Palladium-catalyzed rearrangement of allylic sulfoximines: Application to the asymmetric synthesis of chiral allylic amines

Article abstract of DOI:10.1021/jo9605105

The palladium(0)-catalyzed reactions of the primary and secondary allylic sulfoximines 7, 9, 11, 13, 15, 17, and 19 gives allylic sulfinamides without 1,3-allylic rearrangement. These compounds were not isolated but were converted to their corresponding N-tosyl allylic amines, primary and secondary 8, 10, 12, 14, 16, 18, and 20, respectively. In the case of the optically active secondary allylic sulfoximines 17 and 19, chiral N-tosyl allylic secondary amines were formed in high enantiomeric purities.

Full text of DOI:10.1021/jo9605105

J . Org. Chem. 1996, 61, 5517-5522
5517
P a lla d iu m -Ca ta lyzed Rea r r a n gem en t of Allylic Su lfoxim in es:
Ap p lica tion to th e Asym m etr ic Syn th esis of Ch ir a l Allylic Am in es
Stephen G. Pyne* and Zemin Dong
Department of Chemistry, University of Wollongong, Wollongong, New South Wales, 2522, Australia
Received March 15, 1996X
The palladium(0)-catalyzed reactions of the primary and secondary allylic sulfoximines 7, 9, 11,
13, 15, 17, and 19 gives allylic sulfinamides without 1,3-allylic rearrangement. These compounds
were not isolated but were converted to their corresponding N-tosyl allylic amines, primary and
secondary 8, 10, 12, 14, 16, 18, and 20, respectively. In the case of the optically active secondary
allylic sulfoximines 17 and 19, chiral N-tosyl allylic secondary amines were formed in high
enantiomeric purities.
In tr od u ction
corresponding allylic sulfinamides, must be relatively
large.
Chiral amines are important compounds in organic
synthesis. They have been employed as chiral bases,1a
nucleophiles,1b auxiliaries,1c and ligands1d for asymmetric
synthesis. In particular, allylic amines are useful com-
pounds for organic synthesis2 and have been featured as
the key structural components of peptide isosteres.3 We
recently reported a novel method for the synthesis of
primary N-tosyl allylic amines 3 via the palladium(0)-
catalyzed rearrangement of R-substituted allylic sulfox-
imines 1 to allylic sulfinamides 24,5 (eq 1).
Resu lts a n d Discu ssion
The primary allylic sulfoximines 7, 9, 11, 13, and 15
(Table 1) were prepared from racemic or (S)-N-tosyl-,9
N-methoxycarbonyl-,10 or N-methyl-11 S-methyl-S-phenyl-
sulfoximines 4, 5, a n d 6 respectively, according to the
general literature procedures12 (eq 2). In general, a
(2)
(1)
This type of rearrangement reaction has been reported
to occur under thermal induction but only in the case of
γ-phenyl allylic sulfoximines.6 In these compounds the
phenyl substituent may facilitate the rearrangement
process by providing stabilization of an ion pair or other
intermediate. These thermally induced rearrangements,
however, proceed with poor regioselectivity and poor
yields of conversion.6 Interestingly, semiempirical7 and
ab initio8 calculations indicate that allylic sulfinamides
are thermodynamically much more stable than their
isomeric allylic sulfoximines and that the free energy
barrier, for conversion of allylic sulfoximines to their
mixture of the vinyl sulfoximine A and the allylic
sulfoximine B was obtained. Treatment of this mixture
with KOMe/THF gave exclusively the desired allylic
sulfoximine B.13
Treatment of a THF solution of the acyclic allylic
sulfoximines 7 or 9 (E:Z ) 58:42) with 5 mol % of tetrakis-
(triphenylphosphine)palladium(0) (Pd(PPh3)4) at room
temperature for 10 min resulted in a bright red solution.
Evaporation of the THF in vacuo and exposure of the
crude reaction mixture to 10% aqueous sodium hydroxide
and MeOH (1:10) at room temperature for 2 h gave the
primary N-tosyl allylic amines 8 and 10, respectively, in
good yields (Table 1, entries 1 and 2). In both cases the
rearrangement reactions were completely regioselective
and resulted in products without 1,3-allylic rearrange-
ment. In the case of 9 a 90:10 mixture of the (E) and (Z)
geometric isomers of 10 was obtained. The regiochem-
istry of these reactions can be understood in terms of the
formation of the Pd-allylic cation complex C followed by
X Abstract published in Advance ACS Abstracts, J uly 15, 1996.
(1) For some recent examples, see: (a) Nishibayashi, Y.; Arikawa,
Y.; Ohe, K.; Uemura, S. J . Org. Chem. 1996, 61, 1172. (b) Davies, S.
G.; McCarthy, T. D. Synlett 1995, 700. (c) Matulenko, M. A.; Meyers,
A. I. J . Org. Chem. 1996, 61, 573. (d) Miao, G.; Rossiter, B. E. J . Org.
Chem. 1995, 60, 8424.
(2) Wei, Z.-Y.; Knaus, E. E. Synthesis 1994, 1463 and references
cited therein.
(3) Spaltenstein, A.; Carpino, P. A.; Miyake, F.; Hopkins, P. B. J .
Org. Chem. 1987, 52, 3759.
(4) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem. Soc.,
Chem. Commun. 1995, 445.
(9) J ohnson, C. R.; Kirchhoff, R. A.; Reischer, R. J .; Katekar, G. F.
J . Am. Chem. Soc. 1973, 95, 4287.
(5) Pyne, S. G.; Dong, Z. Tetrahedron Lett. 1995, 36, 3029.
(6) Gais, H.-J .; Scommoda, M.; Lenz, D. Tetrahedron Lett. 1994, 35,
7361.
(7) Harmata, M.; Claassen, R. J ., II. Tetrahedron Lett. 1991, 32,
6497. Pyne, S. G.; Boche, G. Tetrahedron 1993, 49, 8449.
(8) Harmata, M.; Glaser, R.; Chen, G. S. Tetrahedron Lett. 1995,
36, 9145.
(10) J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J . Am. Chem.
Soc. 1973, 95, 7424.
