A novel case of 1,3-asymmetric induction in rhodium-catalyzed hydroformylation of an allylic double bond using perbenzylated C-glucosides as chiral directors

Article abstract of DOI:10.1016/j.tetasy.2005.09.030

1-(2′,3′,4′,6′-Tetra-O-benzyl-α-d- glucopyranosyl)-2-propene 1a and 1-(2′,3′,4′,6′-tetra-O- benzyl-β-d-glucopyranosyl)-2-propene 1b were hydroformylated at different temperatures affording linear and branched aldehydes in either a 1:1 or 2:1 regioisomeric

Full text of DOI:10.1016/j.tetasy.2005.09.030

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3661–3666
A novel case of 1,3-asymmetric induction in rhodium-catalyzed
hydroformylation of an allylic double bond using perbenzylated
C-glucosides as chiral directors
Raffaello Lazzaroni,a,* Silvia Rocchiccioli,a Anna Iuliano,a
Laura Cipollab and Francesco Nicotrab
a
`
Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, via Risorgimento 35, 56126 Pisa, Italy
`
Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, P.za della Scienza 2, 20126 Milano, Italy
b
Received 26 July2005; revised 14 September 2005; accepted 19 September 2005
Available online 14 November 2005
Abstract—1-(20,30,40,60-Tetra-O-benzyl-a-D-glucopyranosyl)-2-propene 1a and 1-(20,30,40,60-tetra-O-benzyl-b-D-glucopyranosyl)-2-
propene 1b were hydroformylated at different temperatures affording linear and branched aldehydes in either a 1:1 or 2:1 regioiso-
meric ratio, depending on the stereochemistryof the starting substrate. The diastereoisomeric ratio of the branched isomer depended
on the reaction temperature as well as the alkene structure, the highest value (85:15) being obtained in the case of hydroformylation
of the a-isomer at 0 °C.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
glucals6a and C-vinyl glucosides6b also suggests that
sugar derivatives containing a different kind of double
bond could be stereoselectivelyhydroformylated.
The hydroformylation of olefins is an attractive syn-
thetic transformation that introduces an aldehyde func-
tion bymeans of atom economic formation of a C–C
bond, which represents a starting point for additional
carbon skeleton expanding operations.1 Furthermore,
addition of CO and H2 can lead to the formation of
one or even two new stereocenters, depending on the ste-
Prompted bythese considerations, we became interested
in investigating the hydroformylation of 1-(20,30,40,
60-tetra-O-benzyl-a-D-glucopyranosyl)-2-propene and
1-(20,30,40,60-tetra-O-benzyl-b-D-glucopyranosyl)-2-pro-
pene 1a and 1b (Fig. 1),7 where a methylene group sep-
arates the alkene function from the C-glucoside. Much
effort has been devoted to the functionalization of the
allylic appendage of C-glycosides, such as oxidative deg-
radation,8 palladium-mediated oxidation,9 or hydroxy-
iodination.10 In this context, the possibilityoffered by
the hydroformylation reaction to perform a one-pot
reochemical features of the olefin substrate. Stereoselec-
tivitycan be induced using chiral diphosphines
2
as
ligands of rhodium (I), as well as via substrate control
3
bya chiral starting alkene. Substrate control has been
realized using chiral conformationallydefined bicyclic
structures, for example, in the diastereoselective hydro-
formylation of a-pinene,4 or byintroducing catalsyt
directing groups on the alkene skeleton. This is a group
that is able to precoordinate the catalytically active spe-
cies, giving rise to the selective positioning of the catalyst
at one of the two diastereotopic faces of the olefin, such
as in the case of methallylic alcohols.5 Sugar derivatives
have also been used as chiral architectures for substrate
controlled stereoselective hydroformylation.6 The good
stereoselectivity obtained in the hydroformylation of
Bn
Bn
O
O
H
H
H
H
Bn
Bn
O
O
O
O
O
O
O
O
H
H
H
Bn
Bn
Bn
1b
Bn
H
H
H
1a
*
Corresponding author. Tel.: +39 050 2219 227; fax: +39 050 2219
260; e-mail: lazza@dcci.unipi.it
Figure 1.
