Solid state conformations of α,β-unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine

Article abstract of DOI:10.1016/j.tetasy.2017.07.009

α,β-Unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine consistently adopt a defined conformation and undergo highly diastereoselective conjugate addition reactions with lithium a

Full text of DOI:10.1016/j.tetasy.2017.07.009

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
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Tetrahedron: Asymmetry
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Solid state conformations of a,b-unsaturated hydroxamates derived
from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(10-naphthyl)-
ethyl-O-tert-butylhydroxylamine
⇑
Stephen G. Davies , James A. Lee, Paul M. Roberts, James E. Thomson, Jingda Yin
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
a r t i c l e i n f o
a b s t r a c t
,b-Unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(10-naphthyl)
ethyl-O-tert-butylhydroxylamine consistently adopt defined conformation and undergo highly
Article history:
a
Received 22 June 2017
Accepted 25 July 2017
Available online xxxx
a
diastereoselective conjugate addition reactions with lithium amide reagents. The configuration of the
N-1-(10-naphthyl)ethyl group dictates the position of the O-tert-butyl group and also the configuration
adopted by the pyramidal nitrogen atom via a ‘chiral relay’ effect. Conjugate addition of lithium amide
reagents to these substrates proceeds on the face opposite to both the O-tert-butyl group and nitrogen
lone-pair with high levels of diastereoselectivity.
Dedicated to the memory of Dr. Howard D.
Flack (1943–2017)
Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction
electronic control) to give 3 with high levels of diastereoselectivity
(Fig. 1).
We have reported a protocol for the preparation of enantiopure
a
-stereogenic aldehydes or ketones 4 via the alkylation of enolates
X
R'
derived from N-1-(10-naphthyl)ethyl-O-tert-butylhydroxamates
such as 1 (incorporating our ‘chiral Weinreb amide’ auxiliary), fol-
lowed by treatment of the intermediate hydroxamates 3 with
either LiAlH4 or MeLi.1,2 A ‘chiral relay’3–5 mechanism was pro-
posed to rationalise the observed stereochemical outcome and a
mechanistic study of this highly diastereoselective reaction
revealed that a combination of evidence gained through experi-
mental observations (including modification of the auxiliary struc-
ture), physical measurements, and molecular mechanics
calculations, was found to validate this hypothesis.6 In this ‘chiral
relay’ model, the configuration of the N-1-(10-naphthyl)ethyl group
dictates the position of the O-tert-butyl group and also the config-
uration adopted by the pyramidal nitrogen atom. A fully staggered
arrangement is adopted in which minimisation of steric interac-
tions between the C(10)-methyl and O-tert-butyl groups leaves
the C(10)-hydrogen and carbonyl oxygen atoms eclipsing, minimis-
ing syn-pentane interactions. Minimisation of lone pair–lone pair
repulsion controls the configuration of the pyramidal nitrogen
atom, with alkylation occurring on the face opposite to both the
O-tert-butyl group (steric control) and nitrogen lone pair (stereo-
Me
O
R
O
N
KHMDS
H
1-Nap
R
H
N
OtBu
1-Nap
O
tBu
enolate
formation
1
2
alkylation favoured
anti to tert-butyl group
and N-lone pair
O
O
LiAlH4
or MeMgBr
R
R
R''
N
1-Nap
(R'' = H, Me)
R'
R'
OtBu
3, >95:5 dr
4, >95:5 er
Figure 1. Diastereoselective alkylation of hydroxamates 1. [1-Nap = 1-naphthyl].
Based on these alkylation studies we envisaged that a,b-unsat-
urated hydroxamates such as 6 and 7 (also derived from our ‘chiral
Weinreb amide’ auxiliary) would undergo conjugate addition reac-
tions of lithium amides7,8 with high levels of diastereocontrol at
the b-position. This was indeed found to be the case and we were
able to propose reactive conformation 8 using the tool of double
asymmetric induction as a mechanistic probe;9,10 as expected,
the doubly diastereoselective ‘matched’ conjugate addition of
(R)-5 to
a,b-unsaturated hydroxamates 6 (R = Me) and 7 (R = Ph)
occurs via conformation 8 (R = Me or Ph) on the face opposite to
⇑
Corresponding author.
