Asymmetric synthesis of allylic secondary alcohols: Anewgeneral approach for the preparation of α-amino acids

Article abstract of DOI:10.1016/j.tet.2010.05.066

A new general approach for the synthesis of optically active a-amino acids has been developed.The key steps involve a ruthenium catalysed cross-coupling reaction to give a range of α,β-unsaturated ketones, which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine.A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these were converted under standard conditions to the target α-amino acids in good overall yields.

Full text of DOI:10.1016/j.tet.2010.05.066

Tetrahedron 66 (2010) 5349e5356
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Asymmetric synthesis of allylic secondary alcohols: a new general approach for
the preparation of
a
-amino acids
*
Lorna J. Drummond, 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:
A new general approach for the synthesis of optically active
a-amino acids has been developed. The key
Received 2 March 2010
Received in revised form 27 April 2010
Accepted 17 May 2010
steps involve a ruthenium catalysed cross-coupling reaction to give a range of a,b
which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine.
A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these
-unsaturated ketones,
Available online 9 June 2010
were converted under standard conditions to the target
a
-amino acids in good overall yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Overman rearrangement
Asymmetric reduction
Amino acids
Cross metathesis
1. Introduction
R
R'
Cl3CCN
Base
R
R'
HN
O
The crucial role and vital importance of a-amino acids both as
OH
structural building blocks for peptides and proteins and for nu-
merous biological functions are well established.1 As well as the 20
CCl3
proteinogenic a-amino acids, a significant number of structurally
Δ or Pd(II)
varied analogues have been found in nature from sources such as
bacteria and fungi.2 These have been used as key synthetic building
blocks for the preparation of a wide range of biologically and
pharmacologically active compounds, which are employed in the
pharmaceutical, agrochemical and food industries.3 Furthermore,
R
R'
R
CO2H
NH2
HN
O
modified a-amino acids are being increasingly used for the prep-
CCl3
aration of synthetic enzymes, hormones and immunostimulants as
well as finding application as biological probes.4 Structurally hin-
Scheme 1. Synthesis of a-amino acids using the Overman rearrangement.
dered
and peptidomimetics, which have enhanced metabolic stability.5
This widespread application of -amino acids in many disciplines
a-amino acids are also utilised in the design of new peptides
This approach can be used for the synthesis of optically active
-amino acids using either allylic alcohols prepared from the chiral
a
a
has resulted in the continued development of new methods for
pool8bed,g,jen or chiral palladium(II)-catalysts during the Overman
rearrangement.8i In addition to these methods, Walsh and co-
workers generated a series of allylic secondary alcohols in excellent
enantioselectivity by the addition of vinylzinc reagents to benzal-
dehyde in the presence of catalytic amounts of an isoborneol-de-
rived amino alcohol.8h Overman rearrangement and oxidation then
their synthesis.6
A strategy commonly employed for the synthesis of a wide range
of highly functionalised
a-amino acids involves the thermal or
palladium-catalysed Overman rearrangement of allylic tri-
chloroacetimidates7 followed by oxidation of the resulting alkene
moiety to the corresponding carboxylic acid (Scheme 1).8
gave the
a-amino acids in good yields. This remains the only
reported example of the use of asymmetric synthesis for the gen-
eral preparation of optically active allylic secondary alcohols for
direct application via the Overman rearrangement for
synthesis.
a-amino acid
* Corresponding author. Tel.: þ44 141 330 5936; fax: þ44 141 330 4888; e-mail
address: andrews@chem.gla.ac.uk (A. Sutherland).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.05.066

5350
L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
Table 1
Asymmetric reduction of
oxazaborolidine 9
We were interested in developing an alternative approach for
the general asymmetric synthesis of optically active allylic sec-
ondary alcohols for application in -amino acid synthesis. We now
report such an approach using cross-metathesis for the synthesis of
a series of -unsaturated ketones, which were then subjected to
asymmetric reduction using a CBS oxazaborolidine.9 The conver-
a
,b
-unsaturated ketones 4e8 using (S)-(ꢁ)-2-methyl-CBS-
a
Ph
Ph
a,b
O
N
B
O
OH
Me
sion of these optically active allylic secondary alcohols to
acids via the Overman rearrangement is also described.
a-amino
9
Ph
R
Ph
R
BH3.THF
20 oC, THF
2. Results and discussion
4 R = n-Bu
10 R = n-Bu
5 R = CH2CH2Ph
6 R = CH2t-Bu
11 R = CH2CH2Ph
12 R = CH2t-Bu
The initial stage of this work focused on a short and efficient
route to the key -unsaturated ketones from hydrocinnamic acid
7 R = CH2CH2CH2CN
13 R = CH2CH2CH2CN
14 R = (S)-CH2CH(OTBDMS)CH3
8 R = (S)-CH2CH(OTBDMS)CH3
a,b
as shown in Scheme 2. Hydrocinnamic acid 1 was selected as the
starting material as it is an inexpensive and readily available car-
boxylic acid with a side-chain unlikely to participate in any of the
subsequent reactions. Hydrocinnamic acid 1 was converted to the
morpholine amide 2 in 94% yield by conversion to the acid chloride
followed by reaction with morpholine.10 Treatment of 2 with
vinylmagnesium bromide gave the key cross metathesis partner,
vinyl ketone 3 in 74% yield. Cross metathesis of 3 with a series of
terminal alkenes was then done using Grubbs second generation
catalyst11 (4e5 mol %), which gave the corresponding E-alkenes
4e8 in modest to high yields (47e89%). Analysis of the crude ma-
terial from the cross metathesis reactions by 1H NMR spectroscopy
showed the presence of only the E-alkenes highlighting the excel-
lent stereoselectivity achieved using these types of cross metath-
esis partners.12
Entry
R
9 (equiv)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
CH2CH2CH2CH3
CH2CH2CH2CH3
CH2CH2CH2CH3
CH2CH2Ph
CH2C(CH3)3
CH2CH2CH2CN
(S)-CH2CH(OTBDMS)CH3
0.2
0.5
1.0
1.0
1.0
1.0
1.0
57
100
99
69
77
31
71
84
75
69
63
87
87
100c
a
Isolated yields.
Determined by chiral HPLC.
Single diastereomer.
b
c
alcohols 11e13 in high yields (63e77%) and enantioselectivities
(69e87%, entries 4e6). Reduction of chiral -unsaturated ketone
a,b
8 gave allylic alcohol 14 in 87% yield and as a single diastereomer
(entry 7).
O
The optically active allylic alcohols 10e13 were then converted
to the corresponding allyic trichloroacetamides 15e18 by prepa-
ration of the allylic trichloroacetimidates followed by an Overman
rearrangement (Scheme 3). Initially, the Overman rearrangement
was carried out using bis(acetonitrile)palladium(II) chloride.15 This
generated relatively complex mixtures, which yielded the allylic
trichloroacetamides in only modest yields (e.g., 39% for 15). Ther-
mal rearrangement in the presence of potassium carbonate was
more effective and gave allylic trichloroacetamides 15e18 more
cleanly and in higher yields over the two steps (67e100%).16 Oxi-
dation of the allylic trichloroacetamides was carried out according
a, b
CO2H
Ph
N
Ph
O
2
1
c
O
O
d
Ph
R
Ph
4 R = n-Bu (75%)
5 R = CH2CH2Ph (47%)
6 R = CH2t-Bu (58%)
3
7 R = CH2CH2CH2CN (53%)
8 R = (S)-CH2CH(OTBDMS)CH3 (89%)
CCl3
Scheme 2. Reagents and conditions: a. SOCl2 (neat), rt; b. morpholine, CH2Cl2, 0 ꢀC to
, 94% over two steps; c. vinylmagnesium bromide solution (1.0 M in THF), THF, 0 ꢀC,
74%; d. Grubbs second generation catalyst, CH2Cl2,
, H2C¼CHR.
OH
a, b
D
O
NH
D
Ph
R
Ph
R
10-13
15 R = n-Bu (67%)
16 R = CH2CH2Ph (73%)
17 R = CH2t-Bu (100%)
The next stage involved the asymmetric reduction of a,b-un-
18 R = CH2CH2CH2CN (81%)
saturated ketones 4e8 using CBS oxazaborolidine 9 (Table 1).
Optimised conditions were initially developed using (E)-1-phe-
nylnon-4-en-3-one 4. The use of catalytic amounts of CBS oxaza-
borolidines such as 9 for the asymmetric reduction of ketones is
well known and thus, our first attempt under standard conditions
employed 0.2 equiv of 9 (entry 1).13 However, this gave allylic al-
cohol 10 in only 57% yield and in 31% enantiomeric excess.14 The use
of 0.5 equiv of 9 led to a substantial increase in both the yield and
enantioselectivity (entry 2). The best results were obtained using
a stoichiometric amount of 9, which gave allylic alcohol 10 in 99%
yield and 84% enantiomeric excess (entry 3). As a stoichiometric
amount of 9 was required for generation of allylic alcohol 10 with
high enantioselectivity, these conditions were used to reduce the
c, d
CCl3
NH2
e
O
NH
HO2C
R
MeO2C
R
23 R = n-Bu (98%)
19 R = n-Bu (34%)
24 R = CH2CH2Ph (100%)
25 R = CH2t-Bu (100%)
20 R = CH2CH2Ph (42%)
21 R = CH2t-Bu (62%)
22 R = CH2CH2CH2CN (58%)
26 R = CH2CH2CH2CONH2 (100%)
Scheme 3. Reagents and conditions: a. Cl3CCN, DBU, CH2Cl2; b.
