Benzoxazole directing-groups

Wu has shown that benzoxazole moiety can efficiently serve as the directing group under conditions similar to those developed in [48, 72], Reactions proceed best in refluxing trifluoroacetic acid and require the presence of silver acetate as the halide removing agent (Scheme 19). 

Lahm G, Opatz T (2014) Unique regioselectivity in the C(sp )-H oi-alkylation of amines the benzoxazole moiety as a removable directing group. Org Lett 16 42014-203... 

With Palladium Ackermans group [90] has been active in this area. In 2012, they reported a palladium-catalyzed direct C-H bond alkynylation of heteroarenes using ge/w-dichloroalkenes [90b]. The substrates used were oxazole, benzoxazole, and benzothiazole, and the catalyst formed from Pd(OAc)2 and the ligand Bis-[2-(diphenylphosphino)phenyl]ether (DPEPhos) (Figure 4.46). The scope was excellent, the procedure being tolerant of lots of functional groups. This method allowed for step-economical, environmentally benign, and direct functionalizations of various heteroarenes. 

The use of nonactivated secondary alkyl halides as electrophiles in a copper-catalyzed direct alkylation of benzoxazoles has been described. Although methods exist for the direct alkylation of aromatic heterocycles, such as radical alkylations " and coupling of heterocycles with alkyl electrophiles, such methods are restricted to the incorporation of primary alkyl groups only. Secondary alkyl groups can be introduced by metal-catalyzed hydroarylation of olefins but in these cases examples are usually confined to activated alkyls such as benzyl or allyl. 

Newman et al. reported an approach to 2-bromobenzofurans using an intramolecular copper catalyzed C—O coupling of gm-dibromovinyl phenols (Scheme 24.29, disconnection D-2 and Scheme 24.31) [115]. This process is directly analogous to their palladium-catalyzed route to indoles via gem-dihalovinylaniline precursors (Scheme 24.3). Like the indole synthesis, further development of this chemistry has focused on harnessing the synthetic potential of the second bromine atom. To this end, several research groups have reported routes incorporating a tandem direct arylation leading to 2-aryl [116] and heteroaryl [27,117] benzoxazoles. 

Very recently, Gu, Li, and coworkers described an iron-catalyzed tandem oxidative process for the synthesis of benzoxazoles from easily available substrates, in which an alkyl C(sp )-H bond adjacent to an oxygen atom was directly aminated with a N-H bond (Scheme 9.9) [11]. In addition, excellent functional group tolerance under relatively mUd conditions and great regioselectivity were exhibited. 

Soon after, Xue s group also demonstrated a visible-light photocatalytic transformation of chloroamines to nitrogen-centered radicals. This strategy was utilized for the direct C-H amination of benzoxazoles in a one-pot, two-step process (Eq. (13.27)) [76]. This one-pot process circumvents the needs for purification of the chloroamines, showing the potential of this amination for synthetic applications. 

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