Synthesis of epoxides from aldehydes and tosylhydrazone salts catalysed by triphenylarsine: Complete trans selectivity for all combinations of coupling partners

Article abstract of DOI:10.1039/b204252e

Triphenylarsine catalyses the formation of epoxides from carbonyl compounds and tosylhydrazone salts. This convergent synthesis gives complete trans selectivity for all aldehyde and tosylhydrazone salt coupling partners.

Full text of DOI:10.1039/b204252e

Synthesis of epoxides from aldehydes and tosylhydrazone salts catalysed
by triphenylarsine: complete trans selectivity for all combinations of
coupling partners†
Varinder K. Aggarwal,* Mamta Patel and John Studley
School of Chemistry, Bristol University, CantockAs Close, Bristol, UK BS8 1TS.
E-mail: V.aggarwal@bristol.ac.uk; Fax: (+44) 117-929861; Tel: (+44) 117-99546315
Received (in Cambridge, UK) 3rd May 2002, Accepted 27th May 2002
First published as an Advance Article on the web 19th June 2002
Triphenylarsine catalyses the formation of epoxides from
carbonyl compounds and tosylhydrazone salts. This con-
vergent synthesis gives complete trans selectivity for all
aldehyde and tosylhydrazone salt coupling partners.
It is known that non-4 or semi-stabilised5 arsonium ylides
react with aldehydes to give trans epoxides with high
diastereoselectivity (in contrast, semi-stabilised6 and stable7,8
arsonium ylides react with aldehydes to give alkenes).9 Thus, if
arsines could be employed in our catalytic process not only
should high trans selectivity result, but the potential to use sub-
stoichiometric amounts and not have to manipulate the toxic
reagent over several steps (as is required using conventional
arsonium ylide chemistry) provides very significant operational
advantages. However, literature precedent was not in our
favour: although there were several reports on the formation of
stable arsonium ylides through reaction of stable diazo-
compounds with arsines these all employed copper cata-
lysts,8,9a,10 which we knew were not compatible with our
catalytic process. There were no examples on the use of
Rh2(OAc)4 to promote ylide formation and furthermore no
examples employing less stable diazo compounds which are the
substrates required for epoxidation (stable diazocompounds
would lead to stabilised arsonium ylides which would give
alkenes).
We recently reported a novel catalytic process for the direct
coupling of aldehydes with tosylhydrazone salts to give
epoxides.1 Catalytic amounts of Rh2(OAc)4 and sulfide are
employed in this process and the reaction proceeds through the
intermediacy of diazocompounds, metal carbenes and sulfur
ylides (Scheme 1).
Although high trans diastereoselectivity was observed in
reactions of neutral or electron deficient aryl tosylhydrazone
salts with aromatic aldehydes, much lower diastereoselectivity
was observed with aliphatic aldehydes e.g. C6H11CHO gave a
65+35 ratio of trans+cis epoxides. The problem of low
diastereocontrol was further exacerbated when electron rich
aryl tosylhydrazone salts were employed e.g. p-methoxyaryl
tosylhydrazone salt gave a 67+33 ratio of trans+cis epoxides
with benzaldehyde. The variable diastereoselectivity in the
above cases results from the degree of reversibility in betaine
formation. High trans selectivity is a consequence of reversible