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.09.030

3662
R. Lazzaroni et al. / Tetrahedron: Asymmetry 16 (2005) 3661–3666
reaction able to elongate or branch the allylic residue is
veryattractive.
CDCl3, carried out directlyon the crude reaction mix-
ture after removing the reaction solvent and catalyst.
This determination is straightforward because the pro-
ton resonances of the formyl group of linear and
branched aldehydes are well separated as well as those
of the two diastereoisomeric products. The reaction is
regioselective in the case of 1b, affording a prevalence
of the branched isomer (regioisomeric ratio 2b/3b ffi 2),
while a similar amount of the two isomers is obtained
starting from 1a. Reaction temperature does not affect
the regioisomeric ratio to a significant extent with either
substrate, at least within the examined range (0–40 °C).
In both cases, the linear aldehyde can be easily separated
from the branched one, byflash chromatography, also
allowing a complete characterization of both regioisom-
ers. As far as the diastereoselectivityis concerned, a
significant prevalence of one diastereomer is observed
in both cases. C-Glucoside 1a afforded a prevalence of
the diastereomer whose CH@O proton resonates
at lower NMR frequencies. In contrast, starting from
1b a prevalence of the diastereomer whose CH@O
proton resonates at higher NMR frequencies is
achieved.
Our experience in the field of stereoselective hydro-
formylation indicates that a good level of asymmetric
induction can be achieved with open chain olefin sub-
strates possessing a stereogenic center in b to the double
bond, provided additional electronic factors are present,
such as in the case of vinyl ethers.11 In this regard, the
use of chiral substrates 1a and 1b is also of interest in
order to check the possibilityof obtaining good levels
of 1,3-asymmetric induction in the hydroformylation
of an isolated terminal double bond.
2. Results and discussion
2.1. Hydroformylation
Taking into account the well-known high reactivityof
allyl-substrates against unmodified rhodium catalysts,12
hydroformylation of 1a and 1b was carried out with
Rh4(CO)12 at 80 atm of CO and H2 (1:1) and low tem-
peratures (0–40 °C). These mild reaction conditions
can be adapted to investigate the influence of substrate
structure on both regioselectivityand diastereoselectiv-
ityof the reaction. Since the rate determining step of
the hydroformylation reaction is the formation of the
catalytically active Rh–H species,13 to perform the runs
at 0 °C, this species was generated byreacting
Rh4(CO)12 with CO (40 atm) and H2 (40 atm) at 40 °C
for 30 min, then freezing the reaction mixture at 0 °C
and introducing the substrate at that temperature.
Reaction temperature significantlyinfluenced the diaste-
reoisomeric ratio in the case of 1a: bylowering the tem-
perature from 40 to 0 °C the diastereomeric ratio
increased from 70:30 (entry1) to 85:15 (entry3). Con-
versely, the temperature did not affect the diastereoselec-
tivityof 1b hydroformylation, which afforded the same
diastereoisomeric ratio in passing from 40 to 0 °C
(entries 4–6).
2.2. Configuration assignment
As expected, the hydroformylation of the two substrates
gives the linear 3 and branched 2 regioisomers, the last
one being formed as a mixture of diastereoisomers.
The results obtained are reported in Table 1.
The assignment of the absolute configuration of the new
stereocenter was determined byNMR after oxidation of
aldehydes 2a and 2b with NaClO2/NaH2PO4 to the
14
corresponding carboxylic acids 4a and 4b, respectively,
and subsequent double derivatization with phenylgly-
cine methyl esters (PGME) in both the enantiomeric
forms [(R)-PGME and (S)-PGME] to derivatives 5
and 6, respectively( Scheme 1).
