New biphenyl iminium salt catalysts for highly enantioselective asymmetric epoxidation: Role of additional substitution and dihedral angle

Article abstract of DOI:10.1039/c6ob00542j

New biaryl iminium salt catalysts for enantioselective alkene epoxidation containing additional substitution in the heterocyclic ring are reported. The effects upon conformation and enantioselectivity of this additional substitution, and the influence of dihedral angle in these systems, has been investigated using a synthetic approach supported by density functional theory. Enantioselectivities of up to 97% ee were observed.

Full text of DOI:10.1039/c6ob00542j

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New biphenyl iminium salt catalysts for highly
enantioselective asymmetric epoxidation: role of
additional substitution and dihedral angle†
Cite this: DOI: 10.1039/c6ob00542j
Philip C. Bulman Page,*a Christopher J. Bartlett,a Yohan Chan,a Steven M. Allin,b
Michael J. McKenzie,c Jérôme Lacourd and Garth A. Jonesa
New biaryl iminium salt catalysts for enantioselective alkene epoxidation containing additional substitution
in the heterocyclic ring are reported. The effects upon conformation and enantioselectivity of this
additional substitution, and the influence of dihedral angle in these systems, has been investigated using a
synthetic approach supported by density functional theory. Enantioselectivities of up to 97% ee were
observed.
Received 11th March 2016,
Accepted 15th March 2016
DOI: 10.1039/c6ob00542j
www.rsc.org/obc
Introduction
Asymmetric epoxidation of alkenes to generate non-racemic
chiral epoxides is an extremely powerful synthetic tool,1 and
the development of effective organocatalytic systems for epoxi-
dation has received considerable attention.2 The most success-
ful organocatalytic methods for epoxidation are those utilizing
dioxiranes and those utilizing oxaziridinium salts. Chiral
ketones used as precursors to dioxiranes, such as those of
Yang,3 Denmark,4 Armstrong,5 and especially Shi,6 have
achieved high enantioselectivities, with observed enantiomeric
excesses exceeding 97% in the best cases. Oxaziridinium salts,
first reported by Lusinchi in 1976,7 are also reactive reagents
for oxygen transfer to nucleophilic substrates such as sulfides
and alkenes, and may be generated catalytically by use of
iminium salts in the presence of a stoicheiometric oxidant,
typically Oxone.8 We have developed a range of catalysts based
on biphenylazepinium (e.g. 1), binaphthylazepinium (e.g. 2)
and dihydroisoquinolinium (e.g. 3) moieties containing a
chiral appendage on the nitrogen atom for epoxidation reac-
tions, with the most successful to date containing the 1,3-
dioxane motif of (S,S)-acetonamine 4 (Fig. 1).9 We have also
shown that alternative oxidants may be used in iminium salt-
Fig. 1 Iminium salt catalysts.
catalysed epoxidation reactions such as hydrogen peroxide,10
sodium hypochlorite,11 and electrochemically-generated oxi-
dants.12 Amines have also been used as iminium precursors in
related epoxidation processes by us13 and others.14
We reported the first very high enantioselectivities in the
asymmetric epoxidation of alkenes using iminium salt cata-
lysts, and we have developed non-aqueous conditions for these
processes using tetraphenylphosphonium monoperoxysulfate
(TPPP)15 as the oxidant.16 We have used the process in the
syntheses of levcromakalim,17 (−)-lomatin, (+)-trans-khellac-
tone,18 and scuteflorin19 utilizing catalysts 1 and 3.
We have shown that incorporation of a pseudo-axial substi-
tuent at the prochiral carbon atom α- to the nitrogen atom in
biaryl systems 1 and 2 affords higher enantioselectivities, with
the addition of a methyl group found to have the greatest influ-
ence.20 It has also been reported that the level of enantiocon-
trol imparted by biaryl azepinium salt catalysts in the
epoxidation of alkenes is in part correlated with the dihedral
angle around the biphenyl axis in the iminium species,21
suggesting a parallel pattern of dihedral angles between the
iminium parents and the putative derived oxaziridinium oxi-
dative intermediates. It was further suggested that this angle is
both larger and nearer to the optimum in the octahydrobi-
naphthyl series than in the parent binaphthyl series.
aSchool of Chemistry, University of East Anglia, Norwich Research Park,
Norwich NR4 7TJ, UK. E-mail: p.page@uea.ac.uk
bDepartment of Chemistry, Nottingham Trent University, Clifton,
Nottinghamshire NG11 8NS, UK
cCharnwood Molecular Ltd, 7 Beaumont Court, Prince William Road, Loughborough,
Leicestershire LE11 5GA, UK
dDépartement de Chimie Organique, Université de Genève, Quai Ernest Ansermet 30,
CH-1121 Genève 4, Switzerland
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c6ob00542j
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Fig. 2 New biaryl catalysts.
We were interested to investigate this potential correlation
between dihedral angles in the iminium species and in the
oxaziridinium oxidative intermediates, and if any correlation
might also be observed between dihedral angles and induced
enantioselectivities. Consequently, geometry optimizations
were carried out on oxaziridinium intermediates, as well as the
iminium species, at the B3LYP/6-31G* level of theory. These
calculations indeed suggest that there is little change in di- Scheme 1 Synthesis of 6,6’-dimethylbiphenyl azepines. Reagents and
conditions: (i) HCl, NaNO2; then Cu2SO4, (NH4OH)2·H2SO4, NH4OH,
<5 °C, 58%; (ii) LiAlH4 (3 equiv.), Et2O, r.t., 96%; (iii) PCC (3 equiv.),
CH2Cl2, r.t., 87%, (iv) Amine 4 (1 equiv.), NaBH3CN (2.2 equiv.), MeOH,
AcOH, r.t., 24 h, [10Rax, 49%] and [10Sax, 26%]; (v) quinine, EtOH (90%),
hedral angles between the iminium and oxaziridinium species
in the lowest energy conformations (vide infra).
We were interested to learn if related structural modifi-
cations would also improve the enantioselectivity of our other
biaryl-containing catalysts. We report herein the design and
use of new iminium salt catalysts combining both of these
modifications (Fig. 2).
crystallization then (b) 3 M HCl, 70%.
(+)-8Sax was found to be identical to 10Sax, allowing us to attri-
bute the absolute configurations of 10Rax and 10Sax.
Oxidation of 10Rax, 10Sax separately using NBS followed by
counter-ion exchange gave the corresponding tetraphenylbo-
rate iminium salts 5Rax and 5Sax in 61% and 83% yields
respectively. Diastereoselective addition of methyl magnesium
bromide gave 11Rax and 11Sax as single diastereoisomers, the
methyl groups being introduced into a pseudo-axial position
in each case, as we have previously observed,20 controlled by
the axial chirality of the biphenyl backbone, and appearing in
the 1H NMR spectra at high field (11Rax: 0.21 ppm; 11Sax:
0.14 ppm).
Oxidation of 11Rax, 11Sax and anion exchange gave
α-methylated iminium salts 6Rax, 6Sax as single diastereo- and
regio-isomers in 28% and 32% yields over the three steps,
respectively (Scheme 2), resulting from loss of the more acces-
sible single remaining axial hydrogen atom in each case.20,23
Results and discussion
Synthesis
To begin with, we focused on synthesis of the simpler 6,6′-di-
methylbiphenyl backbone, with iminium salts 5Rax, 5Sax and
6Rax, 6Sax as targets. The synthesis of racemic bis-carboxalde-
hyde ( )-7 was achieved following literature procedures.21,22
Formation of the diazonium salt from 3-methylanthranilic
acid followed by coupling of the radical generated in situ gave
bis-acid ( )-8 in 58% yield. High concentration of the diazo-
nium salt and careful temperature control are key factors to
obtain an acceptable yield of ( )-8, as formation of the corres-
ponding diazo compound, a bright yellow solid, competes
with the desired reaction. We first used the racemic bis-acid,
ultimately to access both diastereoisomers 5Rax and 5Sax in
order to assess separately their potential as catalysts, in the
expectation of finding ‘matched’ and ‘mismatched’ systems,
and reasoning that separation of the diastereoisomers would
be more practical on sufficient scale than resolution of the bis-
acid. Reduction of ( )-8 to the diol ( )-9 with lithium alu-
minium hydride proceeded in 96% yield. Oxidation of the two
alcohol moieties of ( )-9 using PCC yielded the desired bis-car-
boxaldehyde ( )-7 in 87% yield. Reductive cycloamination of
( )-7 with enantiomerically pure (S,S)-acetonamine 4 gave dia-
stereoisomers 10Rax, 10Sax, which were separated using silica
gel column chromatography, in 49% and 26% yields respect-
ively (Scheme 1).
Resolution of bis-acid ( )-8 using quinine following a litera-
ture procedure provided us with the means to prepare a single
diastereoisomer of 10.22 By comparison of spectroscopic data
Scheme 2 Synthesis of 6,6’-dimethylbiphenyl catalysts. Reagents and
conditions: (i) NBS (1.1 equiv.), CH2Cl2, 0 °C then reflux, 2 h, then
NaBPh4, EtOH, 5 min; (ii) MeMgBr (10 equiv.), THF, −78 °C to r.t.; (iii) NBS
and optical rotation, the amine diastereoisomer obtained from (1.1 equiv.), CH2Cl2, 0 °C then reflux, 2 h, then NaBPh4, EtOH, 5 min.
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Scheme 3 Synthesis of octahydrobinol derivatives. Reagents and con-
ditions: (i) Pd/C, H2 (3.5 bar), AcOH, 80 °C, 10 d, 45%; (ii) Tf2O (3 equiv.),
DMAP (0.4 equiv.), 2,6-lutidine (3 equiv.), −30 °C to r.t., 16 h, 99%; (iii)
Pd(OAc)2 (0.15 equiv.), dppp (0.15 equiv.), MeOH (50 equiv.), DMSO,
DIPEA, CO (2 bar), 80 °C, 48 h, 85%; (iv) LiAlH4 (2 equiv.), Et2O, 99%.
