Studies on the aza-Claisen rearrangement of 4,5-dihydroxylated allylic trichloroacetimidates: the stereoselective synthesis of (2R,3S)- and (2S,3S)-2-amino-3,4-dihydroxybutyric acids

Article abstract of DOI:10.1016/j.tet.2008.07.062

Two new synthetic approaches, involving substrate directed aza-Claisen rearrangements and aza-Claisen rearrangements mediated by chiral Pd(II) catalysts, have been developed for the stereoselective synthesis of (2R,3S)-2-amino-3,4-dihydroxybutyric acid, a

Full text of DOI:10.1016/j.tet.2008.07.062

Tetrahedron 64 (2008) 9521–9527
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Studies on the aza-Claisen rearrangement of 4,5-dihydroxylated allylic
trichloroacetimidates: the stereoselective synthesis of (2R,3S)- and
(2S,3S)-2-amino-3,4-dihydroxybutyric acids
*
Michael D. Swift, Andrew Sutherland
WestCHEM, Department of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Two new synthetic approaches, involving substrate directed aza-Claisen rearrangements and aza-Claisen
rearrangements mediated by chiral Pd(II) catalysts, have been developed for the stereoselective synthesis
Received 2 June 2008
Accepted 17 July 2008
Available online 22 July 2008
of (2R,3S)-2-amino-3,4-dihydroxybutyric acid, a dihydroxylated
a-amino acid from the edible mush-
room, Lyophyllum ulmarium and its (2S,3S)-unnatural diastereomer.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Palladium catalysis
Aza-Claisen rearrangement
Directing effect
Amino acids
1. Introduction
presence of an adjacent MOM-ether results in a highly effective
directed rearrangement giving erythro products in diastereomeric
ratios of up to 16:1.5 More recently, a series of substrates were
prepared to investigate the influence of this directing effect and this
showed that both oxygen atoms from the MOM group are required
for a highly diastereoselective process (Scheme 2).6 The products of
The aza-Claisen rearrangement of allylic trichloroacetimidates
(Scheme 1), commonly known as the Overman rearrangement,
has found widespread application for the total synthesis of ni-
trogen-containing natural products.1 This is due to the mild
conditions employed for this transformation as well as the ex-
cellent transfer of chirality during the rearrangement via well-
defined chair-like transition states.1,2 This is particularly the case
for the metal-catalysed reaction, where understanding of the
cyclisation-induced rearrangement mechanism has lead to the
development of highly effective chiral Pd(II) catalysts, which give
the allylic trichloroacetamides in high yields and in excellent
enantioselectivity.3
MOM
MOMO
R
O
[Pd]
Pd(II)
R
HN
HN
O
O
CCl3
CCl3
MOM
H
H
O
R
R
H
Δ or Pd(II)
R
O
[Pd]
HN
HN
O
[Pd]
R
HN
O
O
HN
+
O
O
CCl3
CCl3
Cl3C
Cl3C
- Pd(II)
Scheme 1. Rearrangement of allylic trichloroacetimidates.
MOMO
R
In our research, we initiated a programme to study how the
Overman rearrangement can be influenced by stereogenic centres
within the molecule.4 Extensive experimentation revealed that the
O
HN
CCl3
* Corresponding author. Tel.: þ44 141 330 5936; fax: þ44 141 330 4888.
E-mail address: andrews@chem.gla.ac.uk (A. Sutherland).
Scheme 2. MOM-ether directed Pd(II)-catalysed rearrangement via the cyclisation-
induced pathway.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.062

9522
M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
the MOM-ether directed rearrangements are excellent synthetic
intermediates and have been oxidised to give -hydroxy- -amino
acids or used in combination with ring closing metathesis (RCM)
reactions for the synthesis of piperidine natural products.7
In an effort to extend the scope of this process for highly func-
with DIBAL-H to give the corresponding allylic alcohol 4 in 94%
yield (Scheme 3). This was then treated with trichloroacetonitrile
and DBU to give allylic trichloroacetimidate 5, which was used in all
rearrangement reactions without further purification.
b
a
Although MOM-ethers are the most effective at directing the
Overman rearrangement, it was proposed that the acetonide pro-
tected allylic trichoroacetimidate 5 would still undergo a directed
rearrangement using the oxygen atom at the 4-position. Therefore,
5 was treated with bis(acetonitrile)palladium(II) chloride under
standard conditions (Table 1, entry 1). This gave the two di-
astereomeric allylic trichloroacetamides 6 and 7 in 36% yield and in
a 1:7 ratio. The low yield of 6 and 7 is due to a competing pathway
involving Pd(II)-catalysed hydrolysis of the acetonide followed by
1,3-rearrangement of the allylic trichloroacetimidate by a non-
concerted ionisation pathway resulting in the formation of allylic
trichloroacetamide 8.7a,9 While Pd(II)-mediated hydrolysis re-
actions of acetals and ketals are known in aqueous acetonitrile, it
was surprising to observe this process occurring in anhydrous
dichloromethane.10 Rearrangement of 5 was also done using other
metal catalysts known to effect the Overman rearrangement such
as Pt(II), Au(I) and Au(III).5b,11 Unfortunately, these reactions yiel-
ded similar results as described for the Pd(II)-catalysed rear-
rangement. As these metal complexes all acted as Lewis acids,
resulting in hydrolysis of the acetonide, it was proposed that
a bulky, sterically hindered metal complex would be unable to ef-
fectively deprotect the 1,2-diol, leading to higher yields of the de-
sired allylic trichloroacetamides 6 and 7. Overman and co-workers
have developed chiral palladium(II) catalysts such as (S)-COP-Cl 9,
which catalyse the rearrangement of allylic trichloroacetimidates in
high yields and excellent enantioselectivities.3e,f,k It was reasoned
that the use of such chiral catalysts would not only prevent hy-
drolysis of the acetonide but also give an enhancement in diaster-
eoselectivity. In the event, treatment of allylic trichloroacetimidate
5 with (S)-COP-Cl 9 gave allylic trichloroacetamides 6 and 7 in 81%
yield and in an excellent 52:1 ratio (96% de, entry 2). (S)-COP-Cl is
known to give allylic trichloroacetamides with the same absolute
configuration as C-3 of 6, resulting from the catalyst complexing to
the back face of the allylic trichloroacetimidate. The stereocentre
already present in allylic trichloroacetimidate 5 prevents attack for
the front face. Thus, this is an example of a matched pairing be-
tween substrate and catalyst, and this double stereodifferenation
leads to an enhanced diastereoselective outcome for this reaction.
