Simple preparation of trans-epoxides via ylide intermediates

Article abstract of DOI:10.1055/s-2004-834885

A practical route to epoxides with control of the relative and absolute stereochemistry has been developed, allowing epoxides to be readily prepared on a 20 mmol scale by generating the reactive intermediate (the diazo compound) in situ from benzaldehyde tosylhydrazone sodium salt. In this paper, we describe the optimum conditions for three procedures to obtain the desired racemic and enantiomerically enriched epoxides (Scheme 1). High diastereoselectivities (98-100%) and very high yields of epoxide were obtained. Asymmetric epoxidation was carried out using the chiral camphor-derived [2.2.1] bicyclic sulfide 4 and the desired epoxide was obtained with excellent enantioselectivity (94%). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2004-834885

1
378
PRACTICAL SYNTHETIC PROCEDURES
Simple Preparation of Trans-Epoxides via Ylide Intermediates
L
V
arge-Scale Prepa
a
rationof Tr
r
ans-Epox
i
ide
s
vi
n
a
Y
lide Inte
r
d
mediates er K. Aggarwal,* Cristina Aragoncillo, Caroline L. Winn
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
Fax +44(117)9298611; E-mail: v.aggarwal@bristol.ac.uk
Received 24 August 2004
This paper is dedicated to Professor Manfred Reetz, in appreciation of his inspirational work.
PSP
No47
Abstract: A practical route to epoxides with control of the relative and absolute stereochemistry has been developed, allowing epoxides to
be readily prepared on a 20 mmol scale by generating the reactive intermediate (the diazo compound) in situ from benzaldehyde tosylhy-
drazone sodium salt. In this paper, we describe the optimum conditions for three procedures to obtain the desired racemic and enantiomer-
ically enriched epoxides (Scheme 1). High diastereoselectivities (98–100%) and very high yields of epoxide were obtained. Asymmetric
epoxidation was carried out using the chiral camphor-derived [2.2.1] bicyclic sulfide 4 and the desired epoxide was obtained with excellent
enantioselectivity (94%).
Key words: asymmetric catalysis, diazo compounds, epoxidations, sulfur ylides, epoxides
O
S
R
R = Ph
Ph (±) 1
Na
Ts
O
R
N
chiral sulfide 4
RCHO
Rh2(OAc)4
PTC
+
+
+
Ph
N
R = Ph
Ph
2
S
O
Ph3As
R =
R
O
chiral sulfide 4
Ph (±)3
Scheme 1
employs catalytic quantities of sulfide would be more at-
tractive.
Introduction
In our group we have recently developed a ‘user-friendly’
Epoxides are versatile substrates and important building catalytic cycle for carbonyl epoxidation which employs
blocks in synthetic chemistry for the construction of more catalytic quantities of sulfide and metal catalyst
1
6
complex structures. For example, they can undergo ste- (Scheme 2). In this process, a tosyl hydrazone salt is con-
reospecific nucleophilic ring opening to give highly func- verted into a diazo compound which reacts with a metal
2
tionalized compounds. Hence, the development of catalyst furnishing a metal carbene, which in turn reacts
practical methods for their stereocontrolled preparation is with a sulfide to generate a sulfur ylide. Finally, the ylide
of interest. Epoxides can be prepared asymmetrically reacts with the aldehyde to give an epoxide.
from a carbonyl group by Wittig olefination followed by
The catalytic epoxidation cycle using chiral sulfur ylides
3
enantioselective oxidation of the double bond or by enan-
is an effective and complementary method to enantiose-
tioselective alkylidenation using either an ylide, a car-
lective alkene oxidation methodology for the preparation
4
bene, or Darzens reagent. In this context, the reaction of
of enantiomerically pure epoxides. The process is partic-
sulfur ylides with carbonyl compounds provides an im-
ularly attractive since both metal and sulfide are used in
portant tool for the preparation of chiral epoxides in or-
substoichiometric quantities.
ganic synthesis. However, sulfur ylide reactions have
A significant operating problem associated with the cycle
traditionally been carried out with stoichiometric amounts
7
5
in the original protocol, involved the pre-generation, and
manipulation of diazo compounds. Due to their high tox-
of sulfonium salt. To make this method more practical,
especially for the asymmetric reaction, a procedure that
8
icity, instability and potentially explosive nature, the
practicality and the scalability of the process were limited.
