Application of chiral sulfides to catalytic asymmetric aziridination and cyclopropanation with in situ generation of the diazo compound

Article abstract of DOI:10.1002/1521-3773(20010417)40:8<1433::AID-ANIE1433>3.0.CO;2-E

Imines and alkenes can be converted into the corresponding aziridines and cyclopropanes (see scheme, PTC = phase-transfer catalyst, Ts = toluene-4-sulfonyl) in good yield with moderate to high d.r. and high ee values using tosylhydrazone salts with catalytic quantities of chiral sulfide (5-20 mol%) and metal catalyst (1 mol%). The process is particularly suited to the synthesis of conformationally locked cyclopropyl amino acids, which can now be prepared in only three steps from commercially available material in 100% ee.

Full text of DOI:10.1002/1521-3773(20010417)40:8<1433::AID-ANIE1433>3.0.CO;2-E

COMMUNICATIONS
[3] a) V. K. Aggarwal, J. G. Ford, S. Fonquerna, H. Adams, R. V. H. Jones,
R. Fieldhouse, J. Am. Chem. Soc. 1998, 120, 8328 ± 8339; b) V. K.
Aggarwal, J. G. Ford, A. Thompson, R. V. H. Jones, M. Standen, J.
Am. Chem. Soc. 1996, 118, 7004 ± 7005; c) V. K. Aggarwal, Synlett
1998, 329 ± 336.
epoxides with high enantioselectivity. Herein we describe the
extension of this work to the asymmetric aziridination of
imines[1] and to the asymmetric cyclopropanation of electron-
deficient alkenes.[2]
[4] M. Regitz, G. Maas, Diazo Compounds: Properties and Synthesis,
Academic Press, London, 1996. Over a period of five years we
experienced three explosions when distilling phenyldiazomethane and
this encouraged us to seek alternative protocols. Because of these
problems, we did not contemplate scaling up the reaction beyond
1 mmol.
We previously reported that 1,3-oxathiane 1 gave good
yields and high enantioselectivity in aziridination[3] and
cyclopropanation[4] reactions. However, these processes are
[5] For related work, see W. R. Bamford, T. S. Stevens, J. Chem. Soc. 1952,
4735 ± 4740.
[6] For related work, see S. Wulfman, S. Yoousefian, J. M. White, Synth.
Commun. 1978, 8, 569 ± 572.
[7] We have also used this procedure for homologation of aldehydes:
V. K. Aggarwal, J. De Vicente, B. Pelotier, I. P. Holmes, R. V. Bonnert,
Tetrahedron Lett. 2000, 41, 10327 ± 10331; see also: S. R. Angle, M. L.
Neitzel, J. Org. Chem. 2000, 65, 6458 ± 6461.
S
S
O
O
O
S
1
2a
2b
[8] a) E. Vedejs, T. H. Eberlein, D. J. Mazur, C. K. McClure, D. A. Perry,
R. Ruggeri, E. Schwartz, J. S. Stuls, D. L. Varie, R. G. Wilde, S.
Wittemberger, J. Org. Chem. 1986, 51, 1556 ± 1562; b) E. Vedejs, J. S.
Stuls, R. G. Wilde, J. Am. Chem. Soc. 1988, 110, 5452 ± 5460.
[9] a) Y. Tokoro, Y. Kobayashi, Chem. Commun. 1999, 807 ± 808; b) J.-N.
potentially hazardous, cannot be easily scaled up, and the
sulfide cannot be fully recovered. We successfully solved these
problems in the epoxidation reaction by generating the diazo
compound in situ and by developing a new class of chiral
sulfides 2,[5] which were completely stable to the reaction
conditions. We were keen to examine whether these new
conditions and new sulfides were compatible with the
aziridination and cyclopropanation processes.
