Metal-free reactions

The use of substoichiometric amounts of organic molecules, which absorb hght and induce photochemical transformations by sensitization either by energy or electron transfer to reaction partners, is a weU-recognized strategy in organic photochemistry. Benzophenone derivatives have been widely used in this context. 

Since a few years, ruthenium- and iridium-based polypyridyl complexes are privileged photocatalysts in visible light photocatalysis. However, organic dyes should constitute a valuable alternative not only due to their relatively lower cost and wider availability but also by giving access to new transformations. The direct arylation of heteroarenes (e.g., furan, thiophene, and pyrrole) 

SCHEME 29.20 Photochemically sensitized radical tandem addition cyclization reaction. 

SCHEME 29 6 Photocatalytic access to phenol from boronic acid. 

Ninomiya, I., Yamauchi, S., Kiguchi, X, Shinohara, A., Naito, X (1974) J. Chem. Soc., Perkin Xrans 1, 1747-1751. 

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A water-mediated, transition metal free reaction ... 

The template effect has been recognized to show two or three aspects. The thermodynamic template effect involves the removal of a product from an equilibrium by stabilization of its metal complex (Scheme 29). This phenomenon has also been termed the equilibrium template effect,112 but some authors5 draw a distinction between these two types of effects. They reserve the equilibrium template effect for reactions which result in the formation of different products in the metal-assisted and metal-free reactions. 

The position of the equilibrium between imine and carbonyl may be perturbed by interaction with a metal ion. We saw in Chapter 2 how back-donation of electrons from suitable orbitals of a metal ion may stabilise an imine by occupancy of the jc level. It is possible to form very simple imines which cannot usually be obtained as the free ligands by conducting the condensation of amine and carbonyl compounds in the presence of a metal ion. Reactions which result in the formation of imines are considered in this chapter even in cases where there is no evidence for prior co-ordination of the amine nucleophile to a metal centre. Although low yields of the free ligand may be obtained from the metal-free reaction, the ease of isolation of the metal complex, combined with the higher yields, make the metal-directed procedure the method of choice in many cases. An example is presented in Fig. 5-47. In the absence of a metal ion, only low yields of the diimine are obtained from the reaction of diacetyl with methylamine. When the reaction is conducted in the presence of iron(n) salts, the iron(n) complex of the diimine (5.23) is obtained in good yield. 

Figure 5-79. Attempts to prepare the ligand of Figure 5-78 in a metal-free reaction of biacetyl with 2-aminoethanethiol are unsuccessful. The thiol sulfur is too nucleophilic, and attacks the imine in an intramolecular process.

A similar complexity of rearrangements is observed in the related compound 6.42, which is derived from the metal-free reaction of 2,6-diacetylpyridine with 1,2-diamino-benzene (Fig. 6-41). In this case, the steric interactions between the methyl groups and the... 

Complexes of Cr, W, Mo, Fe, Ru, V, Mn and Rh form stable, isolable arene if -complexes. Among them, arene complexes of Cr(CO)3 have high synthetic uses. When benzene is refluxed with Cr(CO)6 in a mixture of dibutyl ether and THF, three coordinated CO molecules are displaced with six-7r-electrons of benzene to form the stable i/fi-benzene chromium tricarbonyl complex (170) which satisfies the 18-electron rule (6 from benzene + 6 from Cr(0) + 6 from 3 CO = 18). Complex formation is facilitated by electron-donating groups on benzene, and no complex of nitrobenzene is formed. Complex formation has a profound effect on reactivity of arenes, and the resulting complexes are used in synthetic reactions. The metal-free reaction products can be isolated easily after decomplexation by mild oxidation using low-valent Cr. Cycloheptatriene also forms a stable complex with Cr(CO)3 and its synthetic applications are discussed below. 

An overview of some metal-free reactions, for example oxidation, amination, and halogenation, is given in Table 7. 

Yield of allenes 47a-e from sulfides unbranched in a-position to sulfur are moderate to high. However, a-branching to sulfur lead to lower yields (allenes 47f-h) and is accompanied by competing formation of sulfoxides by 0-transfer from oxaziridine 44. The metal-free reaction conditions allow synthesis of particularly sensitive allenes or those derived from sensitive sulfides... 

Organocatalysts are inexpensive, readily available, and nontoxic. The products are free from the contamination of metals, so various highly enantioselective, metal free reactions have been developed to obtain biologically active compounds based on... 

The macrocycle L1 [structure (1)] having an inner ring of 18-member atoms has been synthesized (as its metal complexes) by the use of large metal ions as templates for the [2 + 2] Schiff base condensation of two molecules of 2,6-pyridinedicarboxaldehyde with two molecules of 1,2-benzenediamine.2 The template action of the metal ion is evidenced by the observation that only oils or gums are obtained in metal-free reactions. When the Ba2+ ion (ionic diameter 2.84 A)2 is employed as template, the product complex has a 2 1 ligand metal stoichiometry (Part A), whereas, for the Ca2+, Sr2 or Pb2+ ions (ionic diameter 2.24, 2.52, and 2.58 A, respectively), the products have a 1 1 metal-to-ligand stoichiometry. Smaller metal ions are ineffective as templates for the synthesis of L1. 

