Acyclic metalation routes

The chemistry of azomethine ylide 1,3-dipoles, especially that of acyclic azomethine ylides, has completely changed since 1978. Methods of generating azomethine ylides, which were seriously limited before then to the aziridine route (Section II,A) and the deprotonation route (Section II,D), have been much extended. New methods, such as the desilylation route (Section II,B), the tautomerization route (Section II,C), the decarboxylation route (Section II,E), the N-oxide route (Section II,F), and the N-metallation route (Section II,G), are now known and the types of azomethine ylides available have been widely expanded. 

Scheme 16.1 Metalation routes for acyclic aminocarbenes starting from amidinium (Y = NR R ) and related precursors (Y = OR SR, aryl, alkyl, silyl).

Oxazoline and thiazoline derivatives metalated at the 2-position can also be prepared by the combination of acyclic precursors, namely by the reaction of a-metalated isocyanides with ketones or thioketones (Scheme 141) [76LA183 77AG(E)339 79PAC1347]. Although this route is normally used to produce 2-unsubstituted derivatives via protonation, there is presumably no reason why other electrophiles could not also be utilized instead. 

Several examples of the use of (4a) catalyzed cross metathesis of protected allylic sugars, or vinyl substituted heterocycles or vinylated functional groups have been reported. Vinylphosphonate-linked nucleotide dimers were synthesized by cross metathesis using complex (4a), achieving products with E Z ratios of >20 1 in moderate to good yields (equation 17). A metal-mediated route to acyclic nucleosides developed by Agrofoglio and coworkers produced nucleosides in two steps from parent pyrimidines and purines. ... 

A useful metalation approach that has little precedent in cyclic carbene chemistry [18] is the use of 2-chloroamidinium or chloroiminium ions as precursors for acyclic carbene ligands. Fiirstner and coworkers prepared cationic Pd complexes of acyclic diamino-, aminooxy-, aminoarjd, and aminothiocarbenes by oxidative addition of chloroiminium precursors to Pd(PPhs)4 (route d. Scheme 16.1), an approach that was also effective for ADC-Ni complexes [19]. This route permits complexation of sterically nonhindered acyclic carbenes that would not be stable in the free state. Chloroamidinium precursors can be meta-lated without a change in metal oxidation state via lithium-halogen exchange followed by transmetalation (route e). This strategy has been successfully employed with Pd", Rh, and Ir [20]. 

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