(11) Schaffner-Sabba, K.; Tomaselli, H.; Henrici, B.; Renfroe, H. B.
J . Org. Chem. 1977, 42, 952.
(12) Pyne, S. G. J . Org. Chem. 1986, 51, 81.
(13) Gais, H.-J .; Muller, H.; Bund, J .; Scommoda, M., Brandt, J .;
Raabe, G. J . Am. Chem. Soc. 1995, 117, 2453.
S0022-3263(96)00510-5 CCC: $12.00 © 1996 American Chemical Society

5518 J . Org. Chem., Vol. 61, No. 16, 1996
Pyne and Dong
Ta ble 1. Syn th esis of N-P r otected Allylic Am in es via
Tr ea tm en t of Allylic Su lfoxim in es w ith P a lla d iu m (0) a n d
Th en w ith Ba se
Sch em e 1
anti Pd-allylic cation complexes that could arise from
the reaction of (Z)- and (E)-9 with Pd(PPh3)4, respec-
tively.14 The palladium-catalyzed reactions of the cyclic
N-tosyl allylic sulfoximines 11, 13a , and 15 were also
completely regioselective and gave, after base hydrolysis,
the N-tosyl primary allylic amines 12, 14a , and 16,
respectively, without 1,3-allylic transposition and in good
overall yields (Table 1, entries 3, 4, and 7). The N-
methoxycarbonyl and N-methyl allylic sulfoximines, 13b
and 13c, also underwent rearrangement to their corre-
sponding allylic sulfinamides with Pd(PPh3)4; however,
those reactions were much slower than that of the related
N-tosyl analogue 13a . Qualitatively, the relative rates
of the reactions of 13a , 13b, and 13c correlated closely
with the electron-withdrawing ability of the N-substitu-
ent of the sulfoximine. Thus while 13a reacted in 10 min,
13b required a reaction time of 30 min while the reaction
of N-methyl compound 13c was complete only after 1 h.
In the later reaction the yield of the N-methyl allylic
amine 14c was low (21%, isolated as its less volatile
N-tosyl derivative) and the major product isolated was
N-methyl phenyl sulfinamide (68%). This major product
is thought to arise via deprotonation of the intermediate
Pd-allylic cation complex by the relatively basic N-
methyl phenyl sulfinamide counteranion. This would
also eventually give 3-methylenecyclohexene that was not
isolated due to its volatility.
Ch ir a l r-Su bstitu ted Allylic Su lfoxim in es
a
b
Time for the palladium catalyzed reaction. After base treat-
In principle the palladium(0)-catalyzed rearrangement
reaction of optically active R,γ-disubstituted allylic sul-
foximines can give rise to optically active allylic amines.
The success of this reaction depends upon the regiose-
lectivity and diastereoselectivity of the rearrangement
reaction. Methylation of the (S)-allylic sulfoximines 11,
13a , and 13b (ee ) 96%) by first deprotonation with LDA
at -78 °C and then methylation with MeI gave the
corresponding methylated allylic sulfoximines 17, 19a ,
and 19b, respectively in 96-98% de. Sulfoximines 17
and 19a were unstable and their attempted purification
by chromatography on silica gel gave complex mixtures
that included rearranged allylic sulfinamides. Heating
a THF solution of 19a at reflux for 6 h, followed by
purification on silica gel, gave an inseparable 45:55
mixture of the rearranged N-tosyl allylic amines 20a and
21, respectively, in a combined yield of 73%. These
compounds could be separated by preparative HPLC. The
ment with aqueous sodium hydroxide and then purification by
column chromatography on silica gel. c Yield of the corresponding
N-tosyl derivative that was formed by treating the crude reaction
mixture with tosyl chloride/pyridine. Overall yield from their
respective sulfoximines 11, 13a , and 13b.
d
addition of the sulfinamide anion to the least substituted
terminus of the allylic cation moiety of C (eq 3).
(3)
Formation of the more stable syn complex C (R ) Et)
would be expected from the initial mixture of syn and
(14) Frost, C. G.; Howarth, J .; Williams, J . M. J . Tetrahedon:
Asymmetry 1992, 3, 1089.

Rearrangement of Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 16, 1996 5519
Sch em e 2
absolute (S) stereochemistry of 20a was determined by
a comparison of the specific rotation of its N-tosyl(1-
cyclohexylethyl)amine derivative 22 ([R]23 -10° (c 0.4,
D
CHCl3) with that prepared from tosylation of com-
mercially available (R)-(1-cyclohexylethyl)amine accord-
ing to Scheme 1. (R)-N-tosyl(1-cyclohexylethyl)amine
had a specific rotation of [R]23 +24.0° (c 0.5, CHCl3).
D
The absolute stereochemistry assigned to 21 is more
tenuous and is based on mechanistic considerations
(Scheme 2). The (E) stereochemistry of 21 was estab-
lished by a NOESY experiment that showed a cross peak
between the alkene proton and the NH group. The
enantiomeric purities of 20a and 21 were determined to
be 88% and 87%, respectively (92% and 91% ee corrected
for the ee of 4), by 1H NMR studies using the chiral shift
agent europium tris[3-[(heptafluoropropyl)hydroxymeth-
ylene]-(+)-camphorate]. These studies resulted in well-
resolved separate signals for the R-methyl group of 20a
and the vinyl methyl group of 21 for the two enantiomers
of these compounds respectively, in both racemic and
optically active preparations of these compounds.
Treatment of the crude methylation products 17, 19a ,
or 19b with 5 % mol Pd(PPh3)4 in THF, followed by base
hydrolysis, gave the related N-protected allylic amines
18, 20a , or 20b, respectively (Table 1). These reactions
were completely regioselective and gave none of the 1,3-
allylic rearrangement products (e.g. 21). The stereo-
chemical sense of all these reactions were identical and
like 20a , which was obtained from the thermal rear-
rangement of 19a , these compounds had the (S) absolute
stereochemistry. While the enantiomeric purities of 18
and 20a were high [both had an ee of 88% (92%
corrected)] that of 20b was only moderate (ee 34% from
analysis by chiral HPLC).
