Asymmetric atom economical

There are rather few reactions that can be described as fully atom economical , i.e. when there are no co-products and all the atoms in the starting material(s) appear in the product(s). However, all isomerisation reactions necessarily fall into this category. The use of a transition metal to catalyse such a process with an appropriate substrate brings the possibility of effecting asymmetric isomerisation, a very efficient method to generate enantiomerically enriched products. Indeed, the asymmetric Rh-catalysed isomerisation of an allylamine to an enamine, which proceeds in over 96% ee, was scaled up a number of years ago for industrial production. The enamine product forms a multi-tonne feedstock for menthol and perfumery synthesis. In contrast, the cyclo-isomerisation of dienes, an equally atom-economical process that generates synthetically useful cyclic products, has seen relatively little development despite the reaction having been known for some 30 years. 

Catalytic alcoholysis of silanes by a variety of transition metal based catalysts is a useful method to form silyl ethers under mild conditions (Scheme 19). The process is atom-economical hydrogen gas is the only byproduct. This mild method has not been fully exploited for the preparation of unsymmetrical bis-alkoxysilanes. A catalytic synthesis using silicon alcoholysis would circumvent the need of bases (and the attendant formation of protic byproducts), and eliminate the need for excess silicon dichlorides in the first silyl ether formation. We sought catalytic methods that would ultimately allow formation of chiral tethers that are asymmetric at the silicon center (Scheme 20). Our method, once developed, should be easily transferable for use with high-value synthetic intermediates in a complex target-oriented synthesis therefore, it will be necessary to evaluate the scope and limitation of our new method. 

Therefore, carbon-carbon bond forming reactions, asymmetric synthesis, the design of new chiral ligands, environmental-friendly reactions and atom economical syntheses are the major aims of present-day research. 

The Morita-Baylis-Hillman (MBH) reaction is an important 100% atom economic transformation that allows the formation in one step of a flexible allylic alcohol motif. Efforts in this field have been directed recently to the solution of two problems to enhance the generally sluggish reaction rate and to achieve asymmetric catalytic versions. Scheme 1.15 gives the catalytic cycle of the MBH reaction. The catalyst is a highly nucleophilic tertiary amine, generally DABCO, or a tertiary phosphine, which adds to the oc,P-unsaturated electrophile in a 1,4 fashion to deliver an enolate that, in turn, adds to the aldehyde. A critical step is the proton transfer from the enolizable position to the oxygen atom this process is catalysed by an alcohol that plays the role of a proton shuttle between the two positions. Water has also been reported to strongly speed up the reaction at a well-defined concentration. Moreover, the... 

The asymmetric insertion of a-diazoesters into the O—H bond of water provides an extremely simple approach for the synthesis of chiral a-hydroxyesters in an efficient and atom-economical way. The challenges of asymmetric O—H insertion of water are mainly attributed to two considerations first, the active metal carbene intermediates are generally sensitive to water and secondly, the small molecular structure of water makes chiral discrimination quite difficult. Zhou and co-workers discovered a highly enantioselective O—H insertion of water catalyzed by chiral spiro Cu [112] and Fe catalysts [111]. Under mild conditions, both Cu andFe complexes of ligand (S, 5,5)-23a... 

Our first approach, which looked very attractive, was based on a catalytic asymmetric hetero Diels-Alder reaction between butadiene and trityloxyacetaldehyde (Fig. 3). This reaction would have been highly atom economic, and if it could be done with a chiral catalyst, would lead directly to 2-(S)-trityloxymethyl-3,6-dihydro-2H-pyran 6 (Fig. 4) that could be used to make 1. There is a precedent in the literature for such a hetero Diels-Alder reaction, where benzyloxyacetaldehyde reacts... 

This unique asymmetric transformation has become one of the most efficient, practical, and atom-economical methods for the construction of chiral compounds from simple prochiral starting material.5 The transformation can offer either (R)- or (5)-stereoisomer, can have exquisite substrate-to-catalyst (S 1C) ratio (100,000 1), and by selecting the appropriate substrate and catalyst, generality can often exceed the merits of a biotransformation. Furthermore, the reaction can proceed with high turnover number (TON), turnover frequency (TOF), and enantiomeric excess (ee). The operations of the reaction,... 