D, K2CO3, p-xylene;
remaining
a
,b
-unsaturated ketones (entries 4e7). This gave allylic
c. RuCl3$xH2O, NaIO4, CCl4, MeCN, H2O; d. SOCl2, MeOH, ; e. 6 M HCl, D.
D

L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
5351
to the Sharpless protocol using catalytic ruthenium(III) trichloride
hydrate and sodium metaperiodate.17 The resulting carboxylic acids
were then converted to methyl esters 19e22 before isolation and
purification. Finally, deprotection under standard acidic conditions
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 rela-
tive to tetramethylsilane as the standard. Proton and carbon as-
signments are based on two-dimensional COSY and DEPT
experiments, respectively. Infrared spectra were recorded using
sodium chloride or potassium chloride plates on a JASCO FTIR 410
spectrometer and mass spectra were obtained using a JEOL JMS-
700 spectrometer. Optical rotations were determined as solutions
gave the desired a
-amino acids 23e26 in good overall yield.18 It
should be noted that acid hydrolysis of 22 also led to conversion of
the side-chain nitrile to the corresponding amide 26.
In a similar fashion, allylic trichloroacetimidate 27 was formed
in 87% yield (over two steps) from 14 using a thermal Overman
rearrangement (Scheme 4). Attempted oxidation of 27 using the
standard Sharpless ruthenium(III)/sodium metaperiodate protocol
resulted in very low yields of the corresponding carboxylic acid and
subsequent methyl ester. Therefore, a modified procedure using
potassium permanganate19 was employed and the resulting car-
boxylic acid was converted to methyl ester 28 using trimethylsi-
irradiating with the sodium D line (
l
¼589 nm) using an AA series
Automatic polarimeter.
[
a
]
D
values are given in units
10ꢁ1 deg cm2 gꢁ1. The chiral HPLC methods were calibrated with
their corresponding racemic mixtures.
4.1.1. 1-Morpholin-4-yl-3-phenylpropan-1-one (2)21. A stirred so-
lution of hydrocinnamic acid 1 (0.50 g, 3.33 mmol) in thionyl
chloride (1.20 mL, 16.7 mmol) was allowed to stir at room tem-
perature for 4.5 h before being concentrated in vacuo. Toluene
(2ꢂ20 mL) was used to azeotrope the residue to give 3-phenyl-
propionyl chloride as a yellow oil (0.55 g, 97%), which was used
without further purification. dH (400 MHz, CDCl3) 3.02 (2H, t, J
7.4 Hz, 3-H2), 3.21 (2H, t, J 7.4 Hz, 2-H2), 7.17e7.34 (5H, m, 5ꢂArH).
lyldiazomethane. Acid mediated deprotection of 28 gave (2S,4S)-g-
hydroxynorvaline 29 (30% yield over the three steps), which
showed optical activity and NMR spectra consistent with published
values.20
CCl3
OH
OTBDMS
A
stirred solution of 3-phenylpropionyl chloride (0.55 g,
a, b
O
NH
OTBDMS
3.24 mmol) in dichloromethane (10 mL) was cooled to 0 ꢀC, and
morpholine (1.42 mL, 16.2 mmol) was added dropwise. The
resulting suspension was heated under reflux for 20 h. The re-
action mixture was allowed to cool to room temperature and
dichloromethane (50 mL) was added. The organic layer was
washed with water (2ꢂ30 mL) and then dried (MgSO4), filtered
and concentrated in vacuo. Purification was carried out by flash
column chromatography and elution with 1:1 ethyl acetate/pe-
troleum ether gave 1-morpholin-4-yl-3-phenylpropan-1-one 2 as
a pale yellow oil (0.68 g, 94%). Rf (50% EtOAc/petroleum ether)
0.17; dH (400 MHz, CDCl3) 2.62 (2H, t, J 7.6 Hz, CH2), 2.98 (2H, t, J,
7.6 Hz, CH2), 3.36 (2H, t, J 4.4 Hz, CH2), 3.51 (2H, t, J 4.4 Hz, CH2),
3.60e3.65 (4H, m, 2ꢂCH2), 7.21e7.31 (5H, m, 5ꢂArH); dC
(100 MHz, CDCl3) 31.5 (CH2), 34.9 (CH2), 42.0 (CH2), 46.0 (CH2),
66.5 (CH2), 66.9 (CH2), 126.3 (CH), 128.5 (2ꢂCH), 128.6 (2ꢂCH),
141.1 (C), 171.0 (C); m/z (CI) 220 (MHþ, 100%), 219 (7), 172 (2), 130
(1), 81 (3).
Ph
Ph
14
27
c, d
CCl3
NH2 OH
e
O
NH
OTBDMS
HO2C
MeO2C
28
29
Scheme 4. Reagents and conditions: a. Cl3CCN, DBU, CH2Cl2; b.
87%; c. KMnO4, NaIO4, K2CO3, t-BuOH, H2O; d. TMSCHN2, MeOH, toluene; e. 6 M HCl, D,
30% over three steps.
D
, K2CO3, p-xylene,
3. Conclusion
4.1.2. 5-Phenylpent-1-en-3-one (3)22. A stirred solution of 1-mor-
pholin-4-yl-3-phenylpropan-1-one 2 (0.55 g, 2.50 mmol) in THF
(20 mL) was cooled to 0 ꢀC before vinylmagnesium bromide solu-
tion (1.0 M in THF, 10 mL, 10 mmol) was added dropwise. The re-
action mixture was stirred at 0 ꢀC for 2 h before being quenched by
pouring into glacial acetic acid (10 mL) and then concentrated in
vacuo. The residue was then partitioned between dichloromethane
(50 mL) and a saturated solution of ammonium chloride (50 mL)
and the organic phase was dried (MgSO4), filtered and concentrated
in vacuo. Purification was carried out by flash column chromatog-
raphy, and elution with 1:9 ethyl acetate/petroleum ether gave
5-phenylpent-1-en-3-one 3 as a colourless oil (0.30 g, 74%). Rf (50%
EtOAc/petroleum ether) 0.69; dH (400 MHz, CDCl3) 2.89e2.98 (4H,
m, 4-H2 and 5-H2), 5.83 (1H, d, J 10.8 Hz, 1-HH), 6.22 (1H, d, J
17.6 Hz, 1-HH), 6.36 (1H, dd, J 17.6, 10.8 Hz, 2-H), 7.20e7.31 (5H, m,
5ꢂArH); dC (100 MHz, CDCl3) 29.8 (CH2), 41.2 (CH2), 126.1 (CH),
128.3 (CH2), 128.4 (2ꢂCH), 128.5 (2ꢂCH), 136.5 (CH), 141.1 (C), 199.8
(C); m/z (CI) 161 (MHþ, 100%), 160 (5), 91 (3).
In summary, a new general approach for the preparation of
optically active allylic secondary alcohols has been developed using
a ruthenium catalysed cross metathesis reaction and a CBS oxaza-
borolidine mediated reduction as the key steps. Conversion to the
allylic trichloroacetimidates followed by a thermal Overman rear-
rangement gave the corresponding allylic trichloroacetamides,
which were oxidised and deprotected to give a series of
acids. While we have synthesised only -amino acids in this project,
both enantiomers of CBS oxazaborolidine 9 are commercially
available and hence, access to both - and -amino acids should
be possible using this approach. Further application of this work for
a-amino
L
L
D-a
the preparation of novel non-proteinogenic
rently underway.
a-amino acids is cur-
4. Experimental section
4.1. General methods
All reagents and starting materials were obtained from com-
mercial sources and used as received. All dry solvents were purified
using a PureSolv 500 MD solvent purification system. All reactions
were performed under an atmosphere of argon unless otherwise
mentioned. Flash column chromatography was carried out using
Fisher matrix silica 60. MachereyeNagel aluminium-backed plates
pre-coated with silica gel 60 (UV254) were used for thin layer
4.1.3. (5E)-9-Phenylnon-5-en-7-one (4)23. To a stirred solution of
Grubbs second generation catalyst (0.26 g, 0.31 mmol) in
dichloromethane (20 mL), 5-phenylpent-1-en-3-one
3 (1.00 g,
6.24 mmol) dissolved in dichloromethane (10 mL) was added, fol-
lowed by 1-hexene (1.55 mL, 12.5 mmol). The reaction mixture was
then heated under reflux for 22 h before being concentrated in

5352
L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
vacuo and purified by flash column chromatography. Elution with
1:19 ethyl acetate/petroleum ether gave (5E)-9-phenylnon-5-en-7-
one 4 as a brown oil (0.99 g, 75%). Rf (20% EtOAc/petroleum ether)
0.68; dH (400 MHz, CDCl3) 0.91 (3H, t, J 7.2 Hz, 1-H3), 1.30e1.49 (4H,
m, 2-H2 and 3-H2), 2.17e2.23 (2H, m, 4-H2), 2.84e2.96 (4H, m, 8-H2
and 9-H2), 6.09 (1H, dt, J 15.6, 1.6 Hz, 6-H), 6.82 (1H, dt, J 15.6,
7.2 Hz, 5-H), 7.17e7.30 (5H, m, 5ꢂArH); dC (100 MHz, CDCl3) 13.9
(CH3), 22.3 (CH2), 30.1 (CH2), 30.2 (CH2), 32.2 (CH2), 41.6 (CH2),
126.1 (CH), 128.4 (2ꢂCH), 128.5 (2ꢂCH), 130.3 (CH), 141.3 (C), 147.9
(CH), 199.7 (C); m/z (CI) 217 (MHþ, 100%), 203 (15), 189 (4), 159 (9),
97 (5), 85 (32), 69 (29).
