Ja. Campbell et al., CHIROSPECIFIC SYNTHESES OF PRECURSORS OF CYCLOPENTANE AND CYCLOPENTENE CARBOCYCLIC NUCLEOSIDES BY [3-COUPLING AND TRANSANNULAR ALKYLATION(3]), Journal of organic chemistry, 60(14), 1995, pp. 4602-4616
A new method is reported for the preparation of enantiomerically pure
)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, S)-1-amino-2-fluoro
-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-
2-cyclopentene, advanced precursors to carbocyclic nucleosides. The me
thod involves initial conversion of D-serine into an aldehyde with 9-p
henylfluorenyl protection at nitrogen and O-benzyl protection at oxyge
n. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate der
ived from tert-butyl 3-iodopropionate gave the corresponding anti-lact
one in high yield. Regioselective hydrogenolysis of the amine protecti
ng group, accompanied by intramolecular O- to N-cyclization formed a l
actam. After suitable nitrogen protection and functional group manipul
ation, transannular alkylation afforded the corresponding 2-benzyl- or
enzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group m
odification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy a
nd 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) an
alogue was converted to an N-BOC imide containing an olefinic Linkage
at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to
a reduction-deprotection sequence then afforded the desired carbocycli
c analogues. The [3 + 3]-coupling method also allowed improved and exp
edient access to an advanced tribenzylated lactam previously used in t
he racemic syntheses of the hydroxylated alkaloids D-mannonolactam, de
oxymannojirimycin, and prosopinone, providing a formal asymmetric synt
hesis of these alkaloids.