Stereoselective conjugate addition of mixed organoaluminum reagents to α,β-unsaturated N-acyloxazolidinones derived from carbohydrates

Article abstract of DOI:10.1055/s-2004-831173

The stereoselective synthesis of β-branched carboxylic acid derivatives was accomplished by conjugate addition of mixed organoaluminum reagents to chiral α,β-unsaturated N-acyloxazolidinones. Mixed organoaluminum reagents were generated in situ by transmetalation of Grignard or organolithium compounds with methylaluminum dichloride. Efficient stereocontrol was achieved using different bicyclic glycosamine-derived oxazolidinones, yielding alternatively (R)- or (S)-configured β-branched carboxylic acid derivatives.

Full text of DOI:10.1055/s-2004-831173

PAPER
2153
Stereoselective Conjugate Addition of Mixed Organoaluminum Reagents to
a,b-Unsaturated N-Acyloxazolidinones Derived from Carbohydrates
Conjugate
A
dd
t
ition
o
e
f
Mixe
d
O
r
p
ganoaluminu
h
m
Reagentsan Elzner,a Steffen Maas,a,b Stefan Engel,a,b Horst Kunz*a
a
Institut für Organische Chemie, Johannes-Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
Fax +49(613)13924786; E-mail: hokunz@mail.uni-mainz.de
b
BASF AG, 67056 Ludwigshafen, Germany
Received 2 April 2004; revised 21 April 2004
Dedicated to Professor Herbert Meier on the occasion of his 65th birthday.
Mixed methylalkylaluminum chlorides and trimethyla-
lkylaluminates, generated by transmetalation of organo-
lithium or Grignard compounds with MeAlCl2 or Me3Al,
respectively, proved to be useful reagents in 1,4-addition
Abstract: The stereoselective synthesis of b-branched carboxylic
acid derivatives was accomplished by conjugate addition of mixed
organoaluminum reagents to chiral a,b-unsaturated N-acyloxazoli-
dinones. Mixed organoaluminum reagents were generated in situ by
transmetalation of Grignard or organolithium compounds with reactions, thereby extending the methodology beyond the
methylaluminum dichloride. Efficient stereocontrol was achieved
limited number of commercially available dialkylalumi-
num chlorides.10
using different bicyclic glycosamine-derived oxazolidinones, yield-
ing alternatively (R)- or (S)-configured b-branched carboxylic acid
derivatives.
In this article, the stereoselective conjugate addition of
mixed organoaluminum reagents to a,b-unsaturated ac-
ceptors is described. The given conversions are based on
bicyclic carbohydrate oxazolidinones as efficient stereo-
differentiating tools.
Key words: stereoselective Michael additions, organoaluminum
compounds, chiral carboxylic acids, carbohydrates, auxiliaries
Among organoaluminum compounds, the dialkylalumi-
num chlorides have shown the most favourable reactivity
and selectivity in 1,4-addition reactions to the N-acylox-
azolidinone acceptors (for example, 1).8,9 The reaction
was restricted by the fact that only a few dialkylaluminum
chlorides are commercially available and that syntheses of
these air-sensitive compounds are often rather demand-
ing, requiring, for example, the use of organomercury or
organotin compounds.11
The synthesis of carboxylic acids branched at the b-posi-
tion can efficiently be accomplished by Michael addition
or analogous 1,4-addition reactions of carbon nucleo-
philes to enone systems. Whereas organoaluminum com-
pounds play an important role as Lewis acids and catalysts
in the polymerization of olefins,1 conjugate addition reac-
tions of organoaluminum reagents have only rarely been
reported, in contrast to analogous reactions of organocu-
prates and Grignard compounds. The conjugate addition
of organoaluminum reagents obviously suffers from de-
creased reactivity and regioselectivity of these nucleo-
philes.2 A few examples of conjugate addition reactions of
alkenyl groups from organoaluminum reagents have been
reported. Hexenyl diisobutylalane, for example, transfers
the alkenyl moiety to a,b-unsaturated ketones in 35%
yield.3 The conjugate addition of alkynyl groups was also
achieved by the application of mixed organoaluminum
compounds.4
Under the reaction conditions for conjugate addition to 1
(toluene, –78 to –45 °C), the Me-Al bond shows no reac-
tivity. It was demonstrated, in detailed studies, that even
at elevated temperature (–20 °C) and with larger excess,
dimethylaluminum chloride fails to deliver a methyl
group to a,b-unsaturated acceptors, whereas this reaction
proceeds efficiently under UV-irradiation (Scheme 1).9
PivO
PivO
PivO
PivO
OPiv
O
OPiv
O
Me AlCl
2
Recent studies have shown that the chemoselective 1,4-
addition of dialkylaluminum chlorides to alkylidenema-
lonic acid esters is efficiently accomplished.5 The stereo-
selective version of this reaction was successfully
performed by applying chiral oxazolidinones derived
from amino acids6 or carbohydrates.7–9 In the latter case,
b-branched carboxylic acid derivatives were obtained
with excellent stereoselectivity, especially when an O-
pivaloyl protected bicyclic galactosamine-derived oxazo-
lidinone (9) was used as the auxiliary.
4 equiv
hν, 5 h
N
O
N
O
toluene/n-hexane
Ph
Ph
O
O
–78 °C
O
O
2
1
82%
R:S >98:2
Scheme 1 1,4-Addition of dimethylaluminum chloride9
Mixed organoaluminum species selectively transfer non-
methyl groups in 1,4-addition reactions.5,9,10
SYNTHESIS 2004, No. 13, pp 2153–2164
Advanced online publication: 17.08.2004
DOI: 10.1055/s-2004-831173; Art ID: T04004SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4
In transmetalation processes, various alkyl, alkenyl (vi-
nyl), aryl and alkynyl aluminum compounds 3a–f can be
generated by subjecting commercially available MeAlCl2

2154
S. Elzner et al.
PAPER
Table 1 Conjugate Addition of Mixed Aluminum Reagents to Glu-
cose-Derived N-Acyloxazolidinones 6
to reaction with organolithium or Grignard compounds in
toluene at –50 °C. In an analogous manner, aluminates 4
can be produced as Michael reagents from Me3Al
(Scheme 2).
OPiv
O
OPiv
O
PivO
PivO
PivO
PivO
a) 1 equiv MeAlCl2
b) 3a–c/5
N
O
N
O
toluene, –40 °C
O
O
RM + MeAlCl2
RMeAlCl
toluene
–50 °C
O
R
O
RM =n-BuLi
3a R = n-Bu
3b R = t-Bu
3c R = hexynyl
3d R = Ph
3e R = cyclohexyl
3f R = vinyl
6
7
t-BuLi
hexynylLi
PhLi
Product
Reagent
(equiv)
R
Yield
Conver- dra
sion (%) (3R):(3S)
cyclohexylMgBr
(%)
vinylMgBr
7a
7b
7c
7d
3a (10)
3b (10)
5 (8)
n-Bu
t-Bu
55
85
90
75
68
75:25b
34:66c
33:67
46:54
31
RLi +
RAlMe3 Li+
-
AlMe
3
toluene
–50 °C
hexenyl 38
hexynyl 40
4a R = t-Bu
4b R = Ph
3c (5)
Scheme 2 Generation of mixed organoaluminum reagents by trans-
a Determined by 1H NMR, unless otherwise indicated.
b Determined by 13C NMR.
metalation reactions
c Determined by HPLC.
A more general access to organoaluminum compounds
for the transfer of alkenyl groups is the hydroalumination
of alkynes, yielding trans-configured alkenyl aluminum
compounds.12 Accordingly, an appropriate diisobutyl-
alane 5 was synthesized from 1-hexyne and diisobutyl
aluminum hydride at 45 °C in toluene (Scheme 3).
1,4-addition of hexynylmethylaluminum chloride 3c pro-
ceeded with lower selectivity (7d).
Galactosamine-derived chiral template 19 was shown to
be a more efficient stereodifferentiating tool in compari-
son to the glucosamine auxiliary in acceptor 6. In addi-
tion, sterically more demanding cinnamic acid acceptors
like 1 should be superior to crotonic acid derivatives such
as 6. In order to enhance the stereoselectivity of the addi-
tion, the application of acceptor 1 was investigated
(Table 2).
i-Bu2AlH
i-Bu2Al
+
toluene, 45 °C
Bu
Bu
5
Scheme 3 Synthesis of mixed organoaluminum reagent by hydro-
alumination of 1-hexyne
Indeed, the conjugate addition to a,b-unsaturated N-acyl-
oxazolidinone 1 proceeded with significantly higher dia-
stereoselectivity (Table 2). b-Branched carboxylic acid
derivatives were formed in diastereomeric ratios from
84:16 up to almost enantiomerically pure products (8a). In
With the exception of commercially available Et2AlCl
and (i-Bu)2AlCl, the reagents investigated in the follow-
ing conjugate addition reactions were prepared in situ, ac-
cording to Scheme 2 and Scheme 3, prior to the 1,4-
addition reaction.
Among the glycosamine-derived oxazolidinones efficient
in 1,4-addition reactions of dialkylaluminum chlorides,
the glucosamine-derived Michael acceptor 6 was first in-
vestigated in reactions with mixed diorganyl (3) and trior-
ganyl aluminum (5) reagents.
Table 2 1,4-Addition Reactions of Mixed Aluminum Reagents to
Galactose-Based Acceptor 1
PivO
PivO
OPiv
O
OPiv
O
a) 1 equiv MeAlCl2
b) 3a–c/5
PivO
PivO
N
O
N
O
toluene, –40 °C
Ph
Ph
O
O
The reactions were carried out at –40 °C with toluene as
the solvent. Prior to the 1,4-addition reaction, the a,b-un-
saturated acceptor was subjected to one equivalent of a
strong Lewis acid (MeAlCl2) to form a chelating complex
with the acyl and oxazolidinone carbonyl groups. The
mixed aluminum reagent used for 1,4-addition should also
form a chelating complex with substrate 6, but our inves-
tigations have shown that subjecting the acceptor to
MeAlCl2 prior to the conjugate addition significantly in-
creases the stereoselectivity.9
O
R
O
8
1
Product Reagent
(equiv)
R
Yield
(%)
Conver- dra
sion (%) (3R):(3S)
8a
8b
8c
8d
3a (10)
n-Bu
77
58
quant.
90
99:1
3bb (10) t-Bu
11:89
11:89
16:84
5 (10)
hexenyl 44
hexynyl 33
85
As shown in Table 1, conjugate addition reactions of alu-
minum nucleophiles 3a, 3b and 5 to Michael acceptor 6
yielded the b-branched carboxylic derivatives 7a–c with
diastereomeric ratios in the range of 70:30, whereas the
3c (10)
83
a Determined by 1H NMR.
b BF3 was added to minimize b-H elimination.
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

PAPER
Conjugate Addition of Mixed Organoaluminum Reagents
2155
OAc
order to reduce the competing b-hydrogen transfer, which
was observed in the transfer of sterically demanding
groups,5,10 BF3 was added for the preparation of 8b.
OPiv
a,b
O
O
OAc
OPiv
11
12
In general, the products from transfer of the n-butyl group
(7a, 8a) were obtained in the highest stereoselectivity and
yield. The transfer of hexenyl and tert-butyl moieties re-
sulted in similar yield and selectivity using acceptor 1 as
well as acceptor 6 (adducts 7b, 7c and 8b, 8c). As shown
in Table 1 and Table 2, various carbon nucleophiles, even
those containing sterically demanding (adducts 7b, 8b)
and unsaturated substituents (adducts 7c, 7d, 8c and 8d),
can be introduced in the b-position of the carboxylic acid
by this method. The absolute configuration of the major
diastereomers of type 7 and 8 was deduced by comparing
the optical rotation data of known free carboxylic acids
obtained after release from the auxiliary (see also
Scheme 6) with compounds described in the literature.9
Unfortunately, some reactions suffered from incomplete
conversion even when ten equivalents of the reagent were
used.
c
OPiv
OPiv
OPiv
OPiv
O
O
d
HO
O2NO
N3
N3
14
13
e
OPiv
OPiv
OPiv
OPiv
O
O
O
f,g
NH
N
R
O
O
O
O
10
15
R = Me
16 R = Ph
Scheme 4 Synthesis of D-arabinose-derived bicyclic oxazolidinone
acceptors 15 and 16. Reagents and conditions: (a) NaOMe, MeOH,
20 °C; (b) pivaloyl chloride, pyridine, 20 °C, 88% over two steps; (c)
Our next interest concerned the expansion of the de-
scribed method to access the opposite enantiomers of the NaN3, Ce(NH4)2(NO3)6, MeCN, –25 °C, 33%; (d) NaNO2, dioxane–
H2O, 61%; (e) PPh3, CO2, dioxane, 20 °C, 64%; (f) MeMgCl, THF, 0
°C; (g) 1.1 equiv crotonoyl chloride (15) or cinnamoyl chloride (16),
–78 °C→0 °C, 74–82%.
b-branched carboxylic acids. Since preparation of the bi-
cyclic oxazolidinone from L-galactose was not a realistic
option, D-arabinose was used as the source for the auxilia-
ry.13 The only difference between L-galactose and D-ara-
saturated acceptor was treated with 1.5 equivalents of
MeAlCl2 prior to the reaction. Commercially available
Et2AlCl and (i-Bu)2AlCl gave excellent yield and stereo-
selectivity (adducts 18a, 18b). The sterically more de-
manding and less reactive (i-Bu)2AlCl chloride reacted
smoothly under these conditions (17a, 18b).
binose is the absence of the C-5 hydroxymethyl group in
D-arabinose. However, as the 1,4-addition occurs in prox-
imity of C-2, C-3 and C-4,9 the missing substituent should
have only a marginal effect on the stereodifferentiating
potential of the D-arabinose auxiliary 10 (Figure 1).
Mixed organoaluminum reagents showed lower reactivity
as they required ten equivalents of reagent for high rates
of conversion. Indeed, good yields could be achieved, es-
pecially with alkyl nucleophiles (17a, 17b, 18a–c). Use of
cyclohexylmagnesium bromide in Et2O, instead of the
lithium compound (in hexane), for transmetalation with
MeAlCl2 resulted in lower diastereoselectivity (18e). The
more nucleophilic aluminate 4a gave a slightly higher
yield in the addition reaction to the cinnamoyl acceptor
16, compared to the product obtained by reaction with di-
alkylaluminum chloride 3b, but in this case the diastereo-
selectivity was lower.
PivO
PivO
OPiv
OPiv
OPiv
O
O
O
HN
NH
O
O
O
10
9
Figure 1 Bicyclic carbohydrate auxiliaries
Synthesis of 10 was accomplished in analogy to that of
chiral auxiliary 99 (Scheme 4). From readily accessible
acetylated arabinal 11,14 O-acetyl groups were replaced
by O-pivaloyl groups under Zemplen conditions for
deprotection, and subsequently esterified with pivaloyl
chloride (12). After azidonitration according to Lemieux15
(13) and hydrolysis of the nitrate16 using aqueous sodium
nitrite (14), the bicyclic oxazolidinone 10 was formed in a
Staudinger–aza-Wittig reaction sequence with triphenyl
phosphine and carbon dioxide. The a,b-unsaturated acyl
oxazolidinones 15 and 16 were obtained by deprotonation
of 10 with methylmagnesium chloride, followed by treat-
ment with crotonoyl or cinnamoyl chloride, respectively.
Analogous addition reactions of methylphenylaluminum
chloride (3d) and methylvinylaluminum chloride (3f) to
a,b-unsaturated acceptor 15 or 16 failed. In both cases, the
starting material was recovered.
In order to increase the reactivity of the phenyl alane, ad-
dition with phenyltrimethylaluminate 4b was examined.
Even after prolonged reaction times, HPLC analysis of the
crude reaction mixture showed only 50% conversion, and
a mixture of products from phenyl addition (18h) and
methyl addition (19) was formed in a ratio of 1:2.3
(Scheme 5).
The conjugate addition of various aluminum nucleophiles
to these Michael acceptors 15 and 16 were examined un-
der standard conditions at –55 °C (Table 3). The a,b-un-
To confirm the stereochemical outcome of the reaction
performed with bicyclic oxazolidinone 10, the product of
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

