Novel catalytic and asymmetric process for aziridination mediated by sulfur ylides

Full text of DOI:10.1021/jo961754s

8368
J . Org. Chem. 1996, 61, 8368-8369
Sch em e 1
Novel Ca ta lytic a n d Asym m etr ic P r ocess
for Azir id in a tion Med ia ted by Su lfu r Ylid es
Varinder K. Aggarwal,*,† Alison Thompson,†
Ray V. H. J ones,‡ and Mike C. H. Standen‡
Department of Chemistry, University of Sheffield,
Sheffield S3 7HF, U.K., and Zeneca Manufacturing
Partnership, Process Technology Department, Earls Road,
Grangemouth, Stirlingshire FK3 8XG, U.K.
Received September 12, 1996 (Revised Manuscript Received
October 25, 1996)
Sch em e 2
Like epoxides, aziridines are versatile synthetic inter-
mediates.1 However, only a limited number of methods
for asymmetric aziridination exist: addition of carbenoids
to imines2 or copper-catalyzed additions of nitrenoids to
alkenes.3 Superior results have been obtained by the
latter method, although high enantioselectivity is still
limited to a small subset of alkenes and only N-Ts
aziridines are accessible. This is a severe limitation of
this methodology, especially as harsh conditions are
required for cleavage of the strong sulfonamide bond.
Despite recent advances, the tosyl group remains a
difficult group to remove from sensitive substrates.4
An alternative strategy for aziridination involves the
addition of sulfur ylides to imines.5 However, this
reaction normally5e requires stoichiometric amounts of
reagents and is currently racemic. We have previously
shown that in related epoxidation reactions such limita-
tions can be overcome: sulfur ylides can be generated
by the reaction of a sulfide with a carbenoid in the
presence of an aldehyde and so only catalytic amounts
of sulfides are required.6 Furthermore, the use of chiral
sulfides gives non racemic epoxides.7 We now report the
development of a novel, catalytic, and asymmetric route
to aziridines based on this methodology.
Ta ble 1. P r ep a r a tion of Azir id in es fr om Im in es a n d
P h en yld ia zom eth a n e
equiv of
Me2S
ratio
(trans:cis)
entry
R1
R2
yielda/%
1
2
3
4
5
6
Ph
Ph
Ph
Ph
p-ClC6H4
p-MeC6H4
Ts
1.0
0.2
0.2
0.2
0.2
0.2
90
91
83
92
88
96
4:1
4:1
3:1
3:1
3:1
3:1
Ts
DPP
SES
SES
SES
a
The yield refers to the total yield of trans and cis isomers.
diazocompound or carbenoid and aldehyde did not occur.
For aziridination, direct reaction between the carbenoid
and imine needed to be avoided and this could be
achieved by employing electron-withdrawing groups on
the imine nitrogen.9 Such groups would also enhance the
rate of addition of the sulfur ylide to the imine. Thus,
we initially chose N-tosylbenzaldimine and carried out
the reaction shown in Scheme 2. We were delighted to
find that the corresponding aziridine was formed in
excellent yield (Table 1, entry 1). Even with catalytic
quantities of sulfide (0.2 equiv), high yields of aziridine
were obtained (Table 1, entry 2). We confirmed that the
reactions were occurring via the sulfur ylide as in the
absence of sulfide no aziridine was isolated. This experi-
ment confirmed that we had successfully eliminated the
direct coupling between the metal carbenoid and imine.
Having successfully shown that N-tosylimines partici-
pated in the aziridination process, we wanted to test
alternative groups on nitrogen10 that similarly activated
the imine toward nucleophilic attack but were easier to
remove. Thus, N-(diphenylphosphinyl)benzaldimines
(DPP))11 and N-[â-(trimethylsilyl)ethanesulfonyl]benzal-
dimines (â-(trimethylsilyl)ethanesulfonyl ) (SES))12 were
prepared and subjected to the catalytic cycle. Again,
using just catalytic quantities of sulfides, high yields of
the corresponding aziridine were obtained (Table 1,
entries 3 and 4). As the SES imines were more easily
prepared than the DPP imines, several aryl imines with
this group were prepared and tested in the cycle, and
again, high yields of the corresponding aziridines were
obtained (Table 1, entries 5 and 6). In all cases a 3:1
Our proposed catalytic cycle for aziridination is shown
in Scheme 1 and involves the slow addition of a diazo
compound8 to a solution of a suitable metal salt, sulfide,
and imine. From our previous work, we knew that sulfur
ylides could be generated in the presence of aldehydes
by this method and that direct reaction between the
† University of Sheffield.
‡ Zeneca Manufacturing Partnership.
(1) (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599-619.
(b) For a review of methods in aziridination see: Evans, D. A.; Faul,
M. M.; Bilodeau, M. T. J . Am. Chem. Soc. 1994, 116, 2742-2753.
(2) (a) Hansen, K. B.; Finney, N. S.; J acobsen, E. N. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 676-678. (b) Rasmussen, K. G.; J orgensen,
K. A. J . Chem. Soc., Chem. Commun. 1995, 1401-1402. (c) Zhu, Z.;
Espenson, J . H. J . Org. Chem. 1995, 60, 7090-7091.
