Synthesis routes cross-coupling

The von Richter cinnoline process was further extended to solid-phase synthesis. The route began from benzylaminomethyl polystyrene and the required diverse o-haloaryl resins represented by 21 were prepared from substituted o-haloanilines. A Pd-mediated cross-coupling reaction with 21 and the alkynes provided the alkynylaryl derivatives represented by alkyne 22. The von Richter cyclization reaction with hydrobromic or hydrochloric acid in acetone/HaO and cleavage from the resin occurred in the same step to furnish the cinnoline derivatives 23 in 47-95% yield and 60-90% purity (no yield reported for each entry). 

The Cp Ti(amidinate) fragment provides a particularly useful platform for the synthesis of novel titanium imido complexes and the study of their unusual reactivity. Numerous single-, double-, and cross-coupling and imido-transfer reactions were investigated using these compounds. The synthetic routes leading to CpTi and Cp Ti amidinate derivatives are outlined in Scheme... 

The Suzuki cross coupling reaction features in a synthesis of 4-arylcoumarins from the 4-halogeno derivatives c96JCS(Pl)2591> and in a route to the thieno[3,4-c]coumarin (8) from which coumarin 3,4-quinodimethane (9) can be thermally generated <96T3117>. 

We have developed asymmetric syntheses of isocarbacyclin [3] (Scheme 1.3.2) and cicaprost [4] (Scheme 1.3.3) featuring a Cu-mediated allylic alkylation of an allyl sulfoximine [5-7] and a Ni-catalyzed cross-coupling reaction of a vinyl sulf-oximine [8-10], respectively, transformations that were both developed in our laboratories. The facile synthesis of an allyl sulfoximine by the addition-elimination-isomerization route aroused interest in the synthesis of sulfonimidoyl-sub-stituted aiiyititanium complexes of types 1 and 2 (Fig. 1.3.2) and their application as chiral heteroatom-substituted allyl transfer reagents [11]. 

Similarly, Torres et al. also reported the preparation of perylene-Pc assemblies 5 (Fig. 5). The synthesis of these triads was thereby accomplished via palladium-catalyzed cross-coupling pursuing two different routes [46], First preparing the perylenediimide with two bromine units in positions 1 and 7 and subsequent... 

Dichloropyridine reacts in the dark (88% of disubstitution), whereas 2,6- and 3,5-dichloropyridines require photostimulation to afford ca. 80% yield of disubstitution products [26]. Aryltrialkylstannanes are valuable intermediates in organic synthesis, and the fact that they can be easily synthesized through the SRN1 mechanism, opens up important synthetic routes to different reaction schemes. For over a decade, the Pd(0)-catalyzed cross-coupling of organotin compounds with electrophiles, known as the Stille reaction, has been a very important tool in product design [104]. 

This anionic remote Fries rearrangement provides a general route to highly substituted biaryls 146 which, due to steric effects, may be difficult to prepare directly by Suzuki-Miyaura cross-coupling, as evidenced in the comparison with the synthesis of dibenzopyr-anones 147 (Scheme 39) [66]. The efficient acid-catalyzed cyclization to dibenzopyranones shows broad scope both for unusually substituted (148-150, Scheme 40) and various heterocyclic analogues (151-153, Scheme 40) [65, 67]. 

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

Many other related but alternative routes to benzene derivatives are conceivable. One inter-intra cascade carbopalladation route which is potentially highly selective is shown in Eq. 1 of Scheme 46 [11]. Another proceeds via cyclic allenylpalladation of alkynes followed by cross-coupling with PhB(OH)2 [127] (Eq. 2 of Scheme 46). Yet another related process is the synthesis of naphthalene derivatives shown in Eq. 3 of Scheme 46 [128]. If the regioselectivity problem could be overcome, it would provide an attractive route to naphthalenes. 

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