2156
S. Elzner et al.
PAPER
Table 3 Conjugate Addition of Mixed Organoaluminum Compounds to Arabinose-Derived a,b-Unsaturated Acceptors 15 and 16
OPiv
OPiv
OPiv
OPiv
O
O
O
O
a) 1.5 equiv MeAlCl2
b) 3a–c/5
N
N
R
R
O
O
toluene, –55 °C
O
R'
O
15R = Me
R = Ph
17a-e
R = Me
18a-i R = Ph
16
Reagent
Equiv
Acceptor
R
R1
Reaction
time
Product
Yield/
Conversion (3S):(3R)
dr
(h)
(%)
i-Bu2AlCl
10
10
10
10
12
3
15
15
15
15
15
16
16
16
16
16
16
16
16
15
16
Me
Me
Me
Me
Me
Ph
i-Bu
3
10
16
18
72
18
5
17a
17b
17c
17d
17e
18a
18b
18c
18d
18d
18e
18f
75
73:27a
72:28b
28:72a
25:75b
35:65b
96:4c
95:5c
96:4c
5:95c
9:91c
29:71c
19:81b
19:81b
–
3a (n-BuMeAlCl)
3b (t-BuMeAlCl)
5 [hexenyl(i-Bu)2Al]
3c (hexynylMeAlCl)
Et2AlCl
n-Bu
71
t-Bu
42
hexenyl
hexynyl
Et
46/90
41
83
i-Bu2AlCl
6
Ph
i-Bu
76
3a (n-BuMeAlCl)
3b (t-BuMeAlCl)
4a (t-BuMe3Al–Li+)
10
10
10
Ph
n-Bu
18
18
16
16
40
72
72
72
69
Ph
t-Bu
54
Ph
t-Bu
57
3e (cyclohexylMeAlCl)
5 [hexenyl(i-Bu)2Al]
3c (hexynylMeAlCl)
3d (PhMeAlCl)
10
10
10
10
10
Ph
cyclohexyl
hexenyl
hexynyl
Ph
50/75
41/90
16/55
–
Ph
Ph
18g
18h
18i
Me
Ph
3f (vinylMeAlCl)
vinyl
–
–
a Determined by 13C NMR.
b Determined by 1H NMR.
c Determined by HPLC.
OPiv
OPiv
the reaction mixture by aqueous extraction. Comparison
of the optical rotation value with that of an authentic sam-
ple of carboxylic acid 20 described in the literature18
proved the absolute configuration of 20 to be S. Thus, the
arabinose-derived oxazolidinone 10 serves as pseudo-
enantiomeric auxiliary to 9 and, therefore, leads to the (S)-
enantiomer of the b-branched carboxylic acid as the major
stereoisomer (Scheme 6).
O
O
N
O
O
OPiv
O
19
+
a) 1.5 equiv MeAlCl2
b) 4b
OPiv
OPiv
O
N
OPiv
toluene, –55 °C, 72 h
O
In summary, concerning yield and stereoselectivity, com-
parable results in the synthesis of the enantiomeric b-
branched carboxylic acids can be achieved by applying ei-
ther the galactose- or arabinose-derived bicyclic oxazoli-
dinones. The glucose-derived auxiliary is somewhat less
efficient.
N
O
15
O
O
O
18h
O
19:18h = 2.3:1
50% conversion
Scheme 5 Reaction of lithium phenyltrimethylalanate 4b with ac-
ceptor 15
The results described herein show that a great variety of
aluminum carbon nucleophiles, particularly mixed orga-
noaluminum reagents, can be utilized in 1,4-addition reac-
tions. The b-branched carboxylic acids can be synthesized
with high stereoselectivity. Chiral auxiliaries derived
ethyl addition (18a, dr = 97:3) was subjected to hydroly-
sis with LiOH–H2O2 in THF–H2O (Scheme 6).8,17 Auxil-
iary 10 and carboxylic acid 20 were readily isolated from
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

PAPER
Conjugate Addition of Mixed Organoaluminum Reagents
2157
1H NMR (200 MHz, CDCl3): d = 1.16, 1.18 (2 s, 18 H, C(CH3)3),
3.96 (m, 2 H, H-5a, H-5b), 4.85 (dd, 1 H, J = 5.9, 5.4 Hz, H-2), 5.13
(q, 1 H, J = 4.9, 4.4, 3.9 Hz, H-4), 5.35 (dd, 1 H, J = 4.9, 3.9 Hz, H-
3), 6.45 (d, 1 H, J = 6.3 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): d = 26.50, 27.15 [C(CH3)3], 38.72,
38.86 [C(CH3)3], 62.71 (C-5), 62.88, 66.22 (C-3, C-4), 97.74 (C-2),
147.51 (C-1), 177.27, 177.56 (CO, pivaloyl).
OPiv
OPiv
O
O
NH
OPiv
OPiv
O
O
10 81%
LiOH, H2O2
N
O
THF, H2O, 0 °C
O
O
Anal. Calcd for C15H24O5 (284.36): C, 63.36; H, 8.51. Found: C,
63.72; H, 8.73.
HO
18a
FD-MS (+): m/z = 284.7 [M]+, 183.5 [M – PivOH]+.
O
20 86%
2-Azido-2-deoxy-3,4-di-O-pivaloyl-D-arabinopyranosyl nitrate
(13)15
Scheme 6 Detachment of b-branched carboxylic acid 20 from the
chiral template and confirmation of the absolute configuration
To 12 (46 g, 161 mmol) in dry degassed MeCN (800 mL), NaN3
(15.5 g, 238 mmol) and Ce(NH4)2(NO3)6 (300 g, 547 mmol) was
added at –50 °C under argon atmosphere. The yellow solution was
stirred overnight at –25 °C. The reaction mixture was diluted with
ice-cold Et2O (900 mL) and ice-cold H2O (900 mL). The organic
layer was separated, washed with ice-cold H2O (3 × 900 mL), dried
with MgSO4 and concentrated in vacuo (bath temperature <35 °C).
The crude product was purified by flash chromatography in LPE–
EtOAc (15:1).
from D-galactose on the one hand and D-arabinose on the
other hand offer an alternative access to either (R)- or (S)-
configured b-branched carboxylic acids.
Solvents were dried and distilled before use. Analytical TLC was
performed on aluminum-backed TLC plates coated with silica gel
60F254 (E. Merck, Darmstadt). Column chromatography was per-
formed on silica (63–200 mm, Baker or 40-63 mm, E. Merck, Darm-
stadt). Melting points were measured on a Dr. Tottoli apparatus
(Büchi) and are uncorrected. Optical rotation values were measured
on a Perkin-Elmer 241 polarimeter. NMR spectra were recorded on
a Bruker WT-200 and a Bruker AM 400 spectrometer; chemical
shifts are given in ppm downfield from tetramethylsilane. FD-MS
spectra were measured on a MAT 95-spectrometer (Finnigan). ESI-
MS were measured on a Navigator (ThermoQuest) between 200 and
1300 amu at a cone voltage of 70 eV using a flow rate of 0.75 mL/
min MeCN–H2O (70:30 v/v) and a nitrogen flow of 300 L/h. A ba-
sic marathon autosampler was employed for sample injection (20
mL at 0.1 g/L). Analytical HPLC analyses were performed on a
Knauer system (LKB 2150) equipped with a diode array detection
(LKB2140) and a LUNA C18-2 column (Phenomenex, 250 × 4.6
mm, 5 mm particle size) in MeCN–H2O using a flow rate of 1 mL/
min. HPLC-MS analysis was performed on a Navigator system de-
scribed above and Knauer HPLC system with a LUNA C18-2 col-
umn (Phenomenex, 75 × 4.6 mm, 3 mm particle size) in combination
with a flow splitter (ratio 10:1). Preparative HPLC was performed
on a Knauer system equipped with a LUNA C18-2 column (Phe-
nomenex, 250 × 50 mm, 10 mm particle size) and a diode array UV
detector at a flow rate of 20 mL/min. Light petroleum ether is ab-
breviated throughout as LPE.
Yield: 20.7 g (53.3 mmol, 33%); colourless oil; Rf = 0.48 (LPE–
EtOAc, 6:1); [a]D21 –117.7 (c = 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 1.19, 1.23 [s, 18 H, C(CH3)3], 3.83
(dd, 1 H, J = 13.2, 2.0 Hz, H-5a), 4.13 (m, 2 H, J = 13.2, 3.4 Hz, H-
2, H-5b), 5.22 (dd, 1 H, J = 3.4, 11.2 Hz, H-3), 5.36 (d, 1 H, J = 1.5
Hz, H-4), 6.34 (d, 1 H, J = 3.9 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): d = 26.50, 26.96 [C(CH3)3], 38.86,
40.19 [C(CH3)3], 56.97 (C-2), 63.31 (C-5), 67.46, 68.21 (C-3, C-4),
97.8 (C-1), 177.0 (CO, pivaloyl).
C15H24N4O8 (388.38).
FD-MS (+): m/z = 389.1 [M + H]+.
2-Azido-2-deoxy-3,4-di-O-pivaloyl-D-arabinopyranose (14)16
To a solution of 13 (20 g, 51.4 mmol) in dioxane (233 mL) was add-
ed NaNO2 (12.85 g, 186 mmol) in H2O (42 mL), and the reaction
mixture was stirred at 80 °C for 5 h. Then, H2O (150 mL) was added
and the mixture was extracted with CH2Cl2 (3 × 150 mL). The or-
ganic layer was dried with MgSO4, concentrated in vacuo, and the
crude product was purified by flash chromatography in LPE–
EtOAc (8:1).
Yield: 11.3 g (32.9 mmol, 61%); colourless oil; Rf = 0.63 (LPE–
EtOAc, 1:1); [a]D22 –81.8 (c = 1.0, CHCl3); anomeric ratio 2.5:1
(200 MHz 1H NMR).
1H NMR (200 MHz, CDCl3): d = 1.18, 1.21, 1.22, 1.24 [s, 18 H,
C(CH3)3], 3.44 (br s, 1 H, OH), 3.59–3.76 (m, 2 H, J = 12.7, 7.8, 1.5
Hz, H-2, H-5a), 4.14 (dd, 1 H, J = 12.7, 1.0 Hz, H-5b), 4.60 (d, 1 H,
J = 7.8 Hz, a-H-1), 4.82 (dd, 1 H, J = 3.4, 0.7 Hz, a-H-3), 5.16 (m,
a-H-4), 5.30 (br d, 1 H, J = 1.5 Hz, b-H-4), 5.34–5.40 (m, 2 H,
J = 3.4 Hz, 3J1,2 = 7.8 Hz, b-H-3, b-H-1).
13C NMR (50.3 MHz, CDCl3): d = 26.97, 27.04, 27.13, 27.45
[C(CH3)3], 38.86, 38.94, [C(CH3)3], 59.16, 63.07 (C-2), 60.66,
64.48 (C-5), 67.37, 68.05, 68.50, 71.14 (C-3, C-4), 92.67, 96.66 (C-
1), 177.34, 177.62 (CO, pivaloyl).
Synthesis of chiral auxiliary 10 and acceptors 15 and 16:
1,5-Anhydro-3,4-di-O-pivaloyl-2-deoxy-D-erythro-pent-1-eni-
tol (12)
To a solution of arabinal 1114 (94.6 g, 470 mmol) in dry MeOH (440
mL) was added NaOMe in dry MeOH (0.5 M, 266 mL, 133 mmol)
at 0 °C. After 15 min, the ice bath was removed and the solution was
stirred for additional 3 h at 20 °C. Then the solvent was removed in
vacuo. The deacetylated crude product was dissolved in pyridine (5
L). Pivaloyl chloride (180 mL, 1.5 mol) was added at 0 °C under ar-
gon atmosphere. After 3 d, additional pivaloyl chloride (20 mL, 167
mmol) was added and stirring was continued for 1 d. Then, pyridine
was removed in vacuo. The residue was dissolved in CH2Cl2 (2 L)
and washed with 2 N HCl (3 × 350 mL), sat. NaHCO3 (3 × 500 mL)
and sat. NaCl (1 L). The organic layer was dried with MgSO4 and
concentrated in vacuo. The crude product was purified by flash
chromatography in LPE–EtOAc (12:1).
Anal. Calcd for C15H25N3O6 (343.38): C, 52.47; H, 7.34; N, 12.24.
Found: C, 52.52; H, 7.39; N, 12.28.
ESI-MS: m/z = 366.2 [M + Na]+, 382.3 [M + K]+.
1,2-Dideoxy-1,2-(epoxycarbonylimino)-3,4-di-O-pivaloyl-b-D-
arabinopyranose (10)
A solution of 14 (4.52 g, 13.2 mmol) in dry degassed dioxane (135
mL) was treated with a stream of dry CO2 gas at 20 °C. After 1 h,
Yield: 118 g (415 mmol, 88%); colourless oil; Rf = 0.51 (LPE–
EtOAc, 9:1); [a]D21 +160.1 (c = 1.0, CHCl3).
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

