LED lighting as a simple, inexpensive, and sustainable alternative for Wolff rearrangements

Article abstract of DOI:10.1039/c4ra15670f

The Wolff rearrangement is one of the best methods for chain homologation. However, it still suffers from many drawbacks with respect to its practical execution in the laboratory. We wish to demonstrate the use of commercial LED lamps as a sustainable alternative for the classic experimental protocols typically used for Wolff rearrangements. This journal is

Full text of DOI:10.1039/c4ra15670f

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LED lighting as a simple, inexpensive, and
sustainable alternative for Wolff rearrangements†
Cite this: RSC Adv., 2015, 5, 13311
a
b
a
*
Barbara Bernardim, Andrea M. Hardman-Baldwin and Antonio C. B. Burtoloso
Received 2nd December 2014
Accepted 19th January 2015
DOI: 10.1039/c4ra15670f
www.rsc.org/advances
The Wolff rearrangement is one of the best methods for chain 1930 when general methods to prepare diazoketones were
homologation. However, it still suffers from many drawbacks with developed.11,12
respect to its practical execution in the laboratory. We wish to
Initially, Ludwig Wolff found that heating solutions of select
demonstrate the use of commercial LED lamps as a sustainable diazoketones to temperatures above 100 C,10 or use of freshly
alternative for the classic experimental protocols typically used for prepared silver(I)oxide in basic media,13 were suitable for
ꢀ
Wolff rearrangements.
carrying out the transformation. Nowadays, thermolysis is
generally avoided as it cannot be applied to sensitive substrates
and is usually accompanied by formation of many undesired
products. As a result, silver(I) salts14–22 (particularly silver
benzoate) and photolysis23–32 have been the methods of choice.
In the case of silver salts, the main disadvantage is the cost and
need of high catalyst loadings (20–50 mol%). Experimental
protocols can also require slow addition of the catalyst and
heating for complete substrate consumption. For some
substrates, super-stoichiometric amounts or high loadings of
expensive silver salts must be employed, as described in the
works of Nicolaou33 and Burtoloso34 (Scheme 2, Charts A and B,
respectively).
Introduction
The Wolff rearrangement is a useful transformation in chem-
istry consisting of a 1,2-rearrangement from diazoketones to
ketenes.1–9 These ketenes, in the course of the reaction, can
react with various nucleophiles (Arndt–Eistert homologation) or
unsaturated compounds to provide carboxylic acid derivatives
or cycloadducts, respectively (Scheme 1). Discovered by Ludwig
Wolff in 1902,10 this rearrangement was not well explored until
Contrary to reactions with silver catalysts, photolysis benets
from mild reaction conditions and high yields of Wolff rear-
rangement products.1 However, a major limitation of photolysis
Scheme 1 General scheme for the Wolff rearrangement, showing its
application in synthesis.
a
´
˜
˜
˜
Instituto de Quımica de Sao Carlos, Universidade de Sao Paulo, CEP 13560-970, Sao
Carlos, SP, Brasil. E-mail: antonio@iqsc.usp.br
bDepartment of Chemistry and Biochemistry, The Ohio State University, 100 West 18th
Avenue, Columbus, Ohio 43210, USA
Scheme 2 Two examples that excess of the catalyst or expensive
silver salts need to be employed for the Wolff rearrangement to occur
satisfactorily.
† Electronic supplementary information (ESI) available: NMR data and copy of
spectra of all compounds. See DOI: 10.1039/c4ra15670f
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is the use of special medium- and high-pressure xenon and
mercury arc lamps. These lamps are expensive, energy
consuming, and emit large amounts of heat. A sustainable
alternative for the photochemical Wolff rearrangement utilizing
commercially available light sources has yet to be investigated
in great detail. Although two single examples24,29,35 are described
in the literature for the Wolff rearrangement employing a
compact uorescent lamp (CFL) in ow systems, to the best of
our knowledge, no study is described using light emitting diode
(LED) lamps. In the last few years, the use of LED lamps is
increasing exponentially as a durable and energy-saving light
source36 when compared to the traditional CFL and incandes-
cent lamps. The impact of LED lamps as a sustainable and
important source of light resulted in the 2014 Nobel Prize in
physics to Isamu Akasaki, Hiroshi Amano, and Shuji Nakamura
for the discovery of the blue LED light.
As a part of our ongoing studies in the chemistry of diazo-
ketones, we decided to investigate the outcome of the Wolff
rearrangement in the presence of LED light. Not only we will
demonstrate that these sources of light are efficient to carry out
this rearrangement, but also that this method can be applied to
several structurally different substrates under mild conditions
with practical execution in the laboratory.
Fig. 1 The use of different substrates and oxygen nucleophiles for the
Wolff rearrangement.
aer 24 h (entries 4 and 7, respectively). It is also worth noting
that while the CFLs caused considerable heating of the reaction
solution, this was not observed when the LED lamps were
employed.
Aer determining that the 18 W white LED lamp was the best
source of light to carry out the Wolff rearrangements, we eval-
uated the reaction between diazoketone 1 and various hydroxyl
nucleophiles. These included hindered isopropyl, t-butyl and
menthyl alcohols, as well as allyl alcohol, benzyl alcohol,
phenol, and water. As illustrated in Scheme 3, the reaction of 1
with all of these structurally different hydroxyl nucleophiles led
to isolated yields of the corresponding esters in the range of 63–
100%. Even when weakly nucleophilic phenol and highly
