New stable N-H oxaziridines - Synthesis and reactivity

Article abstract of DOI:10.1002/ejoc.200901029

A number of stable new N-H oxaziridines have been designed and prepared, and their reactivity as electrophilic sources of nitrogen investigated. 3-tert-Butyl-3-phenyloxaz-ridine is the most efficient and stable and has potential for use as a general reagent for this purpose.

Full text of DOI:10.1002/ejoc.200901029

FULL PAPER
DOI: 10.1002/ejoc.200901029
New Stable N-H Oxaziridines – Synthesis and Reactivity
Sylvain Blanc,[a] Céline A. C. Bordogna,[b] Benjamin R. Buckley,[a] Mark R. J. Elsegood,[a]
and Philip C. Bulman Page*[c]
Keywords: Oxaziridine / Amination / Nitrogen / Small ring systems
A number of stable new N-H oxaziridines have been de- iridine is the most efficient and stable and has potential for
signed and prepared, and their reactivity as electrophilic
use as a general reagent for this purpose.
sources of nitrogen investigated. 3-tert-Butyl-3-phenyloxaz-
promoted by acid, forming an N-protonated oxaziridine
which is believed to be the active oxidizing species.[8]
Nitrogen transfer has also been performed, mainly using
N-H, N-alkyl-, N-aryl-, N-acyl-, N-carboxamido- or N-(alk-
oxycarbonyl)oxaziridines, with sulfur, nitrogen, phosphorus
and carbon nucleophiles.[9] However, few electrophilic ami-
nations have been carried out with enantiomerically pure
chiral N-substituted oxaziridines.[10] To date, only a handful
of reports of enantiomerically pure chiral N-acyloxazirid-
ines have been published.[10,11]
N-H oxaziridines, first reported in the early 1960s,[12] can
be effective for the amination of nitrogen, oxygen, sulfur
and carbon nucleophiles,[13] and are potentially of great
value today as relatively “green” sources of electrophilic ni-
trogen. Due to their general instability, however, very few
N-H oxaziridines have been prepared, and fewer used for
their ability to transfer nitrogen.[14] N-H oxaziridines also
offer the attractive additional potential as enantioselective
nitrogen transfer agents by incorporation of chiral elements
into their structure.
The first enantiomerically pure chiral N-H oxaziridines
1 and 2, which were prepared in our laboratories, were de-
rived from (R,R)-(+)-camphor and the related (–)-fenchone
respectively.[15] These two N-H oxaziridines showed remark-
able stability, and may readily be functionalized at nitrogen
using a range of standard electrophilic reagents; for exam-
ple, reaction of 1 with cyclohexyl isocyanate gives oxazirid-
ine 3 in 67% yield. They are able to transfer their nitrogen
atom to carbon nucleophiles such as anions derived from
esters and nitriles.[16] In these reactions, a new carbon–
nitrogen bond is formed, but the camphor or fenchone unit
is retained in the product structure through an imine link-
age, and the ester or nitrile moiety is hydrolysed and in
some cases decarboxylated, we believe as a consequence of
the reaction mechanism (e.g. Scheme 1), in which cleavage
of the N–O bond of the oxaziridine induced by attack of
the nucleophile is followed by cyclization; ring-opening and
tautomerization leads to the observed products. Moderate
Introduction
Chemical reactions involving electrophilic sources of ni-
trogen commonly require toxic or otherwise undesirable
reagents, including tosyl azide, nitroso compounds, di-
imides, or azodicarboxylates, and new reagents are therefore
desirable; indeed, the use of green sources of electrophilic
nitrogen has been identified as an “aspirational reaction”
by the pharmaceutical manufacturers.[1] Oxaziridines, char-
acterized by a reactive strained C,N,O three-membered
ring, have shown interesting reactivities as nitrogen and
oxygen atom transfer reagents, and the synthesis and chem-
istry of oxaziridines has been widely studied.[2] It has been
established that the attack of a nucleophile occurs at either
the oxygen or the nitrogen atoms of the ring, depending
upon the nature of the nucleophile and the substituents on
the oxaziridine, especially at the nitrogen atom. For exam-
ple, oxaziridines bearing electron-withdrawing substituents
on the nitrogen atom or on both the nitrogen and the car-
bon atoms of the three-membered ring have been developed
for their ability to transfer oxygen atoms to nucleophiles. In
particular, N-(fluoroalkyl)oxaziridines,[3] N-phosphanylox-
aziridines[4] and N-sulfonyloxaziridines[5] have proved to be
efficient reagents for the oxidation of sulfides to sulfoxides,
the asymmetric hydroxyation of enolates, and the stereose-
lective epoxidation of olefins. Davis in particular has shown
that N-substituted camphoryl oxaziridines transfer oxygen
to various nucleophiles with very good stereoselectivity,
perhaps due to the steric hindrance close to the oxaziridine
ring.[6] Oxygen transfer may also be performed with hin-
dered oxaziridines and hindered nucleophiles,[7] and may be
[a] Department of Chemistry, Loughborough University,
Leicestershire LE11 3TU, UK
[b] School of Chemistry, University of East Anglia,
Norwich NR4 7TJ, UK
[c] School of Chemistry, University of East Anglia,
Norwich NR4 7TJ, UK
Fax: +44-1603-593008
E-mail: p.page@uea.ac.uk
882
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New Stable N-H Oxaziridines
stereoselectivity is observed. We report here the synthesis of yllithium or Grignard reagents to nitriles to give the corre-
a number of new stable N-H oxaziridines, together with sponding primary imines after work-up,[18] followed by oxi-
their reactivity as sources of electrophilic nitrogen towards dation with mCPBA (Scheme 2). These new oxaziridines
carbon nucleophiles.
have proved to be stable in the laboratory for months at
room temperature.
An unusual feature of nitrogen-containing three-mem-
bered heterocycles is that there is rather a high barrier to
inversion at nitrogen.[19] Indeed, each of our three new N-
1
H oxaziridines displays pairs of signals in their H NMR
spectra at room temperature, presumably corresponding to
slow inversion at the pyramidal nitrogen atom, with the ra-
Table 1. Electrophilic amination of nitriles using N-H oxaziridines
4–6.[a]
Scheme 1. Nitrogen transfer to nucleophiles.
Results and Discussion
Because of the dearth of reports of stable N-H oxazirid-
ines, we initiated an investigation into the optimum steric
and electronic requirements for the synthesis of stable N-H
oxaziridines that might be used as effective nitrogen transfer
reagents. 3,3-Di-tert-butyloxaziridine and 3,3-diphenyl ox-
aziridine have previously been reported,[17] and we prepared
N-H oxaziridines related to these two structures, as it ap-
peared that the presence of at least one tert-butyl or phenyl
group was necessary for stability in these simple cases.