Complete substrate conversion was obtained after 7 h at
40 °C, while at 0 °C much more time was necessary
(24 h). Both regioisomeric and diastereoisomeric ratios
1
were determined by H NMR spectra at 600 MHz in
Table 1. Hydroformylation of 1a and 1b
OBn
OBn
OBn
H
H
H
H
Rh4(CO)12, toluene,
H
H
O
O
O
+
BnO
BnO
BnO
BnO
BnO
BnO
H
H
H
CO (40 atm)
H2 (40 atm)
CHO
H
H
H
*
*
*
OBn
OBn
OBn
H
H
H
CHO
2a: ∗ = α
2b: ∗ = β
3a: ∗ = α
3b: ∗ = β
1a: ∗ = α
1b: ∗ = β
EntryAlkene
Temp (
°C)
Time (h)a
2/3 ratiob
Diastereomeric ratio of 2b (S/R)
1
2
3
4
5
6
1a
1a
1a
1b
1b
1b
40
25
0
40
25
0
7
7
24
7
7
24
47/52
50/50
50/50
64/36
66/34
66/34
70:30
80:20
85:15
30:70
30:70
30:70
a All the reactions were carried out to complete substrate conversion.
b Determined by 1H NMR analysis.

R. Lazzaroni et al. / Tetrahedron: Asymmetry 16 (2005) 3661–3666
3663
OBn
O
OBn
Ph
4'
BnO
BnO
H
b
O
COOMe
5'
O
OBn
BnO
BnO
2'
N
H
a
3'
1''
1'
2a
5a
H
OBn
COOH
OBn
4a
O
BnO
BnO
c
H
Ph
O
COOMe
OBn
6a
N
H
OBn
Ph
H
O
O
COOMe
5'
BnO
BnO
4'
2'
OBn
N
b
1'
OBn
5b
3'
H
O
BnO
BnO
a
1''
2b
COOH
OBn
H
4b
OBn
c
H
O
Ph
O
BnO
BnO
COOMe
N
OBn
H
6b
Only the absolute configuration of the prevailing stereoisomer is indicated
Scheme 1. Reagents and conditions: (a) NaClO2, 1.25 M aq NaH2PO4, CH3CN; (b) (R)-PGMEÆHCl, PyBroP, DIPEA, DMF; (c) (S)-PGMEÆHCl,
PyBroP, DIPEA, DMF.
Table 2. Chemical shifts (ppm) of the relevant protons of derivatives 5
and 6 for the configuration assignment
NOEs experiments on compounds 5 and 6 are in agree-
ment with a planar arrangement of the C-20-C-50 chain,
as depicted in Figure 2 for the (R)-PGME derivatives, as
H100
H-10a
H-10b
15
alreadyreported with different PGME derivatives.
5a
6a
1.21
1.81
1.89
+0.08
1.34
1.93
1.97
+0.04
2.02
Given this conformation, R1 protons will be more
shielded bythe phenyl group in the ( R)-PGME deriva-
tives then those of the (S)-PGME, hence the absolute
configuration of the stereocenter can be determined.
1.15
À0.06
1.03
Dd(d(S) À d(R)
)
5b
6b
1.07
1.27
1.96
Dd(d(S) À d(R)
)
+0.04
À0.07
À0.08
Chemical shifts of the relevant protons and Dd(d(S)
À
d
(R)) values for derivatives 5 and 6 are reported in Table
2; an (S)-configuration was determined for the major
isomer 4a, hence aldehyde 2a, and an (R)-configuration
for derivative 4b, and aldehyde 2b.
3. Conclusion
1-(20,30,40,60-Tetra-O-benzyl-a-D-glucopyranosyl)-2-pro-
pene 1a and 1-(20,30,40,60-tetra-O-benzyl-b-D-glucopyr-
anosyl)-2-propene 1b have proven to be suitable chiral
synthons for the 1,3-asymmetric induction in the stereo-
selective hydroformylation, providing diastereoisomeric
excesses up to 70%. The extent of diastereoselectivity
as well as the sense of asymmetric induction depends
on the absolute configuration of the C-anomeric center.
Starting from the a-anomer, a higher diastereoisomeric
Shielded
H
O
Ph
R1
OCH3
R2
N
H
H
O
Figure 2.