The reactive conformation of 19a would be expected
to be that shown in Scheme 2 from stereoelectronic
considerations14,17 and in order to minimize allylic A1,3
strain.17 Attack of palladium(0) on the conformation 19a
would be expected to occur anti to the sulfoximine leaving
group for stereoelectronic reasons to give the Pd-allylic
cation complex 24 with the planar chirality shown.
Addition of the sulfinamide anion to the allylic cation
moiety would be expected to occur anti to palladium14 to
give sulfinamide 25 with the (S)-stereochemistry at the
carbon of the newly created C-N bond. The thermal
rearrangement of 19a may proceed via the intimate ion
pair 27, followed by collapse of this intermediate to give
25 or 26. Alternatively, some or all of 26 may arise from
a [2,3]-sigmatropic rearrangement.18 In the later sce-
nario, collapse of the ion pair intermediate 27 would
necessarily be regioselective and give only 25.
The R-methylated allylic sulfoximines 17, 19a , and 19b
were too unstable to prepare crystals for X-ray crystal-
lographic analysis. However, on the basis of our previous
work,15 we would predict that these compounds had the
(S) stereochemistry at the R-carbon (eq 4). Our suggested
From this study, however, it is not possible to distin-
guish between the different possible reaction pathways.
In conclusion, the palladium(0)-catalyzed rearrange-
ment of certain primary and secondary allylic sulfox-
imines to give N-protected allylic amines has been shown
to be highly regioselective and in the case of the later
compounds highly enantioselective. Further extensions
and applications of this methodology for asymmetric
synthesis are under active investigation.
Exp er im en ta l Section
(4)
General procedures were as described previously.19 All
NMR spectra were recorded in CDCl3 solution at 400 MHz (1H
NMR) or 100 MHz (13C NMR) unless otherwise noted. Chiral
HPLC analysis was carried out using a Waters pump model
510 and a Regis D-naphthylalanine (Pirkle) 4.6 × 250 mm
column at a flow rate of 0.6 mL/min using isopropyl alcohol/
hexane (0.5:99.5) as eluent. The UV detector was a Waters
series 450 variable wavelength detector operating at 254 nm.
structure (23) for lithiated 13a is shown in eq 4. This
type of structure is also supported by single-crystal X-ray
structural studies by Gais on related lithiated allylic
sulfoximines.16 Methylation of 23 would be expected to
occur syn to lithium and anti to the S-Ph group (eq 4).
If this stereochemical assignment is correct then the
thermal and palladium(0)-induced rearrangement reac-
tions on 19a can be rationalized as depicted in Scheme
2.
(17) Hoffman, R. W. Angew. Chem., Int. Ed. Engl. 1979, 18, 563.
(18) For the [2,3]-sigmatropic rearrangements of allylic selenil-
imines, sulfilimines, and tellurimides, see refs a, b, and c, respec-
tively: (a) Frankhauser, J . E.; Peevey, R. M.; Hopkins, P. B. Tetrahe-
dron Lett. 1984, 25, 15. (b) Tamura, Y.; Sumoto, K.; Minamikawa, J .;
Ikeda, M. Tetrahedron Lett. 1972, 4137. (c) Nishibayashi, Y.; Srivas-
tava, S. K.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1995, 36, 6725. (d)
For more recent references, see: Dolle, R. E.; Li, C.-S.; Novelli, R.;
Kruse, L. I.; Eggleston, D. J . Org. Chem, 1992, 57, 128. Nishibayashi,
Y.; Chiba, T.; Ohe, K.; Uemura, S. J . Chem. Soc. Chem. Commun. 1995,
1243 and references cited therein.
(15) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem.
Soc., Chem. Commun. 1994, 751.
(16) Gais, H.-J .; Lenz, D.; Raabe, G. Tetrahedron Lett. 1995, 36,
7437.
(19) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem.
Soc., Perkin Trans. 1 1994, 2607.

5520 J . Org. Chem., Vol. 61, No. 16, 1996
Pyne and Dong
Racemic samples were always run to ensure separation of both
enantiomers.
139.4, 134.2, 129.6, 129.2, 127.8, 126.6, 76.2, 67.8, 41.2, 40.5,
29.5, 29.4, 21.7, 21.6, 21.5.
1-[N-(Meth oxyca r bon yl)-S-p h en ylsu lfon im id oyl]m eth -
ylcycloh exa n ol (28d ). Yield 22%. 1H NMR: δ 7.96-7.94
(2H, m), 7.70-7.66 (1H, m), 7.63-7.59 (2H, m), 4.69 (1H, s),
3.61 (3H, s), 3.53 (1H, d, J ) 14 Hz), 3.26 (1H, d, J ) 14 Hz),
2.06-2.02 (1H, m), 1.79-1.68 (4H, m), 1.55-1.42 (4H, m), 1.32-
1.25 (1H, m). 13C NMR (75 MHz): δ 158.6, 139.2, 133.9, 129.7,
127.5, 71.9, 65.6, 53.1, 38.6, 36.9, 25.2, 21.7, 21.6.
P r ep a r a tion of Allylic Su lfoxim in es, A Gen er a l P r o-
ced u r e:
1-[N -Me t h y l-S -p h e n y ls u lfo n im id o y l]m e t h y lc y c lo -
h exa n ol (28e). Yield 78%. 1H NMR (300 MHz): δ 7.90-7.86
(2H, m), 7.63-7.54 (3H, m), 6.44 (1H, br), 3.27 (1H, d, J )
13.5 Hz), 3.12 (1H, d, J ) 13.5 Hz), 2.62 (3H, s), 2.20-2.10
(1H, br), 1.97-1.86 (1H, m), 1.82-1.50 (5H, m), 1.41-1.24 (3H,
m). 13C NMR: δ 139.1, 133.0, 129.5, 128.9, 71.7, 64.4, 39.2,
36.7, 28.9, 25.4, 22.0, 21.7.
Allylic su lfoxim in es: (E)-N-Tosyl-S-p h en yl-S-(3-p h en -
yl-2-p r op en yl)su lfoxim in e (7). Yield 29% overall from 4.