Optimization of the conditions for aziridination of the N-
SES-activated imine derived from benzaldehyde[6] (this imine
is easily prepared and provides a readily cleavable group) with
sulfide 2a revealed that 1,4-dioxane was the best solvent. A
broad study of different activating groups on the nitrogen
atom showed that sulfonylimines[7] led to aziridines in good
yield, high enantioselectivities, but low diastereoselectivities
(Table 1, entries 1 ± 3). A notable example is the naphthylsul-
fonylimine, which gave excellent results and this group is
considerably easier to deprotect[8] than the toluene-4-sulfonyl
(tosyl) group. Improved diastereoselectivity was observed
Ä
Denis, A. E. Greene, A. Aaraa Serra, M.-J. Luche, J. Org. Chem. 1986,
51, 46 ± 50.
[10] L. He, H. S. Byun, R. Bittman, Tetrahedron Lett. 1998, 39, 2071 ±
2074.
[11] For a discussion of the diastereoselectivity, see V. K. Aggarwal, S.
Calamai, J. G. Ford, J. Chem. Soc. Perkin Trans. 1 1997, 593 ± 599.
[12] Alkylation of sulfide 6 with benzyl bromide gave a single sulfonium
salt whose stereochemistry was determined by X-ray analysis. Full
details will be published elsewhere.
Application of Chiral Sulfides to Catalytic
Asymmetric Aziridination and
Cyclopropanation with In Situ Generation of
the Diazo Compound**
Varinder K. Aggarwal,* Emma Alonso, Guangyu Fang,
Marco Ferrara, George Hynd, and Marina Porcelloni
Table 1. Effect of the nitrogen substituent on the yield, diastereoselectiv-
ity, and enantioselectivity.[a]
In the preceding paper we described a highly efficient
catalytic process for converting carbonyl compounds into
+
R
N
Na
R
+
_
Rh2(OAc)4 (1 mol%)
BnEt3N+Cl– (10 mol%)
N
N
Ph
[*] Prof. V. K. Aggarwal,[‡] Dr. E. Alonso, G. Fang, M. Ferrara,
Dr. G. Hynd, M. Porcelloni
Ph
N
Ts
Ph
Ph
1,4-dioxane,40 °C
sulfide 2a (20 mol%)
1.5 equiv
Department of Chemistry
University of Sheffield
Brook Hill, Sheffield, S3 7HF (UK)
Entry
R
Yield [%][b]
d.r.[c]
(trans:cis)
ee [%][d]
‡
[ ] Current address:
1
2
3
4
5
6[g]
SES
Ts
SO2C10H7
Boc
TcBoc
SES
75
68
70
33[e,f]
71
2.5:1
2.5:1
3:1
8:1
6:1
94
98
97
89
90
95
School of Chemistry
Bristol University
Cantockꢁs Close, Bristol, BS8 1TS (UK)
Fax : (‡44)117-9298611
E-mail: V.Aggarwal@bristol.ac.uk
66
2.5:1
[**] We thank Avecia (M.P.), the EPSRC (M.F.), the EU for a Marie Curie
Fellowship (E.A.; HPMF-CT-1999-00076), Luꢁan Teacherꢁs College
and the Education Minister of The Peoples Republic of China (G.F.),
and Sheffield University for financial support. We thank Dr. J. Blacker
(Avecia), Dr. R. V. H. Jones (Zeneca Agrochemicals), and Dr. R.
Fieldhouse (Zeneca Agrochemicals) for their interest and support of
this work.
[a] Tosylhydrazone salt (1.5 equiv), imine (1.0 equiv), phase-transfer cata-
lyst (PTC, 0.1 equiv), Rh2(OAc)4 (0.01 equiv), 1,4-dioxane (0.33m), chiral
sulfide 2a (0.2 equiv), 408C. [b] Yield of isolated product. [c] The trans:cis
ratio was determined by 1H NMR spectroscopy. [d] Enantiomeric excess
values were determined on a Chiralcel OD column; the absolute config-
uration was 1R,2R. [e] 0.05 equiv of PTC were used. [f] trans-stilbene oxide
was obtained as the main side product. [g] 5 mol% of sulfide was used.
