Lithiation-electrophilic trapping of N-sulfonyl-activated ethylene aziridines

Article abstract of DOI:10.1039/b815957b

A detailed study on the lithiation-electrophilic trapping of N-sulfonyl ethylene aziridines is described. The optimum results required use of a N-2,4,6-tri-iso-propylbenzenesulfonyl activating group and lithiation using 3 equiv. of s-BuLi-PMDETA for 1 min

Full text of DOI:10.1039/b815957b

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Lithiation-electrophilic trapping of N-sulfonyl-activated ethylene aziridines†
Jianhui Huang,a Stephen P. Moore,a Peter O’Brien,*a Adrian C. Whitwood‡a and John Gildayb
Received 11th September 2008, Accepted 15th October 2008
First published as an Advance Article on the web 17th November 2008
DOI: 10.1039/b815957b
A detailed study on the lithiation-electrophilic trapping of N-sulfonyl ethylene aziridines is described.
The optimum results required use of a N-2,4,6-tri-iso-propylbenzenesulfonyl activating group and
lithiation using 3 equiv. of s-BuLi–PMDETA for 1 minute before addition of the electrophile. In situ
trapping with Me3SiCl was also successful. Electrophilic trapping with aldehydes provided a
stereoselective route to syn-hydroxy aziridines. Alternatively, keto aziridines could be stereoselectively
reduced to syn-hydroxy aziridines using NaBH4–CeCl3. The relative stereochemistry in two of the
hydroxy aziridines was established unequivocally by X-ray crystallography.
the lithiation of aziridine borane 5 using s-BuLi in THF at -78 ◦C
Introduction
and subsequent trapping with a range of electrophiles (50–95%
yields).10 An asymmetric variant (ca 85 : 15 er) was subsequently
Deprotonation and subsequent electrophilic trapping is one of the
fundamental strategies for the construction of organic molecules.
Within the context of our ongoing studies into the chemistry of
lithiated aziridines,1–7 we envisaged a new strategy for the synthesis
optimised using s-BuLi–(-)-sparteine-mediated deprotonation.11
Finally, in 2008, Hodgson et al. reported the successful lithiation-
external trapping of N-tert-butylsulfinyl aziridine 6 (LTMP,
TMEDA, THF, -98 ◦C; 52–8◦1% yields) and N-Bus aziridine 7
of trans-1,2-disubstituted aziridines 3 starting from N-sulfonyl-
(s-BuLi, TMEDA, THF, -105 C; 51–96% yields).12 These results
activated ethylene aziridines 1 (Scheme 1). In step 1, lithiation-
trapping of ethylene aziridines 1 would be carried out to give
demonstrate that the lithiation-trapping of N-sulfonyl, N-sulfinyl
monosubstituted aziridines 2. Then, in step 2, lithiation-trapping
and N-Boc ethylene aziridines is not straightforward and either
at the terminal end of aziridines 2 should afford disubstituted
required use of in situ electrophilic trapping (with its associated
aziridines 3. In 2005, Hodgson et al. reported a detailed study on
limitations on compatible electrophiles) or temperatures of ca.
◦
step 2 for the conversion of N-Bus activated aziridines 2 into 3
(Bus = tert-butylsulfonyl) where R1 = alkyl and R2 = SiMe3, D,
SnBu3, C(OH)R3R4, C(O)R3 and SO2Ph.8 However, at the outset
of our studies, much less was known about the lithiation-trapping
of ethylene aziridines 1 (step 1).
-100 C. As a result, our attention focused on developing useful
lithiation conditions for N-sulfonyl ethylene aziridines (step 1).
In this paper, we report our studies on the lithiation-trapping
of N-sulfonyl aziridines 7–9 (Fig. 1). In particular, we have
developed a convenient protocol for the lithiation-trapping of
a N-Tris-activated ethylene aziridine 9 (Tris = 2,4,6-tri-iso-
propylbenzenesulfonyl), and show its synthetic potential with
a stereoselective route to syn-hydroxy aziridines. Of note, our
methodology requires neither an in situ electrophilic trap nor
inconveniently low temperatures (ca. -100 ◦C).
Scheme 1 Reagents and conditions: i, (a) Base; (b) R1+. ii, (a) Base, R2+
.
To the best of our knowledge, there are three previous reports
on the lithiation-trapping of ethylene aziridines. In 1994, Beak
et al. described the lithiation (s-BuLi, TMEDA, Et2O, -78 ◦C) and
in situ Me3SiCl-trapping of N-Boc aziridine 4 (80% yield of sily-
lated aziridine).9 Attempts at external trapping of N-Boc aziridine
4 were unsuccessful. Then, in 1997, Vedejs and Kendall reported
aDepartment of Chemistry, University of York, Heslington, York, UK YO10
5DD. E-mail: paob1@york.ac.uk; Fax: +44 1904 432516; Tel: +44 1904
432535
bAstraZeneca, Process R & D, Avlon Works, Severn Road, Hallen, Bristol,
UK BS10 7ZE
Fig. 1 Selection of N-activated ethylene aziridines.
† Electronic supplementary information (ESI) available: Additional ex-
perimental procedures. CCDC reference numbers 695489 and 695490. For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/b815957b
‡ Author to whom correspondence regarding the X-ray crystal structure
should be addressed.
Results and discussion
Initially, we decided to compare the lithiation-trapping of N-
sulfonyl aziridines 7–9 equipped with tert-butylsulfonyl (Bus),
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4-methylbenzenesulfonyl (Ts) and 2,4,6-tri-iso-propylbenzene-
sulfonyl (Tris) activating groups. N-Sulfonyl aziridines 7–9 were
synthesised from ethanolamine as outlined in Scheme 2. Using
a protocol for the preparation of a related N-Bus aziridine,13
N- and O-sulfinylation of ethanolamine was accomplished using
t-BuSOCl.14 Then, m-CPBA oxidation was followed by base-
mediated cyclisation to give N-Bus aziridine 7 (48% yield of 3
steps). A different procedure was used for the preparation of the
arylsulfonyl aziridines 8 and 9. N-Sulfonylation of ethanolamine
was followed by a two-step procedure of O-mesylation and
cyclisation.15,16
adduct 11 was generated in 22% yield (entry 2). ortho-Lithiation
of arylsulfonyl groups is precedented by ourselves15 and others.17
Next, we attempted to increase the yield for silylation of N-Tris
aziridine 9. Use of (-)-sparteine in place of PMDETA as the ligand
gave a 12% yield of silyl aziridine 12 and 52% recovered starting
material (entry 4), clearly showing that PMDETA is the preferred
ligand. The enantiomeric ratio (er) of silyl aziridine 12 generated
from the s-BuLi–(-)-sparteine reaction was not determined but
lithiations using s-BuLi–(-)-sparteine in THF generally give low
levels of enantioselectivity, as we have previously demonstrated in
an aziridine lithiation process.3
After the 1 hour lithiation time at -78 ◦C, there was no
improvement in◦silylation either by leaving the reaction for another
3 hours at -78 C (63% yield of 12, entry 5) or by allowing the
reaction to warm to room temperature over 3 hours (58% yield of
12, entry 6). Finally, the use of 3 equiv. of s-BuLi–PMDETA was
optimal: lowering the amount of s-BuLi–PMDETA to 1.2 equiv.
gave only a 28% yield of 12 and 59% starting material (entry
7). Overall, the best lithiation-silylation conditions involved using
N-Tris aziridine 9 and 3 equiv. of each of s-BuLi, PMDETA
and Me3SiCl which gave a 66% yield of silyl aziridine 12 (entry
3). It is notable that, under these in situ trapping conditions,
significant amounts of starting aziridines 7–9 were recovered from
the reactions.
We then optimised conditions for the lithiation-silylation of
N-Tris aziridine 9 under external trapping conditions, a more
synthetically appealing protocol. The procedure adopted was as
follows: s-BuLi and ligand (PMDETA, TMEDA or (-)-sparteine)
were premixed in THF at -78 ◦C and then added to a solution of
the aziridine in THF at -78 ◦C. After 1 minute, Me3SiCl was added
and the reactions were quenched with NH4Cl(aq) after 1 hour. The
results are summarised in Table 2.
t
Scheme 2 Reagents and conditions: i, (a) 2.2 eq BuSOCl, 5 : 1 MeCN–
DMF, Et3N, 0 ◦C → rt, 16 h; (b) 2.2 eq m-CPBA, CH2Cl2, rt, 16 h; (c)
K2CO3, MeCN, reflux, 16 h. ii, (a) 1.0 eq ArSO2Cl, CH2Cl2, Et3N, 0 ◦C →
rt, 16 h; (b) Py, MsCl, CH2Cl2, reflux, 6 h; (c) K2CO3, MeCN, reflux, 16 h.
To start with, aziridines 7–9 were compared in the
lithiation-Me3SiCl in situ trapping using s-BuLi and PMDETA
(PMDETA = pentamethyldiethylenetriamine) (Table 1). s-BuLi
and PMDETA (3 equiv. of each) were premixed in THF at -78 ◦C
and then added to the aziridine and Me3SiCl in THF at -78 ◦C. The
reactions were quenched with NH4Cl(aq) after 1 hour. Under these
conditions, the highest yield of silylated aziridine was obtained
using the N-Tris-activated aziridine 9 (66% yield of 12, entry
3). Use of the N-Bus aziridine 7 gave 50% recovered starting
material (entry 1). The N-Ts aziridine 8 suffered from competing
ortho-lithiation of the arylsulfonyl group and a doubly silylated
Under the standard external trapping conditions, 3 equiv. of
s-BuLi–PMDETA was optimal and a 94% yield of silyl aziridine
Table 1 In situ lithiation-Me3SiCl trapping of N-sulfonyl activated
aziridines 7–9
Table 2 External lithiation-Me3SiCl trapping of N-sulfonyl activated
aziridine 9
Entrya SMb
R
Prodc Yield (%)d Yield of SM (%)e
Equiv. of
Yield of Yield of Yield of
Entrya s-BuLi–ligand Ligand
12 (%)b
13 (%)b
SM (%)b,c
1
2
3
7
8
9
9
9
9
9
t-Bu
10
11
12
12
12
12
12
36
22
66
12g
63
58
28
50
22
28
52
30
18
59
1
2
3.0
2.5
1.2
3.0
3.0
2.5
1.5
3.0
PMDETA
PMDETA
PMDETA
PMDETA
TMEDA
TMEDA
TMEDA
94
46
0
0
0
0
78
62
54
0
0
40
—
0
0
0
—
—
4-MeC6H4
2,4,6-i-Pr3C6H2
2,4,6-i-Pr3C6H2
2,4,6-i-Pr3C6H2
2,4,6-i-Pr3C6H2
2,4,6-i-Pr3C6H2
d
4f
5h
6i
7j
3
4e
5
0
34
22
0
6
d
7
a Reaction conditions: i, 3 eq s-BuLi–PMDETA, 3 eq Me3SiCl, THF,
-78 ◦C, 1 h (in situ). b SM = starting material. c Prod = product. d Yield
of product after chromatography. e Yield of recovered starting material
after chromatography. f Reaction carried out using (-)-sparteine in place
of P◦MDETA. g Enantiomeric ratio (er) not determined. h Reaction left at
-78 C for 4 h. i Reaction allowed to warm to rt over 3 h. j Reaction carried
out using 1.2 eq s-BuLi–PMDETA.