3664
R. Lazzaroni et al. / Tetrahedron: Asymmetry 16 (2005) 3661–3666
ratio (85:15) was achieved with the newlyformed stere-
ogenic center of the prevalent diastereomer having an
(S)-absolute configuration. The b-isomer affords lower
prevalence (70:30) of the diastereomer having an (R)-
configuration at the new stereogenic center. Conversely
little or no regioselectivitywas observed; although the
separation byflash chromatographyof the regioisomers
allowed us to obtain isomericallypure products. These
results open new perspectives concerning the use of
different glycosides as chiral synthons for the 1,3-asym-
metric induction in the stereoselective hydroformylation
of their C-allyl derivatives. Studies are currently in pro-
gress on this topic aimed at using the hydroformylation
of the C-allyl glycosides not only to study the stereose-
lectivityof the reaction but also to obtain sugar deriva-
tives, which can be further functionalized as well as
linked to solid matrixes.
20H, CH2–Ph, CH2–O), 7.32 (m, 40H, Ar), 9.64 (d,
J = 0.8 Hz, 1H, CHOmajor diastereomer), 9.66 (d, J =
0.8 Hz, 1H, CHOminor diastereomer).
13C NMR (50 MHz, CDCl3) d 14.5, 30.0, 42.6, 69.2,
71.7, 72.1, 73.3, 73.8, 75.3, 75.7, 80.0, 82.3, 97.3,
127.9–128.7, 138.3–138.9, 204.5.
22
4.2.2. Characterization of 3a. ½aŠ ¼ þ36:8 (c 1.1,
D
1
CH2Cl2). H NMR (600 MHz, CDCl3) d 1.61–1.75 (m,
4H, CH2), 2.47–2.40 (m, 2H, CH2), 3.78–3.55 (m, 4H,
CHgluc), 4.00 (m, 1H, anomericH), 4.94–4.45 (m, 10H,
CH2–Ph, CH2–O), 7.32 (m, 20H, Ar.), 9.74 (t,
J = 1.4 Hz, 1H, CHO) 13C NMR (50 MHz, CDCl3) d
18.1, 24.0, 43.3, 69.1, 71.1, 73.2, 73.4, 73.8, 75.0, 75.4,
78.1, 80.1, 82.4, 127.5–128.4, 138–138.7, 202.2.
4.2.3. Characterization of 2b and 3b. 1H NMR
(600 MHz, CDCl3)
d
1.07 (d, J = 6.6 Hz, 3H,
4. Experimental
4.1. General
CH3-minor diastereomer), 1.10 (d, J = 6.6 Hz, 3H,
CH3-major diastereomer), 1.65–1.86 (m, 4H), 2.19–2.15 (m,
2H), 2.57–2.42 (m, 6H), 3.72–3.23 (m, 15H, CHring),
4.93–4.49 (m, 30H, CH2–Ph, CH2–O), 7.3 (m, 60H,
Ar), 9.59–9.58 (d, J = 2 Hz, 1H, CHOminor diastereomer),
9.62–9.61 (d, J = 2 Hz, 1H, CHOmajor diastereomer), 9.72
(t, J = 1.8 Hz, 1H, CHOlinear). 13C NMR (50 MHz,
CDCl3) d 13.5, 18.3, 30.9, 33.0, 42.9, 43.7, 68.9, 69.1,
73.5, 74.9, 75.1, 75.2, 75.5, 76.5, 78.4, 78.6, 78.9, 82.0,
87.2, 87.3, 127.6–128.4, 138.1–138.5, 202.5, 204.5.
1H and 13C NMR spectra were recorded in CDCl3 on
either a Varian Gemini-200 MHz, a Varian Mercury-
400 MHz or a Varian Inova-600 MHz NMR spectro-
meters, using TMS as an internal standard. The following
abbreviations are used: s = singlet, d = doublet,
dd = double doublet, t = triplet,
m = multiplet,
br = broad. TLC analyses were performed on silica gel
60 Macherey-Nagel sheets; flash chromatography sepa-
rations were carried out on adequate dimension columns
using silica gel 60 (230–400 mesh). Optical rotations
were measured with a JASCO DIP-360 digital polarim-
eter. Toluene was dried over molecular sieves and dis-
tilled under nitrogen. Rh4(CO)12 was prepared
according to a known procedure.16 C-Allyl glucosides
were prepared as described elsewhere and matched the
reported characteristics.7 Unless otherwise stated, the
reagents were used without anyfurther purification.
