Lawrence R. Sita, Richard D. Synthesis and crystal structure of the first stannacyclopropene derivative. Journal of the American Chemical Society , 15 , Sato, Hiroshi. Okazaki, Junzo. Otera, Hitosi. A new strategy for 1,4- and 1,4,7-polycarbonyl compounds. Robert K. Boeckman Jr. To date, the macrocyclization remains a robust but highly challenging synthetic strategy, which usually calls for very low concentrations to avoid intermolecular polymerization To further demonstrate the practicality of our method, we adapted the visible-light-mediated direct deoxygenation C—C coupling to an elegant macrocyclization under optimized conditions in aqueous solution.
As shown in Fig. The ketones produced in this reaction were versatile building blocks for chemical bond formation 41 , 42 and could undergo a broad array of downstream organic transformations to construct structurally diverse nitrogen-containing heterocycles 22, 24, 26, and 28, Fig.
This indicates that an acyl radical pathway could be possible 44 , 45 , 46 , The intramolecular hydroacylation of 2-allylbenzoic acid 29 further exemplified the intermediacy of the acyl radical species Fig. When potassium benzoate was employed in place of benzoic acid, 3d was obtained in moderate yield, which suggests that the triphenylphosphine radical cation reacts with an aromatic carboxylate anion Fig.
The resulting radical cation 31 reacts with carboxylate anion to generate the phosphoryl radical The acyl radical 33 generated in this way then selectively attacks the alkene to form the radical species 34 , which is capable of undergoing an SET with reductive IrII species to afford the corresponding ketone in the presence of water.
Alternatively, the homocoupling of acyl radicals 33 can afford a little amount of 1,2-diketones as byproducts. Three-component reductive coupling Based on this reductive quenching mechanism, we extended this deoxygenative catalytic system to an attractive three-component reductive coupling reaction of carboxylic acids 1 , primary amines 36 , and aromatic aldehydes This catalytic system enables direct deoxygenation of aromatic acids to generate acyl radical in the presence of a broad variety of biomolecules.
This ketone synthesis strategy allows practical and friendly reaction conditions, which significantly broadens the substrate scope, improves the functional group compatibility, and emphasizes the synthetic application in complex molecules.
Based on the direct deoxygenative mechanism, a reductive three-component coupling reaction of amines, aldehydes and acids has been achieved.
It offers not only a strategy for the streamlined synthesis of structurally diverse ketones from abundant carboxylic acids, but also a photoredox radical activation mode beyond the redox potential of carboxylic acids. Methods See Supplementary Methods for further details.
General procedure for the synthesis of 3 To a 10 mL Schlenk tube equipped with a magnetic stir bar was added aromatic carboxylic acid 1 0. The alkenes 2 0. Cockle and Pak-Hing Leung. Organometallics , 29 4 , The Journal of Organic Chemistry , 74 4 , Barry M. Trost,, Zachary T. Ball, and, Kai M. Journal of the American Chemical Society , 28 , Francisco Alonso,, Irina P.
Beletskaya, and, Miguel Yus. Chemical Reviews , 6 , Journal of the American Chemical Society , 39 , Ernest Wenkert, K. IR Nujol : , , , , cm—1. Diastereomeric mixture: yellow oil. Calcd for C26H25NO5 Calcd for C19H27NO4 Major diastereomer: yellow viscous oil. Calcd for C28H29NO7 Minor diastereomer: yellow viscous oil. Calcd for C26H27NO4 Calcd for C24H27NO5Visible-light photoredox catalysis enables the direct deoxygenation of acids as acyl sources with triphenylphosphine and represents a distinct perspective on activation. The reaction was stirred for 1 h, and then treated with distillated H2O 50 mL. Calcd for C19H19NO4 The solution was filtered and concentrated until the volume was reduced to 4 mL WARNING: the complete evaporation of the solvent leads to nitrous acid elimination and then passed through a short pad of silica gel 3 g washing with fresh EtOAc 20 mL.
The intramolecular hydroacylation of 2-allylbenzoic acid 29 further exemplified the intermediacy of the acyl radical species Fig. As shown in Fig.
Minor diastereomer: yellow oil. ACS Catalysis , 6 5 , The Journal of Organic Chemistry , 80 15 , Beletskaya, and, Miguel Yus.
General procedure for the synthesis of 9—17 To a 10 mL Schlenk tube equipped with a magnetic stir bar was added aromatic carboxylic acid 1 0. Synthesis ; 10b Ono N. This protocol allows practical and friendly reaction conditions which significantly broadens the substrate scope and emphasizes the synthetic application in complex molecules.
It is noteworthy that 4-bromo 3g and 4-iodo 3h benzoic acids tolerate the conditions well, and this provides an extremely important choice for downstream C—C coupling via palladium catalysis. Journal of the American Chemical Society , 40 ,
Denmark and Lindsey R. The combined organic layer was dried over anhydrous Na2SO4, then the solvent was removed under vacuo. The total synthesis of. Herein we achieved the direct deoxygenative ketone synthesis in aqueous solution from readily available aromatic carboxylic acids and alkenes, affording structurally diverse ketones in moderate to good yields. The solution was filtered and concentrated until the volume was reduced to 4 mL WARNING: the complete evaporation of the solvent leads to nitrous acid elimination and then passed through a short pad of silica gel 3 g washing with fresh EtOAc 20 mL.