E-mail address: steve.davies@chem.ox.ac.uk (S.G. Davies).
http://dx.doi.org/10.1016/j.tetasy.2017.07.009
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Davies, S. G.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.07.009

2
S. G. Davies et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
both the O-tert-butyl group and nitrogen lone-pair to give 9
(R = Me) and 10 (R = Ph) in ꢀ80% yield and >95:5 dr (Fig. 2).11
2. Results and discussion
Bromo-substituted ,b-unsaturated hydroxamates 14–16 were
a
prepared by coupling our ‘chiral Weinreb amide’ auxiliary (S)-N-
1-(10-naphthyl)ethyl-O-tert-butylhydroxylamine 17 [which is
stored as the corresponding (+)-camphorsulfonic acid salt 17ꢁ(+)-
CSA] with commercially available bromo-substituted trans-cin-
namic acids 11–13, via the intermediacy of the corresponding acid
chlorides, to give 14–16 in 42–70% yield after chromatographic
purification (Scheme 1).
conjugate addition
on opposite face to
tert-butyl group
Ph
Ph
Ph
N
Li
Ph
N
and nitrogen lone pair
(R)-5
O
Li
Me
O
H
R
R
N
OtBu
1-Nap
N
1-Nap
O
doubly
diasteroselective
"matched" reaction
pairing
t
Bu
6, R = Me
8
7, R = Ph
(COCl)2, DMF, CH2Cl2
0 °C to rt 1 h then
Ph
O
syn-pentane
interaction
minimised
R
Me
(S)-17·(+)-CSA
O
O
Ph
N
K2CO3, CH2Cl2, rt, 18 h
O
O
tBu
R
OH
R
N
1-Nap
R
N
OtBu
1-Nap
1-Nap
H
OtBu
syn-pentane
interaction
minimised
11, R = -BrC 6H4
14, R = -BrC H , 70%
o
6 4
9, R = Me, 81%, >95:5 dr
o
HN
OtBu
17
1-Nap
10, R = Ph, 80%, >95:5 dr
12, R = m-BrC6H4
13, R = p-BrC 6H4
15, R = m-BrC6H4, 65%
16, R = p-BrC6H4, 42%
Figure 2. The doubly diastereoselective ‘matched’ conjugate addition of (R)-5 to
b-unsaturated hydroxamates 6 and 7. [1-Nap = 1-naphthyl].
a,
Scheme 1. [1-Nap = 1-naphthyl].
As part of this study we noticed some differences between the
crystal structures of ,b-unsaturated hydroxamates 6 and 7:
a
Recrystallisation of 14–16 from CHCl3/heptane gave, in each
case, colourless blocks which were subjected to separate X-ray
diffraction analyses. Selected structural details for 14, 15 and 16
are included in Table 1. For all structures, the Flack x parameter13,14
was refined and was found to satisfy the criteria for a reliable
assignment of absolute configuration of a material known to be
enantiopure. In accordance with our previous observations con-
cerning derivatives of (S)-N-1-(10-naphthyl)ethyl-O-tert-butylhy-
droxylamine 171,2,6,11 the conformation of the ‘chiral Weinreb
amide’ auxiliary was found to be very similar in all cases: minimi-
sation of steric interactions between the C(10)-methyl and O-tert-
butyl groups leaves the C(10)-hydrogen and carbonyl oxygen atoms
eclipsing, minimising syn-pentane interactions. The nitrogen atom
is pyramidalised, and minimisation of lone pair–lone pair repulsion
controls its configuration (Fig. 4). However, there were again vari-
ations observed in the conformation of the alkenoyl substituents.15
In this respect the structures of the parent C(3)-phenyl substituted
compound 7 and the C(3)-m-bromophenyl substituted analogue 15
were found to be very similar in that they both exhibit significant
deviations from planarity about the C(1)AC(2) bond with
OAC(1)AC(2)AC(3) dihedral angles of >35° in both cases. For the
C(3)-o-bromophenyl and C(3)-p-bromophenyl substituted ana-
logues 14 and 16 the OAC(1)AC(2)AC(3) dihedral angle was less
than 20° in each case (both structures have two distinct conforma-
tions present within the asymmetric unit), although the
C(2)AC(3)AC(10)AC(20) dihedral angle was greater for C(3)-o-bro-
mophenyl substituted 14 which may be due to minimisation of
allylic strain (Table 2). The conformations of 6, 7 and 14–16 were
also investigated by IR and UV spectroscopic analyses. Whilst there
were no significant trends observed in the UV spectroscopic data
(in CHCl3), it was interesting to note the discrepancy between
the IR spectra recorded in the solid state (KBr disc) and solution
phase (CHCl3 cell) for the C(3)-phenyl and C(3)-m-bromophenyl
substituted compounds 7 and 15: for both compounds the mmax
values for the absorptions corresponding to the C@C bonds were
found to be anomalously high in the solid state. This may be
indicative of a reduced degree of conjugation which would be con-
sistent with the crystal structure data for these compounds as both
structures have large (>35°) OAC(1)AC(2)AC(3) dihedral angles.
