Synthesis of C-glycosyl amino acids: Scope and limitations of the tandem Tebbe/Claisen approach

Article abstract of DOI:10.1016/j.tetasy.2004.11.035

Amino acids may be used as coupling partners for esterification with 3-hydroxy glycals as substrates for the tandem Tebbe/Claisen approach to the synthesis of C-glycosyl amino acids. Whilst esters of substituted α-amino acids do not successfully undergo T

Full text of DOI:10.1016/j.tetasy.2004.11.035

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 45–55
Synthesis of C-glycosyl amino acids: scope and limitations of
the tandem Tebbe/Claisen approach
David J. Chambers,a Graham R. Evansb and Antony J. Fairbanksa,*
aChemistry Research Laboratory, Oxford University, Mansfield Road, Oxford OX1 3TA, UK
bCelltech R&D, Granta Park, Great Abington, Cambridge CB1 6GS, UK
Received 21 October 2004; accepted 17 November 2004
Available online 24December 2004
Abstract—Amino acids may be used as coupling partners for esterification with 3-hydroxy glycals as substrates for the tandem
Tebbe/Claisen approach to the synthesis of C-glycosyl amino acids. Whilst esters of substituted a-amino acids do not successfully
undergo Tebbe, or other, methylenation, esters of b- or c-amino acids are methylenated to yield vinyl ethers, which then undergo
smooth thermal rearrangement to yield b-C-glycoside products. tert-Butyl esters are found to be unreactive to the Tebbe reagent,
and as such tert-butyl protection may be used for other carboxylic acids.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
tandem approach (Fig. 1) initially involves esterification
of a glycal possessing a free 3-hydroxyl with a carboxylic
acid. Tebbe methylenation7 of the resultant ester can
then be followed by [3,3] sigmatropic rearrangement8,9
yielding the C-glycoside product in a predictable and en-
tirely stereoselective fashion.
Naturally occurring glycoproteins, glycopeptides and
peptidoglycans constitute an enormously diverse array
of biologically important molecules in which carbohy-
drates are covalently linked to amino acids via a variety
of different linkages. For example, carbohydrates are
covalently linked to N-linked and O-linked glycopro-
teins via direct glycosidic linkages between the anomeric
position of either N-acetyl glucosamine or N-acetyl
galactosamine residues, and asparagine or serine/threo-
nine side chains, respectively.1 In contrast the carbohy-
drate–amino acid linkages found in peptidoglycans,
which constitute major components of bacterial cell
walls, generally consist of ester linkages formed between
amino acid and carbohydrate hydroxyls.2
The attraction of this approach is that the a-carboxylic
group of any proteinogenic a-amino acid, or the b- or c-
carboxylic groups of aspartic or glutamic acids may be
used for the esterification step, thus implying ready ac-
cess to a wide range of C-glycosyl amino acid materials.
Herein full details of investigations into the applicability
of the tandem Tebbe/Claisen approach for the synthesis
O
O
O
O
Significant interest has recently arisen in the synthesis of
C-glycosyl amino acids,3,4 in which carbohydrate and
amino acid are linked via a carbon–carbon bond at
the anomeric centre of the sugar, particularly as poten-
tial building blocks for the synthesis of C-glycopeptides
as non-hydrolysable N- or O-linked glycopeptide mimet-
ics.5 In principle the Tebbe/Claisen approach, which as
recently reported allows stereospecific access to a range
of C-glycoside materials,6 could be advantageously ap-
plied to the synthesis of C-glycosyl amino acids. This
R'O
R'O
R'O
R'O
+
R
OH
OH
O
R
Tebbe
O
O
R
R'O
R'O
Claisen
R'O
R'O
O
O
R
*
Corresponding author. Tel.: +44 1865275647; fax: +44 1865275674;
e-mail: antony.fairbanks@chem.ox.ac.uk
Figure 1.
0957-4166/$ - see front matter ꢀ 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.11.035

46
D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
of C-glycosyl amino acids are provided, and delineated
the scope and limitations of this methodology are given.
b-amino and c-amino acids 6 and 7 were also esterified
with the glucal 1, to yield the esters 8 and 96c as sub-
strates for Tebbe methylenation (Scheme 1). Another as-
pect of the research programme was to investigate the
feasibility the general approach using the side chain car-
boxylic acids of aspartic acid and glutamic acid. This
strategy would require protection of the a-carboxylic
acid in both cases, and it was reasoned that this could
be possible by protection as the corresponding tert-butyl
esters. In order to investigate the compatibility of tert-
butyl ester protection with the Tebbe reaction glucal 1
was esterified with the carboxylic acid 10, to yield the
diester 11 (Scheme 1). Finally a variety of aspartic acid
and glutamic acid side chain esters were also synthesised
by reaction of the commercially available protected
aspartic acid and glutamic acid derivatives 12 and 16
with silyl protected glucal 1, and also with the sterically
less encumbered 4,6-O-benzylidene protected glucal
14,12 to yield the esters 13, 15 and 17 as substrates for
subsequent methylenation reactions (Scheme 1).
2. Results and discussion
2.1. Synthesis of ester substrates
The two glycals initially selected for esterification reac-
tions were the easily accessible 4,6-O-di-tert-butylsilyl
protected glucal and allal derivatives 1 and 2 (Fig. 2),
which were readily accessed using published synthetic
routes.6 Previous studies had also revealed that Boc pro-
tection of nitrogen functionality was compatible with
Tebbe/Claisen approach in so far as that tert-butyl car-
bamates were unreactive to the Tebbe reagent.6 A vari-
ety of commercially available N-Boc protected amino
acids 3a–e were therefore selected as coupling partners.
The D-serine derivative 3f, which is the enantiomer of
GarnerÕs acid,10 was accessed by base mediated hydroly-
sis of the corresponding known methyl ester.11 A series
of esterification reactions, mediated by dicyclohexylcar-
bodiimide (DCC) with catalytic dimethylamino pyridine
(DMAP) in dichloromethane (DCM), then yielded the
corresponding glucal (4a, 4b,6c 4c, 4d, 4f) and allal esters
(5b, 5e, 5f) all in high yield (Fig. 2).
O
(i)
(i)
(i)
O
NHBoc
But2Si
1 +
HO2C
O
8
6
7
O
O
O
One particular aim of the programme was to investigate
the effect of the length of the methylene linker between
carboxylic acid and amino functions on the efficiency
of the Tebbe reaction. Therefore the N-Boc protected
O
NHBoc
O
1 +
But2Si
HO2C
NHBoc
O
O
O
9
O
O
CO2But
O
O
O
NHBoc
1 +
1 +
O
HO2C
But2Si
But2Si
But2Si
10
O
O
O
OH
OH
O
O
O
11
2
1
R
CO2But
O
O
N
O
O
NHBoc
CO2H
But2Si
OH
O
(i)
CO2H
3a R = H
3b R = Me
3c R = CH2Ph
3d R = CH2CHMe2
3e R = CH2CH2SMe
Boc
O
BocHN
CO2But
3f
12
BocHN
13
CO2But
O
O
O
O
O
O
But2Si
O
But2Si
O
O
O
(i)
OH
+
Ph
O
O
O
O
O
O
Ph
O
BocHN
CO2But
12
O
OH
14
R
NHBoc
R
NHBoc
BocHN
4a R = H
15
5b R = Me
5e R = CH2CH2SMe
CO2But
4b R = Me
4c R = CH2Ph
4d R = CH2CHMe2
O
O
OH
O
O
O
O
O
O
O
(i)
+
Ph
O
But2Si
But2Si
Ph
O
O
O
O
O
BocHN
CO2But
OH
14
O
O
O
O
17
16
4f
5f
NBoc
NBoc
BocHN
CO2But
O
O
Scheme 1. Reagents and conditions: (i) DCC, DMAP, CH2Cl2, rt; 8,
81%; 9, 92%; 11, 97%; 13, 93%; 15, 93%; 17, 98%.
Figure 2.

D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
47
2.2. Methylenation reactions
O
O
O
O
O
(i)
But2Si
But2Si
O
O
Methylenation reactions by the Tebbe reagent were at-
tempted on a wide selection of the esters derived from
substituted a-amino acids (4b–d,f, 5b,e,f). However in
all cases the predominant product obtained was the gly-
cal alcohol 1 or 2, presumably formed by ester cleavage,
rather than the desired methylenated product. In certain
cases (e.g., reaction of 4b) the methylenated product was
observed, but never in more that 10% yield, making this
route synthetically impractical. In light of these prob-
lems a variety of alternative reagents13 were screened,
but none were capable of methylenating any of these
esters in reasonable yield.
O
O
11
21
CO2But
(i)
CO2But
O
O
O
O
O
O
But2Si
But2Si
O
O
O
BocHN
BocHN
13
22
CO2But
CO2But
O
O
(i)
O
O
O
O
Ph
Ph
In order to more precisely investigate the failure of these
methylenation reactions, Tebbe reagent mediated meth-
ylenation was attempted on esters 4a, 8 and 9, all of
which are derived from amino acids that are not substi-
tuted at the position a to the carbonyl, and which con-
O
O
O
BocHN
BocHN
15
23
CO2But
CO2But
stitute
a homologous series in which additional
O
O
(i)
O
O
O
O
methylene units are incorporated between the ester
and amino functional groups. In contrast to the esters
derived from substituted a-amino acids successful meth-
ylenation was achieved in all three cases, yielding the de-
sired enol ether products 18, 19 and 206c in 44%, 80%
and 82% yields, respectively (Scheme 2). It is clear from
this result that increasing the number of methylene units
between amine and ester from one to two or more
improves the efficiency of Tebbe methylenation
markedly.14
Ph
Ph
O
O
O
17
24
BocHN
CO2But
BocHN
CO2But
Scheme 3. Reagents and conditions: (i) Tebbe reagent, THF, pyridine,
ꢁ40 ꢁC to rt, 16 h; 21, 83%; 22, 6%; 23, 22% (50% based on recovered
starting material); 24, 47%.
The lack of successful methylenation of esters derived
from substituted a-amino acids indicated that the
Tebbe/Claisen approach could probably only be usefully
applied to esters derived from the side chains of aspartic
and glutamic acids. Firstly in order to investigate if tert-
butyl ester protection was indeed compatible with Tebbe
reaction, methylenation of diester 11 was undertaken.
Reaction occurred smoothly to yield the desired methyl-
enated product 21 in 83% yield, and importantly no
competitive reaction of the tert-butyl ester was observed
(Scheme 3). Tebbe methylenation was then attempted on
tert-butylsilyl protected aspartic acid ester 13. Unfortu-
nately the desired product 22 could only be isolated in
extremely low yield (ꢀ6%) though in contrast to the
studies on the a-amino acid esters the remainder of the
mass balance was unreacted ester. It was reasoned that
this lack of reactivity may be due to steric effects. Indeed
when the less encumbered benzylidene protected aspar-
tic acid ester 15 was reacted under identical conditions
the methylenated product 23 was formed in an apprecia-
bly better, but still rather unsatisfactory yield (22%, 50%
based on recovered starting material). However the cor-
responding benzylidene protected glutamic acid ester 17
did undergo satisfactory methylenation, to yield the de-
sired product 24 (47% yield).
