Phosphinamide-directed benzylic lithiation. Application to the synthesis of peptide building blocks.
N-benzyldiphenylphosphinamides are deprotonated at the NCalpha position diastereospecifically upon treatment with t-BuLi in diethyl ether at low temperature. The reaction of the anions with alkyl, acyl, and tin halides, aliphatic and aromatic aldehydes, and Michael acceptors allowed installation of a variety of functional groups into the benzylic arm in excellent yields. Cleavage of the P-N linkage affords 1,2-amino alcohols and alpha-, beta-, and gamma-amino acids.
Burgos
Pascual Oña
PO
Area de Química Orgánica, Universidad de Almería, Carretera de Sacramento s/n, 04120 Almería, Spain.
Fernández
Ignacio
I
Iglesias
María José
MJ
García-Granda
Santiago
S
Ortiz
Fernando López
FL
D000588:Amines / Q000138:chemical synthesis; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010647:Phenyl Ethers / Q000737:chemistry; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D000605:Amino Alcohols; D001555:Benzene Derivatives; D009943:Organophosphorus Compounds; D010455:Peptides; D010647:Phenyl Ethers; D008094:Lithium