2158
S. Elzner et al.
PAPER
PPh3 (3.9 g, 14.9 mmol) in dry dioxane (23 mL) was added drop-
wise over 30 min. Treatment with CO2 was continued for 8 h, then
the reaction mixture was stirred overnight. The solvent was re-
moved in vacuo and the product was purified by flash chromatogra-
phy in LPE–EtOAc (8:1).
13C NMR (50.3 MHz, CDCl3): d = 26.89, 27.10 [C(CH3)3], 38.74,
38.97 [C(CH3)3], 53.88 (C-2), 63.02 (C-5), 65.83, 69.41 (C-3, C-4),
96.89 (C-1), 116.84 (PhCH=CH), 128.71, 128.90, 130.85 (C-Ar),
134.38 (C-ipso), 147.00 (PhCH=CH), 150.78 (CO, urethane),
164.38 (CO, acyl), 177.21 (CO, pivaloyl).
Yield: 2.86 g (64%); colourless, amorphous solid; Rf = 0.28 (LPE–
Anal. Calcd for C25H31NO8 (473.53): C, 63.41; H, 6.60; N, 2.96.
Found: C, 63.34; H, 6.76; N, 3.12.
EtOAc, 4:1); mp 195 °C; [a]D22 –82.6 (c = 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 1.19, 1.21 [s, 18 H, C(CH3)3], 3.76
(dd, 1 H, J = 7.3, 6.3 Hz, H-2), 3.94 (dd, 1 H, J = 12.7, 2.9 Hz, H-
5a), 4.26 (q, 1 H, J = 12.7 Hz, H-5b), 5.21 (m, 1 H, H-4), 5.28 (dd,
1 H, J = 7.3, 3.9 Hz, H-3), 5.92 (d, 1 H, J = 6.4 Hz, H-1), 6.98 (s, 1
H, N-H).
13C NMR (50.3 MHz, CDCl3): d = 26.96, 27.09 [C(CH3)3], 38.85,
38.94 [C(CH3)3], 53.39 (C-2), 63.14 (C-5), 65.99, 71.69 (C-3, C-4),
98.34 (C-1), 157.96 (CO, urethane), 177.15, 177.85 (CO, pivaloyl).
FD-MS (+): m/z = 474.0 [M + H]+.
1,4-Addition Reactions, General Procedures:
Preparation of Organoaluminum Reagents 3–5
Method A (mixed dialkylaluminum chlorides 3): Toluene was
cooled to –40 °C in a dried flask under argon atmosphere. MeAlCl2
(1 M in hexane) and equimolar amounts of the Grignard or organo-
lithium reagent were added through a rubber septum using a sy-
ringe. The mixture was stirred for 1 h at this temperature.
Anal. Calcd for C16H25NO7 (343.38): C, 55.97; H, 7.34; N, 4.08.
Found: C, 55.91; H, 7.35; N, 4.03.
ESI-MS: m/z = 366.2 [M + Na]+, 709.4 [2 M + Na]+.
Method B (ate-complexes 4): In a dried flask, toluene and Me3Al (2
M in pentane) were placed at –50 °C under argon atmosphere. Or-
ganolithium or Grignard compound was added and the mixture was
stirred for 1 h.
1,2-Dideoxy-1,2-[(E)-N-(2-butenoyl)epoxycarbonylimino]-3,4-
di-O-pivaloyl-b-D-arabinopyranose (15)
Method C (hexenyldiisobutylalane 5): Dry toluene, DIBAL-H and
1-hexyne were placed in a dried flask and stirred at 45 °C for 2 h un-
der argon atmosphere.
To a solution of 10 (3 g, 8.7 mmol) in THF (140 mL) at 0 °C was
added methylmagnesium chloride (3.2 mL, 9.7 mmol, 3 M in THF,
1.1 equiv). After 15 min the reaction mixture was cooled to –78 °C,
and freshly distilled crotonoyl chloride (0.92 mL, 9.61 mmol) was
added via syringe. Stirring was continued for 15 min at this temper-
ature. After raising the temperature to 0 °C, stirring was continued
until complete conversion was detected (ca. 1 h). The reaction mix-
ture was poured into sat. NH4Cl (35 mL) and the THF was removed
under reduced pressure. Et2O (200 mL) was added to the mixture,
then the organic layer was washed with sat. NaHCO3 and dried with
MgSO4. The solvent was removed in vacuo, and the residue was pu-
rified by flash chromatography in LPE–EtOAc (10:1).
1,4-Addition of Organoaluminum Reagents to a,b-Unsaturated
N-Acyl Oxazolidinones 1, 6, 15 and 16:
The a,b-unsaturated acceptor (1, 6, 15 or 16) in toluene (details are
quoted for every compound) was cooled to –55 °C and 1–1.25 equiv
MeAlCl2 (1 M in hexane) were added via syringe. After stirring for
1 h, the aluminum reagent [prepared in a separate flask according to
method A-C or commercially available Et2AlCl or (i-Bu2)AlCl] was
added rapidly via syringe. The reaction mixture was stirred at
–55 °C or –40 °C, typically for 18–20 h. The reaction was terminat-
ed by addition of sat. NH4Cl (100 mL) and then extracted with
CH2Cl2 (3 × 30 mL). The combined organic layers were washed
with aq sat. NH4Cl (40 mL) and then dried with MgSO4. The solvent
was evaporated in vacuo and the residue was purified by flash chro-
matography (LPE–EtOAc, 15:1) except for 7c, 8c, 17d and 18f,
which were purified by preparative HPLC.
Yield: 2.65 g (74%); colourless, amorphous solid; Rf = 0.55 (LPE–
EtOAc, 4:1); mp 143 °C; [a]D22 +11.3 (c = 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 1.16, 1.23 [s, 18 H, C(CH3)3], 1.93
(d, 3 H, J = 5.4 Hz, CH3), 3.97 (dd, 1 H, J = 12.7, 3.4 Hz, H-5a),
4.11 (dd, 1 H, J = 12.7, 2.0 Hz, H-5b), 4.73 (dd, 1 H, J = 5.9, 7.8 Hz,
H-2), 5.17 (dd, 1 H, J = 3.4, 2.0 Hz, H-4), 5.25 (dd, 1 H, J = 7.3, 3.9
Hz, H-3), 5.89 (d, 1 H, J = 6.4 Hz, H-1), 7.11 (m, 2 H, CH=CH).
13C NMR (50.3 MHz, CDCl3): d = 18.53 (=CH-CH3), 26.86, 27.09
[C(CH3)3], 38.70, 38.94 [C(CH3)3], 53.74 (C-2), 62.96 (C-5), 65.80,
69.33 (C-3, C-4), 96.78 (C-1), 121.77 (MeCH=CH), 147.59
(MeCH=CH), 150.65 (CO, urethane), 164.06 (CO, acyl), 177.18
(CO, pivaloyl).
1,2-Dideoxy-1,2-[N-(3-methylheptanoyl)epoxycarbonylimino]-
3,4,6-tri-O-pivaloyl-a-D-glucopyranose (7a)
According to general procedure, method A. Reagents: MeAlCl2 (1
M in hexane, 5.7 mL, 5.7 mmol), n-BuLi (1.6 M in pentane, 3.6 mL,
5.76 mmol), toluene (50 mL); 6 (300 mg, 0.57 mmol), MeAlCl2 (1.0
M in hexane, 0.6 mL, 0.6 mmol), toluene (50 mL).
Yield: 182 mg (55%); colourless, amorphous solid; Rf = 0.62 (LPE–
EtOAc, 5:1); [a]D22 –24.4 (c = 1.0, CHCl3); diastereomeric ratio
75:25 (CHN, 100.6 MHz 13C NMR).
Anal. Calcd for C20H29NO8 (411.46): C, 58.38; H: 7.10; N: 3.40.
Found: C, 58.24; H, 7.24; N, 3.30.
FD-MS (+): m/z = 413.0 [M + H]+.
1H NMR (400 MHz, CDCl3): d = 0.84–0.91 [m, 6 H, (CH2)3CH3,
CHCH3], 1.12, 1.16, 1.18 [s, 27 H, C(CH3)3], 1.10–1.34 [m, 6 H,
(CH2)3], 1.91–2.00 (m, 1 H, CHCH3), 2.68 (dd, 1 H, J = 17.0, 7.9
Hz, CH2CO), 2.80 (dd, 1 H, J = 17.0, 5.3 Hz, CH2CO), 4.00–4.04
(m, 1 H, H-5), 4.16 (dd, 1 H, J = 12.3, 5.3 Hz, H-6a), 4.22 (dd, 1 H,
J = 12.3, 2.6 Hz, H-6b), 4.58 (dd, 1 H, J = 6.8, 5.0 Hz, H-2), 5.04
(dd, 1 H, J = 8.7, 6.3 Hz, H-4), 5.35 (dd, 1 H, J = 6.5, 5.0 Hz, H-3),
5.90 (d, 1 H, J = 7.0 Hz, H-1).
1,2-Dideoxy-1,2-[(E)-N-(3-phenyl-2-propenoyl)epoxycarbon-
ylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (16)
The synthesis of 16 was accomplished in analogy to that of 15 from
10 (1.3 g, 3.79 mmol) and freshly distilled cinnamoyl chloride (694
mg, 3.9 mmol). The product was purified by flash column chroma-
trography in LPE–EtOAc (10:1).
Yield: 1.42 g (82%); colourless, amorphous solid; Rf = 0.57 (LPE–
(minor diastereomer) d = 2.65 (dd, 1H, J = 17.0, 7.9 Hz, CH2CO),
5.34 (dd, 1H, J = 6.5, 4.7 Hz, H-2).
EtOAc, 4:1); mp 126 °C; [a]D22 –11.4 (c = 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): d = 1.18, 1.27 [s, 18 H, C(CH3)3], 3.97
(dd, 1 H, J = 12.7, 2.9 Hz, H-5a), 4.11 (dd, 1 H, J = 12.7, 1.96 Hz,
H-5b), 4.73 (dd, 1 H, J = 7.8, 5.9 Hz, H-2), 5.17 (ddd, 1 H, J = 3.4,
2.9, 1.96 Hz, H-4), 5.25 (dd, 1 H, J = 7.8, 3.4 Hz, H-3), 5.89 (d, 1
H, J = 5.9 Hz, H-1), 7.37 (m, 3 H, m-Ar, p-Ar), 7.58 (m, 2 H, o-Ar),
7.80 (m, 2 H, CH=CH).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.99
[(CH2)3CH3], 19.72 (CHCH3), 22.71 (CH2), 26.94, 26.98, 27.04
(C(CH3)3), 29.12 (CH2), 29.20 (CHCH3), 36.39 (CHCH2CH2),
38.66, 38.80 [C(CH3)3], 42.72 (CH2CO), 55.18 (C-2), 62.01 (C-6),
65.73, 69.71, 70.21 (C-3, C-4, C-5), 95.08 (C-1), 150.88 (CO, ure-
thane), 171.86 (CO, acyl), 176.23, 176.45, 177.46 (CO, pivaloyl).
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