Three new N-H oxaziridines, the tert-butyl/phenyl 4, isopro-
pyl/phenyl 5, and isopropyl/tert-butyl 6, were prepared
using a straightforward two-step procedure using the corre-
sponding nitrile as the starting material, by addition of alk-
Scheme 2. Generation of N-H oxaziridines 4–6. (i) tBuLi, THF,
78 °C to room temp., 15 h; NH3, –78 °C to room temp.; 70%; (ii)
mCPBA, –40 °C, CH2Cl2; 79%; (iii) iPrMgCl, THF, ∆, 15 h; NH3,
–78 °C to room temp.; 65%; (iv) mCPBA, –40 °C, CH2Cl2; 30%;
(v) tBuLi, THF, –78 °C to room temp., 15 h; NH3, –78 °C to room
temp.; (vi) mCPBA, –40 °C, CH2Cl2; 67% (two steps).
[a] Conditions: i) LHMDS, nitrile, THF, –78 °C, 1 h; ii) oxaziridine
addition at –78 °C, then room temp.
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P. C. B. Page et al.
FULL PAPER
tios: 4 (4:1); 5 (2.3:1); 6 (1.2:1). These three oxaziridines camphor oxaziridine 1, where both hydrolysis of the nitrile
were then used in the electrophilic amination of three ni- and hydrolysis/decarboxylation of the ester were observed
triles (Table 1) by deprotonation α to the nitrile using lith- as reaction pathways.[15,16]
ium hexamethyldisilazide followed by addition of the N-H
3-tert-Butyl-3-phenyloxaziridine (4) was the most stable
oxaziridine in THF solution at –78 °C, conditions that are and appears to be the best general reagent for nitrogen
very successful for the “parent” camphor N-H oxaziridine transfer. Other structures based on oxaziridine 4 were there-
1.
fore investigated; for example, substituents were added at
Each oxaziridine was effective for nitrogen transfer to the the phenyl group in an attempt to increase reactivity. Three
nitriles. After work-up and purification, the products 7–12 further new N-H oxazirdines 13–15 were synthesized fol-
were obtained in moderate to good yields as the corre- lowing the procedure described for 4–6 (Scheme 3).
sponding primary amides, as we have previously observed.
2,2-Dimethyl-1-[4-trifluoromethyl)phenyl]propan-1-imine
In the case of the product 9, it was interesting to note that (16) and propanimine 17 were not sufficiently stable to be
only the nitrile group is attacked and hydrolysed, and not
the ester moiety. This result shows a difference of reactivity
between these new N-unprotected oxaziridines and N-H
Table 2. Electrophilic amination of nitriles using N-H oxaziridines
13–15.[a]
Scheme 3. Generation of N-H oxaziridines 13–15. (i) tBuLi, THF,
–78 °C to room temp., 15 h; NH3, –78 °C to room temp.; 64%; (ii)
mCPBA, –40 °C, CH2Cl2; 38%; (iii) tBuLi, THF, –78 °C to room
temp., 15 h; NH3, –78 °C to room temp.; (iv) mCPBA, –40 °C,
CH2Cl2; 43% (two steps); (v) tBuLi, THF, –78 °C to room temp.,
15 h; NH3, –78 °C to room temp.; (vi) mCPBA, –40 °C, CH2Cl2;
60% (two steps).
Figure 1. Structure of N-H oxaziridine 13 with two molecules in
the asymmetric unit linked via N–H···O and N–H···π interactions.
[a] Conditions: i) LHMDS, nitrile, THF, –78 °C, 1 h; ii) oxaziridine
addition at –78 °C, then room temp.
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New Stable N-H Oxaziridines
leum ether (5 mL/mmol) was added to the mixture. The precipi-
tated m-chlorobenzoic acid was removed by filtration, and the rest
of this by-product washed from the resulting solution with aqueous
sodium hydroxide. The organic phase was dried (MgSO4), and the
solvent removed under reduced pressure to give the crude product,
which was purified by column chromatography on silica gel (light
petroleum/ethyl acetate) to afford the desired oxaziridine.
purified and were used directly in the oxidation step with-
out further purification. All of these oxaziridines again dis-
play pairs of signals in their 1H NMR spectra at room tem-
perature, with ratios: 13 (7.3:1); 14 (2.3:1); 15 (1.5:1), and
are air-stable, no decomposition being observed over several
days at room temperature. While all of the other oxazirid-
ines described here are colourless oils, oxaziridine 13 was
isolated as a colourless crystalline material, and was sub-
jected to single-crystal X-ray analysis (Figure 1). The crys-
tal structure shows hydrogen bonding between the NH hy-
drogen atom of one molecule and the oxygen atom of an-
other, plus a possible interaction between the NH hydrogen
atom of one molecule and the aromatic ring of the other.
These oxaziridines were used as described above for elec-
trophilic amination reactions of two nitriles (Table 2).
While these new N-H oxaziridines were all able to trans-
fer nitrogen to give products 18–23, no improvement in
yields or reactivity over 3-tert-butyl-3-phenyloxaziridine (4)
was observed. The electron-donating character of the meth-
oxy group may explain the reduced reactivity of the 3-tert-
butyl-3-(2-methoxyphenyl)-1,2-oxaziridine (13).
General Procedure for the Reaction of Oxaziridines with Phenyl-
acetonitrile or α-Methylphenylacetonitrile: A solution of phenylace-
tonitrile or α-methylphenylacetonitrile in THF (5 mL/mmol) was
added dropwise to a cooled (–78 °C) stirring solution of lithium
bis(trimethylsilyl)amide (1.0  in THF, 1.1 equiv.) in dry THF
(2.5 mL/mmol). After one hour at –78 °C, a solution of oxaziridine
(1.5 equiv.) in dry THF (2 mL/mmol) was added dropwise, and the
reaction allowed to reach room temperature over a period of two
hours. Saturated aqueous ammonium chloride (10 mL/mmol) was
added, and the mixture extracted with dichloromethane
(3ϫ10 mL/mmol). The combined organic extracts were dried
(MgSO4), and the solvents removed under reduced pressure to give
an oil, which was purified by column chromatography on silica gel
(light petroleum/ethyl acetate). The product was recrystallized from
a mixture of chloroform and hexane to afford the desired product.
3-tert-Butyl-3-phenyloxaziridine (4): Prepared according to the ge-
neral procedure using (300 mg, 1.64 mmol) of the corresponding
imine, the title compound 4 was isolated as a colourless oil (231 mg,
Conclusions
79%). IR (neat): ν
= 3202 (NH), 2969, 1481, 1329, 1128, 902,
˜
max.
735, 702 cm–1. Oxaziridine 4 shows in its 1H NMR spectrum a
We have developed a new range of chiral N-H oxazirid-
ines capable of electrophilic amination of nitrile derivatives.