To confirm this, allylic trichloroacetimidate 5 was treated with (R)-
COP-Cl and as expected, this mismatched pairing results in a sig-
nificantly slower reaction giving allylic trichloroacetamide 7 as the
major diastereomer in only a 6:1 ratio. Furthermore, significant
tionalised
synthesis of (2R,3S)-2-amino-3,4-dihydroxybutyric acid 1, a dihy-
droxylated -amino acid from the edible mushroom, Lyophyllum
a-amino acids, we recently reported the stereoselective
a
ulmarium, using the MOM-ether directed rearrangement.8 We now
report a new five-step synthesis of (2S,3S)-2-amino-3,4-dihydroxy-
butyric acid 2, which involves a matched substrate–catalyst pairing
to effect a highly diastereoselective aza-Claisen rearrangement. We
also report in full the synthesis of (2R,3S)-2-amino-3,4-dihydroxy-
butyric acid 1 using the MOM-ether directed rearrangement
as well as new results, which show that an erythro-allylic
tri-chloroacetamide can be generated in high diastereoselectivity
using a mismatched substrate–catalyst pairing.
OH
OH
CO2H
HO
HO
CO2H
NH2
NH2
1
2
2. Results and discussion
Our strategy for the preparation of amino acids 1 and 2 was to
synthesise a protected 4,5-dihydroxylated allylic alcohol and then
use an Overman rearrangement to create the key allylic tri-
chloroacetamide, which could then be oxidised and deprotected to
give the desired targets. Thus, commercially available ethyl (2E,4S)-
4,5-O-isopropylidene-4,5-dihydroxypenten-2-oate 3 was reduced
O
O
a
O
O
O
CO2Et
OH
4
3
b
O
HN
O
CCl3
quantities of allylic trichloroacetamide
8 were also isolated,
5
showing that deprotection of the 1,2-diol by (R)-COP-Cl is just as
facile than complexing to the more hindered front face of the al-
kene to effect the Overman rearrangement.
Scheme 3. Reagents and conditions: (a) DIBAL-H (2.2 equiv), Et2O, ꢀ78 ꢁC to rt, 94%;
(b) Cl3CCN, DBU, CH2Cl2.
Table 1
OH
O
O
Cat.
O
(3 mol%)
HO
O
O
O
+
+
CH2Cl2,
38 °C
HN
O
O
O
HN
O
NH
CCl3
HN
CCl3
CCl3
CCl3
5
6
7
8
Entry
Catalyst
Reaction time (h)
Yielda (%)
Ratiob (6/7/8)
1c
2
PdCl2(MeCN)2
(S)-COP-Cl
(R)-COP-Cl
24
168
336
36
81
23
1:7:7
52:1:0
1:6:5
3
a
Isolated combined yields of 6 and 7 from E-allylic alcohol 4.
Ratio in crude reaction mixture.
Catalyst loading: 10 mol %.
b
c

M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
9523
2
OH
O
O
Cl
a
d
Pd
HO
CO2Et
CO2Et
N
3
10
O
Ph
Co
Ph
Ph
b, c
Ph
OMOM
9
OMOM
TBDPSO
TBDPSO
TBDPSO
CO2Et
OH
12
11
With sufficient quantities of threo-diastereomer 6 available via
the highly selective (S)-COP-Cl catalysed rearrangement, the ster-
eoselective synthesis of (2S,3S)-2-amino-3,4-dihydroxybutyric acid
2 was completed. Oxidation of allylic trichloroacetamide 6 with
catalytic ruthenium(III) trichloride hydrate and sodium metaper-
iodate gave the corresponding carboxylic acid (Scheme 4).12
Deprotection of the amino and 1,2-diol functional groups was then
carried out using 6 M hydrochloric acid, which gave amino acid 2 in
47% yield over the two steps.
e
OMOM
HN
O
CCl3
13
Scheme 5. Reagents and conditions: (a) 2 M HCl, 94%; (b) TBDPSCl, imidazole, THF,
100%; (c) MOMBr, EtN(i-Pr)2, CH2Cl2, 86%; (d) DIBAL-H (2.2 equiv), Et2O, ꢀ78 ꢁC to rt,
86%; (e) Cl3CCN, DBU, CH2Cl2.
O
OH
a, b
O
HO
CO2H
4-position normally produces modest diastereoselectivities
(w5:1).6 Thus, the 4:1 ratio of diastereomers generated from the
Pd(II)-catalysed rearrangement of 13 suggests that the presence of
the bulky tert-butyldiphenylsilyl ether prevents effective co-
ordination of both MOM-ether oxygen atoms to the catalyst and
that only the adjacent 4-oxygen atom can participate, resulting in
the observed diastereoselectivity. Nevertheless, the use of Pd(II)
catalyst does allow rapid access to the erythro-diastereomer in good
yield. It should be noted that the rearrangement of 13 was also
carried out using (R)-COP-Cl, which gave 14 and 15 in 68% yield and
in a 1:16 ratio (entry 5). While this is a mismatched pairing be-
tween substrate and catalyst resulting in a slow reaction, the chiral
catalyst is still able to induce an asymmetric reaction generating 14
and 15 in high diastereoselectivity (88% de).
To complete the synthesis of (2R,3S)-2-amino-3,4-dihydroxy-
butyric acid 1, allylic trichloroacetamide 15 was oxidised to the
corresponding carboxylic acid 16 in 71% yield using the Sharpless
protocol (Scheme 6).12 Deprotection of 16 was then achieved in
a two-step protocol involving TBAF removal of the silyl ether. Acid-
mediated hydrolysis of the MOM and trichloroacetamide groups
then gave natural product 1, in 44% yield over the two steps.
O
HN
NH2
CCl3
2
6
Scheme 4. Reagents and conditions: (a) RuCl3$xH2O, NaIO4, CCl4, MeCN, H2O; (b) 6 M
HCl, , 47% over two steps.
D
Although rearrangement of allylic trichloroacetimidate 5 did
allow access to allylic trichloroacetamide 6 for the synthesis of
(2S,3S)-2-amino-3,4-dihydroxybutyric acid 2, the labile nature of
the acetonide protecting group prevented efficient synthesis of the
erythro-diastereomer using the directed rearrangement. To over-
come this, the acetonide group was replaced with protecting
groups known to be stable to the reaction conditions of metal-
catalysed rearrangements.5–7 Thus, acid hydrolysis of commercially
available acetonide 3 gave 1,2-diol 10 in 94% yield (Scheme 5). The
primary hydroxyl was protected as the tert-butyldiphenylsilyl
ether, followed by protection of the secondary hydroxyl as the
MOM-ether, which gave 11 in 86% yield over the two steps. It
should be noted that the MOM-ether was selected to protect the
4-hydroxyl as MOM-ethers are the most effective at directing the
Overman rearrangement. Ester 11 was then reduced using DIBAL-H
in good yield and the resulting allylic alcohol 12 was converted to
the corresponding allylic trichloroacetimidate 13 using tri-
chloroacetonitrile and DBU.
