Lewis‐Säure‐dirigierte regioselektive Metallierungen an Pyridazin

Abstract

Ein-oder zweizähnige Lewis-Säuren leiten eine regioselektive Magnesierung oder Zinkierung an Pyridazin in Position C3 (ortho-Produkt) oder C4 (meta-Produkt) ein. Die Regioselektivitätd er Metallierung wurde mithilfe der berechneten pK s -Werte von sowohl Pyridazin als auchden Pyridazin-Lewis-Säure-Komplexen erklärt.

Recent Advances of the Halogen–Zinc Exchange Reaction

“…[26] With this information at hand, the generation of dialkylzinc organometallics,c omplexed with lithium alkoxides were investigated. [27] 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, am ixed zinc species, tentatively described as [ROZnEt·ROH] (90)i so btained.…”

“…Upon addition of sBuLi (2.0 equiv), di-sec-butylzinc complexed with two lithium alkoxides of the formula sBu 2 Zn·2LiOR (91)i sp roduced (Scheme 13). [27] This exchange reagent is highly reactive towards iodine or bromine-zinc exchange reactions. Indeed,t he iodine-zinc exchange of 3-iodoanisole (92)i sc omplete after only 1minute, providing the diarylzinc 93 (Scheme 14).…”

“…Similarly,afunctionalized pyridine 95 or ap yridone derivative 96 are suitable substrates for this exchange reaction, leadingt oz inco rganometallics 97-98.A fter copper-mediated acylation or allylation, ketone 99 and lactam 100 are obtained in 85-96 %y ield (Scheme 14). [27] Since zinc organometallics possess ap articularly unreactive carbon-zinc bond, highly sensitivef unctionalg roups such as triazines, aldehydes, ketones or nitro-groups are tolerated. Unders tandard reaction conditions, an aryl iodide bearing a triazine functional group (101 a)i sc onverted to the diarylzinc 102 a and quenched with allyl bromide, providing 103 a in 72 %y ield (Scheme 15).…”

“…Unders tandard reaction conditions, an aryl iodide bearing a triazine functional group (101 a)i sc onverted to the diarylzinc 102 a and quenched with allyl bromide, providing 103 a in 72 %y ield (Scheme 15). [27] In some cases, slight modifications of the exchange reagent are required. Thus, when 2,4dinitroiodobenzene (101 b)i st reated with pTol 2 Zn·2LiOR (104, 0.6 equiv, À15 8C, 15 min), as mooth iodine-zinc exchange takes place, affording 102 b,w hich, after allylation, leads to the dinitroarene 103 b in 79 %y ield.…”

“…Hence, 5-iodo-2-furaldehyde (101 c)i s treated with the exchange reagent 105 (0.8 equiv,0 8C, 10 min), leading to biarylzinc 102 c.A fter an allylation, the furyl aldehyde 103 c is obtained in 66 %y ield (Scheme 15). [27] Finally,t he high reactivity of these alkoxide complexed dialkylzincr eagents allow ab romine-zinc exchange reaction. Therefore, various functionalized (hetero)aryl bromides (106 ad)a re treated with 91 (0.8 equiv,2 58C, 30 min-5 h), producing biarylzincs 107 a-d.A fter various electrophilic trapping reactions, ap lethora of functionalized arenes andh eteroarenes 108 a-d are obtainedi n6 0-77 %yield (Scheme16).…”