Hydroxylated pyrrolidines. Enantiospecific synthesis of all-cis 2,3,4,5-substituted pyrrolidine derivatives from serine.
We report the enantiospecific synthesis of the sterically congested all-cis 2,3,4,5-substituted pyrrolidines 4, 5, and 6, from either D- or L-serine. Hemiaminal intermediate 13 is converted to the fully substituted pyrrolidine 15 by way of a tandem Wittig-Michael reaction. The endo stereochemistry of the C-3 methyl group of compound 15 is set by stereoselective reduction of the double bond in 11, driven by a preference for hydrogenation from the rear side of the molecule. The all-cis configuration of these fully substituted pyrrolidines has been established by X-ray analysis of compound 6. Removal of the benzenesulfonyl group from the highly substituted and functionalized intermediate 15 is successfully accomplished by sodium naphthalenide reduction.
Verma
Sharad K
SK
Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.
Atanes
M Nieves
MN
Busto
J Hector
JH
Thai
Dung L
DL
Rapoport
Henry
H
D002384:Catalysis; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D011759:Pyrrolidines; D012694:Serine