Key words
coupling - catalysis - green chemistry - solvents - biomass
Fine chemicals are desirable targets within the modern chemical industry. Their synthesis
often entails a series of intricate steps for the sequential formation of C–C, C–H
and C–X bonds, including stereoselective transformations, protection/deprotection
protocols, and extensive purification procedures. Such processes demand considerable
investments of time, energy, and auxiliary resources. Consequently, the resultant
manufacturing procedures frequently do not meet the sustainability standards required
for large-scale development.
The search for green methodologies, oriented towards optimizing synthetic procedures,
represents a continual objective of current research. In this context, catalysis offers
a promising opportunity for simplifying the synthesis of target molecules. The research
efforts in this domain have already produced significant fruit, with virtually all
organic reactions now featuring catalytic variants that offer notable advantages in
terms of energy and materials consumption.
Nonetheless, many catalytic processes of paramount synthetic importance encounter
constraints due to their reliance on solvents possessing specific physicochemical
properties. Often, these solvents come burdened with unfavorable attributes stemming
from their production methods, hazardous nature, toxicity, and environmental impacts.
Polar aprotic solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO)
and acetonitrile serve as illustrative examples; albeit indispensable in reactions
that form C–C, C–H and C–X bonds, they are accompanied by one or more of the aforementioned
unfavorable attributes. The significance of these drawbacks is underscored by the
actions of numerous manufacturers that have introduced their own guidelines and are
promoting greener options in the market.
New types of solvents have been proposed, with structures and functions focused on
sustainability and reducing the environmental impact of chemical reactions. These
have been termed ‘neoteric’ solvents. They often originate from residual biomass,
e.g., through the refinement and conversion of lignocellulosic fractions. Examples
include γ-valerolactone (GVL), ethyl lactate (EL), and Cyrene™. Alternatively, some
are derived from oily fractions of plants or fruits, such as limonene. Additionally,
new solvents of non-biomass origin have been proposed, such as methyl tert-butyl ether (MTBE) and tert-amyl alcohol.
Academic researchers are actively involved in demonstrating the applicability of these
alternative solvents in key catalytic processes of synthetic relevance, often claiming
their synthetic advantages over traditional ones, and their versatility across a broader
spectrum of chemical transformations.
Our research group is deeply engaged in this emerging field of research. We have recently
introduced a novel class of solvents obtained through the ketalization of lactic acid,
and have showcased their efficacy in both the Heck reaction and in energy storage
applications.
Considering the above information, this Graphical Review aims to thoroughly examine
the primary findings related to the utilization of neoteric solvents (Figure [1]) in catalyzed coupling reactions. The exclusion of established solvents, such as
ethanol and ethyl acetate, is intentional since their widespread use does not classify
them as neoteric. The insights gained from this systematic investigation underscore
the fact that further steps are being taken towards the full adoption of the principles
of green chemistry.
Figure 1 Solvents collection[1`]
[b]
[c]
[d]
[e]
[f]
[g]
[h]
[i]
[j]
[k]
[l]
[m]
[n]
[o]
[p]
[q]
[r]
[s]
[t]
[u]
Figure 2 Suzuki coupling in EL[2a]
[b]
Figure 3 Suzuki coupling in 2-MeTHF (part 1)[3]
Figure 4 Suzuki coupling in 2-MeTHF (part 2)[4a] and eucalyptol[4b]
Figure 5 Suzuki coupling in Cyrene™ (part 1)[5]
Figure 6 Suzuki coupling in Cyrene™ (part 2)[6a] and PC[6b]
Figure 7 Suzuki coupling in DMI[7a] and GVL[7b]
Figure 8 Suzuki coupling in i-PrOAc[8a]
[b]
Figure 9 Olefin metathesis in 2-MeTHF[9`]
[b]
[c]
Figure 10 Olefin metathesis in EL[10a] and 4-MeTHP (part 1)[10b]
Figure 11 Olefin metathesis in 4-MeTHP (part 2)[10b] and p-cymene[11]
Figure 12 Ring-opening metathesis polymerization (ROMP) in 2-MeTHF[12a]
[b]
Figure 13 C–H activation in 2-MeTHF (part 1)[13a]
[b]
Figure 14 C–H activation in 2-MeTHF (part 2)[14`]
[b]
[c]
Figure 15 C–H activation in 2-MeTHF (part 3)[15`]
[b]
[c]
[d]
Figure 16 C–H activation in 2-MeTHF (part 4)[16a] and GVL (part 1)[16b]
[c]
Figure 17 C–H activation in GVL (part 2)[17a]
[b]
Figure 18 C–H activation in GVL (part 3)[18a] and CPME (part 1)[18b]
Figure 19 C–H activation in CPME (part 2),[18b] eucalyptol[4b] and DEC[18b]
Figure 20 C–H activation in p-cymene[19`]
[b]
[c]
[d]
[e]
[f] and Heck reactions in GVL (part 1)[19g]
Figure 21 Heck reactions in GVL (part 2)[20`]
[b]
[c]
Figure 22 Heck reactions in GVL (part 3)[20c] and Cyrene™[21]
Figure 23 Heck reactions in DMI,[5] PC and EC,[22a] LA-H,H[22b] and other neoteric solvents (part 1)[22c]
Figure 24 Heck reactions in glycerol-based solvents[23a] and Heck–Cassar/Sonogashira coupling in pyrrolidone solvents[23b]
Figure 25 Heck–Cassar/Sonogashira coupling in HEP,[24a] DMI[5] and GVL,[24b] and Hiyama coupling in GVL[24b]
Figure 26 Buchwald–Hartwig coupling in 2-MeTHF (part 1)[25a]
[b]
Figure 27 Buchwald–Hartwig coupling in 2-MeTHF (part 2)[26a]
[b]
Figure 28 Buchwald–Hartwig coupling in 2-MeTHF (part 3)[27]
Figure 29 Buchwald–Hartwig coupling in CPME (part 1)[28a]
[b]
Figure 30 Buchwald–Hartwig coupling in CPME (part 2)[29]
Figure 31 Buchwald–Hartwig coupling in CPME (part 3)[30a]
[b]
Figure 32 Buchwald–Hartwig coupling in CPME (part 4)[31a] and eucalyptol[31b]
Figure 33 Buchwald–Hartwig coupling and pyridine dearomatization in CPME, 2-MeTHF and eucalyptol[30b]
[32]
Figure 34 Chiral neoteric solvents that induce asymmetry in coupling reactions[33a]
[b]
Figure 35 General conclusions