Ts ˆ tosyl ˆ toluene-sulfonyl.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1433 $ 17.50+.50/0
1433

COMMUNICATIONS
with carbamoylimines (entries 4 and 5),[9] and of the two
tested the TcBoc-protected[9] imine gave the higher yield (the
Boc-protected imine partially hydrolyzed during the course of
the reaction). The sulfide loading could be reduced to just
5 mol% without a significant reduction in the yield, and the
aziridine was obtained with the same enantioselectivity
(entry 6).
This study of activating groups on the nitrogen atom
revealed that sulfonyl- or TcBoc-activated imines provided
the best combination of yield, enantioselectivity, and diaster-
eoselectivity to date in a practical, user-friendly catalytic
process.[10] These groups were therefore tested with a range of
imines derived from aromatic, heteroaromatic, unsaturated,
and even aliphatic aldehydes and ketones[11] (Table 2). As
sulfonyl-substituted imines were easier to prepare than
synthetic utility of the process was demonstrated by further
manipulation of the unsaturated aziridine. Unsaturated
aziridines are very useful intermediates which are known to
undergo ring expansion under a variety of conditions to give
SES
H
N
a), b)
SiMe3
N
Me3Si
N
Ts
Ph
82% yield
78:22 trans:cis
3
4
trans: 94% ee
cis: 73% ee
1.5 equiv
SES
Ph
N
O
c)
52% yield
93% ee
trans-4
5
Scheme 1. Reagents and conditions: a) LiHMDS (1.5 equiv), THF,
788C, 1 h; b) PhCHNSES (1 equiv), Rh2(OAc)4 (1 mol%), phase-trans-
fer catalyst (PTC, 10 mol%), sulfide 2a (20 mol%), 1,4-dioxane, 408C,
12 h; c) [Pd2(dba)3 ´ CHCl3] (15 mol%), PPh3 (1.3 equiv), PhH, CO (1 atm),
508C, 12 h. HMDS ˆ 1,1,1,3,3,3-hexamethyldisilazane, SES ˆ 2-(trimethyl-
silyl)ethanesulfonyl, dba ˆ trans,trans-dibenzylideneacetone.
Table 2. Asymmetric aziridination of a range of imines.[a]
+
R3
R3
N
Rh2(OAc)4 (1 mol%)
BnEt3N+Cl– (10 mol%)
Na
_
N
N
R2
R1
Ph
+
Ph
N
Ts
R1
R2
1,4-dioxane,40 °C
sulfide 2a (20 mol%)
either b-[12] or d-lactams.[13] Treatment of trans-aziridine 4 with
Pd and CO led cleanly to the d-lactam 5 in good yield and with
the same high enantiomeric excess. This selectivity for the
formation of the d-lactam must be a consequence of a
directing effect of the silyl group since a similar compound
without the silyl group gave the b-lactam under the same
conditions.[12b] The origin of this selectivity is the subject of
further investigations.
1.5 equiv
Entry R1
R2 R3
Yield d.r.[c] ee [%]
[%][b]
(trans:cis)[d]
1
2
3
4
5
6
7
8
p-ClC6H4
p-ClC6H4
C6H11
H
H
H
H
H
H
H
TcBoc
SES
SES
Ts
SES
SES
Ts
56
82
50
53
59
60
72
6:1 94:90
2:1 98:81
2.5:1 98:89
2:1 73:95
8:1 94
tBu
ˆ
trans-PhCH CH
p-MeOC6H4
3-furfuryl
Ph
2.5:1 92:78
8:1 95
Having developed a highly efficient, practical process for
asymmetric aziridination, we focused our attention to the
cyclopropanation of electron-deficient alkenes. The reaction
of chalcone with sulfide 2a was initially chosen, and once
again 1,4-dioxane emerged as the optimal solvent (Table 3,
entry 1). However, although high enantioselectivity was
obtained, the yield was rather poor. Since six membered ring
sulfides were found to be superior to five membered ring
sulfides in cyclopropanation reactions,[4] we decided to test the
novel [2.2.2] bicyclic sulfide 2b. Sulfide 2b did indeed give
improved yields in the cyclopropanation of chalcone (Table 3,
entry 2)[14] and so studies were extended to a range of Michael
acceptors. It was found that phenyl ketones were excellent
substrates (Table 3, entries 2 and 3), whilst methyl ketones
were less good (Table 3, entries 4 and 5). Although unsub-
stituted acrylates (Table 3, entry 6) were not very effective
substrates, we found that a-amino-substituted acrylates per-
formed extremely well to give cyclopropanes in high yields,
high enantioselectivities, and high diastereoselectivities
(Table 3, entries 7 and 8). In all cases, high enantioselectivity
was obtained and the sulfide could be recovered in quanti-
tative yield.