PAPER
Conjugate Addition of Mixed Organoaluminum Reagents
2159
(minor diastereomer) d = 19.66 (CHCH3), 29.04, 36.44
(CHCH2CH2), 55.26 (C-2).
[C(CH3)3], 31.52, 31.98 (CH2), 32.69 (CHCH3), 38.58, 38.72
[C(CH3)3], 42.40 (CH2CO), 55.15 (C-2), 61.91 (C-6), 65.60, 69.66,
70.09 (C-3, C-4, C-5), 95.01 (C-1), 129.50, 133.82 (CH=), 150.75
(CO, urethane), 171.23 (CO, acyl), 176.15, 176.38, 177.66 (CO,
pivaloyl).
Anal. Calcd for C30H49NO10 (583.73): C, 61.73; H, 8.46; N, 2.40.
Found: C, 61.74; H, 8.54; N, 2.20.
1,2-Dideoxy-1,2-[N-(3,4,4-trimethylpentanoyl)epoxycarbon-
ylimino]-3,4,6-tri-O-pivaloyl-a-D-glucopyranose (7b)
According to general procedure, method A. Reagents: MeAlCl2 (5.7
mL, 5.7 mmol, 1.0 M in hexane), t-BuLi (3.8 mL, 5.7 mmol, 1.7 M
in hexane), toluene (50 mL), 6 (300 mg, 0.57 mmol), MeAlCl2 (0.6
mL, 0.6 mmol, 1.0 M in hexane), toluene (50 mL). The product was
purified by preparative HPLC in MeCN–H2O (75:25).
(minor diastereomer) d = 20.26 (CHCH3), 22.00 (CH2), 32.44
(CHCH3), 42.73 (CH2CO), 55.11 (C-2), 61.94 (C-6), 65.67, 69.62,
70.21 (C-3, C-4, C-5), 129.43 (CH=), 171.11 (CO, acyl).
Anal. Calcd for C32H51NO10 (609.77): C, 63.03; H, 8.43; N, 2.30.
Found: C, 63.13; H, 8.41; N, 2.09.
1,2-Dideoxy-1,2-[N-(3-methylnon-4-ynoyl)epoxycarbonylimi-
no]-3,4,6-tri-O-pivaloyl-a-D-glucopyranose (7d)
According to general procedure (method A). Reagents: MeAlCl2
(2.9 mL, 2.9 mmol, 1.0 M in hexane), 1-hexynyllithium (2.9 mmol,
from 1-hexyne in toluene and 1.05 equiv n-BuLi), 6 (300 mg, 0.57
mmol), MeAlCl2 (0.6 mL, 0.6 mmol, 1.0 M in hexane), toluene (50
mL).
Yield: 102 mg (31%); 90% conversion; colourless, amorphous sol-
id; Rf = 0.62 (LPE–EtOAc, 5:1); [a]D22 –15.3 (c = 1.0 CHCl3); dia-
stereomeric ratio 66:34 (HPLC, MeCN–H2O, 75:25).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.83 [s, 9 H,
C(CH3)3], 0.80–0.91 (m, 3 H, CH3CH), 1.11, 1.16, 1.18 [s, 27 H,
C(CH3)3], 1.79–1.88 (m, 1 H, CHCH3), 2.61 (dd, 1 H, J = 17.3, 10.6
Hz, CH2CO), 2.94 (dd, 1 H, J = 17.5, 2.5 Hz, CH2CO), 4.00–4.08
(m, 1 H, H-5), 4.17 (dd, 1 H, J = 12.3, 5.0 Hz, H-6a), 4.22 (dd, 1 H,
J = 12.3, 2.6 Hz, H-6b), 4.59 (dd, 1 H, J = 6.8, 5.0 Hz, H-2), 5.06
(dd, 1 H, J = 8.7, 7.2 Hz, H-4), 5.33 (dd, 1 H, J = 6.9, 5.1 Hz, H-3),
5.90 (d, 1 H, J = 6.7 Hz, H-1).
Yield: 161 mg (40%); 68% conversion; colourless, amorphous sol-
id; diastereomeric ratio 54:46 (CH2CO, 400 MHz 1H NMR).
major diastereomer: Rf = 0.53 (LPE–EtOAc, 5:1); [a]D22 –45.1
(c = 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.87 [t, 3 H, J = 7.2 Hz,
(CH2)3CH3], 1.14, 1.18, 1.19 [s, 27 H, C(CH3)3], 1.13–1.46 [m, 7 H,
CHCH3, (CH2)2], 2.10 (dt, 2 H, J = 6.9, 1.7 Hz, CH2C≡), 2.86–3.00
(m, 2 H, CH2CO,CHCH3), 3.06 (dd, 1 H, J = 16.8, 7.4 Hz, CH2CO),
4.04 (ddd, 1 H, J = 8.2, 5.5, 2.7 Hz, H-5), 4.18 (dd, 1 H,
J = 12.1, 5.5 Hz, H-6a), 4.23 (dd, 1 H, J = 12.1, 2.7 Hz, H-6b), 4.58
(dd, 1 H, J = 7.0, 4.7 Hz, H-2), 5.05 (dd, 1 H, J = 8.4, 6.5 Hz, H-4),
5.36 (dd, 1 H, J = 6.3, 4.7 Hz, H-3), 5.93 (d, 1 H, J = 6.7 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): d = 13.54 [(CH2)3CH3], 18.36 (CH2),
21.35 (CHCH3), 21.86 (CH2), 21.87 (CHCH3), 26.94, 26.99, 27.05
[C(CH3)3], 31.05 (CH2), 38.62, 38.82 [C(CH3)3], 42.96 (CH2CO),
55.08 (C-2), 62.09 (C-6), 65.70, 69.87, 69.87 (C-3, C-4, C-5),
80.99, 82.66 (C≡), 95.14 (C-1), 150.82 (CO, urethane), 170.23 (CO,
acyl), 176.29, 176.41, 177.78 (CO, pivaloyl).
(minor diastereomer) d = 0.84 [s, 9 H, CHC(CH3)3], 2.68 (dd, 1 H,
J = 17.2, 11.0 Hz, CH2CO), 2.88 (dd, 1 H, J = 17.2, 2.2 Hz,
CH2CO), 5.03 (dd, 1 H, J = 8.4, 6.3 Hz, H-4), 5.35 (dd, 1 H,
J = 6.0, 4.8 Hz, H-3).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 15.00
(CHCH3), 26.94, 26.98, 27.04, 27.08 [C(CH3)3], 32.73 (CH2CO),
38.40 (CHCH3), 38.57, 38.66, 38.80 [C(CH3)3], 55.55 (C-2), 61.85
(C-6), 65.70, 69.76, 70.78 (C-3, C-4, C-5), 95.23 (C-1), 150.74
(CO, urethane), 172.62 (CO, acyl), 176.23, 176.49, 177.75 (CO,
pivaloyl).
(minor diastereomer) d = 27.12 (CHCH3), 32.68 (CH2CO), 38.49
(CHCH3), 55.13 (C-2), 62.06 (C-6), 94.99 (C-1), 150.89 (CO, ure-
thane), 172.72 (CO, acyl).
Anal. Calcd for C30H49NO10 (583.73): C, 61.73; H, 8.46; N, 2.40.
Found: C, 61.89; H, 8.51; N, 2.31.
minor diastereomer: Rf = 0.58 (LPE–EtOAc 5:1); [a]D22 –36.6
(c = 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.86 [t, 3 H, J = 7.0 Hz,
(CH2)3CH3], 1.13, 1.17, 1.19 [s, 27 H, C(CH3)3], 1.13–1.44 [m, 7 H,
CHCH3, (CH2)2], 2.08 (dt, 2 H, J = 6.9, 2.0 Hz, CH2C≡), 2.83 (dd,
1 H, J = 17.0, 6.5 Hz, CH2CO), 2.92 (tq, 1 H, J = 6.7, 2.1 Hz,
CHCH3), 3.21 (dd, 1 H, J = 16.8, 7.0 Hz, CH2CO), 4.05 (ddd, 1 H,
J = 8.4, 5.5, 2.7 Hz, H-5), 4.18 (dd, 1 H, J = 12.5, 5.5 Hz, H-6a),
4.23 (dd, 1 H, J = 12.1, 2.7 Hz, H-6b), 4.60 (dd, 1 H, J = 6.9, 4.9
Hz, H-2), 5.06 (dd, 1 H, J = 8.6, 6.7 Hz, H-4), 5.34 (dd, 1 H,
J = 6.7, 5.1 Hz, H-3), 5.92 (d, 1 H, J = 6.7 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): d = 13.52 [(CH2)3CH3], 18.33 (CH2),
21.34 (CHCH3), 21.83 (CH2), 22.04 (CHCH3), 26.94, 26.98, 27.04
[C(CH3)3], 31.05 (CH2), 38.67, 38.82 [C(CH3)3], 42.79 (CH2CO),
55.32 (C-2), 61.98 (C-6), 65.63, 69.90, 70.31 (C-3, C-4, C-5),
80.82, 82.92 (C≡), 95.27 (C-1), 150.74 (CO, urethane), 170.44 (CO,
acyl), 176.22, 176.54, 177.78 (CO, pivaloyl).
1,2-Dideoxy-1,2-[N-(3-methylnon-4-enoyl)epoxycarbonylimi-
no]-3,4,6-tri-O-pivaloyl-a-D-glucopyranose (7c)
According to general procedure (method C). Reagents: DIBAL-H
(3.0 mL, 4.5 mmol, 1.5 M in CH2Cl2), 1-hexyne (0.5 mL, 4.44
mmol), toluene (50 mL), 6 (300 mg, 0.57 mmol), MeAlCl2 (0.6 mL,
0.6 mmol, 1.0 M in hexane), toluene (50 mL).
Yield: 132 mg (38%); 75% conversion; colourless, amorphous sol-
id; Rf = 0.48 (LPE–EtOAc, 5:1); [a]D22 –25.5 (c = 1.0, CHCl3); dia-
stereomeric ratio 67:33 (H-1, 400 MHz 1H NMR).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.81–0.88
[m, 3 H, (CH2)2CH3], 0.98 (d, 3 H, J = 6.5 Hz, CHCH3), 1.10, 1.16,
1.18 [s, 27 H, C(CH3)3], 1.10–1.32 [m, 4 H, (CH2)2], 1.87–1.92 (m,
2 H, CH=CHCH2), 2.58–2.66 (m, 1 H, CHCH3), 2.68 (dd, 1 H,
J = 16.6, 6.9 Hz, CH2CO), 2.79 (dd, 1 H, J = 16.6, 6.0 Hz, CH2CO),
4.00–4.04 (m, 1 H, H-5), 4.15 (dd, 1 H, J = 12.3, 5.3 Hz, H-6a), 4.21
(dd, 1 H, J = 12.3, 2.3 Hz, H-6b), 4.55 (dd, 1 H, J = 6.8, 5.0 Hz, H-
2), 5.04 (dd, 1 H, J = 8.5, 6.8 Hz, H-4), 5.26–5.41 (m, 3 H, H-3,
CH=CH), 5.89 (d, 1 H, J = 7.1 Hz, H-1).
Anal. Calcd for C32H49NO10 (607.75): C, 63.24; H, 8.13; N, 2.30.
Found: C, 63.19; H, 8.16; N, 2.08.
1,2-Dideoxy-1,2-[N-(3-phenylheptanoyl)epoxycarbonylimino]-
3,4,6-tri-O-pivaloyl-a-D-galactopyranose (8a)
According to general procedure (method A). Reagents: MeAlCl2
(5.1 mL, 5.1 mmol, 1.0 M in hexane), n-BuLi (3.2 mL, 5.12 mmol,
1.6 M in pentane), toluene (50 mL), 1 (300 mg, 0.51 mmol),
MeAlCl2 (0.6 mL, 0.6 mmol, 1.0 M in hexane), toluene (50 mL).
(minor diastereomer) d = 0.99 (d, 3 H, J = 6.5 Hz, CHCH3), 2.84
(dd, 1 H, J = 16.6, 7.5 Hz, CH2CO), 2.99 (dd, 1 H, J = 16.4, 6.5 Hz,
CH2CO), 5.02 (dd, 1 H, J = 8.5, 6.5 Hz, H-4), 5.87 (d, 1 H, J = 6.8
Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.77
(CH2CH3), 20.31 (CHCH3), 22.03 (CH2), 26.84, 26.90, 26.95
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