131.6 (CH), 141.1 (C), 143.9 (CH), 199.1 (C); m/z (EI) 227 (Mþ, 3%), 207
(3), 159 (20), 122 (9), 105 (16), 91 (16), 77 (18); HRMS (EI): Mþ,
found 227.1308. C15H17NO requires 227.1310.
4.1.7. (4S)-4-[(tert-Butyldimethylsilyl)oxy]-1-pentene25. To a stirred
solution of (4S)-(þ)-4-penten-2-ol (0.62 g, 7.23 mmol) in
dichloromethane (30 mL), triethylamine (2.00 mL, 14.5 mmol) and
4-dimethylaminopyridine (0.09 g, 0.72 mmol) were added. This
solution was then cooled to 0 ꢀC before tert-butyldimethylsilyl
chloride (1.42 g, 9.40 mmol) was added slowly. The resulting re-
action mixture was allowed to stir at 0 ꢀC for 0.2 h, and then at
room temperature for 21 h before water (50 mL) and dichloro-
methane (20 mL) were added. The layers were separated and the
aqueous layer was further extracted using dichloromethane
(30 mL). The combined organic layers were then washed with
a saturated solution of aqueous copper sulfate (2ꢂ40 mL) and
water (40 mL) before being dried (MgSO4), filtered and concen-
trated in vacuo. Purification was carried out by flash column
chromatography, and elution with 1:30 diethyl ether/petroleum
ether gave (4S)-4-[(tert-butyldimethylsilyl)oxy]-1-pentene as
a colourless oil (0.75 g, 52%). Rf (20% EtOAc/petroleum ether) 0.62;
4.1.4. 1,7-Diphenylhept-3-en-5-one (5)24. The reaction was carried
out as described for 4 using 5-phenylpent-1-en-3-one 3 (0.50 g,
3.13 mmol), 4-phenyl-1-butene (0.94 mL, 6.27 mmol) and Grubbs
second generation catalyst (0.11 g, 0.13 mmol). Purification by
flash column chromatography, eluting with 3:17 diethyl ether/
petroleum ether gave 1,7-diphenylhept-3-en-5-one 5 as a col-
ourless oil (0.39 g, 47%). Rf (20% EtOAc/petroleum ether) 0.53; dH
(400 MHz, CDCl3) 2.47e2.53 (2H, m, 2-H2), 2.77 (2H, t, J 7.2 Hz, 1-
H2), 2.81e2.95 (4H, m, 6-H2 and 7-H2), 6.11 (1H, d, J 15.8 Hz, 4-
H), 6.84 (1H, dt, J 15.8, 7.2 Hz, 3-H), 7.14e7.32 (10H, m, 10ꢂArH);
dC (100 MHz, CDCl3) 30.1 (CH2), 34.1 (CH2), 34.4 (CH2), 41.7 (CH2),
126.1 (CH), 126.2 (CH), 128.3 (2ꢂCH), 128.4 (2ꢂCH), 128.5
(4ꢂCH), 130.7 (CH), 140.7 (C), 141.2 (C), 146.3 (CH), 199.5 (C); m/z
(EI) 264 (Mþ, 13%), 159 (54), 131 (8), 105 (15), 91 (100), 65 (12),
44 (49).
[
a
]
24 þ18.1 (c 1.0, CHCl3); dH (400 MHz, CDCl3) 0.05 (6H, s, 2ꢂSiCH3),
D
0.89 (9H, s, SiC(CH3)3), 1.13 (3H, d, J 6.0 Hz, 5-H3), 2.11e2.25 (2H, m,
3-H2), 3.84 (1H, q, J 6.0 Hz, 4-H), 4.99e5.06 (2H, m,1-H2), 5.75e5.86
(1H, m, 2-H); dC (100 MHz, CDCl3) ꢁ5.7 (CH3), ꢁ5.6 (CH3), 17.2 (C),
22.4 (CH3), 24.9 (3ꢂCH3), 43.3 (CH2), 67.4 (CH), 115.5 (CH2), 134.6
(CH); m/z (CI) 201 (MHþ, 4%), 193 (9), 167 (8), 151 (7), 113 (29), 95
(22), 69 (100).
4.1.5. (4E)-2,2-Dimethyl-8-phenyloct-4-en-6-one (6). The reaction
was carried out as described for 4 using 5-phenylpent-1-en-3-one 3
(0.77 g, 4.80 mmol), 4,4-dimethyl-1-pentene (1.40 mL, 9.60 mmol)
and Grubbs second generation catalyst (0.16 g, 0.19 mmol). Purifi-
cation was carried out by flash column chromatography, and elu-
tion with 1:9 ethyl acetate/petroleum ether gave (4E)-2,2-
dimethyl-8-phenyloct-4-en-6-one 6 as a yellow oil (0.65 g, 58%). Rf
(20% EtOAc/petroleum ether) 0.65; nmax (NaCl) 2960 (CH), 1670
4.1.8. (2S,4E)-2-[(tert-Butyldimethylsilyl)oxy]-8-phenyloct-4-en-6-
one (8). The reaction was carried out as described for 4 using
5-phenylpent-1-en-3-one
3 (0.10 g, 0.62 mmol), (4S)-4-[(tert-
butyldimethylsilyl)oxy]-1-pentene (0.15 g, 0.75 mmol) and Grubbs
second generation catalyst (0.03 g, 0.03 mmol). Purification was
carried out by flash column chromatography, and elution with 1:19
diethyl ether/petroleum ether gave (2S,4E)-2-[(tert-butyldime-
thylsilyl)oxy]-8-phenyloct-4-en-6-one 8 as a colourless oil (0.18 g,
89%). Rf (20% EtOAc/petroleum ether) 0.59; nmax (NaCl) 2929 (CH),
(CO), 1474, 1367, 1095, 908, 734 cmꢁ1
; dH (400 MHz, CDCl3) 0.92
(9H, s, C(CH3)3), 2.08 (2H, d, J 8.0 Hz, 3-H2), 2.85e2.96 (4H, m, 7-H2
and 8-H2), 6.08 (1H, d, J 15.6 Hz, 5-H), 6.84 (1H, dt, J 15.6, 8.0 Hz, 4-
H), 7.17e7.31 (5H, m, 5ꢂArH); dC (100 MHz, CDCl3) 29.4 (3ꢂCH3),
30.2 (CH2), 31.5 (C), 41.7 (CH2), 47.0 (CH2), 126.1 (CH), 128.4 (2ꢂCH),
128.5 (2ꢂCH), 132.3 (CH), 141.3 (C), 145.2 (CH), 199.4 (C); m/z (EI)
230 (Mþ, 12%), 215 (11), 174 (6), 159 (100), 105 (18), 91 (46), 84 (42),
57 (56); HRMS (EI): Mþ, found 230.1674. C16H22O requires 230.1671.
1674 (CO), 1632, 1454, 1375, 1256, 1128, 1003, 836 cmꢁ1; [
a]
22 þ14.2
D
(c 1.0, CHCl3); dH (400 MHz, CDCl3) 0.03 (3H, s, SiCH3), 0.04 (3H, s,
SiCH3), 0.87 (9H, s, SiC(CH3)3), 1.14 (3H, d, J 6.5 Hz, 1-H3), 2.32 (2H, t,
J 6.5 Hz, 3-H2), 2.84e2.96 (4H, m, 7-H2 and 8-H2), 3.92 (1H, sex, J
6.5 Hz, 2-H), 6.10 (1H, d, J 16.0 Hz, 5-H), 6.83 (1H, dt, J 16.0, 6.5 Hz,
4-H), 7.18e7.30 (5H, m, 5ꢂArH); dC (100 MHz, CDCl3) ꢁ4.7 (CH3),
ꢁ4.4 (CH3), 18.1 (C), 23.9 (CH3), 25.9 (3ꢂCH3), 30.1 (CH2), 41.5 (CH2),
42.8 (CH2), 67.7 (CH), 126.1 (CH), 128.4 (2ꢂCH), 128.6 (2ꢂCH), 132.3
(CH), 141.3 (C), 144.5 (CH), 199.4 (C); m/z (CI) 333 (MHþ, 81%), 275
(11), 237 (9), 201 (9), 181 (9), 159 (43), 137 (12), 97 (53), 71 (100);
HRMS (CI): MHþ, found 333.2253. C20H33O2Si requires 333.2250.
4.1.6. (4E)-1-Nitrile-8-phenyloct-4-en-6-one (7). To a stirred solu-
tion of 5-phenylpent-1-en-3-one
3 (0.97 g, 6.07 mmol) in
dichloromethane (25 mL), 5-hexenenitrile (1.2 mL, 10.6 mmol),
Grubbs second generation catalyst (0.21 g, 0.24 mmol) was added.