3-tert-Butyl-3-phenyloxaziridine (4) is the most efficient and
stable and has potential for use as a general reagent for this
purpose.
signal pair of diastereoisomers (A and B) at N-H in a 4:1 ratio (the
1
major isomer is represented by A). H NMR (400 MHz, CDCl3):
δ = 7.39–7.31 (m, CHAr, 5 HA, 5 HB), 4.41 (br. s, NH, 1 HB), 3.86
(br. s, NH, 1 HA), 1.07 (s, CCH3, 9 HB), 1.02 (s, CCH3, 9 HA) ppm.
13C NMR (100 MHz, CDCl3): δ = 137.9 (CAqAr), 136.5 (CBqAr),
128.5 (CHAr), 128.1 (CHAr), 128.0 (CHAr), 127.7 (CHAr), 127.6
(CHAr), 127.4 (CHAr), 86.26 (N-CBq-O), 86.23 (N-CAq-O), 35.2
(CBqCH3), 35.0 (CAqCH3), 25.55 (CCAH3), 25.48 (CCBH3) ppm.
MS (FAB+): m/z = 178 [M + H]+, 105, 77. HRMS (FAB+)
C11H16NO [M + H]+ calcd. 178.12319; found 178.12342.
Experimental Section
General Procedure for the Synthesis of Imines: A solution of nitrile
in dry THF (1 mL/mmol) cooled to –78 °C was added dropwise to
a solution of tert-butyllithium (1.5 equiv., 1.7  in pentane) or a
Grignard reagent (1.5 equiv., 2  or 3  in THF) and the mixture
stirred at room temperature (when tert-butyllithium was used), or
under reflux (when Grignard reagents were used), for 15 h. After
cooling to –78 °C, ammonia gas was bubbled through and the reac-
tion was stirred vigorously for 15 min. The mixture was allowed to
reach room temperature, the white precipitate removed by fil-
tration, and the solvent removed under reduced pressure. Purifica-
tion by kugelrohr distillation afforded the desired imines.
3-Isopropyl-3-phenyloxaziridine (5): Prepared according to the gene-
ral procedure using (1.25 g, 4.85 mmol) of the corresponding imine,
the title compound 5 was isolated as a colourless oil (243 mg, 30%).
IR (neat): ν
= 3200 (NH), 2969, 1577, 1469, 1294, 756, 699
˜
max.
1
cm–1. Oxaziridine 5 shows in its H NMR spectrum a signal pair
of diastereoisomers (A and B) at N-H in a 2.3:1 ratio (the major
isomer is represented by A). 1H NMR (400 MHz, CDCl3): δ =
7.40–7.13 (m, CHAr, 5 HA, 5 HB), 4.14 (br. s, NH, 1 HB), 3.69 (br.
s, NH, 1 HA), 2.30 (septet, J = 6.9 Hz, CHCH3, 1 HA), 2.29 (septet,
J = 6.9 Hz, CHCH3, 1 HB), 0.948 (d, J = 6.9 Hz, CHCH3, 3 HB),
0.946 (d, J = 6.9 Hz, CHCH3, 3 HB), 0.91 (d, J = 6.9 Hz, CHCH3,
3 HA), 0.89 (d, J = 6.9 Hz, CHCH3, 3 HA) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.9 (CAqAr), 136.5 (CBqAr), 128.8
(CHAr), 128.6 (CHAr), 128.5 (CHAr), 128.1 (CHAr), 127.0
(CHAr), 126.1 (CHAr), 83.6 (N-CBq-O), 83.7 (N-CAq-O), 33.8
(CBCH3), 32.3 (CAHCH3), 17.8 (CCAH3), 17.5 (CHCBH3), 17.1
(CHCBH3), 16.4 (CCAH3) ppm. MS (FAB+): m/z = 164 [M + H]+,
105, 91, 77. HRMS (FAB+) C10H14NO [M + H]+ calcd. 164.10754;
found 164.10721.
General Procedure for the Synthesis of Oxaziridines from Imines: A
solution of purified mCPBA (1 equiv.) in dry dichloromethane
(5 mL/mmol) was cooled to between –30 °C and –40 °C, causing
some of the peracid to crystallize from the solution. Upon addition
of a solution of the imine in dry dichloromethane (3 mL/mmol) to
the reaction mixture over a period of 4–5 min, the solution became
homogeneous. The reaction mixture was stirred overnight at be-
tween –30 and –40 °C, and allowed to reach room temperature. The
reaction mixture was stirred at room temperature for a further two
hours until all of the peracid had reacted, by which time much
of the m-chlorobenzoic acid by-product had crystallized from the
solution. The solution was concentrated under reduced pressure
until approximately 25% of the original volume remained. Petro-
leum ether was added and the solution again concentrated under
reduced pressure until approximately 25% of the original volume
remained. This process was repeated once more, and finally petro-
3-tert-Butyl-3-isopropyloxaziridine (6): A solution of isobutyro-
nitrile (1.35 mL, 15 mmol) in THF (2.5 mL) cooled to –78 °C, was
added dropwise to a solution of tert-butyllithium (1.7  in pentane,
13.2 mL, 22.5 mmol) and the mixture was stirred at room tempera-
ture for 15 h. After cooling to –78 °C, ammonia gas was bubbled
through and the reaction was stirred vigorously for 15 min. The
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P. C. B. Page et al.
FULL PAPER
mixture was then allowed to reach room temperature, the precipi-
tate was filtered and the solvent was removed under reduced pres-
sure to afford the imine which was used immediately due to its
instability. Then, prepared according to the general procedure, the
title compound 6 was isolated as a colourless oil (1.45 g, 67% over
32.3 Hz, CBqArCF3), 128.5 (CBHAr), 128.1 (CAHAr), 124.7 (q,
3
3JC-F
=
3.7 Hz, CAHArCCF3), 124.5 (q, JC-F
=
3.8 Hz,
CBHArCCF3), 124.0 (q, JC-F = 270.5 Hz, CBqF3), 123.8 (q, JC-F
=
270.6 Hz, CAqF3), 86.0 (N-CBq-O), 85.9 (N-CAq-O), 35.1
(CBqCH3), 35.0 (CAqCH3), 25.4 (CCAH3), 25.3 (CCBH3) ppm. MS
(FAB+): m/z = 246 [M + H]+, 228, 199, 172, 145. HRMS (FAB+)
C12H15NOF3 [M + H]+ calcd. 246.10275; found 246.11120.
two steps). IR (neat): ν
= 3220 (NH), 2968, 1481, 1465, 1368,
˜
max.