Allylic trichloroacetimidate 13 was rearranged using the stan-
dard metal catalysts for this reaction (Table 2, entries 1–4). As
expected, only the two diastereomeric 3,3-products 14 and 15 were
isolated from these reactions, indicating the stability of the silyl and
MOM-ethers to the reaction conditions. Rearrangement of 13 using
platinum(II) chloride, hydrogen tetrachloroaurate(III) hydrate or
gold(I) chloride gave 14 and 15 in modest yields and diastereomeric
ratios. The best results were obtained using bis(acetoni-
trile)palladium(II) chloride as the catalyst, which gave after only
12 h, a 68% yield of 14 and 15 (over two steps) and in a 1:4 ratio
(entry 4). Our studies on the origin of the MOM-ether directing
effect during these rearrangements have shown that to obtain high
diastereoselectivities (>10:1), both oxygen atoms are required
to participate, while the availability of only the oxygen at the
3. Conclusion
In summary, our studies on the rearrangement of 4,5-
dihydroxylated allylic trichloroacetimidates have led to the
development of a five-step synthesis of (2S,3S)-2-amino-3,4-dihy-
droxybutyric acid 2, which utilises a commercially available chiral
Pd(II) catalyst, (S)-COP-Cl, to effect a highly diastereoselective
rearrangement giving the threo-product in 96% de. Problems
associated with transition metal-catalysed hydrolysis of the ace-
tonide protecting group were overcome by synthesising a new
allylic trichloroacetimidate bearing silyl ether and MOM-ether
protecting groups. Directed rearrangement using bis(acetoni-
trile)palladium(II) chloride led to a fast, highly efficient reaction,
giving the diastereomeric products in 68% yield and in a 4:1 ratio.
The diastereomeric outcome could be enhanced using (R)-COP-Cl,
and while this is a mismatched pairing, this reaction still generated
the products in an excellent 16:1 ratio. Oxidation and deprotection
then completed the synthesis of (2R,3S)-2-amino-3,4-dihydroxy-
butyric acid
1 from L. ulmarium. Further studies utilising

9524
M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
Table 2
OMOM
HN
OMOM
HN
OMOM
HN
Cat.
TBDPSO
TBDPSO
TBDPSO
(10 mol%)
+
Toluene,
rt
O
O
O
CCl3
CCl3
CCl3
13
14
15
Entry
Catalyst
Reaction time (h)
Yielda (%)
Ratiob (14/15)
1
2
3
PtCl2
HAuCl4$3H2O
AuCl
PdCl2(MeCN)2
(R)-COP-Cl
168
48
168
12
25
49
40
68
68
1:4
1:2
1:3
1:4
1:16
4
5c
336
a
Isolated combined yields of 14 and 15 from E-allylic alcohol 12.
Ratio in crude reaction mixture.
Reaction carried out in CH2Cl2 at 38 ꢁC.
b
c
OMOM
HN
warm to room temperature and stirred overnight. The solution was
then filtered through a pad of CeliteÒ and washed with diethyl
ether (50 mL). Concentration in vacuo then yielded the crude
product as a clear oil, which was purified by flash column chro-
matography (20% diethyl ether/petroleum ether), which gave
(2E,4S)-4,5-(O-isopropylidene)-4,5-dihydroxyprop-2-en-1-ol 4 as
OMOM
CO2H
a
TBDPSO
TBDPSO
O
O
HN
CCl3
CCl3
15
16
25
24
a colourless oil (0.37 g, 94%). [
a
]
þ33.7 (c 1.0, CHCl3) (lit.13
[a]
D
D
b, c
þ33.9 (c 3.6, CHCl3)); dH (400 MHz, CDCl3) 1.40 (3H, s, CH3), 1.43
(3H, s, CH3), 3.61 (1H, br t, J 8.1 Hz, 5-HH), 4.10 (1H, dd, J 8.1, 7.0 Hz,
5-HH), 4.16 (2H, d, J 5.0 Hz, 1-H2), 4.54 (1H, dt, J 14.1, 7.0 Hz, 4-H),
5.72 (1H, dd, J 15.5, 7.0 Hz, 3-H), 5.95 (1H, dt, J 15.5, 5.0 Hz, 2-H); dC
(100 MHz, CDCl3) 25.9 (CH3), 26.7 (CH3), 62.5 (CH2), 69.4 (CH2), 76.5
(CH),109.4 (C), 128.3 (CH), 133.2 (CH); m/z (CI) 159 (MHþ,100%),141
(27), 83 (49).
OH
HO
CO2H
NH2
1
Scheme 6. Reagents and conditions: (a) RuCl3$xH2O, NaIO4, CCl4, MeCN, H2O, 71%; (b)
TBAF, THF; (c) 6 M HCl, , 44% over two steps.
4.1.2. Synthesis of allylic trichloroacetimidate 5
D
(2E,4S)-4,5-(O-Isopropylidene)-4,5-dihydroxyprop-2-en-1-ol 4
(0.2 g, 1.3 mmol) was dissolved in dichloromethane (20 mL)
and cooled to 0 ꢁC under a nitrogen atmosphere. 1,8-Diaza-
bicyclo[5.4.0]undec-7-ene (0.2 mL, 1.5 mmol) and trichloro-
acetonitrile (0.2 mL, 1.9 mmol) were then added, and the mixture
was allowed to warm to room temperature and then stirred for 2 h.
The reaction mixture was then filtered through a short pad of silica
gel, which was then washed with diethyl ether (75 mL). Concen-
tration in vacuo yielded the product as a brown oil (0.44 g), which
was then immediately carried forward to the rearrangement re-
action without further purification. dH (400 MHz, CDCl3),1.40 (3H, s,
CH3),1.45 (3H, s, CH3), 3.63 (1H, t, J 7.7 Hz, 5-HH), 4.14 (1H, dd, J 11.5,
7.7 Hz, 5-HH), 4.57 (1H, q, J 7.7 Hz, 4-H), 4.81 (2H, d, J 7.5 Hz,
1-H2), 5.87 (1H, ddt, J 15.5, 7.7,1.2 Hz, 3-H), 6.01 (1H, dt, J 15.5, 7.5 Hz,
2-H), 8.36 (1H, br s, NH).
4,5-dihydroxylated allylic trichloroacetamides for natural product
synthesis is currently underway.
4. Experimental
4.1. General methods
All reactions were performed under a nitrogen atmosphere
unless otherwise noted. Reagents and starting materials were
obtained from commercial sources and used as-received. Brine
refers to a saturated solution of sodium chloride. Flash column
chromatography was carried out using Fisher Matrex silica 60.
