Grignard-type reactions metal activation

Conventionally, organometallic chemistry and transition-metal catalysis are carried out under an inert gas atmosphere and the exclusion of moisture has been essential. In contrast, the catalytic actions of transition metals under ambient conditions of air and water have played a key role in various enzymatic reactions, which is in sharp contrast to most transition-metal-catalyzed reactions commonly used in the laboratory. Quasi-nature catalysis has now been developed using late transition metals in air and water, for instance copper-, palladium- and rhodium-catalyzed C-C bond formation, and ruthenium-catalyzed olefin isomerization, metathesis and C-H activation. Even a Grignard-type reaction could be realized in water using a bimetallic ruthenium-indium catalytic system [67]. 

The conventional Grignard reaction (Fig. 2, route I) would generate both a stoichiometric amount of halide waste and a stoichiometric amount of metal waste. It also requires multistep synthesis of the halides. On the other hand, an alternative Grignard-type reaction via catalytic C-H activation in water (Fig. 2, route II) would preclude the use of flammable organic solvents and also avoid the wasteful process of drying them. Obviously, it would provide a cleaner solution for organic synthesis and provide a theoretical 100% atom-efficiency. 

It had remained the favourite metal for Reformatsky reactions though, and was utilized on and oflf for Grignard-type syntheses - preferably to be named Saytzeff reactions (see Sect. 1.2.4). In modern organic chemistry zinc has come back as the preferred metal in many different types of less traditional reactions, not least because of new developments in activating techniques to overcome its sluggishness in the initiation of such reactions. 

A simple synthetic route to compounds of the type R Mg(NR R ) is the reaction of equimolar amounts of MgR and a secondary amine, HNR R . By this method sterically hindered 1,3,6,8-tetra-t-butylcarbazole and diethylmagnesium in THF afford 52 as the bistetrahydrofuran adduct, and hexamethyldisilazane (HN(TMS)2) and "BuMg Bu in heptane form nonsolvated 53 [23]. Metalation of activated G-H groups by the amide bases Mg(TMP)2 (TMPH = 2,2,6,6-tetramethylpiperidine) or Mg(N Pr2)2 can also produce organomagnesium amides. Reactions of metal amide (MNR R (M = Li or Na)) with the appropriate Grignard reagent have been used to produce 54 [24] and 55 [25] (Scheme 3.31). 

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