To our delight, the problem was solved by generation of
the diazo compound in situ from the corresponding tosyl-
SYNTHESIS 2005, No. 8, pp 1378–1382
x
x
.
x
x
.2
0
0
4
Advanced online publication: 21.10.2004
DOI: 10.1055/s-2004-834885; Art ID: Z16304SS
Georg Thieme Verlag Stuttgart · New York
©

PRACTICAL SYNTHETIC PROCEDURES Simple Preparation of Trans-Epoxides via Ylide Intermediates
1379
Rh2(OAc)4
R2S
CHPh
RCHO
O
Ph
N2
PTC, 40 o
C
Na
Ts
R
N2
N
Ph
N
Ph
R2S
Rh=CHPh
Scheme 2
hydrazone salt in the presence of a phase transfer catalyst A broad range of tosylhydrazone salts derived from aro-
9
at 40 °C. Thus, the development of an optimized and matic, heteroaromatic, and a,b-unsaturated aldehydes was
practical process for the preparation of epoxides 1–3 is also examined, and good yields and high diastereoselec-
now at hand.
tivities were obtained in most cases.
Optimization of the formation of each individual epoxide
on a 20 mmol scale has been accomplished and we now
report the conditions required to obtain good yields and
S
1
0
good diastereo- and enantioselectivities.
5
Figure 1
Scope and Limitations
Extensive studies to map out the scope and limitations of
the process have been carried out in order to determine An examination of the metal counterion on the course of
which classes of carbonyl compounds and diazo precur- the reaction was also undertaken (using lithium, sodium
sors could be employed for the preparation of epoxides.11 and potassium). The sodium salt was found to be the most
efficient in terms of giving the highest yield and hence,
was the starting material of choice to perform the epoxi-
dations.
A range of aromatic, heteroaromatic, aliphatic, a,b-unsat-
urated, and acetylenic aldehydes were screened, providing
the corresponding epoxides in high yields and moderate to
very high diastereoselectivities. However, reactions using Rhodium (II) acetate as a transition metal catalyst was
ketones as the substrate were less successful. In this case, found to be very efficient in the catalytic process.14
a substantial amount of the by-product 2-tolyltetrahy-
In the epoxidation reaction we have observed the forma-
drothiophene (5), formed from competing Sommelet
tion of two main by-products: stilbenes (cis and trans) and
1
2
Hauser rearrangement reaction,
was observed
15
by-product 6 (Scheme 3). Stilbenes are formed by reac-
(Figure 1).
tion of the diazo compound with the rhodium carbene, but
Low diastereoselectivities were observed when aliphatic their formation can be minimized by the slow addition of
aldehydes were used, however the use of triphenylarsine the diazo compound. This problem has been solved by
in place of tetrahydrothiophene provided the correspond- slow generation of the diazo compound in situ from the
ing epoxides with complete control of diastereoselectivi- hydrazone sodium salt.
1
3
ty.
Na
Rh
Ph
N
Ph
Rh
Ph
N
+
Ph
Ph
N
Ph
N
N2
Ph
Ts
Na
Ts
N
+
N
N
Ph
N
Ph
N
Ph
N
2
) proton source
6
Scheme 3
Synthesis 2005, No. 8, 1378–1382 © Thieme Stuttgart · New York

1
380
V. K. Aggarwal et al.
PRACTICAL SYNTHETIC PROCEDURES
6
is presumably formed by attack of the sodium salt onto
phenyldiazomethane, but as yet, despite extensive investi-
gation, the origin of the proton source remains unknown.