4.3. Oxidation of aldehydes 2a and 2b: general procedure
Aldehyde 2a or 2b (0.151 mmol) was dissolved in
CH3CN (2 mL), then NaClO2 (5 equiv) and a 1.25 M
aqueous solution of NaH2PO4Æ2H2O (5 equiv) were
added. The solution was stirred for 1 h, the reaction
quenched with sodium thiosulfate and the solvent
reduced in vacuo. The residue was diluted with diethyl
ether, filtered, and the solution evaporated to dryness
affording 4a or 4b as a colorless oil (0.092 g, quantitative
yield). The crude acids, as a mixture of diastereoisomers,
were used for the subsequent derivatization without any
further purification.
4.2. Hydroformylation of C-allyl glucosides 1a and 1b:
general procedure
A solution of C-allyl glucoside 1a or 1b and Rh4(CO)12
(ratio substrate/Rh = 100/1) in toluene was introduced
bysuction into an evacuated 25 mL stainless steel reac-
tion vessel. Carbon monoxide was introduced and the
autoclave then rocked, while being kept at the desired
temperature with hydrogen introduced rapidly to
100 atm (CO/H2 = 1:1) total pressure. The reaction
NMR data refers to the major isomer (aromatic signals
are omitted).
4.3.1. Characterization of 4a. 1H NMR (400 MHz,
CDCl3) d 1.27 (d, 3H, J = 6.9 Hz, H-100), 1.75 (ddd,
1H, J = 13.5, 12.0, 3.8 Hz, H-10a), 2.03 (ddd, 1H,
J = 13.5, 10.3, 3.0 Hz, H-10b), 2.59–2.65 (m, 1H, H-20),
3.46–3.70 (m, 6H, H-2, H-3, H-4, H-5, H-6), 4.13
(ddd, 1H, J = 12.0, 5.0, 3.0 Hz, H-1), 4.36–4.48 (m,
2H, PhCH2O), 4.51–4.58 (m, 3H, PhCH2O), 4.65–4.74
(m, 2H, PhCH2O), 4.85 (d, 1H, J = 10.8 Hz, PhCH2O).
13C NMR (100.57 MHz, CDCl3) d 18.7 (q, C-100), 28.6
(t, C-10), 35.8 (d, C-20), 69.3, 73.2, 73.9, 75.5, 75.9 (5t,
4PhCH2O, C-6), 71.8, 72.3, 78.3, 80.0, 82.5 (5 d, C-1,
C-2, C-3, C-4, C-5), 182.0 (s, C@O).
was monitored byTLC (SiO , CH2Cl2/acetone = 98:2).
2
After removing the solvent at reduced pressure the crude
products were purified byflash chromatography(SiO
,
2
CH2Cl2/acetone = 98/2) affording the pure aldehydes
as brown solids (80% yield).
4.2.1. Characterization of 2a. 1H NMR (600 MHz,
CDCl3) d 1.09 (d, J = 7.2 Hz, 3H, CH3-minor diastereomer),
1.15 (d, J = 7.2 Hz, 3H, CH3-major diastereomer), 1.76–1.82
(m, 4H, –CH2), 2.12 (m, 2H, CH–CH3), 3.55–3.78 (m,
8H, CHring), 4.06 (m, 1H, anomericHmajor diastereomer),
4.16 (m, 1H, anomericHminor diastereomer), 4.45–4.94 (m,
4.3.2. Characterization of 4b. 1H NMR (400 MHz,
CDCl3) d 1.01 (d, 3H, J = 7.1 Hz, H-100), 1.42 (ddd,
1H, J = 13.9, 10.0, 4.0 Hz, H-10a), 2.12 (ddd, 1H,

R. Lazzaroni et al. / Tetrahedron: Asymmetry 16 (2005) 3661–3666
3665
J = 13.9, 10.0, 2.5 Hz, H-10b), 2.63–2.70 (m, 1H, H-20),
3.14–3.29 and 3.52–3.68 (m, 7H, H-1, H-2, H-3, H-4,
H-5, H-6), 4.35–4.90 (m, 8H, PhCH2O). 13C NMR
(100.57 MHz, CDCl3) d 18.4 (q, C-100), 36.0 (t, C-10),
36.3 (d, C-20), 69.3, 73.8, 75.2, 75.5, 75.9 (5t, 4PhCH2O,
C-6), 78.7, 79.1, 79.3, 82.6, 87.5 (5 d, C-1, C-2, C-3, C-4,
C-5), 182.1 (s, C@O).