(3) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328-5329. (b) Li, Z.;
Conser, K. R.; J acobsen, E. N. J . Am. Chem. Soc. 1993, 115, 5326-
5327. (c) Mu¨ller, P.; Baud, C.; J acquier, Y. Tetrahedron 1996, 52, 1543-
1548.
(4) Vedejs, E.; Lin, S. J . Org. Chem. 1994, 59, 1602-1603. (b) It
has recently been shown that p-nitroaryl sulfonamides can be cleaved
by addition of thiols; Fukuyama, T.; J ow, C. K.; Cheung, M. Tetrahe-
dron Lett. 1995, 36, 6373-6374.
(5) (a) Franzen, V.; Driesen, H. E. Chem. Ber. 1963, 96, 1881-1890.
(b) Corey, E. J .; Chaykovsky, M. J . Am. Chem. Soc. 1965, 87, 1353-
1364. (c) Tewari, R. S.; Awasthi, A. K.; Awasthi, A. Synthesis 1983,
330-331. (d) Li, A. H.; Dai, L. X.; Hou, X. L. J . Chem. Soc., Chem.
Commun. 1996, 491-492. (e) Dai has recently reported the preparation
of vinylic aziridines using catalytic amounts of sulfide under basic
conditions; Li, A. H.; Dai, L. X.; Hou, X. L. J . Chem. Soc., Perkin Trans.
1 1996, 867-869.
(9) It has been shown that the nature of the group on nitrogen
determines the efficiency of the addition of carbenoids to imines.
Electron-donating groups result in high yields; electron-withdrawing
groups result in low yields. See ref 2b. This issue would become
important in the development of an asymmetric process.
(10) Neither silyl nor phenyl groups on nitrogen are sufficiently
electron withdrawing to activate the imine toward nucleophilic attack
by the sulfur ylide.
(11) J ennings, W. B.; Lovely, C. J . Tetrahedron 1991, 47, 5561-
5568. The DPP group may be easily removed from aziridines by
treatment with MeOH/BF3.OEt2: Osborn, H. M. I.; Sweeney, J . B.
Synlett 1994, 145-147.
(6) Aggarwal, V. K.; Abdel-Rahman, H.; J ones, R. V. H.; Lee, H. Y.;
Reid, B. D. J . Am. Chem. Soc. 1994, 116, 5973-5974.
(7) Aggarwal, V. K.; Ford, J . G.; Thompson, A.; J ones, R. V. H.;
Standen, M. C. H. J . Am. Chem. Soc. 1996, 118, 7004-7005.
(8) Slow addition is required to limit the extent of dimerisation of
the diazocompound: Doyle, M. P.; Griffin, J . H.; Bagheri, V.; Dorow,
R. L. Organometallics 1984, 3, 53-61.
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Communications
entry
J . Org. Chem., Vol. 61, No. 24, 1996 8369
Ta ble 2. Asym m etr ic Azir id in a tion of N-SES-a ld im in e (Sch em e 4)
R1
equiv of 1
ML2
yielda/%
ratio (trans:cis)
eeb,c/%
1
2
3
4
5
6
7
Ph
Ph
Ph
p-MeC6H4
p-MeC6H4
p-ClC6H4
p-ClC6H4
1.0
1.0
0.2
1.0
0.2
1.0
0.2
Rh2(OAc)4
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
Cu(acac)2
Rh2(OAc)4
Cu(acac)2
55
83
62
88
50
70
44
3:1
3:1
3:1
3:1
3:1
3:1
3:1
97 (R,R)d
95 (R,R)d
90 (R,R)d
95 (R,R)e
88 (R,R)e
88 (R,R)e
85 (R,R)e
a
b
The yield refers to the total yield of trans and cis isomers. Enantiomeric excess determined by HPLC using a Chiralcel OD column.
c All aziridines had a positive optical rotation. The absolute configuration of trans N-[â-(trimethylsilyl)ethanesulfonyl]-2,3-diphenylaziridine
d
was deduced by correlation to stilbene oxide (see ref 20). e By analogy with benzaldimine it is assumed that the absolute configuration is
the same.
Sch em e 3
Sch em e 4
dimerization of the diazo compound compared to Rh2-
(OAc)4.17 Thus, Cu(acac)218 was used in the catalytic cycle
in place of Rh2(OAc)4, and a higher yield (83%) of the
corresponding aziridine was obtained (Table 2, entry 2).