Macherey–Nagel aluminium backed plates pre-coated with silica
gel 60 (UV254) were used for thin layer chromatography and were
visualised by staining with KMnO4. 1H NMR and 13C NMR spectra
were recorded on a Bruker DPX 400 spectrometer with chemical
shift values in parts per million relative to residual chloroform (dH
7.28 and dC 77.2) as standard. Infrared spectra were recorded using
Golden Gate apparatus on a JASCO FTIR 410 spectrometer and mass
spectra were obtained using a JEOL JMS-700 spectrometer. Optical
rotations were determined as solutions irradiating with the sodium
4.1.3. Rearrangement of 5 using PdCl2(MeCN)2
Allylic trichloroacetimidate 5 (0.38 g, 1.25 mmol) was dissolved
in dichloromethane (10 mL) under a nitrogen atmosphere. Bis-
(acetonitrile)palladium(II) chloride (0.03 g, 0.1 mmol) was then
added and the reaction mixture was stirred at 38 ꢁC for 24 h. The
mixture was then filtered through a short pad of CeliteÒ and
washed with diethyl ether (40 mL). Concentration under vacuum
gave a viscous oil. Purification by flash column chromatography
(elution with 10% diethyl ether/petroleum ether) yielded (3R,4S)-
4,5-(O-isopropylidene)-3-(trichloromethylcarbonylamino)-4,5-di-
hydroxypenta-1-ene 6 and then (3S,4S)-4,5-(O-isopropylidene)-3-
D line (
l
¼589 nm) using an AA series Automatic polarimeter. [
a]
D
values are given in units 10ꢀ1 deg cm2 gꢀ1
.
4.1.1. (2E,4S)-4,5-(O-Isopropylidene)-4,5-dihydroxyprop-
2-en-1-ol 413
(trichloromethylcarbonylamino)-4,5-dihydroxypenta-1-ene 7 as
Ethyl (2E,4S)-4,5-(O-isopropylidene)-4,5-dihydroxypenten-2-
oate 3 (0.5 g, 2.5 mmol) was dissolved in diethyl ether (30 mL) and
cooled with stirring under a nitrogen atmosphere to ꢀ78 ꢁC. DIBAL-
H (1.0 M in hexanes) (5.5 mL, 5.5 mmol) was then added dropwise
to the reaction mixture. The reaction mixture was then allowed to
colourless oil (0.14 g, 36% combined yield, 1:7 ratio). Further elution
(90% diethyl ether/petroleum ether) then yielded (2E,4S)-1-(tri-
chloromethylcarbonylamino)-4,5-dihydroxypent-2-ene 8 as a col-
ourless oil (0.11 g, 32%). Data for 6: nmax/cmꢀ1 (neat) 3418 (NH),
23
2988 (CH), 1719 (CO), 1506 (C]C), 1373, 1217, 1068; [
a
]
þ34.4
D

M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
9525
(c 1.0, CHCl3); dH (400 MHz, CDCl3) 1.30 (3H, s, CH3),1.41 (3H, s, CH3),
3.64 (1H, dd, J 8.6, 6.5 Hz, 5-HH), 4.04 (1H, dd, J 8.6, 6.5 Hz, 5-HH),
4.28 (1H, td, J 6.5, 2.4 Hz, 4-H), 4.41–4.46 (1H, m, 3-H), 5.22–5.31
(2H, m, 1-H2), 5.81 (1H, ddd, J 17.1, 10.5, 5.7 Hz, 2-H), 6.99 (1H, br d, J
6.9 Hz, NH); dC (100 MHz, CDCl3) 24.7 (CH3), 26.4 (CH3), 53.9 (CH),
66.4 (CH2), 76.6 (CH), 92.6 (C),110.0 (C),117.7 (CH2),133.9 (CH),162.0
4.1.7. Ethyl (2E,4S)-4,5-dihydroxypent-2-enoate 1015
Ethyl (2E,4S)-4,5-(O-isopropylidene)-4,5-dihydroxy-2-pente-
noate 3 (2.0 g, 10 mmol) was dissolved in ethanol (20 mL). Hydro-
chloricacid (2 M,10 mL) wasthen added andthe solutionwas stirred
at room temperature for 3 h. The reaction was quenched by the
addition of small lumps of sodium hydrogen carbonate (6.0 g). In-
soluble material was then removed by filtration and the mixturewas
concentrated in vacuo. Further insoluble material was removed by
filtration and the solution was dried over MgSO4. Purification by
filtration through a pad of silica gel gave after concentration, ethyl
(2E,4S)-4,5-dihydroxypent-2-enoate 10 as a clear oil (1.51 g, 94%).
(C); found (CI): 306.0055,
C
10H15O3N35Cl37Cl2 requires MHþ
306.0062. Data for 7: nmax/cmꢀ1 (neat) 3418 (NH), 2988 (CH), 1719
(CO), 1506 (C]C), 1373, 1217, 1068; dH (400 MHz, CDCl3) 1.28 (3H, s,
CH3),1.39 (3H, s, CH3), 3.78 (1H, dd, J 9.1, 5.0 Hz, 5-HH), 4.02 (1H, dd,
J 9.1, 6.3 Hz, 5-HH), 4.22–4.27 (1H, m, 4-H), 4.40–4.46 (1H, m, 3-H),
5.25–5.32 (2H, m, 1-H2), 5.78 (1H, ddd, J 16.7, 10.3, 6.2 Hz, 2-H), 6.98
(1H, br d, J 6.9 Hz, NH); dC (100 MHz, CDCl3) 24.7 (CH3), 26.1 (CH3),
55.8 (CH), 65.5 (CH2), 76.1 (CH), 92.5 (C), 110.2 (C), 117.7 (CH2), 131.6
25
25
[a
]
ꢀ5.0 (c 0.5, CHCl3) (lit.15
[
a
]
ꢀ5.5 (c 1.6, CHCl3)); dH (400 MHz,
D
D
CDCl3) 1.29 (3H, t, J 7.1 Hz, OCH2CH3), 2.61 (2H, br s, 2ꢂOH), 3.53 (1H,
dd, J 11.5, 7.1 Hz, 5-HH), 3.74 (1H, dd, J 11.5, 3.4 Hz, 5-HH), 4.19 (2H, q, J
7.1 Hz, OCH2CH3), 4.39–4.45 (1H, m, 4-H), 6.13 (1H, dd, J 15.7, 1.8 Hz,
2-H), 6.90 (1H, dd, J 15.7, 4.4 Hz, 3-H); dC (100 MHz, CDCl3) 14.2
(CH3), 60.8 (CH2), 65.6 (CH2), 71.7 (CH), 121.9 (CH), 146.3 (CH), 166.7
(C); m/z (CI) 161 (MHþ, 100%), 99 (57), 75 (30).