formation of the syn betaine which only cyclises slowly to give
cis epoxide and essentially irreversible formation of the anti
betaine which cyclises rapidly to give the trans epoxide. This
has been proved experimentally2 and underpinned through
calculation.3 In contrast, reaction of the same benzyl stabilised
ylide with aliphatic aldehydes gives syn and anti betaines
irreversibly leading to low diastereocontrol. The use of electron
rich aryl-stabilised ylides leads to even less reversibility in
betaine formation as the ylide is less stable and therefore again
leads to low diastereocontrol. Attempts to solve this problem by
changing reaction conditions were not successful so we
considered more fundamental changes, and in particular the use
of arsines in our catalytic process in place of sulfides.
Thus, AsPh3 was initially tested in our process using
benzaldehyde tosylhydrazone salt with aromatic and aliphatic
aldehydes (Table 1).
We were delighted to find that the reaction was highly
efficient providing high yields and complete trans selectivity
with all of the aldehydes employed (Table 1, entries 1–5).11 We
did note that reactions with aliphatic aldehydes were slightly
lower yielding and small amounts of alkene by-products were
also observed (entries 3–5). Using sub-stoichiometric amounts
of AsPh3 high yields were again obtained with aromatic
aldehydes (entries 6,7) but now a significant reduction in yield
was observed with aliphatic aldehydes (entries 8–10). This was
presumably due to the small amount of competing alkene
formation which consumes the arsine catalyst, lowering its
concentration further and preventing it from re-entering the
ylide cycle. Reactions with more electron rich aryl tosylhy-
drazone salts were also tested. When these were employed in
our sulfur ylide-mediated process low diastereoselectivity was
observed even with aromatic aldehydes.1 However, using
Ph3As complete diastereoselectivity was obtained with both
aromatic and aliphatic aldehydes (entries 11–18). No competing
alkene formation was observed in these cases, presumably
because the intermediates are even less stabilised arsonium
ylides and so epoxide formation occurs exclusively. However,
whilst good yields were maintained when aromatic aldehydes
were employed with sub-stoichiometric amounts of Ph3As, a
significant reduction in yield was observed with aliphatic
aldehydes. We cannot account for this finding at present.
In summary, we have found that complete trans selectivity
can be achieved in coupling reactions of aryl tosylhydrazone
salts (especially those derived from electron rich aromatics)
with both aromatic and aliphatic aldehydes using catalytic
quantities of Ph3As and Rh2(OAc)4. This provides a direct,
convergent and completely diastereoselective route to this
general class of epoxides from readily available reagents.
Furthermore, as the conditions are exceptionally mild, (the
reaction will tolerate base-, acid- and oxidatively-sensitive
Scheme 1 One-pot coupling of a carbonyl compound with a tosylhydrazone
salt to give an epoxide, Ts = toluene-4-sulfonyl.
† Electronic supplementary information (ESI) available: new compounds.
See http://www.rsc.org/suppdata/cc/b2/b204252e/
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CHEM. COMMUN., 2002, 1514–1515
This journal is © The Royal Society of Chemistry 2002