Scheme 5 Synthesis of octahydrobinaphthyl catalysts. Reagents and
conditions: (i) NBS (1.1 equiv.), CH2Cl2, r.t., 30 min then NaBPh4, EtOH,
73%; (ii) MeMgBr (10 equiv.), THF, −78 °C to r.t., 16 h, 79%; (iii) NBS (1.1
equiv.), CH2Cl2, r.t., 30 min then NaBPh4, EtOH, 71%.
The yield of the oxidation step was moderated by competing
bromination of the methyl groups at the 6,6′ positions.
We next turned our attention to the preparation of similar
Amine 17 was oxidized using NBS to afford iminium salt 19
catalysts using the octahydrobinaphthyl backbone, where the in 73% yield. The corresponding α-methylated azepinium salt
iminium salt possesses large dihedral angles.21 Octahydrobi- was obtained through a similar sequence to that described
naphthyl-2,2′-bis-methanol 12 was obtained following litera- above, involving diastereoselective Grignard reagent addition
ture procedures (Scheme 3).21,24 (R)-Binol was hydrogenated to to give 20 followed by oxidation and anion exchange to give 21
(R)-octahydrobinol 13 using palladium on carbon under hydro- in 56% yield over the two steps. Again, the α-methylated
gen pressure in 45% yield. Triflation of the phenolic hydroxyl iminium salt 21 was obtained as a single regio- and diastereo-
moieties to give 14, followed by palladium-catalysed carbonyla- isomer with a pseudo-axial methyl group (Scheme 5).20
tion to give 15,25 and reduction using lithium aluminium
Calculations
hydride gave (R)-octahydrobinaphthyl-1,1′-methanol 12 in 83%
yield over the three steps.
Geometry optimizations were carried out on a range of these
iminium species and their putative derived oxaziridinium
ions, at the B3LYP/6-31G* level using Gaussian 09,26 to deter-
mine the dihedral angles ϕ and θ in the lowest energy confor-
mations. Both possible diastereoisomers were investigated in
the case of each oxaziridinium ion. All stationary point struc-
tures were characterized by harmonic frequency analysis, and
shown to be genuine energy minima (Tables 1 and 2). Carte-
sian co-ordinates of the optimized structures can be found in
ESI.†
Compound 12 was converted into the corresponding (R)-
bis-carboxaldehyde 16 in quantitative yield. Tertiary amine 17
was, however, only obtained in 67% yield using the reductive
cycloamination protocol. An alternative procedure consisting
of displacing two bromide ions using (S,S)-acetonamine 4 was
therefore used. Diol 12 was successfully bis-brominated to give
18 using phosphorus tribromide in 90% yield; double displace-
ment with (S,S)-acetonamine 4 gave the desired amine 17 in
an excellent 97% yield (Scheme 4).
For the oxaziridinium ions (Table 1), the calculations
demonstrate a clear increase in dihedral angles upon moving
from the biphenyl species (around 38–42°) to the 6,6′-di-
methylbiphenyl (around 54–58°) and the octahydrobinaphthyl
(around 55–64°) species. Larger dihedral angles were also
observed as expected in the binaphthyl species (around
54–59°).
It is interesting to note that the pair of diastereoisomeric
oxaziridinium ions in each case display similar dihedral
angles, with the differences varying from 0.3° to 6.8° for ϕ and
0.1° to 3.7° for θ, the larger figures being observed for the octa-
hydro species. Similar calculations carried out on the derived
iminium ions suggest that similar dihedral angles also obtain
for the iminium and derived oxaziridinium species; the calcu-
lations suggest that the dihedral angles differ by no more than
6.3° from those of the corresponding iminium species.
Incorporation of a methyl substituent at the prochiral
carbon atom α- to the nitrogen atom in the heterocyclic ring
does not, however, greatly affect the dihedral angles for either
Scheme 4 Synthesis of octahydrobinaphthyl azepine. Reagents and
conditions: (i) PCC (1 equiv.), CH2Cl2, r.t., 2 h, 99%; (ii) 4 (1 equiv.),
NaBH3CN (2.2 equiv.), AcOH, r.t., 24 h, 67%; (iii) PBr3 (3 equiv.), pyridine
(0.1 equiv.), toluene, 60 °C, 3 h, 90%; (iv) Amine 4 (1 equiv.), K2CO3
(3 equiv.), MeCN, reflux, 16 h, 97%.
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Table 1 Dihedral angles calculated for oxaziridinium species
Table 2 Dihedral angles calculated for iminium species
Structure
ϕ/θ
Structure
ϕ/θ
Structure
ϕ/θ
Structure
ϕ/θ
ϕ = −40.1
θ = −41.3
ϕ = −37.9
θ = −40.4
ϕ = −34.9
θ = −39.6
ϕ = −33.8
θ = −37.6
ϕ = −52.2
θ = −53.0
ϕ = −52.2
θ = −52.2
ϕ = 38.9
θ = 41.7
ϕ = 39.4
θ = 40.8
ϕ = −53.1
θ = −53.7
ϕ = −52.7
θ = −52.5
ϕ = −38.7
θ = −39.2
ϕ = −37.7
θ = −39.7
ϕ = 52.4
θ = 53.7
ϕ = 52.7
θ = 53.3
ϕ = −58.5
θ = −54.8
ϕ = −56.4
θ = −54.0
ϕ = −59.7
θ = −58.0
ϕ = −60.0
θ = −57.3
ϕ = −58.1
θ = −54.0
ϕ = −56.0
θ = −53.9
ϕ = −57.8
θ = −54.7
ϕ = −56.3
θ = −54.4
the iminium or oxaziridinium species (no more than about
2°). In the biphenyl cases 22 and 23, and the precursor
iminium species 1 and 30, where interconversion between the
atropoisomers is readily possible, the S,S-acetonamine unit
induces a preference for the R-axial chirality in the biaryl unit.
The methyl substituents in 23 and 30 occupy pseudo-axial
positions, as is observed in the other methyl-substituted
examples.
ϕ = 56.3
θ = 55.0
ϕ = 57.5
θ = 54.7
ϕ = −57.7
θ = −53.9
ϕ = −55.6
θ = −54.3
Epoxidation reactions
ϕ = 57.2
θ = 54.9
ϕ = 57.5
θ = 54.3
Iminium salts 5Rax, 5Sax, 6Rax, 6Sax, 19, and 21 were used in
the asymmetric epoxidation of a number of alkenes under
optimized reaction conditions,27 and the results compared
with known results from species 1 and 30 (Table 3).20 We have
previously observed that the related binaphthyl catalysts 2 and
31 display somewhat different profiles of reactivity and selecti-
vity from those of the biphenyl series,9a,20 and these catalysts
are therefore not included in this analysis.
Aqueous conditions using Oxone as oxidant and a mixture
of acetonitrile and water as solvent gave the highest reactivities
and enantioselectivities. Non-aqueous conditions using TPPP
as oxidant and acetonitrile as solvent were less successful,
however; for example, use of chloroform as solvent gave an ee
lower than 5%. The enantioselectivity observed when
18-crown-6 and a biphasic system28 were used was also poor.
ϕ = −63.0
θ = −58.3
ϕ = −57.3
θ = −54.6
ϕ = −63.8
θ = −57.6
ϕ = −57.0
θ = −54.9
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While the incorporation of a methyl substituent α to the
nitrogen atom generally increases the enantiocontrol, it has a
detrimental or no effect on the mismatched diastereoisomers
5Sax and 6Sax. The sense of stereochemical induction in the
epoxidation process is controlled by the configuration of the
biaryl backbone. Catalyst 6Rax, with the added methyl group, is
in most cases superior to catalyst 5Rax. The octahydrobi-
naphthyl catalyst 21, with an additional methyl group, pro-
vides the highest enantioselectivities that we have seen for the
epoxidation of 1-phenylcyclohexene, at 96% ee, and for
1-phenyl dihydronaphthalene, at 97% ee.
Table 3 Asymmetric epoxidation mediated by iminium salts 1, 5, 7a–b,
8a–b, 9, 10
Substrate
Cat.
Time
Conv.b/%
eec/%
Config.d
1a
5 min
0.5 h
0.8 h
1 h
1.8 h
3 h
100
100
99
99
99
99
99
99
99
90
100
99
98
99
99
77
99
99
87
95
99
99
99
99
99
99
80
95
99
99
99
99
60e
82e
87e
92e
82e
82e
90f
80f
96f
41
78
89
81
85
82
78
93
86
97
37
67
73
60
48
60
63
69
5
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(+)-(1R,2R)
(+)-(1R,2R)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(+)-(1R,2S)
(+)-(1R,2S)
(+)-(1R,2S)
(+)-(1R,2S)
(+)-(1R,2S)
(−)-(1S,2R)
(−)-(1S,2R)
(+)-(1R,2S)
(+)-(1R,2S)
(+)-(1R,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(+)-(1R,2R)
(+)-(1R,2R)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(−)-(1S,2S)
(+)-(1R,2R)
(+)-(1R,2R)
30a
5Rax
6Rax
5Sax
6Sax
19
0.6 h
1 h
19a
21a
1a
1.5 h
3 min
0.5 h
0.5 h
0.3 h
1 h
2 h
6 h
0.7 h
1.3 h
3 h
5 min
3 h
30a
5Rax
5Rax
6Rax
5Sax
6Sax
19
a
Conclusions
The results described herein provide further evidence that
addition of additional methyl substituents adjacent to the
nitrogen atom in the heterocyclic ring can provide improve-
ments in enantioselectivities in catalysed epoxidation reac-
tions, with the α-methylated octahydrobinaphthyl catalyst 21
giving the best results of this series; particularly noteworthy
are the epoxidations of 1-phenylcyclohexene, at 96% ee, and of
1-phenyl dihydronaphthalene, at 97% ee.