The mmax values for the absorptions corresponding to the
C@C bonds in solution (CHCl3 cell) showed greater parity and
despite there being excellent parity between the conformation of
the ‘chiral Weinreb amide’ auxiliary in both cases, the conforma-
tion of the alkenoyl substituent for 7 was found to deviate signifi-
cantly from planarity [OAC(1)AC(2)AC(3) dihedral angle = 35.5°,
C(2)AC(3)AC(10)AC(20) dihedral angle = 17.3°] (Fig. 3).12 We there-
fore sought to examine this phenomenon further by analysing the
conformations of a range of aryl substituted analogues and we
selected the corresponding C(3)-o-bromophenyl, C(3)-m-bro-
mophenyl and C(3)-p-bromophenyl substituted
a,b-unsaturated
hydroxamates for this investigation.
O
2
4
3
3
1
1'
Me
N
1-Nap
1-Nap
OtBu
6
O
1
2
1'
1''
N
OtBu
2'
7
Figure 3. Overlaid molecular structures of 6 [green] and 7 [blue], all H atoms are
omitted for clarity.
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S. G. Davies et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
Table 1
Crystallographic data and refinement details for compounds 14–16
Compound
14
15
16
Empirical formula
Formula weight
Crystal habit, colour
Crystal system
Space group
a (Å)
C
25H26BrNO2
C25H26BrNO2
452.39
C25H26BrNO2
452.39
Block, colourless
Triclinic
P1
9.6178(8)
11.079(1)
11.8824(11)
63.168(4)
83.430(4)
86.420(3)
1122.31(18)
2
452.39
Block, colourless
Monoclinic
P21
13.8684(3)
7.8789(2)
19.8764(4)
90
90.714(1)
90
2171.68(8)
4
Block, colourless
Orthorhombic
P212121
8.1480(2)
10.1341(2)
26.5460(5)
90
b (Å)
c (Å)
a
(°)
b (°)
90
90
c
(°)
Volume (Å3)
2191.97(8)
4
1.371
Z
Density (calc. g cmꢂ3
Temperature (K)
Radiation type/k (Å)
)
1.384
150
Mo K
1.913
1.339
150
Mo Ka/0.71073
1.851
150
a/0.71073
Mo K
a/0.71073
Absorption coeff. (mmꢂ1
F(000)
)
1.896
936
936
468
Crystal size (mm)
Reflections measured
Independent reflections
0.18 ꢃ 0.23 ꢃ 0.28
0.12 ꢃ 0.16 ꢃ 0.20
23566
4741
0.10 ꢃ 0.14 ꢃ 0.25
28077
17907
8355
5639
Observed reflns. [I > 2.0
Number of parameters
Goodness-of-fit on F2
r
(I)]
6996
524
0.930
3504
263
0.993
4733
524
1.009
Final R indices [I > 2.0
R indices [all data]
x (Flack)
r(I)]
R1 = 0.038, wR2 = 0.072
R1 = 0.052, wR2 = 0.082
0.008(8)
R1 = 0.037, wR2 = 0.070
R1 = 0.051, wR2 = 0.075
0.001(8)
R1 = 0.089, wR2 = 0.240
R1 = 0.098, wR2 = 0.247
0.080(2)
D
qmax
,
D
qmin (e Åꢂ3
)
0.80, ꢂ0.76
0.55, ꢂ0.63
1.59, ꢂ0.78
CCDC deposition no.
817636
817637
817638
may be indicative of a greater degree of conjugation in solution
than in the solid state (Table 2).