8f
(-)-Sparteine
0
0
d
a Reaction conditions: i, (a) s-BuLi–ligand, THF, -78 ◦C, 1 min; (b) 3 eq
Me3SiCl, -78 ◦C, 1 h (external). b Yield of product after chromatography.
c SM = starting material. d The H NMR spectrum of the crude product
1
showed only starting material. e Reaction left at -78 ◦C for 15 minutes
after lithiation (instead of 1 minute). f Reaction carried out in Et2O.
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Table 3 External lithiation-aldehyde trapping of N-sulfonyl activated
aziridines 9 and 14
12 was obtained (entry 1). Reducing the amount of s-BuLi–
PMDETA gave lower yields of silyl aziridine 12 and significant
amounts of (presumably unreacted) starting material (entries 2–
3). Notably, a very short lithiation time (1 minute) before addition
of Me3SiCl was necessary. When the lithiation time was extended
to 15 minutes, 2,4,6-i-Pr3C6H2SO2NH2 13 was produced as the
only isolable product (78% yield, entry 4). Clearly, the lithiated
aziridine intermediate is not stable in the presence of excess s-BuLi:
it likely undergoes carbenoid insertion into the organolithium
reagent and loss of TsNLi2 (reductive alkylation)1 to give, after
aqueous quench, a volatile alkene (not isolated) and 2,4,6-i-
Pr3C6H2SO2NH2 13. Using PMDETA as the ligand appears to
suppress the reductive alkylation pathway compared to TMEDA:
even using a 1 minute lithiation time with s-BuLi–TMEDA, 2,4,6-
i-Pr3C6H2SO2NH2 13 was produced in 54–62% yield together
with only 22–34% yield of silyl aziridine 12 (entries 5–6). We
note in passing that Hodgson has reported 51–96% yields for
electrophilic trapping using N-Bus aziridine 7 and lithiating with
Yield of
Yield of
Entrya SMb R1
R2
Prodc syn : antid syn (%)e
anti (%)e
1
2
3
4
5
6
7
8
9
9
H
H
H
H
n-Pr
i-Pr
17
18
60 : 40
65 : 35
70 : 30
55 : 45
n.d.g
60 : 40
75 : 25
n.d.g
29f
45
51
38
21h
46
51
25
20
33
25
28
16
23
22
43
9
t-Bu 19
9
Ph
20
21
22
14
14
14
14
Me n-Pr
Me i-Pr
Me t-Bu 23
Me Ph 24
a Reaction conditions: i, (a) s-BuLi/–PMDETA, THF, -78 ◦C, 1 min;
(b) 3 eq R2CHO, -78 ◦C, 1 h; (c) NH4Cl(aq) (external). b SM = starting
material. c Prod = product. d Ratio of syn- and anti-hydroxy aziridines
determined from the 1H NMR spectrum of the crude product. e Yield of
product after chromatography. f 20% yield of SM 9 was recovered. g Not
determined. h 25% yield of SM 14 was recovered.
◦
s-BuLi–TMEDA in THF at -98 C for 5 minutes.9 In contrast,
reductive alkylation was the only reaction observed with N-Bus
aziridine 7 and s-BuLi–PMDETA (1 minute lithiation time) at
-78 ◦C: lithation of N-Bus aziridine 7 with 3.0 equiv. s-BuLi–
PMDETA for 1 minute and external trapping with Me3SiCl gave
t-BuSO2NH2 (83% yield) as the only isolable product. Finally,
an attempted asymmetric lithiation using s-BuLi–(-)-sparteine in
Et2O gave recovered starting aziridine 9 (entry 8).
The optimised conditions for external silylation were also
applied to terminal N-Tris-aziridine activated aziridines 14 and 16
(Scheme 3). Aziridines 14 (72% yield) and 16 (45% yield) were syn-
thesised from 1-amino-2-propanol and 2-amino-2-methylpropan-
1-ol respectively using the procedure previously used to synthesise
aziridine 9. External silylation of 14 gave a 70% yield of 15 and
the trans-stereochemistry was assigned by X-ray crystal structures
of two aldehyde-trapped products (vide infra) and by analogy
with the LTMP-mediated process.8 In contrast, attempted external
silylation of aziridine 16 was unsuccessful and reductive alkylation
occurred to give 2,4,6-i-Pr3C6H2SO2NH2 13 (31% yield) as the only
isolable product.
obtained. In contrast, we did not obtain any isolable adducts from
lithiated 9 and the following electrophiles: n-BuBr, allyl bromide,
Me2SO4, MeSSMe, Bu3SnCl, PhSO2F, Ph2CO, Et2CO, DMF and
PhCONMe2.
However, trapping with different aldehydes gave satisfactory
results for both N-Tris-aziridines 9 and 14 (Table 3). After
lithiation at -78 ◦C in THF for 1 minute using 3 equiv. of s-BuLi–
PMDETA, excess aldehyde was added followed by NH4Cl(aq)
after 1 hour at -78 ◦C. Where possible, the diastereoselectivity
was determined from the 1H NMR spectrum of the crude
product and the diastereomeric adducts were then separated by
chromatography. In general, additions of the lithiated aziridines
to aldehydes proceeded with moderate but useful levels of syn-
stereoselectivity. The best levels of syn-stereoselectivity were
obtained with the most sterically hindered pivaldehyde (entries 3
and 7). The total yield of the diastereomeric adducts were generally
good (65–78%; entries 2–4 and 6–8) except for butanal (37–49%;
entries 1 and 5), presumably reflecting its ease of enolisation. For
unequivocal proof of the assignment of stereochemistry in the
hydroxy aziridines, we obtained X-ray crystal structures of syn-24
and of the p-nitrobenzoate of anti-22 (Fig. 2).
In order to provide an alternative synthetic route to syn-hydroxy
aziridines and to aid in establishing the relative stereochemistry of
all of the hydroxy aziridines, an oxidation–reduction approach
was investigated. Thus, aziridines 9 and 14 were lithiated using
s-BuLi–PMDETA in the usual manner and trapped with six
aldehydes. Then, the crude mixture of hydroxy aziridines was
oxidised with PCC to give keto aziridines 25–30 (44–61% yield
over 2 steps, Table 4). Reduction of keto aziridines 25–30 using
NaBH4 in the presence of CeCl3·7H2O proceeded with ≥90 : 10
syn-stereoselectivity and allowed hydroxy aziridines syn-18–20 and
syn-22–24 to be isolated in good to excellent yields (Table 4).
Such syn-selectivity has been noted in our previous reductions of
N-Ts keto aziridines5 and other keto aziridine reductions;18 it is
Scheme 3 Reagents and conditions: i, (a) 1.0 eq ArSO2Cl, CH2Cl2, Et3N,
0
◦C → rt, 16 h; (b) Py, MsCl, CH2Cl2, reflux, 6 h; (c) K2CO3, MeCN,
reflux, 16 h. ii, (a) 3.0 eq s-BuLi–PMDETA, THF, -78 ◦C, 1 min; (b) 3 eq
Me3SiCl, -78 ◦C, 1 h.
With optimum conditions for the lithiation-silylation of N-
Tris-aziridines 9 and 14 under external trapping established, we
sought to apply the methodology to other electrophiles. We had
some success using 9 and trapping with MeI but an inseparable
1 : 1 mixture of starting material and methylated aziridine were
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Table 4 Aldehyde trapping, oxidation and reduction route tosyn-hydroxy
aziridines
PMDETA for 1 minute and then Me3SiCl was added. After 1 hour
at -78 ◦C, a second lithiation-trapping using the same lithiation-
Me3SiCl trapping conditions was attempted. Unfortunately, there
was no evidence for the formation of the hoped-for disilylated
aziridine 31. Instead, a 50% yield of mono-silyl aziridine 12 was
obtained (Scheme 4).
Yield of
Entrya SMb R1 R2
Ketone Yield (%)c Prodd syn : antie syn (%)c
1
2
3
4
5
6
9
9
H
H
H
i-Pr 25
t-Bu 26
Ph 27
56
61
44
52
57
58
18
19
20
22
23
24
90 : 10 64
>95 : 5
95 : 5
83
93
9
14
14
14
Me i-Pr 28
Me t-Bu 29
Me Ph 30
90 : 10 77
95 : 5 79
90 : 10 88
Scheme 4 Reagents and conditions: i, (a) 3.0 eq s-BuLi–PMDETA, THF,
-78 ◦C, 1 min; (b) 3 eq Me3SiCl, -78 ◦C, 1 h; (c) 3.0 eq s-BuLi–PMDETA,
THF, -78 ◦C, 1 min; (d) 3 eq Me3SiCl, -78 ◦C, 1 h.
a Reaction conditions: i, (a) s-BuLi–PMDETA, THF, -78 ◦C, 1 min; (b)
3 eq R2CHO, -78 ◦C, 1 h; (c) NH4Cl(aq); (d) PCC, CH2Cl2, rt, 2.5 h. ii,
NaBH4, CeCl3·7H2O, MeOH, 0 ◦C, 2 h. b SM = starting material. c Yield
of product after chromatography. d Prod = product. e Ratio of syn- and
anti-hydroxy aziridines determined from the 1H NMR spectrum of the
crude product.
Conclusion
In summary, a convenient procedure for the lithiation-trapping of
N-Tris activated ethylene aziridine 9 is described. The lithiation is
accomplished using s-BuLi and PMDETA in THF at a convenient
temperature (-78 ◦C) and trapping with a range of aldehydes
provides a stereoselective route to syn-hydroxy aziridines. Our
initial attempts at developing a route to disubstituted aziridines
3 via a one-pot approach proved unsuccessful. Nonetheless, with
the appropriate choice of electrophiles, it seems likely that double
functionalisation of a N-sulfonyl aziridine should be possible,
perhaps even via a one-pot procedure.
Experimental
General
Water is distilled water. Et2O and THF were freshly distilled from
benzophenone ketyl; CH2Cl2 was freshly distilled from CaH2.
s-BuLi was titrated against N-benzylbenzamide before use. Petrol
refers to the fraction of petroleum ether with a boiling point range
of 40–60 ◦C. All reactions were carried out under O2-free N2 or Ar
using oven-dried and/or flame dried glassware. PMDETA and
diamines used in lithiation reactions were distilled before use.
Flash column chromatography was carried out using silica gel
60 (0.035–0.070 mm particle size). Thin layer chromatography
was carried out using F254 alumina-backed silica plates. Proton
(400 MHz) and carbon (100.6 MHz) NMR spectra were recorded
using an internal deuterium lock. All samples were recorded
in CDCl3. Chemical shifts are quoted in parts per million
and referenced to CHCl3 (7.27 for 1H NMR and 77.0 for
13C NMR spectroscopy). Carbon NMR spectra were recorded
with broadband proton decoupling and were assigned using
DEPT experiments. Infra-red spectra were recorded on an FT-
IR spectrometer. Melting points were measured on a Gallenkamp
melting point apparatus.
Fig. 2 X-Ray crystal structures of syn-24 and of the p-nitrobenzoate of
anti-22.
consistent with Felkin-Anh stereoselectivity. Assuming that reduc-
tion of the keto aziridines all show the same sense of induction,
the X-ray structures of syn-24 and of the p-nitrobenzoate of anti-
22 enabled us to assign the stereochemistry of hydroxy aziridines
18–20 and 22–24. The stereochemistry of hydroxy aziridines 17
and 21 was assigned by analogy.