The reaction mixture was then heated under reflux for 22 h before
further Grubbs second generation catalyst (0.10 g, 0.12 mmol) was
added and the reaction was stirred at 45 ꢀC for 50 h. Then, further
Grubbs second generation catalyst (0.10 g, 0.12 mmol) was added
and the reaction was stirred at 45 ꢀC for 72 h before further Grubbs
second generation catalyst (0.05 g, 0.06 mmol) was added. The
reaction was then stirred at 45 ꢀC for a further 24 h before being
concentrated in vacuo. Purification was carried out by flash column
chromatography, and elution with 1:3 ethyl acetate/petroleum
ether gave (4E)-1-nitrile-8-phenyloct-4-en-6-one 7 as a pale brown
oil (0.53 g, 53%). Rf (20% EtOAc/petroleum ether) 0.15; nmax (NaCl)
4.1.9. (5E,7R)-9-Phenylnon-5-en-7-ol (10)26. A stirred solution of
(5E)-9-phenylnon-5-en-7-one 4 (0.29 g, 1.30 mmol) in THF (10 mL)
was cooled to ꢁ20 ꢀC before (S)-(ꢁ)-2-methyl-CBS-oxazaborolidine
solution (1.0 M in toluene) (1.30 mL, 1.30 mmol) was added, fol-
lowed by boraneeTHF complex solution (1.0 M in THF) (4.00 mL,
4.00 mmol). The reaction mixture was then stirred at ꢁ20 ꢀC for
2.5 h before being quenched by the slow addition of methanol
(15 mL). Once gas evolution ceased, the reaction mixture was
concentrated in vacuo and purification was carried out by flash
column chromatography. Elution with 1:19 ethyl acetate/petro-
leum ether gave (5E,7R)-9-phenylnon-5-en-7-ol 10 as a colourless
oil (0.29 g, 99%). Chiral HPLC (Chiralcel IB column) analysis using 2%
isopropanol in hexane as the elution solvent indicated 84% ee. Rf
(20% EtOAc/petroleum ether) 0.39; dH (400 MHz, CDCl3) 0.90 (3H, t,
J 7.2 Hz, 1-H3), 1.26e1.40 (4H, m, 2-H2 and 3-H2), 1.45 (1H, br s, OH),
1.75e1.93 (2H, m, 4-H2), 1.99e2.07 (2H, m, 8-H2), 2.62e2.79 (2H, m,
3028 (CH), 2934 (CH), 2246 (CN), 1669 (CO), 1453, 978, 701 cmꢁ1
;
dH (400 MHz, CDCl3) 1.78e1.87 (2H, m, 1-H2), 2.32e2.42 (4H, m, 2-
H2 and 3-H2), 2.84e2.98 (4H, m, 7-H2 and 8-H2), 6.13 (1H, d, J
15.8 Hz, 5-H), 6.73 (1H, dt, J 15.8, 6.8 Hz, 4-H), 7.16e7.33 (5H, m,
5ꢂAr); dC (100 MHz, CDCl3) 16.7 (CH2), 23.8 (CH2), 30.0 (CH2), 31.0
(CH2), 42.2 (CH2), 119.0 (C), 126.2 (CH), 128.4 (2ꢂCH), 128.5 (2ꢂCH),

L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
5353
9-H2), 4.09 (1H, m, 7-H), 5.49 (1H, ddt, J 15.2, 6.8, 1.2 Hz, 6-H), 5.66
(1H, dt, J 15.2, 6.8 Hz, 5-H), 7.16e7.30 (5H, m, 5ꢂArH); dC (100 MHz,
CDCl3) 14.0 (CH3), 22.2 (CH2), 31.4 (CH2), 31.8 (CH2), 31.9 (CH2), 38.9
(CH2), 72.5 (CH), 125.8 (CH), 128.4 (3ꢂCH), 128.5 (2ꢂCH), 132.7
(CH),142.0 (C); m/z (CI) 201 (MHþꢁH2O,100%),187 (11),167 (4),133
(6), 117 (7), 91 (13).
(2ꢂCH), 135.1 (CH), 141.8 (C); m/z (CI) 230 (MHþ, 10%), 212 (100),
184 (8), 149 (4), 107 (27), 79 (30); HRMS (CI): MHþ, found 230.1555.
C15H20NO requires 230.1545.
4.1.13. (2S,4E,6R)-2-[(tert-Butyldimethylsilyl)oxy]-8-phenyloct-4-en-
6-ol (14). The reaction was carried out as described for 10 using
(2S,4E)-2-[(tert-butyldimethylsilyl)oxy]-8-phenyloct-4-en-6-one 8
(0.50 g, 1.50 mmol), (S)-(ꢁ)-2-methyl-CBS-oxazaborolidine solu-
tion (1.0 M in toluene) (1.50 mL, 1.50 mmol) and boraneeTHF
complex solution (1.0 M in THF) (7.52 mL, 7.52 mmol). Purification
by flash column chromatography with 3:17 diethyl ether/petro-
leum ether gave (2S,4E,6R)-2-[(tert-butyldimethylsilyl)oxy]-8-
phenyloct-4-en-6-ol 14 as a colourless oil (0.44 g, 87%). Rf (20%
EtOAc/petroleum ether) 0.43; nmax (NaCl) 3395 (OH), 2961 (CH),
4.1.10. (3E,5R)-1,7-Diphenylhept-3-en-5-ol (11). The reaction was
carried out as described for 10 using 1,7-diphenylhept-3-en-5-one
5 (0.19 g, 0.72 mmol), (S)-(ꢁ)-2-methyl-CBS-oxazaborolidine solu-
tion (1.0 M in toluene) (0.72 mL, 0.72 mmol) and boraneeTHF
complex solution (1.0 M in THF) (2.20 mL, 2.20 mmol). Purification
by flash column chromatography with 3:17 ethyl acetate/petro-
leum ether gave (3E,5R)-1,7-diphenylhept-3-en-5-ol 11 as a col-
ourless oil (0.13 g, 69%). Chiral HPLC (Chiralcel IB column) analysis
using 4% isopropanol in hexane as the elution solvent indicated 75%
ee. Rf (20% EtOAc/petroleum ether) 0.32; nmax (NaCl) 3356 (OH),
1639, 1455, 1254, 1084, 835, 774 cmꢁ1; [
a]
22 þ17.1 (c 1.0, CHCl3); dH
D
(400 MHz, CDCl3) 0.05 (6H, s, 2ꢂSiCH3), 0.88 (9H, s, SiC(CH3)3), 1.12
(3H, d, J 6.0 Hz, 1-H3), 1.43 (1H, br s, OH), 1.76e1.93 (2H, m, 7-H2),
2.10e2.25 (2H, m, 3-H2), 2.63e2.76 (2H, m, 8-H2), 3.83 (1H, sex, J
6.0 Hz, 2-H), 4.05e4.13 (1H, m, 6-H), 5.53 (1H, dd, J 15.4, 6.9 Hz,
5-H), 5.67 (1H, dt, J 15.4, 6.9 Hz, 4-H), 7.15e7.31 (5H, m, 5ꢂArH); dC
(100 MHz, CDCl3) ꢁ4.7 (CH3), ꢁ4.5 (CH3), 18.2 (C), 23.5 (CH3), 25.9
(3ꢂCH3), 31.8 (CH2), 38.8 (CH2), 42.6 (CH2), 68.5 (CH), 75.5 (CH),
125.8 (CH), 128.4 (2ꢂCH), 128.5 (2ꢂCH), 129.0 (CH), 135.0 (CH),
142.0 (C); m/z (FAB) 357 (MNaþ, 100%), 333 (21), 268 (18), 228 (17),
186 (18), 160 (86), 148 (38), 117 (78), 105 (24), 75 (77); HRMS (FAB):
MNaþ, found 357.2221. C20H34NaO2Si requires 357.2226.
2925 (CH), 1602, 1454, 970, 698 cmꢁ1
; dH (400 MHz, CDCl3) 1.40
(1H, d, J 3.2 Hz, OH), 1.70e1.90 (2H, m, 6-H2), 2.37 (2H, dt, J 7.6,
6.8 Hz, 2-H2), 2.57e2.73 (4H, m, 1-H2 and 7-H2), 4.02e4.10 (1H, m,
5-H), 5.50 (1H, dd, J 15.6, 7.0 Hz, 4-H), 5.69 (1H, dt, J 15.6, 6.8 Hz,
3-H), 7.15e7.30 (10H, m, 10ꢂArH); dC (100 MHz, CDCl3) 31.7 (CH2),
33.9 (CH2), 35.6 (CH2), 38.7 (CH2), 72.3 (CH), 125.8 (CH), 125.9 (CH),
128.3 (2ꢂCH), 128.4 (2ꢂCH), 128.5 (4ꢂCH), 131.4 (CH), 133.5 (CH),
141.6 (C), 142.0 (C); m/z (EI) 266 (Mþ, 3%), 248 (10), 161 (21), 144
(28), 105 (42), 91 (100), 83 (18); HRMS (EI): Mþ, found 266.1674.
C19H22O requires 266.1671.
4.1.14. (5S,6E)-9-Phenyl-5-(trichloromethylcarbonylamino)non-6-
ene (15). A stirred solution of (5E,7R)-9-phenylnon-5-en-7-ol 10
(0.25 g, 1.20 mmol) in dichloromethane (10 mL) was cooled to 0 ꢀC
before 1,8-diazabicyclo[5.4.0]undec-7-ene (0.09 mL, 0.60 mmol)
was added, followed by trichloroacetonitrile (0.18 mL, 1.80 mmol).
