Inherently complex,
lignin-derived aromatic monomers comprising
valuable structural moieties present in many pharmaceuticals would
serve as ideal substrates for the construction of biologically active
molecules. Here, we describe a strategy that incorporates all intrinsic
functional groups present in platform chemicals obtained by lignin
depolymerization into value-added amines, using sustainable catalytic
methods and benign solvents. Our strikingly efficient protocol provides
access to libraries of aminoalkyl-phenol derivatives and seven-membered
N-heterocycles directly from wood in two, respectively three, waste-free
steps. Several molecules in these libraries have shown promising antibacterial
or anticancer activities, emphasizing the advantage of this modular
synthetic strategy and the potential for drug discovery. The sustainable
catalytic pathways presented here can lead to significant benefits
for the pharmaceutical industry where reduction of hazardous waste
is a prime concern, and the described strategies that lead to high-value
products from non-edible biomass waste streams also markedly increase
the economic feasibility of lignocellulosic biorefineries.
Primary benzylamines are highly important
building blocks in the
pharmaceutical and polymer industry. An attractive catalytic approach
to access these compounds is the direct coupling of benzyl alcohols
with ammonia via the borrowing hydrogen methodology. However, this
approach is usually hampered by a series of side-reactions, one of
the most prominent being the overalkylation of the formed primary
amine. Herein, we describe a robust catalytic methodology, which utilizes
commercially available heterogeneous Ni catalysts and easy-to-handle
ammonia sources, such as aqueous ammonia or ammonium salts, for the
formation of primary benzylamines with good selectivity and scope.
Notably, our method enables the conversion of potentially lignin-derived
vanillyl alcohol to vanillylamine, which can be used to produce emerging
biobased polymers or as pharma building blocks. Important sugar derived
platform alcohols as well as long chain aliphatic primary alcohols
can be successfully aminated. Moreover, we provide an alternative,
sustainable route to p-xylylenediamine and m-xylylenediamine, important components of heat resistant
polyamides such as Kevlar.
A highly active and easy-to-prepare Ni based catalyst system is presented for the selective N-alkylation of amines with alcohols that is in situ generated from Ni(COD)2 and KOH under ligand-free conditions.
Summary
Lignin, the richest source of renewable aromatics on the planet, is an intriguing raw material for the construction of value-added aromatics. In the past decade, much progress has been made regarding the development of efficient lignin depolymerization methods, able to produce specific monophenol derivatives in high-enough selectivity and yields. This now serves as an excellent basis for developing powerful downstream conversion strategies toward a wide range of products, including fine chemical building blocks. The inherent structural features of lignin-derived platform chemicals undoubtedly inspire the development of novel, creative, atom-economic synthetic routes toward biologically active molecules or natural products. In this perspective we attempt to bridge the structural features of lignin-derived platform chemicals with existing synthetic strategies toward the construction of heterocycles and provide a summary of efforts for the production of natural products from aromatics that can be, in principle, obtained from lignin. Last, we comment on the latest efforts that present entire value-chains from wood to valuable pharmaceutically relevant compounds.
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