(CH), 161.5 (C); found (CI): 306.0055, C10H15O3N35Cl37Cl2 requires
25
MHþ 306.0062; Data for 8: [
a
]
þ1.5 (c 1.0, CHCl3); dH (400 MHz,
D
CDCl3) 2.00 (2H, br s, OH), 4.20 (2H, dd, J 5.0, 1.8 Hz, 1-H2), 4.36 (1H,
t, J 8.0 Hz, 5-HH), 4.78 (1H, dd, J 9.8, 8.0 Hz, 5-HH), 4.92 (1H, q, J
8.0 Hz, 4-H), 5.77 (1H, ddt, J 15.5, 8.0,1.6 Hz, 3-H), 5.95 (1H, dt, J 15.5,
5.0 Hz, 2-H); dC (100 MHz, CDCl3) 62.6 (CH2), 67.9 (CH2), 76.1 (CH),
86.3 (C), 128.2 (CH), 133.3 (CH), 163.3 (C); found (CI): 261.9726,
C7H11NO335Cl3 requires MHþ 261.9729.
4.1.8. Ethyl (2E,4S)-5-(tert-butyldiphenylsilyloxy)-4-hydroxypent-
2-enoate16
Ethyl (2E,4S)-4,5-dihydroxypent-2-enoate 10 (1.0 g, 6.3 mmol)
was dissolved in THF (40 mL) under a nitrogen atmosphere. tert-
Butyldiphenylchlorosilane (2.4 g, 8.7 mmol) and imidazole (0.9 g,
12.5 mmol) were then added, and the solution was stirred at room
temperature overnight. The solution was then diluted with ethyl
acetate (50 mL) and washed with water (50 mL). The organic ex-
tracts were dried (MgSO4) and concentrated in vacuo. Flash column
chromatography (elution with 10% diethyl ether/petroleum ether)
4.1.4. Rearrangement of 5 using (S)-COP-Cl
Synthesis of allylic trichloroacetimidate 5 and subsequent rear-
rangement was carried out as described above using (2E,4S)-4,5-(O-
isopropylidene)-4,5-dihydroxyprop-2-en-1-ol 4 (1.0 g, 6.3 mmol)
and (S)-COP-Cl (0.2 g, 3 mol %). The reaction mixture was stirred at
38 ꢁC for 168 h. Purification by flash column chromatography (elu-
tionwith 10% diethyl ether/petroleum ether) yielded 6 and then 7 as
colourless oil (1.55 g, 81% combined yield, 52:1 ratio). Spectroscopic
data as described above.
yielded the title compound, ethyl (2E,4S)-5-(tert-butyldiphenylsi-
25
lyloxy)-4-hydroxypent-2-enoate, as a clear oil (2.48 g, 100%). [a]
D
22
ꢀ17.8 (c 1.6, CHCl3) (lit.16
[
a
]
ꢀ16.4 (c 0.2, CHCl3)); dH (400 MHz,
D
CDCl3) 1.08 (9H, s, t-Bu), 1.27 (3H, t, J 7.2 Hz, OCH2CH3), 2.74 (1H, br
d, J 4.2 Hz, 4-OH), 3.55 (1H, dd, J 10.2, 4.0 Hz, 5-HH), 3.76 (1H, dd J
10.2, 2.1 Hz, 5-HH), 4.19 (2H, q, J 7.2 Hz, OCH2CH3), 4.38–4.42 (1H,
m, 4-H), 6.14 (1H, dd, J 15.7, 2.2 Hz, 2-H), 6.80 (1H, dd, J 15.7, 4.3 Hz,
3-H), 7.37–7.47 (6H, m, Ar–H), 7.62–7.68 (4H, m, Ar–H); dC
(100 MHz, CDCl3) 14.3 (CH3), 19.3 (C), 26.9 (CH3), 60.5 (CH2), 67.0
(CH2), 71.5 (CH), 122.0 (CH), 127.9 (CH), 130.0 (CH), 132.8 (C), 135.6
(CH), 145.8 (CH), 166.3 (C); m/z (CI) 381 (MHþꢀOH, 14%), 321 (100),
257 (5), 217 (4), 143 (8).
4.1.5. Rearrangement of 5 using (R)-COP-Cl
Synthesis of allylic trichloroacetimidate 5 and subsequent rear-
rangement was carried out as described above using (2E,4S)-4,5-(O-
isopropylidene)-4,5-dihydroxyprop-2-en-1-ol 4 (0.1 g, 0.63 mmol)
and (R)-COP-Cl (0.03 g, 3 mol %). The reaction mixture was stirred at
38 ꢁC for 336 h. Purification by flash column chromatography (elu-
tionwith 10% diethyl ether/petroleum ether) yielded 6 and then 7 as
colourless oil (0.044 g, 23% combined yield, 1:6 ratio). Further elu-
tion (90% diethyl ether/petroleum ether) then yielded 8 as a col-
ourless oil (0.027 g, 16%). Spectroscopic data as described above.
4.1.9. Ethyl (2E,4S)-5-(tert-butyldiphenylsilyloxy)-4-
(methoxymethoxy)pent-2-enoate 1116
4.1.6. (2S,3S)-2-Amino-3,4-dihydroxybutyric acid 214
Ethyl (2E,4S)-5-(tert-butyldiphenylsilyloxy)-4-hydroxypent-2-
enoate (0.1 g, 0.25 mmol) was dissolved in dichloromethane
(20 mL) and cooled to 0 ꢁC under a nitrogen atmosphere. Chloro-
methylmethyl ether (0.1 mL, 1.25 mmol) was added dropwise and
the solution was stirred for 0.5 h. N,N-Diisopropylethylamine
(0.2 mL, 1.25 mmol) was added dropwise and the solution was then
heated under reflux overnight. The solution was diluted with
dichloromethane (20 mL) and washed with water (20 mL), and
then acidified with 2 M hydrochloric acid solution (10 mL). The
organic extracts were then dried (MgSO4) and the filtrate concen-
trated in vacuo. Flash column chromatography (20% diethyl ether/
petroleum ether) yielded ethyl (2E,4S)-5-(tert-butyldiphenylsilyl-
oxy)-4-(methoxymethoxy)pent-2-enoate 11 as a colourless oil
(3R,4S)-4,5-(O-Isopropylidene)-3-(trichloromethylcarbonyl-
amino)-4,5-dihydroxypenta-1-ene 6 (0.5 g, 1.7 mmol) was dis-
solved in tetrachloromethane (14 mL) and acetonitrile (14 mL).