The reaction mixture was stirred at 0 ꢀC for 0.2 h, and then at room
temperature for 26 h. The mixture was then filtered through a plug
of silica and washed with diethyl ether (50 mL) and the filtrates
were concentrated in vacuo to give a yellow oil (0.48 g). The crude
residue was then dissolved in p-xylene (20 mL) and potassium
carbonate (0.06 g) was added. The reaction mixture was then
heated under reflux for 24 h before being concentrated in vacuo.
Purification was carried out by flash column chromatography, and
elution with 1:19 ethyl acetate/petroleum ether gave (5S,6E)-9-
phenyl-5-(trichloromethylcarbonylamino)non-6-ene 15 as a col-
ourless oil (0.28 g, 67%). Rf (20% EtOAc/petroleum ether) 0.61; nmax
4.1.11. (4E,6R)-2,2-Dimethyl-8-phenyloct-4-en-6-ol (12). The re-
action was carried out as described for 10 using (2E)-2,2-dimethyl-
8-phenyloct-4-en-6-one 6 (0.20 g, 0.87 mmol), (S)-(ꢁ)-2-methyl-
CBS-oxazaborolidine solution (1.0 M in toluene) (0.90 mL,
0.90 mmol) and boraneeTHF complex solution (1.0 M in THF)
(2.60 mL, 2.60 mmol). Purification by flash column chromatogra-
phy with 1:9 ethyl acetate/petroleum ether gave (4E,6R)-2,2-di-
methyl-8-phenyloct-4-en-6-ol 12 as a colourless oil (0.16 g, 77%).
Chiral HPLC (Chiralcel IB column) analysis using 3% isopropanol in
hexane as the elution solvent indicated 69% ee. Rf (20% EtOAc/pe-
troleum ether) 0.44; nmax (NaCl) 3609 (OH), 3019 (CH), 1475, 1216,
772 cmꢁ1
; dH (400 MHz, CDCl3) 0.89 (9H, s, C(CH3)3), 1.45 (1H, d, J
3.6 Hz, OH), 1.76e1.98 (4H, m, 3-H2 and 7-H2), 2.63e2.76 (2H, m,
8-H2), 4.07e4.14 (1H, m, 4-H), 5.49 (1H, dd, J 15.2, 7.2 Hz, 5-H), 5.69
(1H, dt, J 15.2, 7.6 Hz, 4-H), 7.16e7.31 (5H, m, 5ꢂArH); dC (100 MHz,
CDCl3) 29.3 (3ꢂCH3), 30.9 (C), 31.8 (CH2), 38.9 (CH2), 46.7 (CH2),
72.5 (CH), 125.8 (CH), 128.3 (2ꢂCH), 128.4 (2ꢂCH), 129.5 (CH), 135.1
(CH), 142.0 (C); m/z (EI) 232 (Mþ, 7%), 214 (9), 161 (26), 143 (24), 127
(46), 91 (100), 83 (51), 57 (98); HRMS (EI): Mþ, found 232.1830.
C16H24O requires 232.1827.
(NaCl) 3423 (NH), 2933 (CH), 1712 (CO), 1509, 908, 741 cmꢁ1
; dH
(400 MHz, CDCl3) 0.89 (3H, t, J 7.0 Hz, 1-H3), 1.21e1.36 (4H, m, 2-H2
and 3-H2), 1.54e1.59 (2H, m, 4-H2), 2.37 (2H, dt, J 7.4, 7.4 Hz, 8-H2),
2.70 (2H, t, J 7.4 Hz, 9-H2), 4.29e4.36 (1H, m, 5-H), 5.35 (1H, dd, J
15.6, 6.4 Hz, 6-H), 5.69 (1H, dt, J 15.6, 7.4 Hz, 7-H), 6.43 (1H, br d, J
7.6 Hz, NH), 7.13e7.30 (5H, m, 5ꢂArH); dC (100 MHz, CDCl3) 13.9
(CH3), 22.4 (CH2), 27.7 (CH2), 34.0 (CH2), 34.5 (CH2), 35.4 (CH2), 53.2
(CH), 92.9 (C), 125.9 (CH), 128.3 (2ꢂCH), 128.5 (2ꢂCH), 129.2 (CH),
132.2 (CH), 141.1 (C), 160.9 (C); m/z (CI) 362 (MHþ, 27%), 329 (46),
293 (80), 259 (35), 233 (76), 219 (100), 201 (36), 145 (51), 101 (25),
81 (48), 71 (46); HRMS (CI): MHþ, found 362.0842. C17H2335Cl3NO
requires 362.0845.
4.1.12. (4E,6R)-1-Nitrile-8-phenyloct-4-en-6-ol (13). The reaction
was carried out as described for 10 using (4E)-1-nitrile-8-phenyl-
oct-4-en-6-one 7 (0.15 g, 0.65 mmol), (S)-(ꢁ)-2-methyl-CBS-oxa-
zaborolidine solution (1.0 M in toluene) (0.65 mL, 0.65 mmol) and
boraneeTHF complex solution (1.0 M in THF) (1.95 mL, 1.95 mmol).
Purification was carried out by flash column chromatography, and
elution with 3:7 ethyl acetate/petroleum ether gave (4E,6R)-1-ni-
trile-8-phenyloct-4-en-6-ol as a colourless oil (0.10 g, 63%). Chiral
HPLC (Chiralcel IB column) analysis using 6% isopropanol in hexane
as the elution solvent indicated 87% ee. Rf (20% EtOAc/petroleum
ether) 0.09; nmax (NaCl) 3448 (OH), 2932 (CH), 2251 (CN), 1454, 910,
4.1.15. (3S,4E)-1,7-Diphenyl-3-(trichloromethylcarbonylamino)hept-
4-ene (16). The reaction was carried out as described for 15 using
(3E,5R)-1,7-diphenylhept-3-en-5-ol 11 (0.10 g, 0.37 mmol), 1,8-
diazabicyclo[5.4.0]undec-7-ene (0.03 mL, 0.18 mmol) and tri-
chloroacetonitrile (0.06 mL, 0.55 mmol). Purification was carried
out by flash column chromatography, and elution with 1:9 ethyl
731 cmꢁ1
; dH (400 MHz, CDCl3) 1.47e1.51 (1H, m, OH), 1.71e1.77
(2H, m, 2-H2), 1.78e1.93 (2H, m, 7-H2), 2.19e2.25 (2H, m, 3-H2),
2.35 (2H, t, J 7.2 Hz, 1-H2), 2.62e2.77 (2H, m, 8-H2), 4.07e4.14 (1H,
m, 6-H), 5.59e5.62 (2H, m, 4-H and 5-H), 7.17e7.32 (5H, m, 5ꢂArH);
dC (100 MHz, CDCl3) 16.5 (CH2), 24.7 (CH2), 31.0 (CH2), 31.8 (CH2),
38.8 (CH2), 72.1 (CH), 119.6 (C), 125.9 (2ꢂCH), 128.5 (2ꢂCH), 129.0
acetate/petroleum
chloromethylcarbonylamino)hept-4-ene 16 as
(0.13 g, 73%). Rf (20% EtOAc/petroleum ether) 0.53; nmax (NaCl) 3422
(NH), 3019 (CH), 1713 (CO), 1509, 1216, 756 cmꢁ1
dH (400 MHz,
ether
gave
(3S,4E)-1,7-diphenyl-3-(tri-
a
colourless oil
;

5354
L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
CDCl3) 1.84e1.98 (2H, m, 2-H2), 2.39e2.47 (2H, m, 6-H2), 2.61 (2H, t,
J 7.6 Hz, 1-H2), 2.70 (2H, t, J 7.6 Hz, 7-H2), 4.33e4.41 (1H, m, 3-H),
5.39 (1H, dd, J 15.6, 6.4 Hz, 4-H), 5.71 (1H, dt, J 15.6, 6.4 Hz, 5-H),
6.48 (1H, d, J 8.0 Hz, NH), 7.12e7.31 (10H, m, 10ꢂArH); dC (100 MHz,
CDCl3) 29.7 (CH2), 32.0 (CH2), 35.5 (CH2), 36.4 (CH2), 53.1 (CH), 92.9
(C), 126.1 (CH), 126.3 (CH), 128.5 (4ꢂCH), 128.6 (2ꢂCH), 128.7
(2ꢂCH), 128.8 (CH), 132.8 (CH), 141.0 (C), 141.4 (C), 161.1 (C); m/z (CI)
410 (MHþ, 12%), 376 (18), 343 (12), 307 (8), 249 (11), 167 (7), 136
(12), 85 (66), 73 (100); HRMS (CI): MHþ, found 410.0847.
C21H2335Cl3NO requires 410.0845.