General procedure A: Lithiation-trapping of N-sulfonyl aziridines
(external)
Finally, we wished to establish whether it was possible to carry
out a one-pot double functionalisation of a N-sulfonyl ethylene
aziridine 1 as a route to disubstituted aziridines 3, as outlined in
Scheme 1. To this end, N-Tris aziridine 9 was lithiated with s-BuLi–
sec-BuLi (1.2–3.0 eq) was added dropwise to a stirred solu-
tion of PMDETA (pentamethyldiethylenetriamine), TMEDA or
(-)-sparteine (1.2–3.0 eq) in THF or Et2O (2 mL) at -78 ◦C under
◦
N2. After stirring for 15 min at -78 C, the solution was added
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dropwise via canula to a stirred solution of aziridine (0.30 mmol)
in THF or Et2O (3 mL) at -78 ◦C under N2. After stirring for
1 min at -78 ◦C, freshly distilled electrophile (0.90 mmol, 3.0 eq)
was added and stirred at -78 ◦C for a further 1 h. Then, saturated
NH4Cl(aq) (10 mL) was added. The layers were separated and the
aqueous layer was extracted with Et2O (3 ¥ 10 mL). The combined
Et2O extracts were dried (MgSO4) and evaporated under reduced
pressure to give the crude product.
reaction mixture was diluted with CH2Cl2 (20 mL). The mixture
was washed with water (20 mL) and brine (20 mL), dried (MgSO4)
and evaporated under reduced pressure to give the crude product.
Purification by flash chromatography on silica with petrol–Et2O
(10 : 1) as eluent gave aziridine 9 (4.67 g, 76%) as a white solid,
mp 94–96 ◦C (from 10 : 1 petrol–Et2O); RF (1 : 1 petrol–Et2O)
0.6; vmax(CH2Cl2)/cm-1 1317 (SO2) and 1151 (SO2); dH (400 MHz,
CDCl3) 7.19 (2 H, s, Ar), 4.32 (2 H, sept, J 7.0, ArCH), 2.91
(1 H, sept, J 7.0, ArCH), 2.38 (4 H, br s, CH2N), 1.27 (12 H, d,
J 7.0, Me) and 1.26 (6 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3)
153.4 (ipso-Ar), 151.1 (ipso-Ar), 131.2 (ipso-Ar), 123.8 (Ar), 34.2
(ArCH), 29.7 (ArCH), 27.1 (CH2N), 24.9 (Me) and 23.5 (Me);
m/z (CI; NH3) 310 [100%, (M + H)+] and 267 (10) [Found (M +
H)+ 310.1840. C17H27NO2S requires M + H, 310.1841].
General procedure B: Lithiation-trapping of N-sulfonyl aziridines
and PCC oxidation
sec-BuLi (3.0 eq) was added dropwise to a stirred solution of
PMDETA (3.0 eq) in THF at -78 ◦C under N2. After stirring for
15 min at -78 ◦C, the solution was added dropwise via canula to a
stirred solution of aziridine (0.60 mmol) in THF at -78 ◦C under
◦
2-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridine 14
N2. After stirring for 1 min at -78 C, freshly distilled aldehyde
(1.8 mmol) was added and stirred at -78 ◦C for a further 1 h. Then,
saturated NH4Cl(aq) (20 mL) was added. The layers were separated
and the aqueous layer was extracted with Et2O (3 ¥ 20 mL). The
combined Et2O extracts were dried (MgSO4) and evaporated under
reduced pressure to give the crude hydroxy aziridines. A solution
of the crude hydroxy aziridines (0.60 mmol) in CH2Cl2 (6 mL) was
added dropwise via a cannula to a stirred solution of pyridinium
chlorochromate (194 mg, 0.9 mmol) in CH2Cl2 (4 mL) at rt under
N2. The resulting mixture was stirred for 2.5 h and then diluted
with Et2O (20 mL). The solid was removed by filtration through
Celite and the filtrate was evaporated to give the crude product.
2,4,6-Tri-iso-propylbenzenesulfonyl chloride (1.21 g, 4.0 mmol)
was added to a stirred solution of 1-amino-2-propanol (300 mg,
4.0 mmol) and Et3N (1.12 mL, 8.0 mmol) in CH2Cl2 (6 mL) at 0 ◦C
under N2. The resulting solution was allowed to warm to rt and
stirred at rt for 16 h. Then, the reaction mixture was washed with
5% NaHCO3(aq) (2 ¥ 10 mL), dried (MgSO4) and evaporated under
reduced pressure to give the crude sulfonamido alcohol. Then,
pyridine (1.83 mL, 20.0 mmol) was added dropwise to a stirred
solution of methanesulfonyl chloride (1.69 mL, 20.0 mmol) in
CH2Cl2 (50 mL) at 0 ◦C under N2. After stirring for 20 min, a
solution of the crude sulfonamido alcohol in CH2Cl2 (5 mL) was
added and the resulting solution was stirred for 20 min. Then, the
solution was heated at reflux for 16 h. The solution was allowed
to cool to rt and washed with brine (20 mL), dried (MgSO4) and
evaporated under reduced pressure to give the crude sulfonamido
mesylate. A stirred mixture of the crude sulfonamido mesylate
and K2CO3 (2.21 g, 16.0 mmol) in MeCN (50 mL) was heated at
45 ◦C under N2 for 16 h. After cooling, the reaction mixture was
diluted with CH2Cl2 (20 mL). The mixture was washed with water
(20 mL) and brine (20 mL), dried (MgSO4) and evaporated under
reduced pressure to give the crude product. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
General procedure C: Reduction of keto aziridines
NaBH4 (1.2 eq) was added portionwise over 45 min to a stirred
solution of keto aziridine (0.2 mmol) and CeCl3·7H2O (1.2 eq)
in MeOH (1 mL) at 0 ◦C under N2. The resulting solution was
◦
stirred at 0 C for 2 h. After warming to rt, saturated NH4Cl(aq)
(2 mL) was added. The mixture was extracted with CH2Cl2 (3 ¥
5 mL) and the combined organic extracts were washed with water
(5 mL), dried (MgSO4) and evaporated under reduced pressure to
give the crude product.
◦
aziridine 14 (934 mg, 72%) as a white solid, mp 73–75 C (from
1-(2,4,6-Triisopropylphenylsulfonyl)aziridine 9
10 : 1 petrol–Et2O); RF (1 : 1 petrol–Et2O) 0.6; vmax(CH2Cl2)/cm-1
1317 (SO2) and 1153 (SO2); dH (400 MHz, CDCl3) 7.17 (2 H, s,
Ar), 4.34 (2 H, sept, J 7.0, ArCH), 2.91 (1 H, sept, J 7.0, ArCH),
2.86–2.80 (1 H, m, CHN), 2.68 (1 H, d, J 7.0, CHAHBN), 2.01
(1 H, d, J 4.5, CHAHBN), 1.26 (18 H, d, J 7.0, Me) and 1.25 (3 H,
d, J 5.5, Me); dC (100.6 MHz; CDCl3) 153.2 (ipso-Ar), 150.9 (ipso-
Ar), 131.6 (ipso-Ar), 123.7 (Ar), 35.3 (CHN), 34.4 (CH2N), 34.1
(ArCH), 29.6 (ArCH), 24.8 (Me), 23.5 (Me) and 17.0 (Me); m/z
(CI; NH3) (CI, NH3) 341 [20%, (M + NH4)+] and 324 (100) [Found
(M + H)+ 324.1991. C18H29NO2S requires M + H, 324.1997].
2,4,6-Tri-iso-propylbenzenesulfonyl chloride (6.05 g, 20.0 mmol)
was added to a stirred solution of ethanolamine (1.22 g,
20.0 mmol) and Et3N (5.6 mL, 40.0 mmol) in CH2Cl2 (30 mL)
at 0 ◦C under N2. The resulting solution was allowed to warm to
rt and stirred at rt for 16 h. Then, the reaction mixture was washed
with 5% NaHCO3(aq) (2 ¥ 10 mL), dried (MgSO4) and evaporated
under reduced pressure to give the crude sulfonamido alcohol.
Then, pyridine (9.24 mL, 100.0 mmol) was added dropwise
to a stirred solution of methanesulfonyl chloride (8.58 mL,
100.0 mmol) in CH2Cl2 (200 mL) at 0 ◦C under N2. After stirring
for 20 min, a solution of the crude sulfonamido alcohol in CH2Cl2
(5 mL) was added and the resulting solution was stirred for
20 min. Then, the solution was heated at reflux for 16 h. The
solution was allowed to cool to rt and washed with brine (20 mL),
dried (MgSO4) and evaporated under reduced pressure to give
the crude sulfonamido mesylate. A stirred mixture of the crude
sulfonamido mesylate and K2CO3 (11.2 g, 80.0 mmol) in MeCN
(200 mL) was heated at 45 ◦C under N2 for 16 h. After cooling, the
2,2-Dimethyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridine 16
2,4,6-Tri-iso-propylbenzenesulfonyl chloride (3.03 g, 10.0 mmol)
was added to a stirred solution of 2-amino-2-methylpropan-1-ol
(890 mg, 10.0 mmol) and Et3N (2.8 mL, 20.0 mmol) in CH2Cl2
(15 mL) at 0 ◦C under N2. The resulting solution was allowed
to warm to rt and stirred at rt for 16 h. Then, the reaction
mixture was washed with 5% NaHCO3(aq) (2 ¥ 10 mL), dried
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(MgSO4) and evaporated under reduced pressure to give the crude
sulfonamido alcohol. Then, pyridine (4.58 mL, 50.0 mmol) was
added dropwise to a stirred solution of methanesulfonyl chloride
(4.23 mL, 50.0 mmol) in CH2Cl2 (200 mL) at 0 ◦C under N2. After
stirring for 20 min, a solution of the crude sulfonamido alcohol in
CH2Cl2 (5 mL) was added and the resulting solution was stirred
for 20 min. Then, the solution was heated at reflux for 16 h. The
solution was allowed to cool to rt and washed with brine (20 mL),
dried (MgSO4) and evaporated under reduced pressure to give
the crude sulfonamido mesylate. A stirred mixture of the crude
sulfonamido mesylate and K2CO3 (5.55 g, 40.0 mmol) in MeCN
(100 mL) was heated at 45 ◦C under N2 for 16 h. After cooling, the
reaction mixture was diluted with CH2Cl2 (20 mL). The mixture
was washed with water (20 mL) and brine (20 mL), dried (MgSO4)
and evaporated under reduced pressure to give the crude product.
Purification by flash chromatography on silica with petrol–Et2O
(10 : 1) as eluent gave aziridine 16 (152 mg, 45%) as a white solid,
mp 66–67 ◦C (from 10 : 1 petrol–Et2O); RF (1 : 1 petrol–Et2O)
0.6; vmax(CH2Cl2)/cm-1 1315 (SO2) and 1153 (SO2); dH (400 MHz,
CDCl3) 7.16 (2 H, s, Ar), 4.38 (2 H, sept, J 7.0, ArCH), 2.91 (1 H,
sept, J 7.0, ArCH), 2.46 (2 H, s, CH2N), 1.56 (6 H, s, Me), 1.27
(12 H, d, J 7.0, Me) and 1.25 (6 H, d, J 7.0, Me); dC (100.6 MHz;
CDCl3) 152.7 (ipso-Ar), 150.3 (ipso-Ar), 134.3 (ipso-Ar), 123.6
(Ar), 47.8 (NCMe2), 42.1 (CH2N), 34.2 (ArCH), 29.6 (ArCH),
24.8 (Me), 23.6 (Me) and 23.0 (Me); m/z (CI; NH3) (CI, NH3)
338 [100%, (M + H)+] [Found (M + H)+ 338.2154. C19H31NO2S
requires M + H, 338.2154].