hindered t-butyl alcohol were used, a 63% yield was obtained for
compounds 8 and 4.
Results and discussion
We began our work by evaluating the ability of ve different
white CFL and LED lamps to perform the Wolff rearrangement
from diazoketone 1 in MeOH (Arndt–Eistert homologation) to
obtain methyl ester 2 (Table 1). Diazoketone 1 was chosen as a
model substrate since it is known to provide good results when
classical conditions for the Wolff rearrangement are
employed37,38 (entries 1 and 2, Table 1). This would permit a fair
comparison between the methods. As depicted in Table 1,
medium potency CFL and LED lamps are needed for total
consumption of 1 and to provide quantitative yields of ester 2
With the exception of water and solid nucleophiles, where a
solution of the nucleophile in ethyl acetate was employed, the
Table 1 Wolff rearrangement using CFL and LED lamps as the light source
Temperature of reaction
solution aer 24 h
Entry
Conditions
Color temperature
Yielda (%)
1 (ref. 37)
2 (ref. 38)
20 mol% AgOBz, Et3N, MeOH, 50 ꢀC, 1 h
300 W high pressure Xe arc lamp, 4 h
White CFL 15 W lamp, 24 h
White CFL 45 W lamp, 24 h
White CFL 25 W lamp, 24 h
White LED 5 W lamp, 24 h
—
63
98
65
92
83
10
100
0
—
6000 K
6500 K
6500 K
2700 K
2700 K
2700 K
—
30 ꢀC
38 ꢀC
40 ꢀC
39 ꢀC
27 ꢀC
27 ꢀC
27 ꢀC
3b
4b
5b
6b
7b
8b
White LED 18 W lamp, 24 h
Without lamp (blank)
a
Yields determined by NMR with 1,2,4,5-tetramethylbenzene as an internal standard. b 0.05 M in MeOH at 27 ꢀC. Reactions were carried out with 10
mg of 1.
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method could be applied to other nucleophiles as the experi-
mental procedure requires only the preparation of a solution of
the diazoketone and nucleophile. This new protocol avoids the
use of expensive and energy consuming Hg and Xe medium and
high pressure arc lamps as well as tedious experimental
procedures involving the use of expensive silver salts.
Experimental
General procedures for photochemical Wolff rearrangement
with LEDs
Method A: using alcohols as solvent.
Scheme 3 The photochemical Wolff rearrangement from 1 in the
presence of various oxygen nucleophiles.
reactions were carried out using the nucleophile as solvent.
Alcohols are claimed to be one of the greenest solvents39 and
could be easily recovered from the reaction in high purity.
During the course of this evaluation, another study revealed
that the concentration of the reaction solution is crucial for
high performance. For example, a 100% yield of 2 was obtained
when solutions in the order of 0.025–0.05 M were used, whereas
only 49% was obtained in a 0.5 M solution aer 24 hours.
However, longer reaction times (48 h) can permit the use of
more concentrated solutions. For the procedures employing
ethyl acetate as the solvent, 10 equivalents of the alcohol is
necessary to guarantee high yields of product.
Next, we decided to investigate the synthetic utility of this
photochemical method in the presence of other diazoketones.
Diazoketones 10–12 were prepared and irradiated with the 18 W
white LED lamp in the presence of several alcohols. For this
study, hindered-, aryl-, chiral- and amino acid-derived diazo-
ketones were employed, providing the corresponding esters and
acids 13–22 in 50–89% isolated yields (Fig. 1). It is well known
that a-amino acid-derived diazoketones are important precur-
sors for the preparation of b-amino acids and esters via the
Wolff rearrangement. Another point that deserves attention is
that no signicant change in the chemical yield was observed by
increasing the scale of the reaction. For example, experiments
with 0.2 and 2.0 mmol of diazoketone 11 furnished 81% and
78% of compound 13, respectively.
In a 4 mL vial, diazoketones (0.174 mmol) were dissolved in 3.5
mL of desired alcohol. The vial was closed with a cap and a
needle added (to vent the nitrogen gas formed during the
reaction). Next, the light yellow diazoketone solution was irra-
diated with a Philips Master LEDspot PAR 38 MV Dimmable (18
W, 2700 K, 50–60 Hz typ, 90 mA) lamp for 24 h under magnetic
stirring at room temperature (nitrogen gas evolution observed;
the solution tends to become colorless with the consumption of
the diazoketone). Aer the reaction was complete, the solvent
was removed with a rotary evaporator. Purication by ash
column chromatography afforded the ester products. The
schematic setup of the experiment is described above.
Method B: using ethyl acetate as solvent. In a 4 mL vial,
diazoketones (0.174 mmol) were dissolved in 3.5 mL of dry
EtOAc (MeCN can be also used as solvent) followed by the
addition of 10 equiv. of desired alcohol. The resulting solution
was irradiated with a Philips Master LEDspot PAR 38 MV
Dimmable (18 W, 2700 K, 50–60 Hz typ, 90 mA) lamp for 24 h
under magnetic stirring at room temperature (nitrogen gas
evolution observed). Aer the reaction was complete, the
solvent was evaporated in rotary evaporator. Purication, when
necessary, was performed by ash column chromatography to
afford the desired products.
Conclusions
Acknowledgements
In conclusion, we have demonstrated the use of simple,
commercially available LED lamps as a practical and sustain- We would like to thank FAPESP (Research Supporting Foun-
able alternative for carrying out Wolff rearrangements. This dation of the State of Sao Paulo) for nancial support (2013/
method is broad with respect to the alcohol nucleophile and 25504-1) and a fellowship to B.B. (2012/22274-2). We also
diazoketone providing moderate to excellent yields of the thank CNPq for a research fellowship to A.C.B.B. (301079/2012-
desired Arndt–Eistert homologation products. Moreover, this 9), IQSC-USP for facilities and NMR analysis.
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