Substrate Scope and Catalysts

Allylic substitution was initially conducted with palladium complexes lacking any added dative ligands or with palladium complexes containing classic aromatic phosphine ligands. More recently, catalyst development for this reaction has focused on the design and synthesis of new ligands for enantioselective allylic substitution processes. These ligands were presented as part of Section 18.6 on enantioselective allylic substitution. 

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Although much recent progress has been made with peptide catalysts, there is still room for improvement in terms of substrate scope and catalyst loading in the reaction systems discussed in this chapter. Undoubtedly, the full potential and power of peptide catalysis has not yet been realised. Thus, further discoveries of new peptide-catalysed transformations and further developments with this versatile type of organocatalysis are to be expected. 

The high-valent iron-oxo sites of nonheme iron enzymes catalyze a variety of reactions (halogenation and hydroxylation of alkanes, desaturation and cyclization, electrophilic aromatic substitution, and cis-dihydroxylation of olefins) [lb]. Most of these (and other) reactions have also been achieved and studied with model systems [Ic, 2a-c]. With the bispidine complexes, we have primarily concentrated on olefin epoxidation and dihydroxylation, alkane hydroxylation and halogenation, and sulfoxidation and demethylation processes. The focus in these studies so far has been on a thorough analysis of the reaction mechanisms rather than the substrate scope and catalyst optimization. 

After Akiyama et al. reported the first organocatalzyed inverse electron-demand aza-Diels-Alder reaction (Povarov reaction) between o-hydroxyaniline-derived imines and alkyl vinyl ethers [6], Liu et al. developed a three-component Povarov reaction of aldehydes 3, anilines 7, and benzyl A-vinylcarbamates 8a that efficiently afforded enantioenriched (2,4-c )-4-amino-l,2,3,4-terahydroquinoline 35 with a wild substrate scope (Scheme 2.9) [15a], Subsequently, a full study of the mechanism, substrate scope, and catalyst loading of this transformation was made, which revealed that this type of three-component Povarov reaction underwent a stepwise mechanism [15b]. Very recently, He, Shi, and others proved independently that the hydroxystyrenes 8b or 8c can also act as good dienophiles in asymmetric three-component Povarov reactions, thus providing efficient methods to access structurally diverse multisubstituted tetrahydroquinolines 35a or 35b in high stereoselectivities [16]. 

The metal-catalyzed [5 + 2]-cycloaddition reaction of VCPs and 7t-systems provides a new concept for seven-membered ring construction that has been significantly advanced over the last decade in the areas of catalyst development, chemo-, diastereo-, and enantioselectivity, substrate scope, and applications to total synthesis. 

These reports announced the rapid development of a large variety of monodentate ligands for rhodium-catalyzed enantioselective hydrogenation. It was shown that the substrate scope for catalysts based on monodentate ligands is most probably at least as big as for their bidentate counterparts. Also, initial doubts about the activity and stability of the monodentate ligand-catalysts have been taken away. Several reports show that substrate catalyst ratios (SCRs) of 103 or higher, essential for industrial application, are possible. In addition, reaction rates are in the studied cases comparable to those reached by catalysts based on state-of-the-art bidentate ligands [16]. 

Pyrrolidin-2-yltetrazole has been found to be a versatile organocatalyst for the asymmetric conjugate addition of nitroalkanes to enones.45 Using this catalyst, this transformation requires short reaction times, tolerates a broad substrate scope, and possibly proceeds via generation of an iminium species. 

This chapter will cover the recent developments in palladium-catalyzed amination of aryl halides and sulfonates. The nickel-catalyzed process requires much higher catalyst loads and has a more narrow substrate scope, and will not be reviewed [70,71]. The first sections will cover the development of different palladium catalysts for the... 

This method is comparable to similar, catalytic Sim-mons-Smith-type methods employing the titanium TADDOL catalyst 20 (95 5 er) or the Ci-symmetric bis-sulfonamide catalyst 32 (93 7 er) for the cyclopropanation of the allylic alcohol 22 (eq 6). However, due to the preliminary nature of these earlier investigations, substrate scope and generality have not been extensively documented. All of the aforementioned methods are limited by their dependence on the allylic alcohol functionality. Only one method for Simmons-Smith-type cyclopropanation of other substrate classes has been developed. Use of a stoichiometric, chiral dioxaborolane [CAS 161344-85-0] additive allows for selective cyclopropanation of allylic ethers, homo-ally lie alcohols and allylic carbamates. ... 

Later, Kiindig and coworkers extended the substrate scope of catalysts 24 and 25 from weso-l,4-diol complexes such as 26 to simple meso- 1,2-diols 28 [31c], In the presence of 2 mol% of the catalyst, all of the tested cyclic and acyclic 1,2-meso-diols, except for substrates incorporating phenyl groups, were efficiently desymmetrized to... 

Transition metal catalysts from across the periodic table have been investigated for this transformation. [56b, 57] Early transition metal catalysts [58] are of particular interest due to their high reactivities, with reduced air and moisture sensitivity compared with the rare earth metal systems, and lower cost and toxicity compared with the late transition metal catalysts. The A,0-ligands generating tight four-membered metallacycles described above have been studied as precatalysts for hydroamination methodologies that display promising substrate scope and reactivity. 

Enzymes are perfectly equipped to convert substrates into products in high enantio-, regio-, or chemoselectivity, a property that is commonly used in industry to prepare optically active fine-chemical intermediates [5]. More specifically, lipases appeared as ideal catalysts as a result of their high enantioselectivity, broad substrate scope and stability. In addition, lipases are powerful catalysts for the preparation of polyesters, polycarbonates and even polyamides, as is reviewed in Chapters 4 and 5 of this book. Moreover, a variety of different polymer architectures such as block copolymers, graft copolymers etc have been prepared using lipases as the catalyst (see Chapter 12). 

While in the presence of 0.5 mol% Sm(OTf)3-lc complex in CH2CI2, the absolute configuration of products 68 was reversed from (5) to (7 ) (Table 6.8). This highly efficient system also showed broad substrate scope and insensitivity to the electronic properties of the substituents. It should be noted that this catalytic protocol allowed the catalyst loading to be as low as 0.01 mol% without considerable loss in both reactivity and enantioselectivity. 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

It has been shown that the Lewis-acid nature of the Zr centres is key for this reaction. Zirconium-containing catalysts are amongst some of the most active heterogeneous catalysts for this process in the literature, with a wide substrate scope and water tolerance. Moreover, in recent years there has been a minirenaissance in the development of catalysts for the conversion of ethanol to butadiene - some of the most effective utilise Zr02, illustrating its importance in this area. ... 

Njardarson and coworkers successfully extended this methodology to rearrange vinylthiiranes to 2,5-dihydrothiophenes. The electrophilic Cu(hfacac)2 catalyst is not only efficient for dihydrothiophene formation but also effective for suppressing the desulfurization and 1,2-dithiine formation, highly competitive pathways that are usually observed with vinylthiirane substrates. This methodology has a broad substrate scope, and substituted 2,5-dihydrothiophenes can be synthesized in good to excellent yields f Scheme 11.58). 

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