Modification cycloaddition reactions

Chapters 9, 10 and 11 describe methods for substitution directly on the ring with successive attention to Nl, C2 and C3. Chapters 12 and 13 are devoted to substituent modification as C3. Chapter 12 is a general discussion of these methods, while Chapter 13 covers the important special cases of the synthesis of 2-aminoethyl (tryptaminc) and 2-aminopropanoic acid (tryptophan) side-chains. Chapter 14 deals with methods for effecting carbo cyclic substitution. Chapter 15 describes synthetically important oxidation and reduction reactions which are characteristic of indoles. Chapter 16 illustrates methods for elaboration of indoles via cycloaddition reactions. 

Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed... 

The covalent methods previously discussed for fullerene modification using cycloaddition reactions also can be applied to carbon nanotubes. This strategy results in chemically linking molecules to the graphene rings on the outer surface of the cylinder, resulting in stable... 

In this paper we review the techniques and applications of microwave irradiation in cycloaddition reactions. This mode ofheating requires not only appropriate micro-wave equipment and glassware, but also a new experimental outlook. A special section will focus on modifications of chemo-, regio- and stereoselectivity which result from use of microwaves, and possible explanations of this behavior will be given. 

The ability of nitrile oxides to undergo addition and cycloaddition reactions makes it possible to use them in polymer chemistry and technology. Major trends might be synthesis, modification, cross-linking of polymers, addition of nucleophiles, and 1,3-dipolar cycloaddition of nitrile oxides. Taking into account the scarcity of reviews devoted to this topic, not only recent but also previous references will be cited in this subsection. 

Figure 9 (a) Protein modification with PEG through a copper-catalyzed cycloaddition reaction, (b) Protein modification with fluorescein through Staudinger ligation. 

Process Improvements. Phase 1 Benzene was replaced with a safer solvent, toluene, which was also used for the [2 + 2] cycloaddition reaction, thus facilitating the telescoping of the two reactions. However, dichloromethane was added during the work-up to prevent product precipitation. The product was ciystallized from 2-propanol in 80% yield. The phase I of development eliminated the use of benzene and allowed for telescoping of the two chemical steps. However, a solvent exchange from toluene-dichloromethane to 2-propanol was still needed to crystallize the product. The color of the product after this modification was dark-brown. 

An example of the second type of modification is the application of the Diels-Alder cycloaddition reaction to polders and copol ers containing pendant or backbone furan moieties. The use of bis-dienophiles such as propiolic acid and its esters or bis-maleimides provides a means of crosslinking based on multiple bridging by the double interchain lycloadditions. The thermal reversibility of these reactions allows the return to the original linear structure (thermoplastic material) by simply heating the gel. 

This modification is based on the consideration that such bidentate dienophiles would form rigid complexes with a chiral Lewis acid, resulting in high reactivity and a good level of TT-facial selectivity during the cycloaddition reaction. 

This is mainly due to their laborious purification procedures and their required chemical modification for solubilization. Only recently, Prato et al. reported the electrochemistry of carbon nanotubes functionalized using the 1,3-dipolar cycloaddition reaction.120 The cyclic voltammogram obtained is shown in Fig. 8.9. 

The high reactivity of dihydroazines enhances their ability to cause chemical modifications and to form new heterocyclic systems. The presence in 1,4-dihydropyridines of an enamine double bond increases their ability to cause cycloaddition reactions. 

Lantos et al. (68) suggested a modification of Hanaoka s mechanism where an imminium intermediate (143) would undergo a retrograde conjugate addition to a Schiff base (146). Its cycloaddition reaction via the enolate would produce the cis compound selectively. 

Fluorous aminoesters have been employed in 3-component 1,3-dipolar cycloaddition reactions and post-condensation modifications in the synthesis of a bridged-tricyclic ring system 30 (Scheme 21) [49]. 

In general, on chemical modification carbon nanotubes exhibit much less toxicity or nontoxicity to living cell lines that have been investigated so far.117,118 For instance, Dumortier et al. conducted an in vitro cell uptake study of the functionalized SWNTs with B and T lymphocytes and macrophages.117 Two types of functionalized SWNTs were used, one prepared via 1,3-dipolar cycloaddition reaction and the other obtained through oxidation/amidation treatment. Both types of the functionalized nanotubes were rapidly taken up by lymphocytes and macrophages without affecting the overall... 

Among the carbonylative cycloaddition reactions, the Pauson-Khand (P-K) reaction, in which an alkyne, an alkene, and carbon monoxide are condensed in a formal [2+2+1] cycloaddition to form cyclopentenones, has attracted considerable attention [3]. Significant progress in this reaction has been made in this decade. In the past, a stoichiometric amount of Co2(CO)8 was used as the source of CO. Various additive promoters, such as amines, amine N-oxides, phosphanes, ethers, and sulfides, have been developed thus far for a stoichiometric P-K reaction to proceed under milder reaction conditions. Other transition-metal carbonyl complexes, such as Fe(CO)4(acetone), W(CO)5(tetrahydrofuran), W(CO)5F, Cp2Mo2(CO)4, where Cp is cyclopentadienyl, and Mo(CO)6, are also used as the source of CO in place of Co2(CO)8. There has been significant interest in developing catalytic variants of the P-K reaction. Rautenstrauch et al. [4] reported the first catalytic P-K reaction in which alkenes are limited to reactive alkenes, such as ethylene and norbornene. Since 1994 when Jeong et al. [5] reported the first catalytic intramolecular P-K reaction, most attention has been focused on the modification of the cobalt catalytic system [3]. Recently, other transition-metal complexes, such as Ti [6], Rh [7], and Ir complexes [8], have been found to be active for intramolecular P-K reactions. 

Another modification of a cyclopentene moiety was achieved by the cycloaddition reaction of the 1,3-dithiolane derivative 483 with singlet oxygen O2 to form the endoperoxide 484, which upon treatment with either triethyl-amine, triphenylphosphine, or bromine gave the corresponding hydroxy ketone 485, a mixture of the epoxide 486 and the enonc 487, or a mixture of isomeric adducts 488 and 489, respectively (Scheme 69) <1995JOC1333>. 

Another modification of this cycloaddition reaction which leads to 3-monosubstituted aretidinoiiee is the use of l-etho alkynes as pre-oursors for the labile monoalkylketenes. At elevicted temperattirc.s the aoet enic ethera undergo Iragnientatioii to the aldoketene and... 

The cycloaddition reaction of oxyallylic cations was First reported by Fort during an apparent study of the Favorskii rearrangement." Since then, the research in this area has received increasing attention and several reviews have appeared in literature. One of the most exciting modifications is the use of cyclic oxyallyls in the 4+3 cycloaddition reaction, which allows an opportunity for creating more complicated and... 

---