Concise preparation of 2,2-difluorohomopropargyl carbonyl derivatives. Application to the synthesis of 4,4-difluoroisoquinolinone congeners.
A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a magnesium-promoted Barbier reaction of substituted difluoropropargyl bromides with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective precursors in the synthesis of homopropargylic amides-by aminolysis using AlMe3, as well as of ketones-through the reaction of the corresponding Weinreb amides with Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne carbonyl compounds furnished six-membered diene products, which were used as susbstrates in a Diels-Alder reaction to afford 4,4-difluoroisoquinolin-3-ones. The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave 4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.
Arimitsu
Satoru
S
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
Fernandez
Begoña
B
Pozo
Carlos Del
CD
Fustero
Santos
S
Hammond
Gerald B
GB
D000480:Alkynes / Q000737:chemistry*; D003500:Cyclization; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D000480:Alkynes; D004952:Esters; D006845:Hydrocarbons, Fluorinated; D007546:Isoquinolines; D008274:Magnesium