Ph SO2C8H7 50
±
84
[a] Tosylhydrazone salt (1.5 equiv), imine (1.0 equiv), PTC (0.1 equiv),
Rh2(OAc)4 (0.01 equiv), 1,4-dioxane (0.33m), chiral sulfide 2a (0.2 equiv),
408C. Bn ˆ benzyl. [b] Yield of isolated product. [c] Determined by
1H NMR spectroscopy. [d] Enantiomeric excess values were determined
on a Chiralcel OD column. See the Supporting Information.
TcBoc-substituted ones, most studies were conducted with
the former group. In all cases good yields and high enantio-
selectivities were observed, although the diastereoselectivity
was found to be dependent on both the nature of the nitrogen
activating group and on the imine substituent. Most encour-
agingly was the observation that good diastereoselectivity
could be achieved with sulfonyl activating groups on the
imines derived from cinnamaldehyde (Table 2, entry 5) and
3-furfural (Table 2, entry 7). High enantioselectivity was
obtained from imines derived from aliphatic aldehydes
(Table 2, entry 3), although curiously the tert-butyl imine only
gave high enantioselectivity in the formation of the cis-
aziridine (Table 2, entry 4). The origin of this unusual
selectivity is not known at present and is currently under
investigation. The imine derived from benzophenone could
also be employed and allowed access to trisubstituted
aziridines (Table 2, entry 8).
The cyclopropanes derived from the amino acrylates could
be converted in one step into the corresponding amino acids
(Scheme 2) or the Boc-protected amino esters (Scheme 3).
Furthermore, a single recrystallization either before or after
deprotection led to enantiomerically pure material
(Schemes 2 and 3). The acrylates are made in one step[15, 16]
and thus provides the most efficient route to this important
class of conformationally locked amino acids. This cyclo-
The process could also be extended to alkenyldiazome-
thanes and again good yields, high enantioselectivities, and
good diastereoselectivities were obtained with the N-SES-
activated imine derived from benzaldehyde (Scheme 1). The
1434
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1434 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 8

COMMUNICATIONS
Table 3. Catalytic asymmetric cyclopropanation of electron-deficient alkenes.[a]
H
Rh2(OAc)4 (1 mol%)
BnEt3N+Cl– (20 mol%)
R3
R2
+
H
H
Ph
R3
Na
_
N
+
R1
R1
Ph
N
Ts
1,4-dioxane, 40 °C
sulfide 2a/b (20 mol%)
R2
1.5 equiv
Entry
R1
R2
R3
Sulfide
Yield [%][b]
d.r. (trans:cis)
ee [%][d]
Absolute config.
1
2
3
4
5
6
7
8
Ph
Ph
CH3
Ph
CH3
H
H
H
H
H
H
H
COPh
COPh
COPh
COCH3
COCH3
CO2Et
CO2Et
CO2Me
2a
2b
2b
2b
2b
2b
2b
2b
30[e]
73
50
5
12
10
55
72
5:1[c]
4:1[c]
4:1[c]
±
1:1:1[f]
7:1[c]
1:7[c]
1:6[c]
89
91
90
±
±
±
1R,1R
1R,1R
1R,1R
±
±
±
H
H
N-succinimide
N(Boc)2
91
92
1S,1S
1S,1S
[a] Tosylhydrazone salt (1.5 equiv), alkene (1.0 equiv), sulfide 2a/2b (0.2 equiv), PTC (0.2 equiv), Rh2(OAc)4 (0.01 equiv), in dioxane (0.13m) at 408C. Bn ˆ
benzyl. [b] Combined yield of all isomers. These can be separated except in those cases indicated. [c] Ratio of trans:cis isomers was determined by 1H NMR
spectroscopy. [d] Enantiomeric excess values were determined on a Chiralcel OD column. See the Supporting Information. [e] 50% of enone was recovered.
