Convergent access to polycyclic cyclopentanoids from α,β-unsaturated acid chlorides and alkynes through a reductive coupling, nazarov cyclization sequence.
Reductive coupling of α,β-unsaturated acid chlorides A with alkynoyls B provides convergent access to Nazarov cyclization precursors, α-carboxy divinyl ketones C. Cyclization of C gives an intermediate oxyallyl cation intermediate D, which can be trapped with tethered arenes (Ar). The resultant products can be further cyclized through nucleophilic displacement of suitable leaving groups X by tethered OH groups to give lactones (in a subsequent step). Where X is a suitable chiral auxiliary (e.g., oxazolidinone) this strategy affords access to homochiral cyclopentanoids.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.
Jason H
JH
Chaplin
Kristal
K
Jackson
Jonathan M
JM
White
Bernard L
BL
Flynn
D000480:Alkynes / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry*; D003500:Cyclization; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000737:chemistry*
D000480:Alkynes; D002712:Chlorides; D003517:Cyclopentanes; D011083:Polycyclic Compounds; D014753:Vinyl Compounds