1286, 969, 896 cm–1. Oxaziridine 6 shows in its 1H NMR spectrum
a signal pair of diastereoisomers (A and B) at N-H in a 1.2:1 ratio
(the major isomer is represented by A). 1H NMR (400 MHz,
CDCl3): δ = 3.81 (br. s, NH, 1 HB), 3.56 (br. s, NH, 1 HA), 2.43
(septet, J = 6.9 Hz, CHCH3, 1 HA), 2.28 (septet, J = 6.8 Hz,
CHCH3, 1 HB), 0.96 (s, CCH3, 9 HB), 0.92 (s, CCH3, 9 HA), 0.93–
0.91 (m, CHCH3, 6 HA), 0.78 (d, J = 6.8 Hz, CHCH3, 3 HB), 1.32
(J = 6.8 Hz, CHCH3, 3 HB) ppm. 13C NMR (100 MHz, CDCl3): δ
3-tert-Butyl-3-[4-(methylsulfonyl)phenyl]-1,2-oxaziridine (15):
A
solution of 4-(methylthio)benzonitrile (865 mg, 5.8 mmol) in THF
(2.5 mL) cooled to –78 °C in dry diethyl ether was added dropwise
to a solution of tert-butyllithium (1.7  in pentane, 5.1 mL,
8.7 mmol) and the mixture was stirred overnight at room tempera-
ture. After cooling to –78 °C, ammonia gas was bubbled through
and the reaction was stirred vigorously for 15 min. Then, the mix-
ture was allowed to reach room temperature, the white precipitate
was filtered and the solvent was removed under reduced pressure
to afford the imine as an orange oil. Because of its instability, the
imine was not purified and was used immediately. Prepared accord-
ing to the general procedure, the title compound 15 was isolated as
a colourless solid (881 mg, 60% over two steps), m.p. 143–144 °C.
=
86.4 (N-CAq-O), 86.2 (N-CBq-O), 36.0 (N-CBq-O), 35.9
(CAqCH3), 26.7 (CBHCH3), 26.5 (CAHCH3), 25.2 (CCAH3), 20.1
(CCBH3), 20.4 (CHCAH3), 20.2 (CHCAH3), 18.3 (CHCBH3), 17.6
(CHCBH3) ppm. MS (FAB+): m/z = 143 [M]+, 128, 101, 84, 70, 57.
HRMS (FAB+) C8H17NO [M]+ calcd. 143.13101; found 143.13151.
3-tert-Butyl-3-(2-methoxyphenyl)-1,2-oxaziridine (13): Prepared ac-
cording to the general procedure using (920 mg, 4.8 mmol) of the
corresponding imine, the title compound 13 was recrystallized from
a mixture of chloroform/hexane and isolated as a colourless crys-
IR (neat): ν
= 3202 (NH), 2970, 2871, 1482 cm–1. Oxaziridine
˜
max.
15 shows in its 1H NMR spectrum a signal pair of diastereoisomers
(A and B) at N-H in a 1.5:1 ratio (the major isomer is represented
by A). 1H NMR (400 MHz, CDCl3): δ = 7.96–7.92 (m, CHAr, 2
talline material (385 mg, 38%), m.p. 52–53 °C. IR (neat): ν
=
˜
max.
3220 (NH), 2977, 1599 cm–1. Oxaziridine 13 shows in its H NMR HA, 2 HB), 7.64–7.58 (m, CHAr, 2 HA, 2 HB), 4.48 (br. s, NH, 1
1
spectrum a signal pair of diastereoisomers (A and B) at N-H in a
HB), 3.87 (br. s, NH, 1 HA), 3.08 (s, SO2CH3, 3 HA), 3.04 (s,
SO2CH3, 3 HB), 1.09 (s, CCH3, 9 HB), 1.04 (s, CCH3, 9 HA) ppm.
7.3:1 ratio (the major isomer is represented by A). 1H NMR
(400 MHz, CDCl3): δ = 7.34–7.29 (m, CHAr, 2 HA, 2 HB), 6.97– 13C NMR (100 MHz, CDCl3): δ = 143.6 (CAqAr), 142.5 (CBqAr),
6.88 (m, CHAr, 2 HA, 2 HB), 4.44 (br. s, NH, 1 HB), 4.00 (br. s,
NH, 1 HA), 3.83 (s, OCH3, 3 HA, 3 HB), 1.06 (s, CCH3, 9 HB),
1.00 (s, CCH3, 9 HA) ppm. 13C NMR (100 MHz, CDCl3): δ =
156.8 (CqAr), 129.8 (CHAr), 129.7 (CHAr), 126.37 (CqAr), 119.8
140.7 (CAqAr SO2CH3), 140.3 (CBqAr SO2CH3), 129.2 (CBHAr),
128.7 (CAHAr), 126.9 (CAHAr), 126.7 (CBHAr), 85.9 (N-CBq-O),
85.8 (N-CAq-O), 44.5 (SO2CBH3), 44.4 (SO2CAH3), 35.0
(CA+BqCH3), 25.4 (CCAH3), 25.3 (CCBH3) ppm. MS (FAB+): m/z
(CHAr), 110.41 (CHAr), 83.5 (N-Cq-O), 55.11 (OCH3), 35.8 = 256 [M + H]+, 154, 107, 77, 57. HRMS (FAB+) C12H18NO3S
(CqCH3), 25.3 (CCH3) ppm. MS (FAB+): m/z = 208 [M + H]+, [M + H]+ calcd. 256.10095; found 256.10074. C12H17NO3S·0.1H2O
190, 175, 135, 91, 77. HRMS (FAB+) C12H18NO2 [M + H]+ calcd. (257.14): calcd. C 56.04, H 6.75, N 5.44; found C 55.92, H 6.51, N
208.13375; found 208.13375. C12H17NO2 (207.27): calcd. C 69.54,
H 8.27, N 6.76; found C 69.63, H 8.34, N 9.97.
5.16.
2-(2,2-Dimethyl-1-phenylpropylidenamino)-2-phenylacetamide (7):
Prepared according to the general procedure using phenylacetoni-
trile (132 µL, 1.15 mmol), the title compound 7 was isolated as a
CCDC-757772 (for 13) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
yellow solid (265 mg, 78%), m.p. 142–143 °C. IR (DCM): ν
=
˜
max.
3265 (NH2), 3058, 2965, 1682 (C=O) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.24–7.09 (m, 9 H, CHAr), 6.92 (br. s, 1 H, CHAr),
6.38 (br. s, 1 H, NH2), 5.75 (br. s, 1 H, NH2), 4.41 (s, 1 H,
PhCHCO), 1.12 (s, 9 H, CCH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 181.2 (Cq=O), 175.0 (Cq=N), 140.19 (CqAr), 136.0
(CqAr), 128.3 (CHAr), 128.0 (CHAr), 127.4 (CHAr), 127.0
(CHAr), 126.9 (CHAr), 69.2 (PhCHCO), 40.5 (CqCH3), 28.3
(CCH3) ppm. MS (FAB+): m/z = 295 [M + H]+, 317, 250, 162, 106,
91. HRMS (FAB+): calcd. for C19H23N2O [M + H]+ 295.18109;
found 295.18130. C19H22N2O (294.17): calcd. C 77.50, H 7.54, N
9.51; found C 77.02, H 7.47, N 9.50.