O
O
O
O
(i)
O
O
But2Si
X
But2Si
O
O
O
O
4b-d,f, 5b,e,f
R
NHBoc
R
NHBoc
NHBoc
O
O
O
(i)
O
But2Si
But2Si
O
O
O
O
4a
18
NHBoc
O
O
O
O
(i)
O
O
But2Si
But2Si
O
8
O
19
O
NHBoc
NHBoc
O
O
O
O
(i)
O
O
But2Si
But2Si
O
O
O
9
20
2.3. Claisen rearrangements
NHBoc
NHBoc
With a selection of methylenated substrates finally in
hand Claisen rearrangement was undertaken (Scheme
Scheme 2. Reagents and conditions: (i) Tebbe reagent, THF, pyridine,
ꢁ40 ꢁC to rt, 16 h; 18, 44%; 19, 80%; 20, 82%.

48
D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
only allows the synthesis of C-glycosyl amino acids de-
rived from the c-acid of glutamic acid in reasonable
yield. However tert-butyl esters have been demonstrated
to be unreactive to the Tebbe regent, and tert-butyl pro-
tection allows selective methylenation of one ester in the
presence of another, a process, which expands the scope
of the Tebbe/Claisen approach. Further studies on the
use of this tandem approach to C-glycoside synthesis
are currently in progress, and the results will be reported
in due course.
O
O
O
O
(i)
O
O
But2Si
But2Si
O
O
O
NHBoc
25
18
NHBoc
(i)
O
O
O
O
O
O
But2Si
But2Si
O
19
26
NHBoc
NHBoc
(i)
4. Experimental
4.1. General
O
O
O
O
O
O
But2Si
But2Si
O
O
20
27
NHBoc
Melting points were recorded on a Kofler hot block.
Proton nuclear magnetic resonance (dH) spectra were re-
corded on Varian Gemini 200 (200 MHz), Bruker AC
200 (200 MHz), Bruker DPX 400 (400 MHz), Bruker
AV 400 (400 MHz) or Bruker AMX 500 (500 MHz)
spectrometers. Carbon nuclear magnetic resonance
(dC) spectra were recorded on a Bruker DPX 400
(100.6 MHz) or a Bruker AMX 500 (125.75 MHz) spec-
trometer. Multiplicities were assigned using APT or
DEPT sequence. All chemical shifts are quoted on the
d-scale. Infrared spectra were recorded on a Perkin–
Elmer 150 Fourier transform spectrophotometer. Mass
spectra were recorded on VG Micromass 30F, ZAB
1F, Masslab20–250, Micromass Platform 1 APCI or
Trio-1 GCMS (DB-5 column) spectrometers, using
desorption chemical ionisation (NH3 DCI), electron im-
pact (EI), electron spray ionisation (ESI), chemical ioni-
sation (NH3 CI), atmospheric pressure chemical
ionisation (APCI) and fast atom bombardment (FAB)
techniques as stated. Optical rotations were measured
on a Perkin–Elmer 241 polarimeter with a path length
of 1 dm. Concentrations are given in g/100 mL. Micro-
analyses were performed by the microanalytical services
of the Inorganic Chemistry Laboratory, Oxford. Thin
layer chromatography (TLC) was carried out on Merck
glass backed sheets, pre-coated coated with 60F254 silica.
Plates were developed using 0.2% w/v cerium (IV) sul-
fate and 5% ammonium molybdate in 2 M sulfuric acid.
Flash chromatography was carried out using Sorbsil
C60 40/60 silica. Solvents and available reagents were
dried and purified before use according to standard pro-
cedures; dichloromethane (DCM) was distilled from cal-
cium hydride immediately before use.
NHBoc
O
O
O
O
O
O
(i)
But2Si
But2Si
O
O
CO2But
21
28
CO2But
(i)
O
O
O
O
O
O
Ph
O
Ph
O
29
BocHN
CO2But
24
BocHN
CO2But
Scheme 4. Reagents and conditions: (i) 180 ꢁC, Bu3N; 25, 77%; 26,
65%; 27, 97%; 28, 86%; 29, 47%.
4). Vinyl ethers 18, 19 and 20 all underwent smooth
thermal reaction after heating to 180 ꢁC in tributyl-
amine, to yield the corresponding b-C-glycoside prod-
ucts 25, 26 and 276c (77%, 65% and 77% yields,
respectively, Scheme 4). Likewise vinyl ether 21 under-
went rearrangement to yield the b-C-glycoside ester 28
in 86% yield. Finally the vinyl ether 24 derived from glu-
tamic acid underwent successful rearrangement to yield
the b-C-glycosyl glutamic acid derivative 29, in a
respectable 47% yield.
3. Conclusions
4.2. General procedure A: esterification
In conclusion it is clear that glycal esters derived from
substituted a-amino acids do not undergo methylena-
tion by the Tebbe, or other similar reagents. However
glycal esters derived from b-, c- or d-amino acids are
methylenated, though the efficiency of methylenation
depends on the steric accessibility of the ester. Vinyl
ethers derived from these glycal esters undergo smooth
thermal Claisen rearrangement to yield a variety of C-
glycosides in an entirely stereoselective manner. Unfor-
tunately the limitations of the methylenation step
currently mean that as far as the proteinogenic amino
acids are concerned the tandem Tebbe/Claisen approach
Glycal (1.0 equiv) and carboxylic acid (1.2–1.5 equiv)
were dissolved in anhydrous DCM, and N,N0-di-
methyl-4-amino pyridine (DMAP, 0.2 equiv) and then
dicyclohexylcarbodiimide (DCC, 2.0 equiv) were added.
The reaction mixture was stirred under an atmosphere
of argon until TLC indicated the complete consumption
of starting material. The reaction mixture was concen-
trated in vacuo, the residue taken up in ethyl acetate
and the suspension filtered through Celiteꢂ. The solu-
tion was concentrated in vacuo, and the residue purified
by flash column chromatography.

D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
49
19
D
4.3. General procedure B: Tebbe methylenation
½aŠ ¼ ꢁ53:4 (c 0.9, CHCl3); mmax (thin film) 3558 (br,
NH), 1740 (s, ester), 1722 (s, amide I), 1647 (m, C@C–
O), 1515 (m, amide II) cmꢁ1; dH (400 MHz, CDCl3)
0.98, 1.05 (18H, 2 · s, 2 · SiC(CH3)3), 1.46 (9H, s,
OC(CH3)3), 3.88–3.93 (1H, m, H-5), 3.93–4.01 (3H, m,
H-6, C(O)CH2), 4.10–4.18 (1H, m, H-4), 4.17–4.21
(1H, m, H-60), 4.73 (1H, dd, J1,2 6.0 Hz, J2,3 1.8 Hz,
H-2), 5.04 (1H, br s, NH), 5.42–5.49 (1H, m, H-3),
6.33 (1H, dd, J1,3 1.5 Hz, H-1); dC (100.6 MHz, CDCl3)
19.8, 22.7 (2 · s, 3 · C(CH3)3), 26.8, 27.4, 28.3 (3 · q,
3 · C(CH3)3), 42.5 (t, NHCH2), 65.7 (t, C-6), 72.8,
73.3, 73.5 (3 · d, C-3, C-4, C-5), 100.0 (d, C-2), 145.4
(d, C-1), 155.5, 170.3 (2 · s, 2 · C@O); m/z (ES+) 4 4 4
(5, M+H+), 461 (18, M+NHþ4 ), 466 (100%, M+Na+).
(HRMS (ES+) calcd for C21H37NO7SiNa (M+Na+)
466.2237. Found, 466.2237).
The enol ether (1.0 equiv) was dissolved in a 4:1 mixture
of anhydrous THF and anhydrous pyridine and the
solution cooled to ꢁ40 ꢁC under an atmosphere of
argon. Tebbe reagent (0.5 M in toluene, 2.0–4.0 equiv
depending on age and quality) was added dropwise,
and the reaction mixture allowed to warm to room tem-
perature with stirring. After 16 h, when TLC indicated
complete consumption of starting material, the reaction
mixture was cooled to 0 ꢁC and quenched by dropwise
addition of sodium hydroxide (0.5 M aqueous solution)
until effervescence ceased. The mixture was diluted with
petrol, stirred for 30 min and sonicated for a further
10 min. The mixture was poured onto a short column
of silica and eluted (petrol and ether with 2% triethyl-
amine), concentrated in vacuo and purified by flash col-
umn chromatography (silica; petrol and ether with 2%
triethylamine).
4.6. 3-O-(N-tert-Butoxycarbonyl-L-phenylalanine)-4,6-O-
di-tert-butylsilanediyl-D-glucal 4c
4.4. 2,2-Dimethyloxazolidine-(4R)-3,4-dicarboxylic acid
3-tert-butyl ester 3f
General procedure A: glucal 1 (Rf 0.5 (petrol–ethyl ace-
tate, 4:1), 557 mg, 1.94 mmol), N-tert-butoxycarbonyl-
L-phenylalanine 3c (640 mg, 2.53 mmol), N,N0-di-
methyl-4-amino pyridine (47 mg, 0.39 mmol) and dic-
yclohexylcarbodiimide (802 mg, 3.89 mmol) in DCM
2,2-Dimethyloxazolidine-(4R)-3,4-dicarboxylic acid 3-
tert-butyl ester 4-methyl ester11 (2.75 g, 10.6 mmol)
was dissolved in a mixture of THF (20 mL) and water
(10 mL), and lithium hydroxide (713 mg, 17.0 mmol)
was added. The mixture was stirred for 5 h 40 min, at
which time TLC (petrol–ethyl acetate, 4:1) indicated
the consumption of starting material (Rf 0.7) and the
formation of a single product (Rf 0.4). The reaction mix-
ture was concentrated in vacuo, dissolved in ethyl ace-
tate (200 mL) and washed with sodium hydrogen
sulfate (3 · 150 mL of a 1 M aqueous solution). The
organic layer was extracted with sodium bicarbonate
(4 · 150 mL), and the resulting aqueous layers neutra-
lised with solid sodium hydrogen sulfate and extracted
with ethyl acetate (5 · 150 mL). The organic layer was
dried (MgSO4), filtered and concentrated in vacuo.