1H NMR (300 MHz): δ 7.92-7.88 (4H, m), 7.71-7.64 (1H, m),
7.58-7.50 (2H, m), 7.35-7.17 (7H, m), 6.31 (1H, d, J ) 15.9
Hz), 6.01 (1H, dt, J ) 15.9, 7.5 Hz), 4.42 (2H, dddd, J ) 0.9,
7.5, 0.9, 7.5 Hz), 2.38 (3H, s). 13C NMR (75 MHz) δ 142.8,
141.1, 140.8, 135.3, 135.2, 134.3, 129.24, 129.21, 128.8, 128.7,
128.6, 126.7, 126.6, 113.0, 62.3, 21.5. MS (ES + ve): m/ z 412
(M + H+, 15), 296 (20), 251 (30), 183 (35), 117 (100).
(E)- a n d (Z)-N-Tosyl-S-p h en yl-S-(2-p en t en yl)su lfox-
im in e (9). Yield 49% overall from 4. 1H NMR (300 MHz):
(major, (E)-isomer) δ 7.92-7.85 (4H, m), 7.67 (1H, tt, J ) 7.5,
1.5 Hz), 7.58-7.53 (2H, m), 7.24 (2H, d, J ) 8.1 Hz), 5.51 (1H,
dt, J ) 15.6, 6.3 Hz), 5.38-5.27 (1H, m), 4.27-4.12 (2H, m),
2.38 (3H, s), 1.97 (2H, pent, J ) 7.5 Hz), 0.84 (3H, t, J ) 7.5
Hz); (minor, (Z)-isomer) δ 5.78-5.69 (1H, m), 4.42-4.25 (2H,
m), 1.63 (2H, dpent, J ) 7.5, 1.5 Hz), 0.67 (3H, t, J ) 7.5 Hz).
13C NMR (75 MHz) (on mixture): δ 145.5, 143.0, 142.6, 141.0,
135.4, 134.2, 134.1, 129.13, 129.06, 128.5, 126.6, 113.8 (E),
113.4 (Z), 62.0 (E), 57.0 (Z), 29.6 (Z), 25.6 (E), 21.4 (E), 20.6
(Z), 13.1 (Z), 12.7 (E); MS (ES + ve): m/ z 364 (M + H+, 22),
296 (100), 125 (20). HRMS calcd for C18H21NO3S2 ) 363.09626;
found 363.09684.
To a solution of the sulfoximine (5, 6, or 7) (1 mmol) in dry
THF (3 mL) at -78 °C was added n-BuLi or LDA (1.3 equiv)
and the solution was stirred at -78 °C under N2 for 40 min.
The carbonyl compound (1.2 equiv) was added, and the
reaction mixture was stirred for a further 1 h and then
quenched by the addition of a saturated solution of aqueous
NH4Cl (0.2 mL) at -78 °C. Water (15 mL) was added, and
the mixture was extracted with CH2Cl2 (2 × 20 mL). The
combined extracts were dried (MgSO4) and evaporated and the
crude products were purified by column chromatography on
silica gel. Elution with ethyl acetate/hexane gave the corre-
sponding alcohol. In the case of alcohols 28 (R1 ) Ph, R2 ) H,
R3 ) Ts) and 28 (R1 ) Et, R2 ) H, R3 ) Ts) the crude products
were used in the next reaction directly. The purified or crude
alcohol (1 mmol) was dissolved in dry CH2Cl2 (6 mL) and the
solution was cooled to 0 °C. Triethylamine (5 equiv) was added
then methanesulfonyl chloride (MsCl) (3 equiv) was added
dropwise over 10 min. After 2 h of stirring at 0 °C, DBU (6
equiv) was added and after 10 min the reaction mixture was
warmed to rt and then stirred for overnight. The reaction was
diluted with ether (40 mL), and the mixture was washed with
water (25 mL), a saturated aqueous solution of NH4Cl (25 mL)
and a 10% aqueous solution of Na2CO3 (25 mL). The ether
layer was dried (MgSO4) and evaporated. The crude reaction
mixture was treated with potassium methoxide in dry MeOH
for 72 h according to the method of Gais.13 The crude reaction
mixtures were purified by column chromatography on silica
gel. Elution with ethyl acetate/hexane gave allylic sulfox-
imines 7, 9, 11, 13a , 13b, 13c, and 15.
Alcoh ols 28: 1-[N-Tosyl-S-p h en ylsu lfon im id oyl]m eth -
ylcyclop en ta n ol (28a ). Yield 95%. 1H NMR (300 MHz): δ
7.95-7.93 (2H, m), 7.77-7.73 (2H, m), 7.66-7.62 (1H, m),
7.56-7.51 (2H, m), 7.21 (2H, d, J ) 7.5 Hz), 3.96 (1H, d, J )
14.4 Hz), 3.53 (1H, d, J ) 14.4 Hz), 3.64-3.30 (1H, br), 2.37
(3H, s), 2.18-1.57 (8H, br). 13C NMR (75 MHz): δ 142.6, 140.4,
138.6, 134.0, 129.3, 129.0, 127.8, 126.3, 79.5, 66.7, 39.9, 39.3,
23.0, 22.7, 21.2.
1-[N -T o s y l-S -p h e n y ls u lfo n i m i d o y l]m e t h y lc y c lo -
h exa n ol (28b). Yield 81%. 1H NMR: δ 8.00-7.97 (2H, m),
7.78 (2H, d, J ) 8.4 Hz), 7.71-7.67 (1H, m), 7.62-7.58 (2H,
m), 7.24 (2H, d, J ) 8.4 Hz), 3.73 (1H, d, J ) 14.4 Hz), 3.59
(1H, s), 3.31 (1H, d, J ) 14.4 Hz), 2.40 (3H, s), 1.74-1.31 (8H,
m). 13C NMR (75 MHz): δ 142.8, 140.6, 139.4, 134.2, 129.5,
129.2, 127.8, 126.5, 72.0, 66.9, 37.7, 37.1, 25.0, 21.54, 21.50,
21.4.