Friedel-Crafts alkylation is one of the most frequently used and widely studied reactions in organic chemistry. Since the initial discovery by Charles Friedel and James Mason Crafts in 1877, a large number of applications have emerged for the construction of substituted aromatic compounds. Friedel-Crafts alkylation processes involve the replacement of C—H bond of an aromatic ring by an electrophilic partner in the presence of a Lewis acid or Bronsted acid catalyst. Particularly, catalytic asymmetric Friedel-Crafts alkylation is a very attractive, direct, and atom-economic approach for the synthesis of optically active aromatic compounds. However, it took more than 100 years from the discovery of this reaction until the first catalytic asymmetric Friedel-Crafts (AFC) alkylation of naphthol and ethyl pyruvate was realized by Erker in 1990. Nowadays, owing to continued efforts in developing... 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

Hydroamination is an atom-economical process for the synthesis of industrially and pharmaceutically valuable amines. The hydroamination reaction has been studied intensively, including asymmetric reactions, and a variety of catalytic systems based on early and late transition metals as well as main-group metals have been developed." However, Group 5 metal-catalysed hydroaminations of alkenes had not been reported until Hultzsch s work in 2011. Hultzsch discovered that 3,3 -silylated binaphtho-late niobium complex 69 was an efficient catalyst for the enantioselective hydroaminoalkylation of iV-methyl amine derivatives 70 with simple alkenes 71, giving enantioselectivities up to 80% (Scheme 9.30). Enantiomerically pure (l )-binaphtholate niobium amido complex 69 was readily prepared at room temperature in 5 min via rapid amine elimination reactions between Nb(NMe2)5 and l,l-binaphthyl-2-ol possessing bullqr 3,3 -silyl substituents. Since the complex prepared in situ showed reactivity and selectivity identical... 

The aza-Morita-Baylis-HiUman reaction is known to be a useful and atom-economical C-C bond-forming reaction of electron-deficient alkenes with imines usually catalyzed by Lewis bases [202]. It formally involves a sequence of reactions including a Michael addition, a Mannich reaction, a proton transfer, and a retro-Michael reaction ( -elimination). Although there are many reports in the field of the enantioselective aza-Morita-Baylis-Hilhnan reaction, only rare examples of asymmetric domino reactions initiated by this reaction have been reported. In 2010, Sasai et al. [203] developed the first organocatalyzed asymmetric domino aza-Morita-Baylis-Hillman/aza-Michael reaction of a,p-unsaturated carbonyl compounds with N-tosylimines, allowing an easy access to chiral cis-1,3-disubstituted isoindolines as single diastereomers. The process was induced by a Hg-BINOL-derived catalyst and provided these products in high yields and enantioselectivities, as shown in Scheme 10.18. 

Enantioselective 1,3-dipolar cycloaddition of imino esters to electron-deficient alkenes is one of the most powerful and atom-economical C-C bond-forming reaction that facilitates the synthesis of a range of structurally and stereochemically rich pyrrolidines [35]. Wang developed the asymmetric 1,3-dipolar cycloaddition of naphthalene-1,4-dione (116) with imino esters 117 catalyzed by the Cu(I) complex of ferrocenyl ligand 115, followed by silica-gel-promoted aromatization [39]. 

Halland N, Hansen T, Jprgensen KA (2003) Organocatalytic Asymmetric Michael Reaction of Cyclic 1,3-DicarbonyI Compounds and a,(3-Unsaturated Ketones - A Highly Atom-Economic Catalytic One-Step Formation of Optically Active Warfarin Anticoagulant. Angew Chem Int Ed 42 4955... 

X. Li, Y. Zhao, H. Qu, Z. Mao, X. Lin, Chem. Commun. 2013,49, 1401-1403. Organocatalytic asymmetric multicomponent reactions of aromatic aldehydes and anilines with P-ketoesters facile and atom-economical access to chiral tetrahydropyridines. 

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