3-tert-Butyl-3-[4-(trifluoromethyl)phenyl]-1,2-oxaziridine (14):
A
solution of 4-(trifluoromethyl)benzonitrile (735 mg, 4.3 mmol) in
THF (2.5 mL) cooled to –78 °C, was added dropwise to a solution
of tert-butyllithium (1.7  in pentane, 3.8 mL, 6.5 mmol) and the
mixture was stirred overnight at room temperature. After cooling
to –78 °C, ammonia gas was bubbled through and the reaction was
stirred vigorously for 15 min. Then, the mixture was allowed to
reach room temperature, the white precipitate was filtered and the
solvent was removed under reduced pressure to afford the imine as
a black foam. Because of its instability, the imine was not purified
and was used immediately. Prepared according to the general pro-
cedure, the title compound 14 was isolated as a yellow oil (455 mg,
2-(2,2-Dimethyl-1-phenylpropylidenamino)-2-phenylpropanamide
(8): Prepared according to the general procedure using α-methyl-
phenylacetonitrile (93 µL, 0.67 mmol), the title compound 8 was
isolated as a white solid (165 mg, 80%), m.p. 157–158 °C. IR
43% over two steps). IR (neat): ν
= 3206 (NH), 2969, 2872,
˜
max.
1619 cm–1. Oxaziridine 14 shows in its H NMR spectrum a signal
1
pair of diastereoisomers (A and B) at N-H in a 2.3:1 ratio (the
(DCM): ν
= 3164 (NH2), 3053, 2967, 1686 (C=O) cm–1. 1H
˜
max.
1
major isomer is represented by A). H NMR (400 MHz, CDCl3):
NMR (400 MHz, CDCl3): δ = 8.65 (br. s, 1 H, NH), 7.22–7.18 (m,
1 H, CHAr), 7.13–7.063 (m, 4 H, CHAr), 6.97–6.91 (m, 4 H,
CHAr), 6.72–6.68 (m, 1 H, CHAr), 5.69 (br. s, 1 H, NH), 1.47 (s,
δ = 7.64–7.59 (m, CHAr, 2 HA, 2 HB), 7.52–7.49 (m, CHAr, 3 HA,
3 HB), 7.10 (d, J = 7.6 Hz, CHAr, 1 HA, 1 HB), 4.45 (br. s, NH, 1
HB), 3.87 (br. s, NH, 1 HA), 1.08 (s, CCH3, 9 HB), 1.03 (s, CCH3, 9 3 H, PhCCH3), 1.11 (s, 9 H, CCH3) ppm. 13C NMR (100 MHz,
HA) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.7 (CAqAr), 140.4 CDCl3): δ = 180.2 (Cq=O), 179.0 (Cq=N), 144.25 (CqAr), 136.9
2
2
(CBqAr), 130.8 (q, JC-F = 32.5 Hz, CAqArCF3), 130.6 (q, JC-F
=
(CqAr), 128.0 (CHAr), 127.6 (CHAr), 127.2 (CHAr), 126.8
886
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 882–889

New Stable N-H Oxaziridines
(CHAr), 126.7 (CHAr), 126.4 (CHAr), 126.3 (CHAr), 67.7
(PhCqCH3), 41.9 (CqCH3), 28.5 (CCH3), 21.8 (PhCCH3) ppm. MS
179.5 (Cq=O), 177.2 (Cq=N), 144.6 (CqAr), 139.3 (CqAr), 128.5
(CHAr), 128.1 (CHAr), 127.2 (CHAr), 127.2 (CHAr), 126.8
(FAB+) m/z 309 [M + H]+, 331, 264, 162, 105, 91. HRMS (FAB+) (CHAr), 126.4 (CHAr), 67.7 (PhCqCH3), 41.3 (CHCH3), 21.9
C20H25N2O [M
+
H]+ calcd. 309.19669; found 309.19625. (PhCCH3), 20.2 (CHCH3), 20.0 (CHCH3) ppm. MS (FAB+): m/z
C20H24N2O (308.42): calcd. C 77.87, H 7.85, N 9.08; found C
77.77, H 7.78, N 9.07.
= 295 [M + H]+, 250, 148, 91. HRMS (FAB+): C19H23N2O [M +
H]+ calcd. 295.18104; found 295.18062. C19H22N2O (294.39): calcd.
C 77.50, H 7.55, N 9.52; found C 77.21, H 7.52, N 9.51.
Ethyl 3-Amino-2-(2,2-dimethyl-1-phenylpropylidenamino)-2-methyl-
3-oxopropanoate (9):
A
solution of ethyl 2-cyanopropionate
2-Phenyl-2-(2,2,4-trimethylpentan-3-ylidenamino)acetamide
(12):
(157 µL, 1.2 mmol) in THF (2.5 mL) was added dropwise to a co-
oled (–78 °C) stirring solution of lithium bis(trimethylsilyl)amide
Prepared according to the general procedure using phenylacetoni-
trile (40 µL, 0.35 mmol), the title compound 12 was isolated as a
(1.0  in THF, 1.45 mL, 1.2 mmol) in dry THF (2.5 mL). After 1 h colourless solid (77 mg, 85%), m.p. 187–188 °C. IR (DCM): ν
˜
max.
at –78 °C, a solution of 4 (200 mg, 1.12 mmol) in dry THF (1 mL)
was added dropwise and the reaction was allowed to reach room
temperature over a period of two hours. Saturated aqueous ammo-
nium chloride (20 mL) was added and the mixture extracted with
DCM (3ϫ25 mL). The combined organic extracts were dried
(MgSO4) and the solvent removed under reduced pressure to give
a yellow oil which was purified by column chromatography on sil-
ica gel (light petroleum/ethyl acetate, 6:4) to afford the title com-
pound 9 (204 mg, 56%) as a colourless solid, m.p. 119–120 °C. IR
= 3145 (NH2), 2965, 1691 (C=O), 1653 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.52–7.50 (m, 2 H, CHAr), 7.33–7.25 (m, 3 H, CHAr),
7.00 (br. s, 1 H, NH2), 5.73 (br. s, 1 H, NH2), 5.48 (s, 1 H,
PhCHCO), 2.97 (septet, J = 7.4 Hz, 1 H, CHCH3), 1.26 (d, J =
7.4 Hz, 3 H, CHCH3), 1.20 (s, 9 H, CCH3), 0.99 (d, J = 7.4 Hz, 3
H, CHCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 183.1 (Cq=O),
175.3 (Cq=N), 140.2 (CqAr), 128.4 (CqAr), 127.4 (CHAr), 126.5
(CHAr), 67.0 (PhCHCO), 42.3 (CqCH3), 29.9 (CHCH3), 27.7
(CCH3), 20.4 (CHCH3), 20.3 (CHCH3) ppm. MS (FAB+): m/z =
261 [M + H]+, 283, 217, 216, 203. HRMS (FAB+) C16H25N2O [M
(DCM): ν
= 3401, 3170 (NH2), 2966, 1731 (C=O ester), 1689
˜
max.