CDCl3) 0.04 (3H, s, SiCH3), 0.05 (3H, s, SiCH3), 0.89 (9H, s, SiC
(CH3)3), 1.18 (3H, d, J 6.0 Hz, 1-H3), 1.60e1.68 (1H, m, 3-HH),
1.71e1.79 (1H, m, 3-HH), 2.37 (2H, q, J 7.0 Hz, 7-H2), 2.70 (2H, t, J
7.0 Hz, 8-H2), 3.82 (1H, q, J 6.0 Hz, 2-H), 4.46 (1H, quin, J 6.8 Hz,
4-H), 5.40 (1H, dd, J 15.4, 6.8 Hz, 5-H), 5.72 (1H, dt, J 15.4, 7.0 Hz,
6-H), 6.52 (1H, d, J 8.0 Hz, NH), 7.14e7.30 (5H, m, 5ꢂArH); dC
(100 MHz, CDCl3) ꢁ4.6 (CH3), ꢁ4.1 (CH3), 18.1 (C), 24.0 (CH3), 25.9
(3ꢂCH3), 34.0 (CH2), 35.4 (CH2), 44.8 (CH2), 50.7 (CH), 65.8 (CH),
92.9 (C), 126.0 (CH), 128.4 (2ꢂCH), 128.5 (2ꢂCH), 129.1 (CH), 132.4
(CH), 141.4 (C), 160.7 (C); m/z (CI) 480 (MHþ, 100%), 444 (75), 410
(19), 352 (14), 318 (5), 159 (11), 133 (8), 81 (4); HRMS (CI): MHþ,
found 480.1490. C22H3535Cl237ClNO2Si requires 480.1477.
4.1.16. (4S,5E)-2,2-Dimethyl-4-(trichloromethylcarbonylamino)-8-
phenyloct-5-ene (17). The reaction was carried out as described
for 15 using (4E,6R)-2,2-dimethyl-8-phenyloct-4-en-6-ol 12 (0.12 g,
0.53 mmol),1,8-diazabicyclo[5.4.0]undec-7-ene(0.04 mL, 0.27 mmol)
and trichloroacetonitrile (0.08 mL, 0.79 mmol). Purification was
carried out by flash column chromatography, and elution with 1:19
ethyl acetate/petroleum ether gave (4S,5E)-2,2-dimethyl-4-(tri-
chloromethylcarbonylamino)-8-phenyloct-5-ene 17 as a colourless
oil (0.19 g, 100%). Rf (20% EtOAc/petroleum ether) 0.59; nmax (NaCl)
4.1.19. Methyl (2S)-2-(trichloromethylcarbonylamino)hexanoate
(19)8h. To
a stirred solution of (5S,6E)-9-phenyl-5-(trichloro-
methylcarbonylamino)non-6-ene 15 (0.14 g, 0.39 mmol) in carbon
tetrachloride (6.0 mL) and acetonitrile (6.0 mL), sodium metaper-
iodate (0.34 g, 1.61 mmol, dissolved in water, 9 mL) was added,
followed by ruthenium(III) chloride hydrate (0.01 g, 0.04 mmol).
The reaction mixture was stirred at room temperature before water
(100 mL) and dichloromethane (100 mL) were added. The organic
layer was then dried (MgSO4), filtered and concentrated in vacuo to
give a dark oil (0.12 g). This residue was then dissolved in methanol
(5.0 mL) and the solution cooled to 0 ꢀC before thionyl chloride
(0.16 mL, 2.21 mmol) was added dropwise. The reaction mixture
was then heated under reflux for 22 h before being concentrated in
vacuo. The residue was partitioned between a saturated solution of
sodium bicarbonate (30 mL) and ethyl acetate (30 mL) and the
organic layer was dried (MgSO4), filtered and concentrated in
vacuo. Purification was carried out by flash column chromatogra-
phy, and elution with 1:9 diethyl ether/petroleum ether gave
methyl (2S)-2-(trichloromethylcarbonylamino)hexanoate 19 as
a colourless oil (0.04 g, 34%). Rf (20% EtOAc/petroleum ether) 0.58;
dH (400 MHz, CDCl3) 0.87e0.93 (3H, m, 6-H3), 1.30e1.40 (4H, m,
4-H2 and 5-H2), 1.72e1.83 (1H, m, 3-HH), 1.92e2.04 (1H, m, 3-HH),
3.81 (3H, s, OCH3), 4.58 (1H, q, J 6.2 Hz, 2-H), 7.14 (1H, d, J 6.2 Hz,
NH); dC (100 MHz, CDCl3) 13.9 (CH3), 22.2 (CH2), 27.0 (CH2), 31.7
(CH2), 52.9 (CH3), 54.0 (CH), 92.2 (C), 161.4 (C), 171.9 (C); m/z (CI)
290 (MHþ, 80%), 256 (100), 222 (20), 179 (10), 127 (5), 85 (40), 69
(55); HRMS (CI): MHþ, found 290.0130. C9H1535Cl3NO3 requires
290.0118.
3338 (NH), 2955 (CH), 1689 (CO), 1518, 1245, 822 cmꢁ1
; dH
(400 MHz, CDCl3) 0.95 (9H, s, C(CH3)3), 1.44 (1H, dd, J 14.4, 8.0 Hz,
3-HH), 1.53 (1H, dd, J 14.4, 4.8 Hz, 3-HH), 2.35 (2H, dt, J 7.2, 7.0 Hz,
7-H2), 2.68 (2H, t, J 7.2 Hz, 8-H2), 4.40e4.49 (1H, m, 4-H), 5.36 (1H,
ddt, J 15.6, 6.8, 1.2 Hz, 5-H), 5.68 (1H, dtd, J 15.2, 7.0, 1.2 Hz, 6-H),
6.41 (1H, d, J 8.0 Hz, NH), 7.14e7.29 (5H, m, 5ꢂArH); dC (100 MHz,
CDCl3) 29.9 (3ꢂCH3), 30.5 (C), 34.0 (CH2), 35.4 (CH2), 48.9 (CH2),
50.8 (CH), 92.9 (C), 125.9 (CH), 128.3 (2ꢂCH), 128.5 (2ꢂCH), 130.8
(CH), 131.0 (CH), 141.5 (C), 160.2 (C); m/z (CI) 376 (MHþ, 31%), 342
(49), 306 (100), 272 (43), 215 (10), 168 (36), 107 (57), 71 (49);
HRMS (CI): MHþ, found 376.1005. C18H2535Cl3NO requires
376.1002.
4.1.17. (4S,5E)-1-Nitrile-4-(trichloromethylcarbonylamino)-8-phenyl-
oct-5-ene (18). The reaction was carried out as described for 15 using
(4E,6R)-1-nitrile-8-phenyloct-4-en-6-ol 13 (0.18 g, 0.79 mmol), 1,8-
diazabicyclo[5.4.0]undec-7-ene (0.06 mL, 0.40 mmol) and tri-
chloroacetonitrile (0.12 mL, 1.19 mmol). Purification was carried out
by flash column chromatography, and elution with 1:4 ethyl acetate/
petroleum ether gave (4S,5E)-1-nitrile-4-(trichloromethylcarbonyl-
amino)-8-phenyloct-5-ene18 asapaleyellowoil(0.24 g, 81%). Rf (20%
EtOAc/petroleum ether) 0.24; nmax (NaCl) 3330 (NH), 2928 (CH), 2250
(CN), 1702 (CO), 1517, 822, 734 cmꢁ1
;
dH (400 MHz, CDCl3) 1.55e1.65
4.1.20. Methyl (2S)-4-phenyl-2-(trichloromethylcarbonylamino)buta-
noate (20). The reaction was carried out as described for 19 using
(3S,4E)-1,7-diphenyl-3-(trichloromethylcarbonylamino)hept-4-
ene 16 (0.10 g, 0.24 mmol), sodium metaperiodate (0.21 g,
1.00 mmol, dissolved in water, 9.0 mL) and ruthenium(III)
chloride hydrate (0.003 g, 0.01 mmol). Purification was carried
out by flash column chromatography, and elution with 1:9 ethyl
acetate/petroleum ether gave methyl (2S)-4-phenyl-2-(tri-
chloromethylcarbonylamino)butanoate 20 as a colourless oil
(0.039 g, 42%). Rf (20% EtOAc/petroleum ether) 0.39; nmax (NaCl)
3344 (NH), 2925 (CH), 1742 (CO), 1713 (CO), 1513, 1455, 1215,
(2H, m, 2-H2), 1.68e1.77 (2H, m, 3-H2), 2.35e2.43 (4H, m, 1-H2 and
7-H2), 2.71(2H, t, J7.4 Hz, 8-H2), 4.30e4.38(1H, m, 4-H), 5.33 (1H, ddt,
J 15.4, 6.8,1.3 Hz, 5-H), 5.73 (1H, dtd, J 15.4, 6.8,1.0 Hz, 6-H), 6.46 (1H,
d, J 8.1 Hz, NH), 7.13e7.31 (5H, m, 5ꢂArH); dC (100 MHz, CDCl3) 16.9
(CH2), 21.7 (CH2), 33.7 (CH2), 33.9 (CH2), 35.2 (CH2), 52.5(CH), 92.8(C),
119.2 (C), 126.1 (CH), 128.2 (CH), 128.4 (2ꢂCH), 128.5 (2ꢂCH), 133.7
(CH), 141.1 (C), 161.3 (C); m/z (CI) 373 (MHþ, 22%), 339 (30), 305 (13),
288 (12), 269 (8), 212 (11),186(17),162(23),132(13),107 (37), 85(23),
79 (100); HRMS (CI): MHþ, found 373.0640. C17H2035Cl3N2O requires
373.0641.