N-Tosyl-S-p h en yl-S-(1-cyclop en t-1-en ylm eth yl)su lfox-
im in e (11). Yield 97% from 28a . 1H NMR (300 MHz): δ
7.91-7.85 (4H, m), 7.69-7.64 (1H, m), 7.57-7.52 (2H, m), 7.24
(2H, d, J ) 8.1 Hz), 5.49 (1H, br), 4.41 (1H, d, J ) 13.8 Hz),
4.35 (1H, d, J ) 13.8 Hz), 2.38 (3H, s), 2.27-2.15 (4H, m),
1.76 (2H, p, J ) 7.5 Hz). 13C NMR (75 MHz) δ 142.6, 141.0,
138.1, 135.9, 134.1, 129.8, 129.1, 129.0, 128.5, 126.6, 60.6, 34.8,
32.8, 23.5, 21.4. MS (ES + ve): m/ z 376 (M + H+, 30), 296
(100), 106 (50), 104 (100). HRMS calcd for C19H21NO3S2
375.09626; found 363.09535.
)
N-Tosyl-S-p h en yl-S-(1-cycloh ex-1-en ylm eth yl)su lfox-
im in e (13a ). Yield 82% from 28b. 1H NMR: δ 7.91-7.85 (4H,
m), 7.69-7.65 (1H, m), 7.58-7.54 (2H, m), 7.24 (2H, d, J )
8.8 Hz), 5.38 (1H, br), 4.21 (1H, d, J ) 14 Hz), 4.06 (1H, d, J
) 14 Hz), 2.39 (3H, s), 2.05-1.78 (4H, m), 1.51-1.41 (4H, m).
13C NMR: δ 142.6, 141.0, 135.6, 134.1, 129.2, 129.1, 128.8,
126.6, 124.9, 66.7, 28.7, 25.7, 22.4, 21.5, 21.2. MS (ES + ve):
m/ z 390 (M + H+, 25), 296 (100), 125 (25).
N-(Met h oxyca r b on yl)-S-p h en yl-S-(1-cycloh ex-1-en yl-
m eth yl)su lfoxim in e (13b). Yield 68% from 28d . 1H NMR
(300 MHz) δ 7.91-7.88 (2H, m), 7.70-7.64 (1H, m), 7.60-7.55
(2H, m), 5.36 (1H, broad), 4.13 (1H, d, J ) 13.5 Hz), 4.03 (1H,
d, J ) 13.5 Hz), 3.68 (3H, s), 2.10-1.80 (4H, m), 1.54-1.43
(4H, m). 13C NMR (75 MHz): δ 159.5, 135.7, 134.8, 133.7,
129.0, 128.5, 125.1, 64.3, 53.0, 28.6, 25.6, 22.4, 21.2. MS (ES
+ ve): m/ z 294 (M + H+, 100), 200 (20), 104 (15). HRMS calcd
for C15H19NO3S ) 293.10854; found 293.109809.
N-Met h yl-S-p h en yl-S-(1-cycloh exen ylm et h yl)su lfox-
im in e (13c). Yield 81% from 28e. 1H NMR (300 MHz): δ
7.83-7.78 (2H, m), 7.61-7.48 (3H, m), 5.32 (1H, broad), 3.76
(2H, s), 2.71 (3H, s), 2.20-2.05 (1H, m), 1.94-1.80 (3H, m),
1.58-1.40 (4H, m). 13C NMR (75 MHz): δ 137.1, 132.9, 132.6,
129.8, 128.9, 126.6, 65.0, 29.8, 28.8, 25.6, 22.6, 21.5. MS (ES
+ ve): m/ z 250 (M + H+, 40), 156 (100), 124 (15).
N -T o s y l-S -p h e n y l-S -(1-c y c lo h e p t y lm e t h y l)s u lfo x -
im in e (15). Yield 96% from 28c. 1H NMR: δ 7.92-7.90 (2H,
m), 7.87-7.85 (2H, m), 7.66-7.65 (1H, m), 7.58-7.54 (2H, m),
1-[N -T o s y l-S -p h e n y ls u lfo n i m i d o y l]m e t h y lc y c lo -
h ep ta n ol (28c). Yield 96%. 1H NMR: δ 8.01-7.97 (2H, m),
7.79-7.77 (2H, m), 7.70-7.67 (1H, m), 7.62-7.57 (2H, m), 7.24
(2H, d, J ) 8 Hz), 3.70 (1H, d, J ) 14.4 Hz), 3.69 (1H, s), 3.30
(1H, d, J ) 14.4 Hz), 2.40 (3H, s), 1.91-1.69 (4H, m), 1.63-
1.48 (4H, m), 1.44-1.25 (4H, m). 13C NMR: δ 142.9, 140.4,

Rearrangement of Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 16, 1996 5521
7.24 (2H, d, J ) 8 Hz), 5.45 (1H, t, J ) 6 Hz), 4.32 (1H, d, J )
13.6 Hz), 4.03 (1H, d, J ) 13.6 Hz), 2.38 (3H, s), 2.21-2.08
(2H, m), 1.93 (2H, broad), 1.70-1.56 (2H, m), 1.42-1.26 (4H,
m). 13C NMR: δ 142.6, 141.0, 140.9, 135.7, 134.1, 130.7, 129.1,
129.0, 128.8, 126.6, 68.9, 33.4, 31.7, 28.8, 26.04, 26.02, 21.5.
MS (ES + ve): m/ z 404 (M + H+, 15), 296 (100), 233 (50).
Gen er a l Meth od of Meth yla tion of Allylic Su lfox-
im in es 11, 13a , a n d 13b. To a solution of the allylic
sulfoximine (11, 13a , or 13b) (1 mmol) in dry THF (3 mL) was
added LDA (1.3 equiv) at -78 °C, and the reaction mixture
was stirred for 40 min. The orange red solution was treated
with CH3I (2 equiv) at -78 °C, and the reaction was stirred
for a further 1 h at -78 °C and was quenched by the addition
of a saturation aqueous solution of NH4Cl (0.5 mL) at -78 °C.
The reaction was warmed to rt, poured into water (10 mL),
and extracted with CH2Cl2 (2 × 20 mL). The extracts were
concentrated and dried under vacuum to leave a light yellow
oil that decomposed upon attempted purification by column
chromatography on silica gel.
