Water plays an essential role in life processes, however its use as a solvent
has been limited in organic synthesis. Despite the fact that it is the cheapest,
safest and most non toxic solvent in the world, its presence is generally
avoided through the dehydrative drying of substrates and solvents. The use of
water as a medium for organic reactions is therefore one of the latest
challenges for modern organic chemists. The present Highlight presents a brief
selection of different organic reactions run in an aqueous medium from the
literature of the past two years. (S)-4-Oxopyrrolidine-2-carboxylic acid Chemical name An excellent review about stereoselective
organic reactions in water have been recently published (Chem. Rev.
2002, 102, 2751.
DOI: 10.1021/cr010122p).
1. Oxidations
Rao and co-workers report a new methodology for a high yielding (90-96%)
chemoselective oxidation of sulphides to sulphoxides using β-cyclodextrin and
N-bromosuccinimide (NBS), at room temperature, and under neutral
conditions. Chemoselectivity (no overoxidation to sulphones) is explained by the
formation of reversible host-guest complexes between the sulphoxide and
catalytic amounts of β-cyclodextrin (Tetrahedron Lett. 2005, 46,
4581.
DOI: 10.1016/j.tetlet.2005.05.011).
Using a chemoenzymic oxidation methodology, Tong and co-workers successfully
epoxidised water-soluble (81-93% yield) and lipophilic alkenes (60-99% yield).
Commercial Glucose Oxidase (GOx) is used to produce in situ hydrogen
peroxide via the enzymic oxidation of glucose. The addition of catalytic amounts
of sodium bicarbonate/manganese sulphate increases the rate and the yield of the
process. In the case of lipophilic alkenes, sodium dodecyl sulphate (SDS) was
used as a surfactant (Tetrahedron 2005, 61, 6009.
DOI: 10.1016/j.tet.2005.04.055).
a) water-soluble alkenes: Glucose (0.2 M), GOx (175
units/mL), O2, NaHCO3 (0.5 M), MnSO4 (0.1
mol%), pH 7.0 phosphate sol.; b) water-insoluble soluble alkenes:
same conditions plus SDS (5 mM).
A highly efficient (88-98% yield) aerobic oxidation of benzylic alcohols, to
the corresponding aldehydes or ketones, was developed by Hu and co-workers. This
is a
TEMPO (1)-catalysed system using DBDMH (2) and NaNO2
as co-catalysts (J. Org. Chem. 2005, 70, 729.
DOI: 10.1021/jo048369k).
2. Dehydrogenation, Hydrogenation, Halogenation and Dehalogenation
Savelli and co-workers developed a mild, high yielding (90%) protocol for the
dehydrogenation of primary amines to nitriles using NiSO4 as catalyst
and K2S2O8 as oxidant (a stable, cheap and easy
to handle salt) in an aqueous surfactant solution of dimethyldodecylamine N-oxide
(DDAO) (Eur. J. Org. Chem.
2005, 3060.
DOI: 10.1002/ejoc.200500047). 1166831-45-3 supplier
An asymmetric transfer hydrogenation of aromatic ketones using the
Noyori-Ikariya Ru-Tsdpen catalyst (3) is now reported by Xiao and
co-workers. The reaction proceeds with high yield (99%) and enantioselection
(85-97% ee) using an aqueous solution of formic acid and Et3N, in
which the amine acts as a pH modulator (pH 5-8). The catalyst was recycled more
than 10 times without loss in enantioselectivity (Angew. PMID:24458656 Chem. Int. Ed.
2005, 44, 3407.
DOI: 10.1002/anie.200500023).
a) ketone (1 mmol), 3 (0.012 mmol),
H2O (0.5 mL), Et3N (2.7
mmol), HCO2H (3.3 mmol), 40ºC.
Nano-palladium particles (ARP-Pd) supported on an amphiphilic
polystyrene-poly(ethylene glycol) (PS-PEG) resin was found to effect the
hydrogenation of styrene and cinnamic derivatives in high yield (81-99% yield).
Uozumi and co-workers found also that this catalytic system can be used in the
hydrodechlorination of chloroarenes (81-99% yield), providing a recyclable,
clean and safe protocol for the detoxification of aqueous pollutants (Org.
Lett.
2005, 7, 163.
DOI: 10.1021/ol047670k).
Stavber and co-workers used
Selectfluor® (4), a commercial, stable and
water-soluble fluorinating reagent, for the selective synthesis of a series of
vicinal fluorohydrins 5 (from phenyl substituted alkenes, 84-86% yield),
α-fluoroketones
6 (from ketones, 85-90% yield) and 7 (from 1,3-diketones or
β-ketoesters, 87-91% yield) and fluorodienones 8 and 9 (from
phenols, 74-78% yield) (Org. Lett.
2004,
6, 4973.
DOI: 10.1021/ol047867c).
Reaction conditions: substrate (1.05-2.1 mmol), 4 (1.1 mmol),
H2O/surfactant (5 mL, 0.05%), 60 ºC,
2-24 h.
3. Allylations
Using a recyclable electrochemical process (up to five cycles with excellent
yield), Zhang and co-workers (Org. Lett. 2005, 7, 1903.