821 cmꢁ1
; dH (400 MHz, CDCl3) 2.05e2.14 (1H, m, 3-HH),
4.1.18. (2S,4S,5E)-2-[(tert-Butyldimethylsilyl)oxy]-4-(tri-
chloromethylcarbonylamino)-8-phenyloct-5-ene (27). The reaction
was carried out as described for 15 using (4E,6R)-2-[(tert-butyldi-
methylsilyl)oxy]-8-phenyloct-4-en-6-ol 14 (0.10 g, 0.30 mmol), 1,8-
diazabicyclo[5.4.0]undec-7-ene (0.02 mL, 0.15 mmol) and tri-
chloroacetonitrile (0.05 mL, 0.45 mmol). Purification was carried
out by flash column chromatography, and elution with 1:19 ethyl
acetate/petroleum ether gave (2S,4S,5E)-2-[(tert-butyldime-
thylsilyl)oxy]-4-(trichloromethylcarbonylamino)-8-phenyloct-5-
ene 27 as a colourless oil (0.12 g, 87%). Rf (20% EtOAc/petroleum
ether) 0.57; nmax (NaCl) 3337 (NH), 2928 (CH), 1702 (CO), 1514,
2.22e2.32 (1H, m, 3-HH), 2.55e2.69 (2H, m, 4-H2), 3.71 (3H, s,
OCH3), 4.56 (1H, q, J 5.2 Hz, 2-H), 7.08e7.25 (5H, m, 5ꢂArH); dC
(100 MHz, CDCl3) 31.3 (CH2), 33.3 (CH2), 52.9 (CH3), 53.7 (CH),
93.6 (C), 126.5 (CH), 128.4 (2ꢂCH), 128.7 (2ꢂCH), 140.0 (C), 161.5
(C), 171.5 (C); m/z (CI) 338 (MHþ, 100%), 304 (45), 270 (4), 233
(4), 117 (3), 69 (12); HRMS (CI): MHþ, found 338.0117.
C13H1535Cl3NO3 requires 338.0118.
4.1.21. Methyl (2S)-4,4-dimethyl-2-(trichloromethylcarbonylamino)
pentanoate (21). The reaction was carried out as described for 19
using (4S,5E)-2,2-dimethyl-4-(trichloromethylcarbonylamino)-8-
phenyloct-5-ene 17 (0.15 g, 0.40 mmol), sodium metaperiodate
1254, 1079, 835, 449 cmꢁ1; [
a
]
22 ꢁ12.0 (c 0.3, CHCl3); dH (400 MHz,
D

L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
5355
(0.35 g, 1.63 mmol, dissolved in water, 9.0 mL) and ruthenium(III)
chloride hydrate (0.008 g, 0.04 mmol). Purification was carried out
by flash column chromatography, and elution with 3:17 ethyl
acetate/petroleum ether gave methyl (2S)-4,4-dimethyl-2-(tri-
5-H3),1.98e2.08 (1H, m, 3-HH), 2.09e2.18 (1H, m, 3-HH), 3.79 (3H, s,
OCH3), 3.95e4.04 (1H, m, 4-H), 4.57 (1H, apparent q, J 5.9 Hz, 2-H),
7.51 (1H, d, J 5.9 Hz, NH); dC (100 MHz, CDCl3) ꢁ4.5 (CH3), ꢁ4.3 (CH3),
18.2 (C), 23.6 (CH3), 26.0 (3ꢂCH3), 40.4 (CH2), 51.8 (CH3), 52.8 (CH),
65.7 (CH), 92.2 (C), 161.5 (C), 171.7 (C); m/z (CI) 408 (MHþ, 25%), 372
(39), 338 (13), 271 (9), 240 (11), 207 (6), 173 (9), 133 (7), 113 (40), 69
(100); HRMS (CI): MHþ, found 408.0746. C14H2735Cl237ClNO4Si re-
quires 408.0748.
chloromethylcarbonylamino)pentanoate 21 as
a yellow solid
(0.075 g, 62%). Mp 76e79 ꢀC; Rf (20% EtOAc/petroleum ether) 0.41;
nmax (NaCl) 3422 (NH), 2960 (CH), 1743 (CO), 1716 (CO), 1516, 1371,
1215, 908 cmꢁ1
; dH (400 MHz, CDCl3) 1.00 (9H, s, C(CH3)3),
1.58e1.70 (1H, m, 3-HH), 1.88 (1H, dd, J 14.6, 3.1 Hz, 3-HH), 3.78
(3H, s, OCH3), 4.62 (1H, td, J 8.6, 3.1 Hz, 2-H), 6.94 (1H, br m, NH); dC
(100 MHz, CDCl3) 29.5 (3ꢂCH3), 30.7 (C), 45.8 (CH2), 51.8 (CH3), 52.8
(CH), 106.9 (C), 161.4 (C), 172.3 (C); m/z (CI) 304 (MHþ, 100%), 270
(86), 236 (19), 186 (3), 158 (4), 113 (9), 81 (32), 69 (29); HRMS (CI):
MHþ, found 304.0264. C10H1735Cl3NO3 requires 304.0274.
4.1.24. (2S)-2-Aminohexanoic acid (23)27. (2S)-2-(Trichlorometh-
ylcarbonylamino)hexanoic acid 19 (0.02 g, 0.08 mmol) was dis-
solved in 6 M hydrochloric acid (3.0 mL) and the reaction mixture
was heated under reflux for 18 h before being washed with diethyl
ether (2ꢂ20 mL). The aqueous phase was then concentrated in
vacuo to give (2S)-2-aminohexanoic acid 23 as a pale yellow solid
(0.02 g, 98%). dH (400 MHz, D2O) 0.87 (3H, t, J 6.8 Hz, 6-H3),
1.30e1.42 (4H, m, 4-H2 and 5-H2), 1.80e2.00 (2H, m, 3-H2), 4.00
(1H, t, J 6.0 Hz, 2-H); dC (100 MHz, D2O) 12.9 (CH3), 21.5 (CH2), 26.2
(CH2), 29.4 (CH2), 53.2 (CH), 172.7 (C); m/z (CI) 132 (MHþ, 100%), 113
(13), 97 (13), 81 (23), 71 (22).
4.1.22. Methyl (2S)-5-nitrile-2-(trichloromethylcarbonylamino)pen-
tanoate (22). The reaction was carried out as described for 19
using (4S,5E)-1-nitrile-4-(trichloromethylcarbonylamino)-8-phe-
nyloct-5-ene 18 (0.12 g, 0.32 mmol), sodium metaperiodate
(0.28 g, 1.37 mmol, dissolved in water, 6 mL) and ruthenium(III)
chloride hydrate (0.007 g, 0.03 mmol). Purification was carried out
by flash column chromatography, and elution with 1:3 ethyl ace-
tate/petroleum ether gave methyl (2S)-5-nitrile-2-(trichloro-
methylcarbonylamino)pentanoate 22 as a pale yellow oil (0.056 g,
58%). Rf (20% EtOAc/petroleum ether) 0.09; nmax (NaCl) 3339 (NH),
2918 (CH), 2253 (CN), 1744 (CO), 1712 (CO), 1521, 1439, 1217, 912,
4.1.25. (2S)-2-Amino-4-phenylbutanoic acid (24)28. Methyl (2S)-4-
phenyl-2-(trichloromethylcarbonylamino)butanoate 20 (0.02 g,
0.05 mmol) was dissolved in 6 M hydrochloric acid (5.0 mL) and the
reaction mixture was heated under reflux for 20 h before water
(25 mL) and diethyl ether (30 mL) were added. The aqueous phase
was then concentrated in vacuo to give (2S)-2-amino-4-phenyl-
butanoic acid 24 as a yellow solid (0.02 g, 100%). dH (400 MHz, D2O)
2.15e2.36 (2H, m, 2-H2), 2.70e2.88 (2H, m, 1-H2), 4.07 (1H, t, J
5.8 Hz, 3-H), 7.27e7.43 (5H, m, 5ꢂArH); dC (100 MHz, D2O) 30.5
(CH2), 31.9 (CH2), 57.4 (CH), 126.6 (CH), 128.5 (2ꢂCH), 128.9 (2ꢂCH),
140.3 (C), 173.3 (C); m/z (CI) 180 (MHþ, 4%), 161 (22), 137 (56), 113
(31), 97 (33), 81 (73), 69 (100).
735 cmꢁ1
; dH (400 MHz, CDCl3) 1.65e1.85 (2H, m, 4-H2), 1.88e1.98
(1H, m, 3-HH), 2.13e2.23 (1H, m, 3-HH), 2.44 (2H, t, J 7.0 Hz, 5-H2),
3.85 (3H, s, OCH3), 4.61 (1H, td, J 7.5, 6.0 Hz, 2-H), 7.33 (1H, d, J
6.0 Hz, NH); dC (100 MHz, CDCl3) 16.8 (CH2), 21.4 (CH2), 31.3 (CH2),
53.1 (CH), 53.3 (CH3), 92.0 (C), 118.8 (C), 161.9 (C), 171.1 (C); m/z
(CI) 301 (MHþ, 69%), 267 (76), 251 (10), 233 (48), 199 (9), 183 (9),
155 (12), 113 (25), 107 (85), 71 (100); HRMS (CI): MHþ, found
300.9900. C9H1235Cl3N2O3 requires 300.9914.
4.1.26. (2S)-2-Amino-4,4-dimethylpentanoic acid (25)29. Methyl
(2S)-4,4-dimethyl-2-(trichloromethylcarbonylamino)pentanoate
21 (0.05 g, 0.15 mmol) was dissolved in 6 M hydrochloric acid
(5.0 mL) and the resulting solution was heated under reflux for 24 h
before water (10 mL) and diethyl ether (20 mL) were added. The
aqueous phase was then concentrated in vacuo to give (2S)-2-
amino-4,4-dimethylpentanoic acid 25 as a pale yellow solid (0.04 g,
100%). dH (400 MHz, D2O) 1.00 (9H, s, C(CH3)3), 1.70 (1H, dd, J 15.0,
5.6 Hz, 3-HH), 2.04 (1H, dd, J 15.0, 5.6 Hz, 3-HH), 4.07 (1H, t, J 5.6 Hz,
2-H); dC (100 MHz, D2O) 28.3 (3ꢂCH3), 29.6 (C), 43.8 (CH2), 50.5
(CH), 173.2 (C); m/z (CI) 146 (MHþ, 100%), 135 (6), 113 (10), 97 (13),
81 (26), 69 (32).
