g, 6.15 mmol) in the same solvent (25 ml). After
24 h TLC (Et2O) revealed the absence of 4 and the pres-
ence of a slower-running product. The reaction mixture
was filtered and the filtrate subsequently washed with
10% aq Na2SO3, 5% aq K2CO3 and brine. The organic
phase was concentrated to a residue that was subjected
IR (neat) 3351 cmꢁ1 (OH). NMR data (300 MHz,
1
0
MeOH-D4): H, d 3.87 (dt, 1H, J1,7a 6.2, J1,2 = J1,2
=
0
8.6 Hz, H-1), 3.57 (dd, 1H, J3,8 5.8, J8,8 10.7 Hz, H-8),
3.51 (dd, 1H, J3,8 5.8 Hz, H-80), 3.24 (dt, 1H, J7,7a 7,
0
J7 ,7a 4.6 Hz, H-7a), 2.91–2.77 (m, 2H, H-5,50), 2.73
0
0
(quin, 1H, J2,3 = J2 ,3 = 6 Hz, H-3), 2.23 (br dt, 1H,
0
0
0
J2,2 12.2 Hz, H-2), 1.88 (dq, 1H, J6,7 = J6 ,7 = 7, J7,7
12.1 Hz, H-7), 1.82–1.63 (m, 3H, H-6,60,70) and 1.58
(br dt, 1H, H-20); 13C (75 MHz): d 77.41 (C-1), 73.17
(C-7a), 67.82 (C-3), 66.70 (C-8), 56.04 (C-5), 39.22 (C-
2), 31.04 (C-7) and 25.74 (C-6). Mass spectrum
(LSIMS): m/z: 157.1099 [M+] for C8H15NO2 157.1103
(deviation +2.2 ppm).
to column chromatography (Et2O) to afford 7 (900 mg,
26
75%) as
a
colourless syrup; ½aꢂD ¼ ꢁ47 (c 0.8,
CHCl3). IR (neat) 3432 (OH), 1699 (CO), 753 and
699 cmꢁ1 (aromatic) NMR data (300 MHz): 1H, d
7.40–7.30 (m, 5H, Ph), 5.19–5.08 (m, 2H, CH2Ph),
4.10–2.45 (6 m, 8H, H-2,5a,5b,10,30,40a,40b,OH) and
2.10–1.90 (m, 6H, H-3a,3b,4a,4b,20a,20b); 13C,
(75 MHz, inter alia) d 136.60, 128.61, 128.19 and 128.00
(Ph), 67.30 (CH2Ph), 63.63 (C-2), 50.75 (C-30), 47.87
and 47.77 (C-40,5), 35.34 (C-20), 27.22 and 24.26 (C-
3,4). Mass spectrum (LSIMS): m/z: 314.1362 [M++Na]
for C16H21NO4Na 314.1368 (deviation +2.0 ppm).
Acknowledgements
The authors are deeply grateful to the Spanish Ministe-
´
rio de Ciencia y Tecnologıa (Project PPQ2002-01303)
´
and Junta de Andalucıa (CVI-250) for their financial
support.
4.4. (1R,3R,7aS)-1-Acetyloxy-3-acetyloxymethyl-
pyrrolizidine 10
Compound 7 (900 mg, 3.1 mmol) in anhydrous MeOH
(20 ml) was hydrogenated under the presence of 10%
Pd–C (80 mg) at 65 psi for 15 h. TLC (MeOH) revealed
no 7 but compounds with very low mobility. The cat-
alyst was filtered off washed with MeOH and the filtrate
and washings concentrated to a residue that was conven-
tionally acetylated in pyridine (1 ml) with Ac2O (1 ml)
and DMAP (50 mg) for 3 h. TLC (MeOH) then showed
a faster-running product. The acetylation reaction was
concentrated to a residue that was dissolved in CH2Cl2
and washed with water. The aqueous phase was basified
with Na2CO3 and extracted with EtAcO. The combined
organic extracts were concentrated and the residue puri-
References
1. Izquierdo, I.; Plaza, M.-T.; Tamayo, J. A. Org. Biomol.
Chem., in press.
2. (a) Asano, N.; Kuroi, H.; Ikeda, K.; Kizu, H.; Kameda,
Y.; Kato, A.; Adachi, I.; Watson, A. A.; Nash, R. J.;
Fleet, G. W. J. Tetrahedron: Asymmetry 2000, 11, 1–8; (b)
Yamashita, T.; Yasuda, K.; Kizu, K.; Kameda, Y.;
Watson, A. A.; Nash, R. J.; Fleet, G. W. J.; Asano, N.
J. Nat. Prod. 2002, 65, 1875–1881; (c) Asano, N.; Ikeda,
K.; Kasahara, M.; Arai, Y.; Kizu, H. J. Nat. Prod. 2004,
67, 846–850.