The resulting residue was recrystallised (petrol) to give
(20 mL) gave ester 4c (1.14g, quant.) as a white foam;
24
D
(Rf 0.7); ½aŠ ¼ ꢁ51:3 (c 0.8, CHCl3); mmax (thin film)
3385 (br, NH), 1718 (s, ester/amide I), 1648 (m, C@C–
O), 1498 (m, amide II); dH (400 MHz, CDCl3) 0.99,
1.07 (18H, 2 · s, 2 · SiC(CH3)3), 1.43 (9H, s,
OC(CH3)3), 3.05–3.17 (2H, m, PhCH2), 3.88–4.02 (2H,
m, H-5, H-6), 4.16–4.22 (2H, m, H-4, H-60), 4.63–4.67
(2H, m, H-2, CH2CH), 5.03 (1H, d, JNH,CH 7.6 Hz,
NH), 5.37–5.39 (1H, m, H-3), 6.33 (1H, dd, J1,2
6.4Hz, J1,3 1.4Hz, H-1), 7.17–7.30 (5H, m, 5 · Ar-H);
dC (100.6 MHz, CDCl3) 19.8, 19.8, 22.7 (3 · s,
3 · C(CH3)3), 26.8, 27.4, 28.3 (3 · q, 3 · C(CH3)3),
38.4(t, PhCH 2), 54.6 (d, PhCH2CH), 65.7 (t, C-6),
72.9, 73.5, 76.7 (3 · d, C-3, C-4, C-5), 99.9 (d, C-2),
127.0, 128.4, 129.5 (3 · d, 5 · Ar-C), 135.9 (s, Ar-C),
145.3 (d, C-1), 155.0 (s, CHC@O), 171.6 (s, OC(O)N);
m/z (ES+) 592 (M+NHþ4 +MeCN, 100), 556 (M+Na+,
40), 551 (M+NHþ4 , 55), 534(M+H +, 90%). (HRMS
(ES+) calcd for C28H47O7N2Si (M+NHþ4 ) 551.3153.
Found 551.3149). (Found: C, 59.20; H, 9.10; N, 2.99.
C28H43O7NSi requires C, 59.35; H, 8.92; N, 2.88).
carboxylic acid 3f (2.58 g, 99%) as a white crystalline so-
24
D
lid, mp 56–59 ꢁC; ½aŠ ¼ þ63:1 (c 1.1, CHCl3); mmax
(KBr disc) 2980 (br, OH), 1704(s, acid), 1682 (s,
amide) cmꢁ1; dH (500 MHz, CDCl3, 363 K) 1.42 (9H,
s, C(CH3)3), 1.45, 1.56 (6H, 2 · s, 2 · CH3), 3.92–3.94
(1H, m, NHCHCHH0), 4.09–4.13 (1H, m,
NHCHCHH0), 4.27–4.29 (1H, m, NHCH), 6.20 (1H,
m, CO2H); dC (125.7 MHz, CDCl3, 363 K) 28.9 (q,
5 · CH3), 60.4(d, NHCH), 67.1 (t, NHCH CH2), 79.9,
94.5 (2 · s, (CH3)2CON, (CH3)3C), 152.1, 173.0 (2 · s,
2 · C@O); m/z (ESꢁ) 244 (MꢁH, 100%). (HRMS
(ESꢁ) calcd for C11H18NO5 (MꢁH) 244.1185. Found
244.1184).
4.7. 3-O-(N-tert-Butoxycarbonyl-L-leucine)-4,6-O-di-
tert-butylsilanediyl-D-glucal 4d
General procedure A: glucal 1 (Rf 0.5 (petrol–ethyl ace-
tate, 4:1), 204 mg, 0.71 mmol), N-tert-butoxycarbonyl-
L-leucine 3d (201 mg, 0.93 mmol), N,N0-dimethyl-4-ami-
no pyridine (17 mg, 0.14mmol) and dicyclohexylcarbo-
diimide (293 mg, 1.42 mmol) in DCM (20 mL) gave
4.5. 3-O-(N-tert-Butoxycarbonyl-20-amino-ethanoyl)-4,6-
O-di-tert-butylsilyldiyl-D-glucal 4a
ester 4d (375 mg, quant.) as a white foam; (Rf 0.6);
24
D
½aŠ ¼ ꢁ61:8 (c 1.1, CHCl3); mmax (thin film) 3378 (br,
General procedure A: glucal 1 (Rf 0.55 (petrol–ethyl ace-
tate, 4:1), 278 mg, 0.97 mmol), N-tert-butoxycarbonyl-
L-glycine 3a (221 mg, 1.3 mmol), N,N0-dimethyl-4-
amino pyridine (24mg, 0.19 mmol), dicyclohexylcarbo-
diimide (400 mg, 1.94 mmol) in DCM (5 mL) gave ester
4a (435 mg, quant.) as a colourless oil; (Rf 0.6);
NH), 1748 (s, ester), 1719 (s, amide I), 1648 (m, C@C–
O), 1502 (m, amide II); dH (400 MHz, CDCl3) 0.95
0
(3H, d, JCH ,CH 6.6 Hz, CH3), 0.95 (3H, d, J
CH3,CH
3
6.6 Hz, CH03), 0.98, 1.06 (18H, 2 · s, 2 · SiC(CH3)3)
1.44 (9H, s, OC(CH3)3), 1.48–1.55 (1H, m,
NHCHCHH0), 1.60–1.66 (1H, m, NHCHCHH0), 1.70–

50
D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
L-alanine 3b (574mg, 3.03 mmol), N,N0-dimethyl-4-ami-
no pyridine (59 mg, 0.48 mmol) and dicyclohexylcarbo-
diimide (962 mg, 4.66 mmol) in DCM (20 mL) gave
1.76 (1H, m, (CH3)2CH), 3.92–4.02 (2H, m, H-5, H-6),
4.10–4.21 (2H, m, H-4, H-60), 4.35–4.40 (1H, m,
NHCH), 4.37 (1H, dd, J1,2 6.0 Hz, J2,3 2.1 Hz, H-2),
4.90 (1H, d, JNH,CH 8.4 Hz, NH), 5.43–5.45 (1H, m,
H-3), 6.32 (1H, dd, J1,3 1.2 Hz, H-1); dC (100.6 MHz,
CDCl3) 19.8, 22.6, 22.7 (3 · s, 3 · C(CH3)3), 22.1, 24.7,
(2 · q, 2 · CH3), 24.9 (d, (CH3)2CHCH2), 26.8, 27.3,
28.3 (3 · q, 3 · C(CH3)3), 41.9 (t, (CH3)2CHCH2), 52.4
(d, NHCH), 65.6 (t, C-6), 72.8, 72.9, 73.5 (3 · d, C-3,
C-4, C-5), 100.1 (d, C-2), 145.2 (d, C-1), 155.2 (s,
CHC(O)O), 172.8 (s, NC(O)O); m/z (ES+) 558
ester 5b (1.11 g, quant.) as a colourless oil; (Rf 0.5);
21
D
½aŠ ¼ þ150 (c 1.1, CHCl3); mmax (thin film) 3378 (br,
NH), 1719 (sh, ester, amide I), 1642 (m, C@C–O),
1510 (m, amide II) cmꢁ1; dH (400 MHz, CDCl3) 1.02,
1.06 (18H, 2 · s, 2 · SiC(CH3)3), 1.42 (3H, d, JCH ,CH
7.1 Hz, CHCH3), 1.44 (9H, s, OC(CH3)3), 3.96 (31H,
at, J 10.2 Hz, H-6), 4.08–4.21 (1H, m, H-5), 4.22–4.30
(2H, m, H-4, H-60), 4.31–4.35 (1H, m, CH3CH), 5.05
(1H, at, J 5.9 Hz, H-2), 5.11 (1H, d, JNH,CH 7.1 Hz,
NH), 5.16 (1H, dd, J2,3 6.0 Hz, J3,4 3.9 Hz, H-3), 6.39
(1H, d, J1,2 5.9 Hz, H-1); dC (100.6 MHz, CDCl3), 19.2
(q, CH3CH), 20.1, 22.8 (2 · s, 2 · SiC(CH3)3), 26.9,
27.5 (2 · q, 2 · SiC(CH3)3), 27.4(s, O C(CH3)3), 28.3
(q, OC(CH3)3), 49.4 (d, CH3CH), 66.1 (t, C-6), 66.3
(d, C-3), 68.7 (d, C-5), 72.3 (d, C-4), 97.8 (d, C-2),
146.9 (d, C-1), 154.9 (s, CHC@O), 173.1 (s, NHC@O);
m/z (ES+) 480 (M+Na+, 100%). (HRMS (ES+) calcd
for C22H39O7NSiNa (M+Na+) 480.2394. Found
480.2397).
(M+NHþ4 +MeCN,
100),
522
(M+Na+,
25),
517(M+NHþ4 , 25), 500 (M+H+, 52%). (HRMS (ES+)
calcd for C25H46O7NSi (M+H+) 500.3043. Found
500.3043). (Found: C, 59.20; H, 910; N, 2.99.
C25H45O7NSi requires C, 59.35; H, 8.92; N, 2.88).
4.8. 2,2-Dimethyloxazolidine-(4R)-3,4-dicarboxylic acid
3-tert-butyl ester 4-(4,6-O-di-tert-butyl-silanediyl-3-O-yl-
D-glucal) ester 4f
General procedure A: glucal 1 (Rf 0.45 (petrol–ethyl ace-
tate, 4:1), 250.5 mg, 0.875 mmol), 2,2-dimethyloxazol-
idine-(4R)-3,4-dicarboxylic acid 3-tert-butyl ester 3f
(279 mg, 1.14mmol), N,N0-dimethyl-4-amino pyridine
(21 mg 0.18 mmol) and dicyclohexylcarbodiimide
(361 mg, 1.75 mmol) in DCM (10 mL) gave ester 4f
4.10. 3-O-(N-tert-Butoxycarbonyl-L-methionine)-4,6-O-
di-tert-butylsilanediyl-D-allal 5e
General procedure A: allal 2 (Rf 0.4(petrol–ethyl ace-
tate, 4:1), 329 mg, 1.15 mmol), N-tert-butoxycarbonyl-
L-methionine 3e (372 mg, 1.49 mmol), N,N0-dimethyl-
4-amino pyridine (28 mg 0.23 mmol) and dicyclohexyl-
carbodiimide (473 mg, 2.29 mmol) in DCM (15 mL)
gave ester 5e (476 mg, 80%) as a colourless oil; (Rf
(447 mg, 99%) as a colourless oil; (Rf 0.5); mixture of
21
D
rotamers: major:minor, 1.6:1; ½aŠ ¼ ꢁ6:1 (c 0.9,
CHCl3); mmax (thin film) 1765 (s, ester), 1713 (s, amide),
1646 (w, C@C); dH (400 MHz, CDCl3) major rotamer:
0.98, 1.05 (18H, 2 · s, 2 · SiC(CH3)3), 1.43, 1.50 (9H,
2 · s, OC(CH3)3), 1.55–1.69 (6H, m, ONC(CH3)2),
3.91–4.54 (7H, m, H-4, H-5, H-6, H-60, CH2CHCO2,
CH2CHCO2), 4.72 (1H, dd, J1,2 6.1 Hz, J2,3 2.0 Hz, H-
2), 5.45–5.48 (1H, m, H-3), 6.34 (1H, dd, J1,3 1.5 Hz,
H-1); minor rotamer: 0.98, 1.05 (18H, 2 · s,
2 · SiC(CH3)3), 1.43, 1.50 (9H, 2 · s, OC(CH3)3), 1.55–
1.69 (6H, m, ONC(CH3)2), 3.91–4.54 (7H, m, H-4, H-
5, H-6, H-60, CH2CHCO2, CH2CHCO2), 4.77 (1H, dd,
J1,2 6.1 Hz, J2,3 1.9 Hz, H-2), 5.55–5.57 (1H, m, H-3),
6.31 (1H, dd, J1,3 1.6 Hz, H-1); dC (100.6 MHz, CDCl3)
major rotamer: 19.8 (s, 2 · SiC(CH3)3), 22.7 (s,
OC(CH3)3), 24.4, 25.0 (2 · q, ONC(CH3)2), 26.8, 27.3,
28.4(3 · q, 3 · C(CH3)3), 59.3, 72.9, 73.4, 73.7 (4 · d,
C-3, C-4, C-5, CHCO2), 65.6, 66.3 (2 · t, C-6,
CH2CHCO2), 80.3, 95.1 (2 · s, ONC(CH3)2, (CH3)2C),
100.0 (d, C-2), 145.3 (d, C-1), 151.2 (s, CHC@O), 171.0
(s, NC@O); minor rotamer: 19.8 (s, 2 · SiC(CH3)3),
22.7 (s, OC(CH3)3), 25.2, 26.0 (2 · q, ONC(CH3)2),
26.8, 27.3, 28.4(3 · q, 3 · C(CH3)3), 60.4, 72.6, 72.8,
74.0 (4 · d, C-3, C-4, C-5, CHCO2), 65.6, 66.1 (2 · t,
C-6, CH2CHCO2), 80.8, 84.5 (2 · s, ONC(CH3)2,
(CH3)2C), 100.3 (d, C-2), 145.0 (d, C-1), 151.2 (s,
CHC@O), 170.5 (s, NC@O); m/z (ES+) 536 (M+Na+,
100), 514(M+H +, 20%). (HRMS (ES+) calcd for
C25H43O8NSiNa (M+Na+) 536.2656. Found 536.2651).