The absolute stereochemistries of the cyclopropanes de-
rived from chalcone[4b] and a-succinimidyl acrylate[18] were
determined by comparison of the [a]D values with those
reported in the literature. All other absolute stereochemis-
tries are given by analogy with the above and are in keeping
with the absolute stereochemistries obtained in the related
epoxidation and aziridination reactions.
The high enantioselectivity in the aziridination and cyclo-
propanation reactions can be readily accounted for by using
the same model as described for epoxidation.[5] Further work
is needed to understand the diastereoselectivity, and studies in
this area are ongoing.[19]
Scheme 2. Reagents and conditions: a) Sulfide 2b (20 mol%), Rh2(OAc)4
(1 mol%), PTC (20 mol%), 1,4-dioxane, 408C, 24 h; b) Recrystallization.
c) 6n HCl, reflux, 4 h. Ts ˆ tosyl ˆ toluene-4-sulfonyl.
In summary, we have developed a highly effective, user-
friendly, catalytic asymmetric process for the aziridination of
imines and the cyclopropanation of electron-deficient al-
kenes. The process is general and can be applied to a broad
range of electrophiles and diazo precursors. Further applica-
tions of these new processes in asymmetric synthesis are
Scheme 3. Partial hydrolysis of the protected amino acid. TFA ˆ tri-
fluoroacetic acid, Boc ˆ tert-butoxycarbonyl.
ongoing.
Received: November 22, 2000 [Z16155]
propanation methodology was further illustrated in the
[1] For reviews, see a) E. N. Jacobsen in Comprehensive Asymmetric
Catalysis II (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, pp. 607 ± 620; b) H. M. I. Osborn, J. Sweeney, Tetrahe-
dron: Asymmetry 1997, 8, 1693 ± 1715; c) D. Tanner, Angew. Chem.
1994, 106, 625 ± 646; Angew. Chem. Int. Ed. Engl. 1994, 33, 599 ± 619;
d) for an excellent catalytic asymmetric process, see J. C. Antilla,
W. D. Wulff, J. Am. Chem. Soc. 1999, 121, 5099 ± 5100.
[2] For a recent review on asymmetric cyclopropanation, see A. Pfaltz in
Comprehensive Asymmetric Catalysis II (Eds.: E. N. Jacobsen, A.
Pfaltz, H. Yamamoto), Springer, Berlin, 1999, pp. 513 ± 538. For
noncatalytic asymmetric cyclopropanation of electron-deficient al-
kenes, see A. Solladie-Cavallo, A. Diep-Vohuule, T. Isarno, Angew.
Chem. 1998, 110, 1824 ± 1827; Angew. Chem. Int. Ed. 1998, 37, 1689 ±
1691.
[3] V. K. Aggarwal, A. Thompson, R. V. H. Jones, M. C. H. Standen, J.
Org. Chem. 1996, 61, 8368 ± 8369.
[4] a) V. K. Aggarwal, H. W. Smith, R. V. H. Jones, R. Fieldhouse, Chem.
Commun. 1997, 1785 ± 1786; b) V. K. Aggarwal, H. W. Smith, G. Hynd,
R. V. H. Jones, R. Fieldhouse, S. E. Spey, J. Chem. Soc. Perkin Trans. 1
2000, 3267 ± 3276.
synthesis of protected vinylcyclopropyl amino acid
7
(Scheme 4). In this scheme an unsaturated diazocompound
was prepared in situ using our modified Bamford ± Stevens
reaction.[5] The vinylsilane moiety provides a very use-
ful handle for the incorporation of alternative functional
groups[17] onto the cyclopropane ring and so will allow access
to a much broader range of conformationally locked amino
acids.
