Iodine chemoselective activation

Another approach for the chemoselective and asymmetric iodination of unactivated C H bonds was reported with a palladium catalyst using a chiral auxiliary (Scheme 5.19). Excellent diastereoselectivities were induced by chelating the auxiliary to the palladium catalyst center followed by an electrophilic C—H activation and iodination. Studies showed that I2 acts as both the reactant and the activator to form the reactive catalyst precursor, Pd3(OAc)3. After the reaction was completed, the formed Pdl2 was precipitated from the solution and could be reused several times without losing reactivity and selectivity. 

Difficulties in preparing and handling complex bases, along with their exacting experimental conditions have limited their use. Kondo provided a solution to this with a report on the effectiveness of lithium di-ZerZ-butyltetramethylpiperidinozincate (TMP-zincate) as a highly chemoselective base [9]. It was determined that pre-complexation of LTMP 20 with di-zerz-butylzinc was required to generate the active species 21. The reaction with pyridine at room temperature was found to proceed smoothly to produce the 2-lithio species that could be treated with iodine to afford 2-iodopyridine 22. 

This very active, chemoselective, sterically hindered base was employed to seleaively zincate 3,6-dibromopyridazine (42) in >95% yield (Scheme 19). Subsequent transmetalation with CuCN-2LiCl followed by benzoylation with benzoyl chloride gave (3,6-dibromopyridazin-4-yl)(phenyl)methanone (43) in 86% yield (Scheme 19). Treatment with other electrophiles, such as iodine and allylic bromides, furnished the respective dibromopyridazines in good yields. 

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