2160
S. Elzner et al.
PAPER
Yield: 253 mg (77%); colourless, amorphous solid; Rf = 0.46 (LPE–
EtOAc, 5:1); [a]D22 –30.5 (c = 1.0, CHCl3); diastereomeric ratio
99:1 (H-3, 400 MHz 1H NMR).
Yield: 151 mg (44%); 85% conversion; colourless, amorphous sol-
id; Rf = 0.46 (LPE–EtOAc, 5:1); [a]D22 –26.6 (c = 1.0, CHCl3); dia-
stereomeric ratio 89:11 (CH2CO, 400 MHz 1H NMR).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.78 (t, 3 H,
J = 7.0 Hz, CH3), 0.99–1.38 [m, 4 H, (CH2)2], 1.13, 1.15, 1.21 [s, 27
H, C(CH3)3], 1.55–1.67 (m, 2 H, CH2), 2.96 (dd, 1 H, J = 16.1, 5.6
Hz, CH2CO), 2.97–3.06 (m, 1 H, CHPh), 3.36 (dd, 1 H,
J = 16.1, 8.2 Hz, CH2CO), 4.00 (dd, 1 H, J = 11.5, 6.5 Hz, H-6a),
4.09 (dd, 1 H, J = 11.5, 7.0 Hz,H-6b), 4.31 (t, 1 H, J = 6.8 Hz, H-5),
4.43 (dd, 1 H J = 8.5, 5.6 Hz, H-2), 5.10 (dd, 1 H, J = 8.5, 3.2 Hz,
H-3), 5.34 (d, 1 H, J = 2.9 Hz, H-4), 5.52 (d, 1 H, J = 5.6 Hz, H-1),
7.13–7.26 (m, 5 H, Ar).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.83 [t, 3 H,
J = 7.0 Hz, (CH2)2CH3], 1.02, 1.17, 1.23 [s, 27 H, C(CH3)3], 1.12–
1.28 [m, 4 H, (CH2)2], 1.91–1.96 (m, 2 H, =CHCH2), 3.12 (dd, 1 H,
J = 17.0, 6.5 Hz, CH2CO), 3.46 (dd, 1 H, J = 17.0, 8.2 Hz, CH2CO),
3.75–3.82 (m, 1 H, CHPh), 4.02 (dd, 1 H, J = 11.5, 6.5 Hz, H-6a),
4.12 (dd, 1 H, J = 11.5, 7.0 Hz, H-6b), 4.35 (t, 1 H, J = 6.7 Hz, H-
5), 4.62 (dd, 1 H, J = 8.5, 5.6 Hz, H-2), 5.09 (dd, 1 H, J = 8.5, 3.2
Hz, H-3), 5.36 (d, 1 H, J = 2.6 Hz, H-4), 5.36–5.59 (m, 2 H,
CH=CH), 5.87 (d, 1 H, J = 5.9 Hz, H-1), 7.13–7.27 (m, 5 H, Ar).
(minor diastereomer) d = 5.04 (dd, 1 H, J = 8.5, 3.2 Hz, H-3).
(minor diastereomer) d = 1.14, 1.16, 1.22 [s, 27 H, C(CH3)3], 3.06
(dd, 1 H, J = 16.4, 6.2 Hz, CH2CO), 3.51 (dd, 1 H, J = 16.3, 9.0 Hz,
CH2CO), 4.46 (dd, 1 H, J = 8.5, 5.6 Hz, H-2).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.85
[(CH2)3CH3], 22.14 (CH2), 26.76, 27.02, 27.12 [C(CH3)3], 31.44,
32.06 [(CH2)2], 38.58, 38.73, 39.07 [C(CH3)3], 41.15 (CH2CO)
44.11 (CHPh), 53.38 (C-2), 61.02 (C-6), 64.75, 70.50, 70.83 (C-3,
C-4, C-5), 97.04 (C-1), 126.41, 127.45, 128.52 (C-Ar), 131.25,
132.04 (CH=), 143.29 (C-ipso), 150.37 (CO, urethane), 170.50
(CO, acyl), 176.53, 177.15, 177.71 (2 C, CO, pivaloyl).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.85
[(CH2)3CH3], 22.45 (CH2), 26.82, 26.98, 27.08 [C(CH3)3], 29.52,
35.94 [(CH2)2], 38.65, 38.68, 39.03 [C(CH3)3], 41.90 (CH2CO),
41.96 (CHPh), 53.38 (C-2), 60.69 (C-6), 64.72, 70.36, 70.73 (C-3,
C-4, C-5), 96.93 (C-1), 126.41, 127.62, 128.30 (C-Ar), 144.09 (C-
ipso), 150.20 (CO, urethane), 171.10 (CO, acyl), 176.52, 177.21,
177.66 (CO, pivaloyl).
Anal. Calcd for C35H51NO10 (645.80): C, 65.10; H, 7.96; N, 2.17.
Found: C, 64.93; H, 8.01; N, 2.01.
Anal. Calcd for C37H53NO10 (671.84): C, 66.15; H, 7.95; N, 2.08.
Found: C, 65.70; H, 7.83; N, 1.84.
1,2-Dideoxy-1,2-[N-(4,4-dimethyl-3-phenylpentanoyl)epoxy-
carbonylimino]-3,4,6-tri-O-pivaloyl-a-D-galactopyranose (8b)
According to general procedure (method A). Reagents: MeAlCl2
(5.1 mL, 5.1 mmol, 1.0 M in hexane), t-BuLi (3.4 mL, 2.1 mmol,
1.7 M in hexane), toluene (50 mL), BF3·OEt2 (0.61 mL, 4.96 mmol),
1 (300 mg, 0.51 mmol), MeAlCl2 (0.6 mL, 0.6 mmol, 1.0 M in hex-
ane), toluene (50 mL).
1,2-Dideoxy-1,2-[N-(3-phenylnon-4-ynoyl)epoxycarbonylimi-
no]-3,4,6-tri-O-pivaloyl-a-D-galactopyranose (8d)
According to general procedure (method A). Reagents: MeAlCl2
(5.1 mL, 5.1 mmol, 1.0 M in hexane), 1-hexynyllithium (5.1 mmol,
from 1-hexyne in toluene and 1.05 equiv n-BuLi); toluene (50 mL);
1 (300 mg, 0.51 mmol), MeAlCl2 (0.6 mL, 0.6 mmol, 1.0 M in hex-
ane), toluene (50 mL).
Yield: 192 mg (58%); colourless, amorphous solid; Rf = 0.51 (LPE–
EtOAc, 5:1); [a]D22 –24.5 (c = 1.0, CHCl3, major diastereomer);
diastereomeric ratio 89:11 (H-1, 400 MHz 1H NMR).
Yield: 114 mg (33%); 83% conversion; colourless, amorphous sol-
id; Rf = 0.48 (LPE–EtOAc, 5:1); [a]D22 –19.9 (c = 1.0, CHCl3); dia-
stereomeric ratio 84:16 (H-2, 400 MHz 1H NMR).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.87 [s, 9 H,
C(CH3)3], 1.13, 1.17, 1.19 [s, 27 H, C(CH3)3], 2.92 (dd, 1 H,
J = 16.9, 3.1 Hz, CH2CO), 2.97 (dd, 1 H, J = 11.4, 2.9 Hz, CHPh),
3.77 (dd, 1 H, J = 16.7, 11.2 Hz, CH2CO), 4.00 (dd, 1 H,
J = 11.4, 6.5 Hz, H-6a), 4.08 (dd, 1 H, J = 11.4, 7.0 Hz, H-6b), 4.33
(t, 1 H, J = 6.7 Hz, H-5), 4.41 (dd, 1 H, J = 8.5, 5.6 Hz, H-2), 5.10
(dd, 1 H, J = 8.5, 3.2 Hz, H-3), 5.34 (d, 1 H, J = 2.9 Hz, H-4), 5.52
(d, 1 H, J = 5.6 Hz, H-1), 7.14–7.25 (m, 5 H, Ar).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.86 [t, 3 H,
J = 7.2 Hz, (CH2)3CH3], 1.11, 1.17, 1.24 [s, 27 H, C(CH3)3], 1.26–
1.48 [m, 4 H, (CH2)2CH3], 2.15 (dt, 2 H, J = 7.0, 2.1 Hz, CH2C≡),
3.00 (dd, 1 H, J = 17.2, 4.6 Hz, CH2CO), 3.55 (dd, 1 H, J = 17.0, 9.7
Hz, CH2CO), 4.04 (dd, 1 H, J = 11.4, 6.5 Hz, H-6a), 4.02–4.11 (m,
1 H, CHPh), 4.13 (dd, 1 H, J = 11.4, 7.0, H-6b), 4.36 (t, 1 H, J = 6.9
Hz, H-5), 4.70 (dd, 1 H, J = 8.5, 5.6 Hz, H-2), 5.13 (dd, 1 H,
J = 8.5, 3.2 Hz, H-3), 5.39 (d, 1 H, J = 2.6 Hz, H-4), 5.91 (d, 1 H,
J = 5.6 Hz, H-1), 7.18–7.36 (m, 5 H, Ar).
(minor diastereomer) d = 0.83 [s, 9 H, C(CH3)3], 3.25 (dd, 1 H,
J = 17.6, 3.5 Hz, CH2CO), 3.43 (dd, 1 H, J = 17.9, 10.9 Hz,
CH2CO), 4.30 (t, 1 H, J = 6.7 Hz, H-5), 4.47 (dd, 1 H, J = 8.5, 5.6
Hz, H-2), 4.93 (dd, 1 H, J = 8.5, 3.2 Hz, H-3), 5.30 (d, 1 H, J = 2.9
Hz, H-4), 5.82 (d, 1 H, J = 5.6 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 26.84,
26.99, 27.07 [C(CH3)3], 28.05 [CHC(CH3)3], 33.68 [CHC(CH3)3],
36.16 (CH2CO), 38.65, 38.69, 39.02 [C(CH3)3], 52.03 (CHPh),
53.36 (C-2), 60.98 (C-6), 64.76, 70.42, 70.74 (C-3, C-4, C-5), 96.90
(C-1), 126.37, 127.65, 129.21 (C-Ar), 141.86 (C-ipso), 150.35 (CO,
urethane), 171.74 (CO, acyl), 176.45, 177.21, 177.59 (CO, piv-
aloyl).
(minor diastereomer) d = 0.87 [t, 3H, J = 7.5 Hz, (CH2)3CH3], 3.25
(dd, 1 H, J = 16.4, 7.0 Hz, CH2CO), 3.41 (dd, 1 H, J = 16.6, 7.5 Hz,
CH2CO), 4.55 (dd, 1 H, J = 8.5, 5.9 Hz, H-2), 5.72 (d, 1 H, J = 5.9
Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.48
[(CH2)3CH3], 18.45, 21.85 (CH2), 26.79, 26.96, 27.07 [C(CH3)3],
30.91 (CH2), 33.42 (CHPh), 38.63, 38.68, 39.04 [C(CH3)3], 44.03
(CH2CO), 53.49 (C-2), 60.96 (C-6), 64.74, 70.53, 70.79 (C-3, C-4,
C-5), 80.38, 83.61 (C≡), 97.16 (C-1), 126.97, 127.37, 128.56 (C-
Ar), 141.07 (C-ipso), 150.20 (CO, urethane), 169.84 (CO, acyl),
176.55, 177.33, 177.72 (CO, pivaloyl).
Anal. Calcd for C35H51NO10 (645.80): C, 65.10; H, 7.96; N, 2.17.
Found: C, 65.34; H, 7.89; N, 2.13.
C37H51NO10 (669.82); ESI-MS: m/z = 692.8 [M + Na]+.
1,2-Dideoxy-1,2-[N-(3-phenylnon-4-enoyl)epoxycarbonylimi-
no]-3,4,6-tri-O-pivaloyl-a-D-galactopyranose (8c)
According to general procedure (method C). Reagents: DIBAL-H
(3.4 mL, 5.1 mmol, 1.5 M in CH2Cl2), 1-hexyne (0.55 mL, 4.89
mmol), toluene (50 mL); 1 (300 mg, 0.51 mmol), MeAlCl2 (0.6 mL,
0.6 mmol, 1.0 M in hexane), toluene (50 mL).
1,2-Dideoxy-1,2-[N-(3,5-dimethylhexanoyl)epoxycarbonylimi-
no]-3,4-di-O-pivaloyl-b-D-arabinopyranose (17a)
According to general procedure (reaction time 3 h). Reagents: di-
isobutylaluminum chloride (2.4 mL, 2.4 mmol, 1 M in toluene); 15
(100 mg, 0.243 mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hex-
ane), toluene (20 mL).
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