0.96 mmol) in THF (3 mL) at -78 ◦C under N2. After stirring
for 15 min at -78 ◦C, the solution was added dropwise via a
canula to a stirred solution of aziridine 9 (100 mg, 0.32 mmol)
and trimethylsilyl chloride (0.12 mL, 0.96 mmol) in THF (2 mL)
at -78 ◦C under N2. After stirring for 1 h at -78 ◦C, saturated
NH4Cl(aq) (10 mL) was added. The layers were separated and
the aqueous layer was extracted with Et2O (3 ¥ 10 mL). The
combined Et2O extracts were dried (MgSO4) and evaporated under
reduced pressure to give the crude product. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
silyl aziridine 12 (81 mg, 66%) as a white solid, mp 48–50 ◦C (from
10 : 1 petrol–Et2O); RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1
1317 (SO2), 1252 (SiMe3) and 1154 (SO2); dH (400 MHz, CDCl3)
7.17 (2 H, s, Ar), 4.38 (2 H, sept, J 7.0, ArCH), 2.90 (1 H, sept, J
7.0, ArCH), 2.66 (1 H, dd, J 8.0 and 1.5, CHN), 2.03–1.98 (2 H, m,
CH2N), 1.27–1.24 (18 H, d, J 7.0, Me) and -0.07 (9 H, s, SiMe3); dC
(100.6 MHz; CDCl3) 153.3 (ipso-Ar), 151.0 (ipso-Ar), 131.5 (ipso-
Ar), 123.7 (Ar), 34.2 (ArCH), 30.1 (CH2N), 29.6 (ArCH), 29.0
(CHN), 25.0 (Me), 24.8 (Me), 23.6 (Me) and -3.7 (SiMe3); m/z
(CI; NH3) 382 (100) [Found (M + H)+ 382.2231. C20H35NO2SiS
requires M + H, 382.2236] and starting aziridine 9 (28 mg, 28%).
1-(2,4,6-Triisopropylphenylsulfonyl)-2-(trimethylsilyl)aziridine 12
(Table 2, entry 1)
Usinggeneralprocedure A, sec-BuLi (0.83 mL of a 1.15 Msolution
in cyclohexane, 0.96 mmol, 3.0 eq), PMDETA (0.2 mL, 0.96 mmol,
3.0 eq) in THF (2 mL), aziridine 9 (100 mg, 0.32 mmol) in THF
(3 mL) and trimethylsilyl chloride (0.12 mL, 0.96 mmol) gave the
crude product. Purification by flash chromatography on silica with
petrol–Et2O (10 : 1) as eluent gave silyl aziridine 12 (116 mg, 94%).
1-(4-Methyl-2-(trimethylsilyl)phenylsulfonyl)-2-
(trimethylsilyl)aziridine 11 (Table 1, entry 2)
sec-BuLi (1.28 mL of a 1.2 M solution in cyclohexane, 1.54 mmol)
was added dropwise to a stirred solution of PMDETA (0.32 mL,
1.54 mmol) in THF (3 mL) at -78 ◦C under N2. After stirring
for 15 min at -78 ◦C, the solution was added dropwise via a
canula to a stirred solution of aziridine 8 (100 mg, 0.51 mmol)
and trimethylsilyl chloride (0.20 mL, 1.54 mmol) in THF (2 mL)
at -78 ◦C under N2. After stirring for 1 h at -78 ◦C, saturated
NH4Cl(aq) (10 mL) was added. The layers were separated and
the aqueous layer was extracted with Et2O (3 ¥ 10 mL). The
combined Et2O extracts were dried (MgSO4) and evaporated under
reduced pressure to give the crude product. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
disilyl aziridine 11 (39 mg, 22%) as a colourless oil, RF (1 : 1
petrol–Et2O) 0.6; vmax(CH2Cl2)/cm-1 1322 (SO2), 1249 (SiMe3) and
1162 (SO2); dH (400 MHz, CDCl3) 7.83 (1 H, d, J 8.0, Ar), 7.57
(1 H, s, Ar), 7.30–7.28 (1 H, m, Ar), 2.63–2.61 (1 H, m, SiCHN),
2.42 (3 H, s, Me), 1.99–1.98 (2 H, m, CH2N), 0.44 (9 H, s, SiMe3)
and -0.09 (9 H, s, SiMe3); dC (100.6 MHz; CDCl3) 142.6 (ipso-
Ar), 141.0 (ipso-Ar), 140.5 (ipso-Ar), 137.3 (Ar), 129.8 (Ar), 129.6
(Ar), 30.4 (CH2N), 29.9 (CHSiN), 21.6 (Me), 1.1 (SiMe3) and -3.7
(SiMe3); m/z (CI; NH3) 342 [20%, (M + H)+] and 270 (100) [Found
(M + H)+ 342.1378. C15H27NO2Si2S requires M + H, 342.1379] and
starting aziridine 8 (22 mg, 22%).
2-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)-3-
(trimethylsilyl)aziridine 15
Using general procedure A, sec-BuLi (0.93 mL of a 1.0 M
solution in cyclohexane, 0.93 mmol, 3.0 eq), PMDETA (0.19 mL,
0.93 mmol, 3.0 eq) in THF (2 mL), aziridine 14 (100 mg,
0.31 mmol) in THF (3 mL) and trimethylsilyl chloride (0.11 mL,
0.93 mmol) gave the crude product. Purification by flash chro-
matography on silica with petrol–Et2O (10 : 1) as eluent gave silyl
aziridine 15 (85 mg, 70%) as a colourless oil, RF (1 : 1 petrol–Et2O)
0.8; vmax(CH2Cl2)/cm-1 1317 (SO2), 1254 (SiMe3) and 1151 (SO2);
dH (400 MHz, CDCl3) 7.15 (2 H, s, Ar), 4.37 (2 H, sept, J 7.0,
ArCH), 2.89 (1 H, sept, J 7.0, ArCH), 2.68 (1 H, app. pentet, J
6.0, MeCHN), 1.96 (1 H, d, J 6.0, SiCHN), 1.59 (3 H, d, J 6.0,
Me), 1.27 (6 H, d, J 7.0, Me), 1.24 (12 H, d, J 7.0, Me) and -0.05
(9 H, s, SiMe3); dC (100.6 MHz; CDCl3) 152.8 (ipso-Ar), 150.5
(ipso-Ar), 133.7 (ipso-Ar), 123.5 (Ar), 42.3 (CHN), 39.8 (CHN),
34.2 (ArCH), 29.6 (ArCH), 24.9 (Me), 24.8 (Me), 23.6 (Me), 16.3
(Me) and -2.8 (SiMe3); m/z (CI; NH3) 396 [100%, (M + H)+] and
129 (45) [Found (M + H)+ 396.2396. C21H37NO2SiS requires M +
H, 396.2393] and starting aziridine 14 (11 mg, 11%).
1-(1-(2,4,6-Triisopropylphenylsulfonyl)aziridin-2-yl)butan-1-ol
1-(2,4,6-Triisopropylphenylsulfonyl)-2-(trimethylsilyl)aziridine 12
(Table 1, entry 3)
syn-17 and anti-17
Using general procedure A, aziridine 9 (100 mg, 0.32 mmol) in
THF (3 mL), sec-BuLi (0.80 mL of a 1.2 M solution in cyclohex-
ane, 0.96 mmol, 3.0 eq) and PMDETA (0.2 mL, 0.96 mmol, 3.0 eq)
sec-BuLi (0.8 mL of a 1.2 M solution in cyclohexane, 0.96 mmol)
was added dropwise to a stirred solution of PMDETA (0.2 mL,
340 | Org. Biomol. Chem., 2009, 7, 335–345
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in THF (2 mL) and butyraldehyde (0.1 mL, 0.96 mmol) gave the
7.0 and 5.5, CH), 1.68 (1 H, br s, OH), 1.27 (6 H, d, J 7.0, 1.0,
Me), 1.262 (6 H, d, J 7.0, Me), 1.259 (6 H, d, J 7.0, Me), 0.97
(3 H, d, J 7.0, Me) and 0.95 (3 H, d, J 7.0, Me); dC (100.6 MHz;
CDCl3) 153.7 (ipso-Ar), 151.0 (ipso-Ar), 131.0 (ipso-Ar), 123.9
(Ar), 72.3 (CHO), 40.9 (CHN), 34.2 (ArCH), 32.0 (CH), 29.8
(ArCH), 29.7 (CH2N), 24.87 (Me), 24.79 (Me), 23.5 (Me), 18.3
(Me) and 17.6 (Me); m/z (CI; NH3) 382 (100) [Found (M + H)+
382.2427. C21H35NO3S requires M + H, 382.2416].
crude product which contained a 60 : 40 mixture of alcohols syn-
1
17 and anti-17 by H NMR spectroscopy. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
starting aziridine 9 (20 mg, 20%), alcohol syn-17 (36 mg, 29%) as
◦
a white solid, mp 50–52 C (from 10 : 1 petrol–Et2O); RF (1 : 1
petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3551 (OH), 1318 (SO2) and
1153 (SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar), 4.32 (2 H, sept,
J 7.0, ArCH), 3.53–3.47 (1 H, m, CHO), 2.94–2.86 (2 H, m, CHN
and ArCH), 2.71 (1 H, d, J 7.0, CH2N), 2.34 (1 H, d, J 4.5, CH2N),
1.44–1.30 (4 H, m, CH2), 1.27 (12 H, d, J 7.0, Me), 1.25 (6 H, d,
J 7.0, Me) and 0.87 (3 H, t, J 7.0, Me); dC (100.6 MHz; CDCl3)
153.3 (ipso-Ar), 151.0 (ipso-Ar), 131.5 (ipso-Ar), 123.9 (Ar), 69.3
(CHO), 43.4 (CHN), 37.6 (CH2N), 34.2 (ArCH), 30.7 (CH2), 29.8
(ArCH), 24.9 (Me), 23.5 (Me), 18.5 (CH2) and 13.9 (Me); m/z (CI;
NH3) 382 (100) [Found (M + H)+ 382.2413. C21H35NO3S requires
M + H, 382.2416] and alcohol anti-17 (25 mg, 20%) as a colourless
oil, RF (1 : 1 petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3507 (OH), 1317
(SO2) and 1153 (SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar),
4.31 (2 H, sept, J 7.0, ArCH), 3.78–3.77 (1 H, br s, CHO), 2.98–
2.88 (2 H, m, CHN and ArCH), 2.62 (1 H, d, J 7.0, CH2N), 2.33
(1 H, d, J 4.5, CH2N), 1.44–1.30 (4 H, m, CH2), 1.27 (12 H, d,
J 7.0, Me), 1.25 (6 H, d, J 7.0, Me) and 0.87 (3 H, t, J 7.0, Me);
dC (100.6 MHz; CDCl3) 153.7 (ipso-Ar), 151.0 (ipso-Ar), 131.5
(ipso-Ar), 123.9 (Ar), 68.3 (CHO), 42.5 (CHN), 36.1 (CH2N),
34.2 (ArCH), 29.9 (CH2), 29.7 (ArCH), 24.9 (Me), 24.8 (Me), 23.5
(Me), 18.3 (CH2) and 13.9 (Me); m/z (CI; NH3) 382 (100) [Found
(M + H)+ 382.2414. C21H35NO3S requires M + H, 382.2416].
