Multicomponent reaction comprising one-pot installation of bidentate directing group and Pd(II)-catalyzed direct β-arylation of C(sp3) H bond of aliphatic and alicyclic carboxamides (original) (raw)
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Tetrahedron, 2015
Investigations on the Pd-catalyzed 8-aminoquinoline-aided diastereoselective b-arylation of the prochiral 2 sp 3 CeH bonds of various aliphatic carboxamides having substituents at the aor g-positions are reported. The Pd-catalyzed b-arylation of the 2 sp 3 CeH bonds of racemic 2-phenylbutanamides with aryl iodides gave the arylated products (AE)-3ael (anti isomers) with moderate to good diastereoselectivities (dr up to 86:14). Next, the Pd-catalyzed b-arylation of various g-substituted aliphatic carboxamides with aryl iodides furnished the corresponding CeH arylated products with poor diastereoselectivities. Then, the arylation of the C(b)-H bonds of 2-ethyl-N-(quinolin-8-yl)butanamide possessing two prochiral centers with aryl iodides successfully furnished the bis arylated products meso-8eAehA and (AE)-8eBehB (diastereomers). The arylation of (S)-2-phenylbutanamide also gave the corresponding enantiomerically enriched compounds 10aec (anti isomers). The stereochemistry of the products (AE)-3ael (major isomers), meso-8eAehA (major isomers), (AE)-8eBehB (minor isomers) and enantiomerically enriched compounds 10aec (major isomers) were assigned based on the X-ray structures of the major isomers 3b,c,e,l, 8eA, 10c and minor isomers 8eB and 8fB. The limitations and outcome of the stereocontrol in the Pd-catalyzed CeH arylation reactions involving aliphatic carboxamides are illustrated.
The Journal of Organic Chemistry, 2016
The diastereoselective Pd(OAc) 2-catalyzed, bidentate ligand-directed sp 3 C-H activation/arylation followed by ring opening of cyclopropanecarboxamides, which were assembled from cyclopropanecarbonyl chlorides and bidentate ligands (e.g., 8-aminoquinoline and 2-(methylthio)aniline, has been investigated. The treatment of various cyclopropanecarboxamides with excess amounts of aryl iodides in the presence of the Pd(OAc) 2 catalyst, AgOAc and AcOH directly afforded the corresponding multiple β-C-H arylated open-chain carboxamides (anti βacyloxy amides). This method has led to the construction of several anti β-acyloxy amides that possess vicinal stereocenters with a high degree of stereocontrol with the formation of a new CO bond and three new CC bonds. A plausible mechanism for the formation of multiple β-C-H arylated open-chain carboxamides from the Pd-catalyzed, bidentate ligand-directed β-C-H arylation and the ring opening of cyclopropanecarboxamides is proposed based on several control experiments. The observed diastereoselectivity and anti stereochemistry of the β-acyloxy amides were ascertained based on X-ray structural analysis of representative β-acyloxy amides.
2016
Palladium-catalyzed C–C bond formation and C–H activation have become emerging methods of choice in the industrial synthesis of pharmaceutical and agrochemical products. The development of a palladium-catalyzed domino reaction of aryl iodides and aryl bromides to form polycyclic dihydrophenanthrene structures selectively and in high yields is discussed in this thesis. The reaction involves two C–H activations and the formation of three new C–C bonds and demonstrates the high efficiency of domino reaction catalysis. A detailed description of the optimization of two reactions is given, one involving a dimerization of aryl iodides and the other featuring a selective coupling of two distinct aryl bromides. Experiments to demonstrate the scope of these reactions show the tolerance of the optimized systems for a variety of common functional groups.
The Journal of Organic Chemistry, 2016
In this paper, we report our successful attempt on the Pd(II)-catalyzed, bidentate directing group-aided, chemoselective acetoxylation/substitution of remote ε-C(sp 2)-H bonds using heteroaryl-aryl-based biaryl systems. While the bidentate directing group (BDG)-aided, C-H activation and functionalization/acetoxylation of the β-, γand δ-C-H bonds of appropriate carboxamide systems were well documented, there exist only rare reports dealing on the C-H activation and functionalization of remote ε-C-H bonds of appropriate substrates. Especially, the BDG-aided chemoselective acetoxylation of remote ε-C(sp 2)-H bond over cyclization has not been explored well. Accordingly, in this work the treatment of various picolinamides / oxalylamides / pyrazine-2-carboxamides 4/7/9/11, which were derived from the corresponding C-3 arylated furfurylamines or thiophen-2-ylmethanamines with PhI(OAc) 2 in the presence of the Pd(OAc) 2 catalyst successfully afforded the corresponding ε-C-H acetoxylated products. The
Ligand‐Enabled PdII‐Catalyzed Iterative γ‐C(sp3)−H Arylation of Free Aliphatic Acid
Angewandte Chemie International Edition, 2019
C−H functionalization of aliphatic carboxylic acids without attaching exogenous auxiliary has been so far limited at the proximal β‐position. In this work, we demonstrate a ligand enabled palladium catalyzed first regioselective distal γ‐C(sp3)−H functionalization of aliphatic carboxylic acids without incorporating an exogenous directing group. Aryl iodides containing versatile functional groups including complex organic molecules are well tolerated with good to excellent yields during the γ‐C(sp3)−H arylation reaction. Interestingly, weak coordination of carboxylate group can be further extended for sequential hetero di‐arylation. Application of the protocol has been showcased by synthesizing substituted α‐tetralone. Mechanistic investigations have been carried out to shed light on the reaction pathway.
Chemistry - A European Journal, 2012
Optimization of reaction conditions and substrate structures: To confirm that the expected first cyclization proceeds from (halocinnamyl)aniline derivatives, we initially tested the reaction of monobromide 13 under typical palladiumcatalyzed reaction conditions (Scheme 5). As expected, treatment of 13 with [PdA C H T U N G T R E N N U N G (PPh 3) 4 ] (5 mol %) and Cs 2 CO 3 in MeCN gave the desired monocyclization product 14 in 94 % yield. The resulting benzylideneindoline derivative 14 was quantitatively isomerized to the corresponding indole 15 in CDCl 3 within 24 h at room temperature. Next, we tested the palladium-catalyzed double C À H functionalization of dibromides 7 (Table 1). Unfortunately, the reaction of dibromopivalamide 7 a with [PdA C H T U N G T R E N N U N G (PPh 3) 4 ] (5 mol %) and Cs 2 CO 3 in MeCN only gave the monocyclization product 17 a in low yield (28 %; Table 1, entry 1). In contrast, conducting the reaction with an increased amount of [PdA C H T U N G T R E N N U N G (PPh 3) 4 ] (10 mol %) in dioxane partially promoted the double C À H functionalization to afford the desired product 16 a, albeit in low yield (11 %). Investigations using other solvents (N,N-dimethylformamide (DMF), dimethylacetamide (DMA), tetrahydrofuran (THF), toluene, and o-Scheme 2. Preparation of dibromopivalamide 7 a. Scheme 3. Preparation of dihalosulfonamides 7 and 9. Scheme 4. Preparation of substituted dibromosulfonamides 12. Scheme 5. Monocyclization of bromopivalamide 13.