Ortho-functionalized arylboronic acids

The ready availability of ort/io-functionalized arylboronic acids by a direct ortho-metallation-boronation sequence (Scheme 2-45) provides a very useful synthetic link to the cross-coupling protocol. Snieckus has amply demonstrated that the sequence has considerable scope for the synthesis of unsymmetrical biaryls, heterobiaryls, and terphenyls [120]. 

Ortho lithiation of arenes directed by CONRj, OCONRj, OMOM, or NHCOR (Eq. 5), or the halogen-lithium exchange reaction (Eq. 6) provides various aryllithiums regioselectively. In situ treatment of these lithium intermediates with trimethyl- or tri(isopropyl) borate gives variously functionalized arylboronic acids. Trapping aryl-lithium or aryl-magnesium intermediates with trimethylchlorosilane, followed by transmetallation to BClj or is a convenient alterna-... 

The ready availability of ortAo-functionalized arylboronic acids by a metallation-boronation sequence provides a s)mthetic link to the crosscoupling protocol, which allows syntheses of various polycyclic heteroaromatics via cyclization between two ortho functionalities. The synthesis of arylboronic acids having an CONl 2 OCONEt2, NH Boc, or and their coupling with various... 

As first described by Krizan and Martin,6 the in situ trapping protocol, i.e., having the base and electrophile present in solution simultaneously, makes it possible to lithiate substrates that are not applicable in classical ortho-lithiation reactions.7 Later, Caron and Hawkins utilized the compatibility of lithium diisopropylamide and triisopropyl borate to synthesize arylboronic acid derivatives of bulky, electron deficient neopentyl benzoic acid esters.8 As this preparation illustrates, the use of lithium tetramethylpiperidide instead of lithium diisopropylamide broadens the scope of the reaction, and makes it possible to functionalize a simple alkyl benzoate.2... 

Figure 5.39 shows the preparation of an arylboronic acid as an example of the ortho-selective functionalization of an aromatic compound containing an O-bonded DMG. The LTArBlOMefj complex is generated and then hydrolyzed during workup. 

Fig. 5.39. Electrophilic functionalization ortho to an 0-bonded DMG preparation of an arylboronic acid.

Shi and co-workers have developed various types of C—H bond functionalization and C—C bond formation. Recently, they reported a novel transformation to realize ortho-arylation of acetanilides with trialkoxyarylsilanes through direct C—H functionalization (Equation 11.34) [72]. Furthermore, they also demonstrated a novel method for the direct construction of biaryl C—C bonds via Pd(II)-catalyzed cross-coupling of (hetero)arenes and various arylboronic acids [73]. Various aromatic rings show good selectivity, even without directing groups, under mild conditions. 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

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