2,2-Dimethyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)propan-1-ol syn-19 and anti-19
Using general procedure A, aziridine 9 (100 mg, 0.32 mmol) in
THF (3 mL), sec-BuLi (0.80 mL of a 1.2 M solution in cyclohex-
ane, 0.96 mmol, 3.0 eq) and PMDETA (0.2 mL, 0.96 mmol, 3.0 eq)
in THF (2 mL) and trimethylacetaldehyde (0.11 mL, 0.96 mmol)
gave the crude product which contained a 70 : 30 mixture of
alcohols syn-19 and anti-19 by 1H NMR spectroscopy. Purification
by flash chromatography on silica with petrol–Et2O (10 : 1) as
eluent gave starting aziridine 9 (7 mg, 7%), alcohol syn-19 (65 mg,
51%) as a white solid, mp 87–89 ◦C (from 10 : 1 petrol–Et2O); RF
(1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3539 (OH), 1319 (SO2)
and 1153 (SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar), 4.31 (2 H,
sept, J 7.0, ArCH), 3.03–2.96 (2 H, m, CHO and CHN), 2.89
(1 H, sept, J 7.0, ArCH), 2.73 (1 H, d, J 7.0, CHN), 2.25 (1 H,
d, J 4.5, CHN), 1.45 (1 H, d, J 4.5, OH), 1.28–1.24 (18 H, m,
Me) and 0.95 (9 H, s, CMe3); dC (100.6 MHz; CDCl3) 153.8 (ipso-
Ar), 151.1 (ipso-Ar), 130.9 (ipso-Ar), 124.0 (Ar), 78.4 (CHO), 41.0
(CHN), 34.6 (CMe3), 34.2 (ArCH), 31.8 (CH2N), 29.8 (ArCH),
25.6 (CMe3), 24.86 (Me), 24.83 (Me) and 23.5 (Me); m/z (CI;
NH3) 396 (100) [Found (M + H)+ 396.2570. C22H37NO3S requires
M + H, 396.2572] and alcohol anti-19 (32 mg, 25%) as a colourless
oil, RF (1 : 1 petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3542 (OH), 1318
(SO2) and 1153 (SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar), 4.30
(2 H, sept, J 7.0, ArCH), 3.55 (1 H, br s, CHO), 3.11 (1 H, ddd, J
7.0, 4.5 and 2.0, CHN), 2.91 (1 H, sept, J 7.0, ArCH), 2.63 (1 H,
d, J 7.0, CHN), 2.40 (1 H, d, J 4.5, CHN), 1.68 (1 H, br s, OH),
1.28–1.25 (18 H, m, Me), and 0.96 (9 H, s, CMe3); dC (100.6 MHz;
CDCl3) 153.7 (ipso-Ar), 151.0 (ipso-Ar), 131.0 (ipso-Ar), 123.9
(Ar), 74.3 (CHO), 39.7 (CHN), 34.6 (CMe3), 34.2 (ArCH), 30.0
(CH2N), 29.8 (ArCH), 25.8 (CMe3), 24.89 (Me), 24.79 (Me) and
23.5 (Me); m/z (CI; NH3) 396 (100) [Found (M + H)+ 396.2559.
C22H37NO3S requires M + H, 396.2572].
2-Methyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)propan-1-ol syn-18 and anti-18
Using general procedure A, aziridine 9 (100 mg, 0.32 mmol) in
THF (3 mL), sec-BuLi (0.80 mL of a 1.2 M solution in cyclohex-
ane, 0.96 mmol, 3.0 eq) and PMDETA (0.2 mL, 0.96 mmol, 3.0 eq)
in THF (2 mL) and isobutyraldehyde (0.1 mL, 0.96 mmol) gave
the crude product which contained a 65 : 35 mixture of alcohols
syn-18 and anti-18 by 1H NMR spectroscopy. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
starting aziridine 9 (7 mg, 7%), alcohol syn-18 (55 mg, 45%) as
◦
a white solid, mp 56–57 C (from 10 : 1 petrol–Et2O); RF (1 : 1
petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3542 (OH), 1317 (SO2) and
1153 (SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar), 4.32 (2 H,
sept, J 7.0, ArCH), 3.11 (1 H, br td, J 7.0 and 6.0, CHO), 2.97
(1 H, td, J 7.0 and 4.5, CHN), 2.91 (1 H, sept, J 7.0, ArCH), 2.71
(1 H, d, J 7.0, CHN), 2.29 (1 H, d, J 4.5, CHN), 1.69 (1 H, octet,
J 7.0, CH), 1.38 (1 H, d, J 6.0, OH), 1.27 (12 H, d, J 7.0, Me),
1.25 (6 H, d, J 7.0, Me), 0.97 (3 H, d, J 7.0, Me) and 0.94 (3 H, d,
J 7.0, Me); dC (100.6 MHz; CDCl3) 153.8 (ipso-Ar), 151.0 (ipso-
Ar), 130.9 (ipso-Ar), 123.9 (Ar), 75.3 (CHO), 42.0 (CHN), 34.2
(ArCH), 32.9 (CH), 31.2 (CH2N), 29.8 (ArCH), 24.8 (Me), 23.5
(Me), 18.3 (Me) and 18.1 (Me); m/z (CI; NH3) 382 (100) [Found
(M + H)+ 382.2422. C21H35NO3S requires M + H, 382.2416] and
alcohol anti-18 (41 mg, 33%) as a colourless oil, RF (1 : 1 petrol–
Et2O) 0.4; vmax(CH2Cl2)/cm-1 3520 (OH), 1317 (SO2) and 1154
(SO2); dH (400 MHz, CDCl3) 7.19 (2 H, s, Ar), 4.30 (2 H, sept, J
7.0, ArCH), 3.59 (1 H, dd, J 5.5 and 3.0, CHO), 3.04 (1 H, ddd, J
7.0, 4.5 and 3.0, CHN), 2.91 (1 H, sept, J 7.0, ArCH), 2.62 (1 H,
d, J 7.0, CH2N), 2.36 (1 H, d, J 4.5, CH2N), 1.73 (1 H, sept d, J
Phenyl-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-yl)methanol
syn-20 and anti-20
Using general procedure A, aziridine 9 (100 mg, 0.32 mmol) in
THF (3 mL), sec-BuLi (0.80 mL of a 1.2 M solution in cyclo-
hexane, 0.96 mmol, 3.0 eq) and PMDETA (0.2 mL, 0.96 mmol,
3.0 eq) in THF (2 mL) and benzaldehyde (0.1 mL, 0.96 mmol) gave
the crude product which contained a 55 : 45 mixture of alcohols
syn-20 and anti-20 by 1H NMR spectroscopy. Purification by flash
chromatography on silica with petrol–Et2O (10 : 1) as eluent gave
starting aziridine 9 (6 mg, 6%), alcohol syn-20 (51 mg, 38%) as a
colourless oil, RF (1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3539
(OH), 1319 (SO2) and 1153 (SO2); dH (400 MHz, CDCl3) 7.26 (5
H, s, Ph), 7.19 (2 H, s, Ar), 4.50 (1 H, t, J 5.0, CHO), 4.29 (2 H,
sept, J 7.0, ArCH), 3.13 (1 H, ddd, J 7.0, 5.0 and 4.5, CHN), 2.93
(1 H, sept, J 7.0, ArCH), 2.74 (1 H, d, J 7.0, CHN), 2.41 (1 H,
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d, J 4.5, CHN), 2.04 (1 H, d, J 5.0, OH), 1.28 (12 H, d, J 7.0,
Me) and 1.22 (6 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3) 153.8
(ipso-Ar), 151.2 (ipso-Ar), 139.9 (ipso-Ph), 130.8 (ipso-Ar), 128.6
(Ph), 128.2 (Ph), 126.0 (Ph), 124.0 (Ar), 72.9 (CHO), 44.6 (CHN),
34.2 (ArCH), 30.5 (CH2N), 29.8 (ArCH), 24.89 (Me), 24.82 (Me),
23.56 (Me) and 23.54 (Me); m/z (CI; NH3) 396 (100) [Found (M +
H)+ 416.2258. C24H33NO3S requires M + H, 416.2259] and alcohol
anti-20 (37 mg, 28%) as a white solid, mp 98–100 ◦C (from 10 : 1
petrol–Et2O); RF (1 : 1 petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3482
(OH), 1318 (SO2) and 1152 (SO2); dH (400 MHz, CDCl3) 7.30 (5
H, s, Ph), 7.19 (2 H, s, Ar), 4.90 (1 H, br s, CHO), 4.28 (2 H,
sept, J 7.0, ArCH), 3.21 (1 H, ddd, J 7.0, 4.5 and 3.5, CHN), 2.94
(1 H, sept, J 7.0, ArCH), 2.63 (1 H, d, J 7.0, CHN), 2.46 (1 H,
d, J 4.5, CHN), 2.14 (1 H, br s, OH), 1.27 (12 H, d, J 7.0, Me)
and 1.25 (6 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3) 153.7 (ipso-
Ar), 151.1 (ipso-Ar), 139.3 (ipso-Ar), 130.9 (ipso-Ar), 128.6 (Ph),
128.3 (Ph), 126.0 (Ph), 123.9 (Ar), 70.3 (CHO), 43.3 (CHN), 34.2
(ArCH), 30.3 (CH2N), 29.8 (ArCH), 24.88 (Me), 24.84 (Me), and
23.6 (Me); m/z (CI; NH3) 416 (100) [Found (M + H)+ 416.2259.
C24H33NO3S requires M + H, 416.2259].
in cyclohexane, 4.64 mmol, 3.0 eq) and PMDETA (0.97 mL,
4.94 mmol, 3.0 eq) in THF (8 mL) and isobutyraldehyde (0.42 mL,
4.64 mmol) gave the crude product which contained a 60 : 40
mixture of alcohols syn-22 and anti-22 by 1H NMR spectroscopy.
