Recent advances in direct C-H arylation: Methodology, selectivity and mechanism in oxazole series

Abstract

Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki-Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented.

Keywords: ate complex; catalytic direct arylation; mechanism; oxazole; selectivity; transition-metal catalysis.

Scheme 1

Stoichiometric and catalytic direct (hetero)arylation of arenes.

Scheme 2

Stille and Negishi cross-coupling methodologies in oxazole series [,––34].

Scheme 3

Stoichiometric direct (hetero)arylation of (benz)oxazole with magnesate bases [35].

Scheme 4

Ohta's pioneering catalytic direct C5-selective pyrazinylation of oxazole [–37].

Scheme 5

Preparation of pharmaceutical compounds by following the pioneering Ohta protocol [–39].

Scheme 6

Miura’s pioneering catalytic direct arylations of (benz)oxazoles [40]. ^aIsolated yield.

Scheme 7

Pd(0)- and Cu(I)-catalyzed direct C2-selective arylation of (benz)oxazoles [–44].

Scheme 8

Cu(I)-catalyzed direct C2-selective arylations of (benz)oxazoles [,–47].

Scheme 9

Copper-free Pd(0)-catalyzed direct C5- and C2-selective arylation of oxazole-4-carboxylate esters [–5052].

Scheme 10

Iterative synthesis of bis- and trioxazoles [51].

Scheme 11

Preparation of DPO- and POPOP-analogues [53].

Scheme 12

Pd(0)-catalyzed direct arylation of benzoxazole with aryl chlorides [54].

Scheme 13

Pd(0)-catalyzed direct C2-selective arylation of (benz)oxazoles with bromides and chlorides using bidentate ligands [–56].

Scheme 14

Palladium-catalyzed direct arylation of oxazoles under green conditions; (a) Zhuralev direct arylation of 2-azabenzoxazole at low temperature [–58]; (b) Greaney direct arylation of oxazole in water [–60]; (c) Hoarau–Doucet direct arylation of (benz)oxazole in diethylcarbonate [–62].

Scheme 15

Pd(0)-catalyzed C2- and C5-selective (hetero)arylation of oxazole [63].

Scheme 16

Pd(0)-catalyzed C2- and C5-selective (hetero)arylation of ethyl oxazole-4-carboxylate [64].

Scheme 17

Pd(0)-catalyzed direct C4-phenylation of oxazoles; (a) Miura’s procedure [65]; (b) Fagnou’s procedure [66].

Scheme 18

Catalytic cycles for Cu(I)-catalyzed (routeA) and Pd(0)/Cu(I)-catalyzed (route B) direct arylation of oxazoles with halides proposed by Bellina and Rossi [67].

Scheme 19

Base-assisted, Pd(0)-catalyzed, C2-selective, direct arylation of benzoxazole proposed by Zhuralev [58]; (a) Proposed cross-coupling-type mechanism; (b) Ring-close direct C2-arylation.

Scheme 20

Electrophilic substitution-type mechanism proposed by Hoarau [64].

Scheme 21

CMD-proceeding C5-selective direct arylation of oxazole proposed by Strotman and Chobabian [63].

Scheme 22

DFT calculations on methyl oxazole-4-carboxylate and consequently developed methodologies for the Pd(0)-catalyzed C2- and C5-selective direct arylations proceeding by CMD [64]; (a) DFT calculations on oxazole-4-carboxylate; (b) Developed novel CMD direct arylation methodologies. ^aTS CMD Free Gibbs energy; ^bHOMO coefficient; ^cpartial charge (ESP).

Scheme 23

Pd(0)-catalyzed direct arylation of (benz)oxazoles with tosylates and mesylates [71].

Scheme 24

Pd(0)-catalyzed direct arylation of oxazoles with sulfamates [72].

Scheme 25

Pd(II)- and Cu(II)-catalyzed decarboxylative direct C–H coupling of oxazoles with 4- and 5-carboxyoxazoles [73]; (a) procedure; (b) proposed mechanism.

Scheme 26

Pd(II)- and Ag(II)-catalyzed decarboxylative direct arylation of (benzo)oxazoles [74]; (a) procedure; (b) proposed mechanism.

Scheme 27

Pd(II)- and Cu(II)-catalyzed direct arylation of benzoxazole with arylboronic acids [76]; (a) procedure; (b) proposed mechanism.

Scheme 28

Ni(II)-catalyzed direct arylation of benzoxazoles with arylboronic acids under O₂ [76]; (a) procedure; (b) proposed mechanism.

Scheme 29

Rhodium-catalyzed direct arylation of benzoxazole [–79].

Scheme 30

Ni(II)-catalyzed direct arylation of (benz)oxazoles with aryl halides; (a) Itami's procedure [80]; (b) Miura's procedure [81].

Scheme 31

Dehydrogenative cross-coupling of (benz)oxazoles; (a) Pd(II)- and Cu(II)-catalyzed cross-coupling of benzoxazole with thiophene [82]; (b) Pd(II)- and Cu(II)-catalyzed cross-coupling of oxazoles with benzothiophene [83]; (c) Cu(II)-catalyzed direct cross-coupling of (benz)oxazole with arenes [84].