Flavin-catalyzed generation of diimide: An environmentally friendly method for the aerobic hydrogenation of olefins

Article abstract of DOI:10.1021/ja053976q

The first green and practical method for "aerobic hydrogenation" involving the use of hydrazine and an organocatalyst is described. Olefins can be hydrogenated by treatment with hydrazine in the presence of a 5-ethyl-3-methyllumiflavinium perchlorate (FlEt⁺·ClO₄^-) catalyst under O₂ atmosphere to give the corresponding hydrogenated products in excellent yields along with environmentally benign water and molecular nitrogen as the only waste products. Copyright

Full text of DOI:10.1021/ja053976q

Published on Web 09/30/2005
Flavin-Catalyzed Generation of Diimide: An Environmentally Friendly Method
for the Aerobic Hydrogenation of Olefins
Yasushi Imada,* Hiroki Iida, and Takeshi Naota*
Department of Chemistry, Graduate School of Engineering Science, Osaka UniVersity, Machikaneyama,
Toyonaka, Osaka 560-8531, Japan
Received June 15, 2005; E-mail: imada@chem.es.osaka-u.ac.jp; naota@chem.es.osaka-u.ac.jp
The development of new processes for catalytic hydrogenation
has become an important area of research, with the potential to pro-
vide environmentally benign processes as alternatives to the estab-
A typical procedure for aerobic hydrogenation is exemplified
by the reduction of 1-decene (1). A mixture of 1 (140 mg, 1.0
mmol), 5-ethyl-3,7,8,10-tetramethylisoalloxazinium perchlorate (2,
1
+
-
lished technologies based on hydrogen gas (eq 1). Considerable
FlEt ‚ClO
4
, 4.0 mg, 0.01 mmol), and NH
2 2 2
NH ‚H O (60.1 mg,
effort has been devoted to the investigation of alternative hydrogena-
1.2 mmol) in CH
3
CN (4.0 mL) was stirred at 25 °C for 4 h under
tion methods which use organic hydrogen donors (DH
2
) with transi-
oxygen atmosphere (1 atm, O2 balloon). After extraction with
pentane (10 mL × 3), the combined organic layers were washed
with brine, dried over Na SO , and evaporated under reduced
2
3
tion metal or organic catalysts (eq 2). However, despite their safe
and convenient procedures, these methods are always accompanied
by the production of stoichiometric amounts of organic waste (D).
It is this dilemma that has prompted us to develop new methodolo-
2
4
pressure to afford decane (142 mg, 99%) as a colorless oil. The
catalytic activities of a series of functionalized isoalloxazinium
perchlorates were examined for the aerobic hydrogenation of
4
5
gies employing the fusion of flavin and diimide chemistries. In this
communication, we describe the first green and practical method
for “aerobic hydrogenation”. The method is performed using an or-
+
-
decenes. FlEt ‚ClO4 (E°′ ) 306, -389 mV) showed the best
catalytic activity among those examined. Moderate yields of
products were obtained with the 5-ethyl-7,8,10-trimethyl (E°′ )
316, -323 mV) and 5-ethyl-3-methyl-10-phenyl (E°′ ) 427, -274
mV) derivatives; however, electropositive flavins bearing 7-cyano-
5-ethyl-3,10-dimethyl functionalities (E°′ ) 512, -177 mV) and
2
ganocatalyst under O atmosphere and produces environmentally be-
nign water and molecular nitrogen as the only waste products (eq 3).
S + H2 M cat.8 SH2
(1)
(2)
+
-
4b
bulky flavins, such as DMRFlEt ‚ClO
4
(E°′ ) 322, -364 mV),
S + DH2 M cat. or org. cat.8 SH + D
2
gave unsatisfactory results. CH CN was found to be the best solvent;
3
S + 1/2 O + NH NH
8 SH + H O + N (3)
however, other polar solvents, such as DMSO and DMF, can also
be used for the reaction. The specific ability of flavin catalysts to
limit the deactivation of hydrazine was demonstrated by the reaction
of 9-decen-1-ol with 1.0 equiv of hydrazine under standard
conditions (1 mol % of catalyst). After completion of the reduction,
only 13 mol % of hydrazine was converted to molecular nitrogen
2
2
2
2
2
2
org. cat.
Diimide, NHdNH, acts as a mild reducing agent for a variety
of symmetrical unsaturated bonds. This reduction process has the
5
potential to be environmentally benign since nitrogen gas is the
sole waste product. However, the strong reducing properties of the
diimide reagent result in a rapid disproportionation reaction, which
produces molecular nitrogen and hydrazine; therefore, the reagent
using catalyst 2, whereas when using CuSO
4
as catalyst (1 mol
%
), almost half the hydrazine (46 mol %) was deactivated.
Table 1 shows representative results for the FlEt ‚ClO