If the tosylhydrazone salt is washed with pentane, further
improvements in yield of epoxide with reduced levels of
by-product 6 are observed. In fact, occasionally the crude
tosylhydrazone salt, obtained after removal of MeOH un-
der vacuum, has a pale pink appearance indicative of the
diazo compound. Washing with pentane removes the pink
colour and presumably the diazo compound.
In conclusion, a practical and user-friendly method for the
synthesis of three notable examples of epoxides has been
successfully performed. These procedures enable the
preparation of these epoxides to be carried out on a mod-
erate scale (20 mmol), from readily available and inex-
pensive starting materials.
Procedures
Herein, we describe three typical synthetic procedures demonstrat-
ing the synthetic scope of the epoxidation process conducted on 20
mmol scale.
The optimized procedures reported are very simple, use inexpensive
starting materials, and provide good yields of epoxides. All the ep-
oxidation reactions were performed in a 50 mL two-necked, round-
bottom flask equipped with a mechanical stirrer.
In Procedure 1 we report the preparation of the starting material
benzaldehyde tosylhydrazone 7 from commercially available tosyl
hydrazine and benzaldehyde. In the second procedure (Procedure
2
) we describe the formation of the tosylhydrazone sodium salt 8 by
deprotonation of the hydrazone using freshly generated NaOMe in
MeOH.
Procedures 3–5 report the preparation of the epoxides 1–3. Ep-
oxide 1 (Procedure 3) can be prepared in very good yield (98%)
starting from the tosylhydrazone sodium salt 8 (1.5 equiv), benzal-
dehyde, benzyltriethyl ammonium chloride as a phase transfer cat-
alyst, Rh (OAc) as the metal catalyst and tetrahydrothiophene in
2
4
MeCN at 40 °C. It has been observed that when less equivalents of
the tosylhydrazone sodium salt are employed (1.1 equiv and 1.3
equiv) lower yields of the desired epoxide result (74% and 94% re-
spectively). This is due to the formation of by-product 6 in the first
stage of the process, which consumes some of the salt. For this rea-
son, 1.5 equivalents salt has been chosen as the appropriate amount
in the optimized procedures. Procedure 4 reports the formation of
the enantiomerically enriched stilbene oxide 2 using the chiral sul-
Figure 2 HPLC chromatograms and retention times (min) of (a) all
possible products, by-products and starting materials (b) epoxidation
reaction mixture using Procedure 3.
16
fide 4 instead of tetrahydrothiophene.
Following Procedure 3, using 0.20 equivalents of chiral sulfide 4,
we have obtained the corresponding epoxide with very good diaste-
reoselectivity (98:2), high enantioselectivity (94% ee) and very
good yield (87%). Under the same conditions but using 5 mol% sul-
Despite the large number of starting materials and poten-
tial by-products in the reaction mixture, it was possible to fide 4, the epoxide was obtained in only 40% yield but with the
monitor the reaction by reverse phase HPLC, using a Dis- same diastereo- and enantioselectivity. Adding two equal batches of
the tosylhydrazone salt, (0.75 equiv or 1 equiv), the second one after
covery HS C18 column, 50:50 MeCN–H O and 1-chloro-
2
2
4 hours, resulted in much improved yields (63% and 78% respec-
2
-methoxybenzene as an internal standard. Figure 2
tively). Under these conditions the concentration of the hydrazone
salt and therefore the diazo compound are lower, resulting in fewer
side reactions and thus improved yields.
