Isonitriles, domino reactions

A very common combination in Pd-catalyzed domino reactions is the insertion of CO as the last step (this was discussed previously). However, there is also the possibility that CO is inserted as the first step after oxidative addition. This process, as well as the amidocarbonylation, the animation, the arylation of ketones, the isomerization of epoxides, and the reaction with isonitriles will be discussed in this section. 

In this protocol the pyridine- and the pyrrolidine-ring of 1 are built up in a one-pot radical domino reaction." Photolysis of iodopyridone 11 in the presence of hexamethylditin provides radical 56, which attacks the reactive isonitrile 15. The resulting radical 57 reacts with the alkyne group in a 5-exo-dig cyclization (see Chapter 11). Next, the newly formed vinyl radical 58 cyclizes onto the aryl ring generating speeies 59. Final oxidation via a so far unknown mechanism yields 1 with 31 % yield. For the generation of radical 56 by photolysis two ways (A and B) are possible. 

Multicomponent reactions have been described for several syntheses of imidazoles. Highly efficient methods for the syntheses of spiroimidazolinones via microwave-assisted three-component one-pot sequential reactions or one-pot domino reactions have been described <06JOC3137>. Multicomponent reactions between 2-aminopyrimidine, aldehydes and isonitriles afforded imidazo[l,2-a]pyrimidines <06TL947>. Two novel one-step microwave mediated syntheses of arrays of 3-iminoaryl-imidazo[l,2-a]pyridines and imidazo[l,2-a]pyridyn-3-ylamino-2-acetonitriles were synthesized by multicomponent reactions under microwave condition in methanol by simply mixing a-aminopyridines, aldehydes, and trimethylsilylcyanide catalyzed by polymer-bound scandium triflate <06TL2989>. 3-Aminoimidazo[l,2-a]pyridines have been synthesized via the multicomponent reaction of aldehydes, isocyanides and 2-aminopyridines in the presence of the ionic liquid l-butyl-3-methylimidazolium bromide [bmim]Br<06TL3031>. 

Curran s photocatalytically induced radical [4+1] annulation of phenyl isocyanide (13) and bromopyridone (14) represents the key step of the campto-thecin synthesis [80, 81]. The remarkable one-step synthesis of the tetracyclic heterocyclic system starts with photolytic cleavage of hexamethylditin to form the Me Sn radical, which then cleaves the C-Br bond in 14. This new radical reacts with the isonitrile carbon to form 15 which yields the final 16 via two subsequent radical intermediates (eq. (8)) (cascade or domino reaction [65, 66]). 

Curran and coworkers [141] developed a palladium(0)-catalysed domino process for the synthesis of the very potent anticancer natural product (S)-camptothecin (283) [142] and its analogues (Scheme 8.70). Camptothecin (283) contains an ll//-indolizino[l,2- ]quinolin-9-one skeleton, which is also found in mappicine [143] and the promising new analogue DB-67 (287) [144]. A domino-radical reaction has been used for its construction in 40-60% yield [145]. However, the product is also accessible from the isonitrile 284... 

Building on this chemistry, the same authors developed a novel four-component reaction of p-hydroxybenzaldehyde derivatives, benzylamine derivatives, fumaric acid monoethyl ester and isonitriles in water under microwave irradiation to give natural product-like 5,5,6-fused azaspiro tricycle systems 16 as the main products [11]. This transformation can be assmned to proceed through addition of a final aza-Michael step to the previously developed Ugi/Michael domino sequence, and generates six contiguous bonds and fonr stereogenic centres, including one... 

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