19a
21a
1a
5Rax
6Rax
5Sax
6Sax
19
3 h
6 h
6 h
1 h
19a
21a
1a
2 h
Calculations clearly suggest a parallel pattern of dihedral
angles between the iminium parents and the putative derived
oxaziridinium oxidative intermediates.
18 h
5 min
4.3 h
6 h
6 h
6 h
5Rax
6Rax
5Sax
6Sax
15
39
8
Experimental results also support the conjecture that some
correlation may be observed between the dihedral angle found
in the biaryl units of these iminium salt catalysts and the
induced enantioselectivities in the catalysed epoxidation reac-
tions. The 6,6′-dimethylbiphenyl catalysts 5 and 6 (dihedral
angles around 52–54°) are superior to the simpler biphenyl
species 1 and 30 (dihedral angles around 34–40°). The octahy-
drobinaphthyl catalysts 19 and 21 (dihedral angles around
57–60°) induce generally similar enantioselectivities to the
6,6′-dimethylbiphenyl species, perhaps suggesting optimum
dihedral angles of around 50–60° as one factor in the induc-
tion of enantioselectivities in the catalysed epoxidation
reactions.
10
Conditions: oxone® (2 equiv.), NaHCO3 (5 equiv.), catalyst (5 mol%),
MeCN : H2O 10 : 1, 0 °C. a Conditions: oxone® (2 equiv.), NaHCO3 (5
equiv.), catalyst (5 mol%), MeCN : H2O 1 : 1, 0 °C. b Conversions were
evaluated from the 1H NMR spectra by integration of the alkene and
epoxide signals. c ee was determined using CSP HPLC using
a
Chiralcel OD-H column unless otherwise indicated. d Absolute
configurations of the major enantiomers were determined by
comparison of optical rotation with those reported in the literature.
e ee was determined using CSP GC using a Chiraldex B-DM column.
f ee was determined using 1H NMR spectroscopy in the presence
of
europium(III)
tris[3-(heptafluoropropylhydroxymethylene)-
(+)-camphorate] as chiral shift reagent.
From our results, it appears that observed enantioselectivi-
ties indeed increase for the trisubstituted alkenes from
37–60% ee for the simple biphenyl catalyst 1 (78–82% ee for
the methylated derivative 30), with dihedral angles around
34–40°, to 60–93% ee for the matched 6,6′-dimethylbiphenyl
Experimental section
General procedure for the addition of methyl Grignard reagent
to iminium salts
catalyst 5R, with dihedral angles around 52–54°, and the octa- The iminium salt was dissolved in Et2O (50 mL per g of
hydro binaphthyl catalyst 19, with dihedral angles around iminium salt) under an atmosphere of N2. The solution was
57–60° (69–97% ee for the methylated derivatives 6R and 21 cooled to −78 °C. A 3 molar solution of MeMgCl in THF (10
respectively).
equiv.) was added dropwise over 10 min. After 1 h, cooling was
For catalysts 5 and 6, the ‘matched’ diastereoisomers, indu- ceased, and the mixture allowed to reach ambient temperature
cing higher enantioselectivities, are the (Rax) 5Rax and 6Rax, overnight. Saturated aqueous NH4Cl (5 mL per g of iminium
and the ‘mismatched’ ones are the (Sax) 5Sax and 6Sax, which salt) and CH2Cl2 (30 mL per g of iminium salt) were added.
are also generally less reactive. It is interesting to note that the The resulting mixture was transferred to a separating funnel,
relative stereochemistry of diastereoisomers 5Rax and 6Rax and brine (100 mL) added. The organic layer was collected and
corresponds to that seen in the lowest energy atropoisomer of the aqueous layer washed with CH2Cl2 (2 × 50 mL per g of
the simple biphenyl analogue 1.
iminium salt). The combined organic layers were washed with
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water (2 × 100 mL per g of iminium salt) and brine (2 × 7.44 (2 H, d, J = 7.5 Hz), 7.71 (2 H, d, J = 7.5 Hz), 12.28 (2 H,
100 mL per g of iminium salt). The organic fraction was dried broad); δC (125 MHz; d6-DMSO) 19.8, 126.6, 127.3, 132.9,
over MgSO4, and evaporated to dryness under reduced 136.0, 140.7, 168.1.
pressure to yield the desired methyl azepines.
6,6′-Dimethyl-2,2′-bis(hydroxymethyl)biphenyl
( )-9 .4
Compound ( )-8 (2.20 g, 8.2 mmol) was dissolved in Et2O
(30 mL) under a nitrogen atmosphere. The resulting pale
yellow solution was cooled to 0 °C, and LiAlH4 (0.93 g,
General procedure for the synthesis of iminium salts from the
corresponding azepines
The azepine substrate was dissolved in CH2Cl2 (30 mL per g of 24.5 mmol) added slowly at a rate that just maintained the
azepine), and NBS (1.1 equiv.) added. The resulting bright effervescence. The resulting suspension was heated under
yellow solution was stirred for 30 min at room temperature, reflux for 1 h, after which time the reaction mixture was
after which time the solvent was switched to EtOH. To the allowed to cool to room temperature. Solid Na2SO4 (6.0 g) was
ethanolic solution was added NaBPh4 (1.1 equiv.) in the added to the suspension, which was cooled in an ice-bath and
minimum amount of MeCN with stirring, which caused the stirred for 5 min. Water (10 mL) was added dropwise to
iminium salt to precipitate. The solvent was switched to quench the excess LiAlH4. The mixture was stirred for 30 min,
CH2Cl2 and the solution transferred to a separating funnel. filtered through a layered pad of Celite and Na2SO4, and the
The organic layer was washed with water (2 × 60 mL per g of colourless filtrate concentrated under reduced pressure to
azepine) and brine (30 mL per g of azepine). The crude yield ( )-9 as a colourless crystalline solid (1.91 g, 96%);
product isolated after the removal of solvents was recrystallized νmax(neat)/cm−1 3254, 3064, 3017, 2935, 2880, 1679, 1592,
from EtOH. The crystalline product was filtered off and 1458, 1378, 1239, 1211, 1163, 1028, 994, 902, 783, 760, 623; δH
washed with cold EtOH followed by Et2O and hexane. The iso- (500 MHz; CDCl3) 1.86 (6 H, s), 3.19 (2 H, s), 4.08 (2 H, d, J =
lated iminium salt was left to dry under reduced pressure in 11.5 Hz), 4.24 (2 H, d, J = 11.5 Hz), 7.24 (2 H, s, J = 7.5 Hz),
an oven at 60 °C overnight.
7.29 (2 H, t, J = 7.5 Hz), 7.34 (2 H, d, J = 7.5 Hz); δC (125 MHz;
6,6′-Dimethylbiphenyl-2,2′-bis(carboxylic acid) ( )-8 .4 NaNO2 CDCl3) 20.2, 63.1, 127.6, 128.0, 129.9, 136.1, 138.3, 138.5; m/z
(7.8 g, 0.11 mol) was added in one portion to an ice cold solu- (HNES) found for [C16H18O2 + Na]+ 265.1200; [M + Na]+
tion of 2-amino-3-methylbenzoic acid (17.0 g, 0.11 mol) in requires 265.1199.
2.45 M NaOH (60 mL). The mixture was stirred at 0 °C until it
6,6′-Dimethyl-1,1′-biphenyl-2,2′-bis(carboxaldehyde) ( )-7 .29
became homogeneous. An ice-cooled 4 M aqueous solution of PCC (1.33 g, 62.0 mmol) was added in one portion to a solu-
HCl (240 mL) was added to the solution at a rate such that the tion of ( )-9 (0.50 g, 20.7 mmol) in CH2Cl2 (20 mL), producing
temperature remained below 5 °C. The resulting orange solu- a dark-orange solution. The solution was stirred vigorously for
tion of the diazonium salt was stirred at 0 °C for 20 min. 3 h at room temperature. Et2O (20 mL) and a spatula of Celite
Cu2SO4·5H2O (24.0 g, 96 mmol) and water (75 mL) were was added to the resulting black mixture, which was stirred for
added, and the resulting solution cooled in an ice-bath. When a further 30 min. The reaction mixture was filtered through a
the solution had reached 5 °C, 30% w/v NH4OH solution layered pad of Celite and silica gel. Solvents were removed
(47.5 mL) was added in one portion. A freshly prepared solu- under reduced pressure to yield compound ( )-7 as a colour-
tion of NH2OH, prepared from treatment of (NH2OH)·H2SO4 less crystalline solid (0.43 g, 87%); m.p. 108–110 °C;
(8.8 g, 53.5 mmol) with a 3 M ice-cold aqueous solution of δH (500 MHz; CDCl3) 1.98 (6 H, s), 7.50 (2 H, t, J = 7.5 Hz), 7.59
NaOH (38 mL, 0.11 mol), was added to the resulting deep-blue (2 H, d, J = 7.5 Hz), 7.91 (2 H, d, J = 7.5 Hz), 9.60 (2 H, s);
solution. The solution was stirred for 20 min to cool to 0 °C. δC (125 MHz; CDCl3) 19.7, 126.4, 128.6, 134.5, 135.9, 137.6,
The diazonium salt prepared above was added to the copper 140.0, 191.4; m/z (HNES) found for [C16H14O2 + NH4]+:
solution in three equal portions of 50 mL. The temperature 256.1333; [M + NH4]+ requires 256.1332.
