The synthesis of homoallylic amines utilizing a cuprate-based 1,2-metalate rearrangement.
Lithiation of the N-2,4,6-triisopropylbenzenesulfonyl-2-pyrroline (16) and treatment of the resulting cyclic vinyllithium reagent with R2CuCNLi2 produced an acyclic vinyl organometallic species that, when treated with an electrophile (H2O or RX), gave the homoallylic sulfonamides 18a-k in 37-93% yields and in > 95% diastereoselectivity. The deprotection of a representative homoallylic sulfonamide 18d was achieved in 83% yield by sonication in the presence of lithium wire and catalytic 4,4'-di-tert-butylbiphenyl (DBB). The efficacy of this general procedure for the production of homoallylic amine derivatives is demonstrated by the preparation of the diene amine 25, a key intermediate in the synthesis of a squalene synthetase inhibitor.
Neipp
C E
CE
Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Humphrey
J M
JM
Martin
S F
SF
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D007202:Indicators and Reagents; D008094:Lithium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D011759:Pyrrolidines; D013449:Sulfonamides; D003300:Copper; D008094:Lithium