Sodium periodate (1.46 g, 6.8 mmol) in water (22 mL) was added to
the solution. Ruthenium trichloride hydrate (18 mg, 0.08 mmol)
was added to the biphasic solution and the reaction mixture was
then stirred vigorously at room temperature overnight. The re-
action mixture was extracted with dichloromethane (4ꢂ50 mL),
dried (MgSO4) and concentrated in vacuo to yield the crude product
as a brown oil (0.25 g). The brown oil (0.25 g) was dissolved in 6 M
hydrochloric acid (10 mL) and heated under reflux overnight. The
reaction mixture was cooled to room temperature and then
extracted with diethyl ether (10 mL). The aqueous phase was then
concentrated in vacuo to give the crude product. Purification by ion
exchange chromatography (elution with 0.5 M NH4OH solution)
yielded (2S,3S)-2-amino-3,4-dihydroxybutyric acid 2 as a white
25
21
(0.13 g, 86%). [
a
]
þ11.7 (c 2.9, CHCl3) (lit.16
[
a
]
þ12.3 (c 1.7,
D
D
CHCl3)); dH (400 MHz, CDCl3) 1.06 (9H, s, t-Bu), 1.30 (3H, t, J 7.2 Hz,
OCH2CH3), 3.38 (3H, s, OMe), 3.69 (1H, dd, J 11.1, 5.0 Hz, 5-HH), 3.77
(1H, dd, J 11.1, 6.2 Hz, 5-HH), 4.22 (2H, q, J 7.2 Hz, OCH2CH3), 4.35–
4.40 (1H, m, 4-H), 4.67 (1H, d, J 7.1 Hz, OCHHO), 4.72 (1H, d, J 7.1 Hz,
OCHHO), 6.17 (1H, dd, J 16.3, 2.0 Hz, 2-H), 6.90 (1H, dd, J 16.3, 6.4 Hz,
3-H), 7.34–7.48 (6H, m, Ar–H), 7.56–7.72 (4H, m, Ar–H); dC
(100 MHz, CDCl3) 14.3 (CH3), 19.2 (C), 26.8 (CH3), 55.6 (CH3), 60.5
(CH2), 66.1 (CH2), 76.0 (CH), 95.2 (CH2), 122.8 (CH), 127.8 (CH), 129.8
24
26
solid (0.104 g, 47% over two steps). [
a]
ꢀ9.6 (c 1.0, H2O) (lit.14
[a]
D
D
ꢀ10.0 (c 1.0, H2O)); dH (400 MHz, D2O) 3.61 (2H, t, J 5.2 Hz, 4-H2),
3.67 (1H, d, J 4.0 Hz, 2-H), 4.03–4.08 (1H, m, 2-H); dC (100 MHz,
D2O) 56.7 (CH), 63.3 (CH2), 69.3 (CH), 172.7 (C); m/z (CI) 136 (MHþ),
91 (30%), 83 (100), 69 (76).

9526
M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
(CH), 133.1 (C), 135.6 (CH), 145.1 (CH), 166.1 (C); m/z (CI) 443 (MHþ,
2%) 381 (100), 321 (7), 257 (16), 243 (15), 143 (10).
5.31–5.38 (2H, m, 1-H2), 5.93 (1H, ddd, J 17.2, 10.5, 5.0 Hz, 2-H), 7.17
(1H, brd, J 8.4 Hz, NH), 7.38–7.59(6H, m, Ar–H), 7.64–7.62 (4H, m, Ar–
H); dC (100 MHz, CDCl3) 19.2 (C), 26.8 (CH3), 53.5 (CH3), 55.9 (CH),
63.0 (CH2), 78.0 (CH), 93.1 (C), 96.6 (CH2), 116.8 (CH2), 127.9 (CH),
129.9 (CH), 132.7 (C), 134.6 (CH), 135.6 (CH), 161.5 (C); found (CI):
546.1225, C25H33NO4 35Cl2 37ClSi requires MHþ 546.1220; Data for 15:
4.1.10. (2E,4S)-5-(tert-Butyldiphenylsilyloxy)-4-(methoxy-
methoxy)pent-2-en-1-ol 12
Ethyl (2E,4S)-5-(tert-butyldiphenylsilyloxy)-4-(methoxymeth-
oxy)pent-2-enoate 11 (2.8 g, 6 mmol) was dissolved in diethyl ether
(50 mL) and cooled to ꢀ78 ꢁC. DIBAL-H (1 M in hexanes) (14.0 mL,
14 mmol) was then added dropwise to the solution. The reaction
mixture was stirred at ꢀ78 ꢁC for 1 h and then warmed to room
temperature overnight. The solution was then cooled to 0 ꢁC and
a saturated ammonium chloride solution (7 mL) was added. The
reaction mixture was stirred for 1 h and then filtered under vacuum
through CeliteÒ to remove a white precipitate, which was then
washed with diethyl ether (400 mL). The resulting filtrate was dried
(MgSO4) and concentrated to give a yellow oil. Purification by flash
column chromatography (eluting with 50% diethyl ether/petroleum
ether) yielded (2E,4S)-5-(tert-butyldiphenylsilyloxy)-4-(methoxy-
methoxy)pent-2-en-1-ol 12 as yellow oil (2.19 g, 86%). nmax/cmꢀ1
nmax/cmꢀ1 (neat) 3393 (NH), 2931 (CH),1717 (CO),1645 (C]C),1428,
25
1113, 1032, 822; [
a
]
ꢀ28.1 (c 1.0, CHCl3); dH (400 MHz, CDCl3) 1.10
D
(9H, s, t-Bu), 3.40 (3H, s, OMe), 3.65–3.81 (3H, m, 5-H2 and 4-H), 4.64
(1H, d, J 6.7 Hz, OCHHO), 4.69 (1H, d, J 6.7 Hz, OCHHO), 4.71–4.76 (1H,
m, 3-H), 5.30 (1H, dt, J 10.4,1.2 Hz,1-HH), 5.36 (1H, dt, J 17.1,1.2 Hz,1-
HH), 5.79 (1H, ddd, J 17.1, 10.4, 6.6 Hz, 2-H), 7.40–7.49 (6H, m, Ar–H),
7.68–7.73 (4H, m, Ar–H), 8.04 (1H, br d, J 8.0 Hz, NH); dC (100 MHz,
CDCl3) 19.2 (C), 26.9 (CH3), 54.4 (CH3), 55.9 (CH), 63.8 (CH2), 81.7
(CH), 92.9 (C), 97.7 (CH2), 118.8 (CH2), 127.8 (CH), 129.9 (CH), 131.6
(CH), 132.9 (C), 135.6 (CH), 161.4 (C); found (CI): 546.1225,
C
25H33NO4 35Cl2 37ClSi requires MHþ 546.1220.
4.1.12. Rearrangement of 13 using HAuCl3$3H2O
(neat) 3422 (OH), 2931 (CH), 1589 (C]C), 1472, 1428, 1112, 704;
The reaction was carried out as described above using (2E,4S)-
5-(tert-butyldiphenylsilyloxy)-4-(methoxymethoxy)pent-2-en-1-ol
12 (0.05 g, 0.13 mmol) and hydrogen tetrachloroaurate(III) hy-
drate (10 mol %). Flash column chromatography (elution with 5%
diethyl ether/petroleum ether) gave 14, followed by 15 as col-
ourless oil (0.03 g, 49% combined yield, 1:2 ratio). Spectroscopic
data as described above.