was maintained below 7 °C throughout the procedure. After
(+)-(R)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)-1,11-
the addition was complete, the resulting orange/red solution dimethyl-6,7-dihydro-5H-dibenzo[c,e]azepine 10Rax and (+)-(S)-
was heated under reflux for 30 min, and allowed to cool. After 6-((4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl)-1,11-dimethyl-
the red solution had attained ambient temperature, conc. HCl 6,7-dihydro-5H-dibenzo[c,e]azepine 10Sax. Amine 4 (2.70 g,
(37.5 mL) was added slowly and the mixture was allowed to 12.9 mmol) was added to a solution of ( )-7 (2.81 g,
stand overnight to provide for the complete precipitation of 11.8 mmol) in MeOH (160 mL). After stirring for 5 min,
the product. The yellow/brown precipitate was removed by fil- NaBH3CN (1.62 g, 25.8 mmol) and glacial acetic acid (1 mL)
tration using a Büchner funnel, washed with water and air- were added. The solution was stirred for 24 h at room tempera-
dried. The crude material was stirred in boiling EtOH ture. A 1 M aqueous solution of NaOH (20 mL) was added, fol-
(200 mL); any remaining bright yellow solid was removed by lowed by Et2O (100 mL). The organic layer was collected, and
filtration, leaving a clear brown filtrate. Crystallization of the the aqueous layer extracted with Et2O (2 × 30 mL). The organic
bis(carboxylic acid) ( )-8 was induced by the addition of water fractions were combined, washed with brine, and dried over
to the filtrate to yield light brown crystals (8.4 g, 55%); Na2SO4. The solvents were removed under reduced pressure to
m.p. 226–230 °C (dec.); νmax(neat)/cm−1 2982, 2907, 2667, yield a crude oil that was purified by flash column chromato-
2579, 1680, 1583, 1436, 1377, 1316, 1159, 962, 799, 768, 722; graphy, eluting with light petroleum/EtOAc (10 : 1), buffered
δH (500 MHz; d6-DMSO) 1.81 (6 H, s), 7.31 (2 H, t, J = 7.5 Hz), with 2% TEA, to give the desired compound as a mixture of
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diastereoisomers [First eluting 10Rax as a colourless crystalline t, J = 7.7 Hz), 7.71–7.76 (2 H, m), 9.17 (1 H, s); δC (125 MHz;
solid (1.18 g, 49%); and second eluting 10Sax as a colourless acetone-d6) 17.9, 19.1, 19.2, 59.4, 62.1, 67.0, 71.4, 100.8, 121.3,
foam (0.62 g, 26%)].
125.1 (q, J = 2.8 Hz), 125.5, 126.1, 128.1, 128.3, 128.68, 128.74,
First eluting amine 10Rax: [α]D +54.9 (c = 0.97, CDCl3); 129.0, 130.6, 132.1, 134.2, 136.1, 136.2 (q, J = 1.3 Hz), 137.16,
νmax(neat)/cm−1 2990, 2934, 2860, 1452, 1378, 1308, 1263, 137.18, 138.4, 139.3, 140.2, 163.5, 163.9, 164.3, 164.7, 171.2;
1236, 1200, 1172, 1150, 1075, 1027 953, 852, 787, 749, 727, m/z found for [C28H30NO2]+ 412.2268; iminium cation requires
698; δH (400 MHz; CDCl3) 1.58 (3 H, s), 1.64 (3 H, s), 2.11 (6 H, 412.2271.
s), 2.65 (1 H, d, J = 1.9 Hz), 3.16 (2 H, d, J = 12.1 Hz), 3.67 (2 H,
d, J = 12.1 Hz), 4.12–4.21 (2 H, m), 5.10 (1 H, d, J = 3.1 Hz), 1,5,11-trimethyl-6,7-dihydro-5H-dibenzo[c,e]azepine
(5R,11bRa)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)-
11Rax.
6.98–7.02 (2 H, m), 7.14–7.18 (4 H, m), 7.24–7.36 (5 H, m); Prepared according to the general procedure from 5Rax (0.60 g,
δC (100 MHz; CDCl3) 19.3, 20.0, 29.9, 53.2, 60.1, 61.9, 75.3, 1.45 mmol). The title compound 11Rax was isolated as a col-
99.3, 126.4, 126.7, 126.9, 127.5, 127.8, 129.0, 135.4, 136.7, ourless foam (0.34 g, 94%). νmax(neat)/cm−1 3059, 2991, 2921,
138.6, 140.5; m/z found for [C28H31NO2 + H]+ 414.2431; 2859, 1593, 1497, 1452, 1378, 1342, 1265, 1239, 1201, 1156,
[M + H]+ requires 414.2428.
1079, 1029, 955, 910, 885, 853, 787, 744, 700; δH (400 MHz;
Second eluting amine 10Sax: [α]D +121.0 (c = 1.07, CDCl3); CDCl3) 0.21 (3 H, d, J = 7.2 Hz), 1.56 (3 H, s), 1.63 (3 H, s), 2.07
νmax(neat)/cm−1 2990, 2939, 2859, 1497, 1452, 1378, 1332, (3 H, s), 2.13 (3 H, s), 2.91 (1 H, dd, J = 6.0 Hz, 3.9 Hz), 3.35
1263, 1236, 1198, 1168, 1140, 1076 1024, 1001, 952, 853, 787, (1 H, d, J = 11.4 Hz), 3.52 (1 H, d, J = 11.4 Hz), 4.08 (1 H, dd, J =
750, 722, 697, 665; δH (400 MHz; CDCl3) 1.46 (3 H, s), 1.49 (3 12.3 Hz, 2.1 Hz), 4.22 (1 H, dd, J = 12.0 Hz, 4.0 Hz), 4.33 (1 H,
H, s), 2.12 (6 H, s), 3.01 (1 H, br), 3.31 (2 H, d, J = 12.5 Hz), q, J = 7.0 Hz), 5.15 (1 H, d, J = 3.5 Hz), 6.81 (1 H, t, J = 4.4 Hz),
3.46 (2 H, d, J = 12.4 Hz), 3.92 (1 H, d, J = 12.4 Hz), 4.13 (1 H, 6.86 (1 H, dd, J = 6.7 Hz, 2.0 Hz), 7.09–7.15 (4 H, m), 7.20–7.38
d, J = 12.4 Hz), 5.13 (1 H, d, J = 3.0 Hz), 6.80–7.02 (2 H, m), (5 H, m); δC (100 MHz; CDCl3) 19.2, 19.3, 19.4, 21.0, 29.1, 54.0,
7.16–7.27 (4 H, m), 7.33 (2 H, t, J = 7.6 Hz), 7.45 (2 H, d, J = 7.6 59.7, 60.0, 63.2, 74.2, 99.3, 126.0, 126.4, 126.6, 126.8, 127.4,
Hz); m/z found for [C28H31NO2 + H]+: 414.2425; [M + H]+ 127.6, 128.5, 128.7, 135.9, 136.9, 138.9, 139.2, 140.3, 141.3; m/z
requires 414.2428.
(−)-(Ra)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)-1,11- requires 428.2584.
(HNES) found for [C29H33NO2 + H]+ 428.2582; [M + H]+
dimethyl-5H-dibenzo[c,e]azepin-6-ium tetraphenylborate 5Rax.
(5S,11bSa)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)-
Prepared according to the general procedure from 10Rax 1,5,11-trimethyl-6,7-dihydro-5H-dibenzo[c,e]azepine
11Sax.
(1.10 g, 2.66 mmol). The title compound 5Rax was isolated as a Prepared according to the general procedure from 5Sax (0.40 g,
fine yellow powder (1.18 g, 61%). [α]2D0 −190.5 (c = 1.01, MeCN); 0.97 mmol). The title compound 11Sax was isolated as a col-
νmax(neat)/cm−1 3055, 3002, 2161, 2041, 1976, 1629, 1580, ourless foam (0.23 g, 99%). νmax(neat)/cm−1 3059, 2991, 2921,
1478, 1450, 1426, 1382, 1350, 1263, 1238, 1202, 1164, 1107, 2859, 1593, 1497, 1452, 1378, 1342, 1265, 1239, 1201, 1156,
1031, 955, 847, 790, 730, 664, 611; δH (400 MHz; DMSO-d6) 1079, 1029, 955, 910, 885, 853, 787, 744, 700; δH (400 MHz;
1.70 (3 H, s), 1.71 (3 H, s), 1.94 (3 H, s), 2.18 (3 H, s), 3.96 (1 H, CDCl3) 0.14 (3 H, d), 1.47 (3 H, s), 1.50 (3 H, s), 2.05 (3 H, s),
d, J = 12.7 Hz), 4.17 (1 H, d, J = 13.7 Hz), 4.53 (1 H, s), 4.62 2.14 (3 H, s), 3.02 (1 H, dd, J = 6.5 Hz, 4.1 Hz), 3.31 (1 H, d, J =
(1 H, dd, J = 13.7 Hz, 2.9 Hz), 5.55 (1 H, br, ArCH̲2N), 5.82 (1 H, 11.3 Hz), 3.63 (1 H, q, J = 7.1 Hz), 3.90 (1 H, d, J = 11.3 Hz),
d, J = 2.5 Hz), 6.79 (4 H, t, J = 7.1 Hz), 6.92 (8 H, t, J = 7.3 Hz), 4.01 (1 H, dd, J = 12.3 Hz, 2.4 Hz), 4.15 (1 H, dd, J = 12.3 Hz,
7.10–7.29 (14 H, m), 7.36 (1 H, d, J = 7.9 Hz), 7.41–7.48 (2 H, m), 4.0 Hz), 5.20 (1 H, d, J = 4.2 Hz), 6.65–6.71 (1 H, m), 6.95 (1 H,
7.53 (1 H, t, J = 7.8 Hz), 7.71 (1 H, d, J = 7.6 Hz), 8.92 (1 H, s); δC dd, J = 6.6 Hz, 2.1 Hz), 7.02–7.07 (2 H, m), 7.15–7.24 (3 H, m),
(100 MHz; DMSO-d6) 19.3, 20.2, 29.9, 56.2, 61.2, 66.5, 71.3, 7.32 (2 H, t, J = 7.7 Hz), 7.46 (2 H, t, J = 7.1 Hz); δC (125 MHz;
100.8, 122.2, 125.5, 125.8, 125.9, 128.37, 128.38, 128.42, 129.1, chloroform-d) 19.4, 19.5, 19.6, 22.3, 29.0, 50.9, 62.2, 63.1, 67.0,
129.7, 132.2, 136.2, 137.1, 138.3, 139.0, 139.9, 164.0; m/z found 73.7, 99.0, 126.0, 126.5, 126.57, 126.63, 127.2, 127.4, 127.6,
for [C28H30NO2]+ 412.2273, iminium cation requires 412.2271.
