Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition.
The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4-substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee viabeta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.
Davies
Stephen G
SG
Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK. steve.davies@chem.ox.ac.uk
Garner
A Christopher
AC
Goddard
Euan C
EC
Kruchinin
Dennis
D
Roberts
Paul M
PM
Smith
Andrew D
AD
Rodriguez-Solla
Humberto
H
Thomson
James E
JE
Toms
Steven M
SM
D000577:Amides / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D009942:Organometallic Compounds; D011759:Pyrrolidines; D008094:Lithium