26278-74-0

Upstream product

• 491-30-5 1-hydroxyisoquinoline 
• 71-43-2 benzene 
• 1604839-65-7 N-(5-methoxyquinolin-8-yl)benzamide 
• 98-88-4 benzoyl chloride 
• 100-42-5 styrene 
• 89549-37-1 N-pivaloyl benzamide 
• 495-18-1 Benzohydroxamic acid 
• 1293990-69-8 N-((tert-butoxycarbonyl)oxy)benzamide 
• 65-85-0 benzoic acid 
• 51860-35-6 N-((4-methylbenzoyl)oxy)benzamide 
• 21251-12-7 N-benzoyl-O-acetylhydroxylamine 
• 61650-22-4 N-(pivaloyloxy)benzamide 
• 120419-97-8 (E)-N-benzylidene-1,1,1-trimethylsilanamine 
• 2728-04-3 N,N-diethyl-ortho-toluamide 

Downstream Products

• 491-30-5 1-hydroxyisoquinoline 
• 1196-38-9 3,4-dihydroisoquinolin-1(2H)-one 
• 26345-15-3 5,6,7,8-tetrahydro-1(2H)-isoquinolinone 

Relevant academic research and scientific papers

Employing a robustness screen: Rapid assessment of rhodium(III)-catalysed C-H activation reactions This paper is dedicated to Professor Paul A. Wender, a great scientist, teacher and mentor

Following the discovery of new synthetic methodology, an assessment of its potential utility in real synthetic problems is highly desirable to facilitate its application. Herein, we describe an assessment of two contemporary rhodium catalysed C-H activati

Corrigendum: Rhodium(III) Complex with a Bulky Cyclopentadienyl Ligand as a Catalyst for Regioselective Synthesis of Dihydroisoquinolones through C?H Activation of Arylhydroxamic Acids (Chemistry – A European Journal, (2018), 24, (16570–16575), 10.1002/chem.201804050)

In the original article, Scheme 5 describes the reaction of O-Boc-phenylhydroxamic acid with a mixture of alkenes, Scheme 6 describes the reaction of O-Boc- and O-Piv-phenylhydroxamic acid with styrene. Both schemes show the formation of the product 4 p, which was erroneously assigned as 4-phenyl-3,4-dihydroisoquinolinone, based on the previous literature report.[1] Recently, S.-L. You et al. and H. Waldmann et al. have independently discovered that 4 p has in fact the structure of 3-benzylisoindolin-1-one (this was confirmed by X-ray structures of chloro-substituted derivatives).[2, 3] Therefore, we provide the corrected Schemes 5 and 6 and the corresponding text for our article as shown below. The yields and selectivities remain the same. We apologize for any inconvenience caused by the previous incorrect assignment. Recently, another paper with the incorrect assignment of 4 p has been corrected in a similar manner.[4] Corrected description for the Scheme 5. The difference in reactivity of alkenes creates the opportunity of chemoselective reactions. For example, reaction of 1 a with an equimolar mixture of allyl alcohol, styrene and myrcene proceed selectively in the presence of the catalyst 5 to give 4-CH2OH-substituted product 4 e in 89 % yield (Scheme 5). Similar reaction in the presence of the classical catalyst [Cp*RhCl2]2 gave a mixture of three products: 3-benzylisoindolin-1-one 4 p, as well as two CH2OH-substituted isomers 4 e and 3 e in 1.7:1:2.5 ratio (note that myrcene did not react in both cases). 5 Scheme (Figure presented.) Chemoselectivity of reaction of 1 a with a mixture of alkenes. Corrected description for the Scheme 6. Additionally, as it was noted by Corminboeuf and Cramer et al., (References [14, 17] in the original publication) the steric interactions between the cyclopentadienyl ligand and the Boc group are important for selectivity. Indeed, we observed that the reaction of O-Boc-phenylhydroxamic acid 1 a with styrene in the presence of the classical catalyst [Cp*RhCl2]2 gives only the 3-benzylisoindolin-1-one 4 p, while similar reaction of O-pivaloyl-phenylhydroxamic acid 1 b produced the 3-substituted structural isomer 3 p (Scheme 6). The reasons for this striking difference are not fully clear. Unfortunately, both reactions in the presence of the catalyst 5 proceeded slowly and gave mixtures of product. 6 Scheme (Figure presented.) Regioselectivity determined by Boc- or pivalyl group of hydroxamic acid derivative.

Rhodium(III)-Catalyzed C-H Activation: Ligand-Controlled Regioselective Synthesis of 4-Methyl-Substituted Dihydroisoquinolones

Rh-catalyzed C-H functionalization of O-pivaloyl benzhydroxamic acids with propene gas provides access to 4-methyl-substituted dihydroisoquinolones. Good to excellent levels of regioselectivity are achieved using [CptRhCl2]2 as a precatalyst under optimized conditions. Thorough examination of aryl/heteroaryl O-pivaloyl hydroxamic acid substrates, ligand effects on C-H site selectivity, alkene scope, and demonstration of scale are discussed within.

Synthesis of 3-Substituted and 3,4-Disubstituted 3,4-Dihydro-1(2H)-isoquinolones by Condensation of Lithiated N,N-Diethyl-o-toluamide with Imines

Lithiated N,N-diethyl-o-toluamide was condensed with imines to afford 3,4-dihydro-1(2H)-isoquinolones.The products were deprotonated under the reaction conditions, and electrophilic trapping afforded trans-2,3,4-trisubstituted-2,3-dihydro-1(2H)-isoquinolones.This methodology was also applied to the synthesis of 7-substituted 7,8-dihydro-1,6-naphthyridin-5(6H)-ones.

