Lewis Acid Directed Regioselective Metalations of Pyridazine

Abstract

Mono‐ or bidentate boron Lewis acids trigger a regioselective magnesiation or zincation of pyridazine in position C3 (ortho product) or C4 (meta product). The regioselectivity of the metalation was rationalized with the help of calculated pKa values of both pyridazine and pyridazine/Lewis acid complexes.

Recent Advances of the Halogen–Zinc Exchange Reaction

“…In the course of our investigations towards the preparation of more efficient halogen–magnesium exchange reagents, it was found that the addition of alcoholates may drastically increase the reactivity of the halogen–magnesium exchange . With this information at hand, the generation of dialkylzinc organometallics, complexed with lithium alkoxides were investigated . When an aminoalcohol ROH ( 89 , 2.0 equiv, R=CH 2 CH 2 N‐(CH 3 )CH 2 CH 2 N(CH 3 ) 2 ),) is treated with Et 2 Zn in toluene, a mixed zinc species, tentatively described as [ROZnEt⋅ROH] ( 90 ) is obtained.…”

“…Upon addition of s BuLi (2.0 equiv), di‐ sec ‐butylzinc complexed with two lithium alkoxides of the formula s Bu 2 Zn⋅2LiOR ( 91 ) is produced (Scheme ) …”

“…Similarly, a functionalized pyridine 95 or a pyridone derivative 96 are suitable substrates for this exchange reaction, leading to zinc organometallics 97 – 98 . After copper‐mediated acylation or allylation, ketone 99 and lactam 100 are obtained in 85–96 % yield (Scheme ) …”

Regioselective functionalization of aryl azoles as powerful tool for the synthesis of pharmaceutically relevant targets

“…A potential approach to achieve a regioselective metalation at the aryl ring is the avoidance of coordinating solvents such as THF, which competes with the nitrogen atom of the azole ring in complexation of the base 25 . Sterically hindered metal-amide bases, especially magnesium-and zinc-derived TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) have proved to be powerful reagents for the functionalization of various (hetero)arenes [26][27][28][29][30][31][32][33] . The use of hindered metal amides in hydrocarbon solvents should thus be beneficial.…”

Lewis‐Säure‐dirigierte regioselektive Metallierungen an Pyridazin

“…Um die Regioselektivitätz ub estätigen, wurde eine Rçntgenstrukturanalyse von 10 c durchgeführt. [20] Basierend auf diesen Resultate untersuchten wir weitere Mçglichkeiten füre ine Lewis-Säure-dirigierte C4-Metallierung (meta-Produkt). Nach einigen Experimenten entschieden wir uns fürdas zweizähnige Diboranthracen 11,von dem Kaufmann erstmalig berichtete.…”