shows an HPLC trace (a) of all the possible products, by-
products and starting materials, and (b) of the epoxidation
reaction using Procedure 3 (vide infra). A study of the re-
action under different conditions and examination of the
resulting reaction profiles obtained using the HPLC meth-
od have shown that the formation of the hydrazone by-
In the last procedure (Procedure 5) an aliphatic aldehyde was test-
ed. In this case, triphenylarsine was used instead of tetrahy-
drothiophene in order to improve the diastereoselectivity
(
tetrahydrothiophene gave 65:35 trans:cis selectivity). A good yield
product 6 always takes place in the first two hours of the of epoxide 3 (67%, 100% trans) was obtained using a stoichiomet-
reaction. After this period of time the by-product forma- ric amount of triphenylarsine. Using 20% mol of triphenylarsine,
the yield of the epoxide was only 25%. The reaction of the arsonium
tion stops and the epoxide begins to form. The by-product
Synthesis 2005, No. 8, 1378–1382 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES Simple Preparation of Trans-Epoxides via Ylide Intermediates
1381
ylide with cyclohexylcarboxaldehyde also gave a small amount of
alkene (11%) and the corresponding arsine oxide. This could ac-
count for the reduced yields observed when substoichiometric
amounts of arsine were employed.
Procedure 3: Preparation of 1,2-Diphenyloxirane 1
To a 50 mL two-necked round-bottom flask fitted with a N balloon
2
and equipped with a mechanical stirrer, were added sequentially to-
sylhydrazone sodium salt 8 (8.9 g, 30.0 mmol, 1.5 equiv), benzyl-
triethyl ammonium chloride (460 mg, 2.0 mmol, 0.1 equiv),
rhodium (II) acetate dimer (88 mg, 0.2 mmol, 0.01 equiv), tetrahy-
drothiophene (350 mL, 4.0 mmol, 0.2 equiv), benzaldehyde (2.0 mL,
20 mmol, 1.0 equiv) and anhyd MeCN (35 mL). The reaction mix-
ture was stirred vigorously at r.t. for 10 min, then at 40 °C for 24 h.
Procedure 1: Preparation of Benzaldehyde Tosylhydrazone 7
To a vigorously stirred suspension of tosyl hydrazine (5.0 g, 26.8
mmol) in MeOH (10 mL) was added freshly distilled benzaldehyde
(24 mL, 24.0 mmol) dropwise. A mildly exothermic reaction en-
sued (a cooling bath was used to keep the temperature of the reac-
tion mixture at 0 °C), and the hydrazide dissolved. Within 5–10
min, the tosylhydrazone began to precipitate. After approximately
The reaction was quenched by addition of a sat. solution of NH Cl
(20 mL) and EtOAc (20 mL). The aqueous layer was washed with
EtOAc (20 mL) and the combined organic phases were dried over
4
3
0 min, the mixture was cooled to 0 °C, and the product was re-
MgSO , filtered and concentrated in vacuo. The crude product was
analyzed by H NMR to determine the diastereomeric ratio (98:2)
and then purified by flash column chromatography to afford the
4
1
moved by filtration and washed with a small quantity of MeOH.
The solid was purified by recrystallization with hot MeOH to give
the corresponding compound as white needles (Scheme 4). Yield:
pure trans epoxide as a white solid (Scheme 6). Yield: 3.8 g (98%);
1
7
18
5
.4 g (96%); mp 127–128 °C (lit. 128–129 °C).
mp 65–67 °C (lit. 69 °C); R 0.70 (10% EtOAc–petroleum ether).
f
1
1
H NMR (270 MHz, CDCl ): d = 2.37 (s, 3 H, CH ), 7.26–7.37 (m,
Trans-isomer: H NMR (270 MHz, CDCl ): d = 3.85 (s, 2 H, 2 ×
3
3
3
5
9
H, ArH), 7.52–7.61 (m, 2 H, ArH), 7.80 (s, 1 H, CH), 7.89 (d, J =
CH), 7.16–7.37 (m, 10 H, ArH).
.0 Hz, 2 H, ArH), 8.44 (br s, 1 H, NH).
1
Cis-isomer: H NMR (270 MHz, CDCl ): d = 4.28 (s, 2 H, 2 × CH),
.01–7.15 (m, 10 H, ArH).