(C=O amide), 1361, 1258, 1134, 715 cm–1. 1H NMR (400 MHz, + H]+ calcd. 261.19662; found 261.19652. C16H24N2O (260.37):
CDCl3): δ = 8.11 (br. s, 1 H, NH), 7.33–7.27 (m, 3 H, CHAr), 6.99 calcd. C 73.79, H 9.30, N 10.76; found C 73.82, H 9.25, N 10.74.
(br. s, 1 H, CHAr), 6.90–6.87 (m, 1 H, CHAr), 6.17 (br. s, 1 H,
2-[1-(2-Methoxyphenyl)-2,2-dimethylpropylidenamino]-2-phenylacet-
amide (18): Prepared according to the general procedure using
NH), 3.81–3.73 (quintet, J = 7.1 Hz, 1 H, OCH2CH3), 3.80–3.70
(quintet, J = 7.1 Hz, 1 H, OCH2CH3), 1.44 (s, 3 H, CH3), 1.15 (s,
phenylacetonitrile (78 µL, 0.67 mmol), the title compound 18 was
9 H, CCH3), 1.12–1.07 (t, J = 7.1 Hz, 3 H, OCH2CH3) ppm. 13C
isolated as a yellow solid (65 mg, 30%), m.p. 168–170 °C. IR: ν
˜
max.
NMR (100 MHz, CDCl3): δ = 179.9 (Cq), 176.4 (Cq), 170.2 (Cq),
135.4 (CqAr), 128.4 (CHAr), 128.3 (CHAr), 128.0 (CHAr), 127.5
(CHAr), 127.2 (CHAr), 70.5 (CH3CqCO2CH2CH3), 61.2
(OCH2CH3), 41.9 (CqCH3), 28.5 (CCH3), 23.2 (CH3), 13.7
(OCH2CH3) ppm. MS (NSI+): m/z = 305 [M + H]+, 260, 162.
HRMS (NSI+) C17H24N2O3 [M + H]+ calcd. 305.1860; found
305.1859. C17H24N2O3 (304.38): calcd. C 67.06, H 7.96, N 9.20;
found C 67.11, H 8.06, N 9.04.
= (DCM) 3432 (NH2), 2965, 1689 (C=O) cm–1 1H NMR
.
(400 MHz, CDCl3): δ = 7.31 (br. s, 1 H, CHAr), 7.30–7.17 (m, 6
H, CHAr), 6.96–6.92 (m, 1 H, CHAr), 6.87 (d, J = 8.4 Hz, 1 H,
NH2), 5.59 (br. s, 1 H, NH2), 4.47 (s, 1 H, PhCHCO), 3.05 (s, 3 H,
OCH3), 1.19 (s, 9 H, CCH3) ppm. 13C NMR (100 MHz, CDCl3):
δ = 179.5 (Cq=O), 175.2 (Cq=N), 155.5 (CqAr), 139.9 (CqAr), 129.5
(CHAr), 127.3 (CHAr), 127.5 (CHAr), 127.03 (CHAr), 127.00
(CHAr), 125.18 (CqArOMe), 120.0 (CHAr), 110.3 (CHAr), 69.5
(PhCHCO), 54.0 (OCH3), 40.8 (CqCH3), 28.3 (CCH3) ppm. MS
(FAB+ ): m/z = 325 [M + H]+ , 347, 280. HRMS (FAB+ )
2-(2-Methyl-1-phenylpropylideneamino)-2-phenylacetamide
(10):
Prepared according to the general procedure using phenylacetoni-
trile (172 µL, 1.49 mmol), the title compound 10 was isolated as a
C
20H25N2O2 [M + H]+ calcd. 325.19160; found 325.19208.
red solid (289 mg, 70%), m.p. 137–138 °C. IR (DCM): νmax. = 3406
C20H24N2O2 (324.42): calcd. C 74.10, H 7.53, N 8.97; found C
74.03, H 7.47, N 8.63.
˜
1
(NH2), 2963, 1683 (C=O), 1596, 1453, 1224, 708 cm–1. H NMR
(400 MHz, CDCl3): δ = 7.37–7.22 (m, 8 H, CHAr), 6.88–6.84 (m,
2 H, CHAr), 5.90 (br. s, 2 H, NH2), 4.70 (s, 1 H, PhCHCO), 2.85
(septet, J = 6.8 Hz, 1 H, CHCH3), 1.23 (d, J = 6.8 Hz, 3 H,
CHCH3), 1.12 (d, J = 6.8 Hz, 3 H, CHCH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 178.6 (Cq=O), 175.1 (Cq=N), 140.3 (CqAr),
137.1 (CqAr), 128.5 (CHAr), 128.4 (CHAr), 128.3 (CHAr), 127.5
(CHAr), 126.9 (CHAr), 126.3 (CHAr), 69.0 (PhCHCO), 39.0
(CHCH3), 20.2 (CHCH3), 19.8 (CHCH3) ppm. MS (FAB+): m/z =
281 [M + H]+, 236, 106, 91. HRMS (FAB+) C18H21N2O [M +
H]+ calcd. 281.16539; found 281.16558. C18H20N2O·0.2H2O
(283.96): calcd. C 76.12, H 7.25, N 9.86; found C 76.11, H 7.01, N
10.13.
2-[1-(2-Methoxyphenyl)-2,2-dimethylpropylidenamino]-2-phenylprop-
anamide (19): Prepared according to the general procedure using
α-methylphenylacetonitrile (66 µL, 0.48 mmol), the title compound
19 was isolated as a white solid (40 mg, 25%), m.p. 164–166 °C. IR
(DCM): ν
= 3410 (NH2), 2965, 1687 (C=O) cm–1. 1H NMR
˜
max.
