Palladium-catalyzed transfer hydrogenation in alkaline aqueous medium

Article abstract of DOI:10.1016/S0040-4039(00)01365-4

Catalytic transfer hydrogenation using palladium(II) chloride, formate and aqueous sodium hydroxide is effective for the reduction of unsaturated carboxylic acids, azalactones, and α-ketocarboxylic acids. This method is convenient, economical, avoids organic solvents, and uses a stable, nonpyrophoric catalyst. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01365-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7847–7849
Palladium-catalyzed transfer hydrogenation in alkaline
aqueous medium
Jeffrey B. Arterburn,a,* Madhavi Pannala,a Anicele M. Gonzaleza and
Rebecca M. Chamberlinb
aDepartment of Chemistry and Biochemistry MSC 3C, New Mexico State University, PO Box 30001, Las Cruces,
NM 88003, USA
bNuclear and Radiochemistry Group, CST-11, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Received 29 June 2000; revised 7 August 2000; accepted 8 August 2000
Abstract
Catalytic transfer hydrogenation using palladium(II) chloride, formate and aqueous sodium hydroxide
is effective for the reduction of unsaturated carboxylic acids, azalactones, and a-ketocarboxylic acids. This
method is convenient, economical, avoids organic solvents, and uses a stable, nonpyrophoric catalyst.
© 2000 Published by Elsevier Science Ltd.
Catalytic transfer hydrogenation can be an effective method for reducing a variety of organic
substrates, which avoids some of the technical and safety concerns associated with using
compressed hydrogen gas.1 The heterogeneous mixture of PdꢀC and ammonium formate in
alcohol solvent has proven to be a particularly effective reagent in organic synthesis.2 Replacing
organic solvents with water offers economic advantages, improves safety, reduces the environ-
mental impact of the waste stream, and in combination with the development of catalytic
processes offers great opportunities for ‘green’ chemistry.3 We have studied transfer hydrogena-
tion in alkaline aqueous conditions as part of a broad investigation of noble metal-catalyzed
reactions of organic substrates in water. Herein, we report a convenient, effective method for
reducing unsaturated carboxylic acids using the nonpyrophoric catalyst palladium(II) chloride,
formic acid, and sodium hydroxide base in water.
The reduction of cinnamic acid 1 was carried out using 10 mol% PdCl2 and 4 equivalents of
hydrogen donor, in 2.5 M aqueous NaOH solution, heated to 65°C for 16 h. A series of
potential hydrogen donors was investigated, from which formic acid was the most effective
(yield of hydrocinnamic acid 2=98%), followed in decreasing order of effectiveness by: glyoxylic
acid (80%), gluconic acid (35%), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (20%), glycolic
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01365-4

7848
Table 1
Pd-catalyzed transfer hydrogenation with alkaline aqueous formate
acid (20%), and formaldehyde (5%). Formaldehyde is known to produce hydrogen under
alkaline aqueous conditions,4 but was ineffective for the reduction under these conditions. The
reaction was also successful using varying hydroxide concentrations ranging from 0.5 to 5 M;
however, no reduction was evident when 2.5 M Na2CO3 was used as base.5,6

7849
A variety of other unsaturated carboxylic acids were also reduced under these conditions in
excellent yields (Table 1, entries 2–4).7 The a-N-acyldehydroamino acids (entries 5, 6) were
converted to the corresponding N-acylphenylalanine derivatives in very good yields. The readily
available azalactones (entries 7, 8) were also converted directly to the N-acyl amino acids. This
procedure was also effective for reducing the a-keto group of phenylpyruvic acid, giving the
product mandelic acid in very good yield (entry 9).
In summary, PdCl2 is an effective catalyst for transfer hydrogenations using formic acid in
alkaline aqueous media. This procedure is advantageous because no organic solvent is required,
the reagents are inexpensive, and the catalyst is nonpyrophoric. These reaction conditions
should be suitable for the reduction of a wide variety of organic substrates, and offers an
economical, safe, and environmentally benign alternative to available procedures.
Acknowledgements
This research was supported by the Department of Energy Environmental Management
Science Program.
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.