3. Conclusion
The crystal structures of
a,b-unsaturated hydroxamates,
derived from (S)-N-1-(10-naphthyl)ethyl-O-tert-butylhydroxy-
lamine, were studied by X-ray diffraction. In each case the confor-
mation of the N-tert-butoxy and N-1-(10-naphthyl)ethyl groups
was found to be very similar: minimisation of steric interactions
between the C(10)-methyl and O-tert-butyl groups leaves the
C(10)-hydrogen and carbonyl oxygen atoms eclipsing, minimising
syn-pentane interactions. In addition, the nitrogen atom is pyrami-
dalised, and minimisation of lone pair-lone pair repulsion controls
its configuration. Whilst there were significant deviations observed
in the conformations of the alkenoyl substituents, these findings
are consistent with our previous observations concerning the
(S)-N-1-(10-naphthyl)ethyl-O-tert-butylhydroxylamine chiral aux-
iliary, where a ‘chiral relay’ effect may be proposed to rationalise
O
X
2
1'
2'
3
1
1''
N
1-Nap
OtBu
7, X = H
14, X = o-Br
15, X = m-Br
16, X = p-Br
Figure 4. Overlaid molecular structures of 7 [blue], 14 [green], 15 [cyan] and 16
[purple], all H atoms are omitted for clarity.
this trend. In each case, the conformation of the
a,b-unsaturated
Table 2
Selected structural parameters and IR and UV spectroscopic analyses for compounds 6, 7 and 14–16
Compound
6a
7
14a
15
16a
C(3)-Substituent
Me
6.4, 1.0
—
1657
1658
1624
1623
293 (5298)
284 (7167)
279 (9851)
Ph
35.5
17.3
1648
1649
1623
1609
309 (20,715)
290 (18,262)
280 (19,148)
o-BrC6H4
4.8, 1.4
36.6, 20.5
1650
1650
1612
m-BrC6H4
39.5
18.4
1649
1650
1624
1614
299 (18,772)
290 (19,837)
284 (18,982)
p-BrC6H4
16.3, 14.7
10.6, 2.0
1654
1654
1616
1613
310 (19,521)
288 (19,473)
OAC(1)AC(2)AC(3) Dihedral angle/°
C(2)AC(3)AC(10)AC(20) Dihedral angle/°
IR mmax (C@O, KBr)/cmꢂ1
IR mmax (C@O, CHCl3)/cmꢂ1
IR mmax (C@C, KBr)/cmꢂ1
IR mmax (C@C, CHCl3)/cmꢂ1
1611
UV kmax/nm (
e
/Mꢂ1 cmꢂ1
)
315 (22,441)
289 (21,232)
284 (27,352)
a
The crystal structures of 6, 14 and 16 all contain two molecules within the asymmetric unit].
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4
S. G. Davies et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
hydroxamate is consistent with highly selective conjugate addition
of lithium amide reagents on the face opposite to both the O-tert-
butyl group and nitrogen lone-pair, as observed experimentally.
CH2Cl2 (4 mL). Purification via flash column chromatography (gra-
dient elution, 1% ? 20% Et2O in 30–40 °C petrol) gave 15 as a white
solid (190 mg, 65%); mp 98–100 °C; ½a D25
ꢂ26.9 (c 1.0 in CHCl3);
ꢄ
mmax (KBr) 1649 (C@O), 1624 (C@C); dH (500 MHz, PhMe-d8,
343 K) 0.75 (9H, s, CMe3), 1.78 (3H, d, J 6.9, C(100)Me), 6.43–6.63
(1H, br m, C(100)H), 6.69–6.78 (1H, m, Ar), 6.99–7.54 (7H, m, C(2)
H, Ar), 7.56–7.68 (3H, m, Ar), 7.71 (1H, d, J 15.8, C(3)H), 8.55–
8.77 (1H, br m, Ar); dC (125 MHz, CDCl3) 16.4 (C(100)Me), 27.8
(CMe3), 55.8 (C(100)), 83.0 (CMe3), 121.5, 123.7, 124.4, 124.9,
125.6, 125.7, 126.1, 126.6, 127.5, 128.6, 132.6, 133.3, 133.5,
133.6, 135.3, 136.0 (Ar), 130.7 (C(2)), 141.4 (C(3)), 173.1 (C(1));
m/z (ESI+) 927 ([M(79Br)+M(81Br)+Na]+, 100%), 476 ([M(81Br)
+Na]+, 50%), 474 ([M(79Br)+Na]+, 50%); HRMS (ESI+)
4. Experimental
All reagents were used as supplied without prior purification.
Melting points were recorded on a Gallenkamp Hot Stage appara-
tus and are uncorrected. IR spectra were recorded on a Bruker Ten-
sor 27 FT-IR spectrometer as KBr discs. Selected characteristic
peaks are reported in cmꢂ1. NMR spectra were recorded on Bruker
Avance spectrometers in the deuterated solvent stated. Spectra
were recorded at rt. The field was locked by external referencing
to the relevant deuteron resonance. Low-resolution mass spectra
were recorded on either a VG MassLab 20–250 or a Micromass
Platform 1 spectrometer. Accurate mass measurements were run
on a Micromass GCT instrument fitted with a Scientific Glass
Instruments BPX5 column (15 m ꢃ 0.25 mm) using amyl acetate
as a lock mass.