3
7
H
N
MeOH
Ph
H2NNH2
Ph
N
2 4
Rh (OAc) (0.01 equiv)
sulfide (0.2 equiv)
PhCHO (1 equiv)
O
+
Ts
+
-
BnEt3N Cl
0.1 equiv)
7
Na
Ts
O
(
N
Ph
Ph
N
Ph
N2
Scheme 4
CH3CN, ∆
CH3CN, ∆ Ph
1
Scheme 6
Procedure 2: Preparation of Tosylhydrazone Sodium Salt 8
To a dry, argon flushed 50 mL round-bottom flask, equipped with a
magnetic stirring bar, 1 M NaOMe solution was prepared by adding
freshly cut Na (290 mg, 12.5 mmol) to anhyd MeOH (12.5 mL) with
external cooling. Once all of the metal had dissolved, the tosylhy-
drazone (3.4 g, 12.35 mmol) was added, and the mixture was stirred
until the solid had dissolved. The mixture was stirred for a further
Procedure 4: Preparation of (R,R)-1,2-Diphenyloxirane 2
To a 50 mL two-necked round-bottom flask fitted with a N balloon
and equipped with a mechanical stirrer, were added sequentially to-
sylhydrazone sodium salt 8 (5.9 g, 20.0 mmol, 1 equiv), benzyltri-
ethyl ammonium chloride (460 mg, 2.0 mmol, 0.1 equiv), rhodium
2
1
5 min, before MeOH was removed under reduced pressure, at r.t.,
(II) acetate dimer (88 mg, 0.2 mmol, 0.01 equiv), sulfide 4 (250 mg,
to yield the hydrazone salt in quantitative yield. The solid hydra-
zone salt was then ground using a pestle and mortar to give free
1
.0 mmol, 0.05 equiv), benzaldehyde (2.0 mL, 20 mmol, 1.0 equiv)
1
and anhyd MeCN (35 mL). The reaction mixture was stirred vigor-
ously at r.t. for 10 min, then at 40 °C for 24 h, then 1 more equiva-
lent of tosylhydrazone sodium salt (5.9 g, 20 mmol) was added and
the reaction mixture was stirred at the same temperature for one
more day. The reaction was quenched by addition of a sat. solution
flowing powder. Analysis of the crude salt by H NMR in DMSO-
d6 showed the presence of a singlet at 5.7 ppm corresponding to the
methylene proton of phenyl diazomethane. Hence it was necessary
to purify the salt by washing with n-pentane, filtering and then dry-
ing under vacuum for 3 h. The salt was stored at r.t. and exposure to
direct light was avoided (Scheme 5). Yield: 3.2 g (87%); white sol-
id.
of NH Cl (20 mL) and EtOAc (20 mL). The aqueous layer was
4
washed with EtOAc (20 mL) and the combined organic phases were
dried over MgSO , filtered and concentrated in vacuo. The crude
product was analyzed by H NMR to determine the diastereomeric
4
–
1
IR (KBr disk): 3056, 1245, 1129, 1088 cm .
1
1
H NMR (270 MHz, DMSO-d ): d = 2.26 (s, 3 H, CH ), 7.05 (m, 1
ratio (98:2) and then purified by flash column chromatography to
afford the epoxide (Scheme 7) (3.9 g, 78% yield). It was possible to
recover the chiral sulfide in 70% yield by column chromatography
and recycle it for use in further reactions. The enantiomeric excess
was determined by HPLC. A racemic sample was run to check the
retention time of the enantiomers at r.t. using a chiracel OD column.
A diode array detector was used to confirm that the UV traces of the
enantiomers were superimposable. Flow: 1 mL/min, solvent: hex-
ane–i-PrOH (99:1), t (minor): 4.86 min, t (major): 10.84 min with
6
3
H, ArH), 7.12 (d, J = 10.2 Hz, 2 H, ArH), 7.18 (m, 2 H, ArH), 7.34
(m, 2 H, ArH), 7.57 (m, 3 H, ArH, CH).
