Synthesis of 4-aminotropones from [(sulfinyl or sulfonyl)methyl]-substituted p-quinamines.
An efficient synthesis of 4-aminotropones has been achieved in excellent yields by simple treatment of 4-amino-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienones (p-quinamines) with NaH. The method allowed regiocontrolled access to 3-methyl, 5-methyl- and 3,5-dimethyl-substituted derivatives starting from p-quinamines with adequate substituents at the cyclohexadienone moiety and/or at the carbon linked to the sulfur function. The p-quinamines in turn were easily accessible from N-Boc p-anisidines (Boc=tert-butoxycarbonyl) by electrochemical oxidation in MeOH to quinone imine monoketals, followed by addition of a alpha-lithium sulfinyl carbanion to the imino group, and ketal hydrolysis. Oxidation of the sulfoxide gave the sulfonyl-substituted p-quinamines that, upon basic treatment, behave similarly. The p-quinamine 55 and bis-p-quinamine 56, resulting in the addition of the anion derived from dimethyl sulfone to the p-quinonimine ketal 14, also gave the 4-aminotropone. The mechanism involves the initial formation of a alpha-sulfonyl carbanion, which intramolecularly attacks the cyclohexadienone giving a norcaradiene-like enolate intermediate, the evolution of which through a ring-expansion process, pushes off a methyl sulfinate anion or SO2. This efficient process fulfils the criteria of atom economy. The introduction of a proline substituent in the nitrogen of the starting p-quinamine allowed the synthesis of an enantiopure 4-aminotropone, the asymmetric Diels-Alder reactions of which with maleimide occurred in a highly endo and pi-facial diastereoselective manner.
Carreño
M Carmen
MC
Departamento de Química Orgánica C-I, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. carmen.carrenno@uam.es
Ortega-Guerra
Montserrat
M
Ribagorda
María
M
Sanz-Cuesta
M Jesús
MJ
D000470:Alkaloids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000470:Alkaloids; D013457:Sulfur Compounds; C035340:quinamine; D014334:Tropolone; C003730:tropone