Purification by flash chromatography on silica with petrol–Et2O
(7 : 1 then 2 : 1) as eluent gave alcohol syn-22 (282 mg, 45%) as a
colourless oil, RF (1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3521
(OH), 1311 (SO2) and 1148 (SO2); dH (400 MHz, CDCl3) 7.17 (2 H,
s, Ar), 4.29 (2 H, sept, J 7.0, ArCH), 3.35 (1 H, br td, J 8.0 and
3.0, CHO), 2.97 (1 H, qd, J 6.0 and 4.5, CHN), 2.90 (1 H, sept, J
7.0, ArCH), 2.78 (1 H, dd, J 8.0 and 4.5, CHN), 2.70 (1 H, br, s,
OH), 1.77 (1 H, dsept, J 8.0 and 7.0, CH), 1.43 (3 H, d, J 6.0, Me),
1.28 (6 H, d, J 7.0, Me), 1.25 (12 H, d, J 7.0, Me), 1.01 (3 H, d,
J 7.0, Me) and 0.95 (3 H, t, J 7.0, Me); dC (100.6 MHz; CDCl3)
153.3 (ipso-Ar), 150.5 (ipso-Ar), 133.5 (ipso-Ar), 123.7 (Ar), 75.8
(CHO), 54.4 (CHN), 43.7 (CHN), 34.2 (ArCH), 32.7 (CH), 29.8
(ArCH), 24.8 (Me), 23.5 (Me), 18.7 (Me), 18.3 (Me) and 15.3 (Me);
m/z (CI; NH3) 396 (100) [Found (M + H)+ 396.2565. C22H37NO3S
requires M + H, 396.2572] and alcohol anti-22 (143 mg, 23%) as
◦
a white solid, mp 68–69 C (from 10 : 1 petrol–Et2O); RF (1 : 1
petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3509 (OH), 1315 (SO2) and
1151 (SO2); dH (400 MHz, CDCl3) 7.16 (2 H, s, Ar), 4.32 (2 H,
sept, J 7.0, ArCH), 3.58 (1 H, br s, CHO), 3.02–2.97 (2 H, m,
CHN), 2.90 (1 H, sept, J 7.0, ArCH), 1.84 (1 H, s, OH), 1.73 (1 H,
octet, J 7.0, CH), 1.65 (3 H, d, J 6.0, Me), 1.27 (6 H, d, J 7.0,
Me), 1.25 (12 H, dd, J 7.0 and 1.0, Me), 0.94 (3 H, d, J 7.0, Me)
and 0.92 (3 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3) 153.3 (ipso-
Ar), 150.4 (ipso-Ar), 133.8 (ipso-Ar), 123.8 (Ar), 71.8 (CHO), 50.3
(CHN), 41.9 (CHN), 34.2 (ArCH), 31.9 (CH), 29.7 (ArCH), 24.9
(Me), 24.7 (Me), 23.5 (Me), 18.4 (Me), 17.3 (Me) and 13.7 (Me);
m/z (CI; NH3) 396 (100) [Found (M + H)+ 396.2574. C22H37NO3S
requires M + H, 396.2572].
1-(3-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)butan-1-ol syn-21 and anti-21
Using general procedure A, aziridine 14 (100 mg, 0.31 mmol) in
THF (3 mL), sec-BuLi (0.78 mL of a 1.2 M solution in cyclo-
hexane, 0.93 mmol, 3.0 eq) and PMDETA (0.19 mL, 0.93 mmol,
3.0 eq) in THF (2 mL) and butyraldehyde (0.1 mL, 0.93 mmol)
gave the crude product. Purification by flash chromatography on
silica with petrol–Et2O (10 : 1) as eluent gave the starting aziridine
14 (25 mg, 25%), alcohol syn-21 (26 mg, 21%) as a colourless oil, RF
(1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3528 (OH), 1311 (SO2),
and 1149 (SO2); dH (400 MHz, CDCl3) 7.17 (2 H, s, Ar), 4.28 (2 H,
sept, J 7.0, ArCH), 3.73 (1 H, br s, CHO), 2.99 (1 H, qd, J 6.0 and
4.5, CHN), 2.90 (1 H, sept, J 7.0, ArCH), 2.74 (1 H, dd, J 7.0 and
4.5, CHN), 2.61 (1 H, br s, OH), 1.53–1.46 (4 H, m, CH2), 1.43
(3 H, d, J 6.0, Me), 1.28 (6 H, d, J 7.0, Me), 1.25 (12 H, d, J 7.0, Me)
and 0.91 (3 H, t, J 7.0, Me); dC (100.6 MHz; CDCl3) 153.3 (ipso-
Ar), 150.5 (ipso-Ar), 133.6 (ipso-Ar), 123.7 (Ar), 70.1 (CHO), 55.2
(CHN), 42.9 (CHN), 37.2 (CH2), 34.2 (ArCH), 29.8 (ArCH), 24.8
(Me), 24.7 (Me), 23.6 (Me), 18.6 (CH2), 15.4 (Me) and 14.1 (Me);
m/z (CI; NH3) 396 (100) [Found (M + H)+ 396.2570. C22H37NO3S
requires M + H, 396.2572] and alcohol anti-21 (19 mg, 16%) as a
colourless oil, RF (1 : 1 petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3566
(OH), 1316 (SO2), and 1152 (SO2); dH (400 MHz, CDCl3) 7.17 (2
H, s, Ar), 4.33 (2 H, sept, J 7.0, ArCH), 3.66 (1 H, br s, CHO),
2.96–2.87 (3 H, m, ArCH and CHN), 1.83 (1 H, br s, OH), 1.65
(3 H, d, J 6.0, Me), 1.29–1.24 (22 H, m, CH2 and Me) and 0.83
(3 H, t, J 7.0, Me); dC (100.6 MHz; CDCl3) 153.3 (ipso-Ar), 150.5
(ipso-Ar), 133.7 (ipso-Ar), 123.7 (Ar), 68.5 (CHO), 51.6 (CHN),
42.6 (CHN), 36.4 (CH2), 34.2 (ArCH), 29.7 (ArCH), 24.8 (Me),
24.7 (Me), 23.6 (Me), 18.3 (CH2), 14.0 (Me) and 13.9 (Me); m/z
(CI; NH3) 396 (100) [Found (M + H)+ 396.2560. C22H37NO3S
requires M + H, 396.2572].
2,2-Dimethyl-1-(3-methyl-1-(2,4,6-
triisopropylphenylsulfonyl)aziridin-2-yl)propan-
1-ol syn-23 and anti-23
Using general procedure A, aziridine 14 (100 mg, 0.31 mmol) in
THF (3 mL), sec-BuLi (0.83 mL of a 1.2 M solution in cyclohex-
ane, 0.93 mmol, 3.0 eq) and PMDETA (0.2 mL, 0.93 mmol, 3.0 eq)
in THF (2 mL) and trimethylacetaldehyde (0.11 mL, 0.93 mmol)
gave the crude product which contained a 75 : 25 mixture of
alcohols syn-23 and anti-23 by 1H NMR spectroscopy. Purification
by flash chromatography on silica with petrol–Et2O (10 : 1) as
eluent gave alcohol syn-23 (65 mg, 51%) as a colourless oil, RF
(1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3521 (OH), 1312 (SO2)
and 1149 (SO2); dH (400 MHz, CDCl3) 7.17 (2 H, s, Ar), 4.30
(2 H, sept, J 7.0, ArCH), 3.21 (1 H, dd, J 9.0 and 2.0, CHO),
2.96–2.87 (2 H, m, CHN and ArCH), 2.85 (1 H, dd, J 9.0 and 4.5,
CHN), 2.44 (1 H, br s, OH), 1.48 (3 H, d, J 6.0, Me), 1.29 (6 H,
d, J 7.0, Me), 1.27 (12 H, d, J 7.0, Me) and 0.97 (9 H, s, CMe3);
dC (100.6 MHz; CDCl3) 153.3 (ipso-Ar), 150.6 (ipso-Ar), 133.5
(ipso-Ar), 123.8 (Ar), 76.7 (CHO), 52.9 (CHN), 44.8 (CHN), 34.6
(CMe3), 34.2 (ArCH), 29.8 (ArCH), 25.8 (CMe3), 24.8 (Me), 24.7
(Me), 23.54 (Me), 23.53 (Me) and 14.9 (Me); m/z (CI; NH3) 410
(100) [Found (M + H)+ 410.2719. C23H39NO3S requires M + H,
410.2729] and alcohol anti-23 (28 mg, 22%) as a colourless oil, RF
(1 : 1 petrol–Et2O) 0.4; vmax(CH2Cl2)/cm-1 3534 (OH), 1316 (SO2)
and 1152 (SO2); dH (400 MHz, CDCl3) 7.16 (2 H, s, Ar), 4.32 (2 H,
2-Methyl-1-(3-methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-
2-yl)propan-1-ol syn-22 and anti-22
Using general procedure A, aziridine 14 (500 mg, 1.55 mmol)
in THF (8 mL), sec-BuLi (3.51 mL of a 1.32 M solution
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sept, J 7.0, ArCH), 3.45 (1 H, d, J 2.0, CHO), 3.10 (1 H, dd,
J 4.5 and 2.0, CHN), 2.99 (1 H, qd, J 6.0 and 4.5, CHN), 2.90
(1 H, sept, J 7.0, ArCH), 1.69 (3 H, d, J 6.0, Me), 1.28 (6 H, d,
J 7.0, Me), 1.26 (12 H, d, J 7.0, Me) and 0.94 (9 H, s, CMe3);
dC (100.6 MHz; CDCl3) 153.3 (ipso-Ar), 150.4 (ipso-Ar), 133.9
(ipso-Ar), 123.8 (Ar), 74.2 (CHO), 49.0 (CHN), 42.0 (CHN), 34.5
(CMe3), 34.2 (ArCH), 29.8 (ArCH), 25.8 (CMe3), 25.0 (Me), 24.7
(Me), 23.6 (Me) and 13.3 (Me); m/z (CI; NH3) 410 (100) [Found
(M + H)+ 410.2731. C23H39NO3S requires M + H, 410.2729].
2.69 (1 H, sept, J 7.0, CH), 2.50 (1 H, d, J 4.0, CH2N), 1.26 (6 H,
d, J 7.0, Me), 1.24 (12 H, d, J 7.0, Me), 1.04 (3 H, d, J 7.0, Me)
=
and 0.98 (3 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3) 206.5 (C O),
154.1 (ipso-Ar), 151.4 (ipso-Ar), 130.5 (ipso-Ar), 123.9 (Ar), 39.0
(CHN), 38.8 (CH), 34.2 (ArCH), 32.0 (CH2N), 29.8 (ArCH), 24.9
(Me), 24.8 (Me), 23.5 (Me), 17.7 (Me) and 17.3 (Me); m/z (CI;
NH3) 380 (100) [Found (M + H)+ 380.2258. C21H33NO3S requires
M + H, 380.2259].
