This mini-review describes the scope of the halogen-magnesium exchange. It shows that the use of turbo-Grignard reagent (iPrMgCl·LiCl) greatly enhances the rate of the Br- and I-Mg exchange. Furthermore, this magnesium reagent allows the performance of a fast sulfoxide-magnesium exchange. Also, the use of sBuMgOR·LiOR (R = 2-ethylhexyl) enables a Br/Mg-exchange in toluene leading to various Grignard reagents in toluene. Additionally, the new exchange reagent sBu₂Mg·2LiOR (R = 2-ethylhexyl) further increases the rate of the halogen-magnesium exchange allowing to perform a chlorine-magnesium exchange for aromatic chlorides bearing an ortho-methoxy substituent in toluene.

The alkylmagnesium alkoxide sBuMgOR⋅LiOR (R=2-ethylhexyl), which was prepared as a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides (ArMgOR⋅LiOR) in toluene. These Grignard reagents react with a broad range of electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides, epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu Mg⋅2 LiOR (R=2-ethylhexyl) undergoes Cl/Mg exchange with various electron-rich aryl chlorides in toluene, producing diorganomagnesium species of type Ar Mg⋅2 LiOR, which react well with aldehydes and allyl bromides.

Awide range of polyfunctional diaryl-and diheteroarylzinc species were prepared in toluene within 10 min to 5h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R' 2 Zn·2 LiOR (R' = sBu, tBu, pTol). Highly sensitive functional groups,s uch as at riazine, aketone,analdehyde,oranitro group,were tolerated in these exchange reactions,e nabling the synthesis of ap lethora of functionalized( hetero)arenes after quenching with various electrophiles.I nsight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type [R' 2 Zn-(OR) 2 Li 2 ].Organozinc reagents are key intermediates in organic synthesis as they tolerate many functional groups and readily participate in transition-metal-catalyzed carbon-carbon bond-forming reactions. [1] Aryl-and heteroarylzinc halides have been particularly widely used as organometallic reagents for preparing complex organic molecules. [2] Tw or ecently developed alternative synthetic strategies granting access to these valuable organometallics are the direct insertion of zinc powder into organic halides [3] and deprotonative metalation using TMP-zinc bases (TMP = 2,2,6,6-tetramethylpiperidyl). [4] Lithium alkylzincates such as "lower-order" R 3 ZnLi and "higher-order" R 4 ZnLi 2 have been shown to be able to promote halogen/zinc exchange reactions towards aryl halides. [5] Furthermore,anI/Zn exchange of aryl and heteroaryl iodides can be accomplished by adding substoichiometric amounts of Li(acac) to iPr 2 Zn in NMP. [6] Contrasting with the enhanced reactivity of these mixed-metal combinations, monometallic R 2 Zn reagents on their own fail to promote these type of transformations.Forp reparing related organomagnesium derivatives,t he exchange reagent iPrMgCl·LiCl ("turbo-Grignard") has been extensively used and leads to high rates of Br/Mg exchange. [7] This exchange can be accelerated further by replacing LiCl with as tronger donor additive,n amely al ithium alkoxide (ROLi;R= 2-ethylhexyl). Furthermore,t his exchange could be performed in the industrially friendly solvent toluene. [8] Opening new ground in this evolving area, we herein report an ew I/Zn and Br/Zn exchange in toluene based on the use of anovel bimetallic combination sBu 2 Zn·2 LiOR (1), which allows the generation of awide range of polyfunctional aryl-and heteroarylzinc reagents from the corresponding organic iodides or bromides.First, Et 2 Zn reacted in toluene with two equivalents of avariety of alcohols ROH(25 8 8C, 4h), affording the relevant ethylzinc alkoxides co-complexed with the corresponding alcohol (ROZnEt·ROH) of type 2. [9] These ethylzinc alkoxides (2)further reacted with sBuLi (2.0 equiv,inc yclohexane) to produce the bimetallic reagent tentatively represented as the trinuclear monozinc-dilithium complexes sBu 2 Zn·2 LiOR (1,s ee below). Removal of the solvents and subsequent redissolution in toluene provided al ight yellow solution of 1 (c = 0.6-1.0 m in toluene;S cheme 1), ...

A regioselective zincation of the 2-pyridone and 2,7-naphthyridone scaffolds has been developed. Zincations of the methoxyethoxymethyl (MEM)-protected compounds using TMPZn·2MgCl·2LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping with electrophiles provided functionalized 2-pyridones and 2,7-naphthyridones. I/Mg exchange of iodinated 2-pyridone and 2,7-naphthyridone using i-PrMgCl·LiCl afforded magnesiated intermediates that reacted with electrophiles. A second magnesiation of the 2-pyridone scaffold was achieved by using TMPMgCl·LiCl. Additionally, we report CoCl-catalyzed cross-couplings of the 1-chloro-2,7-naphthyridines with arylzinc halides.

CoCl (5%) catalyzes cross-couplings of various halogenated naphthyridines with alkyl- and arylmagnesium halides. Also, arylzinc halides undergo smooth cross-couplings with various naphthyridines in the presence of CoCl·2LiCl (5%) and sodium formate (50%), leading to polyfunctional arylated naphthyridines. Two of these arylated naphthyridines are highly fluorescent, with quantum efficiencies reaching 95% and long excited-state lifetimes of up to 12 ns.