N-Tosyl-N-(1-cyclop en t-1-en yl)m eth yla m in e (12). 1H
NMR (300 MHz): δ 7.75 (2H, dt, J ) 8.4, 1.8 Hz), 7.30 (2H,
dd, J ) 8.4, 0.9 Hz), 5.49 (1H, s), 4.84 (1H, br), 3.60 (2H, d, J
) 4.8 Hz), 2.43 (3H, s), 2.25-2.12 (4H, m), 1.84-1.74 (2H, m).
13C NMR (75 MHz): δ 143.2, 139.3, 137.1, 129.5, 127.5, 127.1,
43.7, 33.1, 32.2, 23.2, 21.4. MS (ES + ve): m/ z 252 (M + H+,
25), 106 (50), 104 (100), 81 (95). HRMS calcd for C13H17NO2S
) 251.09798; found 251.097812.
N-Tosyl-N-(1-cycloh ex-1-en yl)m eth yla m in e (14a ). 1H
NMR: δ 7.43 (2H, d, J ) 8 Hz), 7.30 (2H, d, J ) 8 Hz), 5.34
(1H, s), 4.59 (1H, broad), 3.43 (2H, d, J ) 6.4 Hz), 2.43 (3H,
s), 1.91 (2H, br), 1.85 (2H, br), 1.54-1.45 (4H, m). 13C NMR
(75 MHz): δ 143.2, 137.3, 132.9, 129.5, 127.1, 125.3, 49.6, 26.2,
24.9, 22.3, 22.0, 21.4. MS (ES + ve): m/ z 266 (M + H+, 10),
110 (100). HRMS calcd for C14H19NO2S ) 265.11362; found
265.11318.
N-(Met h oxyca r b on yl)-N-(1-cycloh ex-1-en yl)m et h yl-
a m in e (14b). 1H NMR: δ 5.57 (1H, s), 4.67 (1H, broad), 3.68
(5H, broad, CH2 and CH3), 2.03-1.97 (2H, br), 1.96-1.90 (2H,
br), 1.68-1.52 (4H, m). 13C NMR: δ 157.1, 134.6, 122.8, 52.1,
47.1, 26.3, 24.9, 22.5, 22.3. MS (ES + ve): m/ z 170 (M + H+,
100), 106 (50), 104 (100), 88 (95). HRMS calcd for C9H15NO2
) 169.11026; found 169.110059.
N-Tosyl-S-p h en yl-S-(1-cyclop en t -1-en ylet h yl)su lfox-
im in e (17). 1H NMR (in part): δ 7.84-7.19 (9H, m), 5.46 (1H,
br), 4.31 (1H, q, J ) 7.2 Hz), 2.36 (3H, s), 1.53 (3H, d, J ) 7.2
Hz).
N -Tosyl-S-p h e n yl-S-(1-cycloh e x-1-e n yle t h yl)su lfox-
im in e (19a ). 1H NMR: δ 7.89-7.86 (2H, m), 7.83-7.81 (2H,
m), 7.67-7.63 (1H, m), 7.57-7.53 (2H, m), 7.23-7.21 (2H, m),
5.40 (1H, br), 3.88 (1H, q, J ) 7.4 Hz), 2.38 (3H, s), 1.98-1.83
(2H, m), 1.74-1.69 (2H, m), 1.55 (3H, d, J ) 7.4 Hz), 1.46-
1.32 (4H, m). 13C NMR δ 142.4, 141.2, 135.7, 134.2, 133.9,
129.4, 129.1, 129.0, 128.9, 126.6, 70.2, 26.3, 25.6, 22.4, 21.5,
21.4, 11.8.
N-(Met h oxyca r b on yl)-S-p h en yl-S-(1-cycloh ex-1-en yl-
eth yl)su lfoxim in e (19b). 1H NMR (300 MHz): δ 7.84-7.81
(2H, m), 7.64-7.61 (1H, m), 7.57-7.55 (2H, m), 5.39 (1H, br),
3.92 (1H, q, J ) 7.2 Hz), 2.62 (3H, s), 2.25-1.32 (8H, m), 1.66
(3H, d, J ) 7.2 Hz). 13C NMR (75 MHz): δ 159.5, 133.5, 132.2,
129.9, 129.0, 128.9, 124.7, 65.8, 53.0, 26.4, 25.5, 22.4, 21.5, 12.1.
HRMS calcd for C16H21NO3S ) 307.12419; found 307.126527.
Gen er a l Meth od of P a lla d iu m (0)-Ca ta lyzed Allylic
Su lfoxim in e to Allylic Su lfon a m id e Rea r r a n gem en t. To
a stirred solution of the pure allylic sulfoximine (7, 9, 11, 13a ,
13b, 13c, or 15) or the crude allylic sulfoximine (17, 19a , or
19b) (1 mmol) in dry THF (20 mL) was added freshly prepared
tetrakis(triphenylphosphine)palladium(0) (58 mg, 5 mol %)
under N2 at rt. After TLC analysis indicated complete
consumption of the starting allylic sulfoximine, the reaction
was diluted with ether (20 mL) and then washed with water
(20 mL). The orange solution was concentrated to leave a thick
dark red oil. The oil was dissolved in a 1:10 mixture of 10%
aqueous NaOH (2 mL) and MeOH (20 mL) at room tempera-
ture, and the reaction mixture was stirred for 2 h. The MeOH
was then removed. Water (10 mL) was added, and the mixture
was neutralized by the addition of a 5% aqueous solution of
HCl to pH 7. The mixture was extracted with CH2Cl2 (2 × 20
mL), and the combined extracts were dried (MgSO4) and
concentrated to leave a dark red oil which was purified with
column chromatography. Elution with ethyl acetate/hexane
gave the allylic sulfonamide.