0.4); mixture of rotamers: major:minor, 7:2;
21
D
½aŠ ¼ þ191 (c 1.0, CHCl3); mmax (thin film) 3370 (br,
NH), 1716 (sh, ester, amide I), 1642 (m, C@C–O),
1501 (m, amide II) cmꢁ1; dH (400 MHz, CDCl3) major
rotamer: 1.03, 1.06 (18H, 2 · s, 2 · SiC(CH3)3), 1.45
(9H, s, OC(CH3)3), 1.88–1.97 (1H, m, SCH2CHH0),
2.09 (3H, s, SCH3), 2.13–2.24(1H, m, SCH 2CHH0),
2.48–2.59 (2H, m, CH3SCHH0, CH3SCHH0), 3.94–4.00
(1H, m, H-6), 4.04–4.15 (1H, m, H-5), 4.20–4.24 (1H,
m, H-4), 4.23–4.30 (1H, m, H-60), 4.37–4.45 (1H, m,
NHCH), 5.05 (1H, at, J 6.1 Hz, H-2), 5.12–5.17 (1H,
m, NH), 5.16–5.20 (1H, m, H-3), 6.40 (1H, d, J
5.9 Hz, H-1); minor rotamer: 1.03, 1.06 (18H, 2 · s,
2 · SiC(CH3)3), 1.45 (9H, s, OC(CH3)3), 1.88–1.97
(1H, m, SCH2CHH0), 2.09 (3H, s, SCH3), 2.13–2.24
(1H, m, SCH2CHH0), 2.48–2.59 (2H, m, CH3SCHH0,
CH3SCHH0), 3.94–4.00 (1H, m, H-6), 4.04–4.15 (1H,
m, H-5), 4.20–4.24 (1H, m, H-4), 4.23–4.30 (1H, m, H-
60), 4.37–4.45 (1H, m, NHCH), 4.98 (1H, at, J 5.9 Hz,
H-2), 5.12–5.17 (1H, m, NH), 5.29–5.32 (1H, m, H-3),
6.43 (1H, d, J 6.0 Hz, H-1); dC (100.6 MHz, CDCl3)
15.7 (q, SCH3), 20.1, 22.8, 22.8 (3 · s, 3 · C(CH3)3),
26.9, 27.5, 28.3 (3 · q, 3 · C(CH3)3), 30.1, 32.8 (2 · t,
SCH2CH2, SCH2CH2), 53.1 (d, CH2CH), 66.5 (d, C-
3), 66.1 (t, C-6), 68.7 (d, C-5), 72.3 (d, C-4), 97.7 (d,
C-2), 147.0 (d, C-1), 178.2 (s, CHC@O); minor rotamer:
15.7 (q, SCH3), 20.1, 22.8, 22.8 (3 · s, 3 · C(CH3)3),
26.9, 27.5, 28.3 (3 · q, 3 · C(CH3)3), 29.8, 32.7 (2 · t,
SCH2CH2, SCH2CH2), 52.9 (d, CH2CH), 65.7 (d, C-
3), 66.0 (t, C-6), 68.9 (d, C-5), 72.4(d, C-4), 97.5 (d,
C-2), 147.4 (d, C-1), 171.9 (s, CHC@O); m/z (ES+) 54 0
4.9. 3-O-(N-tert-Butoxycarbonyl-L-alanine)-4,6-O-di-
tert-butylsilanediyl-D-allal 5b
General procedure A: allal 2 (Rf 0.4(petrol–ethyl ace-
tate, 4:1), 688 mg, 2.33 mmol), N-tert-butoxycarbonyl-

D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
51
(M+Na+, 100%), 518 (M+H+, 95%). (HRMS (ES+)
calcd for C24H43O7NSSiNa (M+Na+) 540.2427. Found
540.2419).
3 · C(CH3)3), 35.0, 36.2 (2 · t, NHCH2, NHCH2CH2),
65.6 (t, C-6), 72.4(d, C-3), 72.9 (d, C-5), 73.6 (d, C-4),
100.3 (d, C-2), 145.1 (d, C-1), 155.8, 172.3 (2 · s,
2 · C@O); m/z (ES+) 480 (100, M+Na+). (HRMS
(ES+) calcd for C22H39O7NSiNa (M+Na+) 480.2394.
Found, 480.2393).
4.11. 2,2-Dimethyloxazolidine-(4R)-3,4-dicarboxylic acid
3-tert-butyl ester 4-(4,6-O-di-tert-butylsilanediyl-3-O-yl-
D-allal) ester 5f
4.13. 3-O-(40-tert-Butoxysuccinoyl)-4,6-O-di-tert-butyl-
silanediyl-D-glucal 11
General procedure A: allal 2 (Rf 0.4(petrol–ethyl ace-
tate, 4:1), 207 mg, 0.91 mmol), 2,2-dimethyloxazol-
idine-(4R)-3,4-dicarboxylic acid 3-tert-butyl ester 3f
(290 mg, 1.18 mmol), N,N0-dimethyl-4-amino pyridine
(22 mg 0.18 mmol) and dicyclohexylcarbodiimide
(376 mg, 1.82 mmol) in DCM (10 mL) gave ester 5f
General procedure A: glucal 1 (Rf 0.5 (petrol–ethyl ace-
tate, 4:1), 277 mg, 0.97 mmol), 4-tert-butoxysuccinic
acid 10 (252 mg, 1.45 mmol), N,N0-dimethyl-4-amino
pyridine (24mg, 0.19 mmol), dicyclohexylcarbodiimide
(398 mg, 1.9 mmol) in DCM (10 mL) gave ester 11
(367 mg, 79%) as a colourless oil; (Rf 0.5); mixture of
21
D
rotamers: major:minor, 1.9:1; ½aŠ ¼ þ190 (c 1.0,
(419 mg, 97%) as
a
colourless oil; (Rf 0.7);
25
CHCl3); mmax (thin film) 1755 (s, ester), 1712 (s, amide),
1641 (w, C@C–O); dH (400 MHz, CDCl3) major rot-
amer: 1.02, 1.05 (18H, 2 · SiC(CH3)3), 1.42 (9H, s,
OC(CH3)3), 1.55, 1.69 (6H, 2 · s, ONC(CH3)2), 3.94–
4.53 (7H, m, H-4, H-5, H-6, H-60, CH2CHCO2,
CH2CHCO2), 5.07–5.20 (2H, m, H-2, H-3), 6.38–6.41
(1H, m, H-1); minor rotamer: 1.03, 1.04(18H,
2 · SiC(CH3)3), 1.51 (9H, s, OC(CH3)3), 1.64, 1.67
(6H, 2 · s, ONC(CH3)2), 3.94–4.53 (7H, m, H-4, H-5,
H-6, H-60, CH2CHCO2, CH2CHCO2), 5.07–5.20 (2H,
m, H-2, H-3), 6.38–6.41 (1H, m, H-1); major rotamer:
dC (100.6 MHz, CDCl3) 20.2, 20.3, 22.7 (3 · s,
3 · C(CH3)3), 24.4, 25.1 (2 · q, 2 · ONC(CH3)2), 27.0,
27.2, 28.3 (3 · q, 3 · C(CH3)3), 59.0, 66.3, 69.0, 72.4,
(4 · d, C-3, C-4, C-5, CH2CHCO2), 65.8, 65.9 (2 · t,
C-6, CH2CHCO2), 80.4, 95.1 (2 · s, ONC(CH3)2), 98.0
(d, C-2), 147.0 (d, C-1), 151.4 (s, CHC@O), 170.2 (s,
NHC@O); minor rotamer: 20.5, 20.9, 22.7 (3 · s,
3 · C(CH3)3), 26.3, 26.7 (2 · q, 2 · ONC(CH3)2), 26.9,
27.4, 28.4 (3 · q, 3 · C(CH3)3), 59.2, 66.5, 69.0, 72.5
(4 · d, C-3, C-4, C-5, CH2CHCO2), 65.7, 65.9 (2 · t,
C-6, CH2CHCO2), 80.7, 94.4 (2 · s, ONC(CH3)2), 98.1
(d, C-2), 147.0 (d, C-1), 151.4 (s, CHC@O), 169.7 (s,
NHC@O); m/z (ES+) 536 (M+Na+, 100%). (HRMS
(ES+) calcd for C25H43O8NSiNa (M+Na+) 536.2656.
Found 536.2657).