Table 1 Yields and ratios of epoxides and alkenes obtained using aldehyde 4 and aryl tosylhydrazone salts 1–3 using triphenylarsine
Tosylhydrazone
salt
Yield of
epoxide (%)
Trans+cis
Yield of
alkene (%)
Entrya
Aldehyde (R2CHO)
Ph3As/mol%
selectivityb
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1
1
1
1
1
1
1
1
1
1
2
2
2
2
3
3
3
3
p-Chlorobenzaldehyde
Benzaldehyde
Valeraldehyde
100
100
100
100
100
20
20
20
20
20
82
89
70
53
77
70
62
10
28
30
92
64
76
40
98
85
93
42
100+0
100+0
> 98+2
100+0
100+0
100+0
100+0
100+0
100+0
100+0
> 98+2
> 98+2
100+0
> 98+2
100+0
100+0
100+0
100+0
0c
0c
8
13
12
0c
0c
7
10
8
0
0
0
Isobutyraldehyde
Cyclohexanecarboxaldehyde
p-Chlorobenzaldehyde
Benzaldehyde
Valeraldehyde
Isobutyraldehyde
Cyclohexanecarboxaldehyde
Benzaldehyde
Cyclohexanecarboxaldehyde
Benzaldehyde
Cyclohexanecarboxaldehyde
Benzaldehyde
Cyclohexanecarboxaldehyde
Benzaldehyde
100
100
20
20
0
0
0c
0c
0c
100
100
20
Cyclohexanecarboxaldehyde
20
a Ph3As (20 mol% or 100 mol%), PhCHO (0.33 mmol), CH3CN (1mL), Rh2(OAc)4 (1 mol%), benzyltriethylammonium chloride (20 mol%), tosylhydrazone
salt (1.5 eq.). b Selectivity refers to epoxide geometry. c Traces of alkene were observed by NMR analysis.
8 I. Gosney and D. Lloyd, Tetrahedron, 1973, 29, 1697.
9 For reviews on arsonium ylides: (a) D. Lloyd, I. Gosney and R. A.
Ormiston, Chem. Soc. Rev., 1987, 16, 45; (b) Y. Huang and Y. Sheng,
Adv. Organomet. Chem., 1982, 20, 113; A. W. Johnson, Ylide
Chemistry, Academic Press, New York, 1966.
groups), this convergent and stereoselective reaction will be the
method of choice in many instances.
We thank EPSRC and Avecia for support of this work.
10 B. H. Freeman and D. Lloyd, Tetrahedron, 1973, 29, 1697; J. Nicholas,
Notes and references
C. Hood, D. Lloyd, W. A. Macdonald and T. Maurice Shepherd,
1 V. K. Aggarwal, E. Alonso, G. Hynd, K. M. Lydon, M. J. Palmer, M.
Porcelloni and J. R. Studley, Angew. Chem., Int. Ed., 2001, 8, 1430.
2 V. K. Aggarwal, S. Calamai and J. G. Ford, J. Chem. Soc., Perkin Trans.
1, 1997, 593.
3 V. K. Aggarwal, J. N. Harvey and J. Richardson, J. Am. Chem. Soc.,
2002, 20, 5747.
4 W. C. Still and V. J. Novack, J. Am. Chem. Soc., 1981, 103, 1283.
5 J. B. Ousset, C. Mioskowski and G. Solladie, Tetrahedron. Lett., 1983,
41, 4419; R. Broos and M. J. O. Anteunis, Bull. Soc. Chim. Belg., 1988,
4, 271; J. D. Hsi and M. Koreeda, J. Org. Chem., 1989, 54, 3229; W.-B.
Wang, L.-L. Shi, Z.-Q. Li and Y.-Z. Huang, Tetrahedron Lett., 1991, 32,
3999.
6 R. S. Tewari and S. C. Chaturvedi, Tetrahedron Lett., 1977, 43, 3843.
7 S. Trippett and M. A. Walker, J. Chem. Soc. C, 1971, 1114; L. Shi, W.
Wang, Y. Wang and Y.-Z. Huang, J. Org. Chem., 1989, 54, 2028; J.
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Tetrahedron, 1982, 22, 3355.
11 A typical procedure: to a 5 mL round bottomed flask fitted with a
nitrogen balloon was added sequentially: triphenylarsine (20 mol% or
100 mol%), anhydrous acetonitrile (1.0 mL), rhodium(II) acetate dimer
(1.5 mg, 1 mol%), benzyl triethylammonium chloride (15 mg, 20
mol%), aldehyde 4 (0.33 mmol, 1.0 equiv.) and tosylhydrazone sodium
salt 1–3 (0.50 mmol, 1.5 equiv.). The reaction mixture was stirred
vigorously at room temperature for 10 min, then at 40 °C for 3 h. The
reaction was quenched by the addition of water (0.5 mL) and ethyl
acetate (0.5 mL). The aqueous layer was washed with ethyl acetate (2 3
0.5 mL) and the combined organic phases dried over MgSO4, filtered
and concentrated in vacuo. The crude product was analysed by 1H NMR
to determine the diastereomeric ratio and then purified by flash column
chromatography to afford the corresponding epoxide. Note the tosyl
hydrazone salt is not soluble in MeCN and the PTC is added to aid its
passage from the solid phase to the solution phase, where it fragments
to the diazocompound.
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