Directing Metalation Groups DMGs

A list of common DMGs classified as carbon-based and heteroatom-based DMGs is shown in Table 26.2. DMGs generally provide nseful functionality for further transformation. A good DMG must be a good coordination site bnt a poor electrophile to prevent nucleophilic attack by the base. 

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According to NMR data, reaction of lithium tetramethylpiperidine (TMP) and t-Bu2Zn, in a 1 1 molar ratio (Scheme 6) affords the heteroleptic zincate [f-Bu2Zn(TMP)]Li (36) . An interesting feature of this compound is that it is capable of metalate arenes that contain a directing metalating group (DMG) in ortho-posilion and thus allow further derivatization by reaction of the zincate intermediate with electrophiles (E+). 

Certain derivatives of benzene and naphthalene can be lithiated with sec-butyllithium (sec-BuLi). This reaction is regioselective. It takes place exclusively in the ortho-position (Directed ortho Metalation, DoM) to a so-called Directed-Metalation Group (DMG), whose presence, accordingly, is a prerequisite for such a metalation. Figure 5.37 gives examples of DMGs that are bound through a C, an O, or an N atom to the aromatic compound. 

The concurrent and independent discovery of DoM by Wittig and Gilman over sixty years ago set the stage for the systematic work of Hauser, which was pursued in a number of laboratories in the late 1970s and has led to the current status of Directed Metalation Groups (DMGs), which allow the regioselective ortho introduction of a host of electrophiles (Scheme 2) [9a-c],... 

Substrate—Aromatic bromides or iodides (Ar-X) are rapidly converted to the corresponding aryllithium (Ar-Li) when treated with 1 molar equivalent of n-BuLi or 2 molar equivalents of (-BuLi. However, some substrates may rearrange to a more thermodynamically stable aryllithium via abstraction of a proton from a more acidic site, and this can lead to the formation of unwanted impurities (Scheme 12.5, eq. 2). Similarly, proton abstraction from aryl bromide substrates that contain an ortfto-directing metalation group (DMG) may lead to impurities in the final product. ... 

The discovery of the A-cumyl directed metalation group (DMG) for amides, 0-carbamates, and sulfonamides helps to broaden the scope of new DoM strategies. Synthetic utility is demonstrated by establishing viable routes to 4- and 4,7-substituted saccharin derivatives (eq 50). Thus, BuLi/TMEDA metalation of selected biaryl A -cumylsulfonamides followed by M(Y-diethylcarbamoyl chloride quench results in a regioselective functionalization (eq51). 

Quinn, R. M. (2002) Phosphorus-based directed metalation groups, DMGs Suzuki-Miyaura Cross coupling of di-t-butylphosphine oxide (P(0)t-Bu2) and development of di-t-butylphosphine sulfide (P(S)t-Bu2) for use as a DMG. M.Sc. Thesis. Queen s University, Canada. 

Lithiation ortho to functional groups of arenes followed by trapping with electrophiles is an appealing synthetic methodology. The directed ortho metalation (DoM) is the reaction of an alkyllithium compound with an arene bearing a direct metalation group (DMG) that leads to an ori/jo-lithiated intermediate. The abiHty of DMGs to effect the ortho metalation process... 

TABLE 26.2 Selected Directed Metalation Groups (DMGs)... 

Directed Metalating Group (DMG)-Asslsted C(sp )-H Activations Direct Arylation... 

Figure 11.1 Examples of directed metalation groups (DMGs).

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