86322-98-7

Upstream product

• 13621-30-2 4-(2,3-dimethylphenyl)butanoic acid 
• 917-54-4 methyllithium 
• 36440-59-2 methyl β-(2,3-dimethylbenzoyl)propanoate 
• 86306-28-7 methyl β-(2,3-dimethyl-5-t-butylbenzoyl)propanoate 
• 7397-06-0 4-t-butyl-o-xylene 
• 13621-31-3 methyl γ-(2,3-dimethylphenyl)butanoate 
• 74-88-4 methyl iodide 

Relevant academic research and scientific papers

Enantioselective C-H Amination Catalyzed by Nickel Iminyl Complexes Supported by Anionic Bisoxazoline (BOX) Ligands

The trityl-substituted bisoxazoline (TrHBOX) was prepared as a chiral analogue to a previously reported nickel dipyrrin system capable of ring-closing amination catalysis. Ligand metalation with divalent NiI2(py)4 followed by potassium graphite reduction afforded the monovalent (TrHBOX)Ni(py) (4). Slow addition of 1.4 equiv of a benzene solution of 1-adamantylazide to 4 generated the tetrazido (TrHBOX)Ni(κ2-N4Ad2) (5) and terminal iminyl adduct (TrHBOX)Ni(NAd) (6). Investigation of 6 via single-crystal X-ray crystallography, NMR and EPR spectroscopies, and computations revealed a Ni(II)-iminyl radical formulation, similar to its dipyrrinato congener. Complex 4 exhibits enantioselective intramolecular C-H bond amination to afford N-heterocyclic products from 4-aryl-2-methyl-2-azidopentanes. Catalytic C-H amination occurs under mild conditions (5 mol % catalyst, 60 °C) and provides pyrrolidine products in decent yield (29%-87%) with moderate ee (up to 73%). Substrates with a 3,5-dialkyl substitution on the 4-aryl position maximized the observed enantioselectivity. Kinetic studies to probe the reaction mechanism were conducted using 1H and 19F NMR spectroscopies. A small, intermolecular kinetic isotope effect (1.35 ± 0.03) suggests an H-atom abstraction step with an asymmetric transition state while the reaction rate is measured to be first order in catalyst and zeroth order in substrate concentrations. Enantiospecific deuterium labeling studies show that the enantioselectivity is dictated by both the H-atom abstraction and radical recombination steps due to the comparable rate between radical rotation and C-N bond formation. Furthermore, the competing elements of the two-step reaction where H-removal from the pro-R configuration is preferred while the preferential radical capture occurs with the Si face of the carboradical likely lead to the diminished ee observed, as corroborated by theoretical calculations. Based on these enantio-determining steps, catalytic enantioselective synthesis of 2,5-bis-tertiary pyrrolidines is demonstrated with good yield (50-78%) and moderate ee (up to 79%).

Synthesis of 1,1,5,6-tetramethyl-and 7-isopropyl-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene

4-(2,3-Dimethylphenyl)butanoic acid (4) was treated with excess of methyllithium to yield 5-(2,3-dimethylphenyl)-2-methylpentan-2-ol (6) which was cyclodehydrated using Dowex 50W-X8 resin, trifluoroacetic acid or polyphosphoric acid (PPA) to furnish 1,1,5,6-tetramethyl-1,2,3,4-tetrahydronaphthalene (1). The acid 4 was cyclized with PPA to furnish 5,6-dimethyl-3,4-dihydronaphthalen-1(2H)-one (5) which was converted into 1 by reaction with dimethylzinc and titanium tetrachloride. 4-(4-Isopropylphenyl)butanoic acid (7) on esterification followed by Grignard reaction with methylmagnesium iodide furnished 5-(4-isopropylphenyl)-2-methylpentan-2-ol (9), which was cyclodehydrated as above to yield 7-isopropyl-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene (2).

Synthesis of 1,1,5,6-Tetramethyltetralin, a Nonsesquiterpenic Constituent of Isocoma wrightii

The synthesis of 1,1,5,6-tetramethyltetralin (1) has been achieved starting from 4-t-butyl-o-xylene (3) via the keto ester (6).De-t-butylation of 6 to 8, followed by Clemmensen reduction, Grignard reaction and cyclodehydration gives 1.