C25H2681BrNNaO2 ([M(81Br)+Na]+) requires 476.1020; found
+
476.1024; HRMS (ESI+) C25H2679BrNNaO2+ ([M(79Br)+Na]+) requires
474.1039; found 474.1031.
4.4. (S)-N-tert-Butoxy-N-100-(1000-naphthyl)ethyl (E)-3-(40-bromo-
phenyl)propenamide 16
Following the general procedure, a solution of trans-4-bromocin-
namic acid 13 (300 mg, 1.32 mmol) in CH2Cl2 (3 mL) was reacted
with (COCl)2 (0.18 mL, 2.11 mmol) and a mixture of (S)-17ꢁ(+)-
CSA1 (250 mg, 0.52 mmol) and K2CO3 (725 mg, 5.25 mmol) in
CH2Cl2 (3 mL). Purification via flash column chromatography (gra-
dient elution, 1% ? 20% Et2O in 30–40 °C petrol) gave 16 as a white
4.1. General procedure
A solution of the requisite carboxylic acid (2.5 equiv) in CH2Cl2
at 0 °C was treated with (COCl)2 (5.0 equiv) and DMF (1 drop). The
reaction mixture was allowed to warm to rt over 1 h then concen-
trated in vacuo. The residue was dissolved in CH2Cl2 and the resul-
tant mixture was added to a stirred solution of (S)-17ꢁ(+)-CSA1
(1.0 equiv) and K2CO3 (10.0 equiv) in CH2Cl2 at 0 °C. The reaction
mixture was then allowed to warm to rt and stirred at rt for
18 h. Satd aq NaHCO3 was then added and the resultant mixture
was extracted with three portions of CH2Cl2. The combined organic
extracts were washed with brine, then dried and concentrated in
vacuo.
solid (96 mg, 42%); mp 102–104 °C; ½a D25
ꢄ
–17.2 (c 0.5 in CHCl3);
mmax (KBr) 1654 (C@O), 1616 (C@C); dH (500 MHz, PhMe-d8,
343 K) 0.77 (9H, s, CMe3), 1.76 (3H, d, J 6.9, C(100)Me), 6.47–6.63
(1H, br m, C(100)H), 6.92–7.32 (7H, m, C(2)H, Ar), 7.39–7.49 (1H,
m, Ar), 7.56–7.68 (3H, m, Ar), 7.75 (1H, d, J 15.8, C(3)H), 8.53–
8.78 (1H, br m, Ar); dC (125 MHz, CDCl3) 16.3 (C(100)Me), 27.8
(CMe3), 55.7 (C(100)), 83.1 (CMe3), 119.4 (C(2)), 124.0, 124.4,
124.9, 125.7, 126.1, 126.5, 128.6, 129.1, 129.4, 132.1, 132.6,
133.6, 134.2, 136.0 (Ar), 141.7 (C(3)), 173.3 (C(1)); m/z (ESI+) 476
([M(81Br)+Na]+, 100%), 474 ([M(79Br)+Na]+, 100%); HRMS (ESI+)
4.2.
bromophenyl)propenamide 14
(S)-N-tert-Butoxy-N-100-(1000-naphthyl)ethyl
(E)-3-(20-
C
25H2681BrNNaO+2 ([M(81Br)+Na]+) requires 476.1020; found
476.1010; HRMS (ESI+) C25H2679BrNNaO+2 ([M(79Br)+Na]+) requires
474.1039; found 474.1021.
Following the general procedure, a solution of trans-2-bromocin-
namic acid 11 (1.20 g, 5.25 mmol) in CH2Cl2 (12 mL) was reacted
with (COCl)2 (0.71 mL, 8.40 mmol) and a mixture of (S)-17ꢁ(+)-
CSA1 (1.00 g, 2.10 mmol) and K2CO3 (2.90 g, 21.0 mmol) in CH2Cl2
(10 mL). Purification via flash column chromatography (gradient
elution, 1% ? 20% Et2O in 30–40 °C petrol) gave 14 as a white solid
4.5. Single crystal X-ray diffraction
Single crystal diffraction data for 14–16 were collected using a
(665 mg, 70%); mp 110–112 °C; ½a D25
ꢄ
ꢂ56.9 (c 1.0 in CHCl3); mmax
Nonius
j-CCD diffractometer (Mo-Ka radiation, k = 0.71073 Å) at
150(2) K with an Oxford Cryosystems Cryostream N2 open-flow
cooling device16 and processed using the DENZO-SMN package,17
including unit cell parameter refinement and inter-frame scaling
(which were carried out using SCALEPACK within DENZO-SMN).