1
3
C NMR (DMSO-d ): d = 21.3, 121.9, 124.8, 125.3, 126.2, 127.0,
6
1
28.6, 128.7, 129.6, 136.8.
Anal. Calcd for C H N SO Na: C, 56.8; H, 4.4; N, 9.5. Found: C,
14
13
2
2
5
6.8; H, 4.3; N, 9.2.
R
R
absolute configuration (R, R). Epoxide 2 was obtained with 94% ee.
Na
Ts
H
N
MeOH/Na
N
Procedure 5: Preparation of 2-Cyclohexyl-3-phenyl Oxirane 3
Ph
N
Ph
N
Ts
To a 50 mL two-necked round-bottom flask fitted with a N balloon
2
and equipped with a mechanical stirrer, were added sequentially, to-
sylhydrazone sodium salt (8.9 g, 30 mmol, 1.5 equiv), benzyltrieth-
yl ammonium chloride (460 mg, 2.0 mmol, 0.1 equiv), rhodium (II)
acetate dimer (88 mg, 0.2 mmol, 0.01 equiv), triphenylarsine (6.1 g,
8
Scheme 5
2
1
0 mmol, 1 equiv), cyclohexylcarboxaldehyde (2.4 mL, 20 mmol,
.0 equiv) and anhyd MeCN (35 mL). The reaction mixture was
Synthesis 2005, No. 8, 1378–1382 © Thieme Stuttgart · New York

1
382
V. K. Aggarwal et al.
PRACTICAL SYNTHETIC PROCEDURES
(2) Smith, J. G. Synthesis 1984, 629.
(3) (a) Katsuki, T. In Comprehensive Asymmetric Catalysis,
Vol. 2; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.;
Springer-Verlag: Berlin, 1999, 621–648. (b) Jacobsen, E.
N.; Wu, M. H. In Comprehensive Asymmetric Catalysis,
Vol. 2; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.;
Springer-Verlag: Berlin, 1999, 649–677. (c) Shi, Y. Acc.
Chem. Res. 2004, 37, 488.
Rh2(OAc)4 (0.01 equiv)
sulfide 4 (0.05 equiv)
PhCHO (1 equiv)
+
-
BnEt3N Cl
Na
Ts
(
0.1 equiv)
O
N
Ph
Ph
N
Ph
N2
CH3CN, ∆
CH3CN, ∆
Ph
2
S
(
4) (a) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997,
O
chiral sulfide 4
97, 2341. (b) Aggarwal, V. K. In Comprehensive
Asymmetric Catalysis, Vol. 2; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999, 679–
6
93.
5) Aggarwal, V. K.; Winn, C. L. Acc. Chem. Res. 2004, 37,
11.
Scheme 7
stirred vigorously at r.t. for 10 min, then at 40 °C for 24 h. The re-
(
(
6
6) (a) Aggarwal, V. K.; Ford, J. G.; Fonquerna, S.; Adams, H.;
action was quenched by addition of a sat. solution of NH Cl (20
4
Jones, R. V. H.; Fieldhouse, R. J. Am. Chem. Soc. 1998, 120,
mL) and EtOAc (20 mL). The aqueous layer was washed with
EtOAc (20 mL) and the combined organic phases were dried over
8328. (b) Aggarwal, V. K.; Ford, J. G.; Thompson, A.;
Jones, R. V.; Standen, M. C. H. J. Am. Chem. Soc. 1996, 118,
7004. (c) Aggarwal, V. K. Synlett 1998, 329. (d) Studley, J.
R.; Aggarwal, V. K. (Astra Zeneca) WO98/516666, 1998.
7) Aggarwal, V. K.; Abdel-Rahman, H.; Fan, L.; Jones, R. V.
H.; Standen, M. C. H. Chem.–Eur. J. 1996, 2, 1024.