2,2-Dimethyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)propan-1-one 26
(3-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)(phenyl)methanol syn-24 and anti-24
Using general procedure B, aziridine 9 (200 mg, 0.64 mmol)
in THF (6 mL), sec-BuLi (1.60 mL of a 1.2 M solution in
cyclohexane, 1.92 mmol), PMDETA (0.4 mL, 1.92 mmol) in
THF (4 mL) and trimethylacetaldehyde (0.2 mL, 1.92 mmol)
followed by PCC (207 mg, 0.96 mmol) in CH2Cl2 (10 mL) gave
the crude product. Purification by flash chromatography on silica
with petrol–Et2O (10 : 1) as eluent gave ketone 26 (153 mg, 61%)
as a colourless oil, RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1
Using general procedure A, aziridine 14 (100 mg, 0.31 mmol)
in THF (3 mL), sec-BuLi (0.78 mL of a 1.2 M solution in
cyclohexane, 0.93 mmol, 3.0 eq), PMDETA (0.19 mL, 0.93 mmol,
3.0 eq) in THF (2 mL) and benzaldehyde (0.1 mL, 0.93 mmol)
gave the crude product. Purification by flash chromatography on
silica with petrol–Et2O (10 : 1) as eluent gave starting aziridine
14 (3 mg, 3%), alcohol syn-24 (33 mg, 25%) as a colourless oil,
RF (1 : 1 petrol–Et2O) 0.7; vmax(CH2Cl2)/cm-1 3504 (OH), 1312
(SO2) and 1150 (SO2); dH (400 MHz, CDCl3) 7.31–7.29 (5 H, m,
Ph), 7.19 (2 H, s, Ar), 4.85 (1 H, dd, J 8.0 and 3.0, CHO), 4.31
(2 H, sept, J 7.0, ArCH), 3.25 (1 H, br s, OH), 3.19 (1 H, qd, J
6.0 and 4.5, CHN), 2.98–2.89 (2 H, m, ArCH and CHN), 1.35
(3 H, d, J 6.0, Me), 1.29 (6 H, d, J 7.0, Me) and 1.27 (12 H, d, J
7.0, Me); dC (100.6 MHz; CDCl3) 153.4 (ipso-Ar), 150.6 (ipso-Ar),
140.1 (ipso-Ph), 133.5 (ipso-Ar), 128.6 (Ph), 128.0 (Ph), 125.8 (Ph),
123.8 (Ar), 72.7 (CHO), 55.9 (CHN), 43.2 (CHN), 34.2 (ArCH),
29.8 (ArCH), 24.8 (Me), 23.6 (Me) and 15.5 (Me); m/z (CI; NH3)
430 (100) [Found (M + H)+ 430.2418. C25H35NO3S requires M
+ H, 430.2416] and alcohol anti-24 (57 mg, 43%) as a white solid,
mp 97–99 ◦C (from 10 : 1 petrol–Et2O); RF (1 : 1 petrol–Et2O)
0.4; vmax(CH2Cl2)/cm-1 3479 (OH), 1315 (SO2) and 1151 (SO2); dH
(400 MHz, CDCl3) 7.25–7.21 (5 H, m, Ph), 7.20 (2 H, s, Ar), 4.78
(1 H, d, J 4.0, CHO), 4.35 (2 H, sept, J 7.0, ArCH), 3.22 (1 H, t,
J 4.0, CHN), 3.13 (1 H, qd, J 6.0 and 4.0, CHN), 2.93 (1 H, sept,
J 7.0, ArCH), 2.34 (1 H, br s, OH), 1.68 (3 H, d, J 6.0, Me), 1.32
(6 H, d, J 7.0, Me), 1.31 (6 H, d, J 7.0, Me) and 1.27 (6 H, d, J
7.0, Me); dC (100.6 MHz; CDCl3) 153.2 (ipso-Ar), 150.4 (ipso-Ar),
139.8 (ipso-Ph), 133.8 (ipso-Ar), 128.5 (Ph), 128.1 (Ph), 125.9 (Ph),
123.7 (Ar), 71.1 (CHO), 52.2 (CHN), 42.5 (CHN), 34.2 (ArCH),
29.7 (ArCH), 24.9 (Me), 24.7 (Me), 23.59 (Me), 23.56 (Me) and
13.8 (Me); m/z (CI; NH3) 430 (100) [Found (M + H)+ 430.2410.
C25H35NO3S requires M + H, 430.2416].
=
1717 (C O), 1323 (SO2) and 1163 (SO2); dH (400 MHz, CDCl3)
7.17 (2 H, s, Ar), 4.30 (2 H, sept, J 7.0, ArCH), 3.61 (1 H, dd, J 7.0
and 4.0, CHN), 2.88 (1 H, sept, J 7.0, ArCH), 2.80 (1 H, d, J 7.0,
CH2N), 2.58 (1 H, d, J 4.0, CH2N), 1.26 (6 H, d, J 7.0, Me), 1.24
(6 H, d, J 7.0, Me), 1.23 (6 H, d, J 7.0, Me) and 1.07 (9 H, s, CMe3);
=
dC (100.6 MHz; CDCl3) 206.5 (C O), 154.0 (ipso-Ar), 151.3 (ipso-
Ar), 130.7 (ipso-Ar), 123.9 (Ar), 44.3 (CMe3), 35.6 (CHN), 34.3
(ArCH), 32.2 (CH2N), 29.8 (ArCH), 25.5 (CMe3), 24.9 (Me), 24.8
(Me) and 23.5 (Me); m/z (CI; NH3) 394 (100) [Found (M + H)+
394.2416. C22H35NO3S requires M + H, 394.2416].
Phenyl-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)methanone 27
Using general procedure B, aziridine 9 (200 mg, 0.64 mmol)
in THF (6 mL), sec-BuLi (1.60 mL of a 1.2 M solution in
cyclohexane, 1.92 mmol), PMDETA (0.4 mL, 1.92 mmol) in THF
(4 mL) and benzaldehyde (0.2 mL, 1.92 mmol) followed by PCC
(207 mg, 0.96 mmol) in CH2Cl2 (10 mL) gave the crude product.
Purification by flash chromatography on silica with petrol–Et2O
(8 : 1) as eluent gave ketone 27 (117 mg, 44%) as a white solid,
mp 94–96 ◦C, RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1 1690
=
(C O), 1322 (SO2) and 1163 (SO2); dH (400 MHz, CDCl3) 7.94
(2 H, dd, J 7.0 and 1.0, o-Ph), 7.58 (1 H, br t, J 7.0, p-Ph), 7.42
(2 H, t, J 7.0, m-Ph), 7.18 (2 H, s, Ar), 4.32 (2 H, sept, J 7.0, ArCH),
4.13 (1 H, dd, J 7.0 and 4.0, CHN), 2.95 (1 H, d, J 7.0, CH2N),
2.89 (1 H, sept, J 7.0, ArCH), 2.80 (1 H, d, J 4.0, CH2N), 1.25
(6 H, d, J 7.0, Me), 1.24 (6 H, d, J 7.0, Me) and 1.21 (6 H, d, J 7.0,
2-Methyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)propan-1-one 25
=
Me); dC (100.6 MHz; CDCl3) 191.7 (C O), 154.0 (ipso-Ar), 151.4
(ipso-Ar), 135.7 (ipso-Ph), 133.9 (Ph), 130.7 (ipso-Ar), 128.75 (Ph),
128.68 (Ph), 124.0 (Ar), 37.9 (CHN), 34.2 (ArCH), 32.0 (CH2N),
29.8 (ArCH), 24.78 (Me), 24.75 (Me), 23.52 (Me) and 23.50 (Me);
m/z (CI; NH3) 414 (100) [Found (M + H)+ 414.2097. C24H31NO3S
requires M + H, 414.2103].
Using general procedure B, aziridine 9 (200 mg, 0.64 mmol)
in THF (6 mL), sec-BuLi (1.60 mL of a 1.2 M solution in
cyclohexane, 1.92 mmol, 3.0 eq), PMDETA (0.4 mL, 1.92 mmol,
3.0 eq) in THF (4 mL) and isobutyraldehyde (0.2 mL, 1.92 mmol)
followed by PCC (207 mg, 0.96 mmol) in CH2Cl2 (10 mL) gave the
crude product. Purification by flash chromatography on silica with
petrol–Et2O (10 : 1) as eluent gave ketone 25 (135 mg, 56%) as a
colourless oil, RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1 1721
2-Methyl-1-(3-methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-
2-yl)propan-1-one 28
=
(C O), 1322 (SO2) and 1164 (SO2); dH (400 MHz, CDCl3) 7.19 (2
Using general procedure B, aziridine 14 (200 mg, 0.62 mmol)
in THF (6 mL), sec-BuLi (1.56 mL of a 1.2 M solution in
cyclohexane, 1.86 mmol), PMDETA (0.38 mL, 1.86 mmol) in
H, s, Ar), 4.31 (2 H, sept, J 7.0, ArCH), 3.44 (1 H, dd, J 7.0 and 4.0,
CHN), 2.91 (1 H, sept, J 7.0, ArCH), 2.80 (1 H, d, J 7.0, CH2N),
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THF (4 mL) and isobutyraldehyde (0.2 mL, 1.86 mmol) followed
by PCC (200 mg, 0.93 mmol) in CH2Cl2 (10 mL) gave the crude
product. Purification by flash chromatography on silica with
petrol–Et2O (8 : 1) as eluent gave ketone 28 (127 mg, 52%) as a
colourless oil, RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1 1711
(Ph), 123.7 (Ar), 46.8 (CHN), 45.5 (CHN), 34.2 (ArCH), 29.8
(ArCH), 24.8 (Me), 24.6 (Me), 23.5 (Me) and 13.9 (Me); m/z (CI;
NH3) 428 (100) [Found (M + H)+ 428.2256. C25H33NO3S requires
M + H, 428.2259].
=
(C O), 1322 (SO2) and 1164 (SO2); dH (400 MHz, CDCl3) 7.15 (2
2-Methyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)propan-1-ol syn-18 and anti-18
H, s, Ar), 4.32 (2 H, sept, J 7.0, ArCH), 3.47 (1 H, d, J 4.0, CHN),
3.01 (1 H, qd, J 6.0 and 4.0, CHN), 2.89 (1 H, sept, J 7.0, ArCH),
2.58 (1 H, sept, J 7.0, CH), 1.76 (3 H, d, J 6.0, Me), 1.25 (12 H,
d, J 7.0, Me), 1.23 (6 H, d, J 7.0, Me), 0.93 (3 H, d, J 7.0, Me)
Using general procedure C, ketone 25 (75 mg, 0.2 mmol), NaBH4
(9 mg, 0.24 mmol) and CeCl3.7H2O (90 mg, 0.24 mmol) in MeOH
(2 mL) gave the crude product which contained a 90 : 10 mixture of
alcohols syn-18 and anti-18 by 1H NMR spectroscopy. Purification
by flash chromatography on silica with petrol–Et2O (10 : 1) as
eluent gave alcohol syn-18 (48 mg, 64%) as a colourless oil and
alcohol anti-18 (5 mg, 7%) as a colourless oil.
=
and 0.81 (3 H, d, J 7.0, Me); dC (100.6 MHz; CDCl3) 206.5 (C O),
153.6 (ipso-Ar), 150.8 (ipso-Ar), 133.1 (ipso-Ar), 123.7 (Ar), 48.5
(CHN), 44.9 (CHN), 37.4 (CH), 34.2 (ArCH), 29.7 (ArCH), 24.9
(Me), 24.6 (Me), 23.51 (Me), 23.48 (Me), 17.9 (Me), 17.2 (Me) and
13.7 (Me); m/z (CI; NH3) 394 (100) [Found (M + H)+ 394.2409.
C22H35NO3S requires M + H, 394.2416].
2,2-Dimethyl-1-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
2,2-Dimethyl-1-(3-methyl-1-(2,4,6-
yl)propan-1-ol syn-19 and anti-19
triisopropylphenylsulfonyl)aziridin-2-yl)propan-1-one 29
Using general procedure C, ketone 26 (75 mg, 0.19 mmol), NaBH4
(9 mg, 0.23 mmol) and CeCl3.7H2O (86 mg, 0.23 mmol) in MeOH
(2 mL) gave the crude product which contained a >95 : 5 mixture of
alcohols syn-19 and anti-19 by 1H NMR spectroscopy. Purification
by flash chromatography on silica with petrol–Et2O (10 : 1) as
eluent gave alcohol syn-19 (62 mg, 83%) as a colourless oil.