3. (a) Izquierdo, I.; Plaza, M.-T.; Robles, R.; Franco, F.
Carbohydr. Res. 2001, 330, 401–408; (b) Izquierdo, I.;
Plaza, M.-T.; Franco, F. Tetrahedron: Asymmetry 2002,
fied by chromatography (EtAcO) to afford pure 10
26
´
13, 1503–1508; (c) Izquierdo, I.; Plaza, M.-T.; Rodrı-
guez, M.; Franco, F.; Martos, A. Tetrahedron, in
press.
(200 mg, 27%) as a colourless syrup; ½aꢂD ¼ ꢁ18 (c
0.4, CHCl3). NMR data (300 MHz): 1H, d 4.83 (dt,
1H, J1,2a = J1,2b = 6.4, J1,7a 4.5 Hz, H-1), 4.00 (d, 2H,
J3,8 6.3 Hz, H-8,8), 3.42 (dt, 1H, J7a,7a = J7b,7a = 7.1 Hz,
H-7a), 2.96 (m, 2H, H-3,5a), 2.65 (dt, 1H, J5a,5b 10.9,
4. Compound 3 has been prepared by oxidation of Cbz-L-
prolinol with: SO3–Py complex: (a) Lee, E.; Li, K.-S.; Lim,
J. Tetrahedron Lett. 1996, 37, 1445–1446; Dei, S.; Bellucci,
C.; Buccioni, M.; Ferraroni, M.; Gualtieri, F.; Guandalini,
L.; Manetti, D.; Matucci, R.; Romanelli, M.-N.; Scapec-
chi, S.; Teodori, E. Bioorg. Med. Chem. 2003, 11, 3153–
J
5b,6a = J5b,6b = 6.4 Hz, H-5b), 2.32 (dt, 1H, J1,2b =
J2b,3 = 6.7, J2a,2b 13.4 Hz, H-2b), 2.02 and 1.99 (2 s,
6H, 2CH3CO), 1.91 (ddt, 1H, J 5.7, J 7.5, J7a,7b

I. Izquierdo et al. / Tetrahedron: Asymmetry 16 (2005) 3887–3891
3891
3164; Swern oxidation: (b) Denis, Y.; Chan, T.-H. J. Org.
Chem. 1992, 57, 3079–3085; Nagashima, H.; Gondo, M.;
Masuda, S.; Kondo, H.; Yamaguchi, Y.; Matsubara, K.
Chem. Commun. 2003, 442–443; Dess–Martin periodinane:
(c) Gardiner, J. M.; Bruce, S. E. Tetrahedron Lett. 1998,
39, 1029–1032; PCC oxidation: (d) Izquierdo, I.; Plaza,
M.-T.; Tamayo, J. A. Tetrahedron: Asymmetry 2004, 15,
3635–3642; Reduction of Cbz-L-proline methyl ester with
DIBAL: Langley, D. R.; Thurston, D. E. J. Org. Chem.
1987, 52, 91–97.
W. W. J. Org. Chem. 1997, 62, 4293–4301; (c) Lombardo,
M.; Licciulli, S.; Trombini, C. Tetrahedron Lett. 2003, 44,
9147–9149; (d) Lombardo, M.; Morganti, S.; Trombini, C.
J. Org. Chem. 2003, 68, 997–1006; (e) Lombardo, M.;
Gianotti, K.; Licciulli, S.; Trombini, C. Tetrahedron 2004,
60, 11725–11732, and references cited therein.
8. Singh, S.; Kumar, S.; Chimni, S. S. Tetrahedron: Asym-
metry 2002, 13, 2679–2687.
9. Henbest, H. B.; Wilson, R. A. L. J. Chem. Soc. 1957,
1958–1962; For the cooperative coordination effect of
other functional groups, see also: Jenmalm, A.; Berts, W.;
Luthman, K.; Cso¨regh, I.; Hacksell, U. J. Org. Chem.
1995, 60, 1026–1032.
5. Kiyooka, S.; Nakano, M.; Shiota, F.; Fujiyama, R. J. Org.
Chem. 1989, 54, 5409–5411.
6. Bejjani, J.; Chemla, F.; Audouin, M. J. Org. Chem. 2003,
68, 9747–9752.
7. For a recent review on the synthesis and reactivity of N-
protected-a-amino aldehydes: (a) Gryko, D.; Chalko, J.;
Jurczak, J. Chirality 2003, 15, 514–541; (b) Paquette, L.
A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.; Schomer,
10. Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734–
736.
11. (a) Krasinski, A.; Jurczaka, J. Tetrahedron Lett. 2001, 42,
2019–2021; (b) Singh, S.; Han, H. Tetrahedron Lett. 2004,
45, 6349–6352.