Section A highlights the Pd-catalyzed o -hydroxylation protocol of 2-arylbenzothiazole, while section B describes the o -acetoxylation of 3,5-diarylisoxazole using a Pd catalyst. Here we report the Pd-catalyzed o-acetoxylation of 3,5-diarylisoxazole using the Pd(OAc)2/DIB combination via its N-directed ortho C-H bond.
The optimized conditions were then carried out for o-aroylation of 2-arylbenzothiazole and 2-arylbenzoxazole using various substituted aldehydes. In summary, a simple and efficient protocol was developed for the ortho-arylation of 2-arylbenzoxazoles and 2-arylbenzothiazoles with aldehyde as the arylating partner.
SECTION IIIB: Palladium Catalyzed Regioselective Aroylation of 3,5- Diarylisoxazole via ortho C–H Functionalizations
Based on the results obtained from these control experiments as well as the literature reports, a plausible mechanism consisting of two pathways was proposed (Scheme IIIA.1). The high regioselectivity and a wide range of functional group tolerance make this protocol attractive for the synthesis of functionalized 2-arylbenzoxazoles and 2-arylbenzothiazoles.
Ceric Ammonium Nitrate (CAN): An Efficient Oxidant for Pd(II)- Catalyzed Substrate Directed Decarboxylative o -Aroylation
Ceric Ammonium Nitrate (CAN): An efficient oxidant for Pd(II)-catalyzed substrate-directed decarboxylative o-aroylation. In conclusion, we have demonstrated the use of an inexpensive terminal oxidant CAN for Pd-catalyzed substrate-directed decarboxylative o-aroylation of various conducting arenes.
Based on the extensive crossover experiments performed, a plausible mechanism has been proposed for this process (Scheme VIA.2). Based on the extensive crossing experiments performed, a plausible mechanism for this process has been proposed (Scheme VIB.2).
Ceric Ammonium Nitrate (CAN) Promoted Pd II -Catalyzed
C HAPTER I
- Introduction
- Comparison Between Traditional and Modern Approach
- Challenges to C− − −H Functionalizations −
- Classification of Reactions
- Modern Era of C− − −H Functionalization −
- Cross-dehydrogenative coupling (CDC): The cross-dehydrogenative coupling (CDC) reaction generally refers to a cross-coupling reaction between two C−H bonds or
- An array of exceptions: Reactions which are not included in the above three classes are exemplified below
- Asymmetric C− − − −H Activation
- C− − − −H Activation: A Complementary Tool in Total Synthesis
- References
In addition to the sp2 C−H acetoxylation, the same group also reported a Pd-catalyzed ligand-directed sp3 C−H bond oxygenation using PhI(OAc)2 as the terminal oxidant. Pd-catalyzed ortho sp2 C–H halogenation of 2-phenylpyridine bromination and chlorination at sp3 C − − − H bond of driving substrates.
IIA. Regioselective ortho-Hydroxylation of
IIA.1. Introduction
The same group also reported a Pd-catalyzed ligand-directed sp3 C−H bond oxygenation using PhI(OAc)2 as the terminal oxidant (Scheme IIA.2.2). .6a,d. Gooβen's group demonstrated a regiospecific Cu(II)-catalyzed ortho-alkylation of aromatic carboxylates with concomitant decarboxylation (Scheme IIA.2.3).7 This protocol provides access to the important substrate class of aromatic ethers from widely available carboxylic acids. Recently, a number of Pd- and Cu-catalyzed ortho-sp2- and sp3-C−H alkoxylations using bidentate chelate systems such as picolamide9a, N-(1-methyl-1-(pyridin-2-yl)ethyl)amide9b, 8- aminoquinoline,9c-pyridine-N-oxide9d and S-methyl-S-2-pyridylsulfoximine (MPyS)9e (Scheme IIA.2.5) appeared in the literature.
Scheme IIA.2.6).10a Later Shi group developed a similar palladium-catalyzed o-benzoxylation of ketoximeter via the in situ generation of benzoate iodonium salts.10b. Cheng group demonstrated the use of aromatic carboxylic acids as the ArCOO− source for o-benzoxylation of 2-arylpyridines using rhodium catalyst.11a The same group showed that acid derivatives in the form of carboxylic acid salt,11b anhydride11c and acid chloride11d can for the similar purpose is used (Scheme IIA.2.7). Yu group achieved a highly selective Pd-catalyzed ortho-hydroxylation of potassium benzoates via activation of dioxygen giving synthetically useful salicyclic acid derivatives (Scheme IIA.2.9).14a Apart from this; the same group has too.
