Intermolecular reactions scope

Almost all the crystalline materials discussed earlier involve only one molecular species. The ramifications for chemical reactions are thereby limited to intramolecular and homomolecular intermolecular reactions. Clearly the scope of solid-state chemistry would be vastly increased if it were possible to incorporate any desired foreign molecule into the crystal of a given substance. Unfortunately, the mutual solubilities of most pairs of molecules in the solid are severely limited (6), and few well-defined solid solutions or mixed crystals have been studied. Such one-phase systems are characterized by a variable composition and by a more or less random occupation of the crystallographic sites by the two components, and are generally based on the crystal structure of one component (or of both, if they are isomorphous). 

A variety of intramolecular (6,70) and Intermolecular (71) [2+2] cycloaddition reactions of distyrylbenzenes and related molecules have been reported. The intermolecular reactions are of interest due to the occurrence of photopolymerization both in solution and in the solid state. This topic has recently been reviewed (71) and is beyond the scope of this chapter. 

With the focus on green chemistry, it is actually impossible to think on an industrial chemical reaction, which involves transition metal complexes, that is not efficiently catalytic. The chemical industry demands atom economical reactions, that is, those in which substrates are transformed into products with the only aid of catalytic amounts of the rest of reactants. Although really catalytic PKR appeared only in the mid-1990s, developments from recent years allow us to be moderately enthusiastic. The literature gives a good deal of catalytic protocols that use different cobalt and other metal complexes. Still, a lack of scope is generally observed in these reports. In addition there are few examples of intermolecular reactions performed in catalytic conditions [21]. 

The intramolecular attack of an excited carbonyl on an alkene can occur to provide oxetane products, even in cases when the corresponding intermolecular reaction is imsuccessful. Thus the intramolecular reaction surely benefits from favorable entropic considerations. Jones and Carless have summarized the scope and utility of intramolecular Patemo-BUchi photocycloadditions. There is general agreement that successful implementation of an intramolecular reaction requires that the Norrish type II photoreactionsand other hydrogen abstraction processes be overcome. In addition, the intramolecular reaction provides access to polyoxygenated ring systems that can exhibit remarkable properties because of their strain. 

An intramolecular version of this process has been described, leading to bicyclic 2-pyrones. Diynes in which both alkyne functions are internal and are linked by three-, four- or five-atom chains cycloadd to carbon dioxide in the presence of catalytic Ni° and various trialkylphosphines (equation 51). Terminal diynes require stoichiometric metal and give lower yields, however. Extensive studies of ligand effects on yield and chemoselectivity have established a broad scope for the process and pointed out important practical differences between it and the intermolecular reactions described above. ... 

In conclusion, the ruthenium complexes are the best chiral catalysts developed so far with metals other than Cu and Rh. Excellent diastereo- and enanti-oselectivities were observed with some specific systems, but the scope of the intermolecular reaction is somewhat limited. 

After exploring intermolecular reactions, White and coworkers utilized complex Ll/Pd11 to catalyze the intramolecular oxidative cyclization of 4 to synthesize the macrolide 5 with moderate yield and good regioselectivity (Scheme 7) [23]. Further studies on substrate scope demonstrated that this catalytic system was compatible with various carboxylic acids as nucleophiles, such as aryl acids, vinylic and alkyl acids, leading to the generation of 14- to 19-membered macrolides with remarkable levels of selectivity. 

The scope is further expanded by using catalysts and 4 For example, it allows the preparation of trisubstituted alkenes by an intermolecular reaction for the first time, " and 1,5-cyclooctadienes (e.g., a precursor of aristeriscanolide "). The intramolecular version is a useful preparation of some other interesting molecules. ... 

VolLhardt and coworkers further investigated the scope of these [2+2+2] reactions [99]. They explored the intermolecular reactions between simple A-substituted indoles and diynes. With these substrates 263, the CpCo(CO)2 catalyst used above led only to diyne trimers and ohgomers, but no desired cycloaddition products. However, the use of CpCo(C2H4)2 led to the formation of the desired cycloaddition cobalt complexes in moderate yields. It is interesting to note the difference in reactivity observed for 263 when treated with unsubstituted and trimethylsUyl-substituted diynes (Scheme 70). While the use of unsubstituted 1,6-heptadiyne (264) failed to produce the desired cycloaddition product, the cycloaddition with 1-trimethylsilyl-1,6-heptadiyne (265) resulted in the formation of a single regioisomeric product 266 in 36% yield. In contrast, the reaction of 1,7-octadiyne (267) with 263 produced... 

With respect to the substrate scope, ketones are the most efficient nucleophiles although the intermolecular reaction works also well for esters, amides and Weinreb amides (Fig. 2.7). Regarding the Michael acceptor, enones are the best electrophiles with a wide range of substituents tolerated (alkyl, aryl and heteroaryl ketones). a,p-Unsaturated esters, in the case of the intermolecular cyclopropanation, and a,p-unsaturated diimides for the intramolecular reaction, extends the substrate scope of the process (Fig. 2.7). A transition state model for the intramolecular cyclopropanation reaction has been proposed as depicted in Scheme 2.38 for catalyst 65 [106d]. In this model the ammonium salt adopts a conformation that gives the Z-enolate of the nucleophile on deprotonation with the base. The intramolecular conjugate addition of the enolate then takes place through a boat-type transition state. 

Methods for lactone synthesis by transition metal catalysis involving C—O formation developed over the past 50 years have demonstrated much promise. Indeed, lactones have inspired the discovery of new organometallic transformations, design of metal catalysts, and detailed understanding of reaction mechanisms. Issues of waste minimization and stereoselectivity have been addressed. Future developments for chiral lactone synthesis will likely focus on establishing efficient transformations with broad scope and application in complex molecule total synthesis, especially in regards to macrolactonization where entropic costs often plague intramolecular reactivity with undesired intermolecular reactions. 

In 2012, Kim etal. [85] reported the intermolecular amidation of arenes with sulfonyl azides, which is a direct C-H process (Scheme 4.22). A cationic Rh complex was used in air. The application was showcased by the synthesis of 6-arylpurine derivatives, which show antimycobacterial, cytostatic, and anti-HIV activity. The reaction scope was successfully demonstrated. 

As indicated in Figure 1, the oxygen must diffuse from the aqueous phase through the emulsifier region and into the alkyd particle phase in order to initiate autoxidation. If the emulsifier is capable of retarding the diffusion of oxygen by radical stabilization or a formidable intermolecular reaction, then the crosslinking reaction by autoxidation is slowed. A total explanation of how emulsifiers retard the reaction is not within the scope of this research, but demonstration that the factor exists is clearly made here. 

Initial work in the early 1970s by Stetter and co-workers established the scope of the intermolecular reaction. Aromatic and heteroaromatic aldehydes are smoothly coupled to a,(3-unsaturated ketones, esters and nitriles under sodium cyanide or thiazolylidine catalysis (entries 1-5, 3a-d). In contrast, the coupling of aliphatic aldehydes and activated olefins (entry 6, 3e) is successful only under thiazolylidine catalysis. ... 

This realization led me to study related possible intermolecular electrophilic reactions of saturated hydrocarbons, Not only protolytic reactions but also a broad scope of reactions with varied electrophiles (alkylation, formylation, nitration, halogenation, oxygenation, etc.) were found to be feasible when using snperacidic, low-nucleophilicity reaction conditions. 

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