4.1.23. Methyl (2S,4S)-4-[(tert-butyldimethylsilyl)oxy]-2-(trichloro-
methylcarbonylamino)pentanoate (28). To a stirred solution of
(2S,4S,5E)-2-[(tert-butyldimethylsilyl)oxy]-4-(trichloromethylcar-
bonylamino)-8-phenyloct-5-ene 27 (0.10 g, 0.22 mmol) in tert-bu-
tanol (2 mL), potassium carbonate (0.09 g, 0.67 mmol) in water
(4 mL) was added, followed by sodium metaperiodate (0.14 g,
0.67 mmol) and potassium permanganate (0.03 g, 0.20 mmol). The
reaction mixture was stirred at room temperature for 48 h and then
further potassium carbonate (0.05 g, 0.34 mmol), sodium metaper-
iodate (0.07 g, 0.34 mmol) and potassium permanganate (0.02 g,
0.10 mmol) were added. The reaction was stirred at room temper-
ature for a further 40 h and further potassium carbonate (0.03 g,
0.22 mmol), sodium metaperiodate (0.05 g, 0.22 mmol) and potas-
sium permanganate (0.01 g, 0.07 mmol) were added. The reaction
was stirred again for 18 h before being filtered through a pad of
CeliteÒ, and washed with ethyl acetate (50 mL). Water (50 mL) was
added to the filtrate, and the layers were separated. The aqueous
layer was extracted further using ethyl acetate (3ꢂ50 mL) and the
combined organic layers were dried (MgSO4), filtered and concen-
trated in vacuo to give a yellow oil (0.09 g). This residue was then
dissolvedin methanol (5 mL) and toluene (5 mL)and (trimethylsilyl)
diazomethane solution in diethyl ether (2 M, 2.23 mL, 4.46 mmol)
was added dropwise. The reaction was stirred at room temperature
for 1.75 h before being concentrated in vacuo. Purification was car-
ried out by flash column chromatography, and elution with 1:9
diethyl ether/petroleum ether gave methyl (2S,4S)-4-[(tert-butyl-
dimethylsilyl)oxy]-2-(trichloromethylcarbonylamino)pentanoate
28 as a colourless oil (0.027 g, 30%). Rf (20% EtOAc/petroleum ether)
0.46; nmax (NaCl) 3420 (OH), 2858 (CH), 1638 (CO), 1254, 1142,
4.1.27. (2S)-2-Amino-5-carbamoylpentanoic acid (26)30. (2S)-5-Ni-
trile-2-(trichloromethylcarbonylamino)pentanoate 22 (0.03 g,
0.08 mmol) was dissolved in 6 M hydrochloric acid (5.0 mL) and the
resulting solution was heated under reflux for 24 h before water
(20 mL) and diethyl ether (20 mL) were added. The aqueous phase
was then concentrated in vacuo to give (2S)-2-amino-5-carba-
moylpentanoic acid as an off-white residue (0.02 g, 100%). dH
(400 MHz, D2O) 1.60e1.80 (2H, m, 4-H2), 1.85e2.00 (2H, m, 3-H2),
2.46 (2H, t, J 7.2 Hz, 5-H2), 3.88 (1H, t, J 6.2 Hz, 2-H); dC (100 MHz,
D2O) 19.8 (CH2), 29.2 (CH2), 32.9 (CH2), 53.1 (CH), 172.5 (C), 177.7
(C); m/z (CI) 161 (MHþ, 3%), 135 (23), 113 (62), 85 (72), 71 (90).
4.1.28. (2S,4S)-4-Hydroxy-2-aminopentanoic acid (29)20. (2S,4S)-4-
[(tert-Butyldimethylsilyl)oxy]-2-(trichloromethylcarbonylamino)
pentanoate 28 (0.03 g, 0.06 mmol) was dissolved in 6 M hydro-
chloric acid (4.0 mL) and the resulting solution was heated under
reflux for 16 h before water (20 mL) and diethyl ether (20 mL) were
added. The aqueous phase was then concentrated in vacuo to give
(2S,4S)-4-hydroxy-2-aminopentanoic acid as a pale brown solid
882 cmꢁ1; [
a
]
20 þ25.6 (c 0.8, CHCl3); dH (400 MHz, CDCl3) 0.06 (3H, s,
D
SiCH3), 0.07 (3H, s, SiCH3), 0.88 (9H, s, SiC(CH3)3),1.20 (3H, d, J 6.0 Hz,

5356
L.J. Drummond, A. Sutherland / Tetrahedron 66 (2010) 5349e5356
20 þ18.6 (c 0.2, H2O), lit.20
[a]
20 þ21.0 (c 1.3, H2O);
8. For example, see: (a) Vyas, D. M.; Chiang, Y.; Doyle, T. W. Tetrahedron Lett.
1984, 25, 487e490; (b) Savage, I.; Thomas, E. J. J. Chem. Soc., Chem. Commun.
1989, 717e719; (c) Mehmandoust, M.; Petit, Y.; Larchevêque, M. Tetrahedron
Lett. 1992, 33, 4313e4316; (d) Gonda, J.; Helland, A.-C.; Ernst, B.; Bellus, D.
Synthesis 1993, 729e733; (e) Marshall, J. A.; Garofalo, A. W. J. Org. Chem. 1993,
58, 3675e3680; (f) Estieu, K.; Ollivier, J.; Salaün, J. Tetrahedron Lett. 1995, 36,
2975e2978; (g) Imogaï, H.; Petit, Y.; Larchevêque, M. Tetrahedron Lett. 1996, 37,
2573e2576; (h) Chen, Y. K.; Lurain, A. E.; Walsh, P. J. J. Am. Chem. Soc. 2002,
124, 12225e12231; (i) Anderson, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003,
125, 12412e12413; (j) Jamieson, A. G.; Sutherland, A.; Willis, C. L. Org. Biomol.
Chem. 2004, 2, 808e809; (k) Fanning, K. N.; Jamieson, A. G.; Sutherland, A.
Org. Biomol. Chem. 2005, 3, 3749e3756; (l) Swift, M. D.; Sutherland, A. Org.
Biomol. Chem. 2006, 4, 3889e3891; (m) Swift, M. D.; Sutherland, A. Tetrahe-
dron Lett. 2007, 48, 3771e3773; (n) Swift, M. D.; Sutherland, A. Tetrahedron
2008, 64, 9521e9527.
9. CBS represents the initials of the researchers who discovered the oxazabor-
olidine reagents, namely, Corey, Bakshi and Shibata: (a) Corey, E. J.; Bakshi, R.
K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551e5553; (b) Corey, E. J.; Bakshi,
R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. J. Am. Chem. Soc. 1987, 109,
7925e7926.
10. Martín, R.; Romea, P.; Tey, C.; Urpí, F.; Vilarrasa, J. Synlett 1997, 1414e1416.
11. (a) Scholl, S.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953e956; (b)
Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543e6554.
12. (a) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc.
2003, 125, 11360e11370; (b) Paul, T.; Sirasani, G.; Andrade, R. B. Tetrahedron
Lett. 2008, 49, 3362e3367.
(0.02 g, 100%). [
a
]
D
D
dH (400 MHz, D2O) 1.27 (3H, d, J 6.6 Hz, 5-H3), 1.76e1.84 (1H, m,
3-HH), 2.09e2.15 (1H, m, 3-HH), 3.82 (1H, dd, J 9.4, 4.4 Hz, 2-H),
4.08e4.12 (1H, m, 4-H); dC (100 MHz, D2O) 22.7 (CH3), 38.6 (CH2),
54.2 (CH), 66.7 (CH), 174.7 (C); m/z (CI) 134 (MHþ, 5%), 116 (100), 97
(13), 71 (23).
Acknowledgements
The authors gratefully acknowledge financial support from the
Carnegie Trust for the Universities of Scotland (scholarship to L.J.D.)
and the University of Glasgow.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.05.066.
References and notes
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15. Hollis, T. K.; Overman, L. E. J. Organomet. Chem. 1999, 576, 290e299.
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18. Although
were determined and shown to be of similar value and sign to that reported for
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a-amino acids 23e26 are not enantiomerically pure, optical rotations
€
L
Ohfune, Y.; Shinada, T. Eur. J. Org. Chem. 2005, 5127e5143; (f) Vogt, H.; Brase, S.
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19. de Figueiredo, R. M.; Coudray, L.; Dubois, J. Org. Biomol. Chem. 2007, 5,
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rahedron 2001, 57, ix.
3299e3309.
20. Jacob, M.; Roumestant, M. L.; Viallefont, P.; Martinez, J. Synlett 1997, 691e692.
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