(400 MHz, CDCl3): δ = 8.67 (br. s, 1 H, NH2), 8.50 (br. s, 1 H,
NH2Ј), 7.97–7.15 (m, 10 H, CHAr and CHЈAr), 6.93–6.91 (m, 2
H, CHAr and CHЈAr), 6.83–6.75 (m, 3 H, CHAr and CHЈAr),
6.37–6.33 (td, J = 7.46, J = 0.92 Hz, 1 H, CHAr), 6.25 (d, J =
8.39 Hz, 1 H, CHЈAr), 5.76 (br. s, 2 H, NH2 and NH2Ј), 5.56 (dd,
J = 7.46, J = 1.6 Hz, 1 H, CHAr), 3.77 (s, 3 H, OCH3), 3.13 (s, 3
H, OCH3Ј), 1.59 (s, 3 H, Me), 1.41 (s, 3 H, MeЈ), 1.12 (s, 18 H,
CCH3 and CCH3Ј) ppm. 13C NMR (100 MHz, CDCl3): δ = 180.2
(Cq=O), 179.9 (CЈq=O), 177.2 (Cq=N and CЈq=N), 155.3 (CqAr),
154.8 (CЈqAr), 144.8 (CqArOMe), 141.4 (CЈqArOMe), 129.0
(CHAr), 128.6 (CЈHAr), 128.2 (CHAr), 128.0 (CЈHAr), 127.9
2-(2-Methyl-1-phenylpropylidenamino)-2-phenylpropanamide (11):
Prepared according to the general procedure using α-methylphen-
ylacetonitrile (122 µL, 0.918 mmol), the title compound 11 was iso-
lated as a colourless solid (135 mg, 50%), m.p. 156–157 °C. IR
(DCM): ν
= 3398 (NH2), 2963, 1686 (C=O), 1597 cm–1. 1H (CHAr), 127.0 (CЈHAr), 126.9 (CHAr), 126.7 (CЈHAr), 126.4
˜
max.
NMR (400 MHz, CDCl3): δ = 8.64 (br. s, 1 H, NH2), 7.38–7.33
(m, 1 H, CHAr), 7.16–6.99 (m, 7 H, CHAr), 6.38 (m, 2 H, CHAr), (CHAr), 109.2 (CЈHAr), 68.6 (PhCqCH3), 67.6 (PhCqЈCH3), 54.6
5.86 (br. s, 1 H, NH2), 2.67 (septet, J = 6.8 Hz, 1 H, CHCH3), 1.46 (OCH3), 53.6 (OCЈH3), 41.9 (CqCH3), 41.8 (CqЈCH3), 28.6
(s, 3 H, PhCCH3), 1.18 (d, J = 6.8 Hz, 3 H, CHCH3), 1.07 (d, J = (CCH3), 28.4 (CCЈH3), 22.9 (PhCCH3), 19.1 (PhCCЈH3) ppm. MS
6.8 Hz, 3 H, CHCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = (FAB+): m/z = 339 [M + H]+, 361, 294, 192, 148, 120, 103. HRMS
(CHAr), 126.1 (CЈHAr), 119.2 (CHAr), 118.5 (CЈHAr), 109.4
Eur. J. Org. Chem. 2010, 882–889
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
887

P. C. B. Page et al.
FULL PAPER
(FAB+) C21H27N2O2 [M + H]+ calcd. 339.20725; found 339.20740.
C21H26N2O2 (338.44): calcd. C 74.72, H 7.73, N 8.69; found C
74.45, H 7.75, N 8.28.
NMR (100 MHz, CDCl3): δ = 179.3 (Cq=O), 177.2 (Cq=N), 143.4
(CqAr), 142.8 (CqArCF3), 138.8 (CqAr), 128.3 (CHAr), 128.2
(CHAr), 128.1 (CHAr), 127.2 (CHAr), 126.5 (CHAr), 125.5
(CHAr), 125.4 (CHAr), 68.0 (PhCCH3), 44.4 (SO2CH3), 41.9
(CqCH3), 28.4 (CCH3), 22.4 (PhCCH3) ppm. MS (FAB+): m/z =
387 [M + H]+, 342, 240, 148, 120, 91. HRMS (FAB+) C21H27N2O3S
[M + H]+ calcd. 387.17424; found 387.17375. C21H26N2O3S·
0.2H2O (390.11): calcd. C 64.64, H 6.83, N 7.17; found C 64.64, H
6.83, N 6.84.
2-[2,2-Dimethyl-1-(4-trifluoromethylphenyl)propylidenamino]-2-phen-
ylacetamide (20): Prepared according to the general procedure
using phenylacetonitrile (47 µL, 0.4 mmol), the title compound 20
was isolated as a colourless foam (70 mg, 50%), m.p. 65–66 °C. IR
(DCM): ν
= 3446 (NH2), 2968, 1692 (C=O) cm–1. 1H NMR
˜
max.
(400 MHz, CDCl3): δ = 7.67 (br. s, 1 H, CHAr), 7.44 (br. s, 1 H,
CHAr), 7.29–7.22 (m, 4 H, CHAr), 7.17 –7.15 (m, 3 H, CHAr),
6.57 (br. s, 1 H, NH2), 5.51 (br. s, 1 H, NH2), 4.40 (s, 1 H,
PhCHCO), 1.21 (s, 9 H, CCH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 179.9 (Cq=O), 174.3 (Cq=N), 139.7 (CqAr), 128.5
(CHAr), 127.7 (CHAr), 126.8 (CHAr), 69.4 (PhCHCO), 40.6
(CqCH3), 28.2 (CCH3) ppm. MS (EI+): m/z = 361 [M – H]+, 347,
318, 261, 14, 106, 91. HRMS (EI+) C20H21F3N2O (M+) calcd.
362.16060; found 362.16145. C20H21F3N2O (362.39): calcd. C
66.27, H 5.85, N 7.73; found C 66.60, H 5.89, N 7.57.
Supporting Information (see also the footnote on the first page of
this article): Selected crystal structure determination data for 13.
Acknowledgments
This investigation has enjoyed the support of Loughborough Uni-
versity, the University of East Anglia, and The Royal Society
(RSC) (PCBP: Industry Fellowship). We are also indebted to the
EPSRC Mass Spectrometry Unit, Swansea.
2-[2,2-Dimethyl-1-(4-trifluoromethylphenyl)propylidenamino]-2-phen-
ylpropionamide (21): Prepared according to the general procedure
using α-methylphenylacetonitrile (27 µL, 0.20 mmol), the title com-
pound 21 was isolated as a colourless foam (40 mg, 53%), m.p.
[1] D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey,
J. L. Leazer, R. J. Linderman, K. Lorenz, J. Manley, B. A. Pe-
arlman, A. Wells, A. Zaks, T. Y. Zhang, Green Chem. 2007, 9,
411.
181–183 °C. IR: ν
= (DCM) 3415 (NH2), 2967, 1682 (C=O)
˜
max.