H
N
TMS
N
Ts
CO2Me
N(Boc)2
a), b)
TMS
+
7
N(Boc)2
65 % yield, 6:1 cis:trans
75 % ee
CO2Me
Scheme 4. Reagents and conditions: a) LiHMDS (1.2 equiv), THF,
788C; b) Rh2(OAc)4 (1 mol%), sulfide 2b (100 mol%), BnEt3N Cl
(20 mol%), 1,4-dioxane, 408C, 16 h. Ts ˆ toluene-4-sulfonyl.
[5] V. K. Aggarwal, E. Alonso, G. Hynd, K. M. Lydon, M. J. Palmer, M.
Porcelloni, J. R. Studley, Angew. Chem. 2001, 113, 1479 ± 1482; Angew.
Chem. Int. Ed. 2001, 40, 1430 ± 1433.
‡
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1435 $ 17.50+.50/0
1435

COMMUNICATIONS
[6] For the synthesis of the N-SES-activated imine, see a) W. R. McKay,
G. R. Proctor, J. Chem. Soc. Perkin Trans. 1 1981, 2435 ± 2442; b) for
the synthesis of SES-Cl, see M. Weinreb, C. E. Chase, P. Wipf, S.
Venkatraman, Org. Synth. 1997, 75, 161 ± 169; SES ˆ 2-(trimethylsi-
lyl)ethanesulfonyl.
[7] The imines were prepared by using the methods described in
reference [6a] and by F. Chemla, V. Hebbe, J.-F. Normant, Synthesis
2000, 75 ± 77.
Oxoammonium Resins as Metal-Free, Highly
Reactive, Versatile Polymeric Oxidation
Reagents**
Steffen Weik, Graeme Nicholson, Günther Jung, and
Jörg Rademann*
[8] B. Nyasse, L. Grehn, H. L. S. Maia, L. S. Monteiro, U. Ragnarsson, J.
Org. Chem. 1999, 64, 7135 ± 7139.
Complex organic molecules can be constructed either in
solution or attached to an insoluble polymeric support.
Polymer-assisted solution-phase (PASP) synthesis[1±3] offers a
highly attractive supplement to these concepts by exploiting
the virtues of both traditional approaches. Polymeric re-
agents[4, 5] can be used in high excess and are removed by
filtration, the products can be easily analyzed and further
transformed in solution. They are especially suitable for
parallel combinatorial synthesis.[6, 7] They allow preparation of
complex libraries by multistep syntheses in solution, they can
be utilized in automated and in flow-through systems, and
finally they can be employedÐas will be demonstrated
hereinÐto transform single compounds as well as complex
mixtures.[8]
[9] a) TcBoc imines were prepared by treatment of N-silylimine with the
corresponding chloroformate: R. Kupfer, S. Meier, E.-U. Würthwein,
Synthesis 1984, 688 ± 690; b) The Boc-protected imine (Boc ˆ tert-
butoxycarbonyl) was prepared using the method described by: A. M.
Kanazawa, J.-N. Denis, A. E. Greene, J. Org. Chem. 1994, 59, 1238 ±
1240; TcBoc ˆ 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl.
[10] Compare entry 1 or entry 6 with our previous best results with sulfide
1, which was 55% yield, 97% ee, and 3:1 d.r.[3] Note this result used
stoichiometric amounts of 1 and cannot be easily scaled up (see
citation [3] in ref. [5]). Antilla and Wulffꢁs process (ref. [1d]) is
complementary to ours as it uses preformed diazoesters and give
cis aziridines (ours uses diazoalkanes/diazoalkenes and gives trans -
aziridines).
[11] The ketone-derived imine was prepared using the method described
by: H.-J. Cristau, J.-M Lambert, J.-L. Pirat, Synthesis 1998, 1167 ±
1170.