(E)-N-Tosyl-N-[1-(3-p h en yl-2-p r op en yl)]a m in e (8). 1H
NMR: δ 7.78 (2H, d, J ) 8 Hz), 7.33-7.24 (7H, m), 6.45 (1H,
d, J ) 16 Hz), 6.02 (1H, dt, J ) 16, 6.4 Hz), 4.46 (1H, br), 3.76
(2H, dt, J ) 6.4, 1.2 Hz), 2.43 (3H, s). 13C NMR: δ 143.6, 137.0,
136.0, 133.2, 129.8, 128.6, 128.0, 127.2, 126.4, 124.0, 45.5, 21.5.
MS (ES + ve): m/ z 288 (M + H+, 25), 149 (30), 117 (100), 115
(85), 91 (40). HRMS calcd for C16H17NO2S ) 287.09798; found
287.09776.
N-Meth yl-N-(1-cycloh ex-1-en yl)m eth ylam in e (14c). The
title compound was prepared from 13c (200 mg, 0.8 mmol)
according to the general method described above except that
the crude rearrangement products were dissolved in MeOH
(4 mL) and treated with trifluoroacetic acid (0.12 mL, 1.6
mmol) at 0 °C. The reaction mixture was stirred for 2 h at 0
°C, and the solvent was then removed in vacuo at 35 °C. The
residue was dissolved in ether (10 mL) and extracted with a
15% aqueous solution of HCl (2 × 5 mL). The aqueous layers
were combined and cooled to 5 °C. CH2Cl2 (10 mL) was added,
and the resulting biphasic mixture was carefully neutralized
to pH 9 with solid NaHCO3. The organic layer was separated,
and the aqueous phase was extracted with CH2Cl2 (2 × 10 mL).
The combined organic extracts were washed with water (20
mL) and brine (20 mL) then dried (MgSO4) and concentrated
to give a colorless oil. The title compound was then converted
to its less volatile N-tosyl derivative for characterization using
the following procedure. The oil was dissolved in pyridine (2
mL) and tosyl chloride (152 mg, 0.8 mmol) was added in one
portion at 0 °C. After 10 min, the reaction was warmed to rt
and was then stirred overnight. Water (10 mL) was added,
and the mixture was extracted with CH2Cl2 (2 × 10 mL). The
combined extracts were washed with a 10% aqueous solution
of HCl (10 mL) and then water (20 mL). The extract was dried
(MgSO4) and concentrated to give the crude product which was
purified by column chromatography. Elution with 10% ethyl
acetate/hexane gave 47 mg (21% overall yield) of N-methyl-
N-tosyl-N-(1-cyclohex-1-enyl)methylamine and N-methylphe-
nylsulfinamide (68%) (1H NMR (300 MHz) δ 7.72-7.69 (2H,
m), 7.52-7.50 (3H, m), 4.18 (1H, br), 2.55 (3H, d, J ) 3.9 Hz);
MS (EI + ve) m/ z 156 (M + H+, 30), 64 (100)).
N-Met h yl-N-t osyl-N-(1-cycloh ex-1-en yl)m et h yla m in e
Der iva tive of 14c. 1H NMR (300 MHz): δ 7.66 (2H, d, J )
8.4 Hz), 7.32 (2H, d, J ) 8.4 Hz), 5.55 (1H, s), 3.42 (2H, s),
2.57 (3H, s), 2.43 (3H, s), 2.03-1.95 (4H, br), 1.68-1.52 (4H,
br). 13C NMR (75 MHz): δ 143.1, 132.7, 129.6, 127.6, 127.5,
126.6, 56.9, 33.7, 26.0, 25.2, 22.5, 22.3, 21.5. MS (ES + ve):
m/ z 280 (M + H+, 60), 186 (10), 102 (25), 95 (100).
N-Tosyl-N-(1-cycloh ep t-1-en yl)m eth yla m in e (16). 1H
NMR: δ 7.74 (2H, dt, J ) 8.2 Hz), 7.30 (2H, dd, J ) 8, 0.4
Hz), 5.65 (1H, t, J ) 6 Hz), 4.48 (1H, t, J ) 6 Hz), 3.42 (2H, d,
J ) 5.6 Hz), 2.43 (3H, s), 2.06-2.00 (4H, m), 1.71-1.65 (2H,
m), 1.44-1.37 (4H, m). 13C NMR: δ 143.3, 139.1, 137.0, 130.3,
129.6, 127.1, 51.4, 32.1, 30.6, 28.1, 26.7, 26.6, 21.5. MS (EI +
(E)- a n d (Z)-N-Tosyl-N-(1-p en t-3-en yl)a m in e (10). 1H
NMR (300 MHz): δ 7.75 (2H, d, J ) 8.1 Hz), 7.31 (2H, dd, J
) 8.1, 0.9 Hz), 5.60 (1H, dtt, J ) 15.3, 6.3, 1.2 Hz), 5.30 (1H,
dtt, J ) 15.3, 6.3, 1.5 Hz), 4.34 (1H, br), 3.53 (2H, tq, J ) 6.3,
1.2 Hz), 2.43 (3H, s), 1.95 (2H, pentq, J ) 7.5, 1.2 Hz), 0.91
(3H, t, J ) 7.5 Hz). 13C NMR (75 MHz): δ 143.3, 137.2, 136.5,
129.6, 127.2, 123.5, 45.3, 25.1, 21.4, 13.1. MS (ES + ve): m/ z
240 (M + H+, 55), 206 (100), 172 (85), 104 (50), 69 (95). HRMS
calcd for C12H17NO2S ) 239.09798; found 239.097496.
ve): m/ z 280 (M + H+, 10), 124 (100). HRMS calcd for C15H21
NO2S ) 279.12927; found 279.12959.
-
N-Tosyl-N-1-(1-cyclop en t -1-en yl)et h yla m in e (18). 1H
NMR: δ 7.73 (2H, d, J ) 8 Hz), 7.28 (2H, d, J ) 8 Hz), 5.41
(1H, s), 4.45 (1H, d, J ) 8 Hz), 4.03 (1H, pent, J ) 7.2 Hz),
2.42 (3H, s), 2.19-2.10 (3H, m), 2.00-1.90 (1H, m), 1.80-1.70
(1H, m), 1.69-1.58 (1H, m), 1.2 (3H, d, J ) 7.2 Hz). 13C NMR
(100 MHz): δ 144.1, 143.0, 138.0, 129.4, 127.2, 126.3, 50.1,

5522 J . Org. Chem., Vol. 61, No. 16, 1996
Pyne and Dong
32.0, 31.3, 29.7, 23.0, 21.5, 20.9. MS (ES + ve): m/ z 266 (M
+ H+, 20), 109 (20), 95 (100). ee ) 88%. [R]24D -29.2° (c 0.12,
CHCl3).
