Mn(III)-Based Oxidative Free-Radical Cyclizations of Unsaturated Ketones

Abstract

Mn(III)-based oxidative free-radical cyclization of unsaturated ketones is a versatile synthetic procedure with broad applicability. For example, oxidation of cyclopentanone 1a with 2 equiv of Mn(OAc)(3).2H(2)O and 1 equiv of Cu(OAc)(2).H(2)O in AcOH at 80 degrees C for 1.5 h affords 75% of bicyclo[3.2.1]oct-3-en-8-one 8a and 15% of bicyclo[3.2.1]oct-2-en-8-one 9a. Bridged bicyclic ketones that cannot enolize further are isolated in good yield. Monocyclic beta,gamma-unsaturated ketones that can enolize are oxidized further to give gamma-acetoxy enones. The formation of bicyclo[3.3.1]non-2-en-9-one (57a) in 52% yield from 2-allylcyclohexanone (56a) suggests that kinetically controlled enolization is the rate-determining step in alpha-keto radical formation. A wide variety of examples delineating the scope, limitations, and stereoselectivity of this reaction are presented.

Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

“…The Mn(III)-based oxidative free radical cyclization was extended to cyclopentanones R-substituted by an allylic or benzylic side chain. 188 For example, the precursors 333 are easily prepared by simple alkylation of the corresponding ketones and the cyclizations proceed smoothly to afford functionalized bicyclo[3.2.1]octenones 334 and 335, in moderate to good yields.…”

Palladium catalyzed molecular cascades for the synthesis of ethyl 2-methyl-2-(4-methyl-3-(morpholinomethyl)-2-oxopent-3-en-1-yl)-1-oxo-1,2,3,4,5,6-hexahydro-3aH-indene-3a-carboxylate

“…The commercially available keto-ester 1 was allylated with methallyl chloride 2 in the presence of NaH in dry DMF affording compound 3 in 60% yield as a colourless oil, according to the known procedure. 12 The allyl ester 3 was then triflated under kinetic control experimental conditions with Ph-NTf2; 13 the desired compound 4 was obtained in 76% as a colourless oil, carefully purified to be used in Pd-catalyzed processes (Scheme 2).…”

“…Ethyl 1-(2-methylallyl)-2-oxocyclohexane-1-carboxylate (3) was prepared according to the known procedure. 12 The product was purified by fractional distillation at reduced pressure as a colorless oil in 60% yield: b.p. 89-95 °C/0.2 mmHg.…”

Rhodium‐Catalyzed Deallylation of Allylmalonates and Related Compounds.

“…Pyridine-2,6-dicarboxylic acid dichloride was prepared according to the literature procedure 3 and racemic 2-amino-2-methylpropanamide, 2-amino-2,4-dimethylpentanamide, 2-amino-2,3,3-trimethylbutanamide and 2-amino-2 7,23.0,36.8,64.7,124.1,139.6,149.2,161.5,173.1. Anal…”