IIA.3. Present Work
As shown in Table IIA.3.1, the various oxidants tested, such as iodooxybenzene (PhIO), bis-trifluoroacetoxyiodobenzene (BTI) and hydroxytosyloxyiodobenzene (HTIB) (Table IIA.3.1, entry 6−−−−8), all gave inferior results when compared with DIB (diacetoxyiodobenzene) (Table IIA.3.1, paragraph 4). Notably, the replacement of AcOH with trifluoroacetic acid (TFA) provided a marginal improvement in yield (92%) (Table IIA.3.1, entry . 13), but the former was preferred due to cost considerations. Interestingly, the inexpensive oxidant Oxone® in combination with TFA (Table IIA.3.1, entry 14) gave a similar yield (85%) to that of the DIB/AcOH combination.
Other investigated solvents such as toluene, 1,4-dioxane, DMSO or DMF did not give satisfactory results (Table IIA.3.1, entry 15−−−−−18) under similar catalyst−oxidant combinations. The use of tert-butanol as solvent gave only traces of product under the identical reaction conditions, although it proved to be an effective solvent during o-hydroxylation of 2-arylpyridine.5d Thus the combination of Pd(OAc)2 as catalyst DIB as a co-oxidant in acetic acid at 110 oC (Table IIA.3.1, entry 4) gave the most satisfactory yield, which was used for subsequent reactions. The results illustrated in Scheme IIA.3.1 testify that the method is compatible with a wide range of functionalities.
IIB.1. Introduction
IIB.3. Present Work
Experimental Section
- Crystallographic description
- General procedures for o-hydroxylation and o-acetoxylation
UV-visible spectra were recorded by dissolving the calculated amount of the sample in an appropriate solvent on a Perkin-Elmer Lambda UV-visible spectrophotometer. Then the reaction vessel was kept in an oil bath preheated to 110 oC and allowed to stir for the indicated time. The crude product thus obtained was further purified through silica gel column chromatography (EtOAc/hexane) to give the pure product.
Then the reaction mixture was subjected to reflux in a preheated oil bath at 110°C and stirred for the prescribed time. After completion of the reaction, as judged by TLC, the reaction mixture was cooled and mixed with water (5 ml). The crude product obtained here was further purified by silica gel column chromatography (10% EtOAc/hexane) to afford the pure 2-(5-phenylisoxazol-3-yl)phenylacetate (1'a) (0.172 g, yield 62%). .
Spectral Data
IIA.6
IIB.6
Spectra
IIA.7
IIB.7
Abstract: Efficient protocols have been developed for the ortho-aroylation of 2-arylbenzothiazoles, 2-arylbenzoxazoles, and 3,5-diarylisoxazoles using an aldehyde as an aroyl substituent. Section-A shows the Pd(II)-catalyzed o-aroylation of 2-arylbenzothiazole and 2-arylbenzoxazole, while section-B describes the o-aroylation of another directing substrate 3,5-diarylisoxazole.
IIIA.1. Introduction
Kakiuchi and colleagues achieved a Ru-catalyzed ortho-selective acylation of arylpyridines with acyl chlorides via C-H bond cleavage under oxidant-free conditions.9a In an analogous Pd-catalyzed reaction, selective aromatic C-H bond acylation occurred with readily available carboxylic acid. acids have also been reported by Fu et al.9b Recently, the Gooβen group demonstrated a Rh-catalyzed method for the ortho-acylation of benzoic acid with carboxylic anhydrides (Scheme IIIA.2.1).9c. Using alcohols as the latent aldehyde functionality, a Pd-catalyzed regioselective o-aroylation of aromatic C-H bonds yielded ketones in good yields in the presence of peroxide (Scheme IIIA.2.4).12a Later, several primary alcohols have been used as the aroyl- equivalents for different orthodirecting substrates.12b-e The use of ethers as the aroyl surrogate has also been reported by Kim and co-workers during the directing group-assisted ortho C−H functionalization. For the first time using inert alkylbenzene as the synthetic equivalent of the aroyl group, our group has developed a directing group-assisted orthoaroylation via Pd(II)-catalyzed cross-dehydrogenative coupling in the presence of TBHP (Scheme IIIA.2.5).13 .