½aŠ ¼ ꢁ61:1 (c 1.0, CHCl3); mmax (thin film) 1734(s,
D
C@O), 1647 (w, C@C–O) cmꢁ1; dH (400 MHz, CDCl3)
0.97, 1.05 (18H, 2 · s, 2 · SiC(CH3)3), 1.44 (9H, s,
OC(CH3)3), 2.53–2.57, 2.61–2.65 (4H, m, (H3C)3O-
C(O)CH2, (H3C)3OC(O)CH2CH2), 3.89–4.00 (2H, m,
H-5, H-6), 4.13–4.20 (2H, m, H-4, H-60), 4.71 (1H, dd,
J1,2 6.1 Hz, J2,3 2.1 Hz, H-2), 5.38 (1H, dat, J 2.0, 3.7,
3.7 Hz, H-3), 6.30 (1H, dd, J1,3 2.0 Hz, H-1); dC
(100.6 MHz, CDCl3) 19.8, 22.7 (2 · s, 3 · C(CH3)3),
26.8, 27.4, 28.0 (3 · q, 3 · C(CH3)3), 29.5, 30.4(2 · t,
(H3C)3OC(O)CH2, (H3C)3OC(O)CH2CH2), 65.7 (t, C-
6), 72.4, 72.8, 73.6 (3 · d, C-3, C-4, C-5), 100.5 (d, C-
2), 144.9 (d, C-1), 171.3, 172.4 (2 · s, 2 · C@O); m/z
(ES+) 465 (M+Na+, 100), 460 (M+NHþ4 , 20), 443
(M+H+, 5%). (HRMS (ES+) calcd for C22H38O7NaSi
(M+Na+) 465.2285. Found, 465.2290). (Found: C,
59.67; H, 8.62. C22H38O7Si requires C, 59.70; H, 8.65).
4.14. 3-O-((S)-3-Amino-N-tert-butoxycarbonyl-4-tert-
butylcarboxy-butanoyl)-4,6-O-di-tert-butylsilanediyl-D-
glucal 13
General procedure A: glucal 1 (Rf 0.5, 467 mg,
1.61 mmol), N-butoxycarbonyl L-aspartic acid a-tert-
butyl ester 12 (467 mg, 1.61 mmol), N,N0-dimethyl-4-
amino pyridine (26 mg, 0.22 mmol), dicyclohexylcarbo-
diimide (444 mg, 2.15 mmol) in DCM (25 mL) gave
4.12. 3-O-(N-tert-Butoxycarbonyl-3-amino-propanoyl)-
4,6-O-di-tert-butylsilanediyl-D-glucal 8
ester 13 (558 mg, 93%) as a white crystalline solid, mp
22
D
84–85 ꢁC (petrol); ½aŠ ¼ ꢁ30 (c 1, CHCl3); mmax (thin
film):3426(br, NH), 1732(s, C@O), 1648(m, C@C) cmꢁ1
;
General procedure A: glucal 1 (Rf 0.6 (petrol–ethyl
acetate, 4:1), 235 mg, 0.82 mmol), N-b-tert-butoxycar-
dH (400 MHz, CDCl3) 0.98, 1.09 (18H, 2 · s,
2 · C(CH3)3), 1.44, 1.45 (18H, 2 · s, 2 · CO2C(CH3)3),
2.85 (1H, dd, JCHH ,CH 4.6 Hz, Jgem 17.1 Hz,
(201 mg, 1.06 mmol), N,N0-di-
methyl-4-amino pyridine (20 mg, 0.16 mmol), dicyclo-
0
bonyl-b-L-alanine
6
O2CCHH0CH), 3.05 (1H, dd, JCHH ,CH 4.1 Hz,
0
hexylcarbodiimide (337 mg, 1.6 mmol) in DCM (5 mL)
gave ester 8 (301 mg, 81%) as a colourless oil; (Rf 0.7);
O2CCHH0CH), 3.90 (1H, ddd, J4,5 10.3 Hz, J5,6 10.3 Hz,
0
J5,6 4.8 Hz, H-5), 3.99 (1H, at, J 10.3 Hz, H-6), 4.16
19
D
0
½aŠ ¼ ꢁ48:7 (c 0.8, CHCl3); mmax (thin film) 3460 (br,
(1H, dd, J3,4 7.6 Hz, H-4), 4.19 (1H, dd, J6,6 10.1 Hz, H-
NH), 1734(s, ester), 1721 (s, amide I), 1649 (w, C @CO),
1502 (w, amide II) cmꢁ1; dH (400 MHz, CDCl3) 0.98,
1.05 (18H, 2 · s, 2 · SiC(CH3)3), 1.42 (9H, s,
OC(CH3)3), 2.57 (2H, at, J 6.1 Hz, C(O)CH2), 3.35–
3.44 (2H, m, NHCH2), 3.88–3.95 (1H, m, H-5), 3.94–
4.10 (1H, m, H-6), 4.13–4.17 (1H, m, H-4), 4.17–4.20
(1H, m, H-60), 4.71 (1H, dd, J1,2 6.1 Hz, J2,3 2.0 Hz,
H-2), 5.01 (1H, br s, NH), 5.40–5.42 (1H, m, H-3),
6.32 (1H, dd, J1,3 1.9 Hz, H-1); dC (100.6 MHz, CDCl3)
19.8, 22.7 (2 · s, 3 · C(CH3)3), 26.8, 27.4, 28.4 (3 · q,
60), 4.44–4.48 (1H, m, O2CCH2CH), 4.72 (1H, dd, J1,2
6.1 Hz, J2,3 2.0 Hz, H-2), 5.36 (1H, br d, J 7.6 Hz, H-3),
5.45 (1H, d, JCH,NH 8.4Hz, NH), 6.31 (1H, dd, J1,3
1.3 Hz, H-1); dC (100.6 MHz, CDCl3) 19.8, 22.7 (2 · s,
2 · C(CH3)3), 26.9, 27.3, 27.9, 28.3 (4 · q, 4 · C(CH3)3),
37.3 (t, O2CCH2CH), 50.3 (d, O2CCH2CH), 65.6 (t, C-
6), 72.9 (d, C-5), 73.0 (d, C-3), 73.3 (d, C-4), 79.8, 82.1
(2 · s, 2 · CO2C(CH3)3), 100.2 (d, C-2), 145.1 (d, C-1),
155.5 (s, NHCO2C(CH3)3), 169.7 (s, CHCO2C(CH3)3),
170.7 (s, O2CCH2CH); m/z (FI+) 557 (M, 100%). (HRMS

52
D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
calcd for C27H47O9NSi (M) 557.3020. Found 557.3002).
(Found: C, 58.27; H, 8.36; N, 2.45. C27H47O9NSi requires
C, 58.14; H, 8.49; N, 2.51).
128.3, 129.2 (3 · d, 5 · Ar-C), 136.9 (s, Ar-C), 145.4 (d,
C-1); m/z (ES+) 1061 (2M+Na+, 30), 1056 (2M+NHþ4 ,
15), 542 (M+Na+, 100), 537 (M+NH4þ, 30%). (HRMS
(ES+) calcd for C27H37O9NNa (M+Na+) 542.2366.
Found, 542.2377). (Found: C, 62.70; H, 7.09; N, 2.62.
C27H37O9N requires C, 62.41; H, 7.18; N, 2.70).
4.15. 3-O-((S)-30-Amino-N-tert-butoxycarbonyl-40-tert-
butylcarboxy-butanoyl)-4,6-O-benzylidene-D-glucal 15
General procedure A: glucal 14 (Rf 0.1 (petrol–ethyl ace-
tate, 4:1), 267 mg, 1.1 mmol), N-butoxycarbonyl L-
aspartic acid a-tert-butyl ester 12 (495 mg, 1.7 mmol),
N,N0-dimethyl-4-amino pyridine (28 mg, 0.23 mmol),
dicyclohexylcarbodiimide (470 mg, 2.3 mmol) in DCM
(25 mL) gave ester 15 (536 mg, 93%) as a white crystal-
4.17. 3-O-(30-(N-tert-butoxycarbonylamino)-prop-10-ene-
20-yl)-4,6-O-di-tert-butyl-silanediyl-D-glucal 18
General procedure B: ester 4a (Rf 0.4(petrol–ethyl ace-
tate, 4:1), 144 mg, 0.33 mmol), Tebbe reagent (0.5 M,
2.6 mL, 1.3 mmol) in THF (4mL) and pyridine (1 mL)
gave vinyl ether 18 (63.8 mg, 44%) as a yellow oil; (Rf
0.5); mmax (thin film) 3441 (br, NH), 1718 (s, ester),
1701 (s, amide I), 1653 (m, C@C–O), 1647 (m, C@CO),
1507 (m, amide II) cmꢁ1; dH (400 MHz, C6D6) 0.99,
1.04, 1.42 (27H, 3 · s, 3 · C(CH3)3), 3.66–3.86 (3H, m,
H-5, NHCHH0, NHCHH0), 3.91 (1H, at, J 10.3 Hz,
H-6), 4.01 (1H, s, C@CHH0), 4.10–4.13 (2H, m, H-60,
C@CHH0), 4.22 (1H, dd, J3,4 7.3 Hz, J4,5 10.3 Hz, H-
4), 4.54–4.56 (2H, m, H-3, NH), 4.70 (1H, d, J1,2
6.0 Hz, H-2), 5.99 (1H, d, H-1); dC (100.6 MHz, C6D6)
20.1, 23.0 (2 · s, 3 · C(CH3)3), 27.3, 27.8, 28.6 (3 · q,
3 · C(CH3)3), 44.4 (t, NHCH2), 66.3 (t, C-6), 73.2 (d,
C-5), 75.0 (d, C-4), 75.8 (d, C-3), 78.9 (s, H2C@C),
84.2 (t, H2C@C), 100.3 (d, C-2), 144.6 (d, C-1); m/z
(ES+) 464 (M+Na+, 100%). (HRMS (ES+) calcd for
line solid, mp 122–124 ꢁC (ether/petrol); (Rf 0.2);
24
½aŠ ¼ ꢁ28:3 (c 1.0, CHCl3); mmax (KBr disc) 3414 (s,
D
NH), 1741 (s, ester), 1710 (s, amide I), 1649 (w, C@C–
O), 1501 (m, amide II) cmꢁ1; dH (400 MHz, CDCl3)
2
1.34, 1.41 (18H, 2 · s, 2 · C(CH3)3), 2.80 (1H, dd, J
3
16.8 Hz, J 4.9 Hz, NHCHCHH0), 2.98 (1H, dd, 3J
4.2 Hz, NHCHCHH0), 3.81–3.86 (1H, m, H-6), 3.95–
0
0
4.06 (2H, m, H-4, H-5), 4.38 (1H, dd, J5,6 4.8 Hz, J6,6
10.5 Hz, H-60), 4.41–4.46 (1H, m, NHCH), 4.77 (1H,
dd, J1,2 6.1 Hz, J2,3 2.0 Hz, H-2), 5.45 (1H, d, JNH,CH
8.5 Hz, NH), 5.56 (1H, dat, J 1.9, 1.9, 7.7 Hz, H-3),
5.59 (1H, s, PhCHO2), 6.39 (1H, dd, J1,3 1.3 Hz, H-1),
7.28–7.50 (5H, m, 5 · Ar-H); dC (100.6 MHz, CDCl3)
20.8, 21.0 (2 · s, 2 · C(CH3)3), 27.7, 28.3 (2 · q,
2 · C(CH3)3), 37.2 (t, NHCHCH2), 50.4(d, NHCH),
68.2 (t, C-6), 68.8, 69.2 (2 · d, C-3, C-5), 76.7 (d, C-4),
C22H39O6NNaSi
(M+Na+)
464.2444.