128.5, 128.9, 135.4, 136.3, 136.6, 138.1, 138.9, 140.0, 140.8; m/z
(+)-(Sa)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-[1,3]dioxan-5-yl)-1,11- (HNES) found for [C29H33NO2 + H]+: 428.2579; [M + H]+
dimethyl-5H-dibenzo[c,e] azepinium tetraphenylborate 5Sax. requires 428.2584.
Prepared according to the general procedure from 10Sax
(−)-(5R,11bRa)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-
(0.56 g, 1.35 mmol). The title compound 5Sax was isolated as a yl)-1,5,11-trimethyl-5H-dibenzo[c,e]azepin-6-ium tetraphenyl-
yellow solid (0.83 g, 83%). [α]2D0 +329.8 (c = 0.98, MeCN); borate 6Rax. Prepared according to the general procedure from
νmax(neat)/cm−1 3059, 2989, 2161, 1977, 1623, 1578, 1559, 11Rax (0.34 g, 0.81 mmol). The title compound 6Rax was iso-
1427, 1381, 1359, 1308, 1263, 1239, 1168, 1122, 1086, 1069, lated as a yellow powder (0.18 g, 30%). [α]2D0 −167.2 (c = 1.00,
1031, 1000, 969, 43, 783, 728, 664, 608; δH (400 MHz; DMSO- MeCN); νMAX(neat)/cm−1 3053, 2986, 1632, 1579, 1559, 1540,
d6) 1.72 (3 H, s), 1.75 (3 H, s), 2.03 (3 H, s), 2.23 (3 H, s), 3.83 1478, 1425, 1379, 1298, 1262, 1239, 1201, 1165, 1107, 1085,
(1 H, d, J = 13.2 Hz), 4.19 (1 H, d, J = 13.7 Hz), 4.70 (1 H, dd, J = 1045, 1032; δH (400 MHz; DMSO) 0.78 (3 H, br), 1.68 (3 H, s),
13.8 Hz, 3.9 Hz), 4.83 (1 H, s), 4.97 (1 H, d, J = 13.5 Hz), 5.85 1.70 (3 H, s), 1.90 (3 H, s), 2.16 (3 H, s), 4.26 (1 H, d, J = 13.2
(1 H, d, J = 2.9 Hz), 6.84 (4 H, t, J = 7.2 Hz), 6.98 (8 H, t, J = 7.4 Hz), 4.63–4.68 (2 H, m), 5.76 (1 H, br), 5.82 (1 H, s), 6.79 (4 H,
Hz), 7.10–7.19 (5 H, m), 7.21–7.29 (8 H, m), 7.42 (1 H, d, J = 8.0 t, J = 7.2 Hz), 6.92 (8 H, t, J = 7.4 Hz), 7.10–7.25 (14 H, m),
Hz), 7.49 (1 H, t, J = 7.5 Hz), 7.55 (1 H, d, J = 8.0 Hz), 7.64 (1 H, 7.32–7.40 (2 H, m), 7.59 (1 H, br), 7.71–7.74 (1 H, m), 9.20
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(1 H, s); δC (100 MHz; DMSO) 14.9, 19.3, 19.9, 20.0, 29.9, 62.0, perature overnight. Silica gel was added to the dark brown
65.9, 67.4, 70.8, 101.0, 122.2, 125.2, 125.9, 126.5, 127.5, 128.3, solution, and the mixture stirred for 20 min. The solvents were
128.7, 128.8, 129.7, 131.1, 132.0, 132.1, 136.2, 136.4, 137.7, removed under reduced pressure. The residue was transferred
138.8, 139.2, 140.2, 164.0; m/z found for [C29H32NO2]+: to a sintered glass funnel containing a layer of silica gel and
426.2435, iminium cation requires 426.2428.
washed with hexane until the product had eluted. The solvent
(+)-(5S,11bSa)-6-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5- was removed under reduced pressure to yield compound 14 as
yl)-1,5,11-trimethyl-5H-dibenzo[c,e]azepin-6-ium tetraphenyl- a colourless crystalline solid (28.01 g, 99%); m.p. 119–121 °C;
borate 6Sax. Prepared according to the general procedure from [α]2D0 −259.6 (c = 1.03, CHCl3), lit.28 [α]D20 −260.3 (c = 1.00,
11Sax (0.25 g, 0.58 mmol). The title compound 6Sax was iso- CHCl3); νmax(neat)/cm−1; 2947, 2870, 2836, 1476, 1464, 1451,
lated as a pale yellow powder (0.14 g, 32%). [α]2D0 +310.0 (c = 1410, 1249, 1202, 1182, 1138, 1048, 926, 872, 926, 872, 853,
1.00, MeCN); νmax(neat)/cm−1 3055, 2999, 1625, 1580, 1562, 834, 806, 763, 699, 644; δH (300 MHz; CDCl3) 1.75 (8 H, m),
1478, 1452, 1427, 1383, 1306, 1262, 1202, 1166, 1112, 1085, 2.28 (2 H, dt, J = 6.0 Hz, 17.4 Hz), 2.43 (2 H, dt, J = 6.0, 17.7
1032, 952, 844, 789, 748, 734, 666, 611; δH (400 MHz; DMSO) Hz), 2.86 (4 H, t, J = 6.0 Hz), 7.16 (2 H, d, J = 8.6 Hz), 7.23 (2 H,
0.65 (3 H, d, J = 7.2 Hz), 1.67 (6 H, s), 1.96 (3 H, s), 2.13 (3 H, d, J = 8.6 Hz); δC (75 MHz; CDCl3) 22.2, 22.3, 27.4, 29.3, 118.1,
s), 4.15 (1 H, d, J = 14.3 Hz), 4.65–4.69 (2 H, m), 5.76 (1 H, q, 118.2 (q, J = 322 Hz), 127.1, 130.9, 138.3, 139.3, 144.8.
J = 7.3 Hz), 5.85 (1 H, s), 6.79 (4 H, t, J = 7.2 Hz), 6.92 (8 H, t,
(−)-(Ra)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthyl-2,2′-bis-
J = 7.4 Hz), 7.04–7.22 (13 H, m), 7.38 (1 H, J = 7.4 Hz), (carboxylate) 15 .28 DMSO (90 mL), MeOH (36.0 mL, 1.56 mol)
7.42–7.52 (2 H, m), 7.59 (1 H, t, J = 7.7 Hz), 7.72 (2 H, t, J = 7.7 and Hünig’s base (13.4 mL, 137 mmol) were added to 14
Hz), 8.98 (1 H, s); δC (100 MHz; d6-DMSO) 14.4, 19.3, 19.9, (1.50 g, 17.9 mmol), Pd(OAc)2 (0.61 g, 4.7 mmol) and dppp
20.0, 30.0, 61.6, 68.1, 68.4, 71.8, 101.0, 122.2, 125.9, 126.0, (1.11 g, 4.70 mmol) under an argon atmosphere. The vessel
127.65, 127.70, 128.4, 128.6, 128.9, 129.5, 132.1, 132.3, 132.5, was sealed with a gas manifold and pressurised with CO (g) at
136.17, 136.18, 136.5, 137.9, 139.0, 139.3, 140.1, 141.1, 164.0, 2 bar followed by evacuation of the atmosphere until the
170.7; m/z found for [C29H32NO2]+ 426.2424; iminium cation orange solution just began to boil. The cycle was repeated five
requires 426.2428.
times. During the cycles, the solution turned to opaque black.