28
[
a]
þ31.2 (c 1.0, CHCl3); dH (400 MHz, CDCl3) 1.05 (9H, s, t-Bu),
D
1.29 (1H, br s, 1-OH), 3.37 (3H, s, OMe), 3.63 (1H, dd, J 11.1, 6.0 Hz, 5-
HH), 3.74 (1H, dd, J 11.1, 7.6 Hz, 5-HH), 4.12 (2H, br d, J 5.0 Hz, 1-H2),
4.18–4.24 (1H, m, 4-H), 4.64 (1H, d, J 7.1 Hz, OCHHO), 4.70 (1H, d, J
7.1 Hz, OCHHO), 5.58 (1H, ddt, J 16.3, 8.0, 2.1 Hz, 3-H), 6.80 (1H, dtd,
J 16.3, 5.0, 1.0 Hz, 2-H), 7.36–7.46 (6H, m, Ar–H), 7.66–7.72 (4H, m,
Ar–H); dC (100 MHz, CDCl3) 19.3 (C), 26.8 (CH3), 55.4 (CH3), 63.0
(CH2), 66.8 (CH2), 76.8 (CH), 94.4 (CH2), 127.7 (CH), 128.5 (CH), 129.7
(CH), 132.9 (CH), 133.5 (C), 135.7 (CH); m/z (CI) 401 (MHþ, 3%) 339
(100), 261 (24), 209 (25), 167 (21), 143 (19), 117 (29).
4.1.13. Rearrangement of 13 using AuCl
The reaction was carried out as described above using (2E,4S)-
5-(tert-butyldiphenylsilyloxy)-4-(methoxymethoxy)pent-2-en-1-ol
12 (0.1 g, 0.5 mmol) and gold(I) chloride (10 mol %). Flash column
chromatography (elution with 5% diethyl ether/petroleum ether)
gave 14 followed by 15 as colourless oil (0.06 g, 40% combined yield,
1:3 ratio). Spectroscopic data as described above.
4.1.11. Rearrangement of 13 using PtCl2
(2E,4S)-5-(tert-Butyldiphenylsilyloxy)-4-(methoxymethoxy)-
pent-2-en-1-ol 12 (0.3 g, 0.75 mmol) was dissolved in dichloro-
methane (20 mL) and cooled to 0 ꢁC. Diazabicyclo[5.4.0]undec-7-
ene (0.13 mL, 0.9 mmol) was then added to the solution followed by
the addition of trichloroacetonitrile (0.1 mL, 1.1 mmol). The re-
action was warmed to room temperature and stirred for 2 h. The
reaction mixture was then filtered through a short pad of silica gel
and washed with diethyl ether (200 mL). The resulting filtrate was
then concentrated to give allylic trichloroacetimidate 13 as a brown
oil (0.41 g) that was used without further purification. dH (400 MHz,
CDCl3) 1.04 (9H, s t-Bu), 3.36 (3H, s, OMe), 3.64 (1H, dd, J 10.5,
5.1 Hz, 5-HH), 3.75 (1H, dd, J 10.5, 6.4 Hz, 5-HH), 4.23 (1H, q, J
6.4 Hz, 4-H), 4.64 (1H, d, J 6.7 Hz, OCHHO), 4.70 (1H, d, J 6.7 Hz,
OCHHO), 4.78 (2H, d, J 5.5 Hz, 1-H2), 5.79 (1H, dd, J 15.7, 6.4 Hz,
3-H), 5.93 (1H, dt, J 15.7, 5.5 Hz, 2-H), 7.35–7.45 (6H, m, Ar–H), 7.66–
7.71 (4H, m, Ar–H), 8.32 (1H, br s, NH). Allylic trichloroacetimidate
13 (0.41 g, 0.75 mmol) was dissolved in toluene (10 mL) under
a nitrogen atmosphere. Platinum(II) chloride (0.02 g, 0.08 mmol)
was then added to the solution and the reaction mixture was
stirred at room temperature overnight. The reaction mixture was
then filtered through a short pad of CeliteÒ, washed with diethyl
ether (100 mL) and concentrated under vacuum. Purification by
flash column chromatography (elution with 5% diethyl ether/
petroleum ether) gave (3R,4S)-5-(tert-butyldiphenylsilyloxy)-4-
methoxymethoxy-3-(trichloromethylcarbonylamino)pent-1-ene 14
4.1.14. Rearrangement of 13 using PdCl2(MeCN)2
The reaction was carried out as described above using (2E,4S)-
5-(tert-butyldiphenylsilyloxy)-4-(methoxymethoxy)pent-2-en-1-ol
12 (0.14 g, 0.25 mmol) and bis(acetonitrile)palladium(II) chloride
(10 mol %). Flash column chromatography (elution with 5% diethyl
ether/petroleum ether) gave 14 followed by 15 as colourless oil
(0.13 g, 68% combined yield, 1:4 ratio of diastereomers). Spectro-
scopic data as described above.
4.1.15. Rearrangement of 13 using (R)-COP-Cl
The reaction was carried out as described above using (2E,4S)-5-
(tert-butyldiphenylsilyloxy)-4-(methoxymethoxy)pent-2-en-1-ol
12 (0.14 g, 0.25 mmol), (R)-COP-Cl (10 mol %) and dichloromethane
(10 mL) as the solvent. Flash column chromatography (elution with
5% diethyl ether/petroleum ether) gave 14 followed by 15 as col-
ourless oil (0.13 g, 68% combined yield, 1:16 ratio of diastereomers).
Spectroscopic data as described above.
4.1.16. (2R,3S)-4-(tert-Butyldiphenylsilyloxy)-3-methoxymethoxy-
2-(trichloromethylcarbonylamino)butanoic acid 16
as
a
colourless oil. Further elution with 5% diethyl ether/
(3S,4S)-5-(tert-Butyldiphenylsilyloxy)-4-methoxymethoxy-3-
(trichloromethylcarbonylamino)pent-1-ene 15 (0.2 g, 0.37 mmol)
was dissolved in tetrachloromethane (7 mL) and acetonitrile (7 mL).
Sodium periodate (0.32 g, 1.5 mmol) in water (11 mL) was then
added to the solution. Ruthenium trichloride hydrate (4 mg,
0.03 mmol) was then added tothe biphasic solution and the reaction
mixture was then stirred vigorously at room temperature overnight.