Found,
100.4(d, C-2), 101.7 (d, PhCHO ), 126.3, 128.2, 129.2
464.2439); together with hydrolysis product glucal 1
(37.3 mg, 40% Rf 0.35).
2
(3 · d, 5 · Ar-C), 136.9 (s, Ar-C), 145.6 (d, C-1), 155.4,
169.7, 170.6 (3 · s, 3 · C@O); m/z (ES+) 1033
(2M+Na+, 60), 528 (M+Na+, 100%). (HRMS (ES+)
calcd for C26H35O9NNa (M+Na+) 528.2210. Found,
528.2219). (Found: C, 61.55; H, 6.71; N, 2.66.
C26H35O9N requires C, 61.77; H, 6.98; N, 2.77).
4.18. 3-O-(40-(N-tert-Butoxycarbonylamino)-but-10-ene-
20-yl)-4,6-O-di-tert-butylsilanediyl-D-glucal 19
General procedure B: ester 8 (Rf 0.5 (petrol–ethyl ace-
tate, 4:1), 125 mg, 0.27 mmol), Tebbe reagent (0.5 M,
2.2 mL, 1.1 mmol), in THF (4mL) pyridine (1 mL) gave
vinyl ether 19 (99.5 mg, 80%) as a yellow oil; (Rf 0.6);
mmax (thin film) 3442 (br, NH), 1718 (sh, ester, amide
I), 1646 (m, C@CO), 1510 (m, amide II) cmꢁ1; dH
(400 MHz, C6D6) 1.14, 1.15, 1.57 (27H, 3 · s,
3 · C(CH3)3), 2.19–2.25 (1H, m, NHCH2CHH0), 2.37–
2.45 (1H, m, NHCH2CHH0), 3.30–3.41 (1H, m,
NHCHH0), 3.55–3.63 (1H, m, NHCHH0), 3.85–3.91
(1H, m, H-5), 4.00–4.06 (3H, m, H-6, C@CHH0,
4.16. 3-O-((S)-40-Amino-N-tert-butoxycarbonyl-50-tert-
butylcarboxy-pentanoyl)-4,6-O-benzylidene-D-glucal 17
General procedure A: glucal 14 (Rf 0.4(petrol–ethyl ace-
tate, 2:1), 241 mg, 1.0 mmol), N-butoxycarbonyl L-glu-
tamic acid a-tert-butyl ester 16 (468 mg, 1.54 mmol),
N,N0-dimethyl-4-amino pyridine (25 mg, 0.21 mmol),
dicyclohexylcarbodiimide (425 mg, 2.1 mmol) in DCM
(15 mL) gave ester 17 (526 mg, 98%) as a white foam;
20
D
C@CHH0), 4.23 (1H, dd, J5,6 5.1 Hz, J6,6 10.5 Hz, H-
60), 4.32 (1H, dd, J3,4 7.5 Hz, J4,5 10.2 Hz, H-4), 4.62
(1H, d, H-3), 4.82–4.85 (2H, m, H-2, NH), 6.10 (1H,
dd, J1,2 6.0 Hz, J1,3 1.1 Hz, H-1); dC (100.6 MHz,
C6D6) 20.1, 23.0 (2 · s, 3 · C(CH3)3), 27.4, 27.7, 28.7
(3 · q, 3 · C(CH3)3), 35.8 (t, NHCH2CH2), 38.4(t,
NHCH2), 66.3 (t, C-6), 73.2 (d, C-5), 75.0 (d, C-4),
75.9 (d, C-3), 78.6 (s, H2C@C), 84.9 (t, H2C@C), 100.5
(d, C-2), 144.5 (d, C-1), 160.1 (s, O2CN); m/z (ES+)
478 (M+Na+, 100%). (HRMS (ES+) calcd for
C23H41O6NNaSi (M+Na+) 478.2601. Found, 478.2605).
0
0
(Rf 0.6); ½aŠ ¼ ꢁ45:3 (c 0.8, CHCl3); mmax (KBr disc)
3382 (br, NH), 1737 (s, ester), 1716 (s, amide I), 1642
(w, C@CO), 1503 (w, amide II) cmꢁ1; dH (400 MHz,
CDCl3) 1.44, 1.46 (18H, 2 · s, 2 · C(CH3)3), 1.90–1.99
(1H, m, NHCHCH2CHH0), 2.10–2.19 (1H, m,
NHCHCH2CHH0), 2.35–2.43 (1H, m, NHCHCHH0),
2.45–2.53 (1H, m, NHCHCHH0), 3.87 (1H, at, J
10.2 Hz, H-6), 3.98–4.09 (2H, m, H-4, H-5), 4.16–4.23
0
(1H, m, NHCH), 4.41 (1H, dd, J5,6 4.8 Hz, J6,6
0
0
10.4Hz, H-6 ), 4.82 (1H, dd, J1,2 6.1 Hz, J2,3 2.0 Hz,
H-2), 5.09 (1H, d, JNH,CH 8.3 Hz, NH), 5.54(1H, dat,
J 1.8, 1.8, 7.7 Hz, H-3), 5.62 (1H, s, PhCHO2), 6.40
(1H, dd, J1,3 1.4Hz, H-1), 7.34–7.52 (5H, m, 5 · Ar-
H); dC (100.6 MHz, CDCl3) 28.0, 28.3 (2 · q,
2 · C(CH3)3), 28.3, 30.6 (2 · t, NHCHCH2CH2), 53.4
(d, NHCH), 68.3 (t, C-6), 68.8, 69.1 (2 · d, C-3, C-5),
76.9 (d, C-4), 100.7 (d, C-2), 101.6 (d, PhCHO2), 126.2,
4.19. 3-O-(50-tert-Butyl-carboxy-pent-10-ene-20-yl)-4,6-
O-di-tert-butyl-silanediyl-D-glucal 21
General procedure B: ester 11 (Rf 0.6 (petrol–ethyl ace-
tate, 4:1), 108 mg, 0.24 mmol), Tebbe reagent (0.5 M,

D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
53
2.0 mL, 0.97 mmol) in THF (6 mL) and pyridine
(1.5 mL) gave vinyl ether 21 (88.6 mg, 83%) as a colour-
less oil; (Rf 0.7); mmax (thin film) 1732 (s, C@O), 1643 (w,
C@C–O) cmꢁ1; dH (400 MHz, C6D6) 1.12, 1.15 (18H,
2 · s, 2 · SiC(CH3)3), 1.47 (9H, s, OC(CH3)3), 2.53–
2.66 (4H, m, CH2CH2), 3.91 (1H, dat, J 4.9, 10.4,
10.4Hz, H-5), 4.04(1H, at, J 10.4Hz, H-6), 4.13 (2H,
1.9 mL, 0.94mmol), in THF (6 mL) and pyridine
(1.5 mL) gave vinyl ether (25.7 mg, 22%, 50% based on
recovered starting material) as a pale orange oil; (Rf
0.4); mmax (thin film) 3440 (br, NH), 1717 (sh, ester, amide
I), 1640 (m, C@C–O), 1506 (m, amide II) cmꢁ1; dH
(400 MHz, C6D6) ratio of rotamers major:minor, 2:1;
major rotamer: 1.41, 1.49 (18H, 2 · s, 2 · C(CH3)3),
2.62–2.69 (1H, m, NHCHCHH0), 2.81 (1H, dd, 2J
0
0
br s, C@CH2), 4.24 (1H, dd, J5,6 5.0 Hz, J6,6 10.3 Hz,
H-60), 4.37 (1H, dd, J3,4 7.2 Hz, J4,5 10.4Hz, H-4),
4.71 (1H, dat, J 1.6, 1.6, 7.2 Hz, H-3), 4.92 (1H, dd,
J1,2 6.2 Hz, J2,3 1.8 Hz, H-2), 6.15 (1H, dd, J1,3 1.5 Hz,
H-1); dC (100.6 MHz, C6D6) 20.1, 23.0 (2 · s,
3 · C(CH3)3), 27.3, 27.8, 28.3 (3 · q, 3 · C(CH3)3),
31.5, 33.9 (2 · t, CH2CH2), 66.4(t, C-6), 75.3 (d, C-5),
75.1 (d, C-4), 75.6 (d, C-3), 83.5 (t, C@CH2), 100.6 (d,
C-2), 144.5 (d, C-1), 161.4 (s, C@CH2), 171.8 (s,
C@O); m/z (ES+) 463 (M+Na+, 100%). (HRMS (ES+)
calcd for C23H40O6SiNa (M+Na+) 463.2492. Found,
463.2498).
3
14.3 Hz, J 5.8 Hz, NHCHCHH0), 3.59 (1H, at, J
10.3 Hz, H-6), 3.80 (1H, dat, J 15.3, 15.3, 5.0 Hz, H-5),
0
3.97–4.10 (3H, m, H-4, C@CH2), 4.23 (1H, dd, J5,6
5.0 Hz, J6,6 10.3 Hz, H-60), 4.37–4.82 (2H, m, H-3,
0
NHCH), 4.90 (1H, dd, J1,2 6.8 Hz, J2,3 1.7 Hz, H-2),
5.53–5.60 (2H, m, NH, PhCHO2), 6.13 (1H, d, H-1),
7.20–7.90 (5H, m, 5 · Ar-H); minor rotamer: 1.43, 1.48
(18H, 2 · s, 2 · C(CH3)3), 2.62–2.69 (1H, m,
NHCHCHH0), 2.81 (1H, dd, 2J 14.3 Hz, 3J 5.8 Hz,
NHCHCHH0), 3.59 (1H, at, J 10.3 Hz, H-6), 3.80 (1H,
dat, J 5.0, 15.3, 15.3 Hz, H-5), 3.97–4.10 (3H, m, H-4,
0
0
C@CH2), 4.23 (1H, dd, J5,6 5.0 Hz, J6,6 10.3 Hz, H-
60), 4.37–4.82 (2H, m, H-3, NHCH), 4.90 (1H, dd, J1,2
6.7 Hz, J2,3 1.7 Hz, H-2), 5.53 (1H, s, PhCHO2), 5.68
(1H, d, J 5.4Hz, NH), 6.10 (1H, d, H-1), 7.20–7.90
(5H, m, 5 · ArH); dC (100.6 MHz, C6D6) 28.1, 28.6
(2 · q, 2 · C(CH3)3), 38.4(t, NHCH CH2), 52.1 (d,
NHCH), 68.5 (t, C-6), 69.2 (d, C-5), 73.2 (d, C-3), 78.2
(C-4), 86.2 (t, C@CH2), 100.6 (d, C-2), 101.9 (d,
PhCHO2), 127.0, 127.1, 128.5, 129.2 (4 · d, 5 · Ar-C),
133.0 (s, Ar-C), 140.1 (d, C-1), 160.2 (s, C@CH2),
169.1, 169.2 (2 · s, 2 · C@O); m/z (ES+) 1029
(2M+Na+, 10), 526 (M+Na+, 100), 521 (M+NHþ4 , 20),
504(M+H +, 10%). (HRMS (ES+) calcd for C27H37NO8-
Na (M+Na+) 526.2417. Found, 526.2422); and recov-
ered starting material 15 (Rf 0.3, 78.1 mg, 66%).