(−)-(Ra)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthyl-2,2′-diol The vessel was heated to 80 °C and maintained at a pressure
13 .29 (Ra)-Binol (3.00 g, 11.5 mmol) was divided equally of 2.4 atm. of CO for 48 h. The reaction mixture was trans-
between three test tubes each containing Pd/C 10% w/w ferred to a round-bottomed flask, and solvents were removed
(0.20 g). Glacial acetic acid (4.0 mL) was added to each of the under reduced pressure to yield an oily residue. This crude
test tubes and mixed. The tubes were then placed in a hydro- residue was purified by column chromatography, eluting with
genation apparatus, and were charged and evacuated with H2 light petroleum/EtOAc (5 : 1). Compound 15 was obtained as a
twice. The pressure was increased to 50 bar and the reaction colourless crystalline solid (5.9 g, 88%); m.p. = 99–105 °C;
mixtures stirred at ambient temperature. The reactions were [α]2D0 −2.1 (c = 0.96, CHCl3), lit.28 [α]2D0 −1.9 (c = 1.00, CHCl3);
monitored over 10 days. The combined mixture was filtered νmax(neat)/cm−1 2926, 2853, 1718, 1588, 1430, 1400, 1289,
through celite and washed through with CHCl3. The organic 1251, 1186, 1164, 1124, 1066, 1050, 878, 861, 832, 771, 749;
filtrate was washed with saturated aqueous NaHCO3 (1 × δH (300 MHz; CDCl3) 1.69 (8 H, m), 1.99 (2 H, dt, J = 5.9 Hz,
50 mL), water (2 × 50 mL), and brine (1 × 50 mL). The organic 17.0 Hz), 2.18 (2 H, dt, J = 6.4 Hz, 17.2 Hz), 2.86 (4 H, m), 3.57
layer was dried over MgSO4 and solvents were removed under (6 H, s), 7.13 (2 H, d, J = 8.1 Hz), 7.76 (2 H, d, J = 8.1 Hz); δC
reduced pressure to yield a colourless solid. Column chromato- (75 MHz; CDCl3) 22.4, 23.0, 27.2, 30.2, 51.5, 126.6, 127.1,
graphy was performed, eluting with light petroleum ether/ 128.0, 135.4, 141.7, 141.9, 167.6.
EtOAc (4 : 1), to yield compound 13 as a colourless solid which
(−)-(Ra)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthyl-2,2′-
was crystallized from hexane to give fine colourless needles dimethanol 12 .21 A suspension of LiAlH4 (0.30 g, 7.94 mmol)
(1.63 g, 52%); [α]D20 −42.6 (c = 1.06, CHCl3), lit.29 [α]2D0 −42.5 (c = in Et2O (50 mL) under a nitrogen atmosphere was cooled to
1.00, CHCl3); νmax(neat)/cm−1 3475, 3381, 2929, 2856, 1587, 0 °C. Compound 15 (1.50 g, 3.97 mmol) was added slowly.
1472, 1333, 1287, 1248, 1195, 1152, 936, 828, 812, 726; After the effervescence had ceased, the reaction mixture was
δH (300 MHz; CDCl3) 1.63–1.78 (8 H, m), 2.16 (2 H, dt, J = 17.0 heated under reflux for 30 min. The mixture was cooled in an
Hz, 6.0 Hz), 2.29 (2 H, dt, J = 17.0 Hz, 6.1 Hz), 2.75 (4 H, t, J = ice bath. Na2SO4 (1.50 g) and Celite were added in one portion
6.2 Hz), 4.56 (2 H, br), 6.83 (2 H, d, J = 8.4 Hz), 7.07 (2 H, d, J = and stirred for 10 min followed by the dropwise addition of
8.3 Hz); δC (75 MHz; CDCl3) 22.8, 22.9, 27.0, 29.1, 113.0, 118.8, water (2.0 mL). After 30 min, the mixture was filtered through
130.2, 131.1, 137.2, 151.5.
a pad of Celite and Na2SO4, and washed though with Et2O.
(−)-(Ra)-2,2′-Trifluoromethanesulfonyloxy-5,5′6,6′7,7′,8,8′-octa- The solvents were removed under reduced pressure to yield
hydro-1,1′-binaphthyl 14 .28 Compound 13 (10.0 g, 34 mmol) compound 12 as a colourless foam (1.24 g, 99%); [α]D20 −39.1
was dissolved in CH2Cl2 (250 mL) in a flame-dried flask under (c = 0.96, MeOH), lit.21 [α]D20 −39.0 (c = 1.01, MeOH); νmax(neat)/
an atmosphere of N2. The vessel was cooled to −30 °C. DMAP cm−1 3257, 2923, 2853, 1594, 1433, 1231, 1061, 1005, 899, 815,
(1.66 g, 13.6 mmol), 2,6-lutidine (11.9 mL, 102 mmol) and 740; δH (300 MHz; CDCl3) 1.69 (8 H, m), 2.02 (4 H, m), 2.82
Tf2O (17.2 mL, 102 mmol) were added to the solution and the (4 H, t, J = 8.8 Hz), 2.92 (2 H, s), 4.02 (2 H, d, J = 12.0 Hz), 4.21
mixture stirred for 10 min, and allowed to reach room tem- (2 H, d, J = 12.0 Hz), 7.11 (2 H, d, J = 8.8 Hz), 7.24 (2 H, d, J =
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8.8 Hz); δC (75 MHz; CDCl3) 22.7, 23.2, 27.6, 29.8, 62.9, 127.2, (1 mL) was added followed by NaCNBH3 (44 mg, 2 equiv.,
128.9, 134.8, 135.7, 137.6, 138.3. 0.70 mmol) and glacial acetic acid (0.2 mL). The mixture was
(+)-(Ra)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthyl-2,2′-bis- stirred for 24 h at ambient temperature, and a 1 M aq. solution
(carbaldehyde) 16 .21 Compound 12 (0.11 g, 0.34 mmol) was of NaOH (25 mL) added. The mixture was extracted with Et2O
dissolved in CH2Cl2 (20 mL), and PCC (0.22 g, 1.02 mmol) (3 × 20 mL). The combined organic layers were washed with
added in one portion. The resulting dark orange solution was brine (30 mL) and dried over MgSO4. Solvents were removed
stirred for 2 h, and celite added followed by Et2O (20 mL). The under reduced pressure to yield a pale yellow foam that was
mixture was stirred for 30 min and filtered through a layered purified by column chromatography, eluting with light pet-
pad of silica gel and Celite. The desired compound was eluted roleum ether/EtOAc (5 : 1). Compound 17 was isolated as col-
with Et2O. Solvents were then removed to furnish compound ourless crystals (116 mg, 67%). [α]2D0 −27.7 (c = 0.72, CHCl3);
16 as a colourless crystalline solid (0.11 g, 99%); m.p. νmax(neat)/cm−1 2928, 2832, 1451, 1377, 1291, 1267, 1237,
129–131 °C; [α]D20 +110.4 (c = 0.83, CHCl3), lit.21 [α]2D0 +108.5 (c = 1194, 1172, 1147, 1074, 1053, 1017, 939, 898, 852, 829, 810,
1.00, CHCl3); νmax(neat)/cm−1 2931, 2851, 2747, 1688, 1672, 753, 723, 700, 654, 640, 628; δH (300 MHz; CDCl3) 1.46–1.57
1582, 1441, 1383, 1315, 1292, 1268, 1246, 1230, 1162, 1125, (2 H, m), 1.57 (3 H, s), 1.62 (3 H, s), 1.67–1.82 (6 H, m), 2.13
996, 968, 943, 913, 897, 836, 811, 760; δH (300 MHz; CDCl3) (2 H, dt, J = 5.9 Hz, 11.5 Hz), 2.58–2.65 (3 H, m), 2.75–2.86
1.73 (8 H, m), 2.15 (4 H, m), 2.91 (4 H, t, J = 6.1 Hz), 7.29 (2 H, (4 H, m), 3.09 (2 H, d, J = 12.1 Hz), 3.57 (2 H, d, J = 12.2 Hz),
d, J = 8.1 Hz), 7.82 (2 H, d, J = 8.1 Hz), 9.51 (2 H, s); 4.17 (2 H, m), 5.07 (1 H, d, J = 3.1 Hz), 6.89 (2 H, d, J = 7.6 Hz),
δC (75 MHz; CDCl3) 22.2, 22.7, 27.4, 30.4, 125.1, 129.8, 132.4, 6.98 (2 H, d, J = 7.6 Hz), 7.30 (5 H, m); δC (75 MHz; CDCl3)
136.2, 140.7, 145.2, 191.5.
19.1, 22.7, 22.9, 27.6, 29.4, 29.6, 52.7, 59.8, 61.8, 75.0, 99.1,
(Ra)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-binaphthyl-2,2′-bis- 126.0, 126.7, 127.6, 128.2, 133.6, 135.0, 136.0, 138.2, 140.4; m/z
(bromomethyl) 18 .27 Compound 12 (2.03 g, 6.3 mmol) was (HNES) found for [C34H39NO2 + H]+: 494.3039; [M + H]+:
dissolved in toluene (60 mL) under an atmosphere of N2, and requires 494.3039.
pyridine (0.05 mL, 0.7 mmol) added. Tribromophosphine
(−)-(Ra)-4-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)-
(1.78 mL, 18.9 mmol) was added dropwise. After the addition 8,9,10,11,12,13,14,15-octahydro-3H-dinaphtho[2,1-c:1′,2′-e]-
was complete, the mixture was heated at 60 °C for 3 h. After azepin-4-ium tetraphenylborate 19. Prepared according to the
cooling, water (50 mL) was added, and the resulting biphasic general procedure from 17 (1.47 g, 2.98 mmol) and NBS
mixture transferred to a separating funnel. The organic layer (0.58 g, 3.28 mmol). Ion exchange was performed with NaBPh4
was isolated and washed with saturated aqueous NaHCO3 (1.12 g, 3.28 mmol). The title compound 19 was isolated as a
(20 mL). The organic layers were dried over MgSO4 and de- fine, pale-yellow crystalline solid (1.51 g, 63%). m.p.