Using general procedure B, aziridine 14 (200 mg, 0.62 mmol)
in THF (6 mL), sec-BuLi (1.56 mL of a 1.2 M solution in
cyclohexane, 1.86 mmol), PMDETA (0.38 mL, 1.86 mmol) in
THF (4 mL) and trimethylacetaldehyde (0.2 mL, 1.86 mmol)
followed by PCC (200 mg, 0.93 mmol) in CH2Cl2 (10 mL) gave
the crude product. Purification by flash chromatography on silica
with petrol–Et2O (8 : 1) as eluent gave ketone 29 (143 mg, 57%)
as a colourless oil, RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1
Phenyl-(1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-yl)methanol
syn-20 and anti-20
=
1716 (C O), 1320 (SO2) and 1155 (SO2); dH (400 MHz, CDCl3)
7.13 (2 H, s, Ar), 4.32 (2 H, sept, J 7.0, ArCH), 3.74 (1 H, d, J
4.0, CHN), 3.03 (1 H, qd, J 6.0, 4.0, CHN), 2.88 (1 H, sept, J 7.0,
ArCH), 1.76 (3 H, d, J 6.0, Me), 1.26 (6 H, d, J 7.0, Me), 1.24 (6 H,
d, J 7.0, Me), 1.23 (6 H, d, J 7.0, Me) and 1.08 (9 H, s, CMe3);
Using general procedure C, ketone 27 (75 mg, 0.18 mmol), NaBH4
(8.2 mg, 0.22 mmol) and CeCl3·7H2O (82 mg, 0.22 mmol) in
MeOH (2 mL) gave the crude product which contained a 95 : 5
mixture of alcohols syn-20 and anti-20 by 1H NMR spectroscopy.
Purification by flash chromatography on silica with petrol–Et2O
(10 : 1) as eluent gave alcohol syn-20 (70 mg, 93%) as a colourless
oil and alcohol anti-20 (3 mg, 4%) as a colourless oil.
=
dC (100.6 MHz; CDCl3) 206.9 (C O), 153.4 (ipso-Ar), 150.8 (ipso-
Ar), 133.2 (ipso-Ar), 123.7 (Ar), 45.7 (CHN), 45.0 (CHN), 44.0
(CMe3), 34.2 (ArCH), 29.8 (ArCH), 25.5 (CMe3), 24.8 (Me), 24.7
(Me), 23.55 (Me), 23.52 (Me) and 13.5 (Me); m/z (CI; NH3) 408
(100) [Found (M + H)+ 408.2564. C23H37NO3S requires M + H,
408.2572].
2-Methyl-1-(3-methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-
2-yl)propan-1-ol syn-22 and anti-22
Using general procedure C, ketone 28 (75 mg, 0.19 mmol), NaBH4
(9 mg, 0.23 mmol) and CeCl3·7H2O (86 mg, 0.23 mmol) in MeOH
(2 mL) gave the crude product which contained a 90 : 10 mixture of
alcohols syn-22 and anti-22 by 1H NMR spectroscopy. Purification
by flash chromatography on silica with petrol–Et2O (10 : 1) as
eluent gave alcohol syn-22 (58 mg, 77%) as a colourless oil and
alcohol anti-22 (8 mg, 10%) as a colourless oil.
(3-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
yl)(phenyl)methanone 30
Using general procedure B, aziridine 14 (200 mg, 0.62 mmol)
in THF (6 mL), sec-BuLi (1.56 mL of a 1.2 M solution in
cyclohexane, 1.86 mmol), PMDETA (0.38 mL, 1.86 mmol) in THF
(4 mL) and benzaldehyde (0.2 mL, 1.86 mmol) followed by PCC
(200 mg, 0.93 mmol) in CH2Cl2 (10 mL) gave the crude product.
Purification by flash chromatography on silica with petrol–Et2O
(8 : 1) as eluent gave ketone 30 (230 mg, 58%) as a colourless oil,
2,2-Dimethyl-1-(3-methyl-1-(2,4,6-
triisopropylphenylsulfonyl)aziridin-2-yl)propan-
1-ol syn-23 and anti-23
RF (1 : 1 petrol–Et2O) 0.8; vmax(CH2Cl2)/cm-1 1690 (C O), 1321
=
(SO2) and 1163 (SO2); dH (400 MHz, CDCl3) 7.91 (2 H, dd, J 8.0
and 1.0, o-Ph), 7.57 (1 H, t, J 8.0 and 1.0, p-Ph), 7.41 (2 H, t, J
8.0, m-Ph), 7.12 (2 H, s, Ar), 4.34 (2 H, sept, J 7.0, ArCH), 4.19
(1 H, d, J 4.0, CHN), 3.28 (1 H, qd, J 6.0 and 4.0, CHN), 2.86
(1 H, sept, J 7.0, ArCH), 1.83 (3 H, d, J 6.0, Me), 1.24 (6 H, d,
J 7.0, Me), 1.23 (6 H, d, J 7.0, Me) and 1.21 (6 H, d, J 7.0, Me);
Using general procedure C, ketone 29 (75 mg, 0.18 mmol), NaBH4
(8.4 mg, 0.22 mmol) and CeCl3·7H2O (75 mg, 0.22 mmol) in
MeOH (2 mL) gave the crude product which contained a 95 : 5
mixture of alcohols syn-23 and anti-23 by 1H NMR spectroscopy.
Purification by flash chromatography on silica with petrol–Et2O
(10 : 1) as eluent gave alcohol syn-23 (59 mg, 79%) as a colourless
oil.
=
dC (100.6 MHz; CDCl3) 192.2 (C O), 153.4 (ipso-Ar), 150.7 (ipso-
Ar), 135.8 (ipso-Ph), 133.8 (Ph), 133.2 (ipso-Ar), 128.7 (Ph), 128.5
344 | Org. Biomol. Chem., 2009, 7, 335–345
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(3-Methyl-1-(2,4,6-triisopropylphenylsulfonyl)aziridin-2-
Crystal structure determination of anti-4-nitrobenzoic acid
yl)(phenyl)methanol syn-24 and anti-24
2-methyl-1-[3-methyl-1-(2,4,6-triisopropylbenzenesulfonyl)
aziridin-2-yl]propyl ester
Using general procedure C, ketone 30 (50 mg, 0.12 mmol), NaBH4
(5.3 mg, 0.14 mmol) and CeCl3·7H2O (52 mg, 0.14 mmol) in
MeOH (1.5 mL) gave the crude product which contained a
90 : 10 mixture of alcohols syn-24 and anti-24 by 1H NMR
spectroscopy. Purification by flash chromatography on silica with
petrol–Et2O (10 : 1) as eluent gave alcohol syn-24 (44 mg, 88%)
as a colourless oil and alcohol anti-24 (3 mg, 6%) as a colourless
oil.
Crystal data. C29H40N2O6S, M = 544.69, monoclinic, a =
◦
˚
9.7183(5), b = 19.6987(9), c = 15.3953(7) A, b = 95.6970(10) ,
3
˚
U = 2932.7(2) A , T = 110(2) K, space group P21/n, Z = 4,
m(Mo-Ka) = 0.153 mm-1, 29913 reflections measured, 7272 unique
(Rint = 0.0320) which were used in all calculations. The final R1 was
0.0420 (I > 2sI) and wR2 was 0.1099 (all data). CCDC reference
number 695490.
Acknowledgements
Crystal structure determination of (3-methyl-1-(2,4,6-
triisopropylphenylsulfonyl)aziridin-2-yl)(phenyl)methanol
syn-24
We thank The University of York Wild Fund for funding (to J. H.)
and the EPSRC/AstraZeneca for an Industrial CASE award (to
S. P. M.).
Crystal data. C25H35NO3S, M = 429.60, monoclinic, a =
◦
˚
10.2117(11), b = 13.3903(14), c = 17.8587(19) A, b = 104.642(2) ,
3
˚
U = 2362.7(4) A , T = 110(2) K, space group P21/n, Z = 4, m(Mo-
References
Ka) = 0.162 mm-1, 18118reflections measured, 4156unique (Rint
=
1 (a) P. O’Brien, C. M. Rosser and D. Caine, Tetrahedron Lett., 2003, 44,
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anti-4-Nitrobenzoic acid 2-methyl-1-[3-methyl-1-(2,4,6-
triisopropylbenzenesulfonyl) aziridin-2-yl]propyl ester
A solution of 4-nitrobenzoyl chloride (101 mg, 0.54 mmol) in
CH2Cl2 (2 mL) was added to a stirred solution of hydroxy aziridine
anti-22 (179 mg, 0.45 mmol) and Et3N (0.19 mL, 1.35 mmol) in
CH2Cl2 (3 mL) at 0 ◦C under N2. The resulting pale yellow solution
was allowed to warm to rt and stirred for 14 h. Water (5 mL)
was added and the layers were separated. The aqueous layer was
extracted with CH2Cl2 (2 ¥ 5 mL) and the combined organics were
dried (MgSO4) and evaporated under reduced pressure to give the
crude product. Purification by flash column chromatography on
silica with petrol–Et2O (5 : 1) as eluent gave the anti-ester (29 mg,
12%) as a white crystalline solid, mp 110–111 ◦C; RF (5 : 1 petrol–
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Et2O) 0.3; vmax(CH2Cl2)/cm-1 2966, 1726 (C O), 1531, 1463, 1316
=
(SO2), 1151 (SO2), 1101, 969; dH (400 MHz, CDCl3) 8.30 (2 H,
d, J 9.0, o-C6H4NO2), 8.14 (2 H, d, J 9.0, m-C6H4NO2), 7.16 (2
H, s, Ar), 4.72 (1 H, dd, J 6.5 and 3.5, CHO), 4.33 (2 H, sept, J
6.5, ArCH), 3.06 (1 H, dd, J 6.0 and 3.5, CHN), 2.99 (1 H, qd,
J 6.0 and 4.5, CHN), 2.91 (1 H, sept, J 7.0, ArCH), 1.76 (1 H,
sept d, J 7.0 and 3.5, CHMe2), 1.68 (3 H, d, J 6.0, Me), 1.27 (6 H,
d, J 6.5, Me), 1.19 (6 H, d, J 6.5, Me), 1.26 (6 H, d, J 7.0, Me),
0.94 (3 H, d, J 7.0, Me), 0.87 (3 H, d, J 7.0, Me); dC (100.6 MHz;
14 (a) T. Netscher and H. Prinzbach, Synthesis, 1987, 683; (b) A. V.
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=
CDCl3) 163.8 (C O), 153.4 (ipso-Ar), 150.7 (ipso-Ar), 150.6 (ipso-
Ar), 135.2 (ipso-Ar), 133.4 (ipso-Ar), 130.7 (o-C6H4NO2), 123.6
(2 ¥ CH, Ar), 78.3 (CHO), 46.2 (CHN), 44.7 (CHN), 34.2 (ArCH),
30.7 (ArCH), 29.7 (ArCH), 24.8 (Me), 24.7 (Me), 23.6 (Me), 18.7
(Me) 16.5 (Me), 13.6 (Me); m/z (ESI) 544 [(M + H),+ 100], 438
(7) [Found (M + H)+ 545.2680. C29H40N2O6S requires M + H,
545.2685].
18 For related studies on the reduction of N-alkyl keto aziridines, see:
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4811; (b) J. M. Yun, T. B. Sim, H. S. Hahm and W. K. Lee, J. Org.
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This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 335–345 | 345
©