Polyfunctional substrates

When applied to polyfunctional substrates, iron catalyzed reactions allow either for selective, exhaustive, or consecutive cross-coupling processes to be carried out in "one pot."... 

The Nef reaction was originally carried out under acidic conditions using strong acid such as aqueous HC1.1-3 However, the use of base followed by acid is incompatible with polyfunctional substrates in addition, some compounds are prone to undergo side reactions or fail to react, as discussed in the references.1-3 Thus, various modified methods have been developed, and they... 

Some of the reactions covered here are in principle also possible under strongly acidic or strongly basic conditions or as concerted pericydic reactions at high temperatures [3] for polyfunctional substrates in the synthesis of complex products the advantage of transition metal catalysis under neutral conditions and at low temperatures is obvious. 

The ability of diazomethane to replace hydrogen atoms in "iodic compounds like carboxylic adds, phenolB, and enolB has long been known. Although thw aspect need not be dealt with extensively h tv. it should be stressed that with a polyfunctional substrate diazomethauc can function at several reaction sites. Some discrimination therefore necessary in selecting this reagent for epoxide synthesis. 

Even the most experienced chemist will not be able to foresee all potential pitfalls of a synthesis, specially so if multifunctional, structurally complex intermediates must be prepared. The dose proximity or conformational fixation of functional groups in a large molecule can alter their reactivity to such an extent that even simple chemical transformations can no longer be performed [11]. Small structural variations of polyfunctional substrates might, therefore, bring about an unforeseeable change in reactivity. 

Although an almost completely perfect enantioselection has recently bei observed with photoreactions carried out in rigid media or in supramoleculjj assemblies, diastereoselective photoreactions in solution will remain a methcj of choice for synthetic applications. However, a great effort has still to be mai to improve the diastereodifferentiation of photorearrangement processes and f control the selectivity of photoreactions involving polyfunctional substrates. 

The principal advantage of the Mannich reaction is that it enables two different molecules to be bonded together in one step, as depicted in Eq. 1 (Fig. 3), whereas Eq. 2 stresses the alternatives connected with regioselectivity in polyfunctional substrates, which, on the other hand, also allow interesting cyclization or polymerization reactions to be performed. When the amino group is present in the substrate (Eq. 3), intramolecular Mannich reactions leading to cyclic products or to polymeric derivatives may occur. 

Finally, the Mannich reaction may be applied to the. synthesis of reactive amines used as crosslinking agents of epoxy resins. The process requires the availability of molecules possessing more than two NH groups, which are obtained by reaction of polyfunctional substrates with polyfunctional primary amines (oligomeric polyalkyle-ncamines, diamino cyclohexane, etc.) - (see also 422, Chap. Ill, C). 

Normal Mannich reaction employing three components (bi- or polyfunctional substrate,... 

Cyclization vfL Polyfunctional Substrate with Amine and Aldehyde... 

Larger alkyl groups are required when the Mannich base is used as an additive to fuels, lubricants, etc. In some cases the anticorrosion power is afforded by exhaustive aminomethylation of polyfunctional substrates with aliphatic amines, thus obtaining branched basic derivatives (see, e.g., 499, Sec. A. 1) that arc able to protect the material against acid corrosion.Detergent- (sec also 513, Table 38) and antioxidant - actions can be combined with the anticorrosion ability of certain additives to oils and fuels, although the undesired formation of emulsion or foam may be favored. 

A substantial number of polyfunctional substrates have been studied with lanthanide shift reagents. With two or more donor groups, there are several possible binding mechanisms for polyfunctional substrates. Binding of substrates to the lanthanide ion... 

While the methods needed to achieve any of these conversions are well developed and reliable, it would be sheer madness even to think about their direct application to polyfunctional compounds such as 213-218. The sequence of selective reactions indicated in the scheme is, of course, completely fictitious. Nevertheless, the real synthesis was carried out in full accord with this scheme, but only after the needed polyfunctional substrates were appropriately modified by a very judicial use of protecting groups (see Scheme 2.92). 

Initially, the Pauson-Khand reaction involved heating the substrate in a hydrocarbon solution at elevated temperatures and, as such, was not applicable to labile polyfunctional substrates. Later it was discovered that this cycloaddition could be greatly accelerated under the action of mild oxidants (morpholine... 

Success of the above-mentioned convergent pathways depended critically upon the employment of 1,2-enones as the key starting compounds capable of undergoing controlled Michael addition/enolate alkylation. Additional opportunities for elaboration of convergent strategies can also be generated from consideration of entirely different chemical reactions of polyfunctional substrates. As an illustration of the diversity of available options, we have chosen additional examples from the fast-growing area of the synthetic utilization of radical reactions. ... 

Alfonso I, Gotor V. Biocatalytic and biomimetic aminolysis reactions useful tools for selective transformations on polyfunctional substrates. Chem. Soc. Rev. 2004 33 201-209. 

A new synthetic route to bis-methylene analogues of triphosphate esters has been reported. Lithiated methaneselenophosphonate and methanethiophos-phonate anions can condense several times with polyfunctional substrates such as chlorophosphites and phosphoramidous chlorides prior to esterifica-tion/trans-esterification and selenation or oxidation. A water-soluble phos-phonate-functionalized phosphine ligand (361) has been prepared in eight steps... 

Furfural is easily produced from pentoses rich biomass by cyclodehydration. Various acidic reaction conditions have been applied [110, 111]. The precise order of the different dehydration steps is not known for certain. A plausible mechanism is depicted in Scheme 20 [112]. The worldwide production is currently about 300,000 tons per year. Thus, furfural is a low cost, polyfunctional substrate for the production of numerous bulk and fine chemicals. 

Linear adducts would be produced from monofunctional inputs whatever the number of components employed [Figure 5.2, reaction (a)]. If one aimed at developing multicomponent syntheses of heterocycles, one simple solution would then be the use of polyfunctional substrates since these imply an intramolecular reaction at a certain stage of the sequence, leading eventually to heterocydes [Figure 5.2, reaction (b)[. Some very simple functional groups such as cyanide and carbonic acid are bifunctional in nature, as in the Bucherer-Bergs reaction. 

Using the N-(co-alkynyl)-N-alkyl-a-isocyanoacetamide 41 as a polyfunctional substrate, three-component synthesis of the azaindoline 42 was developed. By simply heating a toluene solution of 41, a primary amine and an aldehyde afforded tricyclic compound 42 in good to excellent yield [32]. A possible reaction sequence that accounted for the formation of 42 is depicted in Scheme 5.13. The sequence involved (a) a three-component synthesis of oxazole 43, (b) intramolecular D-A cycloaddition... 

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