colourized with a spatula of carbon black, and filtered. The 195–199 °C; [α]2D0 −331.9 (c = 1.01, acetone); νmax(neat)/cm−1
solvents were removed under reduced pressure to yield com- 3053, 2982, 2936, 2864, 1615, 1577, 1479, 1450, 1424, 1380,
pound 18 as a colourless powder (2.79 g, 99%); [α]2D0 +34.3 (c = 1304, 1263, 1235, 1198, 1107, 1083, 1010, 954, 941, 904, 835,
2.05, CHCl3), lit.27 [α]D20 +36.5 (c = 1.00, CH2Cl2); νmax(neat)/ 763, 746, 731, 701, 660, 623, 609; δH (400 MHz; acetone-d6,
cm−1 2920, 2851, 1592, 1457, 1376, 1235, 1204, 928, 862, 831, 50 °C) 1.35–1.41 (1 H, m), 1.45–1.56 (1 H, m), 1.67 (3 H, s),
814, 759, 723, 623; δH (300 MHz; CDCl3) 1.71 (8 H, m), 2.07 (2 1.70 (3 H, s), 1.67–1.85 (6 H, m), 2.01–2.06 (1 H, m), 2.24 (1 H,
H, dt, J = 6.4 Hz, 17.6 Hz), 2.34 (2 H, dt, J = 5.5 Hz, 17.0 Hz), J = 7.5 Hz), 2.53–2.62 (1 H, m), 2.70–3.01 (5 H, m), 4.12 (1 H, d,
2.83 (4 H, t, J = 5.9 Hz), 4.10 (2 H, d, J = 9.9 Hz), 4.15 (2 H, d, J = 13.2 Hz), 4.21 (2 H, d, J = 13.7 Hz), 4.41 (1 H, t, J = 2.6 Hz),
J = 10.0 Hz), 7.14 (2 H, d, J = 7.9 Hz), 7.33 (2 H, d, J = 7.9 Hz); 4.63 (1 H, dd, J = 13.7 Hz, 3.0 Hz), 5.18 (1 H, d, J = 13.7 Hz),
δC (75 MHz; CDCl3) 22.6, 22.9, 27.5, 29.9, 32.9, 128.1, 129.6, 5.74 (1 H, d, J = 3.0 Hz), 6.75 (4 H, t, J = 7.2 Hz), 6.89 (8 H, t, J =
132.3, 135.6, 137.9, 138.6.
7.4 Hz), 7.06–7.21 (6 H, m), 7.23–7.40 (11 H, m), 8.73 (1 H, s);
(−)-(Ra)-4-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl)- δC (75 MHz; acetone-d6) 18.0, 21.6, 21.9, 22.0, 22.1, 27.4, 27.5,
4,5,8,9,10,11,12,13,14,15-decahydro-3H-dinaphtho[2,1-c:1′,2′-e]- 28.9, 29.2, 29.8, 57.6, 60.1, 66.0, 71.3, 100.8, 121.6, 124.9,
azepine 17. Method 1: Compound 18 (0.17 g, 0.38 mmol) was 125.0, 125.3, 125.8, 128.1, 128.8, 129.1, 129.4, 130.4, 133.5,
dissolved in MeCN (10 mL) under an atmosphere of N2. K2CO3 134.5, 136.28, 136.32, 137.7, 139.1, 139.9, 140.9, 145.0, 164.3,
(0.15 g, 1.11 mmol) and a solution of amine 4 (79 mg, 169.7; m/z (HNES) found for [C34H38NO2]+: 492.2895; iminium
0.38 mmol) in MeCN (2 mL) were added. The mixture was cation requires 492.2897.
stirred at room temperature for 1 h, heated under reflux over-
(−)-(3R,11cRa)-4-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-
night, and allowed to cool. CH2Cl2 (30 mL) and water (30 mL) yl)-3-methyl-4,5,8,9,10,11,12,13,14,15-decahydro-3H-dinaphtho
were added. The organic layer was separated and the aqueous [2,1-c:1′,2′-e]azepine 20. Prepared according to the general pro-
layer washed with CH2Cl2 (2 × 20 mL). The organic layers were cedure from 19 (1.28 g, 1.57 mmol) and 3 M MeMgBr
combined and dried over MgSO4, and solvents were removed (5.26 mL, 15.7 mmol). The crude mixture was purified by
under reduced pressure to yield 17 in excellent purity as col- column chromatography eluting with light petroleum/EtOAc
ourless crystals (0.18 g, 97%).
(5 : 1), buffered with 2% TEA. The title compound 20 was iso-
Method 2: Compound 16 (0.11 g, 0.35 mmol) was sus- lated as a colourless oil (0.63 g, 79%). [α]2D0 −8.4 (c = 2.04,
pended in MeOH (4 mL) under an atmosphere of N2. A solu- CHCl3); δH (300 MHz; CDCl3) 0.18 (3 H, d, J = 7.1 Hz),
tion of amine 4 (79 mg, 1.1 equiv., 0.38 mmol) in MeOH 1.42–1.63 (2 H, m), 1.55 (3 H, s), 1.63 (3 H, s), 1.68–1.81 (6 H,
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m), 2.09–2.19 (2 H, m), 2.54–2.69 (2 H, m), 2.77–2.82 (4 H, m), MeCN (1 mL) and water (0.1 mL) at 0 °C. After 5 min, alkene
2.91 (1 H, td, J = 4.2 Hz, 2.5 Hz), 3.31 (1 H, d, J = 11.2 Hz), 3.35 (3 mmol) dissolved in MeCN (1 mL), was added. The mixture
(1 H, d, J = 11.2 Hz), 4.09 (1 H, dd, J = 12.3 Hz, 2.4 Hz), 4.21 was stirred at 0 °C until complete conversion of the alkene was
(1 H, dd, J = 12.3 Hz, 4.3 Hz), 4.34 (1 H, q, J = 7.0 Hz), 5.13 observed by TLC, or for up to 6 h. The reaction mixture was
(1 H, d, J = 3.5 Hz), 6.81 (1 H, d, J = 7.6 Hz), 6.81 (1 H, d, J = 7.7 then diluted with Et2O (10 mL) and the resulting suspension
Hz), 6.94 (1 H, d, J = 7.6 Hz), 6.97 (1 H, d, J = 7.7 Hz), 7.22–7.38 filtered through a pad of mixed Na2SO3 and MgSO4. The sol-
(1 H, m); δC (75 MHz; CDCl3) 19.4, 21.0, 22.7, 22.8, 22.9, 27.3, vents were removed under reduced pressure, and analytically
29.0, 29.3, 29.4, 54.3, 59.0, 60.1, 62.9, 74.1, 99.3, 125.9, 126.4, pure samples of the epoxide were obtained by means of flash
126.5, 126.6, 127.6, 128.1, 128.2, 135.2, 135.5, 135.6, 135.7, column chromatography or preparative TLC, typically eluting
136.1, 136.6, 138.4, 138.8, 140.3; m/z (HNES) found for with light petroleum/EtOAc (99 : 1), containing 2% TEA. The
[C35H41NO2 + H]+: 508.3204; [M + H]+ requires 508.3210.
major enantiomer was identified by [α]2D0 measurements and
(−)-(3R,11cRa)-4-((4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5- comparison to the literature; enantioselectivities were deter-
yl)-3-methyl-8,9,10,11,12,13,14,15-octahydro-3H-dinaphtho- mined either by chiral HPLC, or by 1H NMR spectroscopy in
[2,1-c:1′,2′-e]azepin-4-ium
according to the general procedure from 20 (0.62 g,
tetraphenylborate
21. Prepared the presence of a resolving agent.
Method B: A mixture of water (1 ml), MeCN (1 mL) and
1.22 mmol) and NBS (0.24 g, 1.34 mmol). Ion exchange was NaHCO3 (100 mg, 1.2 mmol) was cooled in an ice-bath at 0 °C.
performed using NaBPh4 (0.46 g, 1.34 mmol). The title com- Oxone® (370 mg, 0.6 mmol) was added. After the effervescence
pound 21 was isolated as a pale yellow crystalline solid (0.71 g, had subsided, the catalyst (5 mol%) was added followed, after
71%). m.p. 121–122 °C; [α]2D0 −232.8 (c = 1.00, acetone); 1 min, by the alkene (0.3 mmol). The mixture was stirred at
νmax(neat)/cm−1 3055, 2986, 2936, 2864, 1623, 1575, 1479, 0 °C until complete conversion of the alkene was observed by
1449, 1426, 1381, 1308, 1265, 1236, 1201, 1165, 1107, 1080, TLC, or for up to 6 h. The reaction mixture was diluted with
1031, 1000, 956, 910, 835, 731; δH (400 MHz; acetone-d6) 1.05 Et2O (10 mL per 0.10 g of substrate), and the resulting suspen-
(3 H, d, J = 7.1 Hz), 1.35–1.58 (2 H, m), 1.66–1.90 (6 H, m), 1.69 sion filtered through a pad of mixed Na2SO3 and MgSO4. The
(3 H, s), 1.74 (3 H, s), 2.25 (1 H, dt, J = 10.4 Hz, 5.7 Hz), solvents were removed under reduced pressure, and analyti-
2.47–2.60 (1 H, m), 2.72–2.88 (4 H, m), 2.98 (2 H, dd, J = 11.7 cally pure samples of the epoxide were obtained by either flash
Hz, 6.5 Hz), 4.39 (1 H, dd, J = 0.8 Hz, 13.6 Hz), 4.74 (1 H, t, J = column chromatography or preparative TLC, eluting with light
2.5 Hz), 4.81 (1 H, dd, J = 13.7 Hz, 2.9 Hz), 5.49 (1 H, q, J = petroleum/EtOAc (99 : 1), containing 2% TEA. The major enan-
6.5 Hz), 5.83 (1 H, d, J = 2.8 Hz), 6.78 (4 H, t, J = 7.1 Hz), 6.92 tiomer was identified by [α]2D0 measurements and comparison
(8 H, t, J = 7.4 Hz), 7.02–7.23 (7 H, m), 7.28–7.37 (8 H, m), 7.44 with the literature; enantioselectivities were determined either
(1 H, d, J = 8.0 Hz), 7.60 (1 H, d, J = 8.0 Hz), 9.25 (1 H, s); by chiral HPLC, or by 1H NMR spectroscopy in the presence of
δC (100 MHz; acetone-d6) 14.9, 18.1, 21.6, 22.1, 22.2, 22.4, 27.3, a resolving agent.