4
--
+
6
must be generated in situ. As a result of this, an excess of the di-
catalyzed aerobic hydrogenation of olefins. A variety of linear and
cyclic olefins (entries 1-6) can be converted to the corresponding
hydrogenated products quantitatively, at room temperature and
imide precursor is generally required to produce a complete reac-
tion. The catalytic aerobic oxidation of hydrazine, which would
be the ideal method for generating diimide, also remains problem-
atic from the point of view of green chemistry since a great excess
of hydrazine (10 to >400 equiv) is required to achieve this. Our
strategy for the generation of diimide involves the novel application
of a flavin redox system, which has previously been used for the
catalytic aerobic oxidation of organic substrates.4 The diimide
generated by this system is highly protected from the inevitable
disproportionation reaction. The method thus provides an organo-
catalytic method for the hydrogenation of olefins that requires only
equiv of hydrazine and 1 atm of molecular oxygen (eq 4). This
reaction provides an alternative, highly efficient, safe, facile, and
economic strategy for the catalytic hydrogenation of olefins.
5
7
2
under O atmosphere (1 atm). In contrast to the conventional
8
8
method, the use of 1-2 equiv of hydrazine is sufficient to complete
the reactions. It is noteworthy that the selective cis-1,2-deuteration
of olefins7b can be achieved to complete conversion with little over
1 equiv of deuterium source (entry 3). Reactive substituents, such
as tertiary amino, sulfoxy, and hydroxy groups, are tolerated by
the reaction (entries 2, 4, 5, 6, and 7). Exomethylenes are selectively
reduced in the presence of other substituted olefins (entry 6). R,â-
Unsaturated esters and amides also undergo smooth hydrogenation
under similar conditions (entries 7 and 8). Because the substrates
are completely consumed and the only chemical wastes are nitrogen
gas and water, all of the products can be readily isolated by simple
extraction.
1
A plausible mechanism for the catalytic aerobic hydrogenation
is shown in Scheme 1, with reduction, O incorporation, and oxygen
2
4
transfer to the flavin catalyst acting as crucial steps in the reaction.
To explain the hydrazine efficiency, a mechanism proceeding via
the direct reduction of the olefin with the flavin/diimide complex
+
is proposed. Thus, a flavinium cation FlEt 2 is reduced with
hydrazine to afford the reduced flavin/diimide complex 3; this
14544
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J. AM. CHEM. SOC. 2005, 127, 14544-14545
10.1021/ja053976q CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Flavin-Catalyzed Aerobic Hydrogenation of Olefinsa
stoichiometry was confirmed experimentally, with 0.33 mmol of
O
2
being consumed in the hydrogenation of 0.7 mmol of 9-decen-
1-ol under standard conditions, a result that is consistent with the
mechanism of Scheme 1.
Another important feature of the flavin-catalyzed reaction is the
unprecedented switching control possible in the oxygenation of
heteroatoms. Typically, the treatment of phenyl allyl sulfide (8)
under standard conditions in CH
formation of phenyl n-propyl sulfide (9) with toleration of the thio
functionality (eq 5). However, similar treatment in acidic CF CH
OH affords phenyl n-propyl sulfoxide (10) as the sole product (eq
). The selective formation of 9 in aprotic solvents can be ascribed
3
CN gives rise to the selective
3
2
-
6
to the faster electrophilic oxygenation of hydrazine with 5, due to
the R-effect of hydrazine.12 The drastic change in product selectivity
arises due to the deactivation of the nucleophilic hydrazine by the
4
a
acidic media, which results in preferential S-oxygenation in the
aerobic step of the catalytic cycle. This is a rare case of catalytic
reductions proceeding simultaneously with oxygenation processes.
Efforts are currently underway to investigate the full scope of the
reaction.
a
b
Supporting Information Available: Experimental procedures
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
The reaction was carried out as described in text. ND2ND‚D2O was
used. c At 50 °C. Using DMSO as a solvent.
d
complex then hydrogenates olefins faster than it liberates diimide.
The presence of this anaerobic process has been confirmed by the
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