PAPER
Conjugate Addition of Mixed Organoaluminum Reagents
2161
Yield: 85.8 mg (75%); colourless, amorphous solid; Rf = 0.53
(LPE–EtOAc, 5:1); mp 95 °C; [a]D22 –11.5 (c = 1.0, CHCl3); dia-
stereomeric ratio 73:27 (CH2CH, 13C NMR).
1,2-Dideoxy-1,2-[N-(3,4,4-trimethylpentanoyl)epoxycarbonyl-
imino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (17c)
According to general procedure (method A). Reagents: MeAlCl2
(2.4 mL, 2.4 mmol, 1.0 M in hexane), t-BuLi (1.4 mL, 2.4 mmol,
1.7 M in hexane), toluene (10 mL); 15 (100 mg, 0.243 mmol),
MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
Analytical HPLC: Rt = 12.13 min (MeCN–H2O, 85:15).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.82–0.90
[m, 9 H, CHCH3, CH(CH3)2], 1.05–1.10 [m, 1 H, CH(CH3)2], 1.16,
1.23 [s, 18 H, C(CH3)3], 1.61 [m, 2 H, J = 6.3 Hz, CH2CH(CH3)2],
2.05 (m, 1 H, J = 7.8, 6.3 Hz, CHCH2CO), 2.63 (dd, 1 H J = 16.8,
8.2 Hz, CH2CO), 2.76 (m, 1 H, J = 16.8, 7.8 Hz, CH2CO), 3.97 (dd,
1 H, J = 12.9, 3.1 Hz, H-5a), 4.08 (dd, 1 H, J = 12.9, 1.6 Hz, H-5b),
4.69 (dd, 1 H, J = 7.8, 5.8 Hz, H-2), 5.16 (d, 1 H, J = 1.6 Hz, H-4),
5.19 (dd, 1 H, J = 7.3, 3.9 Hz, H-3), 5.87 (d, 1 H, J = 5.5 Hz, H-1).
Yield: 47 mg (42%); colourless, amorphous solid; Rf = 0.45 (LPE–
EtOAc, 5:1); mp 146 °C; [a]D22 –4.2 (c = 1.0, CHCl3); diastereo-
meric ratio 72:28 (C-2, 100.6 MHz 13C NMR).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.86 [s, 9 H,
C(CH3)3], 0.87–0.94 (m, 3 H, CHCH3), 1.15, 1.23 [s, 18 H,
C(CH3)3], 1.77–1.90 (m, 1 H, CHCH3), 2.64 (dd, 1 H, J = 14.1, 5.9
Hz, CH2CO), 2.91 (dd, 1 H, J = 14.1, 2.7 Hz, CH2CO), 3.98 (dd, 1
H, J = 12.9, 3.1 Hz, H-5a), 4.08 (dd, 1 H, J = 12.9, 1.2 Hz, H-5b),
4.72 (dd, 1 H, J = 5.9, 2.0 Hz, H-2), 5.16 (m, 1 H, J = 3.1 Hz, H-4),
5.20 (dd, 1 H, J = 7.8, 3.1 Hz, H-3), 5.87 (d, 1 H, J = 5.9 Hz, H-1).
(minor diastereomer) d = 2.73 (m, 1 H, CH2CO).
100.6 MHz 13C NMR (50.3 MHz, CDCl3): (major diastereomer)
d = 19.87 (CHCH3), 22.06, 23.16 [CH(CH3)2], 25.19 [CH(CH3)2],
26.91 [C(CH3)3], 27.01 [CH(CH3)], 27.09 [C(CH3)3], 38.72, 38.98
[C(CH3)3], 42.95 (CH2CO), 46.14 [CH2CH(CH3)2], 53.69 (C-2),
62.95 (C-5), 65.85, 69.58 (C-3, C-4), 96.90 (C-1), 150.61 (CO, ure-
thane), 171.92 (CO, acyl), 177.16, 177.21 (CO, pivaloyl).
(minor diastereomer) d = 0.85, 1.16 [s, 18 H, C(CH3)3], 2.66 (dd, 1
H, J = 16.8, 6.8 Hz, CH2CO).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 15.10
(CHCH3), 26.91, 27.10, 27.17 [C(CH3)3], 32.77 (CH2CO), 38.41
(CHCH3), 38.61, 38.64, 38.74 [C(CH3)3], 53.72 (C-2), 62.99 (C-5),
65.85, 69.58 (C-3, C-4), 96.86 (C-1), 150.57 (CO, urethane), 172.90
(CO, acyl), 177.18 (2C, CO, pivaloyl).
(minor diastereomer) d = 19.73 (CHCH3), 21.96, 23.26
[CH(CH3)2], 42.89 (CH2CO), 46.23 [CH2CH(CH3)2], 96.82 (C-1).
C24H39NO8 (469.58); ESI-MS: m/z = 492.3 [M + Na]+, 533.5 [M +
Na + CH3CN] +.
(minor diastereomer) d = 14.99 (CHCH3), 32.81 (CH2CO), 53.78
(C-2).
1,2-Dideoxy-1,2-[N-(3-methylheptanoyl)epoxycarbonylimino]-
3,4-di-O-pivaloyl-b-D-arabinopyranose (17b)
According to general procedure (method A; reaction time 10 h). Re-
agents: MeAlCl2 (2.4 mL, 2.4 mmol, 1 M in hexane), n-BuLi
(1.5 mL, 2.4 mmol, 1.6 M in pentane), toluene (10 mL); 15 (100 mg,
0.243 mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), tolu-
ene (10 mL).
Anal. Calcd for C24H39NO8 (469.58): C, 61.39; H, 8.37; N, 2.83.
Found: C, 61.25; H, 8.45; N, 2.85.
ESI-MS: m/z = 448.4 [M + Na – CO2]+, 492.4 [M + Na]+, 533.6 [M
+ Na + CH3CN]+.
1,2-Dideoxy-1,2-[N-(3-methylnon-4-enoyl)epoxycarbonylimi-
no]-3,4-di-O-pivaloyl-b-D-arabinopyranose (17d)
According to general procedure (method C). Reagents: DIBAL-H
(2.4 mL, 2.4 mmol, 1.0 M in CH2Cl2), 1-hexyne (0.3 mL, 2.7
mmol), toluene (10 mL); 15 (100 mg, 0.243 mmol), MeAlCl2 (0.3
mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
Yield: 81 mg (71%); colourless, amorphous solid; Rf = 0.45 (LPE–
EtOAc, 5:1); mp 97 °C; [a]D22 –11.5 (c = 1.0, CHCl3); diastereo-
meric ratio 73:27 (CH2CH, 100.6 MHz 13C NMR), 72:28 (CH2CO,
CH-Me, 400 MHz 1H NMR).
Analytical HPLC: Rt = 18.38 min (MeCN–H2O, 85:15).
Yield: 53 mg (46%); 90% conversion; colourless, amorphous solid;
Rf = 0.39 (LPE–EtOAc, 6:1); mp 109 °C; [a]D22 +1.5 (c = 1.0,
CHCl3); diastereomeric ratio 75:25 (H-1, 400 MHz 1H NMR).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.84–0.91
[m, 6 H, J = 6.7 Hz, (CH2)3CH3, CHCH3], 1.15, 1.22 [s, 18 H,
C(CH3)3], 1.24–1.33 [m, 6 H, (CH2)3], 1.91–1.99 (m, 1 H, J = 6.7
Hz, CHCH3), 2.62 (dd, 1 H, J = 16.8, 7.2 Hz, CH2CO), 2.83 (dd, 1
H, J = 16.8, 5.4 Hz, CH2CO), 3.97 (dd, 1 H, J = 12.9, 3.1 Hz, H-5a),
4.07 (dd, 1 H, J = 12.5, 1.1 Hz, H-5b), 4.69 (dd, 1 H, J = 7.8, 5.5 Hz,
H-2), 5.15 (m, 1 H, H-4), 5.20 (dd, 1 H, J = 7.8, 3.1 Hz, H-3), 5.87
(d, 1 H, J = 5.5 Hz, H-1).
Analytical HPLC: Rt = 16.45 min (MeCN–H2O, 85:15).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.85 [m, 3
H, (CH2)2CH3], 1.02 (d, 3 H, J = 6.7 Hz, CHCH3), 1.16, 1.22 [s, 18
H, C(CH3)3], 1.26 [m, 4 H, (CH2)2], 1.92 (m, 2 H, CH=CHCH2],
2.62 (m, 1 H, J = 7.1 Hz, CHCH3), 2.75 (dd, 1 H, J = 15.4, 7.1 Hz,
CH2CO), 2.95 (dd, 1 H, J = 15.4, 7.1 Hz, CH2CO), 3.96 (dd, 1 H,
J = 12.9, 3.1 Hz, H-5a), 4.08 (dd, 1 H, J = 12.9, 0.9 Hz, H-5b), 4.66
(dd, 1 H, J = 7.4, 5.9 Hz, H-2), 5.15 (m, 1 H, H-4) 5.19 (dd, 1 H,
J = 7.4, 3.1 Hz, H-3), 5.28–5.43 (m, 2 H, CH=CH), 5.83 (d, 1 H,
J = 5.9 Hz, H-1).
(minor diastereomer) d = 2.71 (m, 1 H, CH2CO), 4.68 (dd, 1 H,
J = 7.8, 5.9 Hz, H-2).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.94
[(CH2)3CH3], 19.73 (CHCH3), 22.78 (CH2), 26.91, 27.10
[C(CH3)3], 29.14 (CH2), 29.40 (CHCH3), 36.39 (CHCH2CH2),
38.72, 38.97 [C(CH3)3], 42.69 (CH2CO), 53.67 (C-2), 62.93 (C-5),
65.82, 69.53 (C-3, C-4), 96.87 (C-1), 150.62 (CO, urethane), 171.99
(CO, ac yl), 177.18 (2C, CO, pivaloyl).
(minor diastereomer) d = 2.82 (m, 1 H, CH2CO), 5.86 (d, 1 H,
J = 4.7 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.94
(CH2CH3), 20.51 (CHCH3), 22.17 (CH2), 26.91, 27.10 [C(CH3)3],
31.63, 32.11 (CH2), 33.02 (CHCH3), 38.74, 38.97 [C(CH3)3] 42.41
(CH2CO), 53.74 (C-2), 62.91 (C-5), 65.80, 69.41 (C-3, C-4), 96.81
(C-1), 129.65, 134.03 (CH=), 150.64 (CO, urethane), 171.43 (CO,
acyl), 177.18 (2C, CO, pivaloyl).
(minor diastereomer) d = 19.66 (CHCH3), 36.47 (CHCH2CH2),
42.58 (CH2CO).
Anal. Calcd for C24H39NO8 (469.58): C, 61.39; H, 8.37; N, 2.83.
Found: C, 61.37; H, 8.44; N, 2.93.
ESI-MS: m/z = 448.5 [M + Na – CO2]+; 492.4 [M + Na]+; 508.5 [M
(minor diastereomer) d = 20.43 (CHCH3), 129.56 (CH=).
+ K]+.
Anal. Calcd for C26H41NO8 (495.62): C, 63.01; H, 8.34; N, 2.83.
Found: C, 62.96; H, 8.26; N, 2.75.
ESI-MS: m/z = 474.4 [M + Na – CO2]+, 518.5 [M + Na]+, 559.5 [M
+ Na + CH3CN]+.
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

2162
S. Elzner et al.
PAPER
1,2-Dideoxy-1,2-[N-(3-methylnon-4-ynoyl)epoxycarbonylimi-
no]-3,4-di-O-pivaloyl-b-D-arabinopyranose (17e)
According to general procedure (method A; reaction time 72 h). Re-
agents: MeAlCl2 (2.91 mmol, 1.0 M in hexane), 1-hexynyllithium
(2.9 mmol, from 1-hexyne in toluene and 1.05 equiv n-BuLi); 15
(100 mg, 0.243 mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hex-
ane), toluene (10 mL).
1,2-Dideoxy-1,2-[N-(5-methyl-3-phenylhexanoyl)epoxycarbon-
ylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18b)
According to general procedure (reaction time 5 h). Reagents: (i-
Bu)2AlCl (1.3 mL, 1.3 mmol, 1.0 M in toluene); 16 (100 mg, 0.212
mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), toluene (20
mL).
Yield: 87 mg (76%); colourless, amorphous solid; Rf (LPE–EtOAc,
5:1) = 0.54; mp 166 °C; [a]D22 +11.4 (c = 1.0, CHCl3); diastereo-
meric ratio: 98:2 (H-2, 400 MHz 1H NMR), 95:5 (HPLC).
Yield: 50 mg (41%); colourless, amorphous solid; Rf = 0.47 (LPE–
EtOAc, 5:1); mp 107 °C; [a]D22 –20.2 (c = 1.0, CHCl3); diastereo-
meric ratio 65:35 (CH2CO, 400 MHz 1H NMR).
Analytical HPLC: Rt = 14.87 (minor diastereomer), 15.37 min (ma-
jor diastereomer) [MeCN–H2O, 85:15].
Analytical HPLC: Rt = 25.12 min (MeCN–H2O, 80:20).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.86 [t, 3 H,
J = 7.4 Hz, (CH2)3CH3] 1.15, 1.21 [s, 18 H, C(CH3)3], 1.16 (m, 3 H,
CHCH3), 1.31–1.44 (m, 4 H, J = 4.3 Hz, CH2), 2.07 (dt, 2 H,
J = 2.0, 7.0 Hz, CH2C≡), 2.83–2.96 (m, 2 H, J = 16.0, 2.0 Hz,
CH2CO, CHCH3), 3.03 (dd, 1 H, J = 16.0, 7.0 Hz, CH2CO), 3.96
(dd, 1 H, J = 12.7, 2.7 Hz, H-5a), 4.07 (d, 1 H, J = 12.1 Hz, H-5b),
4.68 (dd, 1 H, J = 7.4, 5.9 Hz, H-2), 5.16–5.20 (m, 2 H, H-4, H-3),
5.87 (d, 1 H, J = 5.9 Hz, H-1).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.80, 0.85
[d, 6 H, J = 6.7 Hz, CH(CH3)2], 1.17, 1.21 [s, 18 H, C(CH3)3], 1.36–
1.63 (m, 3 H, CH2CH), 2.93 (dd, 1 H, J = 16.4, 5.5 Hz, CH2CO),
3.19 (dd, 1 H, J = 9.4, 5.5 Hz, CHPh), 3.39 (dd, 1 H, J = 16.4, 9.4
Hz, CH2CO), 3.93 (dd, 1 H, J = 12.9, 2.7 Hz, H-5a), 4.02 (d, 1 H,
J = 12.9 Hz, H-5b), 4.46 (dd, 1 H, J = 7.4, 5.9 Hz, H-2), 5.12 (m, 2
H, H-3, H-4), 5.50 (d, 1 H, J = 5.5 Hz, H-1), 7.17–7.28 (m, 5 H, Ar).
(minor diastereomer) d = 1.04 [s, 9 H, C(CH3)3], 4.60 (dd, 1 H,
J = 5.9, 13.3 Hz, H-2), 5.78 (d, 1 H, J = 5.9 Hz, H-1).
(minor diastereomer) d = 1.14 [s, 9 H, C(CH3)3], 3.13 (dd, 1 H,
J = 16.0, 7.0 Hz, CH2CO), 4.74 (dd, 1 H, J = 7.8, 5.9 Hz, H-2), 5.86
(d, 1 H, J = 5.9 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.60
[(CH2)3CH3], 18.37 (CH2), 21.42 (CHCH3), 21.90 (CH2), 22.12
(CHCH3), 26.89, 27.08 [C(CH3)3], 31.08 (CH2), 38.70, 38.94
[C(CH3)3], 42.71 (CH2CO), 53.66 (C-2), 62.96 (C-5), 65.76, 69.54
(C-3, C-4), 81.07, 82.69 (C≡), 96.95 (C-1), 150.54 (CO, urethane),
170.30 (CO, acyl), 177.13, 177.19 (CO, pivaloyl).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 21.64,
23.27 [CH(CH3)2], 25.30 [CH(CH3)2], 26.93, 27.09 [C(CH3)3],
38.74, 38.96 [C(CH3)3], 39.60 (CHPh), 42.35 (CH2CO), 45.42
[CH2CH(CH3)2], 53.77 (C-2), 62.88 (C-5), 65.85, 69.41 (C-3, C-4),
96.87 (C-1), 126.46, 127.72, 128.39 (C-Ar), 144.08 (C-ipso),
150.53 (CO, urethane), 171.26 (CO, acyl), 177.18, 177.25 (CO, piv-
aloyl).
(minor diastereomer) d = 26.81 [C(CH3)3], 96.80 (C-1).
(minor diastereomer) d = 22.19 (CHCH3), 53.80 (C-2), 97.02 (C-1).
Anal. Calcd for C29H41NO8 (531.65): C, 65.52; H, 7.77; N, 2.63.
Found: C, 65.55; H, 7.98; N, 2.67.
Anal. Calcd for C26H39NO8 (493.60): C, 63.27; H, 7.96; N, 2.84.
Found: C, 62.98; H, 8.07; N, 2.59.
ESI-MS: m/z = 510.4 [M + Na – CO2]+, 554.5 [M + Na]+, 595.4 [M
+ Na + CH3CN]+.
1,2-Dideoxy-1,2-[N-(3-phenyl-pentanoyl)epoxycarbonylimino]-
3,4-di-O-pivaloyl-b-D-arabinopyranose (18a)
According to general procedure. Reagents: Et2AlCl (0.35 mL, 0.64
mmol, 1.8 M in toluene); 16 (100 mg, 0.212 mmol), MeAlCl2 (0.3
mL, 0.3 mmol, 1.0 M in hexane), toluene (20 mL).
1,2-Dideoxy-1,2-[N-(3-phenyl-heptanoyl)epoxycarbonylimino]-
3,4-di-O-pivaloyl-b-D-arabinopyranose (18c)
According to general procedure (method A). Reagents: MeAlCl2
(2.1 mL, 2.1 mmol, 1.0 M in hexane), n-BuLi (1.3 mL, 2.1 mmol,
1.6 M in pentane), toluene (10 mL); 16 (100 mg, 0.212 mmol),
MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
Yield: 88 mg (83%); colourless, amorphous solid; Rf = 0.47 (LPE–
EtOAc, 5:1); mp 151 °C; [a]D22 +14.6 (c = 1.0, CHCl3); diastereo-
meric ratio 97:3 (H-2, 400 MHz 1H NMR), 96:4 (HPLC).
Yield: 78 mg (69%); colourless, amorphous solid; Rf = 0.43 (LPE–
EtOAc, 5:1); mp 133 °C; [a]D22 +12.1 (c = 1.0, CHCl3); diastereo-
meric ratio 95:5 (H-1, 400 MHz 1H NMR), 96:4 (HPLC).
Analytical HPLC: Rt = 15.31 (minor diastereomer), 16.24 min (ma-
jor diastereomer) [MeCN–H2O, 80:20].
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.76 (t, 3 H,
J = 7.4 Hz, CH3), 1.16, 1.21 [s, 18 H, C(CH3)3], 1.55–1.75 (m, 2 H,
J = 8.6 Hz, CH2CH3), 2.94–3.06 (m, 2 H, J = 16.4, 8.6 Hz, CHPh,
CH2CO), 3.36 (dd, 1 H, J = 16.4, 8.6 Hz, CH2CO), 3.93 (dd, 1 H,
J = 12.9, 3.1 Hz, H-5a), 4.03 (m, 1 H, H-5b), 4.48 (dd, 1 H, J = 7.8,
5.5 Hz, H-2), 5.11 (m, 1 H, H-4), 5.14 (dd, 1 H, J = 7.8, 3.5 Hz, H-
3), 5.48 (d, 1 H, J = 5.5 Hz, H-1), 7.15–7.27 (m, 5 H, Ar).
Analytical HPLC: Rt = 22.85 (minor diastereomer), 23.35 min (ma-
jor diastereomer) [MeCN–H2O, 80:20].
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.79 (t, 3 H,
J = 6.0 Hz, CH3), 1.00–1.32 [m, 4 H, (CH2)2], 1.16, 1.20 [s, 18 H,
C(CH3)3], 1.55–1.70 (m, 2 H, J = 5.9 Hz, CH2), 2.97–3.10 (m, 2 H,
J = 18.0, 5.5, 8.6, 5.9 Hz, CHPh, CH2CO), 3.37 (dd, 1 H,
J = 16.0, 8.6 Hz, CH2CO), 3.92 (dd, 1 H, J = 12.9, 3.1 Hz, H-5a),
4.03 (d, 1 H, J = 12.9 Hz, H-5b), 4.47 (dd, 1 H, J = 7.4, 5.9 Hz, H-
2), 5.11 (m, 1 H, H-4), 5.14 (m, 1 H, H-3), 5.52 (d, 1 H, J = 5.9 Hz,
H-1), 7.15–7.27 (m, 5 H, Ar).
(minor diastereomer) d = 1.03 [s, 9 H, C(CH3)3], 3.18 (dd, 1 H,
J = 14.5, 7.8 Hz, CH2CO), 4.48 (dd, 1 H, J = 5.5, Hz, H-2), 5.82 (d,
1 H, J = 5.5 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 11.99
(CH2CH3), 26.91, 27.09 [C(CH3)3], 29.27 (CH2CH3), 38.73, 38.94
[C(CH3)3], 41.72 (CHPh), 43.65 (CH2CO), 53.78 (C-2), 62.88 (C-
5), 65.85, 69.38 (C-3, C-4), 96.86 (C-1), 126.48, 127.75, 128.36 (C-
Ar), 143.87 (C-ipso), 150.57 (CO, urethane), 171.30 (CO, acyl),
177.15, 177.22 (CO, pivaloyl).
(minor diastereomer) d = 1.03 [s, 9 H, C(CH3)3], 3.17 (dd, 1 H,
J = 7.4, 2.2 Hz, CH2CO), 4.60 (dd, 1 H, J = 7.4, 5.8 Hz, H-2), 5.82
(d, 1 H, J = 5.8 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.94
[(CH2)3CH3], 22.52 (CH2), 26.91, 27.09 [C(CH3)3], 29.59, 36.07
(CH2), 38.72, 38.94 [C(CH3)3], 38.72 (CH2CO), 38.94 (CHPh),
53.77 (C-2), 62.88 (C-5), 65.83, 69.38 (C-3, C-4), 96.86 (C-1),
126.44, 127.69, 128.37 (C-Ar), 144.17 (C-ipso), 150.57 (CO, ure-
thane), 171.27 (CO, acyl), 177.16, 177.22 (CO, pivaloyl).
Anal. Calcd for C27H37NO8 (503.60): C, 64.40; H, 7.41; N, 2.78.
Found: C, 64.08; H, 7.65; N, 2.73.
ESI-MS: m/z = 482.4 [M + Na – CO2]+, 526.5 [M + Na]+, 544.6 [M
+ K]+.
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