27.6, 29.1, 29.3, 30.0, 61.9, 67.5, 69.8, 71.1, 101.0, 121.6, 124.8,
Method C: A mixture of water (0.8 mL) and NaHCO3
124.9, 125.3, 125.8, 128.0, 128.6, 129.2, 130.2, 130.5, 131.3, (67 mg, 0.80 mmol) was cooled in an ice-bath at 0 °C. Oxone®
136.0, 136.4, 138.1, 139.5, 139.7, 141.2, 147.7, 164.3, 168.6; m/z (132.0 mg, 0.21 mmol) was added, and the solution stirred
(HNES) found for [C35H40NO2]+: 506.3054; iminium cation until the effervescence had ceased. The alkene (0.20 mmol)
requires 506.3043.
was dissolved in CH2Cl2 (0.5 mL) and added. A solution of the
catalyst (5 mol%) and 18-crown-6 (1 mg, 2.5 mol%) in CH2Cl2
(0.7 mL) was cooled to 0 °C, and added with stirring. The reac-
General procedure for the formation of racemic epoxides
The alkene was dissolved in CH2Cl2 (10 mL per g of alkene) tion mixture was vigorously stirred, typically for 2 h at 0 °C.
and the solution cooled to 0 °C. A solution of m-CPBA CH2Cl2 (10 mL) and water (10 mL), both cooled to around
(2 equiv.) in CH2Cl2 (10 mL per g of alkene), dried over MgSO4, 0 °C, were added. The organic layer was collected and dried
was filtered into the solution of alkene. The reaction was allowed over MgSO4. The solvents were removed under reduced
to achieve ambient temperature and stirred until complete con- pressure, and analytically pure samples of the epoxide were
version of the alkene was observed by TLC. Saturated aqueous obtained by either column chromatography or preparative
NaHCO3 (10 mL per g of alkene) was added, and organic layer TLC, eluting with light petroleum/EtOAc (99 : 1), containing
collected and washed with 1 M NaOH (10 mL per g of alkene), 2% TEA. The major enantiomer was identified by
and dried over MgSO4. The solvents were removed under reduced [α]2D0 measurements; enantioselectivities were determined
1
pressure. Analytically pure samples of the epoxides were obtained either by chiral HPLC, or by H NMR spectroscopy in the pres-
by means of flash column chromatography, typically eluting with ence of a resolving agent.
light petroleum/EtOAc (99 : 1), buffered with 2% TEA.
Tetraphenylphosphonium monoperoxysulfate15
General procedures for catalytic asymmetric epoxidation of
alkenes with Oxone® mediated by iminium salts under
aqueous conditions
Tetraphenylphosphonium chloride (15.0 g, 40 mmol) was dis-
solved in CH2Cl2 (200 mL), and the solution cooled to 10 °C. A
solution of Oxone® (15.0 g, 48 mmol) in deionised water
Method A: Oxone® (2 equiv.) and NaHCO3 (5 equiv.) were (300 mL) was cooled to 10 °C, and added over a period of
added with stirring to a solution of the catalyst (5 mol%) in 5 min. The resulting biphasic mixture was stirred vigorously
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for 1 h. The organic layer was separated, and the solvents were (10 H, m); δC (75 MHz; CDCl3) 63.3, 126.0, 128.6, 129.3, 137.6.
removed under reduced pressure at room temperature. The HPLC conditions-hexane/2-propanol (80 : 20), oven temp 20 °C,
crude colourless solid was washed with deionised water (3 × column Chiracel OD-H 01 250 × 4.6 mm, 5 μm particle size,
80 mL). The solid was re-dissolved in CH2Cl2 (150 mL) and flow rate 1 mL min−1, 254 nm: tr-4.98 min (−)-(1S,2S),
dried over MgSO4. Hexane was added until a solid precipitate 6.54 min (+)-(1R,2R).
just began to form, and the flask placed in a freezer overnight.
Dihydronaphthalene oxide.16 Isolated as a colourless oil:
The resulting colourless crystalline solid was collected by fil- νmax(neat)/cm−1 3058, 3028, 2931, 2850, 1602, 1492, 1314,
tration (12.87 g, 71%); νmax(neat)/cm−1 3210, 3060, 1586, 1484, 1129, 1088, 1031, 965; δH (400 MHz; CDCl3) 1.65–1.84 (1 H, m),
1435, 1262, 1226, 1162, 1106, 1058, 1041, 996, 721; 2.33–2.42 (1 H, m), 2.52 (1 H, dd, J = 15.5 Hz, 5.5 Hz),
δH (400 MHz; CDCl3) 7.58–7.69 (8 H, m), 7.71–7.80 (8 H, m), 2.67–2.85 (1 H, m), 3.71–3.80 (1 H, m), 3.81–3.89 (1 H, m), 7.05
7.82–7.86 (4 H, m), 9.18 (1 H, s). The oxygen content, typically (1 H, d, J = 7.2 Hz), 7.18–7.35 (2 H, m), 7.40 (1 H, d, J = 7.1 Hz).
94% peroxide, was estimated by comparing the integrals of the
aromatic and hydroxyl signals.
Triphenylethylene oxide.16 Isolated as a colourless crystal-
line solid: νmax(neat)/cm−1 3061, 3031, 2956, 2924, 2857, 1604,
1595, 1498, 1471, 1448, 1262, 1220, 741, 699; δH (400 MHz;
CDCl3) 4.42 (1 H, s), 7.13–5.50 (15H, m). HPLC conditions-
hexane/2-propanol (90 : 10), oven temp 20 °C, column Chiracel
OD-H 01 250 × 4.6 mm, 5 μm particle size, flow rate 1 mL
General procedure for catalytic asymmetric epoxidation of
alkenes with TPPP mediated by iminium salts under
non-aqueous conditions
A solution of alkene was cooled to the required temperature, min−1, 254 nm: tr – 4.26 min (+)-(S), 7.47 min (−)-(R).
and TPPP was added in one portion with stirring over 2 min.
The catalyst was added as a solid in small portions over 1 min.
The reaction was stirred until complete consumption of the
starting alkene had been observed, or until it was judged that
Acknowledgements
no further conversion was occurring, by TLC. Et2O, cooled to This investigation has enjoyed the support of the EPSRC,
0 °C, was added to precipitate out TPPP and its reduced by-pro- Loughborough University, the University of East Anglia, Charn-
ducts. The suspension was filtered through a thin pad of celite wood Molecular Ltd, and the ERDF (ISCE-Chem & INTERREG
and silica gel to yield the desired epoxide. If column chromato- IVa programme 4061). We acknowledge the support of The
graphy was required, it was typically performed eluting with Royal Society. We are also indebted to the EPSRC Mass Spec-
light petroleum/EtOAc (99 : 1), containing 2% TEA. The major trometry Unit, Swansea. The calculations presented in this
enantiomer was identified by [α]2D0 measurements and com- paper were carried out on the High Performance Computing
parison to the literature; enantioselectivities were determined Cluster supported by the Research and Specialist Computing
1
by either chiral HPLC, or by H NMR spectroscopy in the pres- Support service at the University of East Anglia.
ence of a resolving agent.
(E)-Methylstilbene oxide.30 Isolated as a colourless crystal-
line solid: νmax(neat)/cm−1 3061, 1601, 1495, 1449, 1370, 1278,
1156, 1117, 1065, 1026, 980; δH (300 MHz; CDCl3) 1.46 (3 H, s),
References
3.95 (1 H, s), 7.30–7.45 (10 H, m). HPLC conditions-hexane/2-
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propanol (80 : 20), oven temp 20 °C, column Chiracel OD-H 01
250 × 4.6 mm, 5 μm particle size, flow rate 1 mL min−1
254 nm: tr-4.00 min (−)-(1S,2S), 6.92 min (+)-(1R,2R).
,
1-Phenylcyclohexene oxide.30 Isolated as a colourless oil:
νmax(neat)/cm−1 3083, 1602, 1495, 1445, 1359, 1248, 1174,
1133, 1078, 1030, 993, 974; δH (300 MHz; CDCl3) 1.20–1.33 (1 H,
m), 1.51–1.62 (3 H, m), 1.97–2.05 (2 H, m), 2.16–2.18 (1 H, m),
2.24–2.31 (1 H, m), 3.10 (1 H, t, J = 2.0 Hz), 7.26–7.41 (5 H, m).
1-Phenyldihydronaphthalene oxide.30 Isolated as a colour-
less crystalline solid: νmax(neat)/cm−1 3087, 1601, 1493, 1284,
1176, 1158, 1094, 1072, 1028; δH (300 MHz; CDCl3) 2.10 (1 H,
td, J = 15.5 Hz, 5.6 Hz) 2.48–2.59 (1 H, m), 2.76 (1 H, dd, J =
15.5 Hz, 5.5 Hz) 2.96–3.07 (1 H, m), 3.70 (1 H, d, J = 3.0 Hz),
7.09–3.29 (4 H, m), 7.45–7.60 (5 H, m). HPLC conditions-
hexane/2-propanol (90 : 10), oven temp 20 °C, column Chiracel
OD-H 01 250 × 4.6 mm, 5 μm particle size, flow rate 1 mL
min−1, 254 nm: tr-4.51 min (−)-(1S,2R), 5.94 min (+)-(1R,2S).
(E)-Stilbene oxide.30 Isolated as a colourless crystalline
solid: νmax(neat)/cm−1 3081, 1776, 1602, 1485, 1336, 1155,
1074, 1042, 953; δH (400 MHz; CDCl3) 3.87 (2 H, s), 7.29–7.39
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