Cu-Catalyzed Synthesis

The idea enabled a domino process by combining copper-catalyzed C-O bond formation and thermal Claisen rearrangement. Subjecting allylic alcohol and vinyl iodide to the reaction conditions led to the clean formation of the desired rearrangement product in 55% yield with high stereochemical purity (Eq. 3.1.15). The preparation of two adjacent quartemary stereocenters from geraniols is successfully prepared using the aforementioned reaction conditions (Eq. 3.1.16). 

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First one-pot Cu-catalyzed synthesis of a-hy- 379 droxy-jS-amino acids in water. A new protocol... 

Table 10 Cu-catalyzed synthesis of 3-substituted furans and pyrroles...

Up to now, a variety of heterogeneous Cu-catalyzed cycloaddition reactions for the assembly of bioactive heterocycles have been reported. Most examples are the Huisgen-type 1,3-dipolar cycloadditions, but there are rare reports on the heterogeneous Cu-catalyzed synthesis of heterocycles through other types of cycloaddition reactions. 

These pioneering achievements in heterogeneous Cu-catalyzed synthesis of heterocycles are just the tip of the iceberg, and much more remains to be discovered and explored. 

Scheme 2.9 Cu-catalyzed synthesis of benzoxazoles from nitriles.

Scheme 2.75 Pd/Cu-catalyzed synthesis of benzofurans from vinyl halides and phenols.

Scheme 2.117 Cu-catalyzed synthesis of indoles from o-iodoanilines and ketones.

Scheme 2.137 Cu-catalyzed synthesis of 2-aminohenzothiazoles from TMTD.

Scheme 2.144 Cu-catalyzed synthesis of benzothiazoles with NaSH tiHzO.

Scheme 3.52 Cu-catalyzed synthesis of tetrahydroquinolines from alkynes.

SCHEME 20.43 Cu-catalyzed synthesis of aryl alkyl ethers. 

Alkyne replacements have also been reported. In 2008, Sakai et al. described the use of alkynylsilanes instead of terminal alkynes in the Cu-catalyzed synthesis of propargyl-amines, which was applicable to both secondary and primary aliphatic amines, although the latter afforded the corresponding products in low yield [145]. Very recently. Van der Eycken et al. applied the A -coupling to the C—H alkylation of azoles through a copper-catalyzed hetero-arene-amine-aldehyde/ketone coupling [146]. This reaction is proposed to proceed through the initial condensation of... 

In the same year, Jiao and coworkers developed a Cu-catalyzed synthesis of pyridines from acetaldehydes and nitrogen source [63]. 3,5-Diarylpyridines were produced in good cascade Chichibabin-type cycli-zation, C-(sp )-C(sp ) cleavage, and aerobic oxidation (Scheme 3.28). Azide and ceric ammonium nitrate (CAN) were found as efficient nitrogen donors and with O2 as the oxidant. 

Scheme 3.29 Cu-catalyzed synthesis of pyridines from oximes and enab.

Scheme 12.29 Sequentially Pd-Cu-catalyzed synthesis of 2-(5 -thienyl)furan and-pyrrole (41) and the monodisperse heterooligomer 42.

Alternatively, 2-iodobenzarnides undergo a ligand-free Cul-catalyzed domino cou-pling/q clocondensation reaction with amidines to give quinazolinones 36 (via coupling products 37) [306], or quinazolinones 36 (R = H) can be obtained in a Cu-catalyzed synthesis from 2-bromobenzoic acids and amidine hydrochlorides [307]. 

Alkynylbenzaldehyde 0-alkyl oximes were also used as precursors of isoquinolines (Scheme 16, route c). After intramolecular electrophilic cyclization, Af-alkoxy groups were eliminated to form aldehydes (for example benzaldehyde). Shin et al. synthesized 5-fluoro-3-phenylisoquinoline using a AgOTf/TfOH catalytic system (Scheme 19), [55] while Wu achieved Cu-catalyzed synthesis of several 7-fluoroisoquinoUne derivatives [56]. 

Scheme 28 Cu-catalyzed synthesis of l,3-dlhydrobenzimldazol-2-ones from methyl o-halo-arylcarbamates...

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