DOI: 10.1021/ol050483h)
developed
a tin-mediated protocol for the allylation of aldehydes (95-100% yield).
a) graphite electrode (2.0 V), aldehyde (5 mmol), allyl
bromide (8 mmol), SnCl2 (10 mmol), H2O
(10 mL), r.t., 6-10 h.
4. Coupling of Acyl Chlorides and Alkynes
Ynones are obtained in high yields (51-99%) by coupling acyl chlorides and
alkynes in a new catalytic system, reported by Liu and co-workers, which uses
palladium, copper and a surfactant (sodium lauryl sulfate) in a basic aqueous
medium (Org. Lett. 2004, 6, 3151.
DOI: 10.1021/ol048789w).
a) acyl chloride (2 mmol), alkyne (1 mmol), PdCl2(PPh3)2
(2 mmol%), CuI (5 mmol%), K2CO3 (3 mmol), surfactant
(7 mol%),
H2O (1 mL), 65ºC, 4 h.
5. Heck Reaction
Regioselective diarylation (75-92% yield) and monoarylation of unsubstituted
(69-96% yield) and substituted (42-91% yield, E/Z 70/30-100/0)
α,β-unsaturated carbonyl compounds with aryl iodides is reported by Nájera and
Botella. Best results were obtained using the oxime-derived carbapalladacycle
catalyst 9 and Cy2NMe as a base (J. Org. Chem. 2005,
70, 4360.
DOI: 10.1021/jo0502551).
a) ArI (2 mmol), alkene (3 mmol), Cy2NMe (3 mmol), 9
(0.02-1 mol% Pd),
H2O (3 mL), 120 ºC, pressure tube, 3-23
h; b) ArI (1 mmol), alkene (1.5 mmol), Cy2NMe (1.5 mmol), 9
(0.1-1 mol% Pd), H2O (2 mL) 120 ºC,
pressure tube, 7-38 h; c) ArI (1 mmol), alkene (0.5 mmol), Cy2NMe
(1.5 mmol), 9 (0.1-1 mol% Pd),
H2O (2 mL), 120 ºC, pressure tube, 8-22
h. Cy= cyclohexyl.
6. Wittig Reaction
Bergdahl and co-workers published the first report in the literature describing
that Wittig reactions of stabilised (and poorly water-soluble) ylides with
aldehydes are unexpectedly accelerated in an aqueous media (Tetrahedron Lett.
2005, 46, 4473.
DOI: 10.1016/j.tetlet.2005.04.105).
a) aldehyde (1 mmol), ylide (1.2-1.5 mmol), H2O
(5 mL), 20-90 ºC, 5 min – 4 h. Troc= 2,2,2-trichloroethoxycarbonyl.
7. Mannich-type Reactions
Following an early report (J. Am. Chem. Soc. 2002, 124, 5640.
DOI: 10.1021/ja026094p),
Kobayashi and co-workers published an efficient (up to 94% yield) enantio- and
diastereoselective (syn/anti 8-92 to 92-8, 67-95% ee) protocol for
Mannich-type reactions of a hydrazono ester with silicon enolates in aqueous
medium. One example of a syn adduct from an (E)-silicon enolate
and two examples of
anti
adducts from (Z)-silicon enolates are reported (J. Am. Chem. Soc.
2004, 126, 7768.
DOI: 10.1021/ja048607t).
a) acyl hydrazono ester (0.4 mmol), silyl enol ether (1.2 mmol), ZnF2
(100 mol%),
10 (10 mol%), CTAB (0.02 mmol), H2O
(1.95 mL), 0 ºC, 20 h. CTAB= cetyltrimethylammonium bromide.
8. Intramolecular Diels-Alder Reaction
Taguchi and co-workers demonstrated that the intramolecular
Diels-Alder
reaction of 1,7,9-decatrienoate derivatives can be performed in an aqueous
medium (H2O–iPrOH 6:1) using
indium(III) triflate as a recyclable catalyst (3 runs reported without loss in
yield) to give the corresponding endo cycloadducts in good yield (up to 83%) (Tetrahedron
2005, 61, 7087.
DOI: 10.1016/j.tet.2005.05.062).
a) alkene (0.5 mmol), In(OTf)3 (20 mmol%),
H2O (6 mL), iPrOH (1 mL),
70-80ºC, 8-24 h.
9. Deprotection of Functional Groups
Methods for selective deprotection of functional groups are key tools for
organic chemists. The following examples, performed in water, open new
possibilities for the use of this challenging medium.
9.1 Acetates, Alkyl Ethers and Acetals
Deprotection of several acetates, alkyl ethers and acetals in aqueous media
were recently reviewed (Chem. Rev. 2004, 104, 199.
DOI: 10.1021/cr0200769)
and are
summarized in Table 1.
DOI: 10.1002/anie.199620561
DOI: 10.1055/s-2001-16073
DOI: 10.1016/0040-4039(94)88373-4
DOI: 10.1016/0040-4039(94)88373-4
DOI: 10.1055/s-2001-16073
9.2 Oximes and Imines
Konwar and co-workers (J. Org. Chem.
2005, 70, 1934.
DOI: 10.1021/jo0480287)
reported a simple protocol for the deprotections of oximes and imines under neutral
conditions (yields up to 90%) using a I2/surfactant/water system.
a) oxime or imine (1 mmol), I2 (20 mmol%),
H2O (15 mL), SDS (0.2 mmol), 25-40°C,
3.5-8 h.