8) Regitz, M.; Maas, G. Diazo Compounds: Properties and
Synthesis; Academic Press: London, 1986.
9) Aggarwal, V. K.; Alonso, E.; Hynd, G.; Lydon, K. M.;
Palmer, M. J.; Porcelloni, M.; Studley, J. R. Angew. Chem.
Int. Ed. 2001, 40, 1430.
10) For the preparation of chiral sulfide 4, see ref.
MgSO and filtered. Petroleum ether was added to precipitate out
4
any remaining triphenylarsine (4.1 g, 67% yield). The solid was fil-
tered off and the organic phase was concentrated in vacuo. The
(
(
(
1
crude product was analyzed by H NMR to determine the diastereo-
meric ratio (100:0). The epoxide was purified by column chroma-
tography to give the desired epoxide as a colorless oil (Scheme 8)
(2.7 g, 67% yield). Any remaining arsine was recovered during pu-
rification (0.7 g, 11% yield) (an important factor since arsenic com-
pound are toxic and environmentally hazardous). R 0.41 (5%
f
EtOAc–petroleum ether).
9
(
1
(11) Aggarwal, V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon, K.
M.; Palmer, M. J.; Patel, M.; Porcelloni, M.; Richardson, J.;
Stenson, R. A.; Studley, J. R.; Vasse, J.-L.; Winn, C. L. J.
Am. Chem. Soc. 2003, 125, 10926.
Trans-isomer: H NMR (400 MHz, CDCl ): d = 0.76–2.09 (m, 11
3
H), 2.76 (dd, J = 2.1, 6.8 Hz, 1 H, CHPh), 3.69 (d, J = 2.1 Hz, 1 H,
CHPh), 7.15–7.23 (m, 5 H, ArH).
(
12) For a review on sulfur ylide rearrangements, see: Marko, I.
E. In Comprehensive Organic Synthesis, Vol. 3; Trost, B.
M.; Fleming, I., Eds.; Pergammon: Oxford, 1979, 913–974.
+
-
BnEt3N Cl
0.1 equiv)
Rh2(OAc)4 (0.01 equiv)
Ph3As (1 equiv)
Na
Ts
(
N
Ph
N
Ph
N2
O
CH3CN, ∆
(13) Aggarwal, V. K.; Patel, M.; Studley, J. Chem. Commun.
CHO
Ph
2002, 1514.
(
1 equiv)
3
(14) Rhodium (II) acetate was prepared from rhodium trichloride
trihydrate and anhyd NaOAc in glacial HOAc and EtOH:
Rempel, G. A.; Legzdins, P.; Smith, H.; Wilkinson, G.
Inorg. Synth. 1971, 13, 90.
CH3CN, ∆
Scheme 8
(
15) The structure of 6 was confirmed by preparation of a
reference sample using the tosylhydrazone salt 8 and benzyl
bromide in DMF: Nozaki, H.; Noyori, R.; Sisido, K.
Tetrahedron 1964, 20, 1125.
Acknowledgment
We thank the DTI, Avecia, Syngenta, Johnson Matthey, and the
Marie Curie program for financial support.
(
16) For a full discussion of the factors controlling enantio- and
diastereoselectivity, see: Aggarwal, V. K.; Richardson, J.
Chem. Commun. 2003, 2644.
(
17) McMahon, R. J.; Abelt, C. J.; Chapman, O. L.; Johnson, J.
W.; Kreil, C. L.; LeRoux, J. P.; Mooring, A. M.; West, P. R.
J. Am. Chem. Soc. 1987, 109, 2456.
References
(
1) Rossiter, B. E. Asymmetric Synthesis, Vol. 5; Morrison, J.
D., Ed.; Academic Press: New York, 1985, 193–246.
(18) Imuta, M.; Ziffer, H. J. Org. Chem. 1979, 44, 2505.
Synthesis 2005, No. 8, 1378–1382 © Thieme Stuttgart · New York