RhIII-Catalyzed C?H Activation of Aryl Hydroxamates for the Synthesis of Isoindolinones

RhIII-catalyzed C?H functionalization reaction yielding isoindolinones from aryl hydroxamates and ortho-substituted styrenes is reported. The reaction proceeds smoothly under mild conditions at room temperature, and tolerates a range of functional groups. Experimental and computational investigations support that the high regioselectivity observed for these substrates results from the presence of an ortho-substituent embedded in the styrene. The resulting isoindolinones are valuable building blocks for the synthesis of bioactive compounds. They provide easy access to the natural-product-like compounds, isoindolobenzazepines, in a one-pot two-step reaction. Selected isoindolinones inhibited Hedgehog (Hh)-dependent differentiation of multipotent murine mesenchymal progenitor stem cells into osteoblasts.

Divergent Synthesis of Tunable Cyclopentadienyl Ligands and Their Application in Rh-Catalyzed Enantioselective Synthesis of Isoindolinone

A series of rhodium complexes bearing sterically and electronically tunable cyclopentadienyl ligands, prepared by utilizing Co2(CO)8-mediated [2+2+1] cyclization as a key step, were synthesized. In the presence of 2.5 mol% of CpmRh4, unprecedented enantioselective [4+1] annulation reaction of benzamides and alkenes was achieved with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio-and enantioselectivity (up to 94% yield, 97:3 er). Preliminary mechanistic studies suggest that the reaction involves an oxidative Heck reaction and an intramolecular enantioselective alkene hydroamination reaction.

Corrigendum to: Ligand-Controlled Regiodivergent Pathways of Rhodium(III)-Catalyzed Dihydroisoquinolone Synthesis: Experimental and Computational Studies of Different Cyclopentadienyl Ligands (Chemistry - A European Journal, (2014), 20, 47, (15409-15418), 10.1002/chem.201404515)

The authors became aware that product 4aa was erroneously assigned to 4-phenyl- 3,4-dihydroisoquinolin-1(2H)-one. Reanalysis of the 1H NMR and 13C NMR spectra of product 4aa confirmed that the correct structure corresponds to the constitutional 3-benzyl-isoindolones isomer (Figure 1). 4-Phenyl-3,4-dihydroisoquinolin-1(2H)-one was reported by Ellman and its structure was confirmed by X-ray crystallographic analysis.[1] The corrected isoindolone structure of 4aa matches all data of 3-benzylisoindolone synthesized by a different route.[2]. (Figure presented.).

Rhodium(III) Complex with a Bulky Cyclopentadienyl Ligand as a Catalyst for Regioselective Synthesis of Dihydroisoquinolones through C?H Activation of Arylhydroxamic Acids

Catalytic reaction of arylhydroxamic acids with alkenes represents a convenient method for preparation of biologically active dihydroisoquinolones. Here, the rhodium(III) complex [(C5H2tBu2CH2tBu)RhCl2]2, which allows one to carry out such reactions with high regioselectivity to obtain 4-substituted dihydroisoquinolones in 72–97 % yields, is described. The regioselectivity is provided by the bulky cyclopentadienyl ligand of the catalyst, which is formed through a [2+2+1] cyclotrimerization of tert-butylacetylene. The catalytic reaction tolerates various distant functional groups in alkenes, but is inhibited by bulky (e.g., tBu) or strongly coordinating (e.g., imidazolyl) substituents. Some of the prepared dihydroisoquinolones effectively inhibit growth of phytopathogenic fungi.

Ligand-Controlled Regiodivergent Pathways of Rhodium(III)-Catalyzed Dihydroisoquinolone Synthesis: Experimental and Computational Studies of Different Cyclopentadienyl Ligands

RhIII-catalyzed directed C-H functionalizations of arylhydroxamates have become a valuable synthetic tool. To date, the regioselectivity of the insertion of the unsaturated acceptor into the common cyclometalated intermediate was dependent solely on intrinsic substrate control. Herein, we report two different catalytic systems that allow the selective formation of regioisomeric 3-aryl dihydroisoquinolones and previously inaccessible 4-aryl dihydroisoquinolones under full catalyst control. The differences in the catalysts are computationally examined using density functional theory and transition state theory of different possible pathways to elucidate key contributing factors leading to the regioisomeric products. The stabilities of the initially formed rhodium complex styrene adducts, as well as activation barrier differences for the migratory insertion, were identified as key contributing factors for the regiodivergent pathways. RhIII-catalyzed directed C-H functionalization of aryl hydroxamates enables the selective formation of regioisomeric 3-aryl or 4-aryl dihydroisoquinolones with two different catalytic systems. The different selectivities are examined using DFT and transition state theory. The stabilities of the rhodium complex adducts and migratory-insertion activation barriers are key factors for the regiodivergent pathways (see scheme; rs=regioselectivity).

Cobalt-catalyzed, aminoquinoline-directed coupling of sp2 C-H bonds with alkenes

A method for cobalt-catalyzed, aminoquinoline-directed ortho-functionalization of sp2 C-H bonds with alkenes has been developed. Reactions proceed at room temperature in trifluoroethanol solvent, use oxygen from air as an oxidant, and require Mn(OAc)3 as a cocatalyst. Benzoic, heteroaromatic, and acrylic acid aminoquinoline amides react with ethylene as well as mono- and disubstituted alkenes affording products in good yields. Excellent functional group tolerance is observed; halogen, nitro, ether, and unprotected alcohol functionalities are compatible with the reaction conditions.