(R)-N-Tosyl-N-(1-cycloh exyleth yl)a m in e (22). (R)-(-)-
(1-Cyclohexylethyl)amine (100 mg, 0.8 mmol) was dissolved
in pyridine (2 mL), and tosyl chloride (150 mg, 0.8 mmol) was
added in portions at 0 °C. The reaction mixture was allowed
to warm to rt and was stirred overnight. Water was added,
and the mixture was extracted with CH2Cl2 (2 × 15 mL). The
combined extracts were washed with a 10% aqueous solution
of HCl (10 mL) and water (2 × 10 mL), then dried (MgSO4),
and concentrated to give the crude product that was purified
with column chromatography. Elution with 25% ethyl acetate/
hexane gave (+)-22 (185 mg, 84%). 1H NMR (300 MHz): δ
7.75 (2H, d, J ) 8.4 Hz), 7.29 (2H, d, J ) 8.4 Hz), 4.35 (1H, d,
J ) 8.7 Hz), 3.15 (1H, m), 2.43 (3H, s), 1.74-1.50 (5H, m),
1.30-0.80 (5H, m), 0.93 (3H, d, J ) 6.9 Hz). 13C NMR (100
MHz): δ 142.9, 138.3, 129.4, 126.9, 54.3, 43.4, 28.6, 28.4, 26.2,
N-Tosyl-N-(1-cycloh ex-1-en ylet h yl)a m in e (20a ). 1H
NMR: δ 7.71 (2H, d, J ) 8 Hz), 7.27 (2H, d, J ) 8 Hz), 5.44
(1H, s), 4.61 (1H, broad), 3.83 (1H, p, J ) 6.8 Hz), 2.42 (3H,
s), 1.84-1.75 (3H, m), 1.65-1.60 (1H, m), 1.49-1.44 (1H, m),
1.39-1.31 (2H, m), 1.24-1.19 (1H, m), 1.15 (3H, d, J ) 6.8
Hz). 13C NMR: δ 142.9, 138.1, 136.8, 129.3, 127.3, 123.9, 55.5,
24.8, 23.5, 22.1, 22.0, 21.5, 20.4. MS (ES + ve): m/ z 280 (M
+ H+, 37), 264 (12), 198 (10), 172 (8), 155 (15), 124 (14), 109
(100). HRMS calcd for C15H21NO2S ) 279.12927; found
279.12896. ee ) 88%. [R]22 -8.0° (c 0.2, CHCl3).
D
N -(Me t h o x y c a r b o n y l)-N -(1-c y c lo h e x -1-e n y le t h y l)-
a m in e (20b). 1H NMR: δ 5.60 (1H, br), 4.61 (1H, br), 4.11
(1H, br), 3.66 (3H, s), 2.03-1.86 (4H, m), 1.65-1.53 (4H, m),
1.22 (3H, d, J ) 7.2 Hz). 13C NMR: δ 156.2, 138.5, 121.2, 51.7,
26.7, 25.2, 24.8, 22.6, 22.3, 19.7. MS (ES + ve): m/ z 184 (M
+ H+, 60), 109 (50), 104 (100). HRMS calcd for C10H17NO2 )
183.12591; found 183.126251. ee ) 34%. [R]25D -26.7° (c 0.6,
CHCl3).
26.1, 21.4, 18.1. [R]22 +24.0° (c 0.5, CHCl3).
D
(S)-N-Tosyl-N-(1-cycloh exyleth yl)a m in e (22). A solu-
tion of 20a (100 mg, 0.36 mmol) in ethyl acetate (3 mL) and
CHCl3 (0.2 mL) at rt was stirred overnight in the presence of
10% palladium on carbon (10 mg) under an atmosphere of H2.
The mixture was filtered through a bed of celite 521, and the
celite was washed with ethyl acetate (200 mL). The washings
were concentrated and the crude product was purified by PTLC
Th er m a l Rea r r a n gem en t of 19a . A solution of 19a (440
mg, 1.1 mmol) in dry THF (10 mL) under N2 was heated to
reflux for 6 h, and the solvent was removed. The crude
products were purified by column chromatography on silica
gel. Elution with 10% ethyl acetate/hexane gave a mixture
(225 mg, 73%, 45:55) of 20a and 21. Compounds 20a and 21
could be separated by preparative HPLC.
1
to give of (-)-22 (4 mg, 4%). The H NMR of this compound
was identical to (R)-22 above: [R]23 -10.0° (c 0.4, CHCl3).
D
Ack n ow led gm en t. We thank the Australian Re-
search Council for financial support.
(E)-N-Tosyl-N-(2-eth ylid en ecycloh exyl)a m in e (21). 1H
NMR: δ 7.72 (2H, d, J ) 8 Hz), 7.27 (2H, d, J ) 8 Hz), 5.23
(1H, q, J ) 6.4 Hz), 4.57 (1H, s), 3.74 (1H, s), 2.42 (3H, s),
2.11-2.05 (1H, m), 1.97-1.91 (1H, m), 1.66-1.58 (2H, m), 1.45
(3H, d, J ) 6.4 Hz), 1.54-1.36 (5H, m). 13C NMR: δ 143.0,
138.1, 137.1, 129.3, 127.1, 117.9, 57.5, 34.8, 26.5, 25.5, 23.1,
21.5, 12.4. MS (ES + ve): m/ z 280 (M + H+, 35), 172 (10),
155 (13), 124 (18), 109(100). HRMS calcd for C15H21NO2S )
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR spectra for all compounds (except 17) reported in the
Experimental Section (27 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
279.12927; found 279.12937. [R]27 -25.9° (c 0.6, CHCl3).
J O9605105
D