4.20. 3-O-((S)-40-Amino-N-tert-butoxycarbonyl-50-tert-
butylcarboxy-pent-10-ene-20-yl)-4,6-O-di-tert-butyl-
silanediyl-D-glucal 22
General procedure B: ester 13 (Rf 0.5, 227 mg,
0.41 mmol), Tebbe reagent (0.5 M in toluene, 3.3 mL,
1.6 mmol) in THF (8 mL) and pyridine (2 mL) gave
vinyl ether 22 (14.0 mg, 6%) as a pale orange oil; (Rf
0.6, petrol–ethyl acetate, 4:1); mmax (thin film) 3434 (br,
NH), 1718 (sh, ester, amide I), 1647 (m, C@C–O),
1498 (m, amide II) cmꢁ1; dH (400 MHz, C6D6) ratio of
rotamers major:minor, 1.2:1; major rotamer: 1.03, 1.14
(18H, 2 · s, 2 · SiC(CH3)3), 1.40, 1.41 (18H, 2 · s,
2 · OC(CH3)3), 2.66 (1H, dd, 2J 14.4 Hz, 3J 5.3 Hz,
3
NHCHCHH0), 2.79 (1H, dd, J 5.3 Hz, NHCHCHH0),
3.80–3.97 (1H, m, H-4), 4.00–4.09 (1H, m, H-6), 4.11–
4.19 (1H, m, H-60), 4.20, 4.21 (2H, 2 · s, C@CH2),
4.22–4.34 (1H, m, H-5), 4.72–4.74 (1H, m, H-3), 4.75–
4.82 (1H, m, NHCH), 4.93–4.95 (1H, dd, J1,2 6.1 Hz,
J2,3 1.4Hz, H-2), 5.54 (1H, d, JNH,CH 8.6 Hz, NH),
6.15 (1H, d, H-1); minor rotamer: 1.03, 1.14(18H,
2 · s, 2 · SiC(CH3)3), 1.43, 1.44 (18H, 2 · s,
2 · OC(CH3)3), 2.66 (1H, dd, 2J 14.4 Hz, 3J 5.3 Hz,
4.22. 3-O-((S)-50-Amino-N-tert-butoxycarbonyl-60-tert-
butylcarboxy-hex-10-ene-20-yl)-4,6-O-benzylidene-D-glu-
cal 24
General procedure B: ester 17 (Rf 0.3 (petrol–ethyl ace-
tate, 4:1), 129 mg, 0.25 mmol), Tebbe reagent (0.5 M,
2.0 mL, 0.99 mmol), in THF (6 mL) and pyridine
(1.5 mL) gave vinyl ether 24 (60.0 mg, 47%) as a pale
orange oil; (Rf 0.4); mmax (thin film) 3385 (br, NH),
1716 (sh, ester, amide I), 1638 (m, C@C–O), 1507 (w,
amide II) cmꢁ1; dH (400 MHz, C6D6) 1.26, 1.38 (18H,
2 · s, 2 · C(CH3)3), 1.74–1.85 (1H, m, NHCHCHH0),
2.07–2.19 (3H, m, NHCHCHH0, NHCHCH2CH2),
3.47 (1H, at, J 10.4Hz, H-6), 3.69–3.76 (1H, m, H-5),
3
NHCHCHH0), 2.79 (1H, dd, J 5.3 Hz, NHCHCHH0),
3.80–3.97 (1H, m, H-4), 4.00–4.09 (1H, m, H-6), 4.11–
4.19 (1H, m, H-60), 4.20, 4.21 (2H, 2 · s, C@CH2),
4.22–4.34 (1H, m, H-5), 4.36–4.41 (1H, m, H-3), 4.72–
4.74 (2H, m, H-2, NHCH), 5.79 (1H, d, JNH,CH
8.5 Hz, NH), 6.06 (1H, dd, J1,2 6.1 Hz, J1,3 1.3 Hz, H-
1); dC (100.6 MHz, C6D6) 27.3, 27.5, 28.5, 28.7 (4 · q,
4 · C(CH3)3), 38.9 (t, NHCHCH2), 66.3 (t, C-6), 75.1
(d, C-3), 75.9 (d, C-4), 82.3 (s, C@CH2), 86.9 (d, C-5),
87.2 (t, C@CH2), 101.0 (d, NHCH), 101.3 (d, C-2),
114.3 (d, C-1); m/z (ES+) 578 (M+Na+, 100), 556
(M+H+, 20%). (HRMS (ES+) calcd for C28H49NO8SiNa
(M+Na+) 578.3125. Found, 578.3134).
0
3.86–4.00 (3H, m, H-4, C@CH2), 4.12 (1H, dd, J5,6
5.3 Hz, J6,6 10.3 Hz, H-60), 4.46–4.49 (1H, m, NHCH),
0
4.76 (1H, d, J3,4 7.6 Hz, H-3), 4.83 (1H, dd, J1,2 6.3 Hz,
J2,3 1.4Hz, H-2), 5.00 (1H, d, JNH,CH 8.1 Hz, NH), 5.32
(1H, s, PhCHO2), 6.04(1H, d, H-1), 7.08–7.60 (5H, m,
5 · ArH); dC (100.6 MHz, C6D6) 28.0, 28.6 (2 · q,
2 · C(CH3)3), 30.9 (t, NHCHCH2), 31.9 (t,
NHCHCH2CH2), 54.3 (d, NHCH), 68.5 (t, C-6), 69.2
(d, C-5), 71.6 (d, C-3), 78.2 (d, C-4), 84.0 (t, C@CH2),
4.21. 3-O-((S)-40-Amino-N-tert-butoxycarbonyl-50-tert-
butylcarboxy-pent-10-ene-20-yl)-4,6-O-benzylidene-D-glu-
cal 23
100.4(d, C-2), 101.9 (d, PhCHO ), 126.9, 128.6, 129.2
2
(3 · d, 5 · Ar-C), 138.2 (s, C@CH2), 145.0 (d, C-1),
160.6, 172.2 (2 · s, 2 · C@O); m/z (ES+) 540 (M+Na+,
100), 518 (M+H+, 20%). (HRMS (ES+) calcd for
C28H39O8NNa (M+Na+) 540.2573. Found, 540.2561).
General procedure B: ester 15 (Rf 0.3 (petrol–ethyl ace-
tate, 4:1), 119 mg, 0.24 mmol), Tebbe reagent (0.5 M,

54
D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
4.23. 1-Amino-4,8-anhydro-N-tert-butoxycarbonyl-7,9-
O-di-tert-butylsilanediyl-5,6-didehydro-2-oxo-1,3,5,6-
tetradeoxy-D-glycero-D-gulo-nonitol 25
9), 78.9 (s, C-3), 129.3 (d, C-7), 130.6 (d, C-6), 156.0
(s, O2CN); m/z (ES+) 478 (M+Na+, 35%), 456 (M+H+,
25%). (HRMS (ES+) calcd for C23H42O6NSi (M+H+)
456.2781. Found, 456.2783).
Vinyl ether 18 (63.8 mg, 0.144 mmol) was dissolved in
anhydrous tributylamine (5 mL) and heated to 180 ꢁC
under an atmosphere of argon. After 1 h, TLC (pet-
rol–ethyl acetate, 4:1) indicated complete consumption
of starting material (Rf 0.5) and formation of a major
product (Rf 0.2). The reaction mixture was diluted with
ethyl acetate (50 mL), washed with hydrochloric acid
(2 · 50 mL) and sodium bicarbonate (50 mL), dried
(MgSO4), filtered and concentrated in vacuo. The resi-
due was purified by flash column chromatography (pet-
4.25. 6,10-Anhydro-1-tert-butoxycarboxy-9,11-O-di-tert-
butyl-silanediyl-7,8-didehydro-4-oxo-2,3,5,7,8-penta-
deoxy-D-glycero-D-gulo-undecitol 28
Vinyl ether 21 (82.7 mg, 0.19 mmol) was dissolved in
anhydrous tributylamine (5 mL) and heated to 180 ꢁC
under an atmosphere of argon. After 2 h 30 min, TLC
(petrol–ethyl acetate, 4:1) indicated complete consump-
tion of starting material (Rf 0.8) and formation of a
major product (Rf 0.6) and a minor product (Rf 0.2).
The reaction mixture was diluted with ethyl acetate
(40 mL), washed with hydrochloric acid (3 · 25 mL)
and sodium bicarbonate (2 · 25 mL), dried (MgSO4), fil-
tered and concentrated in vacuo. The residue was puri-
fied by flash column chromatography (petrol–ethyl
rol–ethyl acetate, 5:1) to give b-C-glycoside 25 (49.4 mg,
25
D
77%) as an amorphous solid; ½aŠ ¼ þ7:7 (c 0.8,
CHCl3); mmax (thin film) 3367 (br, NH), 1717 (sh, ketone,
amide I), 1507 (m, amide II) cmꢁ1; dH (400 MHz, C6D6)
1.19, 1.20 (18H, 2 · s, 2 · SiC(CH3)3), 1.52 (9H, s,
0
OC(CH3)3), 1.94(1H, dd, J3,3 15.6 Hz, J3,4 5.1 Hz, H-
3), 2.22 (1H, dd, J3 ,4 8.0 Hz, H-30), 3.55–3.61 (1H, m,
acetate, 12:1) to give b-C-glycoside 28 (71.0 mg, 86%)
0
24
D
0
H-8), 3.70 (1H, dd, JNH,1 4.8 Hz, J1,1 19.6 Hz, H-1),
0
as a colourless oil; ½aŠ ¼ þ16:3 (c 1.2, CHCl3); mmax
3.81 (1H, dd, JNH,1 5.3 Hz, H-10), 3.96 (1H, at, J
(thin film) 1726 (s, C@O); dH (400 MHz, C6D6) 1.20
(18H, s, 2 · SiC(CH3)3), 1.47 (9H, s, OC(CH3)3), 2.23
(1H, dd, J5,5 16.2 Hz, J5,6 5.7 Hz, H-5), 2.27–2.52 (4H,
0
0
10.2 Hz, H-9), 4.24 (1H, dd, J8,9 5.0 Hz, J9,9 10.3 Hz,
H-90), 4.40–4.50 (1H, m, H-4), 4.54–4.58 (1H, m, H-7),
5.10 (1H, br s, NH), 5.29 (1H, d, J5,6 10.4Hz, H-6),
5.94(1H, d, H-5); dC (100.6 MHz, C6D6) 20.4, 23.0
(2 · s, 3 · C(CH3)3), 27.5, 27.8, 28.5 (3 · q,
3 · C(CH3)3), 45.2 (t, C-3), 51.5 (t, C-1), 67.5 (t, C-9),
70.7 (d, C-7), 72.1 (d, C-4), 75.3 (d, C-8), 79.4 (s, C-2),
128.9 (d, C-6), 130.8 (d, C-5); m/z (ES+) 464 (M+Na+,
55), 459 (M+NHþ4 , 40), 442 (M+H+, 20%). (HRMS
(ES+) calcd for C22H40O6NSi (M+H+) 442.2625. Found,
442.2635).
