Substrates for substitution reactions

Alkyl halides (RX) are good substrates for substitution reactions. The nucleophile (Nu ) displaces the leaving group (X ) from the carbon atom by using its electron parr or lone pair to form a new a bond to the carbon atom. Two different mechanisms for nucleophilic substitution are SnI and 8 2 mechanisms. In fact, the preference between S l and 8 2 mechanisms depends on the structure of the alkyl halide, the reactivity and structure of the nucleophile, the concentration of the nucleophile and the solvent in which reaction is carried out. 

Recent work has focused on the use of two specific reduced technetium centers as substrates for substitution reactions TcXg and TcOXi (X = Cl, Br). The chemistry of the TcOXij system has been developed principally by Davison and co-workers ( ). Both of these centers are synthesized from pertechnetate, the starting material for all radiopharmaceutical preparations (2,5), by simple HX reduction e.g.. 

Alkyl sulfonates are versatile substrates for substitution reactions... 

Strong acids promote SnI substitution reactions by converting an electron-rich ( basic ) atom on the substrate into a good leaving group, e.g., for substitution reactions of tert-butyl derivatives. 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

In some cases, the Q ions have such a low solubility in water that virtually all remain in the organic phase. ° In such cases, the exchange of ions (equilibrium 3) takes place across the interface. Still another mechanism the interfacial mechanism) can operate where OH extracts a proton from an organic substrate. In this mechanism, the OH ions remain in the aqueous phase and the substrate in the organic phase the deprotonation takes place at the interface. Thermal stability of the quaternary ammonium salt is a problem, limiting the use of some catalysts. The trialkylacyl ammonium halide 95 is thermally stable, however, even at high reaction temperatures." The use of molten quaternary ammonium salts as ionic reaction media for substitution reactions has also been reported. " " ... 

As we found that furan and thiophene substituted oximes can be used as substrates for the INOC reactions (Eq. 5) [29b] similarly, furan substituted nitro alkane 134 is also a good substrate for INOC reactions (Eq. 13) [40]. The furfuryl derivative 134, prepared via Michael addition of furfuryl alcohol to 4-methoxy- -nitrostyrene, was subsequently transformed without isolation of the intermediate nitrile oxide 135 to the triheterocyclic isoxazoline 136 as a 5 1 mixture of isomers in high yield. 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

The present method is successful with a wide variety of ketones (see Table). Cyclic ketones (entries 1-4, 8) produce benzoannelated products in excellent overall yields. There is no need to purify the intermediate both the nucleophilic addition of methallylmagnesium chloride and the aromatic cyclization take place cleanly. Acyclic ketones (entries 5-7) also provide high yields of benzoannelated product. Aromatic ketones are particularly interesting substrates for this reaction since they provide substituted biphenyls, which are potentially useful materials for liquid crystal synthesis and whose preparation through classical methodology is often not straightforward. The conditions for the cationic cyclization step can be modified to accommodate acid-sensitive functionality. For example, cyclization of 3 to 4, the latter a precursor for 3-methyl-8,14-dehydromorphinan, was accomplished in 77% yield by treatment of 3 at... 

Allene is a versatile functionality because it is useful as either a nucleophile or an electrophile and also as a substrate for cycloaddition reactions. This multi-reactivity makes an allene an excellent candidate for a synthetic manipulations. In addition to these abilities, the orthogonality of 1,3-substitution on the cumulated double bonds of allenes enables the molecule to exist in two enantiomeric configurations and reactions using either antipode can result in the transfer of chirality to the respective products. Therefore, the development of synthetic methodology for chiral allenes is one of the most valuable subjects for the synthetic organic chemist. This chapter serves as an introduction to recent progress in the enantioselective syntheses of allenes. Several of the earlier examples are presented in excellent previous reviews [ ] ... 

In the 1952 paper mentioned above [3], Gilman reported on the formation of lithium dimethylcuprate from polymeric methylcopper and methyllithium. These so-called Gilman cuprates were later used for substitution reactions on both saturated [6] and unsaturated [7, 8, 9] substrates. The first example of a cuprate substitution on an allylic acetate (allylic ester) was reported in 1969 [8], while Schlosser reported the corresponding copper-catalyzed reaction between an allylic acetate and a Grignard reagent (Eq. 2) a few years later [10]. 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

Other less oxophilic electrophiles give C-6 substituted coumarins, but it is unclear whether the substrate for such reactions is the free coumarin or a cation formed by protonation or bonded by a Lewis acid at the carbonyl oxygen. Some typical reactions are shown in Scheme 5.3. 

Reaction with dimethylphenylsilane is catalyzed at room temperature under 250 psi of carbon monoxide. Other silanes tested, triethyl- and triphenylsi-lane, are not effective reagents in this system. A variety of aldehydes are good substrates for the reaction, including benzaldehyde, substituted benzaldehydes, and heterocyclic aldehydes. Aliphatic aldehydes also yield a-siloxy aldehyde products, but the reaction must be run at higher CO pressure (1000 psi) to avoid hydrosilylation. The reaction does not tolerate substrates bearing strong electron-withdrawing substituents, such as p-nitrobenzaldehyde. 

A variety of geminally substituted cyclopropyl ethers are synthesized employing Fischer carbene complexes [(CO)5M=CR (OR2) M = Cr, Mo, W R1 = alkyl, alkenyl and aryl] as alkoxycarbene sources. Electron-deficient alkenes and conjugated dienes are suitable substrates for the reaction (equation 108)237-245. Electron-rich enol ethers and enamines are also... 

Nucleophilic Substitution. Silicon readily expands its valence shell, a property allowing organosilicon compounds to undergo nucleophilic substitution more easily than their carbon analogues. Chlorosilanes are the most common substrates for displacement reactions producing high yields of substitution products, even with weak nucleophiles under mild conditions ... 

The data in Table 18 summarize observations made for the reaction of a series of different oxygenated dienes with benzaldehyde in the presence of several different catalysts. Danishefsky s diene is only a moderate substrate for this reaction giving the pyrone 378 in 56 % ee. High induction for this substitution pattern can be obtained with the diene 379 and the trixylylsilyl substituted catalyst. An in-depth analysis of the effect of the nature of the silicon substituents on the catalyst were made for the reaction of diene 374. Larger substituents not only increase the amount of asymmetric induction, but also increase the yield, and the diastereoselectivity in favor of the cis product. Other BINOL ligands of type 99 (Sch. 47, R = H, Me, Ph) were examined they would only function stoichiometrically and gave less satisfactory results. 

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