The reaction mixture was then extracted with dichloromethane
(4ꢂ40 mL), dried (MgSO4) and concentrated in vacuo to yield the
petroleum ether gave (3S,4S)-5-(tert-butyldiphenylsilyloxy)-4-
methoxymethoxy-3-(trichloromethylcarbonylamino)pent-1-ene 15
as a colourless oil (0.105 g, 25% combined yield,1:4 ratio). Data for 14:
nmax/cmꢀ1 (neat) 3393 (NH), 2931 (CH),1717 (CO),1645 (C]C),1428,
25
1113, 1032, 822; [
a]
þ5.7 (c 1.0, CHCl3); dH (400 MHz, CDCl3) 1.09
D
(9H, s, t-Bu), 3.30 (3H, s, OMe), 3.65 (1H, dd, J 11.1, 8.0 Hz, 5-HH), 3.73
(1H, dd, J 11.1, 7.3 Hz, 5-HH), 3.88–3.92 (1H, m, 4-H), 4.62 (1H, d, J
7.1 Hz, OCHHO), 4.67 (1H, d, J 7.1 Hz, OCHHO), 4.81–4.84 (1H, m, 3-H),

M.D. Swift, A. Sutherland / Tetrahedron 64 (2008) 9521–9527
9527
crude product. The compound was then dissolved in an aqueous
Acknowledgements
solution of sodium hydrogen carbonate (10 mL), extracted with
ethyl acetate (2ꢂ10 mL) and re-acidified by addition of 2 M
hydrochloric acid (15 mL). The aqueous phase was extracted with
ethyl acetate (5ꢂ10 mL), dried (MgSO4) and concentrated in
vacuo to give (2R,3S)-4-(tert-butyldiphenylsilyloxy)-3-methoxy-
The authors gratefully acknowledge financial support from
EPSRC (studentship to M.D.S.) and the University of Glasgow.
References and notes
methoxy-2-(trichloromethylcarbonylamino)butanoic
acid
16
(0.15 g, 71%) as a colourless oil. nmax/cmꢀ1 (neat) 3334 (NH and
1. Overman, L. E.; Carpenter, N. E. Org. React. 2005, 66, 1–107 and references
therein.
2. (a) Fanning, K. N.; Jamieson, A. G.; Sutherland, A. Curr. Org. Chem. 2006, 10,
1007–1020; (b) Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Tetrahedron 2008,
64, 597–643.
24
OH), 2958 (CH), 1652 (CO), 1110, 1027, 820; [
a
]
ꢀ12.5 (c 1.5,
D
MeOH); dH (400 MHz, CD3OD) 0.98 (9H, s, t-Bu), 3.24 (3H, s, OMe),
3.85 (1H, dd, J 10.8, 6.3 Hz, 4-HH), 3.92 (1H, dd, J 10.8, 4.6 Hz, 4-
HH), 3.98–4.02 (1H, m, 3-H), 4.50 (1H, d, J 3.0 Hz, 2-H) 4.56 (1H, d,
J 6.8 Hz, OCHHO), 4.58 (1H, d, J 6.8 Hz, OCHHO), 7.22–7.36 (6H, m,
Ar–H), 7.58–7.63 (4H, m, Ar–H); dC (100 MHz, CD3OD) 20.1 (C), 27.2
(CH3), 56.4 (CH3), 57.8 (CH), 65.8 (CH2), 80.5 (CH), 93.8 (C), 98.2
(CH2), 128.6 (CH), 130.9 (CH), 134.5 (C), 136.8 (CH), 163.0 (C), 173.3
(C); m/z (CI) 562 (MHþ, 3%), 472 (4), 376 (5), 325 (10), 274 (100),
196 (30).
3. (a) Calter, M.; Hollis, T. K.; Overman, L. E.; Ziller, J.; Zipp, G. G. J. Org. Chem. 1997,
62, 1449–1456; (b) Hollis, T. K.; Overman, L. E. Tetrahedron Lett. 1997, 38, 8837–
8840; (c) Uozumi, Y.; Kato, K.; Hayashi, T. Tetrahedron: Asymmetry 1998, 9,
1065–1072; (d) Kang, J.; Kim, T. H.; Yew, K. H.; Lee, W. K. Tetrahedron: Asym-
metry 2003, 14, 415–418; (e) Overman, L. E.; Owen, C. E.; Pavan, M. M.; Richards,
C. J. Org. Lett. 2003, 5, 1809–1812; (f) Anderson, C. E.; Overman, L. E. J. Am. Chem.
Soc. 2003, 125, 12412–12413; (g) Kirsch, S. F.; Overman, L. E.; Watson, M. P.
J. Org. Chem. 2004, 69, 8101–8104; (h) Anderson, C. E.; Donde, Y.; Douglas, C. J.;
Overman, L. E. J. Org. Chem. 2005, 70, 648–657; (i) Weiss, M. E.; Fischer, D. F.;
Xin, Z.-Q.; Jautze, S.; Schweizer, W. B.; Peters, R. Angew. Chem., Int. Ed. 2006, 45,
5694–5698; (j) Jautze, S.; Seiler, P.; Peters, R. Angew. Chem., Int. Ed. 2007, 46,
1260–1264; (k) Watson, M. P.; Overman, L. E.; Bergman, R. G. J. Am. Chem. Soc.
2007, 129, 5031–5044.
4.1.17. (2R,3S)-2-Amino-3,4-dihydroxybutyric acid 117
(2R,3S)-4-(tert-Butyldiphenylsilyloxy)-3-methoxymethoxy-2-(tri-
chloromethylcarbonylamino)butanoic acid 16 (0.12 g, 0.20 mmol)
was dissolved in THF (10 mL). Tetrabutylammonium fluoride (1.0 M
solution in THF) (0.73 mL, 0.73 mmol) was then added and the
solution was stirred at room temperature overnight. The reaction
mixture was then concentrated and the residue redissolved in ethyl
acetate (15 mL). This was washed with water (15 mL), and then the
organic layer was dried (MgSO4) and concentrated to give a brown
oil (0.1 g). This oil was then dissolved in 6 M hydrochloric acid
solution (10 mL) and heated under reflux overnight. The reaction
mixture was cooled to room temperature and then extracted with
diethyl ether (10 mL). The aqueous phase was then concentrated in
vacuo to give the crude product. Purification by ion exchange
chromatography (elution with 0.5 M NH4OH solution) yielded
(2R,3S)-2-amino-3,4-dihydroxybutyric acid 1 as a white solid
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24
25
(11 mg, 44% over two steps). [
a
]
þ10.6 (c 0.5, H2O) (lit.17
[a]
D
D
þ11.4 (c 7.0, H2O)); dH (400 MHz, D2O) 3.58–3.69 (2H, m, 4-H2), 3.85
(1H, d, J 4.0 Hz, 2-H), 3.98–4.04 (1H, m, 3-H); m/z (CI) 136 (MHþ,
5%), 130 (100), 114 (30), 69 (29).
16. Kireev, A. S.; Manpadi, M.; Kornienko, A. J. Org. Chem. 2006, 71, 2630–2640.
´
´
´
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