PAPER
Conjugate Addition of Mixed Organoaluminum Reagents
2163
Anal. Calcd for C29H41NO8 (531.65): C, 65.52; H, 7.77; N, 2.63.
Found: C, 65.49; H, 7.70; N, 2.57.
5a), 4.02 (dd, 1 H, J = 12.9, 4.3 Hz, H-5b), 4.38 (dd, 1 H, J = 5.5,
7.4 Hz, H-2), 5.09 (m, 2 H, H-4, H-3), 5.39 (d, 1 H, J = 5.5 Hz, H-
1), 7.10–7.26 (m, 5 H, Ar).
ESI-MS: m/z = 510.5 [M + Na – CO2]+, 554.6 [M + Na]+, 570.5 [M
+ K]+.
(minor diastereomer) d = 0.97 [s, 9 H, C(CH3)3], 2.95 (m, 1 H,
CHPh), 3.29 (m, 2 H, CH2CO), 4.52 (dd, 1 H, J = 7.3, 5.9 Hz, H-2),
4.96 (d, 1 H, J = 1.95 Hz, H-4), 5.01 (dd, 1 H, J = 7.44, 1.9 Hz, H-
3), 5.79 (d, 1 H, J = 5.9 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 26.35,
30.93, 31.15 (CH2-Cyclohexyl), 26.93, 27.06 [C(CH3)3], 38.61
(CH2CO), 38.72, 38.94 [C(CH3)3], 42.61 (CH-Cyclohexyl), 48.15
(CHPh), 53.77 (C-2), 62.88 (C-5), 65.82, 69.26 (C-3, C-4), 96.79
(C-1), 126.36, 128.14, 128.42 (C-Ar), 143.06 (C-ipso), 150.63 (CO,
urethane), 171.83 (CO, acyl), 177.22 (2C, CO, pivaloyl).
1,2-Dideoxy-1,2-[N-(4,4-dimethyl-3-phenylpentanoyl)epoxy-
carbonylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18d)
a) According to general procedure (method A). Reagents: MeAlCl2
(2.1 mL, 2.1 mmol, 1.0 M in hexane), t-BuLi (1.2 mL, 2.1 mmol,
1.7 M in hexane), toluene (10 mL); 16 (100 mg, 0.212 mmol),
MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
Yield: 61 mg (54%); colourless, amorphous solid; Rf = 0.53 (LPE–
EtOAc, 5:1); mp 160 °C; [a]D22 +14.7 (c = 1.0, CHCl3); diastereo-
meric ratio 97:3 (HPLC), 96:4 (H-1, 400 MHz 1H NMR).
(minor diastereomer) d = 26.77 [C(CH3)3], 38.86 (CH2CO), 43.17
(CH, cyclohexyl), 47.00 (CHPh), 53.71 (C-2), 96.65 (C-1).
b) According to general procedure (method B). Reagents: 1.05 mL
(2.1 mmol) Me3Al (2 M in toluene), 1.2 mL (2.1 mmol) tert-butyl-
lithium (1.7 M in hexane), 10 mL toluene; 100 mg (0.212 mmol) 16,
0.3 mL (0.3 mmol) MeAlCl2 (1.0 M in hexane), 10 mL toluene.
Yield: 66 mg (57%); diastereomeric ratio 91:9 (H-1, 400 MHz 1H
NMR), 93:7 (HPLC).
Anal. Calcd for C31H43NO8 (557.69): C, 66.76; H, 7.77; N, 2.51.
Found: C, 66.60; H, 7.91; N, 2.38.
ESI-MS: m/z = 536.6 [M + Na – CO2]+, 580.5 [M + Na]+, 596.5 [M
+ K]+.
Analytical HPLC: Rt = 13.93 (minor diastereomer), 14.70 min (ma-
jor diastereomer) [MeCN–H2O, 85:15].
1,2-Dideoxy-1,2-[N-(3-phenylnon-4-enoyl)epoxycarbonylimi-
no]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18f)
According to general procedure (method C; reaction time 40 h). Re-
agents: DIBAL-H (2.1 mL, 2.1 mmol, 1.0 M in CH2Cl2), 1-hexyne
(0.3 mL, 2.7 mmol), toluene (10 mL); 16 (100 mg, 0.212 mmol),
MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.88 [s, 9 H,
C(CH3)3], 1.14, 1.18 [s, 18 H, C(CH3)3], 2.98 (m, 2 H, J = 18.0 Hz,
CHPh, CH2CO), 3.75 (dd, 1 H, J = 18.0, 5.5 Hz, CH2CO), 3.92 (dd,
1 H, J = 12.5, 3.5 Hz, H-5a), 4.03 (dd, 1 H, J = 12.5, 1.2 Hz, H-5b),
4.44 (dd, 1 H, J = 7.4, 5.9 Hz, H-2), 5.08 (dd, 1 H J = 3.1, 1.2 Hz,
H-4), 5.10 (dd, 1 H, J = 7.4, 3.1 Hz, H-3), 5.52 (d, 1 H, J = 5.9 Hz,
H-1), 7.14–7.25 (m, 5 H, Ar).
Yield: 48 mg (41%); 90% conversion; colourless, amorphous solid;
Rf = 0.53 (LPE–EtOAc, 5:1); mp 98 °C; [a]D21 +9.0 (c = 1.0,
CHCl3); diastereomeric ratio 81:19 (H-2, 400 MHz 1H NMR).
(minor diastereomer) d = 0.86 [s, 9 H, C(CH3)3], 3.20 (dd, 1 H,
J = 17.2, 3.5 Hz, CH2CO), 3.51 (dd, 1 H, J = 17.6, 6.6 Hz, CH2CO),
4.51 (m, 1 H, H-2), 4.95 (d, 1 H, J = 5.5 Hz, H-3), 5.78 (d, 1 H,
J = 5.5 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 26.91,
27.05 [C(CH3)3], 28.08 [CHC(CH3)3], 33.72 [CHC(CH3)3], 36.26
(CH2CO), 38.72, 38.93, 38.94 [C(CH3)3], 51.93 (CHPh), 53.74 (C-
2), 62.96 (C-5), 65.87, 69.26 (C-3, C-4), 96.81 (C-1), 126.42,
127.75, 129.30 (C-Ar), 141.88 (C-ipso), 150.77 (CO, urethane),
171.99 (CO, acyl), 177.17, 177.27 (CO, pivaloyl).
Analytical HPLC: Rt = 20.85 min (MeCN–H2O, 85:15).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.84 [m, 3
H, 3J = 7.0 Hz, (CH2)2CH3], 1.06, 1.21 [s, 18 H, C(CH3)3], 1.26 [m,
4 H, (CH2)2], 1.94 (m, 2 H, J = 6.7 Hz, =CHCH2), 3.18 (dd, 1 H,
J = 16.8, 6.3 Hz, CH2CO), 3.44 (dd, 1 H, J = 16.8, 7.3 Hz, CH2CO),
3.82 (m, 1 H, J = 7.3, 7.0 Hz, CHPh), 3.94 (dd, 1 H, J = 12.9, 3.9
Hz, H-5a), 4.04 (dd, 1 H, J = 12.9, 0.7 Hz, H-5b), 4.63 (dd, 1 H,
J = 7.4, 5.9 Hz, H-2), 5.06 (d, 1 H, J = 3.1 Hz, H-4), 5.13 (dd, 1 H,
J = 7.4, 3.1 Hz, H-3), 5.40–5.74 (dd, 2 H, J = 15.3, 6.7 Hz,
CH=CH), 5.83 (d, 1 H, J = 5.9 Hz, H-1), 7.14–7.28 (m, 5 H, Ar).
(minor diastereomer) d = 26.70 [C(CH3)3].
(minor diastereomer) d = 1.17, 1.21 [s, 18 H, C(CH3)3], 2.93 (dd, 1
H, J = 16.8 Hz, CH2CO), 4.46 (dd, 1 H, J = 7.8, 5.8 Hz, H-2).
Anal. Calcd for C29H41NO8 (531.65): C, 65.52; H, 7.77; N, 2.63.
Found: C, 65.60; H, 7.73; N, 2.52.
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.92
[(CH2)3CH3], 22.20 (CH2), 26.83, 27.09 [C(CH3)3], 31.46, 32.13
(CH2), 38.66, 38.94 [C(CH3)3], 41.26 (CH2CO), 44.24 (CHPh),
53.75 (C-2), 62.94 (C-5), 65.73, 69.17 (C-3, C-4), 96.79 (C-1),
126.46, 127.48, 128.55 (C-Ar), 131.33, 131.97 (CH=), 143.28 (C-
ipso), 150.72 (CO, urethane), 170.72 (CO, acyl), 177.11 (2C, CO,
pivaloyl).
ESI-MS: m/z = 510.4 [M + Na – CO2]+, 554.5 [M + Na]+, 570.4 [M
+ K] +.
1,2-Dideoxy-1,2-[N-(3-cyclohexyl-3-phenylpropanoyl)epoxy-
carbonylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18e)
According to general procedure (method A). Reagents: MeAlCl2
(2.1 mL, 2.1 mmol, 1.0 M in hexane), cyclohexylmagnesium bro-
mide (1.05 mL, 2.12 mmol, 2.0 M in Et2O), toluene (10 mL); 16
(100 mg, 0.212 mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hex-
ane), toluene (10 mL).
Yield: 59 mg (50%); 75% conversion (H-1, 400 MHz 1H NMR); co-
lourless, amorphous solid; Rf = 0.53 (LPE–EtOAc, 5:1);
mp 148 °C; [a]D22 +14.5 (c = 1.0, CHCl3); diastereomeric ratio
74:26 (H-2, 400 MHz 1H NMR), 71:29 (HPLC).
(minor diastereomer) d = 26.94 [C(CH3)3], 62.90 (C2).
C31H43NO8 (557.69).
ESI-MS: m/z = 536.5 [M + Na – CO2]+, 580.5 [M + Na]+, 621.4 [M
+ Na + CH3CN]+.
1,2-Dideoxy-1,2-[N-(3-phenylnon-4-ynoyl)epoxycarbonylimi-
no]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18g)
According to general procedure (method A; reaction time 72 h). Re-
agents: MeAlCl2 (2.1 mL, 2.1 mmol, 1.0 M in hexane), 1-hexynyl-
lithium (2.1 mmol, from 1-hexyne in toluene and 1.05 equiv n-
BuLi); toluene (10 mL); 16 (100 mg, 0.212 mmol), MeAlCl2 (0.3
mL, 0.3 mmol, 1.0 M in hexane), toluene (10 mL).
Analytical HPLC: Rt = 21.07 (minor diastereomer), 22.43 min (ma-
jor diastereomer) [MeCN–H2O, 85:15).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.74–1.87
(m, 11 H, CH, CH2, cyclohexyl), 1.15, 1.19 [s, 18 H, C(CH3)3], 2.87
(m, 1 H, CHPh), 3.04 (dd, 1 H, J = 16.4, 3.9 Hz, CH2CO), 3.54 (dd,
1 H, J = 16.4, 5.9 Hz, CH2CO), 3.90 (dd, 1 H, J = 12.9, 1.95 Hz, H-
1
Yield: 22 mg (16%); conversion: 59% (H-1, 400 MHz H NMR);
colourless, amorphous solid; Rf = 0.48 (LPE–EtOAc, 4:1);
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York

