Fluoride-catalyzed addition of PhSCF2SiMe3 to N-substituted cyclic imides followed by radical cyclization: general synthetic strategy of gem-difluoromethylenated 1-azabicyclic compounds.
PhSCF(2)SiMe(3) (1) was found, for the first time, to undergo fluoride-catalyzed nucleophilic difluoro(phenylsulfanyl)methylation reaction to cyclic imides 2, affording the corresponding adducts 3 in moderate to good yields. Reductive cleavage of the phenylsulfanyl group of N-alkylated adducts 3 with Bu(3)SnH/AIBN yielded gem-difluoromethylated products 4. Under the same reduction conditions, N-alkenylated and N-alkynylated adducts 3 afforded the corresponding gem-difluoromethylenated 1-azabicyclic compounds 5 and 6 with trans stereoselectivity. These compounds were employed as precursors for preparing substituted gem-difluoromethylenated pyrrolizidinones and indolizidinones 7 and 8 by treatment with Et(3)SiH/BF(3) x OEt(2), and compounds 9 and 10 by nucleophilic displacement of the hydroxyl group, using organosilanes in the presence of BF(3) x OEt(2). The synthesis of highly substituted gem-difluoromethylenated pyrrolizidines 13 and 14 was also demonstrated.
Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
Teerawut
T
Bootwicha
Duanghathai
D
Panichakul
Chutima
C
Kuhakarn
Samran
S
Prabpai
Palangpon
P
Kongsaeree
Patoomratana
P
Tuchinda
Vichai
V
Reutrakul
Manat
M
Pohmakotr
D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D005459:Fluorides / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry; D007094:Imides / Q000737:chemistry*; D017646:Organosilicon Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D053961:Azabicyclo Compounds; D006878:Hydroxides; D007094:Imides; D017646:Organosilicon Compounds; C031356:hydroxide ion; D005459:Fluorides