Use of a catalytic amount of sulfide 1 (20 mol %) also
furnished the correspnding aziridine but in slightly lower
yield (Table 2, entry 3). Other aldimines were tested in
the aziridination process using both rhodium and copper
salts, and high enantioselectivity was maintained (Table
2, entries 4-7). The small reduction in the enantiomeric
excess observed when Cu(acac)2 was used in place of Rh2-
(OAc)4 is presumably due to limited, but competing, direct
reaction between the imine and copper carbenoid, a
pathway that became more pronounced when catalytic
amounts of sulfides were used. From our previous
experiments little or no direct coupling occurred between
the rhodium carbenoid and imine. This is the first
example of the preparation of nonracemic aziridines by
the addition of chiral sulfur ylides to imines. Further-
more, the levels of asymmetric induction for aziridination
are the highest reported to date.
mixture of trans:cis aziridines was obtained.13 Depro-
tection12 of trans-N-[â-(trimethylsilyl)ethanesulfonyl]-2,3-
diphenylaziridine using CsF was facile and furnished
trans-2,3-diphenylaziridine in 89% yield. This demon-
strated the advantage of the current catalytic process
over existing methods.
Encouraged by these results, we explored alternative
diazo compounds (N,N-diethyldiazoacetamide14 and ethyl
diazoacetate) in the catalytic cycle. Higher temperatures
(60 °C) were required for the decomposition of these more
stable diazo compounds, and so tetrahydrothiophene was
used instead of Me2S. As shown in Scheme 3, good to
excellent yields of the corresponding aziridines were
obtained. While the diazoacetamide gave predominantly
the trans aziridine, the diazoester gave the cis aziridine
as the major product. These results show that the new
methodology may be applied to the preparation of func-
tionalized aziridines. We believe that the reaction em-
ploying the diazoester-derived sulfur ylide is under
thermodynamic control and that the cis isomer is the
thermodynamic product.15
In summary, we have developed a new method for the
preparation of aziridines from imines and diazo com-
pounds that requires catalytic amounts of metal salts and
sulfides and operates under neutral conditions. Using
enantiomerically pure sulfides, high enantioselectivity
has been achieved in the aziridination process.
In preliminary studies we have tested chiral sulfides
derived from (+)-camphorsulfonyl chloride in the catalytic
cycle for aziridination (Scheme 4, Table 2). We were
delighted to find that the use of sulfide 116 gave the
required aziridine with high enantiomeric excess (97%),
although in modest yield (55%) (Table 2, entry 1). In
related studies, it was found that, using hindered sul-
fides, Cu(acac)2 gave superior yields of epoxides with less
Ack n ow led gm en t. We gratefully thank Zeneca
Manufacturing Partnership and Sheffield University for
financial support.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for the preparation and analytical data of sulfide 1,
method for the asymmetric aziridination process, and assay
methods for the product aziridines (12 pages).
(12) Weinreb, S. M.; Demko, D. M.; Lessen, T. A. Tetrahedron Lett.
1986, 27, 2099-2102. The SES group has been shown to be easily
removed from amines by fluoride.
(13) From cross-over experiments, we have shown that these reac-
tions are under kinetic control. Full details will be published else-
where.
J O961754S
(14) N,N-Diethyldiazoacetamide was prepared according to the
method of Regitz for the preparation of tert-butyl diazoacetate. N,N-
Diethylacetoacetamide was used in place of tert-butyl acetoacetate:
Regitz, M.; Hocker, J .; Liedhegener, A. Organic Synthesis; Wiley: New
York, 1973; Collect. Vol. V, pp 179-183. Rando, R. R. J . Am.Chem.
Soc. 1972, 94, 1629-1631.
(15) This is presumably because the 1,2 steric interaction on the
three-membered ring between the SES group (this is the largest group)
and either of the substituents is greater than the 1,2 steric interaction
between the substituents themselves. It has also been found that,
under equilibrating conditions, cis-unsaturated N-tosylaziridines were
formed in preference to the trans isomers: Mimura, N.; Ibuka, T.;
Akaji, M.; Miwa, Y.; Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.;
Yamamoto, Y. J . Chem. Soc., Chem. Commun. 1996, 351-352.
(16) In related epoxidation reactions (ref 7), sulfide 1 was found to
give high enantioselectivity in reactions with PhCHO (93% ee).
(17) Aggarwal, V. K.; Abdel-Rahman, H.; Li, F.; J ones, R. V. H.;
Standen, M. C. H. Chem. Eur. J . 1996, 2, 1024-1030.
(18) The quality of the Cu(acac)2 is critical to the success of the
reaction. Use of commercial Cu(acac)2 was ineffective, but use of Cu-
(acac)2 prepared by the method of Cervello´ followed by sublimation
was successful: Cervello´, J .; Marquet, J .; Moreno-Man˜as, M. Synth.
Commun. 1990, 20, 1931-1941.
(19) (R,R)-Stilbene oxide (94% ee) was treated with sodium azide
followed by triphenylphosphine to yield (S,S)-trans-2,3-diphenylaziri-
dine ([R]D -320 (c 0.25 EtOH)). Deprotection of N-SES-trans-2,3-
diphenylaziridine (97% ee) ([R]D 9 (c 1.0 EtOH)) using CsF (see ref 12)
gave trans-2,3-diphenylaziridine in 89% ([R]D +311 (c 0.53 EtOH)). The
absolute configuration of the N-SES-trans-2,3-diphenylaziridine could
thus be deduced to be R,R.