The oxidation of alcohols to carbonyl compounds is one of
the most relevant transformations in organic synthesis, owing
to the large diversity of products that can be obtained from
aldehyde and ketone precursors.[9] Common oxidative agents
for this transformation include dimethyl sulfoxide
(DMSO),[10] periodinanes[11] as well as various heavy-metal
reagents, the latter usually based on either chromium[12] or
ruthenium oxides.[13] There are several examples of polymer-
supported oxidation reagents,[14] including heavy-metal oxides
bound to ion-exchange resins.[15, 16] One resin of this type has
been recently employed in a reaction sequence leading to
heterocyclic compounds.[17] However, low reactivity with non-
benzylic alcohols, potential persistence of highly toxic heavy
metals in the products as well as overoxidation of aldehydes
limits the use of solid-supported metal oxides in parallel
syntheses.
[12] a) G. W. Spears, K. Nakanishi, Y. Ohfune, Synlett 1991, 91 ± 92;
b) D. Tanner, P. Somfai, Bioorg. Med. Chem. Lett. 1993, 3, 2415 ±
2418.
[13] J. G. Knight, S. W. Ainge, A. M. Harm, S. J. Harwood, H. I. Maughan,
D. R. Armour, D. M. Hollinshead, A. A. Jaxa-Chamiec, J. Am. Chem.
Soc. 2000, 122, 2944 ± 2945.
[14] Compare entry 2 with our previous best result with sulfide 1, which
gave 38% yield, 4:1 d.r., and 97% ee.
[15] The 1-pyrrolidineacetic acid a-methylene-2,5-dioxo-ethyl ester was
prepared from ethyl propiolate and succinimide by the method
described by: B. M. Trost, G. R. Dake, J. Am. Chem. Soc. 1997, 119,
7595 ± 7596.
[16] 2-Propenoic acid 2-[bis[(1,1-dimethylethoxy)carbonyl]amino]-methyl
ester was prepared from serine and Boc-ON by the method described
by: P. M. T. Ferreira, H. L. S. Maia, L. S. Monteiro, Tetrahedron Lett.
1998, 39, 9575 ± 9578. We have found that this acrylate can be prepared
in one step from serine methyl ester and (Boc)2O.
[17] W. Kuni, O. Koichiro, U. Kiitiro, Chem. Lett. 1987, 10, 2029 ±
2032.
Â
[18] C. Alcaraz, M. D. Fernandez, M. P. de Frutos, J. L. Marco, M.
Herein we report on the generation of oxoammonium
halides as oxidizing reactive species on a solid support and on
the use of this reagent in the oxidation of single alcohols and
of complex compound collections. Oxoammonium salts have
been postulated as reactive intermediates in oxidations
employing the 2,2,6,6-tetramethylpiperidine 1-oxyl radical
(TEMPO), which is commonly employed under phase-trans-
fer conditions with, for example, sodium hypochlorite as
activating oxidant in the aqueous phase.[18, 19] Recently
TEMPO has been used in solution together with a polymer-
attached oxidizing agent[20] and as a catalyst on silica.[21] No
reports were found about using oxoammonium salts on
insoluble, crosslinked polymers, which would allow the
Â
Bernabe, Tetrahedron 1994, 50, 12443 ± 12456.
[19] We have found from crossover experiments relating to aziridination
that betaine formation is irreversible. Thus, the diastereoselectivity is
controlled by nonbonding interactions that lead to the betaine.
[*] Dr. J. Rademann, Dipl.-Chem. S. Weik, G. Nicholson,
Prof. Dr. G. Jung
Institut für Organische Chemie, Universität Tübingen
Auf der Morgenstelle 18, 72076 Tübingen (Germany)
Fax : (‡49)7071-295560
E-mail: joerg.rademann@uni-tuebingen.de
[**] J.R. gratefully acknowledges generous support from Prof. M. E.
Maier, Tübingen, the Strukturfonds of the Universität Tübingen, and
Merck KGaA, Darmstadt, Germany.
1436
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1436 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 8