Triarylborane catalysed n-alkylation of amines with aryl esters

The ability of halogenated triarylboranes to accept a lone pair of electrons from donor substrates renders them excellent Lewis acids which can be exploited as a powerful tool in organic synthesis. Tris(pentafluorophenyl)borane has successfully demonstrated its ability to act as a metal-free catalyst for an ever-increasing range of organic transformations. Herein we report the N-alkylation reactions of a wide variety of amine substrates including diarylamines, N-methylphenyl amines, and carbazoles with aryl esters using catalytic amounts of B(C6F5)3. This mild reaction protocol gives access to N-alkylated products (35 examples) in good to excellent yields (up to 95%). The construction of a C–N bond at the propargylic position has also been demonstrated to yield synthetically useful propargyl amines. On the other hand, unsubstituted 1H-indoles and 1H-pyrroles at the C3/C2 positions afforded exclusively C–C coupled products. Extensive DFT studies have been employed to understand the mechanism for this transformation

Turning renewable feedstocks into a valuable and efficient chiral phosphate salt catalyst

Solketal, the chiral acetonide of glycerol, has been employed as the starting material in the design of a novel punctually chiral phosphate sodium salt for catalytic applications in organic and asymmetric synthesis. The racemate and the two enantiomers of the substrate are economic and commercially available, straightforwardly prepared in high yields from naturally occurring feedstocks. Therefore, remarkably, both enantiomers of the final catalyst can be synthesized by simple procedures in high yield and in compliance with several principles of green chemistry. To further demonstrate the usefulness of the novel catalyst, its application in a solventless protocol for cyanohydrin synthesis from a series of aldehydes has been presented

An autonomous chemically fuelled small-molecule motor

Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.</p

Diverse exploitation of Br\uc3\ub8nsted acid catalysts-paving the way for simple access to enantioenriched amines

Recent advances in the catalytic enantioselective synthesis of primary and secondary amines are highlighted. These reactions are promoted by chiral Bronsted acid catalysts, which maintain their activity even in the presence of basic amine products. More in detail, a conceptually new approach to the kinetic resolution of racemic amines, based on a condensation process, and two transfer hydrogenation reactions of rarely employed N-alkyl and N-H ketimines with Hantzsch esters, are summarised in this article

Industrial Relevance of Asymmetric Organocatalysis in the Preparation of Chiral Amine Derivatives in Methodologies in Amine Synthesis (Eds.: A. Ricci, L. Bernardi)

This chapter covers the emerging utilization of organocatalytic methodologies in industrial settings directed at the large-scale preparation of enantioenriched amines and N-heterocycles. First, some selected manufacturing processes, based on organocatalytic stereodetermining steps, are commented concisely. Despite the generally high catalyst loadings required, these examples show that the relatively low cost of organic catalysts makes the development of cost-effective industrial routes possible. Then, three case studies (pregabalin, the bicyclic core of telaprevir, and 5-(trifluoromethyl)-2-isoxazolines) are discussed. These chiral targets have been approached through a variety of enantioselective strategies, among which the organocatalytic ones stand out for their versatility and potential for scale-up. Recent applications of organocatalysis in industrial settings are not restricted to a single activation mode or a class of catalysts. They encompass the whole catalyst and reaction repertoire typical of this relatively novel catalytic approach to asymmetric synthesis. Asymmetric organocatalysis proves to be, therefore, a useful and versatile synthetic tool for the industrial preparation of chiral compounds

A technology platform to chiral amines: selected examples in asymmetric organocatalysis

Organocatalysis makes use of small organic molecules to activate reaction partners and is nowadays an established catalytic platform; in fact, despite the relatively young age, its potential and powerful impact is widely appreciated. Importantly, organocatalysis, along with metal- and biocatalysis, is routinely screened in industry during the selection process to target compounds of interest. Among these, chiral amines are one of the most important class of target molecules in industry. Herein we present selected approaches in organocatalysis to access chiral amines both from academia and industry

Boron-Based Lewis Acid Catalysis: Challenges and Perspectives

In the last two decades, boron-based catalysis has been gaining increasing traction in the field of organic synthesis. The use of halogenated triarylboranes as main group Lewis acid catalysts is an attractive strategy. It has been applied in a growing number of transformations over the years, where they may perform comparably or even better than the gold standard catalysts. This review discusses methods of borane synthesis and cutting-edge boron-based Lewis acid catalysis, focusing especially on tris(pentafluorophenyl)-borane [B(C6F5)3], and other halogenated triarylboranes, highlighting how boron Lewis acids employed as catalysts can unlock a plethora of unprecedented chemical transformations or improve the efficiency of existing reactions

Boron-Based Lewis Acid Catalysis: Challenges and Perspectives

In the last two decades, boron-based catalysis has been gaining increasing traction in the field of organic synthesis. The use of halogenated triarylboranes as main group Lewis acid catalysts is an attractive strategy. It has been applied in a growing number of transformations over the years, where they may perform comparably or even better than the gold standard catalysts. This review discusses methods of borane synthesis and cutting-edge boron-based Lewis acid catalysis, focusing especially on tris(pentafluorophenyl)-borane [B(C6F5)3], and other halogenated triarylboranes, highlighting how boron Lewis acids employed as catalysts can unlock a plethora of unprecedented chemical transformations or improve the efficiency of existing reactions