1
cm–1. H NMR (400 MHz, CDCl3): δ = 8.53 (br. s, 1 H, CHAr),
7.48 (d, J = 8.4 Hz, 1 H, CHAr), 7.16–7.04 (m, 4 H, CHAr), 6.92–
6.88 (m, 3 H, 2CHAr), 5.84 (br. d, J = 7.6 Hz, 2 H, NH2), 1.51 (s,
3 H, PhCCH3), 1.14 (s, 9 H, CCH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 179.3 (Cq=O), 177.8 (Cq=N), 143.5 (CqAr), 140.5
(CqAr), 128.1 (CHAr), 127.7 (CHAr), 127.6 (CHAr), 127.1
(CHAr), 126.4 (CHAr), 123.6 (CHAr), 123.5 (CHAr), 68.0
(PhCqCH3), 41.8 (CqCH3), 28.4 (CCH3), 22.2 (PhCCH3) ppm. MS
(FAB+): m/z = 377 [M + H]+, 332, 230, 148, 120, 91. HRMS
(FAB+) C21H24F3N2O [M + H]+ calcd. 377.18407; found
377.18425. C21H23F3N2O·0.2C6H14 (393.66): calcd. C 67.7, H 6.61,
N 7.12; found C 67.92, H 6.21, N 7.19.
[2] W. D. Emmons, J. Am. Chem. Soc. 1957, 79, 5739; L. Horner,
E. Jürgens, Chem. Ber. 1957, 90, 218; H. Krimm, Chem. Ber.
1958, 91, 1057; P. C. B. Page, B. R. Buckley, in: Encyclopedia
of Reagents for Organic Synthesis (Ed.: L. A. Paquette), Wiley,
2005, N-tert-butoxycarbonyl(4-cyanophenyl)oxaziridine.
[3] D. D. Desmarteau, V. A. Petrov, V. Montanari, M. Pregnolato,
G. Resnati, J. Org. Chem. 1994, 59, 2762.
[4] D. R. Boyd, J. F. Malone, M. R. McGuckin, W. B. Jennings,
M. Rutherford, B. M. Saket, J. Chem. Soc. Perkin Trans. 2
1988, 1145; D. R. Boyd, W. B. Jennings, M. R. McGuckin, M.
Rutherford, B. M. Saket, J. Chem. Soc., Chem. Commun. 1985,
582; W. B. Jennings, M. J. Kochanewycz, C. J. Lovely, D. R.
Boyd, J. Chem. Soc., Chem. Commun. 1994, 2569.
[5] F. A. Davis, U. K. Nadir, E. W. Kluger, J. Chem. Soc., Chem.
Commun. 1977, 25; F. A. Davis, A. C. Sheppard, Tetrahedron
1989, 45, 5703, and references cited therein; F. A. Davis, B. C.
Chen, Chem. Rev. 1992, 919, and references cited therein; F. A.
Davis, J. C. Towson, M. C. Weismiller, S. Lal, P. C. Caroll, J.
Am. Chem. Soc. 1988, 110, 8477; P. C. B. Page, J. P. Heer, D.
Bethell, E. W. Collington, D. M. Andrews, Tetrahedron: Asym-
metry 1995, 6, 2911; A. Armstrong, A. G. Draffan, Tetrahedron
Lett. 1999, 40, 4453.
[6] F. A. Davis, R. T. Reddy, W. Han, P. J. Caroll, J. Am. Chem.
Soc. 1992, 114, 1428; F. A. Davis, R. E. Reddy, P. V. N. Kasu,
P. S. Portonovo, P. J. Caroll, J. Org. Chem. 1997, 62, 3625, and
references therein.
2-{2,2-Dimethyl-1-[4-(methylsulfonyl)phenyl]propylidenamino}-2-phen-
ylacetamide (22): Prepared according to the general procedure
using phenyl acetonitrile (52 µL, 0.45 mmol), the title compound
22 was isolated as a colourless solid (100 mg, 60 %), m.p. 191–
192 °C. IR (DCM): ν
= 3443 (NH2), 2967, 1693 (C=O) cm–1.
˜
max.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 7.1 Hz, 1 H, CHAr),
7.77 (d, J = 6.8 Hz, 1 H, NH2), 7.30–7.14 (m, 7 H, CHAr), 6.67
(d, J = 6.9 Hz, 1 H, NH2), 5.83 (br. s, 1 H, CHAr), 4.38 (s, 1 H,
PhCHCO), 3.10 (s, 3 H, SO2CH3), 1.21 (s, 9 H, CCH3) ppm. 13C
NMR (100 MHz, CDCl3): δ = 179.3 (Cq=O), 174.2 (Cq=N), 141.8
(CqAr), 140.3 (CqAr), 139.4 (CqAr), 128.6 (CHAr), 127.8 (CHAr),
126.7 (CHAr), 69.4 (PhCHCO), 44.5 (SO2CH3), 40.6 (CqCH3),
28.1 (CCH3) ppm. MS (FAB+): m/z = 373 [M + H]+, 328, 154, 106,
91. HRMS (FAB+) C20H25N2O3S [M + H]+ calcd. 373.15859;
found 373.15859. C20H24N2O3S·0.3H2O (377.88): calcd. C 63.55,
H 6.57, N 7.45; found C 63.55, H 6.37, N 7.25.
[7] Y. Hata, M. Watanabe, J. Org. Chem. 1981, 46, 610, and refer-
ences cited therein.
[8] G. Hanquet, X. Lusinchi, P. Millet, Tetrahedron Lett. 1988, 29,
2817; L. Bohé, M. Lusinchi, X. Lusinchi, Tetrahedron Lett.
1998, 54, 141; L. Bohé, M. Lusinchi, X. Lusinchi, Tetrahedron
Lett. 1999, 55, 155.
2-{2,2-Dimethyl-1-[4-(methylsufonyl)phenyl]propylidenamino}-2-phen-
ylpropanamide (23): Prepared according to the general procedure
using α-methylphenylacetonitrile (61 µL, 0.46 mmol), the title com-
pound 23 was isolated as a colourless solid (70 mg, 40%), m.p.
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218–219 °C. IR (DCM): ν
= 3416 (NH2), 2965, 1682 (C=O)
˜
max.
cm–1. H NMR (400 MHz, CDCl3): δ = 8.46 (d, J = 5.6 Hz, 1 H,
NH2), 7.80 (dd, J = 8.0, J = 1.8 Hz, 1 H, CHAr), 7.23 (dd, J =
8.0, J = 1.8 Hz, 1 H, CHAr), 7.15–7.13 (m, 2 H, CHAr), 7.08–7.05
(m, 2 H, CHAr), 6.90–6.87 (m, 2 H, CHAr), 6.38 (d, J = 5.3 Hz,
1 H, NH2), 5.95 (dd, J = 8.0, J = 1.3 Hz, 1 H, CHAr), 3.03 (s, 3
1
H, SO2CH3), 2.04 (s, 3 H, PhCCH3), 1.12 (s, 9 H, CCH3) ppm. 13
C
888
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 882–889

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Published Online: January 4, 2010
Eur. J. Org. Chem. 2010, 882–889
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
889