Scheme 59 Metal-catalyzed cross-coupling and metal-free reactions...

Keywords Benzyne C-H functionalization Heteroaromatic A(-oxides Metal-free reactions Nucleophilic addition Organocatalyst Radical reactions... 

Another approach for organocatalytic C-H functionalization of heteroaromatic W-oxides has been reported by using in situ generated ammonium amides and C-nucleophiles (Scheme 29), which are introduced into heteroaromatics through a sequence of the addition and elimination steps to give a-substituted azines under metal-free reaction conditions. 

Metal-free reactions of alkynes via electrophilic iodocarbocychzations 12OBC8041. 

Provided it works (which is not always the case), this transition-metal-free reaction may be viewed as a greener alternative to traditional metal-catalyzed cyclopropanation protocols. 

A metal-free reaction of a-azidomethyl aryl ketones and dialkyl but-... 

The Li group described a potassium-tert-butoxide-mediated stereoselective addition of quinazolines to terminal alkynes, employing mild, transi-tion-metal-free reaction conditions, leading to the formation of the T-selective addition product in moderate-to-good yields (Scheme 47) (13OBC5908). 

Metal-free reactions represent a direct way to study the confinement effects induced by the nanotube itself. Few such reactions have been carried out within CNTs, but notable examples include the formation of linear structures, such as fuUerene [151] and fullerene epoxide oligomers [174], formation of DWCNTs from endohedral fiiUerenes encapsulated in SWCNTs [71,155,156], or from encapsulated ferrocene [165], graphene nanoribbons (GNR) [186,187], the transformation of [Fe(C6oMc5)Cp] into encapsulated C70 [157], or the transformation of adamantane [188] and functionalized diamantine [189] in carbon chains. 

Ligation of nitriles to a metal center changes features of the reaction mechanism. In the case of metal-free reactions, the mechanism is concerted and highly synchronous, that is, the reaction occurs in one step via formation of one cyclic flve-membered transition state (TS), and the changes of chemical bonds directly involved in the process take place simultaneously. The estimated degree of asynchronicity of the reactions between nitrones and uncomplexed nitriles is only 5-15% [43, 45-48]. In contrast, the coordination of nitriles to the metal (Pt or Pd) results in a dramatic increase of the reaction asynchronicity to 19-49%, and, in some cases, the TS of the reaction may become acyclic [47]. At the same time, the global mechanism of the DCA usually remains concerted. 

Two main factors affect the chemoselectivity (i) coordination of N=CR to a metal and (ii) nature of the substituents. In the case of metal-free reactions, the DFT calculations predict that the DCA of nitfones to N=CCH=CH2 or N=CC=CH should occur exclusively at the C=C or C=C bond [47], Coordination of these nitriles to Pt(II) and, in particular, to Pt(IV), dramatically facilitates the DCA at the C=N bond relative to that at the C=C/C=C bond. However, the reaction at the CC bond still remains more preferable. At the same time, the DCA to phenyl-substituted nitrile in the model complexes frany-[PtCl2(L)(N=CCH=CHPh)] (L = NCCHCH2, NCMe) takes place already at the C=N bond [47, 51], Such a switch of the chemoselectivity is accounted for by (i) the steric repulsion between the bulky Ph groups and (ii) the loss of conjugation in phenylnitrone and phenylcyanoalkene upon formation of the TS. Both these effects are more important for the CC than for CN additions and disfavor the reaction along the former channel. 

Azides Despite the practical importance of this reaction leading to tetrazoles (Route III, Scheme 13.1), the number of recent theoretical studies of the metal-assisted DCAs of azides (RN3, N3 ) to nitriles is limited. This reaction usually controlled by both types of the FMO interaction (HOMOdipoie-LUMOni iieand HOMO j,nie-LUMOactivation barrier (when n = 3) or inhibits the reaction by 1.8 kcal/mol (when n = 5). However, when nitrile or both reactants are coordinated to a metal (e.g., Zn(II) or Sn(IV)), the activation barrier decreases by 2-10 kcal/mol compared to the metal-free reactions [54, 55],... 

Antonchick s group [68] developed a PIFA-mediated unprecedented and efficient azidoarylation of alkenes which occurs under mild and metal-free reaction conditions and provides a general approach to the synthesis of biologically interesting 2-oxindoles 93 (Scheme 22). In order to demonstrate the potential of the methodology, the authors performed several post-synthetic transformations of the... 

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