0
m, H-2, H-20, H-3, H-30), 2.49–2.57 (1H, m, H-50),
3.62–3.68 (1H, m, H-10), 4.02 (1H, at, J 10.1 Hz, H-
11), 4.29 (1H, dd, J10,11 5.1 Hz, J11,11 10.0 Hz, H-110),
4.59–4.63 (1H, m, H-9), 4.66–4.71 (1H, m, H-6), 5.48
(1H, dat, J 1.9, 1.9, 10.4Hz, H-8), 5.98 (1H, d, J7,8
10.4Hz, H-7); dC (100.6 MHz, C6D6) 20.4, 21.0, 23.0
(3 · s, 3 · C(CH3)3), 27.5, 27.8, 28.2 (3 · q,
3 · C(CH3)3), 29.3, 38.2 (2 · t, C-2, C-3), 48.0 (t, C-5),
67.7 (t, C-11), 70.9 (d, C-9), 72.3 (d, C-6), 75.3 (d, C-
10), 80.2 (s, C-4), 129.5 (d, C-8), 130.5 (d, C-7), 171.9
(s, C-1); m/z (ES+) 903 (2M+Na+, 55), 463 (M+Na+,
70%). (HRMS (ES+) calcd for C23H44O6NSi
(M+NHþ4 ) 458.2938. Found, 458.2932).
0
0
4.24. 1-Amino-5,9-anhydro-N-tert-butoxycarbonyl-8,10-
O-di-tert-butylsilanediyl-6,7-didehydro-3-oxo-1,2,4,6,7-
pentadeoxy-D-glycero-D-gulo-decitol 26
Vinyl ether 19 (99.5 mg, 0.22 mmol) was dissolved in
anhydrous tributylamine (5 mL) and heated to 180 ꢁC
under an atmosphere of argon. After 1 h, TLC (pet-
rol–ethyl acetate, 4:1) indicated complete consumption
of starting material (Rf 0.6) and formation of a major
product (Rf 0.2). The reaction mixture was diluted with
ethyl acetate (100 mL), washed with water (50 mL),
hydrochloric acid (2 · 50 mL) and sodium bicarbonate
(50 mL), dried (MgSO4), filtered and concentrated in
vacuo. The residue was purified by flash column chro-
4.26. 1-(S) 2-Amino-7,11-anhydro-10,12-O-benzylidene-
N-tert-butoxycarbonyl-1-tert-butoxycarboxy-8,9-didehy-
dro-2,3,4,6,8,9-hexadeoxy-5-oxo-D-glycero-D-gulo-dodec-
itol 29
Vinyl ether 24 (86.0 mg, 0.17 mmol) was dissolved in
anhydrous tributylamine (3 mL) and heated to 180 ꢁC
under an atmosphere of argon. After 3 h, TLC (pet-
rol–ethyl acetate, 4:1) indicated complete consumption
of starting material (Rf 0.5) and formation of a major
product (Rf 0.2). The reaction mixture was diluted with
ethyl acetate (80 mL), washed with hydrochloric acid
(5 · 25 mL), and sodium bicarbonate (2 · 25 mL), dried
(MgSO4), filtered and concentrated in vacuo. The resi-
due was purified by flash column chromatography (pet-
matography (petrol–ethyl acetate, 4:1) to give C-glyco-
25
D
side 26 (65.1 mg, 65%) as a yellow oil; ½aŠ ¼ þ7:2 (c
0.8, CHCl3); mmax (thin film) 3373 (br, NH), 1700 (sh, ke-
tone, amide I), 1507 (w, amide II) cmꢁ1; dH (400 MHz,
C6D6) 1.19, 1.20 (18H, 2 · s, 2 · SiC(CH3)3), 1.53 (9H,
s, OC(CH3)3), 1.91–2.34(2H, m, H-4, H-4 0), 2.22–2.30
(2H, m, H-2, H-20), 3.27–3.36 (2H, m, H-1, H-10),
3.50–3.66 (1H, m, H-9), 3.96–4.03 (1H, m, H-10),
4.26–4.30 (1H, m, H-100), 4.57–4.59 (2H, m, H-5, H-
8), 4.90 (1H, br s, NH), 5.36 (1H, d, J6,7 10.2 Hz, H-
7), 5.97 (1H, d, H-6); dC (100.6 MHz, C6D6) 20.4, 21.2
(2 · s, 3 · C(CH3)3), 27.5, 27.8, 28.6 (3 · q,
3 · C(CH3)3), 35.6 (t, C-1), 43.7 (t, C-2), 48.0 (t, C-4),
67.6 (t, C-10), 70.9, 72.3 (2 · d, C-5, C-8), 75.3 (d, C-
rol–ethyl acetate, 3:1) to give b-C-glycoside 29 (40.1 mg,
15
D
47%) as
a
colourless oil; ½aŠ ¼ þ28:2 (c 1.2,
CHCl3); mmax (thin film) 3395 (br, NH), 1716 (sh, ketone,
amide I), 1501 (amide II) cmꢁ1; dH (400 MHz, CDCl3)
1.45, 1.47 (18H, 2 · s, 2 · C(CH3)3), 1.80–1.88 (1H, m,
H-3), 2.05–2.27 (1H, m, H-30), 2.44–2.65 (3H, m, H-4,
H-40, H-6), 2.70 (1H, dd, J6,6 15.9 Hz, J6 ,7 7.7 Hz, H-
60), 3.61 (1H, m, H-11), 3.75 (1H, at, J 10.2 Hz, H-12),
0
0
0
4.14–4.22 (2H, m, H-2, H-10), 4.29 (1H, dd, J11,12

D. J. Chambers et al. / Tetrahedron: Asymmetry 16 (2005) 45–55
55
4.4 Hz, J12,12 10.2 Hz, H-120), 4.77–4.80 (1H, m, H-7),
0
6. (a) Godage, H. Y.; Fairbanks, A. J. Tetrahedron Lett.
2000, 41, 7589–7593; (b) Godage, H. Y.; Fairbanks, A. J.
Tetrahedron Lett. 2003, 44, 3631–3635; (c) Godage, H. Y.;
Chambers, D. J.; Evans, G. R.; Fairbanks, A. J. Org.
Biomol. Chem. 2003, 1, 3772–3786.
7. (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am.
Chem. Soc. 1978, 100, 3611–3613; (b) Hartley, R. C.;
McKiernan, G. J. J. Chem. Soc., Perkin Trans. 1 2002,
2763–2793.
8. For pioneering use of stereospecific sigmatropic rear-
rangements in carbohydrate chemistry, see: (a) Corey, E.
J.; Shibasaki, M.; Knolle, J. Tetrahedron Lett. 1977, 18,
1625–1626; (b) Fleet, G. W. J.; Spensley, C. R. C.
Tetrahedron Lett. 1982, 23, 109–112; (c) Fleet, G. W. J.;
Gough, M. J. Tetrahedron Lett. 1982, 23, 4509–4512; (d)
Fleet, G. W. J.; Gough, M. J.; Shing, T. K. M.
Tetrahedron Lett. 1983, 24, 3661–3664.
5.08 (1H, d, J 7.6 Hz, NH), 5.59 (1H, s, PhCHO2),
5.70 (1H, dd, J8,9 10.3 Hz, J9,10 5.3 Hz, H-9), 5.98 (1H,
d, H-8), 7.27–7.54(5H, m, 5 · Ar-H); dC (100.6 MHz,
CDCl3) 20.8, 21.0 (2 · s, 2 · C(CH3)3), 28.4, 28.8
(2 · q, 2 · C(CH3)3), 28.7 (t, C-3), 41.2 (t, C-4), 48.2
(t, C-6), 54.7 (d, C-2), 69.8 (t, C-12), 71.3 (d, C-11),
72.8 (d, C-7), 75.5 (d, C-10), 82.6 (s, C-5), 102.4(d,
PhCHO2), 126.7, 128.7, 129.6 (3 · d, 5 · Ar-C), 127.5
(d, C-8), 129.7 (d, C-9), 137.9 (s, Ar-C); m/z (ES+) 54 0
(M+Na+, 100%). (HRMS (ES+) calcd for C28H40NO8
(M+H+) 518.2754. Found, 518.2754).
Acknowledgements
9. For approaches to C-glycosides by Claisen rearrange-
ment, see: (a) Ireland, R. E.; Wilcox, C. S.; Thaisrivongs,
S.; Vanier, R. Can. J. Chem. 1979, 57, 1743–1745; (b)
Fraser-Reid, B.; Dawe, R. D.; Tulshian, D. B. Can. J.
Chem. 1979, 57, 1746–1749; (c) Ireland, R. E.; Wuts, P.
G. M.; Ernst, B. J. Am. Chem. Soc. 1981, 103, 3205–
3207; (d) Ireland, R. E.; Anderson, R. C.; Badoub, R.;
Fitzsimmons, B. J.; McGarvey, G.; Thaisrivongs, S.;
Wilcox, C. S. J. Am. Chem. Soc. 1983, 105, 1988–2006;
(e) Tulshian, D. B.; Fraser-Reid, B. J. Org. Chem. 1984,
49, 518–522; (f) Curran, D. P.; Suh, Y. G. Carbohydr.
Res. 1987, 111, 161–191; (g) Colombo, L.; Casiraghi, G.;
Pittalis, A.; Rassu, G. J. Org. Chem. 1991, 56, 3897–
3900; (h) Vidal, T.; Haudrechy, A.; Langlois, Y. Tetra-
hedron Lett. 1999, 40, 5677–5680; (i) Wallace, G. A.;
Scott, R. W.; Heathcock, C. H. J. Org. Chem. 2000, 65,
4145–4152.
10. Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361–2364.
11. Moriwake, T.; Hamano, S.; Saito, S.; Torii, S. Chem. Lett.
1987, 2085–2088.
12. Chambers, D. J.; Evans, G. R.; Fairbanks, A. J. Tetra-
hedron: Asymmetry 2003, 14, 1767–1769.
13. These included the Petasis reagent Cp2Ti(CH3)2, the Takai
reagent combination (TiCl4, PbCl2, Zn, TMEDA and
CH2Br2 in THF), the Motherwell difluoromethylenation
system (HMPT, CF2Br2, Zn) and the Reddy system (CCl4,
PPh3, THF, reflux).
14. This may indicate the operation of a through-bond
inductive effect that particularly promotes ester cleavage
rather than methylenation in the cases of a-amino
acids.
We gratefully acknowledge financial support from the
EPSRC (Project Studentship to D.J.C.) and from Cell-
tech (CASE award to D.J.C.). We also acknowledge
the use of the Chemical Database Service (CDS) at
Daresbury, UK.
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