The structures were solved using SIR92.18 Refinement was car-
ried out using full-matrix least-squares within the CRYSTALS
suite,19 on F2. All non-hydrogen atoms were refined with anisotro-
pic displacement parameters. The positions and isotropic displace-
ment parameters of hydrogen atoms were refined using restraints
prior to inclusion into the model with riding constraints.20 For all
structures the Flack x parameter13,14 was refined and was found
to satisfy the criteria for a reliable assignment of absolute configu-
ration of a material known to be enantiopure.
(KBr) 1650 (C@O), 1612 (C@C); dH (500 MHz, PhMe-d8, 343 K)
0.76 (9H, s, CMe3), 1.76 (3H, d, J 6.9, C(100)Me), 6.46–6.58 (1H, br
m, C(100)H), 6.67–6.73 (1H, m, Ar), 6.83–6.89 (1H, m, Ar), 6.98–
7.45 (6H, m, C(2)H, Ar), 7.58–7.67 (3H, m, Ar), 8.41 (1H, d, J 15.8,
C(3)H), 8.56–8.74 (1H, br m, Ar); dC (125 MHz, CDCl3) 16.3
(C(100)Me), 27.8 (CMe3), 55.8 (C(100)), 83.1 (CMe3), 120.2, 123.0,
124.4, 124.9, 125.7, 126.1, 126.6, 126.8, 128.6, 130.6, 132.6,
133.6, 136.0, 137.2, 137.5 (Ar), 130.4 (C(2)), 141.4 (C(3)), 173.1
(C(1)); m/z (ESI+) 927 ([M(79Br)+M(81Br)+Na]+, 100%), 476
([M(81Br)+Na]+, 50%), 474 ([M(79Br)+Na]+, 50%); HRMS (ESI+)
+
C
25H2681BrNNaO2 ([M(81Br)+Na]+) requires 476.1020; found
476.1010; HRMS (ESI+) C25H2679BrNNaO2+ ([M(79Br)+Na]+) requires
474.1039; found 474.1024.
4.3.
bromophenyl)propenamide 15
(S)-N-tert-Butoxy-N-100-(1000-naphthyl)ethyl
(E)-3-(30-
Supplementary data
Full crystallographic data for 14–16 have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 817636, 817637 and 817638, respec-
tively. Copies of these data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.
Following the general procedure, a solution of trans-3-bromocin-
namic acid 12 (400 mg, 1.76 mmol) in CH2Cl2 (4 mL) was reacted
with (COCl)2 (0.24 mL, 2.82 mmol) and a mixture of (S)-17ꢁ(+)-
CSA1 (336 mg, 0.70 mmol) and K2CO3 (974 mg, 7.04 mmol) in
Please cite this article in press as: Davies, S. G.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.07.009

S. G. Davies et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
5
8. Davies, S. G.; Fletcher, A. M.; Roberts, P. M.; Thomson, J. E. Tetrahedron:
Asymmetry 2012, 23, 1111.
9. Davies, S. G.; Hermann, G. J.; Sweet, M. J.; Smith, A. D. Chem. Commun. 2004,
1128.
ac.uk/data_request/cif. Supplementary data associated with this
article can be found, in the online version, at http://dx.doi.org/10.
1016/j.tetasy.2017.07.009.
10. Davies, S. G.; Fletcher, A. M.; Hermann, G. J.; Poce, G.; Roberts, P. M.; Smith, A.
D.; Sweet, M. J.; Thomson, J. E. Tetrahedron: Asymmetry 2010, 21, 1635.
11. Davies, S. G.; Lee, J. A.; Roberts, P. M.; Thomson, J. E.; Yin, J. Tetrahedron 2011,
67, 6382.
12. The structures of 6 and 7 were overlaid using the Chem-3D structure mapping
function.
13. Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876.
14. Flack, H. D.; Bernardinelli, G. J. Appl. Crystallogr. 2000, 33, 1143.
15. The structures of 7 and 14–16 were overlaid using the Chem-3D structure
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17. Otwinowski, Z.; Minor, W. Methods Enzymol; Academic Press: New York, 1997;
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Please cite this article in press as: Davies, S. G.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.07.009