COMMUNICATION
Rh(II) catalysed intramolecular C–H insertion of diazo substrates in
water: a simple and efficient approach to catalyst reuse{
Nuno R. Candeias,a Pedro M. P. Goisa and Carlos A. M. Afonso*b
Received (in Cambridge, UK) 16th September 2004, Accepted 16th November 2004
First published as an Advance Article on the web 10th December 2004
DOI: 10.1039/b414233k
less hydrophobic groups such as the n-propoxycarbonyl or di-(2-
methoxy-ethyl)aminocarbonyl gave exclusively the product as a
result of O–H insertion (Table 1, entries 5 and 6). Interestingly,
when the substrate 1a was heated at 80 uC for 70 h in water
without the Rh2(OAc)4 catalyst, complete conversion into the OH
product 4a (Scheme 2) was observed by 31P NMR. Under identical
conditions but in the presence of Rh2(OAc)4 a clean conversion
into the b-lactam 2a was observed (Scheme 1).
Water is an efficient solvent for the Rh2(OAc)4 catalysed
intramolecular C–H insertion of a range of diazo substrates
without competitive water insertion. Due to the high solubility
and stability of the catalyst in water, the catalyst can be
efficiently reused.
The intramolecular C–H insertion of dirhodium(II) carbenoids
prepared from diazocompounds and catalysed mainly by
Rh2(OAc)4 is a very powerful methodology for the synthesis of
a diverse range of valuable compounds.1 The possibility of reusing
the expensive catalysts, including chiral ones, is an important issue.
Several approaches have been developed, such as chemical
immobilisation of the ligand by anchoring it in polyethylene,2
coordination with pyridine functionalised polystyrene,3 absortion
The unexpected high intramolecular C–H insertion reaction
which is apparently dependent on the hydrophobic nature of the
ester and the amide groups as well as of the presence of the
catalyst, suggests that probably the formation of the hydrophobic
carbenoid structure, in which the water does not acquire a position
that can compete with the more favourable intramolecular C–H
insertion, is crucial. Possibly, this organised hydrophobic aggregate
around the rhodium reaction center is comparable to the one
assumed for the efficient Diels–Alder reaction observed in water
for hydrophobic substrates.10 In this case, the catalyst which
dissolves well in water needs to react with the diazo substrate and
form a more hydrophobic rhodium(II) intermediate than the
reagents.
4
on Rh2(perfluorocarboylate)4 on its fluorinated surface and by
dissolution in ionic liquids.5 This transformation is usually
performed above room temperature using chlorinated solvents
such as dichloromethane or 1,2-dichloroethane. If a protic solvent
or reagent is used (e.g. amines, alcohols or thiols) it is generally
assumed that a competitive X–H insertion of the carbenoid
occurs.6 More recently Charette and Wurz7 demonstrated that the
cyclopropanation of Rh carbenoids (also for Ru and Co) from
diazoacetate can be efficiently performed in water if instead of
Rh2(OAc)4 or Rh2(OCOCF3), a more hydrophobic catalyst is used
such as Rh2(C7H15CO2)4 in combination with hydrophobic
alkenes. According to the authors rationalisation, the effectiveness
of this transformation is due to the formation of ‘‘small alkene/
catalyst beads or micelles in water’’ in which the water soluble
diazoacetate migrates to further the reaction inside the hydro-
phobic environment.
The use of water as a solvent not only is advantageous due to it
being the most ‘green’ solvent available10 but also allows a simple,
efficient and robust system for the reuse of the Rh2(OAc)4 catalyst.
In fact, using the model substrate 1a after the reaction, the aqueous
solution containing the Rh2(OAc)4 catalyst and some traces of
diazo 1a was extracted with diethyl ether. To the remaining
aqueous solution containing the Rh2(OAc)4 was added more
substrate 1a and the process was repeated eleven times (see
As a result of our ongoing studies on the C–H insertion of
a-diazo-a-phosphono-acetamides, we observed that this transfor-
mation also occurs in wet organic solvent as well as in ionic liquids
(ILs) containing considerable amounts of water or for ILs
consisting of free hydroxyl groups.5,8 These observations prompted
us to test the transformation for a range of substrates in net water
in which the catalyst Rh2(OAc)4 is completely soluble.{ In Scheme
1 and Table 1 the substrates tested so far in water are presented. As
can be seen, the intramolecular C–H insertion is the only reaction
occurring in water for a range of a-diazo-acetamides including the
ones containing the a-phosphono, a-sulfonyl or a-acetyl groups
(Scheme 1 and Table 1, entries 1–4). These results are comparable
to the ones reported in organic solvents.8,9 Only the substrates with
{ Electronic supplementary information (ESI) available: Experimental
procedures, crude spectral data, pictures of Rh2(OAc)4 in water before and
*carlosafonso@ist.utl.pt
Scheme 1 Rh2(OAc)4 catalysed insertion of a-diazo-N,N-diisopropyl-
acetamides 1a–c in water.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 391–393 | 391
Candeias, Nuno R.