(0.031 g, 94% yield). 1H NMR (400 MHz, CDCl3) d
1.15 (d, 3H, J = 6.8 Hz, H-100), 1.89 (ddd, 1H,
J = 15.0, 12.3, 4.3 Hz, H-10a), 1.97 (ddd, 1H, J = 15.0,
11.0, 4.5 Hz, H-10b), 2.54–2.60 (m, 1H, H-20), 3.47
(ddd, 1H, J = 11.0, 5.4, 4.3 Hz, H-1), 3.53 (dd, 1H,
J = 9.5, 6.2 Hz, H-6a), 3.60–3.84 (m, 8H, H-2, H-3, H-
4, H-5, H-6b, COOCH3), 4.35 and 4.39 (ABq, 2H,
J = 12.0 Hz, PhCH2O), 4.47 and 4.83 (ABq, 2H,
J = 10.8 Hz, PhCH2O), 4.58 and 4.69 (ABq, 2H, J =
11.5 Hz, PhCH2O), 4.78 and 4.96 (ABq, 2H, J =
11.0 Hz, PhCH2O), 5.40 (d, 1H, J = 6.5 Hz, H-40),
7.08 (d, 1H, J = 6.5 Hz, NH). 13C NMR (100.57 MHz,
CDCl3) d 18.3 (q, C-100), 30.1 (t, C-10), 35.8 (d, C-20),
52.9 (d, C-40), 57.3 (q, COOCH3), 70.1, 72.7, 73.6,
75.4, 75.8 (5t, 4PhCH2O, C-6), 70.8, 71.6, 78.7, 80.1,
82.6 (5 d, C-1, C-2, C-3, C-4, C-5), 171.4, 175.5 (2s,
C@O).
4.4. Preparation of PGME amides: general procedure
Acids 4a and 4b (1 equiv) and phenylglycine methyl
esters (1.2 equiv) were dissolved in dryDMF (0.3 mL),
after which PyBroP (1.5 equiv) and DIPEA (4.5 equiv)
were added sequentially. After 1 h, the reaction mixture
was concentrated to dryness. Purification by flash chro-
matography(SiO , light petroleum/EtOAc = 7/3) affor-
2
ded amides 5 and 6.
4.4.1. Characterization of 5a. Compound 4a
(0.052 mmol) was treated with (R)-PGME following
the general procedure to afford 5a as white solid
(0.022 g, 82% yield). 1H NMR (400 MHz, CDCl3) d
1.21 (d, 3H, J = 6.8 Hz, H-100), 1.81 (ddd, 1H,
J = 14.9, 12.0, 3.8 Hz, H-10a), 1.93 (ddd, 1H, J = 14.9,
11.5, 3.9 Hz, H-10b), 2.54–2.59 (m, 1H, H-20), 3.84 (t,
1H, J = 9.5 Hz, H-4), 3.50 (dd, 1H, J = 9.9, 6.0 Hz,
H-6a), 3.57–3.78 (m, 7H, H-2, H-3, H-5, H-6b, COOCH3),
3.87 (ddd, 1H, J = 11.5, 5.3, 3.9 Hz, H-1), 4.37 and 4.44
(ABq, 2H, J = 11.4 Hz, PhCH2O), 4.49 and 4.55 (ABq,
2H, J = 12.4 Hz, PhCH2O), 4.73 and 4.89 (ABq, 2H,
J = 11.0 Hz, PhCH2O), 4.77 and 4.80 (ABq, 2H,
J = 10.8 Hz, PhCH2O), 5.59 (d, 1H, J = 7.2 Hz, H-40),
6.98 (d, 1H, J = 7.2 Hz, NH). 13C NMR (100.57 MHz,
CDCl3) d 18.7 (q, C-100), 30.1 (t, C-10), 36.4 (d, C-20),
53.0 (d, C-40), 56.8 (q, COOCH3), 69.8, 72.6, 73.7,
75.4, 75.8 (5t, 4PhCH2O, C-6), 71.0, 71.6, 78.6, 79.9,
82.5 (5 d, C-1, C-2, C-3, C-4, C-5), 171.3, 175.3 (2s,
C@O).