2164
S. Elzner et al.
PAPER
[a]D22 +4.8 (c = 1.0, CHCl3); diastereomeric ratio 81:19 (H-1, 400
3-Phenylvaleric Acid (20)17
MHz 1H NMR).
To a solution of 18a (198 mg, 0.393mmol) in THF/H2O (3:1, 80
mL), H2O2 (0.3 mL, 35% in H2O) and LiOH (19 mg, 0.79 mmol)
were added at 0 °C. The solution was stirred at r.t. until TLC
showed complete conversion (3 h). NaHSO3 (1.5 M, 2 mL) was
added, the pH of the solution was adjusted to 9 by addition of sat.
NaHCO3, and THF was removed in vacuo. The aqueous layer was
extracted with CH2Cl2. The organic layer was dried with MgSO4
and the solvent was removed in vacuo, yielding the chiral auxiliary
10. The aqueous solution was adjusted to pH 1–2 by the addition of
1 N HCl, and carboxylic acid 20 was extracted with CH2Cl2.
Analytical HPLC: Rt = 14.63 min (MeCN–H2O, 85:15).
1H NMR (400 MHz, CDCl3): (major diastereomer) d = 0.88 [t, 3 H,
J = 7.0 Hz, (CH2)3CH3], 1.14, 1.23 [s, 18 H, C(CH3)3)], 1.30–1.40
(m, 2 H, J = 7.0, 4.7 Hz, CH2), 1.42–1.49 (m, 2 H, J = 5.1, 4.7 Hz,
CH2), 2.16 (dt, 2 H, J = 5.1, 2.0 Hz, CH2C≡), 3.06 (dd, 1 H,
J = 16.8, 7.4 Hz, CH2CO), 3.53 (dd, 1 H, J = 16.8, 9.8 Hz, CH2CO),
3.97 (dd, 1 H, J = 12.9, 3.1 Hz, H-5a), 4.07 (dd, 1 H, J = 13.3, 1.6
Hz, H-5b), 4.13 (m, 1 H, J = 9.8, 7.0, 2.0 Hz, CHPh), 4.72 (dd, 1 H,
J = 7.4, 5.9 Hz, H-2), 5.14 (m, 1 H, H-4), 5.18 (dd, 1 H, J = 7.4, 3.1
Hz, H-3), 5.87 (d, 1 H, J = 5.9 Hz, H-1), 7.19–7.37 (m, 5 H, Ar).
Yield: 109 mg (81%) oxazolidinone 13, 60 mg (86%) acid 20;
[a]D22 +42.3 (c = 5.0, benzene), Lit.18 [a]D25 +46.3 (benzene).
1H NMR (200 MHz, CDCl3): d [ppm] = 0.76 (t, 3 H, J = 7.3 Hz,
CH3), 1.52–1.80 (dd, 2 H, J = 7.3, 6.8 Hz, CH2CH3), 2.61–2.66 (m,
2 H, CH2CO), 2.88–3.06 (dd, 1 H, J = 7.8, 6.8 Hz, CHPh), 7.15–
7.34 (m, 5 H, Ar), 10.78 (broad s, 1 H, COOH).
13C NMR (50.3 MHz, CDCl3): d = 11.86 (CH3), 29.13 (CH2), 41.15
(CH2CO), 43.52 (CHPh), 126.54, 127.50, 128.45 (C-Ar), 143.62
(C-ipso), 178.90 (COOH).
(minor diastereomer) d = 3.27 (dd, 1 H, J = 16.4, 7.1 Hz, CH2CO),
3.43 (dd, 1 H, J = 16.4, 7.4 Hz, CH2CO), 4.57 (dd, 1 H, J = 8.6, 5.9
Hz, H-2), 5.70 (d, 1 H, J = 5.9 Hz, H-1).
13C NMR (50.3 MHz, CDCl3): (major diastereomer) d = 13.62
[(CH2)3CH3], 18.55 (CH2), 21.98 (CH2), 26.91, 27.10 [C(CH3)3],
31.01 (CH2), 33.53 (CHPh), 38.97, 38.73 [C(CH3)3], 44.22
(CH2CO), 53.90 (C-2), 63.04 (C-5), 65.80, 69.26 (C-3, C-4), 80.32,
83.76 (C≡), 97.02 (C-1), 127.04, 127.43, 128.60 (C-Ar), 141.08 (C-
ipso), 155.39 (CO, urethane), 170.03 (CO, acyl), 177.16 (2C, CO,
pivaloyl).
C11H14O2 (178.10).
C31H41NO8 (555.67).
ESI-MS: m/z = 534.5 [M + Na – CO2]+, 578.5 [M + Na]+.
References
(1) For review see: (a) Eisch, J. J. In Comprehensive
Organometallic Chemistry II, Vol. 1; Wilkinson, G.; Stone,
F. A. G.; Abel, E. W., Eds.; Elsevier: Amsterdam, 1995,
431. (b) Eisch, J. J. In Comprehensive Organometallic
Chemistry II, Vol. 11; Wilkinson, G.; Stone, F. A. G.; Abel,
E. W., Eds.; Elevier: Amsterdam, 1995, 277.
(c) Yamamoto, H. In Organometallics in Organic Synthesis;
Schlosser, M., Ed.; J. Wiley and Sons: Chichester, 2002,
535.
(2) Baba, Y. Bull. Chem. Soc. Jpn. 1968, 41, 928.
(3) Hooz, J.; Layton, R. B. Can. J. Chem. 1973, 51, 2098.
(4) (a) Glemo, N. C.; Pattenden, G. J. Chem. Soc., Perkin Trans.
1 1986, 2133. (b) Barbato, S.; De Napoli, L.; Mayol, L.;
Piccialli, G.; Santacrose, C. Tetrahedron Lett. 1987, 28,
5727.
1,2-Dideoxy-1,2-[N-(3-methylbutanoyl)epoxycarbonylimino]-
3,4-di-O-pivaloyl-b-D-arabinopyranose (19)
According to general procedure (method B). Reagents: Me3Al (1.2
mL, 2.4 mmol, 2.0 M in pentane), PhLi (1.35 mL, 2.12 mmol, 1.8
M in cyclohexane–Et2O, 70:30), toluene (10 mL); 15 (100 mg,
0.243 mmol), MeAlCl2 (0.3 mL, 0.3 mmol, 1.0 M in hexane), tolu-
ene (10 mL).
1
Yield: 23.8 mg (23%, isolated); conversion: 50% (200 MHz H
NMR); colourless, amorphous solid; Rf = 0.50 (LPE–EtOAc, 5:1);
mp 111 °C; [a]D22 –13.6 (c = 1.0, CHCl3).
Analytical HPLC-MS: Phenomenex LUNA C18-2 (75 × 4.6 mm,
3mm), MeCN–H2O gradient 80:20 → 100:0 in 10 min, ELS-detec-
tion: ratio 18h:19 = 1:2.3.
(5) Maas, S.; Stamm, A.; Kunz, H. Synthesis 1999, 1792.
(6) Rück, K.; Kunz, H. Angew. Chem., Int. Ed. Engl. 1991, 30,
694; Angew. Chem. 1991, 103, 712.
(7) Kunz, H.; Pees, K. J. J. Chem. Soc., Perkin Trans. 1 1989,
1169.
Rt = 3.12 min: 1,2-Dideoxy-1,2-[N-(3-phenyl-butanoyl)epoxy-
carbonylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (18h)
(C26H35NO8, 489.24); m/z = 406.5 [M + Na – CO2]+, 450.4 [M +
Na]+, 491.4 [M + Na + CH3CN]+.
Rt = 3.75 min: 1,2-Dideoxy-1,2-[N-(3-methyl-butanoyl)epoxy-
carbonylimino]-3,4-di-O-pivaloyl-b-D-arabinopyranose (19)
(C21H33NO8, 427.22); m/z = 468.4 [M + Na – CO2]+, 512.4 [M +
Na]+, 553.5 [M + Na + CH3CN]+.
(8) Rück, K.; Kunz, H. Synlett 1992, 343.
(9) Rück, K.; Kunz, H. Synthesis 1993, 1018.
(10) Maas, S.; Kunz, H. J. Prakt. Chem. 2000, 342, 396.
(11) Neely, T. A.; Schwarz, W. W.; Vaughan, H. V. Jr. Org.
Synth. 1965, 45, 107.
(12) (a) Wilke, G.; Müller, H. Liebigs Ann. Chem. 1960, 629,
222. (b) Ziegler, K.; Gellert, H. G.; Lehmkuhl, H.; Pfohl, W.
Liebigs Ann. Chem. 1960, 629, 1.
1
19: H NMR (200 MHz, CDCl3): d = 0.94 [d, 6 H, J = 6.4 Hz,
CH(CH3)2], 1.16, 1.23 [s, 18 H, C(CH3)3], 2.03–2.17 (m, 1 H,
CH(CH3)3], 2.73 (m, 2 H, CH2CO), 3.97 (dd, 1 H, J = 12.7, 3.0 Hz,
H-5a), 4.09 (dd, 1 H, J = 12.7, 1.0 Hz, H-5b), 4.69 (dd, 1 H, J = 7.3,
5.8 Hz, H-2), 5.16–5.28 (m, 2 H, J = 7.3 Hz, H-3, H-4), 5.88 (d, 1
H, J = 5.4 Hz, H-1).
(13) Kunz, H.; Pfrengle, W.; Sager, W. Tetrahedron Lett. 1989,
30, 4109.
(14) Karrer, P.; Becker, B.; Benz, F.; Frei, P.; Salomon, H.;
Schöpp, K. Helv. Chim. Acta 1935, 18, 1435.
(15) (a) Lemieux, R. U.; Ratcliff, R. M. Can. J. Chem. 1979, 57,
1244. (b) Roth, W.; Pigman, W. Methods Carbohydr. Chem.
1963, 2, 457.
(16) Grundler, G.; Schmitt, R. Liebigs Ann. Chem. 1984, 1826.
(17) Evans, D. A.; Britton, T. C.; Ellmann, J. A. Tetrahedron
Lett. 1987, 28, 6141.
13C NMR (50.3 MHz, CDCl3): d = 22.44, 22.47 (CH3), 24.88
[CH(CH3)2], 26.91, 27.10 [C(CH3)3], 29.27 (CH2CH3), 38.72, 38.99
[C(CH3)3], 44.08 (CH2CO), 53.66 (C-2), 62.93 (C-5), 65.82, 69.55
(C-3, C-4), 96.89 (C-1), 150.62 (CO, urethane), 171.78 (CO, acyl),
177.18 (2C, CO, pivaloyl).
(18) Sorlin, G.; Bergson, G. Ark. Kemi. 1969, 29, 593.
Synthesis 2004, No. 13, 2153–2164 © Thieme Stuttgart · New York