The Wu group recently developed an efficient protocol for Pd-catalyzed orthoaroylation of 2-arylpyridines using arylmethylamines as aroyl source in the presence of TBHP (Scheme IIIA.2.6).14. The Wang group has achieved an efficient carboacylation reaction of 2-arylpyridines with α-diketones via a Pd-catalyzed C–H bond activation and C–C bond cleavage in the presence of TBHP as the radical initiator (Scheme IIIA.2.7). 15. Regarding targeted ortho-aroylation, Ge and co-workers demonstrated a novel Pd-catalyzed protocol to access o-aroylacetanilides via decarboxylative coupling of α-oxoacids with acetanilides.16a Later, the same group performed a similar ortho-acylation of 2 - arylpyridines16b as well as carboxylic acids (Scheme IIIA.2.8).16c.
IIIA.3. Present Work
No substantial effect on product yield (i.e. 72%) was observed when using 10 mol% of the catalyst. The use of copper salts such as Cu(OTf)2, Cu(OAc)2 instead of the palladium catalyst was completely unsatisfactory (Table IIIA.3.1, entries 19-20). Aldehydes containing either the weakly electron-withdrawing groups such as −F (f), −Cl (g-i) or the strongly electron-withdrawing groups such as −CO2Me (j), −NO2 (k-l) yielded the corresponding o-aroylated products (1f -1l ) with better yields regardless of the position of the electron withdrawing group on the phenyl ring.
This is the result of the palladation taking place preferentially at the less sterically hindered ortho site. A plausible mechanism for this transformation can be speculated from some of the basic observations from these experiments. A significant rate retardation in the presence of a radical scavenger, such as 2,2,6,6-tetramethyl piperidin-1-oxyl (TEMPO) and significant decrease in yield (15%) along with the formation of benzoyl- TEMPO adduct (A) in 41% isolated yield (Scheme IIIA.3.4) indicates a radical pathway of the reaction.
IIIB.1. Introduction
IIIB.3. Present Work
Experimental Section
- Crystallographic description
- Synthesis of o-aroylated 2-arylbenzothiazole and 3,5- diarylisoxazole
- Mechanistic investigations
The reaction vessel was then refluxed in an oil bath preheated to 110 oC and the mixture was maintained for the specified period of time. The flask was placed in a condenser and the resulting reaction mixture was stirred in an oil bath preheated to 120 oC for 5 h. The reaction after 5 h gave the benzoyl-TEMPO adduct 2,2,6,6-tetramethylpiperidin-1-yl benzoate (A) in 41% yield along with small yield (15%) of the desired product (1a).
This experiment supports the formation of a benzoyl radical in the medium from benzaldehyde (1), radical induced by Pd(OAc)2/TBHP, and also the radical nature of the mechanism. The flask was placed on a condenser and the resulting reaction mixture was stirred in a preheated oil bath at 120°C for 12 hours. This experiment supports the formation of a benzoyl radical in the medium from benzaldehyde (a), radical induced by Pd/TBHP, and also the radical nature of the mechanism.
Spectral Data
IIIA.6
IIIB.6
Spectra IIIA.7
IIIB.7
CDCl 3 )
- Ceric Ammonium Nitrate (CAN) Promoted Pd II - Catalyzed Substrate-Directed Decarboxylative o -
- Introduction
- Strategies for ortho -Aroylation
- Present Work
- Experimental Section
- References
- Spectral Data
- Spectra
Abstract: Inexpensive cerium ammonium nitrate (CAN) is an efficient oxidant for a Pd-catalyzed substrate-directed decarboxylative o-aroylation process. Cerium ammonium nitrate (CAN) promotes PdII-catalyzed substrate-directed decarboxylation o -catalyzed substrate-directed decarboxylation o -aroylation. Classical synthetic recipes for the synthesis of diaryl or alkylaryl ketones, however, suffer from various drawbacks, such as poor regioselectivity or harsh acidic/basic conditions.3 The emergence of modern techniques such as cross-dehydrogenative coupling (CDC) combined with directing group-assisted techniques shows that possible methods for the synthesis of diaryl or arylalkyl ketones.4 The various methods that have been used for the synthesis of diaryl or arylalkyl ketones can be classified into several types as follows; (i) ortho-selective Friedel-Crafts acylation using carboxylic acids or their derivatives5 (ii) carbonylation processes6 (iii) cross-dehydrogenation coupling with various aroyls.
In the context of decarboxylative aroylation reactions, the use of α-keto acid as the aroyl surrogate was first developed by Gooβen et al. In summary, we have demonstrated the use of the low-cost terminal oxidant CAN as an efficient substitute for a range of expensive oxidants/additives in the Pd- catalyzed substrate-directed decarboxylative o-aroylation processes. General procedure for the synthesis of (2-benzo[d]thiazol-2-yl-phenyl)-phenyl-methanone (la') from 2-phenylbenzo[d]thiazole and phenylglyoxylic acid (a').