4.4.4. Characterization of 6b. Compound 4b
(0.049 mmol) was treated with (S)-PGME following
the general procedure, affording 6b as white solid
(0.037 g, quantitative yield). 1H NMR (400 MHz,
CDCl3) d 1.07 (d, 3H, J = 6.8 Hz, H-100), 1.27 (ddd,
1H, J = 14.0, 11.3, 4.2 Hz, H-10a), 1.96 (ddd, 1H,
J = 14.0, 10.1, 3.0 Hz, H-10b), 2.56–2.62 (m, 1H, H-20),
2.67–2.71 (m, 1H, H-5), 2.87 (ddd, 1H, J = 11.3, 9.0,
3.0 Hz, H-1), 3.05 (t, 1H, J = 9.0 Hz, H-2), 3.20–3.38
(m, 4H, H-3, H-4, H-6) 3.63 (s, 3H, COOCH3), 4.34–
4.82 (m, 8H, PhCH2O), 5.59 (d, 1H, J = 6.5 Hz, H-40),
6.71 (d, 1H, J = 6.5 Hz, NH). 13C NMR (400 MHz,
CDCl3) d 18.3 (q, C-100), 30.1 (t, C-10), 36.9 (d, C-20),
52.9 (d, C-40), 56.4 (q, COOCH3), 69.3, 73.6, 74.9,
75.3, 75.8 (5t, 4PhCH2O, C-6), 76.5, 78.3, 78.9, 83.1,
87.1 (5 d, C-1, C-2, C-3, C-4, C-5), 171.5, 175.2 (2s,
C@O).
References
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4.4.2. Characterization of 5b. Compound 4b
(0.031 mmol) was treated with (R)-PGME following
the general procedure, to afford 5b as a white solid
(0.024 g, quantitative yield). 1H NMR (400 MHz,
CDCl3) d 1.03 (d, 3H, J = 6.8 Hz, H-100), 1.34 (ddd,
1H, J = 14.7, 12.0, 3.8 Hz, H-10a), 2.02 (ddd, 1H,
J = 14.7, 12.7, 3.0 Hz, H-10b), 2.59–2.64 (m, 1H, H-20),
3.15 (t, 1H, J = 9.1 Hz, H-2), 3.35 (t, 1H, J = 9.1 Hz,
H-4), 3.40 (dd, 1H, J = 10.0, 4.3 Hz, H-6a), 3.47 (ddd,
1H, J = 12.0, 9.1, 3.0 Hz, H-1), 3.57 (dd, 1H, J = 10.0,
1.7 Hz, H-6b), 3.63 (s, 3H, COOCH3), 3.67–3.73 (m,
2H, H-5, H-3), 4.21 (br s, 2H, PhCH2O), 4.42 and
4.74 (ABq, 2H, J = 10.8 Hz, PhCH2O), 4.58 and 4.75
(ABq, 2H, J = 10.8 Hz, PhCH2O), 4.82 (br s, 2H,
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J = 7.8 Hz, NH). 13C NMR (100.57 MHz, CDCl3) d
18.1 (q, C-100), 30.1 (t, C-10), 36.5 (d, C-20), 52.9 (d, C-
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4PhCH2O, C-6), 75.8, 77.9, 79.4, 83.6, 87.3 (5 d, C-1,
C-2, C-3, C-4, C-5), 171.5, 175.5 (2s, C@O).
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(0.044 mmol) was treated with (S)-PGME following
the general procedure, affording 6a as white solid
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